Sickle Cell Disease Module Research Articles

The relationship between cumulative risk and health-related quality of life in youth with sickle cell disease: Moderating effects of secondary control engagement coping.

Youth with sickle cell disease (SCD) often experience low health-related quality of life (HRQOL). Engagement in resilience-promoting processes, such as secondary control engagement (SCE) coping, or adapting to stressors, may be linked to contextual risk factors (e.g., poverty status). This study aims to illuminate relationships between a cumulative risk index (CRI), SCE coping, and HRQOL in youth with SCD and test whether SCE coping moderates the relationship between CRI and HRQOL. Participants in this cross-sectional study included 63 youth ages 8-18 with SCD. Participants completed measures to assess SCE coping use (Responses to Stress Questionnaire) and HRQOL (PedsQL SCD Module). Six variables from the electronic medical record were compiled in a CRI. Correlational and regression analyses examined relationships between primary variables and moderating effects of SCE coping, respectively. Model results show that SCE coping and CRI explain variation in HRQOL (p=.001), and a significant interaction exists between SCE and CRI (β=-.29, p=.02), with a stronger inverse relationship between CRI and HRQOL for higher SCE values. This suggests that lower CRI is associated with greater HRQOL for those with higher SCE coping relative to lower SCE coping. SCE coping may selectively benefit children with SCD experiencing lower cumulative risk, warranting encouragement of this strategy in clinical settings. Findings do not support SCE coping benefits for youth with higher risk, suggesting that the strategy may not be useful when risk-related stressors are especially pervasive; alternative protective factors should be identified for this risk group.

Translation, transcultural adaptation, and validation of PedsQL 3.0 Sickle Cell Disease Module into Brazilian Portuguese.

Despite the high prevalence of sickle cell disease (SCD) in Brazil, no studies have described the validation of an SCD-specific health-related quality-of-life (HRQoL) instrument in children. We validated PedsQL 3.0 Sickle Cell Disease Module (PedsQL-SCD) for Brazilian Portuguese, and cross-validated it with PedsQL 4.0 Generic Core Scale (PedsQL-GCS) in children with SCD. PedsQL-SCD was translated and culturally adapted using forward and reverse translations. PedsQL-SCD and PedsQL-GCS were tested in children and adolescents with SCD aged 2-18years and their caregivers. Validity was assessed using the Pearson and intraclass correlation coefficients, and reliability measured with Cronbach's alpha. PedsQL-SCD was validated in 206 children with SCD (median age 14years, range: 8-18) and 201 caregivers. Among patients and caregivers, the mean total score for PedsQL-SCD was 65.7 and 64.1, respectively. The mean total score for PedsQL-GCS was 73.1 and 68.9 among patients and caregivers, respectively. The internal consistency for PedsQL-SCD and PedsQL-GCS was good; Cronbach's alpha coefficients ranged from .59-.93 to .64-.83 among patients and from .60-.95 to .65-.85 among caregivers, respectively. Most intercorrelations between PedsQL-SCD and PedsQL-GCS, for patients and caregivers, had medium to large effect sizes (range: .23-.63 and .27-.64, respectively). Pain and pain impact domains of PedsQL-SCD and physical dimension of PedsQL-GCS had the highest cross-correlation (.63 and .6 for patients; .63 and .64 for caregivers, respectively), confirming convergent construct validity. PedsQL-SCD is a valid, culturally appropriate measure to assess HRQoL in children with SCD in Brazil and is well-correlated PedsQL-GCS.

The Relationships between Family Resources, Parental Stress, and Child Well-Being in Pediatric Sickle Cell Disease

Introduction: Parents and caregivers play an important role in the management of pediatric chronic illness. In sickle cell disease (SCD), families often manage multiple components simultaneously, such as attending clinic appointments, following a medication regimen, and treating pain symptoms. The availability of resources is known to affect disease management. However, it is unknown how children and parents view their resource availability, and how this can impact both parent stress and child quality of life (QoL). The current study examined the ways in which family resources, parental stress, and child well-being interact with and potentially influence each other. We hypothesize the following: 1) There is a relationship between family resources and child well-being such that more family resources leads to higher quality of life reporting; 2) There is a relationship between family resources and parental stress such that more family resources leads to lower parental stress; and 3) Parental stress moderates the relationship between family resources and child well-being. Methods : Parents of youth with SCD reported on the adequacy of their family's resources by completing the 30-item Family Resource Scale (FRS), rating items on a 5-point Likert scale (1 = not adequate at all to 5 = almost always adequate). Parents also reported on their parental stress by completing the 42-item Pediatric Inventory for Parents (PIP), rating items on a 5-point Likert scale (1 = never/not at all to 5 = very often/extremely). Children and parents reported on the child's overall well-being by completing the 43-item PedsQL SCD Module self-report form and 43-item parent proxy-report, rating items on a 5-point Likert scale (0 = never to 5 = almost always). Pearson's correlation coefficients were calculated to measure relationships between family resources (FRS) and child well-being (PedsQL), family resources (FRS) and parental stress (PIP), and parental stress (PIP) and child well-being (PedsQL). Multiple regressions were used to determine if parental stress moderated, or changed the effect of, family resources on child well-being. Results: Seventy-eight primary caregivers of youth aged 7-16 with SCD (Mean age = 10.37, SD = 2.86; 58% female; 68% HbSS; 87% African American or Black; 90% Not Hispanic) completed measures on their family resources and parental stress. Preliminary correlation analyses show the relationship between family resources and child self-reports on QoL was weak, positive, and not significant (r = 0.18, p = .167). The relationship between family resources and parent proxy-reports on QoL, however, was moderate, positive, and significant (r = .36, p = .001). The correlation between family resources and parental stress was moderate, negative, and significant (r = -.42, p < .001). The correlation between parental stress and child QoL self-reports was weak, negative, and significant (r = -.225, p = .05). The correlation between parental stress and parent proxy-reports on child QoL was moderate, negative, and significant (r= -.50, p = <.001). Multiple regression results for parent proxy-reports on child QoL show parental stress significantly and negatively impacts parent proxy-reports on child QoL (b = -5.52, p = .034). The relationship between family resources and parent proxy-reports on child QoL was not moderated by parental stress (b = 2.44, p = .207). Conclusion: There is a relationship between family resources and child well-being such that more resources reflect higher quality of life, but only when the parents are reporting on their child's well-being. Current results also show that as family resources decrease, parental stress moderately increases. Parental stress significantly impacted both self-reports and parent proxy-reports on child quality of life, though there was a weaker relationship shown in child self-reports. It's likely that parents who are more stressed view their child as being more stressed. Future interventions should consider including parent components to 1) further understand the role of parental stress as it relates to pediatric SCD management and 2) identify ways to best support families experiencing resource inadequacy or high levels of parental stress. Developing screeners to give to parents of youth with SCD during clinic appointments could offer a destigmatized way of connecting families to resources and providing tools for parental stress management.

