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OBJECTIVE: Analgesia and sedation for painful procedures in children are safe and effective, yet our experience is that pain management during lumbar puncture is suboptimal. We aim to document factors that influence residents' decisions to use analgesia and sedation during lumbar puncture and to compare pediatric and emergency medicine residents' practices. METHODS: A survey was developed and sent to pediatric and emergency medicine residents from across Canada that inquired about clinical practices, learning experiences, current use of analgesia and sedation for lumbar puncture, and their clinical reasoning for using or abstaining from using analgesia and sedation. The Student's t and chi2 tests were used to compare the 2 resident groups. RESULTS: Of the 374 residents to whom the survey was sent, 245 completed the survey. Pediatric residents reported performing lumbar punctures with no local anesthetic much more frequently. Pediatric residents used EMLA (AstraZeneca, Wilmington, DE) more frequently and injectable lidocaine less frequently. Pediatric residents used sedation for lumbar puncture at least once, more frequently than emergency medicine residents, and used mostly benzodiazepines. Both groups used ketamine at a similar rate. Pediatric residents reported that they witnessed adverse events of sedation more frequently. Although pediatric residents were responsible for teaching trainees the lumbar-puncture procedure significantly more frequently, they reported less educational opportunities during residency themselves and that they were less likely to recommend the use of local anesthetic during lumbar puncture when teaching the procedure. CONCLUSIONS: Several significant differences exist between the pediatric residents and emergency medicine residents we surveyed. Pediatric residents were using less injectable local anesthesia for lumbar puncture in children and more sedation for the procedure and have had notably less training in the use of sedation. Pediatric residents have more teaching responsibilities than their emergency medicine residents colleagues and are inconsistently recommending the use of local anesthetics for lumbar puncture. [ABSTRACT FROM AUTHOR]

Objectives: Evidence-based protocols for managing bleeding emergencies in patients with immune thrombocytopenia (ITP) are lacking. We conducted a systematic review of treatments for critical bleeding in patients with ITP., Methods: We included all study designs and extracted data in aggregate or individually for patients who received one or more interventions and for whom any of the following outcomes were reported: platelet count response, bleeding, disability, or death., Results: We identified 49 eligible studies reporting 112 critical bleed patients with ITP, including 66 children (median age, 10 years), 36 adults (median age, 41.5 years), and 10 patients with unreported age. Patients received corticosteroids (n = 67), IVIG (n = 49), platelet transfusions (n = 41), TPO-RAs (n = 17), and splenectomy (n = 28) either alone or in combination. Studies reported 29 different treatment combinations, the 5 most common were corticosteroids, platelet transfusion and splenectomy (n = 13), corticosteroids and IVIG (n = 13), or splenectomy alone (n = 13); IVIG alone (n = 11); and corticosteroids, IVIG and TPO-RA (n = 8). Mortality among patients with critical bleeds in ITP was 30.6% for adults and 19.7% for children., Conclusions: The effects of individual treatments on patient outcomes were uncertain due to very low-quality evidence. There is a need for a standardized approach to the treatment of ITP critical bleeds., Systematic Review Registration: CRD42020161206., (© 2024 The Author(s). European Journal of Haematology published by John Wiley & Sons Ltd.)

Introduction: Patient re-engagement with primary care physicians (PCPs) after cancer treatment is essential to facilitate survivorship care and to meet non-oncology primary care needs. We identified rates and predictors of PCP visits both during and after treatment among a population-based cohort of children with acute lymphoblastic leukemia (ALL)., Methods: Children of age less than 18 years at ALL diagnosis in Ontario between 2002 and 2012 were linked to administrative data and matched to controls without cancer. PCPs at diagnosis were identified and PCP visit rates during treatment compared between patients and controls. Post-treatment PCP visit rates were also calculated. Predictors included demographic-, disease-, and PCP-related variables., Results: A total of 743/793 (94%) patients and 3112/3947 (79%) controls had a PCP at diagnosis. Almost half of patients (361/743, 45%) did not visit their PCP during treatment. Visit rate during treatment was 0.64 per person per year (PPPY) versus 1.4 PPPY among controls (adjusted rate ratio [aRR] 0.47, 95th confidence interval [95CI]: 0.40-0.54; p < .0001). No disease- or PCP-related factors were associated with visit rates. Total 711 patients completed frontline therapy; 287 (40.4%) did not have a PCP visit after treatment. Nonetheless, survivors overall visited PCPs post treatment more often than controls (aRR 1.4, 95CI: 1.2-1.6; p < .0001). Survivors who saw their PCP during treatment had post-treatment visit rates twice that of other survivors (aRR 2.0, 95CI: 1.6-2.5; p < .0001)., Conclusions: Only a portion of children with ALL see their PCPs during treatment and return to PCP care following treatment completion. Post-treatment engagement with PCPs may be improved by PCP involvement during ALL treatment., (© 2023 The Authors. Pediatric Blood & Cancer published by Wiley Periodicals LLC.)

Pediatric immune thrombocytopenia (ITP) is an acquired disorder associated with autoimmune destruction and impairment of platelet production in children. Some children exhibit poor or transient response to ITP-directed treatments and are referred to as having refractory ITP (rITP). There is currently no consensus on the definition of rITP, nor evidence-based treatment guidelines for patients with rITP. After a survey of pediatric ITP experts demonstrated lack of consensus on pediatric rITP, we pursued a systematic review to examine the reported clinical phenotypes and treatment outcomes in pediatric rITP. The search identified 253 relevant manuscripts; following review, 11 studies proposed a definition for pediatric rITP with no consensus amongst them. Most definitions included suboptimal response to medical management, while some outlined specific platelet thresholds to define this suboptimal response. Common attributes identified in this study should be used to propose a comprehensive definition, which will facilitate outcome comparisons of future rITP studies., (© 2022 Wiley Periodicals LLC.)

