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The impact of residual symptoms following recovery from immune-mediated thrombotic thrombocytopenic purpura (iTTP) on activities of daily living during remission is not routinely discussed or evaluated by hematologists. This study used qualitative methodology to understand 3 issues from the patient’s perspective: the most important symptoms during remission, the impact of these symptoms on their daily activities, and the effectiveness of communication with hematologists. Oklahoma and Ohio patients participated in either focus groups or individual interviews. Eligibility included age ≥18 years, ADAMTS13 deficiency (

OBJECTIVES Patient reported outcome measures, such as the Patient Reported Outcomes Measurement Information System (PROMIS) may be utilized to understand experiences of patients. The purpose of this study was to determine the ability of PROMIS domains to detect changes in pain, physical functioning, and asthma impact over time for children experiencing asthma exacerbation. METHODS Our prospective cohort study included children presenting to the emergency department (ED) for asthma exacerbation. Children completed PROMIS surveys in the ED, 7-10 days, and 1-3 months post-discharge. We used linear mixed models adjusted for age, gender, acute care utilization, and child global health to determine changes in PROMIS T-scores. We used self-reported child health response (Much better now versus a little better now or worse) at discharge as an anchor to determine if change in PROMIS scores corresponded with changes in health. A change was statistically significant if the 95% CI did not include 0. RESULTS Our study included 63 children who presented to the ED for acute asthma exacerbation. We identified that children improved significantly in all domains over time. There was improvement over time following discharge from ED for all pain and physical functioning domains, and asthma impact. Using the clinical anchor, those with considerable improvement in asthma symptoms had improved T scores from 4-17. CONCLUSIONS PROMIS domains of pain, physical functioning, depression, fatigue, peer relationships, and asthma impact are responsive to changes in health states over time. These domains may be used to measure clinically significant change in children experiencing asthma exacerbation.

Background: Sickle cell disease (SCD) is a life-limiting inherited hemoglobinopathy that results in significant complications and affects quality of life. Hematopoietic stem cell transplantation (HSCT) is currently the only curative intervention for SCD; however, guidelines are needed to inform how to apply HSCT in clinical practice. Objective: These evidence-based guidelines of the American Society of Hematology (ASH) are intended to support patients, clinicians, and health professionals in their decisions about HSCT for SCD. Methods: The multidisciplinary guideline panel formed by ASH included 2 patient representatives and was balanced to minimize potential bias from conflicts of interest. The Mayo Evidence-Based Practice Research Program supported the guideline development process, including performing systematic evidence reviews (through 2019). The panel prioritized clinical questions and outcomes according to their importance for clinicians and patients. The panel used the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach, including GRADE Evidence-to-Decision frameworks, to assess evidence and make recommendations, which were subject to public comment. Results: The panel agreed on 8 recommendations to help patients and providers assess how individuals with SCD should consider the timing and type of HSCT. Conclusions: The evidence review yielded no randomized controlled clinical trials for HSCT in SCD; therefore, all recommendations are based on very low certainty in the evidence. Key recommendations include considering HSCT for those with neurologic injury or recurrent acute chest syndrome at an early age and to improve nonmyeloablative regimens. Future research should include the development of a robust SCD registry to serve as a comparator for HSCT studies.

ObjectiveDescribe anxiety and depressive symptoms in children with juvenile idiopathic arthritis (JIA) using Patient Reported Outcomes Measurement Information System (PROMIS) measures and evaluate potential correlations with disease manifestations.MethodsWe performed a cross-sectional study of children with JIA and a parent proxy who completed PROMIS measures on depression, anxiety, stress, and pain. The Childhood Health Assessment Questionnaire (CHAQ) measured mobility, and the clinical Juvenile Arthritis Disease Activity Score in 10 joints (cJADAS10) measured disease activity.ResultsEighty-four patients completed the study. Demographic median values included age (14 yrs), disease duration (4.73 yrs), CHAQ score (0), total active joint count (0), and cJADAS10 (2). Using cJADAS10, 57 patients (70%) had inactive or low disease activity. Mean PROMIS t-scores for depressive and anxiety symptoms were lower in children with JIA compared to the reference population (P < 0.0001). Nineteen patients (23%) had moderate to severe symptoms of anxiety and/or depression. Age and CHAQ score (mobility) correlated with depressive symptoms (r = 0.36, P =0.0008 and r = 0.32, P = 0.0029, respectively) but not anxiety. Depressive and anxiety symptoms correlated with pain (r = 0.64 and r = 0.47, respectively, P < 0.0001) and stress (r = 0.79 and r = 0.75, respectively, P < 0.0001) but not with sex, JIA subtype, disease duration, or disease activity.ConclusionApproximately one-quarter of children with JIA reported moderate to severe symptoms of anxiety and depression. These symptoms are associated with pain and stress, but they are not associated with other disease manifestations. Understanding how mental health symptoms and JIA affect each other is necessary in order to improve patient outcomes and provide well-rounded care.

Key Points • Children with SCD with history of pain and renal and heart/lung comorbidities are at higher risk of worse COVID-19 outcomes. • Adults with SCD with history of pain are at higher risk of worse COVID-19 outcomes., Patients with sickle cell disease (SCD) are at high risk of developing serious infections, therefore, understanding the impact that severe acute respiratory syndrome coronavirus 2 infection has on this population is important. We sought to identify factors associated with hospitalization and serious COVID-19 illness in children and adults with SCD.We established the international SECURE-SCD Registry to collect data on patients with SCD and COVID-19 illness. We used multivariable logistic models to estimate the independent effects of age, sex, genotype, hydroxyurea, and SCD-related and -nonrelated comorbidities on hospitalization, serious COVID-19 illness, and pain as a presenting symptom during COVID-19 illness. As of 23 March 2021, 750 COVID-19 illness cases in patients with SCD were reported to the registry. We identified history of pain (relative risk [RR], 2.15; P < .0001) and SCD heart/lung comorbidities (RR, 1.61; P = .0001) as risk factors for hospitalization in children. History of pain (RR, 1.78; P = .002) was also a risk factor for hospitalization in adults. Children with history of pain (RR, 3.09; P = .009), SCD heart/lung comorbidities (RR, 1.76; P = .03), and SCD renal comorbidities (RR, 3.67; P < .0001) and adults with history of pain (RR 1.94, P = .02) were at higher risk of developing serious COVID-19 illness. History of pain and SCD renal comorbidities also increased risk of pain during COVID-19 in children; history of pain, SCD heart/lung comorbidities, and female sex increased risk of pain during COVID-19 in adults. Hydroxyurea showed no effect on hospitalization and COVID-19 severity, but it lowered the risk of presenting with pain in adults during COVID-19.