The Impact of Socio-Economic Determinants of Health on PedsQL and Pain Outcomes Among Individuals with Sickle Cell Disease

Background: Pain in sickle cell disease (SCD) is the most visible symptom in patients. Many recent studies have shown that socio-economic status such as low income, educational achievement or even less affluent neighborhoods may contribute to the pain experience, with those of lower socioeconomic status (SES) reporting both acute and chronic pain more frequently. Furthermore, living in a less affluent area was associated with frequent use of analgesics after adjustment for pain intensity. The relationships between SES variables, pain-related anxiety, frequency of vaso-occlusive crises and/or acute care utilization have been explored; nevertheless, the relationship between SES and quality of life pain-related measures (pain hurt, pain interference, etc.) has yet to be reported. Methods: The St. Jude Children's Research Hospital Sickle Cell Clinical Research and Intervention Program (SCCRIP) is an observation cohort study of clinical outcomes in patients with SCD. Patients enrolled in SCCRIP were retrospectively evaluated based on various SES measurements. Household SES was evaluated using the Barratt Simplified Measure of Social Status (BSMSS), a composite index of parent education and occupation. The Social Vulnerability Index (SVI) was used to classify individuals based on social vulnerabilities at the neighborhood level. The area deprivation index (ADI) ranks neighborhood in a region of interest based on social risk factors that may predispose individuals to worse clinical outcomes Quality of life measures, Pain Hurt, Pain Impact, and Pain Management/Control, were extracted from the PedsQL SCD Module. High scores on the SVI and ADI are associated with low SES and high scores on the PedsQL indicate better SCD related quality of life (QoL) with lower burden and impact of pain on function. Multivariate linear regression models were used to evaluate the associations of SES with QoL pain-related outcomes, based on a stepwise model selection strategy, with potential covariates including age, gender, disease-modifying therapy (e.g., Hydroxyurea and chronic transfusions), hemoglobin, hemoglobin F (HbF)%, and each SES variable. Results: 944 patients between the ages of 5-61 (Mean=13.75, Standard Deviation=7.57) years diagnosed with SCD completed PedsQL testing and were assessed for SVI and ADI. Multivariate models demonstrated that patients with lower SVI (i.e., higher neighborhood SES) at the neighborhood level displayed higher scores with regards to Pain Hurt (est=-7.44, standard error (SE)=2.84, p=0.01), Pain Impact (est=-9.56, SE=3.18, p=0.003) and Pain Management/Control (est=-9.35, SE=3.81, p=0.01). Similar relationships were observed for patients with lower ADI. Additionally, there was a significant association between pain impact and BSMSS (est=0.20, SE=0.10, p=0.04), suggesting that individuals with higher BSMSS (higher household SES) also had higher pain impact scores (better quality of life). Conclusions: This study demonstrated that neighborhood and household SES have an impact on pain experience in youth with SCD. Patients with increased social vulnerability and area deprivation experienced lower health-related quality of life-related to SCD pain. Increased household SES was associated with greater SCD pain impact independent of the effects of patient age, gender, SCD therapy, and HbF. Our study suggests that social determinants of health, such as SES, play a role in pain experience and QOL related to SCD pain and should be explored further.

Agreement between youth and caregiver report of pain and functioning in pediatric sickle cell disease: PedsQL sickle cell disease module.

Pain is a primary symptom of sickle cell disease (SCD) and is often severe and chronic. To treat SCD-related pain, proper assessment of SCD pain among youth, including the degree of concordance or agreement between youth and caregiver reports of pain, is essential but has not yet been adequately evaluated. In this study, 525 youth with SCD and their parents were evaluated as part of the Sickle Cell Clinical Research and Intervention Program (SCCRIP) to examine pain rating concordance and predictors of concordance. Youth and parents completed the Pediatric Quality of Life Inventory Sickle Cell Disease module (PedsQL-SCD) to measure pain, pain interference, and pain-related constructs. Disease, clinical, and demographic variables were obtained from the SCCRIP database. Intraclass correlations demonstrated moderate-to-poor consistency between youth and caregiver reports of pain and pain interference (ICCs range from 0.17 to 0.54). Analysis of covariance and regression models found that patient age, frequency of hospitalizations and emergency department (ED) visits, economic hardship, and fetal hemoglobin levels were significantly associated with varying pain-rating agreement levels among parent proxy and child self-report pain. Concordance of pain assessments among youth with SCD and their caregivers using the PedsQL-SCD Module was moderate at best, corroborating prior research. Youth factors predicting discordance among pain-related factors included increased ED visits, older age, and female sex. Collectively, these results bolster the use of integrated pain assessments to reduce parent-child discrepancies, thereby improving the adequacy of SCD-related pain assessment and treatment.