Objectives: Health Utilities Preschool (HuPS) was developed to fill the need for a generic preference-based measure (GPM) applicable in early childhood. A GPM has all the properties for higher-order summary measures, such as quality-adjusted life-years, required to inform important policy decisions regarding health and healthcare services., Methods: Development was in accordance with published standards for a GPM, statistical procedures, and modeling. HuPS incorporates key components of 2 existing measurement systems: Health Status Classification System for Preschool Children and Health Utilities Index Mark 3 (HUI3). The study included a series of 4 measurement surveys: definitional, adaptational, quantificational, and evaluational health-related quality of life (HRQL). HuPS measurements were evaluated for reliability, validity, interpretability, and acceptability., Results: Definitional measurements identified 8 Health Status Classification System for Preschool Children attributes in common with HUI3 (vision, hearing, speech, ambulation, dexterity, emotion, cognition, and pain and discomfort), making the HUI3 scoring equation commensurate with HuPS health states. Adaptational measurements informed the content of attribute-level descriptions (n = 35). Quantificational measurements determined level scoring coefficients. HRQL scoring inter-rater reliability (intraclass correlation coefficient = 0.79) was excellent. Continuity of HRQL scoring with HUI3 was reliable (intraclass correlation coefficient = 0.80, P < .001) and valid (mean absolute difference = 0.016, P = .396)., Conclusions: HuPS is an acceptable, reliable, and valid GPM. HRQL scoring is continuous with HUI3. Continuity expands the applicability of GPM (HUI3) scoring to include subjects as young as 2 years of age. Widespread applications of HuPS would inform important health policy and management decisions as HUI3 does for older subjects., (Copyright © 2022 International Society for Pharmacoeconomics and Outcomes Research, Inc. Published by Elsevier Inc. All rights reserved.)

Background: There is a lack of self-management tools for adolescents with cancer (AWC). This study evaluated the feasibility of Teens Taking Charge Cancer , a web-based self-management program. Methods: A pilot randomized control trial (RCT) was conducted across 4 pediatric oncology clinics. AWC (12-18 years) and their caregivers were randomized to either the intervention or control group. All were asked to complete 12 website modules over 12 weeks (at their own pace) and received monthly calls from health coaches. The intervention website was based on cognitive behavioral principals, designed as an interactive self-guided online program, while the control consisted of education and included links to 12 general cancer websites. Outcome assessments occurred at enrollment and 12 weeks post-intervention. The primary outcomes included rate of accrual and retention, adherence to the protocol, acceptability and satisfaction with intervention using questionnaire and semi-structured interviews, adverse events and engagement with the intervention. Results: Eighty-one teen-caregiver dyads were enrolled with a retention rate of 33%. In the intervention group 46% ( n  = 18) logged in at least once over the 12-week period. A mean of 2.4 of 12 modules ( SD 3.0) were completed; and no one completed the program. Thirty-three percent of caregivers in the intervention logged into the website at least once and none completed the full program. Discussion: The results from this pilot study suggest that the current design of the Teens Taking Charge Cancer RCT lacks feasiblity. Future web-based interventions for this group should include additional features to promote uptake and engagement with the program.

Background: Children with Down syndrome (DS) and acute lymphoblastic leukemia (ALL) are at increased risk of treatment-related morbidity and mortality compared to non-DS-ALL, requiring increased supportive care. We examined the healthcare utilization and costs in DS-ALL patients to inform future evaluations of novel therapies., Methods: A provincial registry identified all children (1-17 years) diagnosed with B-lineage ALL in Ontario, Canada between 2002 and 2012. Detailed demographic, disease, treatment, and outcome data were abstracted. Linkage to population-based health services databases identified all outpatient and emergency department (ED) visits, hospitalizations, and physician billings. Healthcare utilization costs were available for patients diagnosed during 2006-2012 using validated algorithms (2018 Canadian dollars). Healthcare utilization rates and costs were compared between DS and non-DS patients using regression models, adjusting for all covariates., Results: Of 711 patients, 28 (3.9%) had DS. Adjusting for all covariates, children with DS-ALL experienced substantially higher rates of ED visits (rate ratio [RR] 1.5, 95% confidence interval [95% CI]: 1.2-2.0; p = .001) and inpatient days (RR 2.5, 95% CI: 1.4-4.5; p = .002) compared to non-DS children. Outpatient visit rates were similar (RR 1.1, 95% CI: 0.9-1.3; p = .41). Among patients with available cost data (N = 533, DS = 19), median 5-year healthcare utilization cost was $247,700 among DS patients (interquartile range [IQR]: 200,900-354,500) and $196,200 among non-DS patients (IQR: 148,900-280,300; p = .02). In adjusted analyses, DS-associated costs were 50% higher (RR 1.5, 95% CI: 1.2-1.9; p < .002)., Conclusions: Healthcare utilization and treatment costs of DS-ALL patients are substantially higher than those of non-DS-ALL. Our data provide a baseline for future DS-specific cost-effectiveness studies., (© 2022 Wiley Periodicals LLC.)

Classification of inherited bone marrow failure syndromes (IBMFSs) according to clinical and genetic diagnoses enables proper adjustment of treatment. Unfortunately, 30% of patients enrolled in the Canadian Inherited Marrow Failure Registry (CIMFR) with features suggesting hereditability could not be classified with a specific syndromic diagnosis. We analyzed the outcome of hematopoietic stem cell transplantation (HSCT) in unclassified IBMFSs (uIBMFSs) and the factors associated with outcome. Twenty-two patients with uIBMFSs and 70 patients with classified IBMFSs underwent HSCT. Five-year overall survival of uIBMFS patients after HSCT was inferior to that of patients with classified IBMFSs (56% vs 76.5%). The outcome of patients with uIBMFS who received cord blood was significantly lower than that of patients who received other stem cell sources (14.8% vs 90.9%). Engraftment failure was higher among patients with uIBMFS who received cord blood than those who received bone marrow. None of the following factors were significantly associated with poor survival: transfusion load, transplant indication, the intensity of conditioning regimen, human leukocyte antigen-identical sibling/alternative donor. We suggest that identifying the genetic diagnosis is essential to modulate the transplant procedure including conditioning agents and stem cell sources for better outcome and the standard cord blood transplantation (CBT) should be avoided in uIBMFS., (© 2021 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Pyruvate kinase deficiency (PKD) is the most common cause of congenital nonspherocytic hemolytic anemia. Although recognition of the disease spectrum has recently expanded, data describing its impact on health-related quality of life (HRQoL) are limited. In this prospective international cohort of 254 patients (131 adults and 123 children) with PKD, we used validated measures to assess the impact of disease on HRQoL (EuroQol 5-Dimension Questionnaire, Pediatric Quality of Life Inventory Generic Core Scale version 4.0, and Functional Assessment of Cancer Therapy-Anemia) and fatigue (Patient Reported Outcomes Measurement Information System Fatigue and Pediatric Functional Assessment of Chronic Illness Therapy-Fatigue). Significant variability in HRQoL and fatigue was reported for adults and children, although individual scores were stable over a 2-year interval. Although adults who were regularly transfused reported worse HRQoL and fatigue compared with those who were not (EuroQol-visual analog scale, 58 vs 80; P = .01), this difference was not seen in children. Regularly transfused adults reported lower physical, emotional, and functional well-being and more anemia symptoms. HRQoL and fatigue significantly differed in children by genotype, with the worst scores in those with 2 severe PKLR mutations; this difference was not seen in adults. However, iron chelation was associated with significantly worse HRQoL scores in children and adults. Pulmonary hypertension was also associated with significantly worse HRQoL. Additionally, 59% of adults and 35% of children reported that their jaundice upset them, identifying this as an important symptom for consideration. Although current treatments for PKD are limited to supportive care, new therapies are in clinical trials. Understanding the impact of PKD on HRQoL is important to assess the utility of these treatments. This trial was registered at www.clinicaltrials.gov as #NCT02053480., (© 2022 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)

