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The article offers information on clinical trial conducted to evaluate occurrence of silent cerebral infarcts, neurologic injury, in children suffering from sickle cell anemia. It states that trial was conducted on children with age of five to 10 years who were divided into groups where one group received treatment with regular blood transfusions and other received standard care. It concludes that group with regular blood transfusions indicated less cerebral infarct as compared to other group.

Allogeneic hematopoietic stem cell transplantation is challenging for patients with transfusion-dependent thalassemia who have experienced iron overload and received chronic transfusion support. A transplantation strategy including a reduced-intensity preparative regimen and tailored immunosuppression to support donor engraftment and prevent graft-versus-host disease (GVHD) was developed for this population. The combination of a pretransplantation immunosuppression phase with reduced dosing of fludarabine/prednisone, a treosulfan-based preparative regimen with reduced cyclophosphamide dosing, and introduction of a calcineurin/methotrexate-free GVHD prophylaxis/engraftment supporting regimen with abatacept/sirolimus/antithymocyte globulin was tested. In the ThalFAbS trial, a prospective pilot trial (ClinicalTrials.gov NCT05426252) of a transplantation strategy designed for higher-risk patients with transfusion-dependent thalassemia, 12 pediatric patients (4 with alpha thalassemia, 8 with beta thalassemia) were treated with this strategy. Descriptive statistics were used to characterize transplantation outcomes and immune recovery. With a median follow-up of 12 months (range, 4 to 26 months) post-transplantation, all 12 patients had prompt and durable trilineage donor engraftment with low transplantation-related morbidity and acute GVHD and are alive without transfusion support at the time of this report. GVHD was limited to 1 patient with skin-only grade II acute GVHD and 3 patients with limited oral chronic GVHD. Early hematologic and immunologic recovery was achieved, with low rates of transfusion support and infection. Neutrophil recovery occurred at a median of 18 days (range, 15 to 24 days), and platelet recovery occurred at a median of 18 days (range, 12 to 36 days). No patients experienced veno-occlusive disease, transplantation-associated thrombotic microangiopathy, or sepsis. This platform was sufficient to support haploidentical donor transplantation in 2 patients. The ThalFAbS approach is tailored to meet the unique needs of transfusion-dependent thalassemia patients. Delivery of this novel regimen is feasible, and it shows excellent early engraftment and transplantation outcomes. Further follow-up of this cohort and expansion of patient numbers is needed before the findings can be generalized, but early experience is promising., (Copyright © 2024 The American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc. All rights reserved.)

Background and Objectives: Sickle cell disease (SCD) is hallmarked by recurrent episodes of severe acute pain and the risk for chronic pain. Remote peer support programs have been shown to effectively improve health outcomes for many chronic conditions. The objective of this study was to examine the feasibility and acceptability of an online peer mentoring program (iPeer2Peer program) for adolescents with SCD., Method: A waitlist pilot randomized controlled trial was conducted. Adolescents randomized to the intervention group were matched with trained peer mentors (19-25 years; successfully managing their SCD), consisting of up to 10 sessions of approximately 30-min video calls over a 15-week period. The control group received standard care. The primary outcomes were rates of accrual, withdrawal, and adherence to iP2P program/protocol, with secondary outcomes identifying topics of mentorship-mentee conversations through qualitative analysis., Results: Twenty-eight participants (14 intervention; 14 control) were randomized to the study (mean age: 14.8 ± 1.7 years; 57% female). Accrual rate was 80% (28/35) and withdrawal rate was 18% (5/28), with 28% (4/14) adhering to the iP2P program; however, 71% (10/14) of adolescents in the intervention completed at least one call. Based on content analysis of 75 mentor-mentee calls, three distinct content categories emerged: impact of SCD, self-management, transitioning to adulthood with SCD, and general topics., Conclusion: The results from this pilot study suggest that the current iteration of the iP2P SCD program lacks feasibility. Future research with the iP2P program can focus improved engagement via personalized mentoring, variable communication avenues, and an emphasis on gender., Competing Interests: The authors declare that there is no conflict of interest., (© The Author(s) 2025.)

The Kids' ITP Tools (KIT) is a questionnaire to assess quality of life of children with immune thrombocytopenia (ITP). The aim of this study was to update this previously validated tool to align with changes in clinical practice, specifically, treatment with thrombopoietin receptor agonists (TPO-RAs). Children aged 1-18 with ITP and/or their families were recruited to participate in interviews to review the KIT. Twenty-six interviews were conducted. Based on interview data from children and families, current guidelines, and expert opinion, five changes were made to the KIT in order to improve its face validity., (© 2024 Wiley Periodicals LLC.)