5613868 THE IMPACT OF SOCIAL SUPPORT ON PERCEIVED SELF-EFFICACY IN HEALTH COMMUNICATION AMONG CHILDREN WITH SICKLE CELL DISEASE

Background: Health communication has been associated with self-reported overall health-related quality of life (HRQL) in children with sickle cell disease (SCD). Yet, we know little about what mechanisms contribute to patients’ perceived self-efficacy in health communication. Studies have shown associations between social support from parents and better overall HRQL for children with SCD. Social support from parents (or other adults) may also be associated with health communication. Aims: To study the direct association of social support from parents and teachers with perceived self-efficacy in health communication in a sample of pediatric patients with SCD. Methods: Youth with SCD between ages 7-16 years completed the parent and teacher subscales of the Social Support Scale for Children (e.g., “Other kids have parents who do want to listen to their children’s problems.”) and the PedsQL SCD Module. A multiple regression analysis was conducted to examine associations between perceived social support from parents and teachers and health communication (PedsQL SCD Module Communication I domain; e.g., “It is hard to tell the doctors and nurses how I feel.”). Higher scores on the social support scale indicates more social support from parents, and higher scores on the PedsQL SCD Module Communication I domain reflects greater ease in talking to medical providers about their health. Results: The current study included 21 pediatric patients diagnosed with SCD in the US (M = 11.38 [SD = 2.78] years), with an almost equal number of girls (n = 11) and boys (n = 10). Reported SCD genotypes included HbSS (n = 14), HbSC (n = 6), and HbS-beta0 thalassemia (n = 1). The results of the multiple regression indicated that the model explained 30.6% of the variance and that social support was positively and significantly associated with perceived self-efficacy in health communication, F(2,17) = 3.75, p <.05. While social support from the parent significantly contributed to the model (B = 27.70, p <.05), social support from the teacher did not (B = -12.26, p =.12). Conclusion: Findings suggest that social support from parents can have a significant impact on patients’ perceived self-efficacy in health communication. Results from this study could inform interventions aimed at addressing social support from parents as a way to enhance children’s comfort in communicating with health care providers about their SCD. Future studies should explore potential moderating and mediating variables affecting the association between social support from parents and health communication to aid in developing and tailoring behavioral interventions.

Association of Sickle Cell Pain & Symptoms on Health-Related Quality of Life Among Pediatric Patients.

Sickle cell disease (SCD) may cause significant complications leading to increased disease burden and poor psychosocial functioning. Yet, little is known about specific disease-related variables associated with decreased health-related quality of life (HRQOL) of this population. This study aims to discover whether pain and disease-related symptoms are associated with the HRQOL of pediatric patients diagnosed with SCD. A total of 150 patient (ages 8-17 years) and parent dyads were enrolled in this cross-sectional quantitative research study. Measures of HRQOL were gathered using the Pediatric Quality of Life (PedsQL) 3.0 SCD module, while the frequency of pain and SCD-related symptoms was reported by parent-proxy. Linear regression was deployed to analyze whether pain and SCD-related symptoms separately predict HRQOL scores in youth with SCD. Study results revealed that the frequency of pain (P < 0.001) and SCD-related symptoms (P < 0.001) predicted lower HRQOL scores in children and adolescents with SCD. Moreover, age (P < 0.05) emerged as a significant predictor of HRQOL in this sample. Pain and disease-related symptoms separately predicted lower HRQOL scores in the study sample, which shows that other SCD-related symptoms aside from pain has the potential to negatively impact youth with SCD. Implications for these findings extend the knowledge of clinicians in the healthcare setting to recognize the detriment of other SCD-related symptoms that may be overlooked, as pain is often the focus.

Health‐related quality of life of patients with sickle cell disease aged 8–17 years at Kamuzu Central Hospital, Malawi

Sickle cell disease (SCD) is characterized by both acute and chronic complications that affect the daily lives of patients and lower their quality of life. To describe the health-related quality of life (HRQoL) and the associated factors in children aged 8-17 years with SCD attending the pediatric hematology clinic at Kamuzu Central Hospital (KCH) in Lilongwe, Malawi. A mixed-methods cross-sectional study was conducted at KCH. Patient data were collected with the aid of a standardized case report form. HRQoL was assessed using PedsQL™ Sickle Cell Disease Module by the child's report. Associations between HRQoL scores and independent variables were evaluated by a linear regression model. In-depth interviews were then carried out and the qualitative data were analyzed using content thematic analysis. A hundred and sixty-three children with SCD were enrolled and 52.1% were females. Their median age was 11.2±2.7 years. The mean global HRQoL score of the children was 62 ±17.3. The highest scores were in the treatment domain (72.5±15.1) while the lowest scores were in the emotions domain (55.2±28.7). The mean pain score was 58.8±16.3. The factors associated with low HRQoL scores were pain (β-coefficient -6.97 CI (-3.07,-15.58); p value .034) and low hemoglobin levels (β-coefficient 2.29 CI (.65-3.91); p value .006). The HRQoL of this population is low. Pain and low hemoglobin were significantly associated with low HRQoL scores. Adequate treatment to control pain and increase the steady-state hemoglobin may improve the HRQoL of children with SCD. Interventions to address low emotional scores are recommended.

The pleiotropic effects of α-thalassemia on HbSS and HbSC sickle cell disease: Reduced erythrocyte cation co-transport activity, serum erythropoietin, and transfusion burden, do not translate into increased survival.

α‐Thalassemia is one of the most important genetic modulators of sickle cell disease (SCD). Both beneficial and detrimental effects have been described previously. We use a 12‐year data set on a large cohort of patients with HbSS (n = 411) and HbSC (n = 146) to examine a wide range of these clinical and laboratory associations. Our novel findings are that α‐thalassemia strongly reduces erythrocyte potassium chloride co‐transporter (KCC) activity in both HbSS and HbSC (p = .035 and p = .00045 respectively), suggesting a novel mechanism through which α‐thalassemia induces a milder phenotype by reducing red cell cation loss. This may be particularly important in HbSC where reduction in mean cell hemoglobin concentration is not seen and where KCC activity has previously been found to correlate with disease severity. Additionally, we show that α‐thalassemia not only increases hemoglobin in patients with HbSS (p = .0009) but also reduces erythropoietin values (p = .0005), demonstrating a measurable response to improved tissue oxygenation. We confirm the reno‐protective effect of α‐thalassemia in patients with HbSS, with reduced proteinuria (p = .003) and demonstrate a novel association with increased serum sodium (p = .0004) and reduced serum potassium values (p = 5.74 × 10−10). We found patients with α‐thalassemia had a reduced annualized transfusion burden in both HbSS and HbSC, but α‐thalassemia had no impact on annualized admission rates in either group. Finally, in a larger cohort, we report a median survival of 62 years in patients with HbSS (n = 899) and 80 years in those with HbSC (n = 240). α‐thalassemia did not influence survival in HbSS, but a nonsignificant trend was seen in those with HbSC.