Purpose: Distress in cancer is defined as multifactorial unpleasant experience of an emotional, psychological, social, or spiritual nature that interferes with ones' ability to cope with cancer and its symptoms and treatment. The aim of this study was to determine clinical and demographic factors associated with the presence of distress in adolescent and young adults (AYAs) with cancer. Methods: Data were collected as part of a field-test study conducted between August 2016 and November 2017 in Canada (Toronto, Edmonton, and Vancouver) to determine the reliability and validity of CDS-AYA (Cancer Distress Scales for Adolescent and Young Adults). The CDS-AYA consist of five independently functioning scales including impact of cancer, physical, emotional, cognitive, and cancer worry. Multivariate logistic regression analyses, using established CDS-AYA cut points, were performed to identify clinical and demographic factors associated with the presence of distress in AYAs of ages 15-39 years with cancer. Results: Across all scales, increased distress was associated with female gender ( p  < 0.05), on-treatment status ( p  < 0.05), and reported poor overall health ( p  < 0.001). For the emotional scale, distress was also associated with being of age 15-19 years ( p  = 0.01). The greatest effect size for all scales was associated with treatment status [ exp(β)  = 1.78-4.6], except for the cognitive scale where gender had a slightly greater effect size. Conclusion: Factors associated with distress in AYA patients with cancer were similar across five CDS-AYA scales. Although it is important to screen all patients for distress, our findings reveal that patients who are female, on treatment, or who report having poorer health may be at a greater risk.

Background: Therapy for childhood acute lymphoblastic leukemia (ALL) is associated with substantial health care utilization and burden on families. Little is known about health care utilization during specific treatment phases., Procedures: We identified children with ALL diagnosed during 2002-2012 in Ontario, Canada and treated according to Children's Oncology Group (COG) protocols. Disease and treatment data were chart abstracted. Population-based health care databases identified all outpatient visits, emergency department (ED) visits, and hospitalizations. In addition to comparing standard and intensified versions of treatment phases, we compared patients receiving different steroids (dexamethasone vs. prednisone) and different versions of interim maintenance (IM) (Capizzi vs. high-dose methotrexate [HD-MTX])., Results: Six hundred thirty-seven children met inclusion criteria. During intensified consolidation, 76.2% of patients were hospitalized at least once, compared to only 32.3% of patients receiving standard consolidation (p < .0001). Similarly, 72.9% of patients receiving intensified delayed intensification (DI) were hospitalized during this phase compared to 50.3% of patients receiving standard DI (p < .0001). Among patients receiving a four-drug induction, those receiving dexamethasone had an 85% higher rate of ED visits (adjusted rate ratio [aRR] 1.85, 95th confidence interval [95CI] 1.14-3.00; p = .01) and a 44% higher rate of hospitalization (aRR 1.44, 95CI 1.24-1.68) compared to those receiving prednisone. Among high-risk B-ALL and T-ALL patients in IM, Capizzi MTX was not associated with an increased rate of ED visits versus HD-MTX., Conclusions: These results can be used to inform anticipatory guidance for families, particularly those undergoing intensified therapy. Our results also suggest that increased toxicity rates associated with dexamethasone during Induction seen in clinical trials reflect real-world practice., (© 2021 Wiley Periodicals LLC.)

Background: Pyruvate kinase deficiency (PKD) is a rare, autosomal recessive red blood cell enzyme disorder, which leads to lifelong hemolytic anemia and associated complications from the disease and its management., Methods: An international, multicenter registry enrolled 124 individuals younger than 18 years old with molecularly confirmed PKD from 29 centers. Retrospective and prospective clinical data were collected., Results: There was a wide range in the age at diagnosis from 0 to 16 years. Presentation in the newborn period ranged from asymptomatic to neonatal jaundice to fulminant presentations of fetal distress, myocardial depression, and/or liver failure. Children <5 years old were significantly more likely to be transfused than children >12 to <18 years (53% vs. 14%, p = .0006), which correlated with the timing of splenectomy. Regular transfusions were most common in children with two severe PKLR variants. In regularly transfused children, the nadir hemoglobin goal varied considerably. Impact on quality of life was a common reason for treatment with regular blood transfusions and splenectomy. Splenectomy increased the hemoglobin and decreased transfusion burden in most children but was associated with infection or sepsis (12%) and thrombosis (1.3%) even during childhood. Complication rates were high, including iron overload (48%), perinatal complications (31%), and gallstones (20%)., Conclusions: There is a high burden of disease in children with PKD, with wide practice variation in monitoring and treatment. Clinicians must recognize the spectrum of the manifestations of PKD for early diagnostic testing, close monitoring, and management to avoid serious complications in childhood., (© 2021 Wiley Periodicals LLC.)

Avoidant/restrictive food intake disorder (ARFID) is a feeding and eating disorder that results in nutritional inadequacies, weight loss, and/or dependence on enteral feeds, and for which three clinical subtypes have been described. We present a unique case of an 11-year-old boy with rigid ARFID since infancy and features of all three ARFID subtypes. The patient presented with a life-long history of sensory aversion, limited intake and phobia of vomiting resulting in restriction to a single food item (yogurt) for more than 5 years. He presented with severe iron-deficiency anaemia, and deficiencies of vitamins A, C, D, E and zinc. We employed a multimodal therapeutic approach that incorporated elements of cognitive-behavioural therapy (CBT), family-based therapy (FBT) and pharmacological management with an antidepressant medication (sertraline) and an atypical antipsychotic agent (olanzapine). Over the course of a 7-week admission, our approach assisted the patient in successful weight restoration and incorporation of at least three new food items into his daily diet. While there are currently no first-line recommendations for ARFID management, our study lends support to the efficacy of CBT, FBT and pharmacological management for ARFID patients, including complex cases with multiple subtype features. Further research is needed to strengthen ARFID clinical guidelines.

