Pediatric Sickle Cell Disease Research Articles

Pediatric Obstructive Sleep Apnea and Sickle Cell Disease: Demographic and Polysomnographic Features.

Obstructive sleep apnea (OSA) is prevalent in children with sickle cell disease (SCD). We compared the demographic, clinical, and polysomnographic characteristics of children with and without SCD. This retrospective chart review included children with SCD (n=89) and without SCD (n=192) ages 1-18 years referred for polysomnography (PSG) for OSA. Children with SCD were predominantly African American when compared to the non-SCD group (95% vs. 28%, p < 0.001). The non-SCD group had a higher BMI z-score (1.3 vs. 0.1, p < 0.001) and a higher percentage of patients classified as obese (52% vs. 13%, p < 0.001). In children with SCD, 43% had severe OSA and 5.6% had no OSA. In the non-SCD group, 67% had severe OSA and 4.7% had no OSA. The SCD compared to the non-SCD group had a lower mean apnea-hypopnea index (AHI) (13.6 vs. 22.4, p=0.006) but a higher percent sleep time below 90% oxygen saturation (10.5% vs. 3.5%, p < 0.001). Predicted probability for severe OSA in children with SCD decreased with increasing age (OR=0.81, 95% CI: 0.70-0.93). Children with SCD referred for PSG are at risk for severe OSA. Compared with the non-SCD group, most children were African American with lower rates of obesity and lower AHIs but longer periods of nocturnal hypoxemia. Likelihood for severe OSA decreased with increasing age for the SCD group. 3, retrospective comparative study Laryngoscope, 133:1766-1772, 2023.

The Prevalence of Cardiovascular Manifestations in Pediatric Sickle Cell Anemia Patients in a Large Tertiary Care Hospital in the Western Region of Saudi Arabia.

Background Sickle cell disease (SCD) is a common hematological disorder with a high prevalence in Saudi Arabia. Despite that, limited studies are available in our region regarding cardiovascular complications. Objectives The objective of the current study was to estimate the prevalence of cardiovascular complications among children with SCD. Design This was a cross-sectional study. Setting The study took place at a single tertiary-care center in Jeddah, Saudi Arabia. Materials and methods The study reviewed 126 electronic records of pediatric patients up to 16 years old diagnosed with SCD between January 2008 and December 2019 in King Abdulaziz Medical City (KAMC) in Jeddah, Saudi Arabia. Of these, 54 patients had a previous echocardiogram evaluation and were eligible for the study. Main outcomes measures The study identified cardiovascular complications in pediatric sickle cell patients. Sample size The study included a total of 54 pediatric sickle cell patients. Results The mean age was 11.9 (3.48) years, the male-to-female ratio was 2:1, the majority (94.4%) had the HbSS-HbSβ0 genotype, the mean baseline hemoglobin F (fetal hemoglobin) was 20.30 (9.03%), and the clinical severity score was severe in 19 (35.2%) and mild/moderate in 35 (64.8%) patients. Cardiovascular complications occurred in 32 (59.3%) patients. Increased systolic blood pressure was detected in 10 (18.5%) patients. Echocardiography showed left ventricular dilatation in nine (16.7%) patients, tricuspid valve insufficiency in six (11.1%) patients, mitral valve insufficiency in four (7.4%) patients, hyperdynamic left ventricle in one (1.9%) patient, and pulmonary hypertension in one (1.9%) patient. Long QTc interval was noticed in three (5.6%) and cardiomegaly was detected in 18 (33.3%) patients. Conclusion Cardiovascular complications occurred at a high frequency in our pediatric population despite high baseline hemoglobin F levels. Early evaluation and continuous monitoring are important for early intervention.

Ketamine use for management of vaso-occlusive pain in pediatric sickle cell disease.

