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Background: Acute chest syndrome (ACS) is a life-threatening complication of sickle cell disease (SCD). The Prevent Acute Chest Syndrome checklist (PACScheck) was created to drive appropriate ordering of opioids, incentive spirometry (IS), intravenous fluids (IVF), evaluation of oxygen desaturation, and bronchodilator use., Objectives: Decrease the development of ACS by 5% in a hospitalized pediatric SCD population., Methods: A multidisciplinary team conducted a quality improvement (QI) project between April 2020 and August 2021 on an inpatient pediatric hematology unit. At-risk hospitalizations were patients with SCD who did not have ACS upon hospital admission. PACScheck was implemented and weekly run charts assessed documentation. Process control (p) charts, geometric control (g) charts, and chi-square tests assessed checklist process measures pre- and post-PACScheck. G chart assessed the number of encounters between ACS events., Results: A total of 483 at-risk hospitalizations were identified in the 12 months prior and 363 during the study period. A g chart demonstrated that fewer encounters developed ACS during PACScheck. A p chart demonstrated that IS documentation increased during PACScheck. A run chart of PACScheck documentation demonstrated a median of 100% documentation at least once per hospitalization during the last six months of the intervention., Conclusion: Development of ACS can be reduced by implementing a best-practices checklist (PACScheck) on an inpatient pediatric hematology unit with a multidisciplinary team., (© 2024 Wiley Periodicals LLC.)

Therapeutic options for sickle cell disease (SCD) have increased recently as well as the development of updated national guidelines. It is not known how these options are being offered or to what degree guidelines are incorporated into clinical practice. This study aimed to describe practice patterns for pediatric hematologists regarding the use of disease-modifying and potentially curative therapies for SCD. A 9-section, cross-sectional electronic survey was disseminated during a 3-month period via SurveyMonkey, to members of the American Society of Pediatric Hematology/Oncology Hemoglobinopathy Special Interest Group (ASPHO HSIG). A total of 88 physician members of the ASPHO HSIG were surveyed. Ninety percent of respondents (72/80) start hydroxyurea routinely in patients with HbSS and HbSβ 0 thalassemia, regardless of disease severity. Laboratory monitoring was recommended every 3 months for stable dosing in 63.8% (51/80). New therapies were recommended for patients on hydroxyurea who were still experiencing SCD complications: L-glutamine 68.5% (37/54) or crizanlizumab 93.1% (54/58). Voxelotor was recommended for patients on hydroxyurea with low hemoglobin in 65.1% (43/66) of cases. Matched sibling transplant was considered for any disease severity by 55.1% (38/69). Gene therapy trials are offered on-site by 29% (20/69). Our study demonstrated the enhanced utilization of hydroxyurea while revealing the unexplored potential of other disease-modifying therapies in SCD. These findings underscore the importance of continued knowledge acquisition about the long-term efficacy of new medical therapies and addressing barriers to the use of proven therapies and guide the development of future studies of optimal SCD management., Competing Interests: T.A.F. served as a consultant for Forma Therapeutics, Novartis, and Global Blood Therapeutics (all completed). The remaining authors declare no conflict of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Patients with sickle cell disease (SCD) are predisposed to a hypercoagulable state due to alterations in the coagulation system. Despite concern for the development of venous thromboembolism (VTE) in this population, there are no standardized guidelines for routine thromboprophylaxis. The objective of this study was to assess thromboprophylaxis practices of adult and pediatric treaters of SCD before and during the coronavirus disease of 2019 (COVID-19) pandemic. A cross-sectional electronic survey was distributed to pediatric and adult hematology oncology practitioners through seven SCD-specific interest groups between May 29, 2020, and July 13, 2020. Of 93 total responses, 14% ( N  = 13) reported they only treat patients more than 21 years old; 38.7% ( N  = 36) only treat patients 0-21 years old and 47.3% ( N  = 44) reported they treat both. Our study showed that before the COVID-19 pandemic, 96% of adult practitioners would recommend pharmacologic thromboprophylaxis, mechanical thromboprophylaxis or both for hospitalized adults with thromboprophylaxis, but only 76% of pediatric treaters would recommend any thromboprophylaxis in hospitalized children ( P  < 0.0001), with 24% of pediatric treaters choosing no thromboprophylaxis at all. During the COVID-19 pandemic, pharmacologic thromboprophylaxis specifically was recommended for adults by 94% of treaters and for pediatric patients by 76% of treaters. These findings suggest that despite the lack of evidence-based thromboprophylaxis guidelines in adults and children with thromboprophylaxis, subspecialty treaters routinely provide pharmacologic thromboprophylaxis in their adult patients and will modify their practice in pediatric patients who are considered at a high risk for VTE., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Acute chest syndrome (ACS) is an important cause of morbidity in sickle cell disease (SCD). A standardized tool for reporting chest radiographs in pediatric SCD patients did not previously exist., Objective: To analyze the interobserver agreement among pediatric radiologists' interpretations for pediatric ACS chest radiographs utilizing a standardized reporting tool. We also explored the association of radiographic findings with ACS complications., Methods: This was a retrospective cohort study of pediatric ACS admissions from a single institution in 2019. ICD-10 codes identified 127 ACS admissions. Two radiologists independently interpreted the chest radiographs utilizing a standardized reporting tool, a third radiologist adjudicated discrepancies, and κ analysis assessed interobserver agreement. Clinical outcomes were correlated with chest radiograph findings utilizing Pearsons' χ 2 , t tests, and Mann-Whitney U tests. Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated., Results: Interobserver agreement was moderate to near-perfect across variables, with κ analysis showing near-perfect agreement for opacity reported in the right upper lobe (0.84), substantial agreement for right lower lobe (0.63), and vertebral bony changes (0.72), with moderate agreement for all other reported variables. On the initial chest radiograph, an opacity located in the left lower lobe (LLL) correlated with pediatric intensive care unit transfer (p = .03). Pleural effusion on the initial chest radiograph had a 3.98 OR (95% CI: 1.35-11.74) of requiring blood products and a 10.67 OR (95% CI: 3.62-31.39) for noninvasive ventilation., Conclusion: The standardized reporting tool showed moderate to near-perfect agreement between radiologists. LLL opacity, and pleural effusion were associated with increased risk of ACS complications., (© 2023 Wiley Periodicals LLC.)