Current recommendations advise against blood transfusion in hemodynamically stable children with iron deficiency anemia. In an observational study of 125 children aged 6 through 36 months, hospitalized with iron deficiency anemia, we found that hemoglobin level predicted red blood cell transfusion (area under the curve 0.8862). A hemoglobin of 39 g/L had sensitivity 92% and specificity 72% for transfusion., Competing Interests: Declaration of Competing Interest Supported by The Hospital for Sick Children Foundation (SP05-602 Pediatric Outcomes Research Team to PCP). The funder had no role in the design and conduct of this work; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the article; nor the decision to submit the article for publication. The authors declare no conflicts of interest., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Current guidelines recommend a preoperative hemoglobin of 10.0 g/dL in patients with sickle cell disease [SCD], however, this threshold continues to be an area of controversy. Previous studies demonstrating the benefits of preoperative transfusions have largely not captured patients with elevated baseline hemoglobin, in part due to low hydroxyurea uptake and exclusion of nonhemoglobin SS SCD., Materials and Methods: We conducted a retrospective chart review of patients with SCD <18 years of age undergoing low and medium-risk procedures at 2 academic medical centers in Canada between 2007 and 2017. The primary objective was to study the association of preoperative transfusion on postoperative complications in patients with SCD with baseline hemoglobin between 9.0 and 10.0 g/dL. Multivariable logistic regression was used to estimate the adjusted effect of preoperative transfusion on the risk of developing postoperative complications., Results: In all, 159 procedures in patients with hemoglobin <9.0 g/dL [Hb <9.0 ] and 173 procedures in patients with hemoglobin between 9.0 and 10.0 g/dL [Hb 9.0-10.0 ] were analyzed. In the absence of preoperative transfusion, Hb 9.0-10.0 patients had lower overall complications [23% vs. 34%] compared with Hb <9.0 patients [OR 0.29, 95% CI 0.12-0.72, P =0.008]. In total, 75% of Hb <9.0 and 21% of Hb 9.0-10.0 patients received a preoperative simple transfusion. Transfusion was associated with increased risk of postoperative complications in Hb 9.0-10.0 [OR 3.02, 95% CI 1.26-7.23, P =0.013], but not Hb <9.0 patients [OR 0.64, 95% CI 0.28-1.45, P =0.30]., Conclusions: Simple transfusion may not be warranted in Hb 9.0-10.0 patients undergoing low-risk procedures. Prospective studies validating these findings are needed., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Thrombopoietin receptor agonists (TPO-RAs) have emerged as a recommended treatment for children with persistent and/or chronic immune thrombocytopenic purpura (ITP). The purpose of this study was to evaluate the cost-effectiveness of TPO-RAs relative to treatment without TPO-RAs (non-TPO-RAs/usual care) for ITP in children who do not respond to first-line therapy and in whom splenectomy is not recommended in Ontario, Canada, from a hospital payer perspective., Procedure: A 2-year Markov model with an embedded decision tree was used. Data on medications used, dose, response rate, bleeding, and emergency treatment events were collected from the Hospital for Sick Children in Toronto. The health outcomes were described in quality-adjusted life-years (QALYs). Health-state utilities were derived from the peer-reviewed literature. Scenario analyses, deterministic, and probabilistic sensitivity analyses were conducted. Economic costs were measured in 2021 Canadian dollars ($1.00 = US$0.80) RESULTS: TPO-RAs are estimated to result in an increased cost of $27,118 and a QALY gain of 0.21 compared to non-TPO-RAs over a 2-year horizon, resulting in an incremental cost-effectiveness ratio (ICER) of $129,133. In a 5-year scenario analysis, the ICER fell to $76,403. In the probabilistic sensitivity analysis, TPO-RAs exhibit a 40.0% probability of being cost-effective at a conventional ($100,000) willingness-to-pay threshold per QALY gained., Conclusions: Further assessment of the long-term efficacy of TPO-RAs is warranted to obtain more precise long-term estimates. As the costs of TPO-RAs decline with the introduction of generic formulations, TPO-RAs may be increasingly cost-effective., (© 2023 Wiley Periodicals LLC.)

Over the last decade, treatment of immune thrombocytopenia (ITP) in children has advanced to include thrombopoietin receptor agonist (TPO-RA) medications. Concurrently, there has been an increased emphasis on patient-reported outcomes-especially quality of life-to guide treatment. Assessing the impact of TPO-RAs on quality of life in paediatric ITP is therefore a priority. In this single-centre integrative mixed-methods study, a cohort of children with ITP prescribed a TPO-RA was identified. These children and/or their caregivers were invited to participate in semi-structured interviews focussed on quality-of-life measures. Independently, a retrospective chart review collected ITP-related data (platelet count, bleeding events) and TPO-RA data (dosing, side effects). Among the 23 eligible patients, 20 were represented in interviews. On chart review, 11/20 patients responded to TPO-RA by meeting platelet count criteria of ≥50 × 10 9 /L for six or more weeks in the absence of rescue therapy. In interviews with these children and/or their parents, 19/20 expressed the TPO-RA had 'worked', with 11/20 reporting benefit to mood and 11/20 reporting increased participation in activities/sports. Concerns were raised in interviews about TPO-RA medication cost (17/20), medication administration (10/20) and potential side effects (10/20). In conclusion, this study suggests that TPO-RA use in children with ITP improves quality of life., (© 2022 British Society for Haematology and John Wiley & Sons Ltd.)