Typical sickle cell disease (SCD) vaso-occlusive pain episode (VOE) management includes opioids, which are often inadequate and can be associated with significant side effects. Ketamine, a dissociative anesthetic, is a potentially effective adjunct to VOE management. This study aimed to characterize ketamine use for VOE management in pediatric SCD. This retrospective case series summarizes a single-center experience regarding the use of ketamine for inpatient management of pediatric VOE in 156 admissions from 2014 to 2020. Continuous low-dose ketamine infusion was most commonly prescribed to adolescents and young adults as an adjunct to opioids (median starting dose 2.0μg/kg/min; median maximum dose 3.0μg/kg/min). Ketamine was started a median of 13.7hours after admission. Median ketamine infusion duration was 3days. In most encounters, ketamine infusion was discontinued prior to opioid patient-controlled analgesia (PCA) discontinuation. The majority of encounters (79.3%) had a reduction in either PCA dose, continuous opioid infusion, or both while receiving ketamine. Low-dose ketamine infusion was associated with side effects noted in 21.8% (n=34) of encounters. The most common side effects included dizziness (5.6%), hallucinations (5.1%), dissociation (2.6%), and sedation (1.9%). There were no reports of ketamine withdrawal. Most patients who received ketamine went on to receive it again during a subsequent admission. Further study is needed to determine the optimal timing of ketamine initiation and dosing. The variability of ketamine administration highlights the need for standardized protocols for ketamine use in VOE management.

Lack of hydroxyurea-associated mutagenesis in pediatric sickle cell disease patients.

Hydroxyurea is approved for treating children and adults with sickle cell anemia (SCA). Despite its proven efficacy, concerns remain about its mutagenic and carcinogenic potential that hamper its widespread use. Cell culture- and animal-based investigations indicate that hydroxyurea's genotoxic effects are due to indirect clastogenicity in select cell types when high dose and time thresholds are exceeded (reviewed by Ware & Dertinger, 2021). The current study extends these preclinical observations to pediatric patients receiving hydroxyurea for treatment of SCA. First, proof-of-principle experiments with testicular cancer patients exposed to a cisplatin-based regimen validated the ability of flow cytometric blood-based micronucleated reticulocyte (MN-RET) and PIG-A mutant reticulocyte (MUT RET) assays to detect clastogenicity and gene mutations, respectively. Second, these biomarkers were measured in a cross-sectional study with 26 SCA patients receiving hydroxyurea and 13 SCA patients without exposure. Finally, a prospective study was conducted with 10 SCA patients using pretreatment blood samples and after 6 or 12 months of therapy. Cancer patients exposed to cisplatin exhibited increased MN-RET within days of exposure, while the MUT RET endpoint required more time to reach maximal levels. In SCA patients, hydroxyurea induced MN-RET in both the cross-sectional and prospective studies. However, no evidence of PIG-A gene mutation was found in hydroxyurea-treated children, despite the fact that the two assays use the same rapidly-dividing, highly-exposed cell type. Collectively, these results reinforce the complementary nature of MN-RET and MUT RET biomarkers, and indicate that hydroxyurea can be clastogenic but was not mutagenic in young patients with SCA.

Referral outcomes from a neurocognitive screening program for pediatric sickle cell disease.

Referral outcomes from a neurocognitive screening program for pediatric sickle cell disease.

The Association Between Caregiver Coping and Youth Clinic Attendance and Health-related Quality of Life in Pediatric Sickle Cell Disease.

Caregivers of youth with sickle cell disease (SCD) influence the youth disease management and psychosocial outcomes. Effective caregiver coping is important for improving disease management and outcomes since caregivers often report high disease-related parenting stress. This study characterizes caregiver coping and examines its relation to youth clinic nonattendance and health-related quality of life (HRQOL). Participants were 63 youth with SCD and their caregivers. Caregivers completed the Responses to Stress Questionnaire-SCD module to assess primary control engagement (PCE; attempts to change stressors or reactions to stress), secondary control engagement (SCE; strategies to adapt to stress), and disengagement (avoidance) coping. Youth with SCD completed the Pediatric Quality of Life Inventory-SCD module. Medical records were reviewed for the hematology appointment nonattendance rates. Coping factors were significantly different ( F [1.837, 113.924]=86.071, P <0.001); caregivers reported more PCE ( M =2.75, SD =0.66) and SCE ( M =2.78, SD =0.66) than disengagement ( M =1.75, SD =0.54) coping. Responses to short-answer questions corroborated this pattern. Greater caregiver PCE coping was associated with lower youth nonattendance (β=-0.28, P =0.050), and greater caregiver SCE coping was related to higher youth HRQOL (β=0.28, P =0.045). Caregiver coping is related to improved clinic attendance and HRQOL in pediatric SCD. Providers should assess caregiver coping styles and consider encouraging engagement coping.