Healthcare utilization and the quality of life of children and adolescents with sickle cell disease.

Youth diagnosed with sickle cell disease (SCD) are at increased risk of poor health-related quality of life (HRQOL) due to the complexities associated with this disease. The literature notes that predictors such as pain and poor mental health are associated with increased healthcare access; however, the connection between healthcare use and their overall well-being has been understudied. This study investigates whether healthcare utilization predicts the HRQOL in youth with SCD. Patients completed the Pediatric Quality of Life (PedsQL) 3.0 SCD module, whereas the researcher conducted a retrospective chart review to gather patient characteristics such as emergency room (ER) and hospitalization occurrences over the past 12 months. The study consisted of 150 pediatric patients with SCD, ages 8-17 years old, and their parents. Patients with≥4 ER visits and hospitalizations reported worse HRQOL scores than their respective counterparts. Additionally, a higher frequency of ER visits (P=0.05) and hospitalizations (P=0.005) predicted lower HRQOL scores. Age (P=0.04) also emerged as a significant predictor for both regression models, as increased healthcare access among older patients with SCD was associated with poorer HRQOL. This study found that as youth with SCD require ER treatment and/or hospital admission, they are at increased risk for lower HRQOL, specifically as they get older. Findings suggest that attention should be paid to patients who require more frequent healthcare intervention. Improvement in outpatient care of pediatric patients with SCD may help to mitigate ER and inpatient use.

Comparison of the Impact of a mHealth Self-Management Intervention on Adolescents Versus Young Adults with Sickle Cell Disease

Introduction: Pain and other symptoms of sickle cell disease (SCD) begin in childhood and contribute to poorer quality of life. Complications, risk of death, and symptom burden increase during transition from adolescence to adulthood; self-management is critical for transition readiness and symptom improvement. A mHealth self-management intervention for children/adolescents with SCD and their caregivers (Voice Crisis Alert V2) was adapted to facilitate transition from parent-led management to adolescent self-management. This abstract presents the preliminary impacts of the intervention on symptoms and QOL outcomes and compares findings between adolescents and young adults.Methods: The names and features of the Voice Crisis Alert V2 application (app) components are in Table 1. Targeted sample sizes were 30 dyads of adolescents with SCD ages 11 - 17 and the parent/caregiver and 15 young adults with SCD ages 18 - 25 who had not transitioned to adult care. Data sources included app use, and surveys at baseline, mid-intervention, end-of-intervention, and post-intervention. Adolescent surveys included: the PROMIS SF for anxiety, depressive symptoms, fatigue, pain interference, and pain intensity; the PedsQL with Sickle Cell Disease Module (SCDM) for health-related quality of life (HRQOL); the Sickle Cell Self-Efficacy Scale; and the STARx for transition readiness. Young adult surveys included: the PROMIS SF for anxiety, depression, fatigue, pain interference, pain intensity, and sleep disturbance; the ASCQ-Me for HRQOL; the Sickle Cell Self-Efficacy Scale; and the STARx for transition readiness. Analysis was conducted using descriptive statistics and Spearman's rho. Independent variables were length of time using the app and frequency of app use total and by component. Dependent variables were pre-post intervention differences in scores for outcomes that were key targets of the intervention. Results are reported with 95% CI.Results: Among both groups (adolescents and young adults), pre-post intervention differences in scores indicated improvement in nearly all symptom outcomes; greatest improvement was in pain interference for both groups and fatigue in young adults. Improvements in HRQOL were also noted in nearly all domains for both groups. Adolescents had greatest improvement in school functioning, total SCDM score and subscales for pain and hurt, pain impact, worry I, emotions, and communication II, and young adults in emotional impact, social impact, and pain impact. No to slight improvements in self-efficacy and transition readiness were observed in both groups. Most correlations across groups had CIs that crossed zero, which suggests associations observed in the population may be positive or negative. Twelve correlations did not cross zero in the adolescent sample compared with 1 in the young adult sample, though 5 additional strong correlations were noted. Of the strongest correlations in young adults, all but 1 indicated more time spent using the app was associated with greater improvement in scores. Of the strongest correlations in adolescents, 5 indicated more frequent app use was associated with greater improvement in scores, 3 indicated more frequent app use was associated with less substantial improvement in scores, 3 indicated more time spent using the app was associated with greater improvement in scores, and 1 indicated more time spent using the app was associated with less substantial improvement in scores.Conclusions: Similarities in pre-post intervention differences in scores suggest consistency in intervention impact on outcomes between adolescents and young adults who have not transitioned to adult care. The intervention may be particularly useful for improving pain interference, emotional impact/functioning, school or social impact/functioning, and pain impact/functioning. Little improvement was noted in transition readiness scores in either group, suggesting the intervention may need to include more robust strategies for transition preparation. There were few consistencies between groups in correlation findings; greater improvement in scores may be attributed to more time spent on app activities in young adults compared with greater frequency of use in adolescents. Future efficacy testing with a larger sample is warranted, to include exploration of associations between app use and outcomes across subgroups with varying characteristics. [Display omitted] DisclosuresKanter: Fulcrum Therapeutics, Inc.: Consultancy; Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Forma: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Agios: Honoraria, Membership on an entity's Board of Directors or advisory committees; Beam: Honoraria, Membership on an entity's Board of Directors or advisory committees; Sanofi: Honoraria, Membership on an entity's Board of Directors or advisory committees; Graphite Bio: Consultancy; GuidePoint Global: Honoraria; Fulcrum Tx: Consultancy.