Immune thrombocytopenia (ITP), an acquired autoimmune disorder of low platelets and risk of bleeding, has a substantial impact on health-related quality of life (HRQoL). Patients with ITP often report significant fatigue, although the pathophysiology of this is poorly understood. In this observational cohort of 120 children receiving second-line therapies for ITP, we assessed reports of fatigue using the Hockenberry Fatigue Scale. Children and adolescents with ITP reported a similarly high level of fatigue with 54% (29/54) of children and 62% (26/42) of adolescents reporting moderate-to-severe fatigue. There was no correlation between fatigue and age or gender. Adolescents with newly diagnosed and persistent ITP had higher mean fatigue scores than those with chronic ITP (P = 0·03). Fatigue significantly improved in children and adolescents by 1 month after starting second-line treatments, and this improvement continued to be present at 12 months after starting treatment. Fatigue scores at all time-points correlated with general HRQoL using the Kids ITP Tool, but did not correlate with bleeding symptoms, platelet count, or platelet response to treatment. Fatigue is common in children and adolescents with ITP and may benefit from ITP-directed treatment even in the absence of bleeding symptoms., (© 2020 British Society for Haematology and John Wiley & Sons Ltd.)

A term infant girl was admitted for evaluation of severe thrombocytopenia. She also had purpura-like skin lesions. A complete blood count showed a platelet count of 40×10/L (normal value: 150 to 400×10/L). She received random donor platelet transfusions and intravenous immunoglobulin therapy; however, thrombocytopenia persisted. She developed bloody stools on day 5 of life and hematemesis on day 9. Upper gastrointestinal endoscopy revealed multiple small, 2 to 5 mm, vascular lesions throughout the stomach body and proximal duodenum. Our multidisciplinary team will discuss an approach towards a term infant with thrombocytopenia and gastrointestinal bleeding, the diagnostic challenges, and patient management.

Progressive cytopenia is a serious complication among paediatric patients with inherited bone marrow failure syndromes (IBMFS). Androgens have been used to improve blood counts in different bone marrow failure conditions. Little is known about efficacy and toxicity with new androgens (i.e., danazol) in different types of IBMFS. We identified 29 patients from the Canadian Inherited Marrow Failure Registry, who received oxymetholone or danazol. Sixteen (55%) had haematological response including patients with unclassified IBMFS (45%). Danazol showed a better toxicity profile and similar efficacy compared to oxymetholone. Androgens are an effective and safe option to ameliorate bone marrow failure in IBMFS., (© 2020 British Society for Haematology and John Wiley & Sons Ltd.)

Inherited bone marrow failure syndromes, such as Fanconi anemia (FA) and Shwachman-Diamond syndrome (SDS), feature progressive cytopenia and a risk of acute myeloid leukemia (AML). Using deep phenotypic analysis of early progenitors in FA/SDS bone marrow samples, we revealed selective survival of progenitors that phenotypically resembled granulocyte-monocyte progenitors (GMP). Whole-exome and targeted sequencing of GMP-like cells in leukemia-free patients revealed a higher mutation load than in healthy controls and molecular changes that are characteristic of AML: increased G>A/C>T variants, decreased A>G/T>C variants, increased trinucleotide mutations at Xp(C>T)pT, and decreased mutation rates at Xp(C>T)pG sites compared with other Xp(C>T)pX sites and enrichment for Cancer Signature 1 (X indicates any nucleotide). Potential preleukemic targets in the GMP-like cells from patients with FA/SDS included SYNE1, DST, HUWE1, LRP2, NOTCH2, and TP53. Serial analysis of GMPs from an SDS patient who progressed to leukemia revealed a gradual increase in mutational burden, enrichment of G>A/C>T signature, and emergence of new clones. Interestingly, the molecular signature of marrow cells from 2 FA/SDS patients with leukemia was similar to that of FA/SDS patients without transformation. The predicted founding clones in SDS-derived AML harbored mutations in several genes, including TP53, while in FA-derived AML the mutated genes included ARID1B and SFPQ. We describe an architectural change in the hematopoietic hierarchy of FA/SDS with remarkable preservation of GMP-like populations harboring unique mutation signatures. GMP-like cells might represent a cellular reservoir for clonal evolution.

Inherited bone marrow failure syndromes (IBMFSs) are genetically heterogeneous disorders with cytopenia. Many IBMFSs also feature physical malformations and an increased risk of cancer. Point mutations can be identified in about half of patients. Copy number variation (CNVs) have been reported; however, the frequency and spectrum of CNVs are unknown. Unfortunately, current genome-wide methods have major limitations since they may miss small CNVs or may have low sensitivity due to low read depths. Herein, we aimed to determine whether reanalysis of NGS panel data by normalized coverage value could identify CNVs and characterize them. To address this aim, DNA from IBMFS patients was analyzed by a NGS panel assay of known IBMFS genes. After analysis for point mutations, heterozygous and homozygous CNVs were searched by normalized read coverage ratios and specific thresholds. Of the 258 tested patients, 91 were found to have pathogenic point variants. NGS sample data from 165 patients without pathogenic point mutations were re-analyzed for CNVs; 10 patients were found to have deletions. Diamond Blackfan anemia genes most commonly exhibited heterozygous deletions, and included RPS19 , RPL11 , and RPL5 . A diagnosis of GATA2 -related disorder was made in a patient with myelodysplastic syndrome who was found to have a heterozygous GATA2 deletion. Importantly, homozygous FANCA deletion were detected in a patient who could not be previously assigned a specific syndromic diagnosis. Lastly, we identified compound heterozygousity for deletions and pathogenic point variants in RBM8A and PARN genes. All deletions were validated by orthogonal methods. We conclude that careful analysis of normalized coverage values can detect CNVs in NGS panels and should be considered as a standard practice prior to do further investigations., Competing Interests: Competing interestsThe authors declare no competing interests., (© The Author(s) 2019.)