Background: Despite the availability of conjugate pneumococcal vaccines, children with high-risk conditions remain vulnerable to invasive pneumococcal disease (IPD). This study sought to describe IPD prevalence, vaccination and outcomes among high-risk children., Methods: We used International Classification of Disease10 discharge and microbiology codes to identify patients hospitalized for IPD at a large pediatric hospital from January 1, 2009, to December 31, 2018. Patients were considered high-risk if they had: primary immunodeficiency, asplenia, transplant, active malignancy, sickle cell disease, cochlear implant, nephrotic syndrome, chronic lung disease, cerebrospinal fluid leak, HIV or used immunosuppressive therapy., Results: In total 94 high-risk patients were hospitalized for IPD. The most common high-risk conditions included malignancy (n = 33, 35%), solid-organ or bone marrow transplant (n = 17, 18%) and sickle cell disease (n = 14, 15%). Bacteremia was the most common presentation (n = 81, 86%) followed by pneumonia (n = 23, 25%) and meningitis (n = 9, 10%). No deaths occurred. Of 66 patients with known pneumococcal vaccination status, 15 (23%) were unvaccinated, and 51 (77%) received at least one dose of a pneumococcal vaccine; 20 received all four recommended pneumococcal conjugate vaccine (PCV) doses. Only three children received PPSV23. Of 20 children with no or partial (<3 doses) immunization, 70% (14) of IPD episodes were due to vaccine-preventable serotypes. Of 66 known IPD serotypes, 17% (n = 11) were covered by PCV13, 39% (n = 26) were covered by PPSV23 and 39% (n = 26) were nonvaccine serotype., Conclusions: Despite the availability of effective pneumococcal vaccines, IPD persists among children with high-risk conditions. Improving PCV13 and PPSV23 vaccination could significantly reduce IPD; most episodes were due to vaccine-preventable serotypes in incompletely immunized patients., Competing Interests: S.M. is the co-PI on an investigator led grant from Pfizer, has served on ad hoc advisory groups with Pfizer and Sanofi Pasteur, has received speaker fees from GSK as well as funding for an unrestricted education event, and speaker fees from Johnson and Johnson China, all of which are unrelated to the topic of this paper. A.M. has funding for investigator-initiated grants from Pfizer and Merck and has received honoraria for participation on advisory boards from Pfizer, Merck, and GSK, all of which were unrelated to this study. The other authors have no conflicts of interest to disclose., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Owing to the unique pathophysiology of anaemia in haemoglobin Bart's hydrops fetalis (HBHF), a transfusion strategy based on beta-thalassemia guidelines is suboptimal for chronically transfused HBHF patients. A more aggressive transfusion aimed at reducing the proportion of non-functional HbH and improving the "functional" haemoglobin (f-Hb) can lead to reduced haemolysis and improved tissue oxygenation. However, the optimal transfusion targets for these parameters are not yet defined. In this retrospective, longitudinal study on four chronically transfused patients with HBHF, we used receiver operating characteristic curves to find a pre-transfusion f-Hb of 106 g/l and a HbH of 16.1% to be the optimal thresholds to achieve a normal soluble transferrin receptor and lactate dehydrogenase, respectively., (© 2022 British Society for Haematology and John Wiley & Sons Ltd.)

Poor access to care is a top patient-oriented research priority for youth with chronic pain in Canada, and the COVID-19 pandemic has exacerbated these concerns. Our patient-oriented project team engaged with marginalized and racialized youth with chronic pain (Black youth with sickle cell disease, Indigenous youth and youth with complex medical needs) and their families to ensure that best practice recommendations for virtual care are inclusive and equitable. Input provided through virtual round-table discussions improved recommendations for leveraging, implementing and selecting best platforms for virtual care for youth with chronic pain and identified new gaps for future research, practice and policy change., (Copyright © 2022 Longwoods Publishing.)

L'anémie falciforme est une maladie multisystémique chronique qui exige des soins globaux. La falciformation des globules rouges entraîne une hémolyse et une occlusion vasculaire. L'anémie hémolytique, les syndromes douloureux et les atteintes organiques en sont des complications. En raison des profils d'immigration et d'une augmentation du dépistage néonatal, les professionnels de la santé pédiatrique du Canada doivent connaître l'anémie falciforme, tant dans les petits que les grands centres. Le présent document de principes porte sur les principes de prévention, de défense d'intérêts et de traitement rapide des complications aiguës courantes de l'anémie falciforme. Les lignes directrices comprennent l'état actuel du dépistage néonatal, les recommandations en matière de vaccination et de prophylaxie antibiotique et une introduction à l'hydroxyurée, un médicament qui réduit à la fois la morbidité et la mortalité chez les enfants atteints d'anémie falciforme. Des scénarios cliniques démontrent les principes de soins en cas de complications aiguës courantes : les épisodes vaso-occlusifs, le syndrome thoracique aigu, la fièvre, la séquestration splénique, les crises aplasiques et les accidents vasculaires cérébraux. Enfin, les principes de transfusion sanguine sont présentés, de même que les indications de transfusion simple ou d'exsanguinotransfusion., (© Société canadienne de pédiatrie 2022. Publié par Oxford University Press pour le compte de la Société canadienne de pédiatrie. Tous droits réservés. Pour obtenir une autorisation, écrivez à journals.permissions@oup.com.)