Vitamin D Levels: Associations with Acute Pain Events and Self-Reported Pain in Children with Sickle Cell Disease

Background/Aims: Individuals with sickle cell disease (SCD) are at high risk for vitamin D deficiency due to dark skin color, limited physical activity, poor nutrition, and renal dysfunction. In smaller retrospective studies, vitamin D deficiency in SCD was associated with increased frequency of acute pain events and higher opioid use, however the impact of vitamin D deficiency on pain related patient reported outcomes has not been described . Supplementation with high dose vitamin D is shown to be associated with fewer pain days per week and higher physical activity scores in patients with chronic pain. Thus, the objective of our study was to evaluate relationship between vitamin D levels, acute health care utilization and self-reported pain among children with SCD. We hypothesized that vitamin D deficiency is associated with increase health care utilization for pain and patient-reported outcomes for pain.Methods: Patients with SCD (1 to 18 years of age), enrolled in Sickle Cell Clinical Research and Intervention Program (SCCRIP), at St. Jude Children's Research Hospital were included in the study (Hankins et.al., Pediatric Blood and Cancer, 2018). Demographic, clinical and laboratory data were extracted from SCCRIP database. Prospective pain event leading to a hospital visit was analyzed. We analyzed pain-related hospitalizations in two ways: the number of pain-related hospitalizations within 2 years prior to and after vitamin D measurement in a cross-sectional design and longitudinally. Generalized linear regression model was used to examine associations between vitamin D and cross-sectional pain events with adjusting for hydroxyurea use. Generalized linear mixed effect model was used to assess the associations between vitamin D and longitudinal pain events, with adjusting for SCD genotype, sex, age, hydroxyurea use and interaction between age and hydroxyurea use.Pediatric Quality of Life Inventory™ Sickle Cell Disease Module (PedsQL™ SCD) was used to measure pain and pain interference using 1) Pain and Hurt and 2) Pain Impact scales. PedsQL™ SCD assessments include a Likert response scale. Items are reverse -scored and transformed to a 0-100 scale where higher scores indicate better health related quality of life in that scale. Two sample t-test or Wilcoxon rank sum test was used to compare mean scores between the two groups.Results: A total of 799 patients (females, n=398; males, n=401) were included in the study. Mean age (Standard Deviation [SD]), range at time of first vitamin D measurement for entire cohort was 8.7 (4.7), (0.8-18 years). Mean (SD) initial vitamin D level for entire cohort was 19.0 (9.4) ng/dl. Mean (SD) number of pain-related hospitalizations within two years of first vitamin D measurement was higher in the vitamin D deficient group as compared to non deficient group [0.81(1.97) vs 0.66 (1.2), (p=0.0034)]. Longitudinal data analyses showed vitamin D deficiency was associated with increased number of pain related hospitalizations (p=0.0091), after adjusting for covariates listed above (Figure 1a).Mean (SD) scores for Pain and Hurt in vitamin D deficient versus non deficient group were [74.5.7(18.2) versus 83.5(15.6), p < 0.001]. Mean (SD) scores for Pain Impact in vitamin D deficient group as compared to non deficient group were [(66.7 (22.7) versus 75.5 (22.3), p <0.001] (Figure 1b)Conclusion: Results indicated that low vitamin D levels predicted higher frequency of painful events leading to a hospital visit and were associated with higher prevalence of self-reported pain and pain interference. Further studies evaluating mechanisms by which vitamin D influences sickle cell pain are warranted and larger controlled trials can help evaluate the therapeutic efficacy of vitamin D for sickle cell pain. [Display omitted] DisclosuresHankins: UpToDate: Consultancy; Bluebird Bio: Consultancy; Vindico Medical Education: Consultancy; Global Blood Therapeutics: Consultancy.

Food Insecurity, Quality of Life, Healthcare Utilization, and Clinical Disease Outcomes in AYA Patients with Sickle Cell Disease

Sickle cell disease (SCD) is a chronic, debilitating condition that negatively impacts patient quality of life (QOL). In addition to causing frequent crises that lead patients to seek medical attention, it can also exacerbate socioeconomic inequities patients with SCD often already face. A specific subset of patients, adolescents and young adults (AYA), defined by the NCI as individuals ages 15-39, are particularly at risk, which can lead to worse outcomes and increased healthcare utilization (HCU). However, analyses on social determinants of health, QOL, HCU, and clinical disease outcomes (CDO) in SCD are limited, particularly among the AYA population. Our group seeks to investigate the impact of social determinants of health on patients with SCD. We have previously reported on food insecurity (FI), QOL, and HCU in children with SCD. This project aims to specifically study the interplay of these metrics further, while also incorporating CDO. Furthermore, we seek to understand these relationships in AYA patients and how they may be uniquely related in this population. We hypothesize that FI is associated with decreased QOL, increased HCU, and worse CDO. We also hypothesize that the magnitude of this association is greater in AYA patients.We designed an observational study where patients with SCD ages 0- 24 years were recruited during routine SCD visits from June 2015- June 2019. We designed a baseline survey to measure FI and QOL using validated instruments, including the USDA Food Security Short Form and the PedsQL TM Sickle Cell Disease module. All patients were also consented to participate in our clinical registry, allowing for abstraction of HCU and CDO. Surveys were scored and transformed via established methods: USDA FS (range 0-6; >1 indicating some level of FI), and PedsQL TM (range 0-100; ≤60 indicating low QOL). Chart review captured number of ER visits, admissions, annual rate of vaso-occlusive crises (VOC) and acute chest syndrome (ACS). Other CDOs were also captured and these included presence of neurocognitive/psychiatric conditions (i.e., silent stroke, DSM diagnosis), ischemic events like avascular necrosis, and surgeries like cholecystectomies. Linear regressions, Chi squared analyses, Wilcoxon rank-sum tests, and Fisher's exact tests were performed to check for differences within and amongst these variables based on AYA status.Of surveyed patients (n=115), 56% were female, 39% were AYA, and 75% had SS disease. Some level of food insecurity (FS score > 1) was present in 34% of our population (compared to 10.5% of households nationally per the USDA) with no difference observed between AYA and non-AYA patients (Coleman 7). Average QOL score was 74, but this differed significantly between AYA and non-AYA patients. Specifically, total QOL scores for AYA patient were 10 points lower (p=0.003) and AYA patients were three times as likely to have QOL scores < 60 (p=0.005). Additionally, as previously reported, all patients in the cohort with FI had lower QOL (p=0.008). FI was also tested against HCU. While no difference was observed in number of ER visits, median admissions were twice as high for those with FI (p=0.07). This relationship was not affected by AYA status, but AYA patients did have 1.5 times as many ER visits and admissions combined (p=0.03). Food insecurity was associated with certain CDO measures such as VOC rates, which were four times higher in FI patients (p=0.03), and ACS rates (p=0.03). VOC/ACS rates did not differ between AYA and non-AYA patients and AYA status did not affect the relationship between FI and these CDO. However, AYA patients did demonstrate higher rates of neurocognitive/psychiatric conditions (p=0.009), cholecystectomies (p=0.03), and avascular necrosis (p=0.003).This study indicates that FI among our SCD patients was highly prevalent, associated with worse QOL, and increased HCU. We also show that FI is associated with worse CDO, which is an impetus for future intervention. Although AYA status did not significantly affect the magnitude of these relationships, it was associated with worsened QOL, increased HCU, and worse CDO. We plan to further study these trends with additional variables associated with sickle cell CDO, the role of preventative care in these populations, and how other social determinants of health impact the care and outcomes of our patients.Coleman, et al. Household Food Security in the United States in 2019, USDA, Economic Research Service. DisclosuresNo relevant conflicts of interest to declare.