In the United States, COVID-19 has disproportionately affected Black persons. Sickle cell disease (SCD) and sickle cell trait (SCT) are genetic conditions that occur predominantly among Black individuals. It is unknown if individuals with SCD/SCT are at higher risk of severe COVID-19 illness compared with Black individuals who do not have SCD/SCT. The objective of our study was to compare COVID-19 outcomes, including the disease manifestations, hospitalization, and death, among individuals with SCD/SCT vs Black individuals who do not have SCD/SCT. We leveraged electronic health record data from a multisite research network to identify Black patients with COVID-19 who have SCD/SCT and those who do not have SCD/SCT. During the study period of 20 January 2020 to 20 September 2020, there were 312 patients with COVID-19 and SCD and 449 patients with COVID-19 and SCT. There were 45 517 Black persons who were diagnosed with COVID-19 but who did not have SCD/SCT. After 1:1 propensity score matching (based on age, sex, and other preexisting comorbidities), patients with COVID-19 and SCD remained at a higher risk of hospitalization (relative risk [RR], 2.0; 95% CI, 1.5-2.7) and development of pneumonia (RR, 2.4; 95% CI, 1.6-3.4) and pain (RR, 3.4; 95% CI, 2.5-4.8) compared with Black persons without SCD/SCT. The case fatality rates for those with SCD compared with Black persons without SCD/SCT were not significantly different. There also were no significant differences in COVID-19 outcomes between individuals with SCT and Black persons without SCD/SCT within the matched cohorts., Key Points • Individuals with SCD are more likely to be hospitalized, develop pneumonia and pain due to COVID-19 than Black individuals without SCD/SCT. • There are no significant differences in COVID-19 outcomes between individuals with SCT and Black individuals without SCD/SCT.

We conducted a prospective cohort study in newly diagnosed systemic light chain (AL) amyloidosis patients (N = 59) to study patient-reported outcomes (PROs) through the first year. The median age was 68 years with 42% female, 8% Black, and 78% lambda subtype. Organ involvement was cardiac in 66%, renal in 58%, with 25% having 3 or greater organs involved. Between baseline and 3 months, all PROMIS®-29 domain scores worsened by 0.4–4.1 points except anxiety which improved by 2.1 points. By 1 year, scores improved compared to the greatest decline at 3 months, most statistically significant for global physical health, physical function, and fatigue. On stage-adjusted survival analysis, in addition to baseline global physical and mental health, domains measuring physical function, fatigue, anxiety, depression, and social roles were associated with 1-year survival. At 1 year, PROMIS measures were associated with NT-proBNP changes and hematologic response. Among patients with an NT-proBNP response, the improvement was seen in physical function, social roles, global mental health, and anxiety. Among patients with an NT-proBNP progression, worsening was seen with anxiety, depression, sleep, and global mental health. Measuring and tracking PROs in patients with AL amyloidosis is important and these important outcomes can be used as correlative endpoints in clinical care/research.

Introduction: By August 1, 2020 in the United States, more than 3 million cases of Coronavirus disease 2019 (COVID-19) had been reported with more than 150,000 deaths due to this disease. Growing evidence suggests that individuals with the pre-existing conditions of hypertension, diabetes, cardiovascular disease and obesity are at a higher risk of more serious COVID-19 illness. However, the impact of COVID-19 on individuals with sickle cell disease and sickle cell trait as compared to those without sickle cell disease or trait is not known. The objective of this study was to determine the rate of hospitalization, disease symptoms and deaths due to COVID-19, in patients with sickle cell disease and sickle cell trait compared to Blacks without sickle cell disease or trait. Methods: We leveraged existing electronic health record (EHR) data from multiple sites that contribute data to a research network, TriNetX. TriNetX query platform was used to identify patients with COVID-19 infection based on ICD diagnoses codes or a positive COVID-19 result from a nucleic acid amplification with probe-based detection test, present any time after January 20, 2020 (this is when the first COVID-19 case was detected in the United States) within the patients' EHR data. We report rates of specific COVID-19 related outcomes among individuals with sickle cell disease and trait, calculated as % of patients in cohort with the particular outcome. Our outcomes of interest included COVD-19 related symptoms, hospitalization, and death, which occurred within 2 weeks of COVID diagnosis. We used propensity score matching (greedy nearest-neighbor matching algorithm with a caliper of 0.1 pooled standard deviations) to create balanced cohorts for comparing outcomes between individuals with sickle cell disease or trait and Blacks without sickle cell disease or trait. Risk ratios and risk differences are reported along with 95% confidence intervals. Given multiple outcomes of interest, we considered a more stringent two-sided alpha of less than Results: As of July 15, 2020, there were 122 COVID-19 patients who had sickle cell disease and 172 COVID-19 patients who had sickle cell trait. Our comparator groups included 15,762 Blacks who were diagnosed with COVID-19 but did not have sickle cell trait/disease. COVID-19 patients with sickle cell disease were significantly younger and a higher proportion had asthma, type 1 diabetes and pre-existing liver conditions compared to Blacks without sickle cell trait/disease (Table 1). COVID-19 patients with sickle cell trait were significantly younger, a higher proportion were females, overweight/obese, and a higher proportion had asthma or type 1 diabetes compared to Blacks without sickle cell trait/disease (Table 1). The rate of respective outcomes for the three groups is shown in Figure 1. Propensity score matching yielded a cohort of patients such that there were no significant differences in demographic and clinical characteristics between patients with sickle cell disease/trait compared to Blacks without sickle cell trait/disease. After matching, COVID patients with sickle cell disease remained at a higher risk of hospitalization, pneumonia and pain compared to Blacks without sickle cell trait/disease (Table 2). The case fatality rates were not significantly different between those with sickle cell disease compared to Blacks. There were no significant differences in COVID outcomes between sickle cell trait and Blacks without sickle cell trait/disease, within the matched cohort. Conclusions: These data provide evidence that sickle cell disease imposes additional risk of severe COVID-19 illness and hospitalization, after balancing for age, gender and other preexisting conditions. The death rate between sickle cell disease and Blacks without sickle cell trait/disease was not significantly different. There are no significant differences in COVID-19 outcomes between sickle cell trait and Blacks without sickle cell trait/disease, after balancing for age, gender and other pre-existing conditions. Disclosures Brandow: NIH / NHLBI: Research Funding; Greater Milwaukee Foundation: Research Funding. Panepinto:HRSA: Research Funding; NINDS: Research Funding; NINDS: Research Funding; NHLBI: Research Funding.

OBJECTIVE: Patient Reported Outcomes Measurement Information System (PROMIS) includes numerous domains to assess functioning among the pediatric population. These domains, however, have not been evaluated for use in children with type 1 diabetes (T1D). The objective of this study was to determine the measurement properties of PROMIS domains (pain behavior, pain quality, physical stress experience, physical activity, strength impact, and profile-25) in children with T1D. METHODS: This is a cross-sectional study of children with T1Drecruited from tertiary care facilities. To determine construct validity, we compared PROMIS T-scores between known-groups based on (a) glycemic control, hemoglobin A1c (HbA1c%) and (b) self-reported general health, using t test or analysis of variance. Reliability was determined using Cronbach’s alpha and item response theory reliability. We also determined agreement between parent-proxy and child self-report PROMIS scores. RESULTS: Our study included 192 children, mean age 12.7 (SD = 2.9) years, eligible to self-report PROMIS surveys. There were significant differences in physical stress experience and pain intensity between children with HbA1c < 10% and those with HbA1c ≥ 10%. There also were significant differences in T-scores for all domains except physical function mobility and strength impact among children with poor/fair, good, very good/excellent general health. All valid domains had reliability >0.70. More than 40% of child-parent pairs were in agreement, with intraclass correlations coefficients (ICC) ranging between 0.41 and 0.63 for all domains, except pain behavior (%agreement = 23%; ICC = 0.29). CONCLUSIONS: Most of the PROMIS domains tested are valid, reliable, and able to differentiate children with T1D who report different general health states. There is moderate agreement between child-parent pairs for all domains except pain behavior.