Urinary Biomarkers for the Assessment of Acute Kidney Injury of Pediatric Sickle Cell Anemia Patients Admitted for Severe Vaso-occlusive Crises.

Sickle cell nephropathy is a progressive morbidity, beginning in childhood, which is incompletely understood partially due to insensitive measures. We performed a prospective pilot study of pediatric and young adult patients with sickle cell anemia (SCA) to assess urinary biomarkers during acute pain crises. Four biomarkers were analyzed with elevations potentially suggesting acute kidney injury: (1) neutrophil gelatinase-associated lipocalin (NGAL), (2) kidney injury molecule-1, (3) albumin, and (4) nephrin. Fourteen unique patients were admitted for severe pain crises and were found to be representative of a larger SCA population. Urine samples were collected at the time of admission, during admission, and at follow-up after discharge. Exploratory analyses compared cohort values to the best available population values; individuals were also compared against themselves at various time points. Albumin was found to be moderately elevated for an individual during admission compared with follow-up ( P = 0.006, Hedge g : 0.67). Albumin was not found to be elevated compared with population values. Neutrophil gelatinase-associated lipocalin, kidney injury molecule-1, and nephrin were not found to be significantly elevated compared with population values or comparing admission to follow-up. Though albumin was found to be minimally elevated, further research should focus on alternative markers in efforts to further understand kidney disease in patients with SCA.

Red Blood Cell Vitamin C Concentration and Its Effect on Deformability in Pediatric Sickle Cell Disease.

Red cell rigidity is common in sickle cell disease (SCD). The contribution of oxidative stress on deformability remains unknown. This study investigated red blood cell (RBC) vitamin C concentrations in pediatric SCD (n=43) compared with healthy controls ( n =23) and developed a protocol to raise RBC vitamin C concentrations to measure the effect on deformability. Sickle cell RBC vitamin C concentrations seem low (20.5μM, SD: 16.2 vs. 51.7μM, SD: 15.8; P <0.0001). Vitamin C can be successfully loaded into sickle cell RBCs but seems to have minimal effect on deformability. Future studies are needed to understand the clinical implications of vitamin C deficiency in pediatric SCD.

Pediatric Sickle Cell Disease and Stroke: A Literature Review.

Both ischemic and hemorrhagic strokes in children can be a complication of sickle cell disease, which also affects adults. The occurrence is high without any screening or preventative care.This review article found that although transcranial Doppler (TCD) has reduced the prevalence of stroke in pediatric patients, there is still a need for an epidemiological survey to define such screening for adults, the ideal dose of hydroxyurea to reduce the incidence of stroke, and to identify silent cerebral stroke to prevent its complications. Increased hydroxyurea prescription and specific antibiotic and vaccination regimes lowered the occurrence of this condition. In pediatric cases with a time-averaged mean of the maximal velocity greater than 200cm/s, transcranial Doppler screeningand preventive chronic transfusion for at least the first year have lowered the occurrence of stroke by up to 10 times. The ideal dose of hydroxyurea is still debatable, but it seems to reduce the risk of the first stroke to a comparable level in the average population. Adult ischemic and hemorrhagic stroke prevention has not yet received the same attention. Though there are fewer studies, sickle cell disease is also more common than age-matched controls in terms of silent cerebral infarctionon magnetic resonance imaging (MRI),as well as other neurological problems such as cognitive impairment, seizures, and headaches. Currently, there is no evidence-supported way to prevent ischemic stroke in adults at any age. Also, there is no defined ideal dose of hydroxyurea that can be helpful in preventing strokes. Data also lack a way to identify a silent cerebral infarction, so its complications can be prevented. An additional epidemiological survey may help in the prevention of the condition. The primary aim of this article was to emphasize the importance of information on clinical, neuropsychological, and quantitative MRI assessment of sickle cell patients to understand the epidemiology and etiology of stroke in sickle cell patients to prevent stroke and its related morbidity.