Background: Degree of cerebrovascular stenosis in pediatric patients with sickle cell anemia (SCA) informs need for chronic transfusion therapy, which has significant risks. Flow artifact, intrinsic to magnetic resonance angiography (MRA), is dependent on technical parameters and can lead to overinterpretation of stenosis. The primary objective of this study was to document any change in stroke prevention therapy that could be attributed to the implementation of a standardized MRA scanning protocol for patients with SCA., Methods: A standardized MRA scanning protocol with an echo time of less than 5 ms was implemented at Montefiore Medical Center (MMC), NY in May 2016. Retrospective chart review identified 21 pediatric patients with SCA, with an MRA head both pre- and post-May 2016. Arterial stenosis on MRA, machine parameters, and treatment plans were compared pre- and post-implementation., Results: Ten of the 21 patients met inclusion criteria. Previously seen stenosis was re-classified to a lower degree in six of the 10 patients, leading to discontinuation of transfusions in five patients. No patients required escalation of therapy to chronic transfusions., Conclusion: Optimizing flow artifact by decreasing echo time to less than 5 ms can improve accurate interpretation of cerebrovascular disease, and ensure appropriate treatment plans are in place for stroke prevention. This is especially important for implementing "TCD With Transfusions Changing to Hydroxyurea (TWiTCH)" clinical trial results in the real-world setting., (© 2022 Wiley Periodicals LLC.)