STUDY OBJECTIVE: The National Heart, Lung, and Blood Institute evidence-based guidelines for timeliness of opioid administration for sickle cell disease (SCD) pain crises recommend an initial opioid within 1 hour of arrival, with subsequent dosing every 30 minutes until pain is controlled. No multisite studies have evaluated guideline adherence, to our knowledge. Our objective was to determine guideline adherence across a multicenter network. METHODS: We conducted a multiyear cross-sectional analysis of children with SCD who presented between January 1, 2016, and December 31, 2018, to 7 emergency departments (EDs) within the Pediatric Emergency Care Applied Research Network. Visits for uncomplicated pain crisis were included, defined with an International Classification of Diseases, Ninth Revision (ICD-9) and ICD-10 code for SCD crisis and receipt of an opioid, excluding visits with other SCD complications or temperature exceeding 38.5°C (101.3°F). Times were extracted from the electronic record. Guideline adherence was assessed across sites and calendar years. RESULTS: A total of 4,578 visits were included. The median time to first opioid receipt was 62 minutes (interquartile range 42 to 93 minutes); between the first and second opioid receipt, 60 minutes (interquartile range 39 to 93 minutes). Overall, 48% of visits (95% confidence interval 47% to 50%) were guideline adherent for first opioid. Of 3,538 visits with a second opioid, 15% (95% confidence interval 14% to 16%) were guideline adherent. Site variation in adherence existed for time to first opioid (range 22% to 70%) and time between first and second opioid (range 2% to 36%; both P.05 for both). CONCLUSION: Guideline adherence for timeliness of SCD treatment is poor, with half of visits adherent for time to first opioid and one seventh adherent for second dose. Dissemination and implementation research/quality improvement efforts are critical to improve care across EDs.

We developed a risk score to predict event-free survival (EFS) after allogeneic hematopoietic cell transplantation for sickle cell disease. The study population (n = 1425) was randomly split into training (n = 1070) and validation (n = 355) cohorts. Risk factors were identified and validated via Cox regression models. Two risk factors of 9 evaluated were predictive for EFS: age at transplantation and donor type. On the basis of the training cohort, patients age 12 years or younger with an HLA-matched sibling donor were at the lowest risk with a 3-year EFS of 92% (score, 0). Patients age 13 years or older with an HLA-matched sibling donor or age 12 years or younger with an HLA-matched unrelated donor were at intermediate risk (3-year EFS, 87%; score, 1). All other groups, including patients of any age with a haploidentical relative or HLA-mismatched unrelated donor and patients age 13 years or older with an HLA-matched unrelated donor were high risk (3-year EFS, 57%; score, 2 or 3). These findings were confirmed in the validation cohort. This simple risk score may guide patients with sickle cell disease and hematologists who are considering allogeneic transplantation as a curative treatment relative to other available contemporary treatments.

Since November 2018, Blood Advances has published American Society of Hematology (ASH) clinical practice guidelines on venous thromboembolism, immune thrombocytopenia, and sickle cell disease. More ASH guidelines on these and other topics are forthcoming. These guidelines have been developed using consistent processes, methods, terminology, and presentation formats. In this article, we describe how patients, clinicians, policymakers, researchers, and others may use ASH guidelines and the many related derivates by describing how to interpret information and how to apply it to clinical decision-making. Also, by exploring how these documents are developed, we aim to clarify their limitations and possible inappropriate usage.

To address the global burden of sickle cell disease and the need for novel therapies, the American Society of Hematology partnered with the US Food and Drug Administration to engage the work of 7 panels of clinicians, investigators, and patients to develop consensus recommendations for clinical trial end points. The panels conducted their work through literature reviews, assessment of available evidence, and expert judgment focusing on end points related to patient-reported outcome, pain (non–patient-reported outcomes), the brain, end-organ considerations, biomarkers, measurement of cure, and low-resource settings. This article presents the findings and recommendations of the end-organ considerations, measurement of cure, and low-resource settings panels as well as relevant findings and recommendations from the biomarkers panel.

To address the global burden of sickle cell disease (SCD) and the need for novel therapies, the American Society of Hematology partnered with the US Food and Drug Administration to engage the work of 7 panels of clinicians, investigators, and patients to develop consensus recommendations for clinical trial end points. The panels conducted their work through literature reviews, assessment of available evidence, and expert judgment focusing on end points related to: patient-reported outcomes (PROs), pain (non-PROs), the brain, end-organ considerations, biomarkers, measurement of cure, and low-resource settings. This article presents the findings and recommendations of the PROs, pain, and brain panels, as well as relevant findings and recommendations from the biomarkers panel. The panels identify end points, where there were supporting data, to use in clinical trials of SCD. In addition, the panels discuss where further research is needed to support the development and validation of additional clinical trial end points.

Visual Abstract, Choosing Wisely is a medical stewardship and quality-improvement initiative led by the American Board of Internal Medicine Foundation in collaboration with leading medical societies in the United States. The American Society of Hematology (ASH) has been an active participant in the Choosing Wisely project. In 2019, ASH and the American Society of Pediatric Hematology/Oncology (ASPHO) formed a joint task force to solicit, evaluate, and select items for a pediatric-focused Choosing Wisely list. By using an iterative process and an evidence-based method, the ASH-ASPHO Task Force identified 5 hematologic tests and treatments that health care providers and patients should question because they are not supported by evidence, and/or they involve risks of medical and financial costs with low likelihood of benefit. The ASH-ASPHO Choosing Wisely recommendations are as follows: (1) avoid routine preoperative hemostatic testing in an otherwise healthy child with no previous personal or family history of bleeding, (2) avoid platelet transfusion in asymptomatic children with a platelet count >10 × 103/μL unless an invasive procedure is planned, (3) avoid thrombophilia testing in children with venous access-associated thrombosis and no positive family history, (4) avoid packed red blood cells transfusion for asymptomatic children with iron deficiency anemia and no active bleeding, and (5) avoid routine administration of granulocyte colony-stimulating factor for prophylaxis of children with asymptomatic autoimmune neutropenia and no history of recurrent or severe infections. We recommend that health care providers carefully consider the anticipated risks and benefits of these identified tests and treatments before performing them.