Sickle cell disease (SCD) is a chronic, multi-system disease that requires comprehensive care. The sickling of red blood cells leads to hemolysis and vascular occlusion. Complications include hemolytic anemia, pain syndromes, and organ damage. Patterns of immigration and an increase in newborn screening mean that paediatric health care providers across Canada, in small and large centres alike, need to be knowledgeable about SCD. This statement focuses on principles of prevention, advocacy, and the rapid treatment of common acute complications. Guidance includes the current status of newborn screening, recommendations for immunizations and antibiotic prophylaxis, and an introduction to hydroxyurea, a medication that reduces both morbidity and mortality in children with SCD. Case vignettes demonstrate principles of care for common acute complications of SCD: vaso-occlusive episodes (VOE), acute chest syndrome (ACS), fever, splenic sequestration, aplastic crises, and stroke. Finally, principles of blood transfusion are highlighted, along with indications for both straight and exchange blood transfusions., (© Canadian Paediatric Society 2022. Published by Oxford University Press on behalf of the Canadian Paediatric Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Sickle cell disease (SCD) has a significant psychosocial impact on affected children. Summer camp has been shown to improve psychological and physical states for children with diabetes and cancer. However, opportunities to attend camp for children with SCD are limited, as many are from low-income families, and many camps are not equipped to care for children with medical complexities. To our knowledge, no literature evaluates how camp can positively affect emotional functioning, social functioning, self-esteem, and physical activity levels in children with SCD. Methods: Children with SCD attending a residential summer camp during 2019 were identified. Participants completed a modified version of the Pediatric Camp Outcome Measure, a validated 29-item questionnaire that evaluates self-esteem, emotional function, social function, and physical activity. Four additional questions related to SCD were included. Results: Nine campers enrolled in the study. Questionnaire results showed a total score of 113.7 (maximum score135, range 84-129), with a self-esteem subscale score of 22.1 (maximum score 25, range 20-25), an emotional subscale score of 32.1 (maximum score 40, range 25-39), a social subscale score of 38.9 (maximum score 45, range 24-45), and a physical activity subscale score of 20.6 (maximum score 25, range 19-25). All campers indicated that they would return to camp. Conclusion: Attending summer camp has a beneficial impact on emotional function, social function, self-esteem, and physical activity. Mean questionnaire scores from children with cardiac disease and cancer are similar to those of children with SCD. Increased funding should be awarded to sickle cell camps to allow for more children to have this beneficial experience., (©2021 by the author(s); Creative Commons Attribution License (CC BY).)

Purpose: To compare ultra-wide-field colour fundus imaging (UWFI) to dilated fundus examination (DFE) for the screening of sickle cell retinopathy (SCR)., Design: This study is a prospective, blinded, multicentre case series., Participants: This study included two groups: an adult group (n=268 eyes) and a paediatric group (n=168 eyes). Sickle cell disease (SCD) types included haemoglobin S homozygous (HbSS), haemoglobin S and C (HbSC) and Hb S with β-thalassaemia (HbSß-Thal)., Methods: Participants underwent DFE and UWFI. Each eye received three independent grades (1-4), documented by three graders: clinical grader, image grader 1 and image grader 2. Three clinically relevant diagnostic thresholds were determined. Based on these thresholds, the sensitivity, specificity, positive predictive value and negative predictive value for all three graders were calculated relative to each other as reference tests., Results: HbSC was associated with the most advanced SCR grades. When compared to the clinical grader, image grader 1 and image grader 2 consistently detected more SCR and higher SCR grades in both adult and paediatric groups. In both groups, image grader 1 and image grader 2 identified twice as many cases of capillary occlusion/anastomosis than clinical grader. To detect the presence of any proliferative SCR, image grader 1 and image grader 2 had a sensitivity of 82%, 71% in the paediatrics group and 90% and 72% in the adult group. The clinical grader sensitivity was 52% in the paediatrics group and 53% in the adult group., Conclusion: The UWFI is a sensitive tool to screen for SCR. It is superior to DFE in detecting capillary occlusion or anastomosis., Competing Interests: Competing interests: The fundus camera (Optos—Daytona) that was used in the paediatric group of this study was provided on loan from Optos to conduct this research. Authors have no other relevant financial disclosures to this project., (© Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

Objectives: With improved access to intrauterine transfusion (IUT), more fetuses with haemoglobin Bart's hydrops fetalis (HBHF; homozygous α 0 -thalassaemia) will survive., Design: To evaluate the long-term outcome of affected fetuses with and without IUT in Ontario, Canada, we retrospectively collected data on IUTs and pregnancy outcomes in all cases of HBHF, from 1989 to 2014. Clinical outcome and neurocognitive profiles of long-term survivors were also collected and compared with data from 24 patients with transfusion-dependent β-thalassaemia (TDT-β)., Results: Of the 99 affected pregnancies (93 prenatally diagnosed), 68 resulted in miscarriage or elective termination of pregnancy. Twelve mothers (12%) continued their pregnancies without IUT, and none of those newborns survived the first week of life. All 13 fetuses that received IUT(s) were live-born, but 3 died due to severe hydrops at birth and 1 died due to infection. The remaining nine survivors, in comparison with TDT-β patients, had earlier iron overload requiring iron chelation therapy. Endocrinopathies and short stature were more frequent in these patients. Neurocognitive outcome was not significantly affected in five patients who were assessed, and none were diagnosed with intellectual impairment. In three patients, MRI studies demonstrated brain white matter changes in keeping with 'silent' ischaemic infarcts., Conclusions: In patients with HBHF, IUT is associated with improved survival. While acceptable neurocognitive outcome can be expected, these patients have more clinical complications compared with their TDT-β counterparts. The clinical and neurocognitive outcomes of HBHF should be discussed in detail when counselling and offering IUT for patients., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