Alteration of grey matter volume is associated with pain and quality of life in children with sickle cell disease

Pain is the most common symptom experienced by patients with sickle cell disease (SCD) and is associated with poor quality of life. We investigated the association between grey matter volume (GMV) and the frequency of pain crises in the preceding 12 months and SCD-specific quality of life (QOL) assessed by the PedsQLTM SCD module in 38 pediatric patients with SCD. Using voxel-based morphometry methodology, high-resolution T1 structural scans were preprocessed using SPM and further analyzed in SPSS. The whole brain multiple regression analysis identified that perigenual anterior cingulate cortex (ACC) GMV was negatively associated with the frequency of pain crises (r=-0.656, P=0.003). A two-group t-test analysis showed that the subgroup having pain crisis/crises in the past year also showed significantly lower GMV at left supratemporal gyrus than the group without any pain crisis (p=0.024). The further 21 pain-related regions of interest (ROI) analyses identified a negative correlation between pregenual ACC (r=-0.551, P=0.001), subgenual ACC (r=-0.540, P=0.001) and the frequency of pain crises. Additionally, the subgroup with poorer QOL displayed significantly reduced GMV in the parahippocampus (left: P=0.047; right: P=0.024). The correlations between the cerebral structural alterations and the accentuated pain experience and QOL suggests a possible role of central mechanisms in SCD pain.

A Developmental Examination of Pain Among Youth with Sickle Cell Disease

Introduction: Sickle cell disease (SCD) related pain is a difficult and challenging clinical problem that has significant negative effects on youth's health-related quality of life (Dampier et al., 2010; Walco & Dampier, 1990). Proper assessment and management of pain in the pediatric population is essential to both improving wellbeing of youth with SCD, and minimizing the development of chronic pain as patients transition into adulthood. Much of the previous research on pain among youth with SCD, however, has been limited by small sample sizes, lack of comprehensive pain assessment, and failure to examine developmental differences in pain across age groups. The current study aimed to compare the expression of pain and pain interference across four developmental stages: toddlers/preschoolers (2-4 years), school-aged children (5-7 years), preadolescents (8-12 years), and adolescents (13-18 years), utilizing both parent and youth reports as appropriate (i.e., school-aged and older). We hypothesized that pain and pain interference would generally be greater among older developmental groups.Methods: The study sample included 386 youth with SCD and their parents who participated in the Sickle Cell Clinical Research and Intervention Program (SCCRIP), a longitudinal lifetime cohort study designed to examine change in health outcomes in SCD. Within SCCRIP evaluations, the Pediatric Quality of Life Inventory Sickle Cell Disease module (PedsQL; Panepinto, Torres, & Varni, 2012) is used to measure health-related quality of life including pain and pain interference. We examined the 2 pain-related subscale outcomes within the PedsQL: the Pain and Hurt and Pain Impact subscale scores in all four developmental groups. Multivariate analyses of variance (MANOVAs) were first conducted to compare, within each age group, youth- and parent-reported pain and pain interference separately. Two sample t-test or Wilcoxon rank sum test and its extended ANOVA or Kruskal-Wallis tests were then used to compare these variables depending on the normality of the data, in any two and multiple groups, respectively. Benjamini & Hochberg method was used to adjust for multiple comparisons to control for false discovery rate at an alpha level of 0.05.Results: Gender and genotype were comparable across the four developmental groups. The proportions of patient exposure to disease-modifying therapy significantly increased by developmental stage: toddler/preschool =0.50, school-aged children =0.65, preadolescents =0.63, and adolescents =0.75 (p= 0.009). Parent-reports of child pain and pain interference gradually decreased from toddlers/preschoolers to school-aged children, and then from school-aged children to preadolescents (p s ranging from <.001 to .01), but no change was observed from preadolescents to adolescents. Similarly, youth-reported pain interference gradually decreased from school-aged children to preadolescents (p= .01), and from school-aged children to adolescents (p=.035), but no change was observed from preadolescents to adolescents. No significant change in youth-reported pain was observed across developmental groups.Conclusions: The current study is the first, to our knowledge, to examine developmental differences in pain from toddlerhood to adolescence among youth with all SCD genotypes. Contrary to our hypothesis, parent- and youth-reported pain and pain interference did not increase across developmental groups, but instead tended to decrease across younger developmental groups, and appeared to plateau approaching adolescence. This latter finding is in contrast to previous research examining similar developmental groups in youth with SCD, where increasing youth-reported pain interference was observed from childhood (8-11 years) to adolescence (12-17 years; Dampier et al., 2016). The reason for the lack of increased pain and pain interference across developmental stages is unclear, but could be partially attributed to factors such as greater exposure to disease-modifying therapy by developmental group in the current sample. Future validation of these findings is warranted. DisclosuresNo relevant conflicts of interest to declare.

Paternal Stress and Child Outcomes in Youth with Sickle Cell Disease.