Sickle cell disease (SCD) is an inherited hemoglobinopathy that can affect nearly every organ system. Individuals living with SCD are at high risk of developing serious infections which can further trigger disease related complications and attribute additional morbidity and mortality. In light of the evolving pandemic caused by SARS-CoV-2, the causative agent of COVID-19 disease, and the potential for future infectious disease epidemics, it is important to understand the impact that COVID-19 has on hospitalization rates and mortality in this medically vulnerable population. The objective of this study was to describe hospitalization and case fatality rates secondary to COVID-19 among individuals living with SCD in different age groups and compare these to the general population. The Medical College of Wisconsin established the international SECURE-SCD Registry to collect data on pediatric and adult COVID-19 infections in individuals living with SCD. Providers are instructed to report confirmed COVID-19 cases to the registry after sufficient time has passed to observe the disease course through resolution of acute illness and/or death. For each case, providers complete a short form that includes the following data: patient demographics, COVID-19 related hospitalization, COVID-19 severity/management strategies, if the patient died due to COVID, and other information about SCD complications. Data are de-identified and without protected health information to facilitate rapid and increased reporting. We calculated the hospitalization rate and case fatality rate for individuals with SCD by specific age group and contrasted it with the rates publicly available for the general Black population. We utilized data from California Department of Public Health for case fatality rate comparison in Blacks and data from COVID-NET for hospitalization rate comparison. We used indirect age adjustment to calculate standardized mortality ratios using COVID-19 data from California state as the reference population. As of July 17th 2020, 218 cases of COVID-19 in Blacks with SCD in the US were reported to the registry. There was a slight predominance of females (52.8%) and 32.1% of reported cases were patients 18 years and under. There were 15 deaths reported with overall mortality rate of 6.9%. Figure 1 shows the distribution of cases and deaths by age group and gender. Mortality rate in SCD patients was highest in the 50-64 years age group (23.1%) in contrast to mortality rate peaks seen in the general population in patients older than 80 years (Table 1). Young adult SCD patients aged 18-34 years had a case fatality rate of 3.3% and those aged 34-50 years had a rate of 14.9%. California Department of Public Health report case fatality rates for Blacks are less than 1% in both of these comparative age groups. Age-standardized mortality ratio shows that individuals with SCD are 7.7 times more likely to die due to COVID-19 infection compared to the general population. The overall hospitalization rate in individuals with SCD was 72.5% and 18.8% of reported hospitalized cases were children. Among hospitalized adults with SCD, stratification by age showed that 85% were aged 18-49, whereas only 25.7% of people 18-49 years in the general Black population were hospitalized (Table 2). Our findings show that individuals with SCD who have COVID-19 infection have higher rates of death due to COVID-19 than the general Black population. Also, a large proportion of COVID hospitalization for the SCD population occurs among the younger age group. Further analysis is planned to examine effects of underlying comorbidities and prior SCD-associated complications on the severity of COVID-19 in individuals with SCD. Disclosures Mucalo: NIH/NHLBI: Research Funding; NIH/NINDS: Research Funding. Brandow:Greater Milwaukee Foundation: Research Funding; NIH / NHLBI: Research Funding. Panepinto:HRSA: Research Funding; NINDS: Research Funding; NINDS: Research Funding; NHLBI: Research Funding.

Although annual transcranial Doppler (TCD) screening is recommended for children with sickle cell anemia (SCA), compliance is low and variable. Our objective was to utilize an electronic health record (EHR)-based registry to improve TCD adherence among children with SCA, 2-16 years of age, at our institution.We developed an in-EPIC real time registry for children with sickle cell disease in year 2016. Since end of year 2016, we have been extracting data quarterly to examine TCD rates and share the list of children who have not received a TCD screen in the past 18 months with the clinical team. The registry also includes a TCD risk score to enhance point of care. We also added Child Life support to increase TCD compliance among children7 years. Control charts are used to examine TCD rates.At baseline, prior to and start of quarterly data audit and feedback, 63% of children received the recommended annual TCD screen. TCD rates steadily increased to 80% by the third quarter of 2017. We observed a dip in TCD rates, driven by failure of screening young children. Since the initiation of Child Life support for children7 years, we have sustained TCD screen rates70%. Overall, our data meet criteria for special cause variation, indicating improvement in TCD rates since 2015.Regular tracking and identification of patients overdue for a TCD screen using an EHR-based registry resulted in sustained improvement in TCD screening rates. Involvement of Child Life support further improved TCD rates.

Background Neuropathic pain is associated with poor health-related quality of life (HRQL) in pain conditions other than sickle cell disease (SCD); this relationship in SCD is unknown. We investigated this relationship and hypothesized neuropathic pain is associated with poor HRQL in adolescents with SCD. Methods We conducted a cross-sectional study of patients with SCD ages 13-18 years during baseline health. Primary outcome was HRQL, assessed by the PedsQL SCD Module (child self-report, parent proxy report). PedsQL is scored from 0 to 100, with higher scores indicating better HRQL. Neuropathic pain was assessed using the painDETECT questionnaire (scored 0-38); higher scores indicated greater likelihood of neuropathic pain. All completed both PedsQL SCD Module and painDETECT questionnaire. Descriptive statistics were used and associations between painDETECT and PedsQL Total Score, Pain Impact, Pain and Hurt, and Pain Management and Control Scores were determined via Pearson correlation. Significance was P Results Twelve patients were enrolled. Median (interquartile range [IQR]) age was 15 (14-16.5) years, 75% were female, and 83% were on hydroxyurea. Higher painDETECT scores were significantly associated with lower PedsQL SCD Module child self-report Pain and Hurt Scores (r = -0.68, P = .01). Higher painDETECT scores were also significantly associated with lower PedsQL parent proxy-report Total Scores (r = -0.64, P = .03) and Pain and Hurt Scores (r = -0.67, P = .02). Conclusions These data suggest that adolescents with SCD and neuropathic pain have poor HRQL even in their baseline state of health. Prospective, larger studies are needed to confirm this preliminary finding and explore a multimodal approach for pain assessment in SCD.

OBJECTIVE: Patient reported outcome measures, such as the Patient Reported Outcomes Measurement Information System (PROMIS) may be used to assess patient functioning for asthma and aid in understanding the impact of asthma exacerbation. These domains may be utilized as endpoints in clinical trials and to guide clinical care. The purpose of this study was to determine psychometric properties of the new PROMIS measures for children with asthma, at baseline and with exacerbation. METHODS: We conducted a cross-sectional analysis of children with acute asthma exacerbation or at baseline health. Psychometric properties of validity (using known groups and correlation) and reliability (using Cronbach’s alpha and IRT) for the new PROMIS measures were determined. RESULTS: Our study included 220 subjects, 102 were enrolled during an acute exacerbated state. Cronbach’s alpha and IRT reliability was greater or equal to 0.75. Our subjects experiencing an acute exacerbated state reported worse T-scores for pain related domains: pain behavior 45.7 vs 53.5 (p

OBJECTIVES The objective was to investigate the serial mediating effects of perceived cognitive functioning, patient health communication, and disease-specific worry in the relationship between pain and overall generic health-related quality of life (HRQOL) in youth with sickle cell disease (SCD) from the patient perspective. METHODS The pain, cognitive functioning, communication and worry scales from the Pediatric Quality of Life Inventory (PedsQL) Sickle Cell Disease Module and the PedsQL Multidimensional Fatigue Scale, and the PedsQL 4.0 Generic Core Scales were completed in a multisite national study by 233 youth with SCD of ages 5-18. Hierarchical multiple regression and serial multiple mediator model analyses were conducted to test the mediating effects of perceived cognitive functioning, health communication, and disease-specific worry as intervening variables in the association between the pain predictor variable and overall generic HRQOL. RESULTS Pain predictive effects on overall generic HRQOL were serially mediated by cognitive functioning, health communication, and disease-specific worry. In predictive analytics models utilizing hierarchical multiple regression analyses with age and gender demographic covariates, pain, cognitive functioning, health communication, and worry accounted for 65% of the variance in patient-reported overall generic HRQOL (P