Hereditary spherocytosis (HS) is a common inherited haemolytic anaemia attributed to disturbances in five different red cell membrane proteins. We performed a retrospective study of 166 children with HS and describe the clinical phenotype according to the genotype. In 160/166 (97%) children with HS a disease-causing mutation was identified. Pathogenic variants in ANK1, SPTB, SLC4A1 and SPTA1 were found in 49%, 33%, 13% and 5% of patients. Children with SLC4A1-HS had the mildest phenotype, showing the highest haemoglobin (P < 0·001), lowest reticulocyte counts (P < 0·001) and lowest unconjugated bilirubin levels (P = 0·006), and none required splenectomy in childhood (P < 0·001). Conversely, children with autosomal recessive SPTA1-HS had the most severe clinical phenotype, with almost all patients undergoing splenectomy in early childhood. Patients with ANK1 and SPTB variants showed a similar clinical phenotype. Within each gene, variant type or location did not predict disease severity or likelihood of splenectomy. Among patients with a genetic diagnosis, 47 (29%) underwent splenectomy (23 partial; 24 total) while 57 (36%) underwent cholecystectomy. Total splenectomy led to greater improvements in haemoglobin (P = 0·02). Select use of genetic testing (especially in patients without a family history) may help predict clinical phenotype in childhood and guide family counselling., (© 2020 British Society for Haematology and John Wiley & Sons Ltd.)

Hepatoblastoma is the most common hepatic malignancy of childhood with known genetic predispositions and perinatal risk factors, with rare case reports occurring in the setting of cirrhosis. This case describes a young patient with cirrhosis attributed to early-onset hereditary hemochromatosis who was diagnosed with hepatoblastoma with uncommon histologic findings, evidence of chemotherapy resistance who ultimately succumbed to her disease. It is important to consider diagnoses beyond hepatocellular carcinoma in this scenario and consider early biopsy. With atypical histology, the tumor may respond poorly to conventional treatment and aggressive surgery or intensive therapy should be contemplated.

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.)

A 19-month-old girl with a history of asthma and atopic dermatitis presented to her pediatrician because of parental concerns of pallor and fatigue. On dietary history, it was discovered that she was a picky eater and consumed 26 oz of homogenous milk daily. Her physical examination was unremarkable aside from pallor, and both her height and weight plotted between the 50th and 75th percentile for age. Therefore, she was investigated for iron deficiency anemia and indeed her blood work was consistent. Despite appropriate iron supplementation and dietary milk restriction, there was no improvement in her hemoglobin or iron studies. Our expert panel examines the case and offers a differential diagnosis for a child presenting with treatment-resistant iron deficiency anemia., Competing Interests: POTENTIAL CONFLICT OF INTEREST: The authors have indicated they have no potential conflicts of interest to disclose., (Copyright © 2018 by the American Academy of Pediatrics.)

Secondary failure of platelet engraftment occurs in 20% of patients undergoing allogeneic HSCT and is associated with poor outcome. Currently, there are no guidelines for treatment of late thrombocytopenia and platelet transfusion is the mainstay of treatment. Here, we describe the use of Eltrombopag to treat secondary failure of platelet recovery following HSCT in a child with severe aplastic anemia. Eltrombopag resulted in recovery of platelet count with no need for platelet transfusion support with no reported side effects. Eltrombopag may be used successfully in children with secondary failure of platelet recovery post-HSCT for SAA., (© 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Deferasirox is an oral iron chelator used to treat patients with transfusion-related iron overload. We report, from two institutions, two children with Diamond-Blackfan anemia who developed Fanconi syndrome secondary to deferasirox administration, along with a review of the literature. The current recommendation for the laboratory monitoring of patients receiving deferasirox does not include serum electrolytes or urine analysis. Thus, despite routine clinic visits and bloodwork, these two patients presented with life-threatening electrolyte abnormalities requiring hospitalization. Hence, we propose the inclusion of serum electrolytes and urine analysis as part of routine monitoring to facilitate the early diagnosis of Fanconi syndrome in the context of high doses of deferasirox therapy., (© 2016 Wiley Periodicals, Inc.)