The relationship between pain and sleep in pediatric sickle cell disease.

Pain and sleep disturbances are prevalent complications experienced by pediatric patients with sickle cell disease (SCD). This study aims to identify associations between pain and sleep, and to characterize sleep chronotype and social jetlag in children and adolescent patients with SCD. We performed a cross-sectional survey of 105 pediatric patients with SCD aged 8-17years using PROMIS (Patient Reported Outcomes Measurement System) pain interference, sleep disturbance, and sleep-related impairment item banks. The μMCTQ (Ultra-short Munich Chronotype Questionnaire) assessed chronotype and social jetlag. Analyses were performed to assess associations between PROMIS measures, sleep patterns, and clinical variables. Female participants reported higher T-scores for sleep-related impairment than males (females: 56.7±10 vs. males 50.2±9.4, p=.0009). Patients with one or more emergency department (ED) visits for pain in the last 12months reported greater sleep disturbance (55.0±8.5 vs. 50.7±10, p=.046) and sleep-related impairment (57.1±9.3 vs. 52.1±10.2, p=.03) than patients without any ED visits for pain in the last 12months. Pain interference was significantly associated with both sleep disturbance (r=.49, p<.0001) and sleep-related impairment (r=.46, p<.0001). The average mid-sleep time was 4:14±1:44 a.m. and the average social jetlag (hh:mm) was 2:32±1:35. Our study demonstrates that pain interference is associated with both sleep disturbance and sleep-related impairment. PROMIS measures can identify patients that suffer from pain and sleep disturbances and highlights the need to conduct longitudinal prospective studies to define the directionality of pain and sleep in SCD.

Inflammatory status in pediatric sickle cell disease: Unravelling the role of immune cell subsets.

Introduction: The mutation of the beta-globin gene that causes sickle cell disease (SCD) results in pleiotropic effects, such as hemolysis and vaso-occlusive crisis that can induce inflammatory mechanisms with deleterious consequences on the organism. Moreover, SCD patients display an increased susceptibility to infections. Few studies are currently available that evaluate a wide immunological profile in a pediatric population. This study proposes an evaluation of the immune profile in subjects with SCD in a pediatric population through a detailed analysis by flow cytometry. Methods and Materials: Peripheral blood samples from 53 pediatric patients with SCD (mean age 9.8years, interquartile range 9years) were obtained and then analyzed by flow cytometry, in order to evaluate changes in the immune populations compared to 40 healthy donors (mean age 7.3years, interquartile range 9.5years). Results: Our data showed an increase in neutrophils (with a reduction in the CD62L + subpopulation) and monocytes (with a decrease in HLA-DRlow monocytes) with normal values of lymphocytes in SCD patients. In the lymphocyte subpopulations analysis we observed lower values of CD4+ T cells (with higher number of memory and central memory T lymphocytes) with increased frequency of CD8+ T cells (with a predominant naive pattern). Moreover, we observed higher values of CD39+ Tregs and lower HLA-DR+ and CD39- T cells with an increased Th17, Th1-17 and Th2 response. Conclusion: We observed immunological alterations typical of an inflammatory status (increase in activated neutrophils and monocytes) associated with a peculiar Treg pattern (probably linked to a body attempt to minimize inflammation intrinsic to SCD). Furthermore, we highlighted a T helper pathway associated with inflammation in line with other studies. Our data showed that immunological markers may have an important role in the understanding the pathophysiology of SCD and in optimizing targeted therapeutic strategies for each patient.