Sickle cell disease (SCD) pain associates with cold temperature and touch. Patients and murine models with SCD have baseline thermal and mechanical pain. In SCD mice, the baseline hypersensitivity is exacerbated by experimental vaso-occlusive crises. We hypothesized that patients with SCD will similarly experience increased hypersensitivity to thermal and mechanical stimuli during acute painful events compared with baseline health. We conducted a prospective study of 24 patients with SCD aged 7 to 19 years. Patients underwent quantitative sensory testing to thermal (cold/heat) and mechanical stimuli on the thenar eminence of the nondominant hand (glabrous skin) and the lateral dorsum of the foot (hairy skin) during baseline health and within 48 hours of hospitalization for acute pain. Primary outcomes were changes in: (1) cold pain threshold (°C), (2) heat pain threshold (°C), and (3) mechanical pain threshold (g). Median age was 10.5 (interquartile range [IQR] 9-14.8) years, 67% were females, and 92% were on hydroxyurea. Patients with SCD had increased cold pain sensitivity in the hand during hospitalization compared with baseline (25.2°C [IQR 18.4-27.5°C] vs 21.3°C [IQR 4.9-26.2°C]; P = 0.011) and increased mechanical pain sensitivity in the foot during hospitalization (0.32 g [IQR 0.09-1.1 g] vs 1.7 g [IQR 0.4-8.3 g]; P = 0.003). There were no differences in heat pain sensitivity. The increased cold (P = 0.02) and mechanical (P = 0.0016) pain sensitivity during hospitalization persisted after adjusting for age, sex, hydroxyurea use, opioid consumption, and numeric pain score. Thus, cold and mechanical pain is significantly worse during an acute SCD painful event as compared to baseline health in patients with SCD.

Recurrent pain causes significant morbidity for individuals with sickle cell disease (SCD) and is a marker of mortality. Considering the current pandemic, it's important to understand how COVID-19 impacts individuals with SCD, a medically vulnerable population. We sought to identify factors associated with more severe COVID-19 illness and hospitalization in the SCD population. We established the international SECURE-SCD Registry to collect COVID-19 data in SCD patients. Providers were instructed to report confirmed COVID-19 cases after the disease course was known. Providers reported demographics, prior SCD complications and COVID-19 related hospitalization, severity/management strategies and death. Data were without protected health information. We used multivariable models to estimate the independent effects of age, sex, genotype, SCD-related and non-related comorbidities grouped by organ systems on the outcomes of severe COVID-19 and hospitalization. We defined the pain variable as 0, 1-2 or >2 prior acute care visits (i.e., emergency department visits, hospitalizations) for pain in the last 3 years. As of October 12th, 2020, 366 COVID-19 cases in SCD patients were reported, 41.5% were children and 52.7% were female. Acute pain was the most common presenting symptom of COVID-19 in SCD patients (54.6%), followed by pneumonia (27.0%). Children who had more than 2 acute care visits for pain had a more severe course of COVID-19 (OR=3.964, 95% CI (1.420, 11.065), p=0.03) and required hospitalization (OR=4.641, 95% CI (1.976, 10.900), p=0.006). Children who had 1-2 acute care visits for pain showed no significant association with COVID-19 severity (p=0.73) or hospitalization (p=0.82). In adults, there was no association between with history of frequent SCD pain and COVID outcomes. Pain is the most common presenting symptom of COVID-19 in SCD patients. Further, more than 2 prior acute care visits for pain is associated with severe COVID-19 course and hospitalization in children with SCD and not in adults. This work was supported by Grant 2020079 from the Doris Duke Charitable Foundation.

Aims The purpose of this work was to (1) compare pharmacokinetic (PK) parameters for hydroxycarbamide in children receiving their first dose (HCnew) versus those receiving chronic therapy (HCchronic), (2) assess the external validity of a published PK dosing strategy, and (3) explore the accuracy of dosing strategies based on a limited number of HC measurements. Methods Utilizing data from two prospective, multicenter trials of hydroxycarbamide (Pharmacokinetics of Liquid Hydroxyurea in Pediatric Patients with Sickle Cell Anemia; NCT01506544 and Single-Dose (SD) and Steady-State (SS) Pharmacokinetics of Hydroxyurea in Children and Adolescents with Sickle Cell Disease), plasma drug concentration versus time profiles were evaluated with a model independent approach in the HCnew and HCchronic groups. Various predictive senerios were analyzed to evaluate if systemic exposure with hydroxycarbamide could be accurately predicted. Results Absorption of hydroxycarbamide was rapid, variable and dose independent. Dose-normalized peak plasma concentrations and drug exposure (AUC) were higher, and weight-normalized apparent oral clearance was lower in the HCnew group. We assessed a PK-guided dosing strategy along with other predictive scenarios and found that inclusion of plasma samples only slightly improved the accuracy of AUC predictions when compared to a population-based method. Conclusions Children naive to hydroxycarbamide exhibit a different PK profile compared to children receiving chronic therapy. Accuracy of population-based dosing is sufficient to target AUCs in individual patients. Further clearance/bioavailability studies are needed to address the factors responsible for variability in the disposition of hydroxycarbamide.

BACKGROUND Little is known about red blood cell (RBC) transfusion practices for children hospitalized for a sickle cell vaso-occlusive pain crisis (VOC). We hypothesized that transfusion would be associated with the development of acute chest syndrome (ACS), lower hemoglobin (Hb) concentration, and lack of hydroxyurea therapy. STUDY DESIGN AND METHODS This is a secondary analysis of all children admitted for a sickle cell pain crisis enrolled in the Magnesium in Crisis (MAGiC) randomized trial; all had HbSS or S-β0 thalassemia. ACS development and transfusion administration were prospectively collected during the parent trial. All Hb values during the hospitalization were recorded, as was parent report of child receiving hydroxyurea. Relative risks (RRs) of transfusion were compared between groups. RESULTS Of 204 enrolled children, 40 (19.6%) received a transfusion. Of the 30 children who developed ACS, 22 (73.3%) received transfusions compared to 18 of 174 (10.3%) without ACS: the RR of transfusion in children with ACS was 7.1 (95% confidence interval [CI], 4.4-11.5). Among those without ACS, the lowest Hb was most strongly associated with transfusions: RR was 3.1 (95% CI 2.0 – 4.7) for each 1 g/dL decrease in lowest Hb. In a binary recursive partitioning model for those without ACS, a lowest recorded Hb level of less than 6.3 g/dL was significantly associated with transfusion during admission (p