Immune thrombocytopenia (ITP) is an autoimmune bleeding disorder with isolated thrombocytopenia and hemorrhagic risk. While many children with ITP can be safely observed, treatments are often needed for various reasons, including to decrease bleeding, or to improve health related quality of life (HRQoL). There are a number of available second-line treatments, including rituximab, thrombopoietin-receptor agonists, oral immunosuppressive agents, and splenectomy, but data comparing treatment outcomes are lacking. ICON1 is a prospective, multi-center, observational study of 120 children starting second-line treatments for ITP designed to compare treatment outcomes including platelet count, bleeding, and HRQoL utilizing the Kids ITP Tool (KIT). While all treatments resulted in increased platelet counts, romiplostim had the most pronounced effect at 6 months (P = .04). Only patients on romiplostim and rituximab had a significant reduction in both skin-related (84% to 48%, P = .01 and 81% to 43%, P = .004) and non-skin-related bleeding symptoms (58% to 14%, P = .0001 and 54% to 17%, P = .0006) after 1 month of treatment. HRQoL significantly improved on all treatments. However, only patients treated with eltrombopag had a median improvement in KIT scores at 1 month that met the minimal important difference (MID). Bleeding, platelet count, and HRQoL improved in each treatment group, but the extent and timing of the effect varied among treatments. These results are hypothesis generating and help to improve our understanding of the effect of each treatment on specific patient outcomes. Combined with future randomized trials, these findings will help clinicians select the optimal second-line treatment for an individual child with ITP., (© 2019 Wiley Periodicals, Inc.)

Introduction: It is unclear which outcome indicators should be used to measure the success of haemophilia transition programs, and what are key elements of a haemophilia transition program to ensure success., Aim: To establish by expert consensus a list of important and feasible outcome indicators of successful haemophilia transition, and a list of key elements of transition planning., Methods: A modified two-stage Delphi survey was developed and disseminated among a panel of Canadian interdisciplinary haemophilia care providers. Participants were asked to rate the importance and feasibility of outcome indicators of effective haemophilia transition and elements of haemophilia transition program. In the second round, participants were asked to choose the top five outcomes suitable for inclusion in a core outcome set of transition effectiveness, and the top five elements that are important and feasible for implementation within the next 5 years., Results: In total, 34/73 (47%) of participants completed the first round and 33 completed the second round, representing a variety of disciplines. Top outcome indicators recommended for a core outcome set include measurement of adherence, change in bleeding rate, self-efficacy skills, haemophilia knowledge, patient and caregiver satisfaction, time gap between last paediatric and first adult clinic, and number of emergency room or hospital admissions. Fourteen elements of transition achieved consensus in importance ratings, while eight were felt to be feasible for implementation within next 5 years., Conclusions: Results will contribute towards the development of a haemophilia transition outcome instrument and provide guidance for future studies of the effectiveness of transition programs., (© 2019 John Wiley & Sons Ltd.)

Background: Accessible self-management interventions are critical for adolescents with sickle cell disease to better cope with their disease, improve health outcomes and health-related quality of life, and promote successful transition to adult health care services. However, very few comprehensive self-management and transitional care programs have been developed and tested in this population. Internet and mobile phone technologies can improve accessibility and acceptability of interventions to promote disease self-management in adolescents with sickle cell disease., Objective: The aim of this study was to qualitatively explore the following from the perspectives of adolescents, parents, and their health care providers: (1) the impact of sickle cell disease on adolescents to identify challenges to their self-management and transitional care and (2) determine the essential components of a digital self-management and transitional care program as the first phase to inform its development., Methods: A qualitative descriptive design utilizing audio-recorded, semistructured interviews was used. Adolescents (n=19, aged 12-19 years) and parents (n=2) participated in individual interviews, and health care providers (n=17) participated in focus group discussions and were recruited from an urban tertiary care pediatric hospital. Audio-recorded data were transcribed verbatim and organized into categories inductively, reflecting emerging themes using simple content analysis., Results: Data were categorized into 4 major themes: (1) impact of sickle cell disease, (2) experiences and challenges of self-management, (3) recommendations for self-management and transitional care, and (4) perceptions about a digital self-management program. Themes included subcategories and the perspectives of adolescents, parents, and health care providers. Adolescents discussed more issues related to self-management, whereas health care providers and parents discussed issues related to transition to adult health services., Conclusions: Adolescents, parents, and health care providers described the continued challenges youth with sickle cell disease face in terms of psychosocial impacts and stigmatization. Participants perceived a benefit to alleviating some of these challenges through a digital self-management tool. They recommended that an effective digital self-management program should provide appropriate sickle cell disease-related education; guidance on developing self-advocacy and communication skills; empower adolescents with information for planning for their future; provide options for social support; and be designed to be engaging for both adolescents and parents to use. A digital platform to deliver these elements is an accessible and acceptable way to address the self-management and transitional care needs of adolescents., (©Yalinie Kulandaivelu, Chitra Lalloo, Richard Ward, William T Zempsky, Melanie Kirby-Allen, Vicky R Breakey, Isaac Odame, Fiona Campbell, Khush Amaria, Ewurabena A Simpson, Cynthia Nguyen, Tessy George, Jennifer N Stinson. Originally published in JMIR Pediatrics and Parenting (http://pediatrics.jmir.org), 25.09.2018.)

Background: To support adolescents through transition from pediatrics to adult care, health care providers and families help teens gain knowledge and develop self-management skills. Peer mentoring can provide meaningful support and has been associated with improved health outcomes in patients with other chronic conditions. Peer mentoring is an appealing way to provide support, but it is imperative to consider the unique needs of adolescents to ensure its success., Objective: The objective of our study was to identify the peer mentoring wants and needs of youth with hemophilia in order to guide the development of a new program., Methods: In this qualitative study, we interviewed a convenience sample of youth with hemophilia from 2 Canadian hemophilia treatment centers. Two iterative cycles of audiorecorded, semistructured individual interviews were conducted. Descriptive statistics and content analyses were used to organize data into categories that reflected emerging themes., Results: In total, we recruited 23 participants aged 12-20 years, with a mean age of 14.91 (2.57) years. When asked about program design, participants weighed the importance of flexibility in delivery (eg, Web-based, in person, text messaging [short message service]), content (eg, structured vs unstructured), frequency of sessions, and length of the program. Participants identified some potential challenges such as scheduling issues, comfort level for disease discussion, and discordant mentor-mentee personality types. The program was viewed as a positive medium for connecting peers with hemophilia., Conclusions: Adolescents with hemophilia expressed interest in a peer mentoring program and provided valuable insight that will be applied in the development of a peer mentoring program for youth with hemophilia., (©Vicky R Breakey, Vanessa Bouskill, Cynthia Nguyen, Stephanie Luca, Jennifer N Stinson, Sara Ahola Kohut. Originally published in JMIR Pediatrics and Parenting (http://pediatrics.jmir.org), 10.07.2018.)