Prevalence and Risk Factors for Pulmonary Embolism in Pediatric Sickle Cell Disease: A National Administrative Database Study

Patients with sickle cell disease (SCD) have a high risk for venous thromboembolism which is associated with increased risk of mortality. Studies examining risk of pulmonary embolism (PE) in children with SCD are lacking. This study was conducted in children with SCD between 0–21 years of age using a nationwide administrative database in the United States- Pediatric Health Information System (PHIS) from January 2010 to June 2021. Diagnostic codes and imaging, procedure, and pharmaceutical billing codes were used to identify PE and potential clinical, demographic, and utilization risk factors. Logistic regression analyses were performed to assess association between risk factors and PE. We identified 22,631 unique patients with SCD with a median age of 10.8 years (range: <0.1–20.9). A total of 120 (0.53%) patients developed a PE with median age of 17.4 years (range: 6.6–20.9) at PE diagnosis. Patients with PE had longer hospitalization and more frequent ICU admissions than patients without PE (p < 0.001). Risk factors significantly associated with PE on multivariable analysis included older age, prior history of central venous line (CVL), acute chest syndrome, and apheresis. Mortality was not significantly different between those with and without PE. The prevalence of PE in hospitalized children with SCD was estimated to be 0.53%. Patients with PE had higher healthcare utilization characteristics. Factors significantly associated with PE suggest that the risk for PE in SCD may be related to the severity of disease state. Future trials are needed for risk stratification and PE prevention strategies in children with SCD.

Intraindividual pain variability metrics for youth with sickle cell disease: Relations to health outcomes.

While the majority of pediatric sickle cell disease (SCD) research has used mean pain intensity as the only pain metric, recent evidence suggests this metric alone is inadequate in describing the intraindividual variability in SCD pain experiences and subsequent impact. There is limited information on other intraindividual pain metrics in youth with SCD, or how they relate to health outcomes in this population. The aims of this study were to describe differing patterns of intraindividual pain metrics derived from ecological momentary assessments (EMAs) of youth with SCD and to characterize the unique relationships between these metrics and health outcomes. Eighty-eight youth with SCD, aged 8-17 (mean age=11.6), were recruited from three regional pediatric SCD clinics in the United States. At baseline, youth and their guardians reported on demographic and disease information. Then youth completed twice daily EMAs for up to 4weeks. Pain metrics derived from EMA data were calculated including mean daily pain intensity (DP), SD-DP (standard deviation of DP), proportion of pain days (PPD), and 90th percentile of DP (p90). Pearson correlations were calculated between pain metrics and health outcomes. High DP and SD-DP were correlated with more anxiety symptoms, while high SD-DP and p90 were correlated with more depression symptoms. High SD-DP was correlated with low self-esteem, and high DP and PPD were correlated with low sickle cell self-efficacy. For healthcare utilization due to pain, high p90 was correlated with more emergency department visits, while high DP, p90, and PPD were correlated with more healthcare contacts. There are distinct associations between pain variability metrics beyond DP and health outcomes. Collectively, the patterns of associations suggest the utility of these pain metrics for determining risk in relation to specific health outcomes for youth with SCD.

Pethidine-related neurotoxicity in pediatric sickle cell disease: a systematic review

Sickle cell disease describes a set of related blood disorders that result from defective production of hemoglobin that causes rigid fibers to form in the red blood cells, bending them into a characteristic sickle shape. These misshapen blood cells are then prone to becoming lodged in smaller blood vessels, resulting in a vaso-occlusive crisis, which can be very painful. Rapid and potent analgesia is crucial in the care of patients presenting with sickle cell crisis, and opioid analgesics, such as pethidine and morphine, have been the mainstay of treatment for decades. However, there are reports in the literature of seizures associated with pethidine use, particularly if used for more than a few days or in patients with kidney disease. A systematic review of the literature was conducted to identify any case reports or studies of the use of pethidine in children presenting with painful sickle cell crisis with a specific focus on the prevalence of seizures in this patient group. The pharmacology and pharmacokinetics of pethidine and its active metabolite norpethidine are briefly explored, along with alternative analgesic approaches, both pharmacological and nonpharmacological.