Background: Sickle cell disease (SCD) is a chronic illness that is associated with frequent admissions for vaso-occlusive episodes (VOE). Opioids are frequently utilized in pain management, but dosing is often provider dependent. Opioids cause both short-term and long-term side effects, so the minimal effective dose is desired. This study examined demand-only patient-controlled analgesia (PCA) in pediatric patients., Methods: A new clinical practice guideline (CPG) for a single institution was implemented, which eliminated basal infusion dosing for PCAs on hospital admission. The primary aim of this retrospective study was to evaluate length of stay (LOS) before and after implementation of a CPG of demand-only PCA and, in a selected subpopulation, addition of short-term methadone. Secondary aims included opioid utilization, acute chest syndrome (ACS), and hypoxia. Inclusion criteria included SCD, ≤21 years of age, uncomplicated VOE admission, and ≥ 3 and ≤ 8 hospital admissions for SCD pain control within one calendar year., Results: LOS decreased postintervention (7.2 ± 5.1 vs 4.5 ± 3.8 days, P < 0.001). Mean total opioid utilization in morphine equivalents mg/kg markedly decreased between the cohorts (13.3 ± 33.8 vs 3.6 ± 3.0, P < 0.001). ACS (21.9% vs 2.8%, P = 0.004) and hypoxia (28% vs 6.9%, P< 0.001) decreased significantly as well., Conclusion: Bolus PCA dosing of opioids resulted in decreased LOS and reductions in opioid utilization, hypoxia, and ACS., (© 2022 Wiley Periodicals LLC.)

Objective: Adolescents and young adults (AYA) with sickle cell disease (SCD) experience high rates of acute care utilization and increased morbidity. At this high-risk time, they also face the need to transition from pediatric to adult services, which, if poorly coordinated, adds to heightened morbidity and acute care utilization. The study objective was to characterize the feasibility, acceptability, and short-term efficacy of a protocolized transition navigator (TN) intervention in AYA with SCD., Methods: We developed a protocolized TN intervention that used ecological assessment and motivational interviewing to assess transition readiness, identify goals, and remove barriers to transition, and to provide disease and pain management education and skills to AYAs with SCD., Results: Ninety-three percent (56/60) of enrolled individuals completed the intervention. Participation in the TN program was associated with significant improvement in mean transition readiness scores (3.58-4.15, P < .0001), disease knowledge scale (8.91-10.13, P < .0001), Adolescent Medication Barriers Scale (40.05-35.39, P = .003) and confidence in both disease (22.5-23.96, P = .048) and pain management (25.07-26.61, P = .003) for youth with SCD., Conclusion: The TN intervention was acceptable to youth with SCD, feasible to implement at an urban academic medical center, and addressed barriers to transition identified by the youth. Longer-term assessment is needed to determine if the TN intervention improved successful transfer to and retention in adult care., (Copyright © 2021 Academic Pediatric Association. Published by Elsevier Inc. All rights reserved.)