Immune thrombocytopenia (ITP) is an acquired autoimmune bleeding disorder which presents with isolated thrombocytopenia and risk of hemorrhage. While most children with ITP promptly recover with or without drug therapy, ITP is persistent or chronic in others. When needed, how to select second-line therapies is not clear. ICON1, conducted within the Pediatric ITP Consortium of North America (ICON), is a prospective, observational, longitudinal cohort study of 120 children from 21 centers starting second-line treatments for ITP which examined treatment decisions. Treating physicians reported reasons for selecting therapies, ranking the top three. In a propensity weighted model, the most important factors were patient/parental preference (53%) and treatment-related factors: side effect profile (58%), long-term toxicity (54%), ease of administration (46%), possibility of remission (45%), and perceived efficacy (30%). Physician, health system, and clinical factors rarely influenced decision-making. Patient/parent preferences were selected as reasons more often in chronic ITP (85.7%) than in newly diagnosed (0%) or persistent ITP (14.3%, P = .003). Splenectomy and rituximab were chosen for the possibility of inducing long-term remission (P < .001). Oral agents, such as eltrombopag and immunosuppressants, were chosen for ease of administration and expected adherence (P < .001). Physicians chose rituximab in patients with lower expected adherence (P = .017). Treatment choice showed some physician and treatment center bias. This study illustrates the complexity and many factors involved in decision-making in selecting second-line ITP treatments, given the absence of comparative trials. It highlights shared decision-making and the need for well-conducted, comparative effectiveness studies to allow for informed discussion between patients and clinicians., (© 2018 Wiley Periodicals, Inc.)

An international, multicenter registry was established to collect retrospective and prospective clinical data on patients with pyruvate kinase (PK) deficiency, the most common glycolytic defect causing congenital nonspherocytic hemolytic anemia. Medical history and laboratory and radiologic data were retrospectively collected at enrollment for 254 patients with molecularly confirmed PK deficiency. Perinatal complications were common, including anemia that required transfusions, hyperbilirubinemia, hydrops, and prematurity. Nearly all newborns were treated with phototherapy (93%), and many were treated with exchange transfusions (46%). Children age 5 years and younger were often transfused until splenectomy. Splenectomy (150 [59%] of 254 patients) was associated with a median increase in hemoglobin of 1.6 g/dL and a decreased transfusion burden in 90% of patients. Predictors of a response to splenectomy included higher presplenectomy hemoglobin ( P = .007), lower indirect bilirubin ( P = .005), and missense PKLR mutations ( P = .0017). Postsplenectomy thrombosis was reported in 11% of patients. The most frequent complications included iron overload (48%) and gallstones (45%), but other complications such as aplastic crises, osteopenia/bone fragility, extramedullary hematopoiesis, postsplenectomy sepsis, pulmonary hypertension, and leg ulcers were not uncommon. Overall, 87 (34%) of 254 patients had both a splenectomy and cholecystectomy. In those who had a splenectomy without simultaneous cholecystectomy, 48% later required a cholecystectomy. Although the risk of complications increases with severity of anemia and a genotype-phenotype relationship was observed, complications were common in all patients with PK deficiency. Diagnostic testing for PK deficiency should be considered in patients with apparent congenital hemolytic anemia and close monitoring for iron overload, gallstones, and other complications is needed regardless of baseline hemoglobin. This trial was registered at www.clinicaltrials.gov as #NCT02053480., (© 2018 by The American Society of Hematology.)

Inherited bone marrow failure syndromes (IBMFSs) comprise a genetically heterogeneous group of diseases with hematopoietic failure and a wide array of physical malformations. Copy number variants (CNVs) were reported in some IBMFSs. It is unclear what impact CNVs play in patients evaluated for a suspected diagnosis of IBMFS. Clinical and genetic data of 323 patients from the Canadian Inherited Marrow Failure Registry from 2001 to 2014, who had a documented genetic work-up, were analyzed. Cases with pathogenic CNVs (at least 1 kilobasepairs) were compared to cases with other mutations. Genotype-phenotype correlations were performed to assess the impact of CNVs. Pathogenic nucleotide-level mutations were found in 157 of 303 tested patients (51.8%). Genome-wide CNV analysis by single nucleotide polymorphism arrays or comparative genomic hybridization arrays revealed pathogenic CNVs in 11 of 67 patients tested (16.4%). In four of these patients, identification of CNV was crucial for establishing the correct diagnosis as their clinical presentation was ambiguous. Eight additional patients were identified to harbor pathogenic CNVs by other methods. Of the 19 patients with pathogenic CNVs, four had compound-heterozygosity of a CNV with a nucleotide-level mutation. Pathogenic CNVs were associated with more extensive non-hematological organ system involvement ( p =0.0006), developmental delay ( p =0.006) and short stature ( p =0.04) compared to nucleotide-level mutations. In conclusion, a significant proportion of patients with IBMFSs harbor pathogenic CNVs which were associated with a more extensive non-hematological phenotype in this cohort. Patients with a phenotype suggestive of IBMFSs but without identification of pathogenic nucleotide-level mutations should undergo specific testing for CNVs., Competing Interests: CONFLICT OF INTEREST All authors declare no conflict of interest.

Background: Adolescence is a vulnerable time for teens with sickle cell disease (SCD). Although there is evidence to support the use of web-based education to promote self-management skills in patients with chronic illnesses, the quality of SCD-related information on the Internet has not been assessed., Procedure: A website review was conducted to appraise the quality, content, accuracy, readability, and desirability of online information for the adolescents with SCD. Relevant keywords were searched on the most popular search engines. Websites meeting predetermined criteria were reviewed. The quality of information was appraised using the validated DISCERN tool. Two physicians independently rated website completeness and accuracy. Readability of the sites was documented using the simple measure of gobbledygook (SMOG) scores and the Flesch Reading Ease (FRE). The website features considered desirable by youth were tracked., Results: Search results yielded >600 websites with 25 unique hits meeting criteria. The overall quality of the information was "fair" and the average DISCERN rating score was 50.1 (±9.3, range 31.0-67.5). Only 12 of 25 (48%) websites had scores >50. The average completeness score was 20 of 29 (±5, range 12-27). No errors were identified. The mean SMOG score was 13.04 (±2.80, range 10.21-22.85) and the mean FRE score was 46.05 (±11.47; range 17.50-66.10), suggesting that the material was written well beyond the acceptable reading level for patient education. The websites were text-heavy and lacked the features that appeal to youth (chat, games, videos, etc.)., Conclusion: Given the paucity of high-quality health information available for the teens with SCD, it is essential that additional online resources be developed., (© 2016 Wiley Periodicals, Inc.)