Rationale: Obstructive sleep apnea and intermittent nocturnal oxygen desaturations are highly prevalent in children with sickle cell disease and have been reported to contribute to associated morbidity, including vasoocclusive disease. Hydroxyurea (HU) is increasingly used to treat children with sickle cell disease and has been shown to decrease the number and severity of vasoocclusive crises. Although there has been an increase in the use of HU, the impact of HU on the prevalence of obstructive sleep apnea and nocturnal hypoxia are not well documented., Objectives: To evaluate whether the use of HU is associated with a decreased frequency of obstructive sleep apnea and higher nocturnal and awake oxygen saturations (SaO2) in children with sickle cell disease., Methods: This was a retrospective, cross-sectional review of children with sickle cell disease referred to the sleep laboratory at the Hospital for Sick Children, Toronto, Canada. Polysomnogram data in children with sickle cell disease receiving HU therapy were compared with those not prescribed HU., Measurements and Main Results: Children with sickle cell disease receiving HU therapy (HU group, n = 37) were matched with children not receiving HU (no-HU group, n = 104). Obstructive sleep apnea was diagnosed in 14 of 37 (38%) and 54 of 104 (52%) in the HU group and no-HU groups, respectively (P = 0.14). The median obstructive apnea-hypopnea index was 0.9 and 1.9 events/h in the HU group and the no-HU group, respectively (P = 0.28). The HU group compared with the no-HU group had a significantly higher median awake SaO2 (98.6 and 96.2%, respectively; P < 0.0001), a significantly higher median sleep SaO2 (98.4 and 96.1%, respectively; P < 0.001), and a significantly higher nadir SaO2 while asleep (91.4 and 85.0%, respectively; P = 0.0002)., Conclusions: In children with sickle cell disease, the use of HU was associated with an increase in awake and nocturnal SaO2, despite there being no difference in the frequency of obstructive sleep apnea and the severity of the obstructive apnea-hypopnea index. Improving nocturnal SaO2 may be an important mechanism of action of HU therapy. The use of HU to improve nocturnal saturations across the severity spectrum of sickle cell disease may be beneficial in decreasing morbidities related to sickle cell disease.

Differentiating between β-thalassemia (β-thal) minor and iron deficiency has important implications in thalassemia carrier screening. Several complete blood count (CBC)-based equations have been proposed for differentiating these two conditions. The applicability of these equations in populations with high rates of iron deficiency and β-thal minor, where patients can have both conditions, is limited. In addition, there have been conflicting reports on the possible effect of iron deficiency on Hb A2 level with possible consequences for thalassemia screening programs. Here, we demonstrate that in our population the Mentzer Index separates individuals with β-thal minor from those without β-thal minor, regardless of their iron status. Iron deficiency also does not reduce Hb A2 levels in β-thal minor patients. Correction of iron deficiency is not required for diagnosis of β-thal minor using high performance liquid chromatography (HPLC).

Over the past 50 years, survival for children in high-income countries has increased from 30% to over 80%, compared to 10-30% in low and middle income countries (LMIC). Given this gap in survival, established paediatric cancer treatment centres, such as The Hospital for Sick Children (SickKids) are well positioned to share clinical expertise. Through the SickKids Centre for Global Child Health, the SickKids-Caribbean Initiative (SCI) was launched in March 2013 to improve the outcomes and quality of life for children with cancer and blood disorders in the Caribbean. The six participating Caribbean countries are among those defined by the United Nations as Small Island Developing States, due to their small size, remote location and limited accessibility. Telemedicine presents an opportunity to increase their accessibility to health care services and has been used by SCI to facilitate two series of interprofessional rounds. Case Consultation Review Rounds are a forum for learning about diagnostic work-up, management challenges and treatment recommendations for these diseases. To date, 54 cases have been reviewed by SickKids staff, of which 35 have been presented in monthly rounds. Patient Care Education Rounds provide nurses and other staff with the knowledge base needed to safely care for children and adolescents receiving treatment. Five of these rounds have taken place to date, with over 200 attendees. Utilized by SCI for both clinical and non-clinical meetings, telemedicine has enhanced opportunities for collaboration within the Caribbean region. By building capacity and nurturing expert knowledge through education, SCI hopes to contribute to closing the gap in childhood survival between high and low-resource settings.

Objectives: To describe a case of ceftriaxone-induced immune hemolytic anemia (CIIHA) in a 6 year-old boy with sickle cell disease (SCD) and perform a systematic literature review to delineate the clinical and laboratory features of this condition., Data Sources: EMBASE (1947-January 2014), MEDLINE (1946-January 2014), and databases from the US Food and Drug Administration and Health Canada were searched, using anemia, hemolytic anemia, hemolysis, and ceftriaxone as search terms. Additional references were identified from a review of literature citations., Study Selection and Data Extraction: All case reports and observational studies describing clinical and laboratory features of CIIHA were included., Data Synthesis: A total of 37 eligible reports of CIIHA were identified, including our index case, and 70% were children. Mortality was 30% in all age groups and 64% in children. The majority of patients had underlying conditions (70%), of which SCD was most commonly reported. Previous ceftriaxone exposure was reported in 65%. Common features included elevated lactate dehydrogenase (70%); early, new-onset hemoglobinuria (59%); acute renal failure (46%); positive direct antibody testing (70%); and anticeftriaxone antibodies (68%). Also, 32% had a preceding, unrecognized, hemolytic episode associated with ceftriaxone., Summary: Given the common use of ceftriaxone worldwide, knowledge of CIIHA, which often goes undiagnosed until late in the course, is essential for clinicians. Based on the findings of this review, we suggest obtaining past history of ceftriaxone exposures and screening for new-onset hemoglobinuria during ceftriaxone therapy in selected patients as potential methods for early diagnosis of this rare but potentially fatal condition., (© The Author(s) 2014.)