Diastolic dysfunction is a known cause of mortality in adults with sickle cell disease (SCD). Left atrial function (LAf) and strain (LAS) are novel echocardiographic parameters to assess early diastolic dysfunction, which have not been assessed in pediatric SCD. Through a retrospective single-center study, we describe echocardiographic parameters of diastology in children with SCD and evaluate their relationship with clinical variables including anemia and blood pressure. Baseline clinical data, 24-hour ambulatory blood pressure monitoring data and echocardiography results were collected. LAf and LAS were measured using volumetric data and speckle-tracking echocardiography, respectively. Sixty-seven children with SCD (13.5±7 y, 47% male, 7% hypertensive) with a mean hemoglobin of 8.8±1.3 g/dL, LAf of 61±8% (n=53) and LAS of 46.3±7.4% (n=28) were included. LAS was significantly associated with hemoglobin (ρ=0.43, P=0.022) but not with maximal left atrial (LA) volume (ρ=-0.05, P=0.79) or any blood pressure parameters. On multivariate analysis, LAS decreased by 3.2% (1.3, 5.1) and LA volume increased by 1.6 mL/m2 (3.1, 0.08) for every 1 g/dL decrease in hemoglobin. Thus, severity of baseline anemia in pediatric SCD correlates with diastolic function as measured by LAS, independent of LA dilation., Competing Interests: The authors declare no conflict of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: Patients with sickle cell disease (SCD) experience recurrent pain crises, which may mimic appendicitis. A prior study found a significantly lower rate of appendicitis in patients with SCD compared with national averages. We investigate the incidence of appendicitis and number of imaging studies for appendicitis in pediatric patients with SCD., Methods: Using a retrospective study design from a single institution, SCD and control cohorts were created. Inclusion criteria included age 0 to 21years and at least one follow-up appointment within 24 months. Length of observation was calculated from initial presentation to either inpatient admission for appendicitis or last clinic visit. Analysis of an SCD subgroup and a control subset (n = 1,596) was used to compare the number of imaging studies. Incidence rates of appendicitis and number of appendicitis studies were determined. Z-tests, binomial enumeration exact tests, and Fischer's exact tests were used., Results: The SCD cohort included 1,064 patients between January 1, 2001, to December 31, 2014, and the control cohort included 115,109 patients without SCD between January 1, 2011, and December 31, 2011. Incidence rate of appendicitis per 10,000 patient-years was significantly lower in the SCD group compared with controls (2.9 cases versus 10.7 cases per 10,000 patient-years; P = .044). Additionally, the SCD group received significantly more ultrasounds (148 versus 60 per 10,000 patient-years; P< .0001) and CTs (94 versus 27 per 10,000 patient-years; P< .0001) for appendicitis, which remained significant when controlling for race. Patients with SCD also received more false-positive scans., Discussion: Patients with SCD had a significantly lower incidence of appendicitis than controls, yet had a higher number of imaging tests performed for appendicitis. Appendicitis should be viewed as a less common cause of acute abdominal pain in SCD. This consideration should help guide imaging strategy., (Copyright © 2020 American College of Radiology. Published by Elsevier Inc. All rights reserved.)

Background Sickle cell disease (SCD), a chronic hemolytic disorder, results in cumulative end-organ damage affecting major organs such as the cardiovascular, renal, and central nervous systems. Effects of modifiable risk factors, such as blood pressure (BP), on the development of end-organ complications in SCD have not been well studied, particularly among the pediatric population. Relative hypertension in patients with SCD increases their risks of stroke, cardiovascular complications, and death. The primary hypothesis of this study was that abnormal BP patterns are common among patients with SCD and they impact end-organ complications. Methods Patients with SCD (HbSS, HbSβ0) were enrolled from the Children's Hospital at Montefiore (N = 100). For each patient, demographic data were collected, biochemical variables in urine and blood samples were analyzed, BP was determined with ambulatory blood pressure monitoring (ABPM), and an echocardiogram was performed. The prevalence of abnormalities in BP parameters was defined, and their relationships with measures of SCD severity and end-organ damage were assessed. Results Sufficient ABPM data were available for 67 patients. Enrolled children were 13 ± 4 years (40% were males). Assessment of diurnal variation demonstrated that 81% of patients had abnormal systolic nocturnal dipping and 61% had abnormal diastolic nocturnal dipping. Abnormalities in the diurnal pattern were associated with reticulocytosis and hyperfiltration. Microalbuminuria was present in 19% (n = 13) of patients, of which 77% (n = 10) were females (p = 0.014). Diastolic load and abnormal nocturnal dipping were associated with hyperfiltration but not with microalbuminuria. Conclusions BP abnormalities detected with ABPM in SCD patients are prevalent and perhaps are a risk factor for end-organ complications. Further studies are required to identify the mechanisms underlying these relationships and their longitudinal changes., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2020, Ranabothu et al.)