Acute neurological changes in sickle cell disease (SCD) patients often raise the suspicion for stroke. Posterior reversible encephalopathy syndrome (PRES) can mimic stroke in its clinical presentation. We aimed to (i) review the PRES literature in SCD patients including clinical presentation, risk factors, pathophysiology, and management and (ii) elucidate the distinction between PRES and stroke in SCD. The exact pathophysiology of PRES in SCD remains elusive but is likely multifactorial and related to sickling, ischemia, and chronic anemia predisposing to vasogenic edema. PRES and stroke in SCD are distinguishable conditions. Our review may help elucidate a clinical approach to this distinction., (© 2016 Wiley Periodicals, Inc.)

Background: Pediatric patients with chronic and/or refractory autoimmune multi-lineage cytopenias present challenges in both diagnosis and management. Increasing availability of diagnostic testing has revealed an underlying immune dysfunction in patients previously diagnosed with Evans Syndrome. However, the data are sparse and the majority of patients are adults., Procedure: We performed a retrospective chart review to document the natural history of 23 pediatric patients with autoimmune multi-lineage cytopenias followed at three tertiary care pediatric hematology clinics., Results: Investigations revealed seven patients (30.4%) with an autoimmune lymphoproliferative-like syndrome and six patients (26.1%) with other primary immunodeficiencies. Only one (4.3%) patient was suspected to have systemic lupus erythematosus and six patients (26.1%) had other types of autoimmunity. Treatment consisted of immunosuppressive therapy, intravenous gammaglobulin, and splenectomy. Supportive care included granulocyte-colony stimulating factor, and blood product transfusions. Two patients (8.7%) died. Complete remission was achieved in 3 patients (13.0%); of the remaining, 14 patients (60.9%) had chronic immune thrombocytopenic purpura, 10 patients (43.5%) chronic autoimmune neutropenia, and 4 patients (17.4%) chronic autoimmune hemolytic anemia with a median follow up of 5 years (2 months-12 years)., Conclusions: These data suggest that pediatric patients presenting with autoimmune multi-lineage cytopenias should undergo investigation for underlying immune dysregulation, including autoimmune lymphoproliferative syndrome, other primary immunodeficiencies and autoimmune disorders. The development of an international registry for such patients is imperative to improve the understanding of their complex natural history., (© 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.)

Adolescents with haemophilia must assume responsibility for their health and management of their disease. An online self-management program was developed to support adolescents during this transition. To determine the feasibility of the program using a randomized control trial (RCT) design in terms of accrual/attrition rates, willingness to be randomized, compliance with the program/outcome measures and satisfaction. Adolescents, ages 13-18, were enrolled in a pilot RCT (NCT01477437) and randomized to either the intervention (8-week program with telephone coaching) or the control arm (no access to the website, weekly telephone call as attention-strategy). All participants completed pre/post-outcome measures. Twenty-nine teens participated (intervention n = 16, control n = 13). Participants in the intervention arm spent an average of 50 min on the website per week and completed the modules in an average of 14 weeks (SD = 4.9). Attrition was higher in the control group compared to the intervention group (54% vs. 25%). 17/18 (94%) who completed the program also completed the poststudy measures. Teens on the intervention arm showed significant improvement in disease-specific knowledge (P = 0.004), self-efficacy (P = 0.007) and transition preparedness (P = 0.046). There was a statistically significant improvement in knowledge in the intervention group when compared to the control group (P = 0.01). Overall, the teens found the website to be informative, comprehensive and easy to use and were satisfied with the program. This pilot RCT study suggests benefit to the program and indicates an RCT design to be feasible with minor adjustments to the protocol., (© 2014 John Wiley & Sons Ltd.)

This study aimed to examine the treatment decision-making process for children hospitalized with newly diagnosed immune thrombocytopenia (ITP). Using focus groups, we studied children with ITP, parents of children with ITP, and health care professionals, inquiring about participants' experience with decision support and decision making in newly diagnosed ITP. Data were examined using thematic analysis. Themes that emerged from children were feelings of "anxiety, fear, and confusion"; the need to "understand information"; and "treatment choice," the experience of which was age dependent. For parents, "anxiety, fear, and confusion" was a dominant theme; "treatment choice" revealed that participants felt directed toward intravenous immune globulin (IVIG) for initial treatment. For health care professionals, "comfort level" highlighted factors contributing to professionals' comfort with offering options; "assumptions" were made about parental desire for participation in shared decision making (SDM) and parental acceptance of treatment options; "providing information" was informative regarding modes of facilitating SDM; and "treatment choice" revealed a discrepancy between current practice (directed toward IVIG) and the ideal of SDM. At our center, families of children with newly diagnosed ITP are not experiencing SDM. Our findings support the implementation of SDM to facilitate patient-centered care for the management of pediatric ITP.

Factor XIII (FXIII) deficiency is a rare congenital bleeding disorder estimated to affect 1 in 2 million live births. Treatment often involves prophylaxis with FXIII concentrate and is especially important in preventing intracranial hemorrhage (ICH) and maintaining pregnancy in women of childbearing age. The rarity of this condition and lack of good quality evidence has resulted in a literature largely based on case reports/case series. A review of the literature was conducted in order to provide information about the optimal management of FXIII deficiency. Articles were identified by searching MEDLINE from 1961 to June 2012. Eligible studies included details on patients with FXIII deficiency that received treatment. Information collected included dose, frequency, duration, hemostatic efficacy and adverse events. Of 606 abstracts reviewed, 43 articles, including a total of 328 patients met the selection criteria. Common bleeding manifestations included umbilical cord bleeding, ICH and hematomas. Patients were generally placed on prophylactic factor replacement therapy upon diagnosis of severe or symptomatic FXIII deficiency, which decreased and/or prevented bleeding episodes. Patients with FXIII deficiency that received prophylactic treatment successfully maintained pregnancies. Alternative treatments included the use of cryoprecipitate or frozen plasma when FXIII concentrate was not available or affordable. Recent studies of a new recombinant FXIII concentrate show promising results in regards to safety and efficacy. There are limited data to guide the optimal treatment of FXIII deficiency. Larger patient registries and international collaborations are needed to improve the evidence and enhance clinical outcomes in this rare bleeding disorder.