The objective of this study was to investigate the relationship between parental stress and health-related quality of life (HRQOL) among children with sickle cell disease (SCD). A cross-sectional correlational survey research design was used for this quantitative study. One hundred-fifty patients between the ages of 8-17 years old and their caregivers were enrolled from an outpatient comprehensive sickle cell program within a hospital setting. Patients completed the Pediatric Quality of Life Scale 3.0 SCD Module, whereas parents completed the Parental Stress Scale and demographic information questionnaire. Multiple regression analysis was used to determine if parental stress scores predicted the HRQOL of children diagnosed with SCD after controlling for demographic variables. The sample included 150 patients (median age: 12 years old; female: 52%) who were diagnosed with SCD along with 150 of their caregivers. Higher levels of parental stress predicted lower HRQOL scores (p < .001). As parents reported elevated levels of stress related to caring for their child with SCD, patients reported worsening HRQOL. More evidence is needed in order to determine, which constructs of parental stress had a significant impact on HRQOL. It may be helpful for healthcare workers to be aware of familial influences of reduced HRQOL among children diagnosed with SCD. Parents reporting increased stress related to raising their child with SCD may benefit from additional support and resources.

Health Related Quality of Life of Children with Sickle Cell Anemia and Their Parents; Quantitative Study in Albaha; Saudi Arabia

Aims: To gain a better understanding of the quality of life (QoL) of children and impact of this disease on parents QoL.&#x0D; Study Design: Cross-sectional study.&#x0D; Place and Duration of Study: The study was conducted in King Fahd Hospital, Albaha city, Albaha, Saudi Arabia, between March2020 and February 2021.&#x0D; Methodology: We included 95 responses. Two different tools were used for the purpose of this study. PedsQL™ Sickle Cell Disease Module was used to measure health-related quality of life (HRQoL) in healthy children and adolescents and those with acute and chronic health conditions. Moreover, PedsQL™ Family Information Form was completed by caregivers. Median and interquartile range were used for numerical variables since they were skewed. Bivariate analyses were carried out using non-parametrical tests and Pearson correlation. The prediction of QoL was accomplished through multivariate analysis.&#x0D; Results: A total of (95) responses were analyzed. Female respondents were 52.6%. The age median was 12 (IQR=10-14). Mothers represented the most frequent informant 46.3% in this current study. Significant association was found between QoL and certain independent factors, some of which is parental level of education (P&lt; .001) and marital support (P&lt; .001).&#x0D; Conclusion: Sickle cell disease (SCD) is a major condition accounts for a huge burden on variable levels. This study reported that low QoL among children affected by SCD. Higher education and current marital status of the parents were significantly associated with high QoL in SCD patients. Number of workdays affected due to child health was significantly correlated with low QoL.

Empirically Derived Profiles of Health-Related Quality of Life in Youth and Young Adults with Sickle Cell Disease.

Determining how the health-related quality of life (HRQOL) is impacted by living with Sickle Cell Disease (SCD) can inform psychosocial interventions. The purpose of the present study is to determine if demographic and treatment variables predict membership into empirically derived subgroups of HRQOL among youth and young adults with SCD. Three hundred and seven youth and young adults with SCD (mean 17.63 years ± 3.74 years, 50.5% female) completed the Pediatric Quality of Life InventoryTM Sickle Cell Disease Module. Latent profile analysis examined subgroups/classes of HRQOL and relationships with demographic and treatment variables. Three distinct classes emerged: High HRQOL (34% of the sample), Moderate HRQOL (44% of the sample), and Low HRQOL (22% of the sample). Being female was associated with increased odds of being in the moderate or low groups. Living with more severe SCD (genotypes HbSS and HbSβ0 thalassemia) was associated with increased odds of being in the Low HRQOL group. Treatment with chronic red blood cell transfusion therapy was associated with increased odds of being in the High HRQOL group. Older age predicted a small increase in the odds of being in the Low versus High HRQOL group. The present study adds to the literature on HRQOL in SCD by exploring person-centered, empirically derived groups of HRQOL. Identification of demographic and treatment factors that predict membership into those groups within a large sample assists in tailoring needed psychosocial interventions for youth with SCD.

Assessment of Impact of a mHealth Self-Management Intervention for Children with Sickle Cell Disease