The Perception of Pediatric Sickle Cell Anemia Patients’ Caregivers toward Bone Marrow Transplantation at NGHA Jeddah, Saudi Arabia

The Perception of Pediatric Sickle Cell Anemia Patients’ Caregivers toward Bone Marrow Transplantation at NGHA Jeddah, Saudi Arabia

Trends in blood transfusion, hydroxyurea use, and iron overload among children with sickle cell disease enrolled in Medicaid, 2004-2019.

There have been significant changes in clinical guidelines for sickle cell disease (SCD) over the past two decades, including updated indications for hydroxyurea, transfusions, and iron overload management. In practice however, there are few studies that examine SCD care utilization over time. We conducted a serial cross-sectional cohort study of pediatric SCD patients from 2004 to 2019 using Georgia Medicaid claims data. For each year, we reported receipt of any transfusion, chronic transfusion, or three or more filled hydroxyurea prescriptions. For children receiving chronic transfusion (six or more annual transfusions), we evaluated iron overload diagnosis, monitoring, and chelation use. Among children with sickle cell anemia (SCA), we examined rates of transfusions and hydroxyurea use. The Cochran-Armitage test was used to assess trend. There were 5316 unique children 2-18years old with SCD enrolled in Georgia Medicaid from 2004 to 2019. Children receiving any transfusion increased from 2004 to 2010, then stabilized. In SCA patients, chronic transfusions initially increased from 2004 to 2010, then stabilized from 2010 to 2019. For chronically transfused children, monitoring of iron burden and filled chelator prescriptions both increased significantly. Hydroxyurea use in SCA patients increased from 12% to 37%, with increases noted within each age group, most notably from 21% to 60% in the 13-18-year-old cohort. We demonstrated changes in SCD care utilization over time, including increased hydroxyurea use, changes in transfusion rates, and increased attention to iron overload management. While trends in clinical management do follow updates in treatment guidelines, there is still delayed and suboptimal uptake of guideline recommendations in pediatric SCD patients.

A dyadic analysis of parent and child pain catastrophizing and health-related quality of life in pediatric sickle cell disease.

The purpose of this study was to examine the dyadic and individual level effects of parent and child pain catastrophizing on child health-related quality of life (HRQOL) in pediatric sickle cell disease. Questionnaires assessing child pain frequency, child and parent pain catastrophizing, and child HRQOL were completed by youth and their primary caregiver. A Common Fate Model was estimated to test the dyadic level relationship between parent and child pain catastrophizing and child HRQOL. An Actor-Partner-Common Fate Model hybrid was estimated to test the relationship between child HRQOL and individual-level child pain catastrophizing and parent pain catastrophizing, respectively. In each model, child HRQOL was modelled as a dyadic variable by factoring parent and child ratings. Patients (N = 100, M age = 13.5 years, 61% female) and their caregivers (M age = 41.8 years, 86% mothers) participated. Dyad-level pain catastrophizing was negatively associated with child HRQOL, demonstrating a large effect (β = -0.809). Individual-level parent and child pain catastrophizing were each uniquely negatively associated with child HRQOL, demonstrating small to medium effects (β = -0.309, β = -0.270). Individual level effects were net of same-rater bias, which was significant for both parents and children. Both the unique and the overlapping aspects of parent and child pain catastrophizing are significant contributors to associations with child HRQOL, such that higher levels of pain catastrophizing are associated with worse child HRQOL. Findings suggest the need for multipronged intervention targeting factors common to parent-child dyads and factors unique to parents and children, respectively.

Echocardiographic Evaluation in Paediatric Sickle Cell Disease Patients: A Pilot Study

Cardiovascular involvement has a great impact on morbidity and mortality in sickle cell disease (SCD). Currently, few studies are available regarding the paediatric setting and, moreover, current guidelines for the echocardiogram screening program in the asymptomatic paediatric population are controversial. We performed a retrospective observational monocentric study on 64 SCD patients (37 male and 27 female, median age 10) at the Bambino Gesù Childrens' Hospital, who had undergone a routine transthoracic echocardiogram. In total, 46 (72%) patients had at least one cardiac abnormality. Left atrial dilatation (LAD) was present in 41 (65%) patients and left ventricular hypertrophy (LVH) was found in 29 (45%) patients. Patients with LAD showed lower median haemoglobin levels (p = 0.009), and a higher absolute reticulocyte count (p = 0.04). LVH was negatively correlated with the median haemoglobin value (p = 0.006) and positively with the reticulocyte count (p = 0.03). Moreover, we found that patients with cardiac anomalies had higher transfusion needs and a lower frequency of pain crises. In our setting, cardiac involvement has a high prevalence in the paediatric cohort and seems to be associated with specific laboratory findings, and with a specific clinical phenotype characterized by complications related to high haemodynamic load.