Background: As adolescents with hemophilia approach adulthood, they are expected to assume responsibility for their disease management. A bilingual (English and French) Internet-based self-management program, "Teens Taking Charge: Managing Hemophilia Online," was developed to support adolescents with hemophilia in this transition. This study explored the usability of the website and resulted in refinement of the prototype., Methods: A purposive sample (n=18; age 13-18; mean age 15.5 years) was recruited from two tertiary care centers to assess the usability of the program in English and French. Qualitative observations using a "think aloud" usability testing method and semi-structured interviews were conducted in four iterative cycles, with changes to the prototype made as necessary following each cycle. This study was approved by research ethics boards at each site., Results: Teens responded positively to the content and appearance of the website and felt that it was easy to navigate and understand. The multimedia components (videos, animations, quizzes) were felt to enrich the experience. Changes to the presentation of content and the website user-interface were made after the first, second and third cycles of testing in English. Cycle four did not result in any further changes., Conclusions: Overall, teens found the website to be easy to use. Usability testing identified end-user concerns that informed improvements to the program. Usability testing is a crucial step in the development of Internet-based self-management programs to ensure information is delivered in a manner that is accessible and understood by users.

Youth frequently access health information online, yet little is known about internet use among adolescents with haemophilia (AWH). A youth-centred, age-appropriate online programme is being developed to address the heightened educational needs of AWH as they transit from paediatric to adult care. To describe internet needs and use among AWH treated at the Hospital for Sick Children and determine the features that would make the website useable and desirable for this population. Semi-structured interviews addressed participants' internet use and thoughts about a website for AWH. The interviews were audio-recorded and transcribed verbatim. Three independent reviewers coded the data to determine descriptive categories and grouped them into themes. Eleven of 12 subjects approached consented to interviews. Data saturation was achieved. Most participants had used the internet to find haemophilia information, although none could recall specific websites they had visited for information. Some felt more comfortable using the internet than asking health care providers. Others liked the 24/7 availability of the internet if questions arose. Overall, they felt a website for AWH would help them to learn about haemophilia and explain it to others. Online social networking with an older peer mentor with haemophilia, as well as with others of their age was cited as a potentially valuable source of support. AWH are interested in a haemophilia website and have identified a variety of features which they believe may help to support them during transition to adult care and beyond. Website development is ongoing., (© 2011 Blackwell Publishing Ltd.)

Childhood immune thrombocytopenia (ITP) is generally a benign self-limiting disorder of young children with <10% of cases requiring regular platelet enhancing therapy at 1 year following diagnosis. Increasingly, children with newly diagnosed ITP, who have isolated thrombocytopenia and no atypical features in the history or physical examination, are managed with minimal investigation and observation alone. The role of up-front, short-course corticosteroid therapy without bone marrow aspiration in this subgroup of cases merits further investigation. For children with clinically significant chronic ITP, the timing of elective splenectomy and the role of splenectomy-sparing strategies such as rituximab continues to be debated. Management of children with combined autoimmune cytopenias secondary to systemic lupus erythematosus, common variable immunodeficiency, and the autoimmune lymphoproliferative syndrome is often a challenge. Splenectomy should be avoided in cases with documented immunodeficiencies because of the increased risk of overwhelming sepsis postsplenectomy. For these cases, as well as for children with resistant primary chronic ITP who have failed splenectomy, the role of therapies such as mycophenolate mofetil, sirolimus, and the thrombopoietins remains to be determined., (© Thieme Medical Publishers.)

Background: On July 1, 2009, in Ontario the maximum period of continuous duty that residents were permitted to work was reduced from 28 to 24 hours. We evaluated the effect of regulation on residents in 3 eras: 2 before (2005 and early 2009) and 1 after (late 2009) the duty-hour reduction., Methods: On-call pediatric residents on pediatric medicine rotations prospectively recorded the numbers of patients (assigned and admitted) and the durations of direct patient care, documentation, staff supervision, and education attended. Sleep was measured with actigraphy., Results: The 51 residents worked 180 duty periods, were assigned a median of 6 (interquartile range: 4 -12) daytime patients and 24 (interquartile range: 19-30) overnight patients. Residents reported spending means of 239 minutes providing direct patient care, 235 minutes documenting, and 243 minutes sleeping and receiving 73 minutes of staff supervision and 52 minutes of education. From early 2009 to after duty-hour reduction, residents provided 47 fewer (19.6%) minutes of direct patient care (P = .056) and received 44 fewer minutes (60.3%) of supervision (P = .0005) but spent similar times documenting, receiving education, and sleeping. In early 2009, residents provided 73 more minutes (30.5%) of direct patient care (P = .0016), spent 63 more minutes (26.8%) documenting, and slept 105 fewer minutes (43.0%) (P = .0062) than in 2005., Discussion: After duty-hour reduction in 2009, we found reduced supervision and direct patient care. Comparison of the 2 periods before duty-hour reduction showed less sleep and longer patient contact in early 2009, which suggests that changes occurred without regulation.

In the last two decades, the transition from paediatric to adult care has received increasing attention. Health care professionals have become more aware of the unique needs of adolescents and young adults with chronic illnesses and efforts have been made to support youth through this challenging time of change. For patients with haemophilia and their families, there is little evidence regarding best practice for transition of care. We reviewed the transition literature and current guidelines for transition for patients with haemophilia. We advocate that comprehensive haemophilia care includes a conscientious approach to transition of care that should start in early adolescence and be developmentally sensitive. In considering the needs of patients and parents, we must engage both paediatric and adult health care providers to make the transfer smooth and ensure the best care possible during this time., (© 2010 Blackwell Publishing Ltd.)

Hepatitis-associated aplastic anemia is a well-described entity after idiopathic fulminant hepatic failure. The hematologic disease ranges from mild-to-severe aplastic anemia and the cause of the disease is unknown. We describe 2 siblings with bone marrow failure. The older child presented with idiopathic fulminant hepatic failure and an early onset of rapidly progressive severe aplastic anemia that developed into myelodysplastic syndrome postliver transplantation. In the process of family screening to locate a donor for hematopoietic stem cell transplantation, the younger sibling was found to have hypocellular bone marrow and later developed acute lymphoblastic leukemia. These familial cases raise the possibility of an inherited bone marrow failure syndrome and suggest that severe hepatitis-associated aplastic anemia may not be always an acquired condition.

We report the clinical course of a child with precursor B-cell acute lymphoblastic leukemia who developed fever, hepatosplenomegaly, and refractory thrombocytopenia after initiation of chemotherapy. Bone marrow aspiration on Day 8 of induction showed new onset of hemophagocytosis and he met clinical, laboratory, and histopathologic criteria for hemophagocytic lymphohistiocytosis. His symptoms improved significantly after an increased dosage of steroids.