Sickle Cell Disease (SCD) is a chronic hemolytic disorder associated with frequent pain episodes, end organ damage and a shortened lifespan. Currently there exist no disease specific targeted therapies for the treatment of acute vaso-occlusive crisis (VOC) and management with analgesics and hydration is purely supportive. Improvement in understanding of disease pathophysiology has resulted in a great interest in disease modifying novel therapies and many are being evaluated in clinical trials. Here we report the results from the pre-specified mid-point analysis of the Phase 2 study of Intravenous Gamma Globulin (IVIG) for the treatment of acute VOC in patients with SCD and lessons learned., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Rationale: Pulmonary complications are the leading cause of morbidity and mortality in sickle cell disease (SCD) patients. Research in SCD has predominantly been conducted on African-Americans, and the disease burden of SCD in other races and ethnicities, including Hispanic patients, is not well characterized., Objective: To compare pulmonary disease burden between Hispanic and non-Hispanic ethnic groups among children with SCD., Methods: In a retrospective chart review on 566 SCD patients followed at the Children's Hospital at Montefiore, NY, we compared the pulmonary disease burden and disease management in Hispanic patients to their non-Hispanic counterparts. We also compared the contribution of demographic and clinical variables to acute chest syndrome (ACS), vaso-occlusive crisis (VOC), and hospitalizations for SCD related complications between the two ethnic groups., Results: Hispanic patients had a greater proportion of ACS, and had lower forced expiratory volume (FEV1), forced vital capacity, and vital capacity, compared to non-Hispanics. Hispanic patients were more likely to be evaluated in pulmonary clinic and to be on inhaled corticosteroids, short-acting β agonizts, and leukotriene receptor antagonists. In addition, Hispanic children were more likely to be on hydroxyurea, and receive exchange transfusions. However, the association of asthma with the proportion of ACS did not differ between Hispanics and non-Hispanics., Conclusion: Hispanic children with SCD had differences in their pulmonary function profile and received more pulmonary evaluations than non-Hispanic children., (© 2020 Wiley Periodicals LLC.)

Rationale: Asthma is a common comorbid condition in sickle cell disease (SCD). However, obstructive lung disease is prevalent in SCD, independent of a diagnosis of asthma. It is speculated that the heightened state of inflammation in SCD, involving pathways distinct from allergic asthma, may underlie the SCD-specific obstructive disease. Objective: The objective of the study was to compare airway and systemic inflammatory markers between SCD patients with pulmonary manifestations and patients with allergic asthma, and correlate the discriminating inflammatory markers with clinical measures of pulmonary disease. Materials and Methods: In a pilot translational study conducted at the Children's Hospital at Montefiore, 15 patients with SCD, and history of asthma, airway obstruction, or airway hyper-reactivity, and 15 control patients with allergic asthma 6-21 years of age were recruited. Inflammatory markers, including peripheral blood T helper cell subsets, serum and exhaled breath condensate (EBC) cytokines and chemokines of the Th-1/Th-17, Th-2, and monocytic pathways, and serum cysteinyl leukotrienes B4 (LTB4), were quantified, compared between the study groups, and correlated with atopic sensitization, pulmonary function tests, and markers of hemolysis. Results: White blood cells ( P  < 0.05) and monocytes ( P  < 0.001) were elevated in the SCD group, while atopic characteristics were higher in the control asthma group. Tumor necrosis factor-alpha ( P  < 0.01), interferon gamma inducible protein (IP)-10 ( P  < 0.05), and interleukin-4 ( P  < 0.01) in serum and monocyte chemotactic protein (MCP)-1 in EBC were higher in the SCD group ( P  ≤ 0.05). Forced vital capacity (FVC) and forced expiratory volume in 1 s (FEV1) in patients with SCD inversely correlated with serum IP-10 and LTB4 levels. Conclusions: Compared with atopic asthmatic patients, inflammatory markers involving Th-1, Th-2, and monocytic pathways were higher in the SCD group, among which Th-1 measures correlated with pulmonary function deficits., Competing Interests: No competing financial interests exist.