Effects of Experienced Discrimination in Pediatric Sickle Cell Disease: Caregiver and Provider Perspectives.

For Black children with sicklecell disease (SCD) and their families, high disease stigmatization and pervasive racism increase susceptibility to discrimination in healthcare settings. Childhood experiences of discrimination can result in medical nonadherence, mistrust of healthcare providers, and poorer health outcomes across the lifespan. Caregivers and medical providers are essential to childhood SCD management and are therefore well-positioned to provide insight into discrimination in the context of pediatric SCD. This mixed-methods study sought caregivers' and providers' perspectives on processes underlying discrimination and potential solutions to mitigate the negative effects of perceived discrimination among children with SCD. Caregivers (N = 27) of children with SCD (≤ 12years old) and providers from their hematology clinics (N = 11) participated in individual semi-structured interviews exploring experiences of discrimination and daily SCD management and completed a quantitative measure of discrimination. Qualitative data were collected until themes reached saturation and subsequently transcribed verbatim, coded, and analyzed using applied thematic analysis. Quantitative and qualitative data converged to suggest the pervasiveness of discrimination in healthcare settings. Three qualitative themes emerged: (1) healthcare system factors underlie discrimination, (2) families' challenging interactions with providers lead to perceptions of discrimination, and (3) experiences of discrimination impact caregiver-provider interactions. Both caregivers and providers highlighted building trusting patient-provider relationships and encouraging patients' self-advocacy as means to reduce experiences and impacts of discrimination. These findings offer potential approaches to tangibly mitigate occurrences of discrimination in pediatric healthcare settings by trust building, accountability keeping, and fostering rapport to improve quality of care and pediatric SCD health outcomes.

Pediatric Sickle Cell Disease Patients on Hydroxyurea Have Higher Rates of Surgical Splenectomy

IntroductionWe sought to investigate whether hydroxyurea therapy is associated with the need for surgical splenectomy among patients with sickle cell disease (SCD). We hypothesized that as hydroxyurea gained widespread use, surgical splenectomy among pediatric patients with SCD occurred at a higher rate and older age among those taking hydroxyurea. MethodsIn this retrospective cross-sectional study, the Pediatric Health Information System was queried for all SCD International Classification of Diseases 9/10 diagnosis codes and splenectomy procedure codes from January 1, 2005, to December 31, 2020. Hydroxyurea use was defined as at least one hospital admission with hydroxyurea listed as a medication. The rates of surgical splenectomy, age at splenectomy, hospital length of stay, and incidence of blood transfusion during the splenectomy admission were compared among patients receiving hydroxyurea versus those not receiving hydroxyurea. Additional subanalysis was performed in the Hemoglobin-SS, Hemoglobin-SC, and Other cohorts separately. ResultsDuring the study period, 28,520 patients were identified. All patients with SCD receiving hydroxyurea had a significantly higher rate of surgical splenectomy compared with the nontreatment group (7.2% versus 3.2%, P = 0.01). The age at surgical splenectomy was significantly younger among Hemoglobin-SS patients receiving hydroxyurea (5.7 [5.1, 6.4] y versus 6.6 [5.8, 7.4] y; P < 0.01). There were no significant differences in length of stay or incidence of blood transfusion during the surgical splenectomy admission between treatment groups. ConclusionsHydroxyurea use in children is associated with higher rates of surgical splenectomy and occurs at a younger age in the Hemoglobin-SS population. Although these findings warrant further investigation for causality, it provides useful information to clinicians and patients alike, allowing for more informed decision-making.