Introduction: Children with sickle cell disease (SCD) frequently experience pain beginning in early childhood progressing throughout the lifespan. SCD-related pain during childhood is associated with decreased physical, psychological, social, and quality of life (QOL) outcomes. As a chronic, multi-organ condition, treatment for SCD may require complicated preventive health and acute treatment regimens necessitating development of self-management strategies for children and their families. mHealth may be an ideal mechanism for implementation of self-management strategies. A mHealth self-management intervention was developed with an end-user-based approach (Voice Crisis Alert V2) and guided by the Pediatric Self-Management model. Initial feasibility testing was conducted. This abstract describes preliminary impacts of the Voice Crisis Alert V2 intervention on symptoms and QOL. Methods: The characteristics and names of application (app) components such as "Crisis Care" and "I'm in Pain" are outlined in Table 1. Targeted sample size was 60 dyads of children with SCD up to age 18 and the parent/caregiver. For assessment of impact, data sources included app use, child and parent/caregiver surveys at baseline, mid-intervention, end-of intervention and post-intervention. Survey instruments included the PROMIS SF for anxiety, fatigue, depressive symptoms, pain interference, pain intensity and sleep disturbance, and the PedsQL and Sickle Cell Disease Module (SCDM) for health-related quality of life (HRQOL). Data analysis was conducted using descriptive statistics, t-tests, Wilcoxon Signed Rank test, and Spearman's rho. Independent variables were number of times and length of time (minutes) using the app and individual app components. Dependent variables were pre-post differences in scores for total PedQL, school functioning, total SCDM, and subscales: pain and hurt, pain intensity, pain management, and treatments. Results are reported with 95% CIs. Results: The most substantial pre- to post-intervention differences in symptoms and QOL scores were noted in children ages 8 - 17. Pre-post-intervention differences in scores demonstrated improvement for all symptoms outcomes except anxiety, with clinically significant improvements in depressive symptoms, fatigue, and pain interference. Improvement in total scores and all subscale scores on the PedsQL and SCDM instruments were also noted from pre- to post-intervention. The majority of correlations had CIs that crossed zero, indicating either negative or positive associations may be observed in the population. Thus, overall, frequency and length of app use was not correlated with degree of improvement in outcomes. Negative correlations were observed between the number of times the Crisis Care component was used and treatment score (rs = -.46, 95% CI [-.75, -.00]), the number of minutes the Crisis Care component was used and the treatment score (rs = -.54, 95% CI [-.80, -.11]), and the number of minutes the Crisis Care component was used and the total SCDM score (rs = -.48, 95% CI [-.77, -.03]). These correlations suggest more frequent and longer use of the Crisis Care component was associated with less substantial improvement in SCDM total score and treatments score. Conclusions: Greater improvement in scores for children ages 8 - 17 compared to children less than 8 years suggests the intervention may be particularly useful in older children with SCD. Changes in scores from pre- to post-intervention and their CIs suggest intervention use may lead to improvement in the following domains: fatigue, pain interference, HRQOL, physical functioning, social functioning, pain and hurt, pain impact, pain management, and treatments. While improvements in scores from pre- to post-intervention were noted in nearly all areas, few meaningful correlations were observed between app use and differences in outcome scores. Improvement in symptoms and QOL outcomes may be attributable to individual characteristics, such as disease severity, or the amount and type of app use required to develop self-management skills may be individualized. Sample sizes were small and future efficacy testing is warranted with a larger sample. Disclosures Kanter: AGIOS: Membership on an entity's Board of Directors or advisory committees; BEAM: Membership on an entity's Board of Directors or advisory committees; NHLBI Sickle Cell Advisory Board: Membership on an entity's Board of Directors or advisory committees; SCDAA Medical and Research Advisory Board: Membership on an entity's Board of Directors or advisory committees; Cowen: Honoraria; Wells Fargo: Honoraria; bluebird bio, inc: Consultancy, Honoraria; Novartis: Consultancy; Sanofi: Consultancy; Medscape: Honoraria; Guidepoint Global: Honoraria; GLG: Honoraria; Jeffries: Honoraria.

Cognitive and Emotional Factors and Pain-Related Outcomes in Youth with Sickle Cell Disease

Children with sickle cell disease (SCD) experience acute episodes of pain that may require visits to emergency department (ED) or hospitalizations. SCD is associated with cognitive deficits that are particularly evident in domains of executive functioning (e.g., attention, working memory). Many patients/parents also report emotional concerns related to SCD. It is not known the degree to which these concerns impact disease self-management and healthcare utilization. This study investigated cognitive and emotional factors as contributors to pain-related healthcare utilization (visits to ED and hospitalizations) in children with SCD. The cohort included 112 youth with SCD (all genotypes) between ages 7-16 years who received care at Children's National Hospital in Washington, DC. Measures of socioeconomic status (e.g., parent education, family income, 1- vs. 2-parent households), cognitive abilities, and emotional functioning were extracted from an existing database of participants who had previously enrolled in the IRB approved study of computerized working memory training. Cognitive measures included the Wechsler Intelligence Scale for Children (WISC-V) Full Scale IQ and attention, working memory, and executive functioning tests from Cogstate, a computerized cognitive assessment. Emotional functioning was measured using the Worry 1 (i.e., anxiety about SCD) and Emotions (i.e., frustration and anger about SCD) domains of both the child- and parent-rated Pediatric Quality of Life Inventory Sickle Cell Disease Module. Healthcare utilization was measured through chart review, separated into ED visits for pain and hospitalizations for pain 1 year and 3 years after enrollment. The mean age of participants was 10.61 (SD=2.91) year with majority being females (n=65; 58%). Eighty-three (74%) had sickle cell anemia (HbSS or HbSβ0 thalassemia). The median number of ED visits for pain was 1 visit (IQR=2) across 1 year after enrollment and 3 visits (IQR=6) across 3 years after enrollment. The median number of hospital admissions for pain was 0 admissions (IQR=1) across 1 year after enrollment and 1 admission (IQR=4) across 3 years after enrollment (pain hospitalizations = 1; IQR=4). Linear regression models were applied to explore whether cognitive and emotional variables were predictive of healthcare utilization for pain. Variables included in the final model were selected by using the Akaike information criterion. Results indicated that attentional abilities were significantly associated with ED visits and hospitalizations for pain, both at 1 year and 3 years after enrollment (p's&amp;lt;.009), such that better performance on the Cogstate attention task was associated with fewer ED visits and hospitalizations. Child-rated emotional quality of life significantly predicted ED visits for pain over 1 year (b=-0.004, p=.049) and hospitalizations for pain over 3 years (b=-0.006, p=.013), such that higher emotional quality of life was predictive of fewer ED visits and hospitalizations. Parent-rated child emotional quality of life was also predictive of hospitalizations for pain over 3 years (b=-0.007, p=.020). Neither SCD genotype nor socioeconomic status significantly impacted healthcare utilization. Results demonstrate that children's cognitive and emotional functioning play an important role in pain management and should be an integral part of comprehensive pain management plans for children with SCD. Attentional abilities emerged as a reliable predictor of pain-related healthcare utilization and may signal that poor attention makes it difficult to implement strategies to distract from pain. It could also suggest that children with poor attention have greater difficulty with behavioral aspects of disease self-management (e.g., medication adherence, avoiding pain triggers). These are important considerations, given that youth with SCD are at risk for disease-related neurological sequelae including reduced attentional abilities. Emotional functioning (specifically, frustration and anger about SCD) also predicted healthcare utilization for pain, highlighting the potential impact of stress on pain onset and management. Clinicians and researchers should consider cognitive and emotional factors when evaluating risk for pain in SCD and incorporate these factors when developing strategies to reduce healthcare utilization and costs. Disclosures Darbari: Hilton Publishing: Consultancy, Other: Expert advisory board for developing gaming app for SCD; Global blood therapeutics: Consultancy, Honoraria, Other: participated in advisory board meeting ; Novartis: Consultancy, Honoraria, Other: steering committee for SPARTAN study .