Study Objectives: Periodic limb movements (PLMs) have been associated with increased risk of stroke, but there is currently scarce research exploring this relationship in the setting of sickle cell disease (SCD). The aim of this study was to explore whether increased PLMs in children with SCD are associated with increased risk of cerebrovascular disease and to determine if there are any clinical or laboratory differences between children with SCD with elevated periodic limb movement index (PLMI) versus those with normal PLMI., Methods: This study is a comprehensive review of medical records of 129 children with SCD (aged ≤ 18 years) who had undergone polysomnography for evaluation of sleep-disordered breathing., Results: Elevated PLMI (PLMI > 5 events/h) was present in 42% (54/129) of children with SCD. Children with elevated PLMI were found to have higher percentage of hemoglobin S, lower total iron, higher arousal index and tendency toward elevated transcranial Doppler velocity ( P = .063, odds ratio = 3.9, 95% CI 0.93-16.22). While association between elevated PLMI and isolated cerebrovascular stenosis ( P = .050, odds ratio 5.6, 95% CI 1.0-31.10) trended toward significance, there was significantly greater proportion of children with elevated PLMI who had cerebrovascular stenosis with Moyamoya disease ( P = .046) as demonstrated by magnetic resonance imaging (MRI)., Conclusions: The prevalence of elevated PLMI in children with SCD was higher than in previously published data. Elevated PLMI was significantly associated with greater rates of cerebrovascular disease as detected by MRI., (Copyright © 2019 American Academy of Sleep Medicine. All rights reserved.)

Background: Thalassemia syndromes are inherited hemoglobin disorders that result when the synthesis of normal hemoglobin is lacking or significantly reduced. For people with thalassemia, long-term red blood cell transfusion remains the mainstay of therapy, which may lead to iron overload causing severe complications and damage in different body organs. Long-term iron chelation therapy is essential for people with thalassemia to minimize the ongoing iron-loading process. In addition, suboptimal adherence can increase adverse events associated with iron overload and result in increased morbidity, mortality, healthcare utilization and cost of care., Objectives: To identify and assess the effects of computer and mobile technology interventions designed to facilitate medication adherence and disease management in individuals with thalassemia, including:- evaluating the effects of using computer and mobile technology interventions for medication adherence and disease management on health and behavioral outcomes;- identifying and assessing the effects of computer and mobile technology interventions specific to different age groups (children, adolescents and adults) and type of modality (e.g. cell phone, the Internet)., Search Methods: We searched CENTRAL (the Cochrane Library), MEDLINE, Embase, CINAHL, PsycINFO, ProQuest Dissertations & Theses Global, Psychology and Behavioral Sciences Collection, Web of Science Science & Social Sciences Conference Proceedings Indexes, IEEE Xplore and ongoing trial databases (22 February 2018). We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group's Haemoglobinopathies Trials Register (20 June 2019). We also searched for unpublished work in the abstract book of nine major conferences in the related field., Selection Criteria: Randomized controlled trials (RCT) and quasi-RCTs comparing single- or multi-component interventions versus no intervention, placebo or standard care, with adherence to iron chelation as the primary outcome were eligible for inclusion. Non-randomized studies of interventions, controlled before-after studies, and interrupted-time-series studies were also eligible for inclusion., Data Collection and Analysis: Three authors independently assessed study eligibility. If we had included any studies, we would have independently assessed risk of bias and extracted data; we planned to assess the quality of the evidence using GRADE., Main Results: We did not identify any eligible studies for inclusion in the review., Authors' Conclusions: Due to lack of evidence, we cannot comment on the efficacy or effectiveness of computer and mobile technology intervention strategies to promote disease management and adherence to iron chelation therapy in people with thalassemia.We concluded that RCTs are needed to examine a variety of computer and mobile technology intervention strategies that may be useful for promoting disease management and increasing adherence to iron chelation therapy in individuals with thalassemia.