Key Clinical Message: Systemic lupus erythematosus should be included in the differential diagnosis of every adolescent with pancytopenia. An accurate diagnosis with the appropriate therapy is vital and can cause lasting reversal of this condition. Systemic lupus erythematosus should be included in the differential diagnosis of every adolescent with pancytopenia. An accurate diagnosis with the appropriate therapy is vital and can cause lasting reversal of this condition.

Children with sickle cell anemia have a higher-than-expected prevalence of poor educational attainment. We test two key hypotheses about educational attainment among students with sickle cell anemia, as measured by grade retention and use of special education services: (1) lower household per capita income is associated with lower educational attainment; (2) the presence of a silent cerebral infarct is associated with lower educational attainment. We conducted a multicenter, cross-sectional study of cases from 22 U.S. sites included in the Silent Infarct Transfusion Trial. During screening, parents completed a questionnaire that included sociodemographic information and details of their child's academic status. Of 835 students, 670 were evaluable; 536 had data on all covariates and were used for analysis. The students' mean age was 9.4 years (range: 5-15) with 52.2% male; 17.5% of students were retained one grade level and 18.3% received special education services. A multiple variable logistic regression model identified that lower household per capita income (odds ratio [OR] of quartile 1 = 6.36, OR of quartile 2 = 4.7, OR of quartile 3 = 3.87; P = 0.001 for linear trend), age (OR = 1.3; P < 0.001), and male gender (OR, 2.2; P = 0.001) were associated with grade retention; silent cerebral infarct (P = 0.31) and painful episodes (P = 0.60) were not. Among students with sickle cell anemia, household per capita income is associated with grade retention, whereas the presence of a silent cerebral infarct is not. Future educational interventions will need to address both the medical and socioeconomic issues that affect students with sickle cell anemia., (© 2014 Wiley Periodicals, Inc.)

The study's objective was to assess the cost-effectiveness of preoperative transfusion compared with no preoperative transfusion in patients with sickle cell disease undergoing low- or medium-risk surgery. Seventy patients with sickle cell disease (HbSS/Sß(0) thal genotypes) undergoing elective surgery participated in a multicentre randomised trial, Transfusion Alternatives Preoperatively in Sickle Cell Disease (TAPS). Here, a cost-effectiveness analysis based on evidence from that trial is presented. A decision-analytic model is used to incorporate long-term consequences of transfusions and acute chest syndrome. Costs and health benefits, expressed as quality-adjusted life years (QALYs), are reported from the 'within-trial' analysis and for the decision-analytic model. The probability of cost-effectiveness for each form of management is calculated taking into account the small sample size and other sources of uncertainty. In the range of scenarios considered in the analysis, preoperative transfusion was more effective, with the mean improvement in QALYs ranging from 0.018 to 0.206 per patient, and also less costly in all but one scenario, with the mean cost difference ranging from -£813 to £26. All scenarios suggested preoperative transfusion had a probability of cost-effectiveness >0.79 at a cost-effectiveness threshold of £20 000 per QALY., (© 2013 The Authors. European Journal of Haematology Published by John Wiley & Sons Ltd.)

This study aimed to demonstrate the validity, reliability and responsiveness of a new disease-specific quality of life (QoL) questionnaire for children and adults with thalassaemia major, the Transfusion-dependent QoL questionnaire (TranQol). 106 participants (51 adults and 55 children) were recruited from six North American thalassaemia treatment centres with a mean age of 20·7 years (standard deviation [SD] 9, range 7-51 years). The mean total TranQol score was 71 (SD 17, 32-97) on a scale of 0-100. Patients with co-morbidities had significantly lower scores (63 vs. 75, P = 0·001). TranQol scores showed substantial agreement (P < 0·001) with the Health Utilities Index Mark 3 (all patients, r = 0·65), the Pediatric QoL (children, r = 0·77) and the Short Form (36) physical (adults, r = 0·69) and mental summary scores (r = 0·76). In the subgroup who rated their QoL as better, there was a 4·0 point (SD 9·0) improvement in TranQol scores, from baseline of 67·1-71·1 one week later (P = 0·008). Test-retest reliability was excellent (intra-class correlation coefficient, 0·93). The TranQol was valid, with acceptable correlation for all administered measures and was reliable and responsive to change. The TranQol can be incorporated into future studies of thalassaemia major., (© 2013 John Wiley & Sons Ltd.)