INTRODUCTION: Pain, the most common complication of sickle cell disease (SCD), presents as both sudden acute pain and chronic daily pain. However, there is wide variability in frequency and presentation of pain despite inheritance of the same monogenic gene defect. SCD has long been recognized as a chronic inflammatory condition. The ongoing effect of repeated vaso-occlusion, ischemia-reperfusion injury and hemolysis contribute to further SCD inflammation and likely pain. Regulation of the immune response can potentially modulate the inflammatory impact on pain. The collective balance of these inflammatory mediators in union in SCD patients and how this balance may change during baseline health and acute pain is unknown. The objective of this work was to determine the balance between patients' inflammatory and immune regulatory response and examine whether this balance changes during acute pain in patients with SCD. METHODS: We conducted a cross sectional analysis involving 3 cohorts: patients with SCD who were in their baseline health state, patients with SCD who had an acute pain episode and healthy African American controls. We used a novel bioassay originally developed for use in type 1 diabetes and applied to cystic fibrosis, inflammatory bowel disease and influenza to determine the inflammatory/immune regulatory response. This response was calculated as a composite Inflammatory Index (I.I.com) from these 3 patient cohorts. Patient plasma was co-cultured with cryopreserved PBMCs from a healthy donor to induce transcription (Figure 1). We identified informative transcripts that differentiate SCD patients from healthy controls thereby defining the disease-specific plasma-induced signature and retained ones differentially expressed between patients with SCD and controls that exhibit a fold change >1.4, ANOVA p-value of RESULTS: Plasma from 16 patients with SCD in baseline health, 27 patients with SCD with an acute pain episode, and 45 African American controls were collected and analyzed. The average age of the study population was 12.6 (SD=3.6) years old and 52.3% were female. Quantitative scoring of plasma-induced signatures showed SCD patients had significantly higher mean I.I.com during baseline health compared to controls (0.713 vs. -1.235-12, p=5.4625-11). In addition, patients with SCD during acute pain episodes had significantly higher I.I.com than patients in baseline health (1.282 vs. 0.713, p=5.2051-8) (Figure 2). Heat map in Figure 3 shows differential gene expression between the cohorts; green and red colors in heat maps represent lower or higher relative expression respectively. CONCLUSION: Our findings show distinct immune signatures in SCD patients compared to controls and distinct signatures in SCD patients during acute pain episodes as compared to baseline health. The novel assay used to assess the inflammatory and immune regulatory gene expression in the three cohorts studied allowed for the determination of the balance between the two immune states. The imbalance between inflammation and immune regulation shown in our results in SCD patients of SCD pain. Further investigation into the specific inflammatory pathways that contribute to altered immune response could lead to novel targets for pain treatment. Disclosures Mucalo: NIH/NINDS: Research Funding; NIH/NHLBI: Research Funding. Jia:NIH/NHBLI: Research Funding; NIH/NINDS: Research Funding. Panepinto:NINDS: Research Funding; HRSA: Research Funding; NINDS: Research Funding; NHLBI: Research Funding. Roethle:NIH/NHLBI: Research Funding; NIH/NINDS: Research Funding. Hessner:NIH/NHLBI: Research Funding; NIH/NINDS: Research Funding. Brandow:NIH / NHLBI: Research Funding; Greater Milwaukee Foundation: Research Funding.

Background The Patient-Reported Outcomes Measurement Information System (PROMIS) includes multiple domains that measure pain and physical functioning which are valid and reliable for use in children with sickle cell disease. The responsiveness of these measures to detect changes in health status over time among children with sickle cell disease is unknown. Procedure We conducted a prospective cohort study of children presenting to emergency department (ED) with vaso-occlusive crises. Children completed PROMIS surveys in the ED and at two follow-up time points (7-10 days and 1-3 months) after their acute care visit. Linear mixed models were used to determine if there were significant changes in PROMIS T scores over time. We used a patient's global assessment of change in pain question to anchor the changes in PROMIS scores (mean and 95% confidence interval). A change was considered statistically significant if the 95% CI did not include 0. Results We found that patients improved significantly in all domains 1 to 3 months after discharge from an acute care visit for pain. In addition, the pain and physical stress experience domains were responsive to change 7 to 10 days after discharge. Using the anchor of change in pain, for children who had considerable improvement in pain, there were significant changes in PROMIS T scores ranging from 6 to 15. Conclusions Relevant PROMIS domains detect changes in children experiencing acute vaso-occlusive crises. These domains can be used in research and clinic settings to measure clinically relevant change in children with sickle cell disease.

BackgroundDonors other than matched siblings and low-intensity conditioning regimens are increasingly used in haematopoietic stem cell transplantation. We aimed to compare the relative risk of donor type and conditioning regimen intensity on the transplantation outcomes of in patients with sickle cell disease.MethodsFor this retrospective cohort study, we collected data from 90 US centres reported to the Center for International Blood and Marrow Transplant Research. Eligible patients were younger than 50 years, had genetically confirmed sickle cell disease (Hb SS) or sickle beta thalassemia (Hb Sβ), and underwent allogeneic haematopoietic cell transplantation between Jan 15, 2008, and Dec 28, 2017. We considered transplants from donor-recipient pairs matched at the allele-level (HLA-A, HLA-B, HLA-C, and HLA-DRB1), including HLA-matched sibling donors, haploidentical related donors, matched unrelated donors, or mismatched unrelated donors. The main outcome was event-free survival. The effect of donor type, conditioning regimen intensity (myeloablative, non-myeloablative, and reduced-intensity regimens), age (≤12 or 13-49 years), sex, performance score, comorbidity index, recipient cytomegalovirus serostatus, graft type (bone marrow, peripheral blood, or umbilical cord blood), and transplantation period (2008-12 and 2013-17) on outcomes was studied using Cox regression models.FindingsOf 996 patients with sickle cell disease and who underwent transplantation in 2008-17, 910 (91%) were included (558 [61%] patients had HLA-matched sibling donors, 137 [15%] haploidentical related donors, 111 [12%] matched unrelated donors, and 104 [11%] mismatched unrelated donors). The median follow-up was 36 months (IQR 18-60) after transplantation from HLA-matched siblings, 25 months (12-48) after transplantation from haploidentical related donors, 37 months (23-60) after transplantation from HLA-matched unrelated donors, and 47 months (24-72) after transplantation from mismatched unrelated donors. Event-free survival was worse in recipients aged 13 years or older than in those younger than 13 years (hazard ratio 1·74, 95% CI 1·24-2·45; p=0·0014) and in those who received a transplant from haploidentical related donors (5·30, 3·17-8·86; p

Patients with sickle cell disease frequently visit the emergency department for pain. The metric of emergency department reliance (EDR) describes emergency department utilization in relation to all ambulatory visits and serves as a quality of care indicator. This study uses Wisconsin Medicaid data from 2011 to 2015 to examine trend of EDR for pain over the period of 5 years. We stratified our cohort (N=750) by patient ages into 4 groups: (1) children; (2) transition group; (3) young adults; and (4) adults. Using a linear mixed model, we estimated longitudinal trends adjusting for age group and hydroxyurea possession calculated as medication possession ratio. Results show that EDR for pain has distinct temporal patterns for each group. EDR for pediatrics continually remained less than the established threshold of 0.33. The EDR for transition group significantly increased over time; however, the EDR for young adults has significantly decreased since 2011. There were no significant differences in EDR over time for adults older than 30 years. Overall, increase in medication possession ratio was associated with lower EDR. The low EDR for pain among children and the improvements among adults indicate the success of efforts for sickle cell disease patients. However, further interventions are needed for the transition age group.