Background: Outdoor workers experience high injury rates in the winter due to slipping on ice and snow. Our testing program has demonstrated that most safety footwear does not provide adequate slip-resistance and/or comfort in icy conditions., Objective: Our objective was to determine which of the most commonly worn safety footwear available to outdoor municipal workers in Toronto, Ontario, Canada would best prevent slips on icy surfaces and which models had good wearability., Methods: We selected 45 of the most popular types of winter footwear worn by these workers and applied our Maximum Achievable Angle (MAA) test method to rate the slip-resistance of the footwear. A ten-point rating scale was used for recording participants' perceptions of wearability. The MAA test measured the steepest ice-covered incline that participants can walk up and down without experiencing a slip., Results: Of the 45 types of footwear tested, only one model achieved an MAA score of 8 degrees that exceeded our cut-off for acceptable performance set at 7 degrees. Secondary measures of performance including thermal insulation; wearability and heaviness of footwear tested were also ranked., Conclusion: Our results demonstrate that footwear manufactures have the opportunity to differentiate their footwear by investing in slip-resistant outsole materials.

Sickle cell disease is an inherited hemoglobinopathy characterized by hemolytic anemia, frequent painful episodes, poor quality of life, end organ damage and a shortened lifespan. Although the seminal event is the polymerization of the abnormal hemoglobin, the downstream pathophysiology of vaso-occlusion results from heterotypic interactions between the altered, adhesive sickle cell RBCs, neutrophils, endothelium, and platelets. Ischemia reperfusion injury, hemolysis and oxidant damage all contribute to heightened inflammation and activation of the hemostatic system. These downstream targets are the focus of emerging treatments with considerable potential to ameliorate disease manifestations. This review summarizes the progress on development of these agents., (Copyright © 2018 Elsevier Inc. All rights reserved.)

This is a protocol for a Cochrane Review (Intervention). The objectives are as follows: To identify and assess the effects of computer and mobile technology interventions designed to facilitate medication adherence and disease management in individuals with thalassemia, including: evaluating the effects of using computer and mobile technology interventions for medication adherence and disease management on health and behavioural outcomes;identifying and assessing the effects of computer and mobile technology interventions specific to different age groups (children, adolescents and adults) and type of modality (e.g. cell phone, the Internet)., Competing Interests: DECLARATIONS OF INTEREST All authors: none known.

Hydroxyurea (HU) is a key drug therapy for individuals with sickle cell anemia (SCA), yet its clinical and hematologic responses can be variable. Various studies have reported the role of α-thalassemia as one of the most prevalent heritable traits that may modify HU response. We provide data from 62 pediatric and adolescent patients with SCA, 26 with co-inherited α-thalassemia trait. Our data suggest that altered hematologic and clinical responses to HU therapy are noted in adolescent SCA individuals with co-inherited α-thalassemia trait. Adolescent patients who co-inherited α-thalassemia trait had a greater reduction in vaso-occlusive episodes compared to those without α-thalassemia, despite a less robust fetal hemoglobin induction as well as a lower maximum HU dose. This clinical improvement was associated with a lower MCH and higher RBC count. Responses to HU in younger SCA children (ages 5-11years) with co-inherited α-thalassemia trait, compared to those without α-thalassemia trait, did not show any difference in number vaso-occlusive episodes, fetal hemoglobin induction and change in MCH and RBC count., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML) suppress normal hematopoietic activity in part by enabling a pathogenic inflammatory milieu in the bone marrow. In this report, we show that elevation of angiopoietin-1 in myelodysplastic CD34(+) stem-like cells is associated with higher risk disease and reduced overall survival in MDS and AML patients. Increased angiopoietin-1 expression was associated with a transcriptomic signature similar to known MDS/AML stem-like cell profiles. In seeking a small-molecule inhibitor of this pathway, we discovered and validated pexmetinib (ARRY-614), an inhibitor of the angiopoietin-1 receptor Tie-2, which was also found to inhibit the proinflammatory kinase p38 MAPK (which is overactivated in MDS). Pexmetinib inhibited leukemic proliferation, prevented activation of downstream effector kinases, and abrogated the effects of TNFα on healthy hematopoietic stem cells. Notably, treatment of primary MDS specimens with this compound stimulated hematopoiesis. Our results provide preclinical proof of concept for pexmetinib as a Tie-2/p38 MAPK dual inhibitor applicable to the treatment of MDS/AML. Cancer Res; 76(16); 4841-9. ©2016 AACR., (©2016 American Association for Cancer Research.)