Background and Objective: Vaso-occlusive episodes (VOEs) are the most common complication of sickle cell disease in children. Treatment with magnesium seems to improve cellular hydration and may result in reduced vaso-occlusion. This study aimed to determine if intravenous (IV) magnesium sulfate (MgSO4) reduces length of stay (LOS) in hospital, pain scores, and cumulative analgesia when compared with placebo., Methods: Randomized, double-blind, placebo-controlled trial in children aged 4 to 18 years requiring admission to hospital with a sickle cell disease VOE requiring IV analgesia. Participating children received IV MgSO4 (100 mg/kg) every 8 hours or placebo in addition to standard therapy. We used a t test or Mann-Whitney test (continuous variables), Fisher's exact test, or χ2 test (frequencies). P values were considered significant if <.05, and 95% confidence intervals were calculated for the difference between groups., Results: One hundred six children were randomly assigned to the study, and 104 were included. Fifty-one (49%) received MgSO4. Children's mean age was 12.4 years (range: 4-18 years; SD: 3.8 years), and 56 (54%) were females. There was no significant difference in the primary outcome measure, LOS in hospital, with a mean of 132.6 and 117.7 hours in the MgSO4 and placebo groups, respectively (P = .41). There was no significant difference between groups for the secondary outcomes of mean pain scores (4.9 ± 2.6 vs 4.8 ± 2.6, respectively; P = .92) or analgesic requirements (continuous morphine infusion [P = .928], boluses of IV morphine [P = .82], acetaminophen [P = .34], ibuprofen [P = .15], naproxen [P = .10]). Only minor adverse events were recorded in both groups. Pain at the infusion site was more common in the MgSO4 group., Conclusions: IV MgSO4 was well tolerated but had no effect on the LOS in hospital, pain scores, or cumulative analgesia use in admitted children with a VOE.

Background: No consensus exists on whether preoperative blood transfusions are beneficial in patients with sickle-cell disease. We assessed whether perioperative complication rates would be altered by preoperative transfusion., Methods: We did a multicentre, randomised trial. Eligible patients were aged at least 1 year, had haemoglobin SS or Sβ(0)thalassaemia sickle-cell-disease subtypes, and were scheduled for low-risk or medium-risk operations. Patients were randomly assigned no transfusion or transfusion no more than 10 days before surgery. The primary outcome was the proportion of clinically important complications between randomisation and 30 days after surgery. Analysis was by intention to treat., Findings: 67 (96%) of 70 enrolled patients-33 no preoperative transfusion and 34 preoperative transfusion-were assessed. 65 (97%) of 67 patients had the haemoglobin SS subtype and 54 (81%) were scheduled to undergo medium-risk surgery. 13 (39%) of 33 patients in the no-preoperative-transfusion group had clinically important complications, compared with five (15%) in the preoperative-transfusion group (p=0.023). Of these, 10 (30%) and one (3%), respectively, had serious adverse events. The unadjusted odds ratio of clinically important complications was 3.8 (95% CI 1.2-12.2, p=0.027). 10 (91%) of 11 serious adverse events were acute chest syndrome (nine in the no-preoperative-transfusion group and one in the preoperative-transfusion group). Duration of hospital stay and readmission rates did not differ between study groups., Interpretation: Preoperative transfusion was associated with decreased perioperative complications in patients with sickle-cell disease in this trial. This approach could, therefore, be beneficial for patients with the haemoglobin SS subtype who are scheduled to undergo low-risk and medium-risk surgeries., Funding: NHS Blood and Transplant., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Primary myelofibrosis (PMF) is rare in children. An allogeneic hematopoietic stem cell transplantation (HSCT) is the only known curative therapy for severe cases. Here, we report the case of a female infant with PMF treated with allogeneic HSCT using an unrelated cord blood unit. She had successful reversal of her disease, but experienced complications related to transplant. This is the seventh reported case of HSCT for PMF in children, and the second using umbilical cord blood. We conclude that cord HSCT is a useful curative treatment option in children with PMF, but that efforts must be taken to reduce complications.

Background: Painful vaso-occlusive crisis (VOC) is the most common reason for hospitalization in children with sickle cell disease., Objective: To benchmark pain outcomes in sickle cell disease, including process outcomes (eg, pain assessment and documentation practices, pain management interventions) and clinical outcomes (eg, pain intensity over hospital stay), to identify areas for improvement., Methods: A retrospective study was conducted on electronic charts of children hospitalized with a primary diagnosis of VOC between July 2007 and August 2008., Results: A convenience sample of 50 admissions was used. In terms of clinical outcomes, patients presented to the emergency department with an initial median pain intensity of 9⁄10 (interquartile range 8⁄10 to 10⁄10). Forty-three per cent had not used opioids for pain relief at home. The mean (± SD) length of stay was 4.0±2.3 days. For most patients, median scores for highest daily pain intensity remained moderate to high throughout hospitalization, although scores did decrease significantly per day of hospitalization. In terms of process outcomes, pain intensity was assessed according to hospital standards on 25% of days in both the emergency department and the ward. There was no discrepancy between prescribed and administered opioid doses and medication use. In 95% of cases, strong opioid use was in a subtherapeutic or low therapeutic dosage range., Conclusions: The results showed three areas to target for improvement: improved pain assessment and documentation using valid pain tools; more aggressive multimodal management for peak VOC pain; and better education and support for pain management at home. Further studies are required to evaluate optimal pain treatment practices.