The Patient Reported Outcomes Measurement Information System (PROMIS) pain interference and pain behavior domains are valid and reliable for children with sickle cell disease (SCD). However, clinical interpretation of the scores is unknown. The objective of this study was to determine the clinical meaning of PROMIS pain scores for children with SCD. We used 2 approaches to determine clinical meaning: dichotomization of item responses and T-score ranges. T-score ranges determined thresholds for no/mild, moderate, and severe pain. We compared the proportion of patients who needed pain medications among pain severity groups using χ2/Fisher’s exact tests. The study included 117 children (mean age, 11.5 years [standard deviation, 2.9 years]). Using the dichotomization approach, 43 children had pain interference T-scores ≤48 reflecting minimal pain, and 30 children had T-scores >60 reflecting substantial pain. For pain behavior, 34 children had T-scores ≤41 reflecting minimal problems, and 23 patients had T-scores >57 reflecting substantial problems with pain. Using T-score ranges, clinical thresholds of no/mild and severe pain interference were determined as ≤48.3 and >63.6, respectively. The thresholds for no/mild and severe pain behavior were ≤41.3 and >57.3, respectively. Overall, the proportion of patients who took pain medications was significantly different among those with no/mild, moderate, and severe pain as identified by pain interference (P = .002) and pain behavior domains (P = .0113). We identified T-scores for PROMIS pain domains that facilitate clinical interpretation and provide necessary information for PROMIS users in a clinical setting.

Objective To determine how infant illness and parent demographics are associated with parent health-related quality of life (HRQL) during and 3 months after hospitalization in the neonatal intensive care unit (NICU). We hypothesized that parents of extremely preterm infants would report lower NICU HRQL than other parents, and that all parents would report improved HRQL after discharge. Study design This prospective study of parent–infant dyads admitted to a level IV NICU for ≥14 days from 2016 to 2017 measured parent HRQL before and 3 months after discharge using the Pediatric Quality of Life Inventory Family Impact Module. Multivariable regression was used to identify risk factors associated with HRQL differences during hospitalization and after discharge. Results Of the 194 dyads, 167 (86%) completed the study (24% extremely preterm; 53% moderate to late preterm; 22% term). During the NICU hospitalization, parents of extremely preterm infants reported lower adjusted HRQL (−7 points; P = .013) than other parents. After discharge, parents of extremely preterm infants reported higher HRQL compared with their NICU score (+10 points; P = .001). Tracheostomy (−13; P = .006), home oxygen (−6; P = .022), and readmission (−5; P = .037) were associated with lower parent HRQL 3 months after discharge, adjusted for NICU HRQL score. Conclusions Parents of extremely preterm infants experienced a greater negative impact on HRQL during the NICU hospitalization and more improvement after discharge than parents of other infants hospitalized in the NICU. Complex home care was associated with lower parent HRQL after discharge. The potential benefit of home discharge should be balanced against the potential negative impact of complex home care.

Severe unpredictable acute pain and chronic daily pain causes significant morbidity for individuals with sickle cell disease (SCD). SCD is shown to be a chronic inflammatory disorder. Regulation of the immune response can potentially modulate the inflammatory impact on pain in SCD. We sought to determine the balance between patients’ inflammatory and immune regulatory response and examine whether this balance changes during acute SCD pain. We conducted a cross sectional analysis involving 3 cohorts: 16 SCD patients in baseline health, 27 SCD patients during acute pain and 45 healthy African American controls. Participant plasma was co-cultured with cryopreserved PBMCs from a healthy donor to induce transcription. We identified transcripts that differentiate SCD patients from healthy controls and retained ones differentially expressed that exhibit a fold change >1.4, ANOVA p-value of

Children with sickle cell disease experience organ damage, impaired quality of life, and premature mortality. Allogeneic bone marrow transplant from an HLA-matched sibling can halt disease progression but is limited by donor availability. A Blood and Marrow Transplant Clinical Trials Network (BMT CTN) phase 2 trial conducted from 2008 to 2014 enrolled 30 children aged 4 to 19 years; 29 were eligible for evaluation. The primary objective was 1-year event-free survival (EFS) after HLA allele-matched (at HLA-A, -B, -C, and -DRB1 loci) unrelated donor transplant. The conditioning regimen included alemtuzumab, fludarabine, and melphalan. Graft-versus-host disease (GVHD) prophylaxis included calcineurin inhibitor, short-course methotrexate, and methylprednisolone. Transplant indications included stroke (n = 12), transcranial Doppler velocity >200 cm/s (n = 2), ≥3 vaso-occlusive pain crises per year (n = 12), or ≥2 acute chest syndrome episodes (n = 4) in the 2 years preceding enrollment. Median follow-up was 26 months (range, 12-62 months); graft rejection was 10%. The 1- and 2-year EFS rates were 76% and 69%, respectively. The corresponding rates for overall survival were 86% and 79%. The day 100 incidence rate of grade II-IV acute GVHD was 28%, and the 1-year incidence rate of chronic GVHD was 62%; 38% classified as extensive. There were 7 GVHD-related deaths. A 34% incidence of posterior reversible encephalopathy syndrome was noted in the first 6 months. Although the 1-year EFS met the prespecified target of ≥75%, this regimen cannot be considered sufficiently safe for widespread adoption without modifications to achieve more effective GVHD prophylaxis. The BMT CTN #0601 trial was registered at www.clinicaltrials.gov as #NCT00745420.

Paradoxical' embolization via intracardiac or intrapulmonary right-to-left shunts (RLS) is an established cause of stroke. Hypercoagulable states and increased right heart pressure, which both occur in sickle cell anaemia (SCA), predispose to paradoxical embolization. We hypothesized that children with SCA and overt stroke (SCA + stroke) have an increased prevalence of potential RLS. We performed contrasted transthoracic echocardiograms on 147 children (aged 2-19 years) with SCA + stroke) mean age 12·7 ± 4·8 years, 54·4% male) and a control group without SCA or stroke (n = 123; mean age 12·1 ± 4·9 years, 53·3% male). RLS was defined as any potential RLS detected by any method, including intrapulmonary shunting. Echocardiograms were masked and adjudicated centrally. The prevalence of potential RLS was significantly higher in the SCA+stroke group than controls (45·6% vs. 23·6%, P < 0·001). The odds ratio for potential RLS in the SCA + stroke group was 2·7 (95% confidence interval: 1·6-4·6) vs controls. In post hoc analyses, the SCA + stroke group had a higher prevalence of intrapulmonary (23·8% vs. 5·7%, P < 0·001) but not intracardiac shunting (21·8% vs. 18·7%, P = 0·533). SCA patients with potential RLS were more likely to report headache at stroke onset than those without. Intrapulmonary and intracardiac shunting may be an overlooked, independent and potentially modifiable risk factor for stroke in SCA.