Primary myelofibrosis (PMF) is a Philadelphia chromosome negative myeloproliferative neoplasm (MPN) with adverse prognosis and is associated with bone marrow fibrosis and extramedullary hematopoiesis. Even though the discovery of the Janus kinase 2 (JAK2), thrombopoietin receptor (MPL) and calreticulin (CALR) mutations have brought new insights into the complex pathogenesis of MPNs, the etiology of fibrosis is not well understood. Furthermore, since JAK2 inhibitors do not lead to reversal of fibrosis further understanding of the biology of fibrotic process is needed for future therapeutic discovery. Transforming growth factor beta (TGF-β) is implicated as an important cytokine in pathogenesis of bone marrow fibrosis. Various mouse models have been developed and have established the role of TGF-β in the pathogenesis of fibrosis. Understanding the molecular alterations that lead to TGF-β mediated effects on bone marrow microenvironment can uncover newer therapeutic targets against myelofibrosis. Inhibition of the TGF-β pathway in conjunction with other therapies might prove useful in the reversal of bone marrow fibrosis in PMF.

Background: Burnout is a work-related syndrome consisting of emotional exhaustion, depersonalization, and diminished feelings of personal accomplishment. Physicians who care for patients with life-threatening illnesses are at high risk for developing burnout. This survey evaluates the prevalence of burnout among pediatric oncologists, and assesses risk factors associated with the development of burnout., Procedure: A questionnaire was sent via email to 1,047 practicing pediatric oncologists. The survey included the 22 question Maslach Burnout Inventory (MBI), as well as questions regarding work-related and lifestyle-related factors associated with developing burnout., Results: Four hundred ten pediatric oncologists (40%) responded to the survey. Thirty-eight percent of pediatric oncologists had high levels of burnout on the MBI, while 72% had at least moderate levels of burnout. Women (47% vs. 32%, P < 0.004) and physicians practicing for <10 years (50% vs. 33%, P < 0.004) had significantly higher rates of burnout. Physicians who reported satisfaction with their lives outside of work were less likely to have burnout (odds ratio 0.238, 0.143-0.396, P < 0.001). The availability of a forum for debriefing, and services for physicians affected by burnout were both associated with lower rates of burnout (24% vs. 46%, P < 0.001 and 23% vs. 46%, P < 0.001). Thirty-six percent of respondents reported their institution has a forum for debriefing and 40% of respondents reported their institution has services available for physicians experiencing symptoms of burnout., Conclusions: Approximately three quarters of pediatric oncologists experience burnout. Further research is needed on the effectiveness of interventions aimed at preventing and treating work-related burnout., (Copyright © 2011 Wiley Periodicals, Inc.)

Background. Chediak-Higashi syndrome (CHS) is a rare, autosomal recessive disorder characterized by oculocutaneous albinism, immunodeficiency, coagulopathy and late-onset, progressive neurological dysfunction. It also has an "accelerated phase" characterized by hemophagocytic lymphohistiocytosis (HLH). The disease is caused by mutations in the CHS1/LYST gene located on chromosome 1, which affects lysosome morphology and function. We report the case of an African-American child with CHS in Case. This 16-month old African-American girl presented with fever and lethargy. The proband had pale skin compared to her parents, with light brown eyes, silvery hair and massive hepatosplenomegaly. Her laboratory evaluation was remarkable for pancytopenia, high serum ferritin and an elevated LDH. Bone marrow aspirate revealed large inclusions in granulocytes and erythrophagocytosis consistent with HLH. Genetic evaluation revealed two novel nonsense mutations in the CHS1 gene: c.3622C > T (p.Q1208X) and c.11002G > T (p.E3668X). Conclusions. Our patient is one of the few cases of CHS reported in the African American population. We identified 2 nonsense mutations in the CHS1 gene, the first mutation analysis published of an African-American child with Chediak-Higashi Syndrome. These two mutations predict a severe phenotype and thus identification of these mutations has an important clinical significance in CHS.