Youth directly exposed to violence are at risk for experiencing elevated rates of emotional and behavioral problems, revictimization, and becoming future perpetrators of violence. Violence intervention and prevention programs throughout the country attempt to alleviate some of this burden. To date, outcomes have been positive but largely qualitative. Patient-reported outcomes offer objective measures to evaluate well-being in youth victimization. Our primary aim was to use objective patient-reported quantitative measures to assess the change in health-related quality-of-life (HRQOL) scores of youth who attended a violence intervention summer camp. This is the first study to evaluate such measures in youth victims of violence during an intervention.Eight- to 18-year-old youth who attended a violence intervention summer camp in a Midwest urban city over a two-year period participated in a HRQOL survey at baseline and at the end of programming (6 weeks). Consented youth used an electronic platform to answer validated HRQOL measures. Mean differences in scores from baseline to six weeks were calculated and reported.A total of 64 youth were recruited and consented to the study. Average change in scores improved in most HRQOL domains with the largest change in scores observed in school functioning (mean diff, +5.00), emotional functioning (mean diff, +5.26), and patient anxiety (mean diff, +3.04). Only participant anger scored worse following the intervention (mean diff, -2.26).A community-based summer program hosting violently injured youth resulted in overall improved HRQOL. This was especially significant in the school, anxiety, and emotional domains. Future evaluation into the effectiveness of youth programs should measure HRQOL to identify at-risk participants and to measure effectiveness.Therapeutic/care management study, level III.

The impact of emergency department (ED) treatment on outcomes of sickle cell disease (SCD) acute pain hospitalizations is not well described. We investigated whether length of stay (LOS) and change in health-related quality of life (HRQL) are affected by initial opioid dose and time to administration. We conducted secondary analyses of data from the randomized-controlled Magnesium for children in Crisis (MAGiC) trial. The primary outcome was LOS. Secondary outcome was change in HRQL, assessed using PedsQL SCD Pain and Hurt and Pain Impact Domains measured in ED and at discharge. Independent variables were (1) time to first IV opioid, (2) total initial opioid dose (mg/kg/hr of morphine equivalents administered between ED and first study drug), and (3) Time to first oral opioid. Spearman correlations determined the associations with LOS. Using two-sample t-tests, we compared mean change in HRQL scores between IV opioid initiated within 60 and60 min, opioid doses in the highest and lowest tertiles, and oral opioid initiated within 24 and24 hr. Two hundred and four patients participated at 8 sites. Mean (SD) age was 13.6 (4.7) years. Earlier initiation of oral opioids was strongly correlated with shorter LOS (r = 0.61, P 0.01). Higher initial opioid dose was weakly correlated with longer LOS (r = 0.34, P 0.01). Higher initial opioid doses (6 vs -2.2; P = 0.01) and oral opioids initiated within 24 hr (5.7 vs -1.7, P = 0.04) were associated with larger mean change in HRQL at discharge. Prospective trials evaluating the impact of ED care on outcomes of pain hospitalizations could improve SCD pain treatment. Am. J. Hematol. 91:1175-1180, 2016. © 2016 Wiley Periodicals, Inc.

Choosing Wisely (CW) is a medical stewardship initiative led by the American Board of Internal Medicine Foundation in collaboration with professional medical societies in the United States. In an effort to learn from and leverage the work of others, the American Society of Hematology CW Task Force developed a method to identify and prioritize CW recommendations from other medical societies of high relevance and importance to patients with blood disorders and their physicians. All 380 CW recommendations were reviewed and assessed for relevance and importance. Relevance was assessed using the MORE(TM) relevance scale. Importance was assessed with regard to six guiding principles: harm avoidance, evidence, aggregate cost, relevance, frequency and impact. Harm avoidance was considered the most important principle. Ten highly relevant and important recommendations were identified from a variety of professional societies. Recommendations focused on decreasing unnecessary imaging, blood work, treatments and transfusions, as well as on increasing collaboration across disciplines and considering value when recommending treatments. Many CW recommendations have relevance beyond the society of origin. The methods developed by the ASH CW Task Force could be easily adapted by other Societies to identify additional CW recommendations of relevance and importance to their fields. Am. J. Hematol. 91:787-792, 2016. © 2016 Wiley Periodicals, Inc.

Adults with sickle cell disease (SCD) report problems in relationship building and information exchange during clinic visits. To explore the origin of these communication challenges, we compare communication in pediatric SCD, diabetes, and asthma visits. We collected visit videos and parent surveys from 78 children ages 9–16 years with SCD, asthma, or diabetes. Coders assessed child, parent, and physician utterances reflecting relationship building, information giving, and information gathering. Associations of engagement with type of chronic disease visit were performed with negative binomial regression. Compared to SCD visits, children in diabetes visits spoke 53% more relationship-building utterances (p < .05) and physicians in asthma visits spoke 48% fewer relationship building utterances to the child (p < .01). In diabetes visits, physicians gave almost twice as much information to children and gave 48% less information to parents (both p < .01) compared to SCD visits. Compared to SCD visits, physicians spoke fewer information-gathering utterances to parents in diabetes and asthma visits (85% and 72% respectively, both p < .001). SCD visits reflect less engagement of the children and greater physician effort to gather information from parents. These differences highlight opportunities to enhance engagement as a mechanism for ultimately improving SCD care.

Background Measuring adolescents’ preferences for health states can play an important role in evaluating the delivery of pediatric healthcare. However, formal evaluation of the common direct preference elicitation methods for health states has not been done with adolescents. Therefore, the purpose of this study is to test how these methods perform in terms of their feasibility, reliability, and validity for measuring health state preferences in adolescents. Methods This study used a web-based survey of adolescents, 18 years of age or younger, living in the United States. The survey included four health states, each comprised of six attributes. Preferences for these health states were elicited using the visual analogue scale, time trade-off, and standard gamble. The feasibility, test-retest reliability, and construct validity of each of these preference elicitation methods were tested and compared. Results A total of 144 participants were included in this study. Using a web-based survey format to elicit preferences for health states from adolescents was feasible. A majority of participants completed all three elicitation methods, ranked those methods as being easy, with very few requiring assistance from someone else. However, all three elicitation methods demonstrated weak test-retest reliability, with Kendall’s tau-a values ranging from 0.204 to 0.402. Similarly, all three methods demonstrated poor construct validity, with 9–50% of all rankings aligning with our expectations. There were no significant differences across age groups. Conclusions Using a web-based survey format to elicit preferences for health states from adolescents is feasible. However, the reliability and construct validity of the methods used to elicit these preferences when using this survey format are poor. Further research into the effects of a web-based survey approach to eliciting preferences for health states from adolescents is needed before health services researchers or pediatric clinicians widely employ these methods. Electronic supplementary material The online version of this article (10.1186/s12887-018-1179-7) contains supplementary material, which is available to authorized users.

Sickle cell disease (SCD) is a group of inherited disorders caused by mutations in HBB, which encodes haemoglobin subunit β. The incidence is estimated to be between 300,000 and 400,000 neonates globally each year, the majority in sub-Saharan Africa. Haemoglobin molecules that include mutant sickle β-globin subunits can polymerize; erythrocytes that contain mostly haemoglobin polymers assume a sickled form and are prone to haemolysis. Other pathophysiological mechanisms that contribute to the SCD phenotype are vaso-occlusion and activation of the immune system. SCD is characterized by a remarkable phenotypic complexity. Common acute complications are acute pain events, acute chest syndrome and stroke; chronic complications (including chronic kidney disease) can damage all organs. Hydroxycarbamide, blood transfusions and haematopoietic stem cell transplantation can reduce the severity of the disease. Early diagnosis is crucial to improve survival, and universal newborn screening programmes have been implemented in some countries but are challenging in low-income, high-burden settings.