Soluble urokinase plasminogen activator receptor is associated with kidney disease and its progression in sickle cell anemia.

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Machine Learning Predicts Acute Kidney Injury in Hospitalized Patients with Sickle Cell Disease.

INTRODUCTION: Acute kidney injury (AKI) is common among hospitalized patients with sickle cell disease (SCD) and contributes to increased morbidity and mortality. Early identification and management of AKI is essential to preventing poor outcomes. We aimed to predict AKI earlier in patients with SCD using a machine-learning model that utilized continuous minute-by-minute physiological data. METHODS: A total of6,278 adult SCD patient encounters were admitted to inpatient units across five regional hospitals in Memphis, TN, over 3 years, from July 2017 to December 2020. From these, 1,178 patients were selected after filtering for data availability. AKI was identified in 82 (7%) patient encounters, using the 2012 Kidney Disease Improving Global Outcomes (KDIGO) criteria. The remaining 1,096 encounters served as controls. Features derived from five physiological data streams, heart rate, respiratory rate, and blood pressure (systolic, diastolic, and mean), captured every minute from bedside monitors were used. An XGBoost classifier was used for classification. RESULTS: Our model accurately predicted AKI up to 12 h before onset with an area under the receiver operator curve (AUROC) of 0.91 (95% CI [0.89-0.93]) and up to 48 h before AKI with an AUROC of 0.82 (95% CI [0.80-0.83]). Patients with AKI were more likely to be female (64.6%) and have history of hypertension, pulmonary hypertension, chronic kidney disease, and pneumonia than the control group. CONCLUSION: XGBoost accurately predicted AKI as early as 12 h before onset in hospitalized SCD patients and may enable the development of innovative prevention strategies.

Hydroxyurea to prevent brain injury in children with sickle cell disease (HU Prevent)-A randomized, placebo-controlled phase II feasibility/pilot study.

Central nervous system (CNS) injury is common in sickle cell disease (SCD) and occurs early in life. Hydroxyurea is safe and efficacious for treatment of SCD, but high-quality evidence from randomized trials to estimate its neuroprotective effect is scant. HU Prevent was a randomized (1:1), double-blind, phase II feasibility/pilot trial of dose-escalated hydroxyurea vs. placebo for the primary prevention of CNS injury in children with HbSS or HbS-ß0-thalassemia subtypes of SCD age 12-48 months with normal neurological examination, MRI of the brain, and cerebral blood flow velocity. We hypothesized that hydroxyurea would reduce by 50% the incidence of CNS injury. Two outcomes were compared: primary-a composite of silent cerebral infarction, elevated cerebral blood flow velocity, transient ischemic attack, or stroke; secondary-a weighted score estimating the risk of suffering the consequences of stroke (the Stroke Consequences Risk Score-SCRS), based on the same outcome events. Six participants were randomized to each group. One participant in the hydroxyurea group had a primary outcome vs. four in the placebo group (incidence rate ratio [90% CI] 0.216 [0.009, 1.66], p = .2914) (~80% reduction in the hydroxyurea group). The mean SCRS score was 0.078 (SD 0.174) in the hydroxyurea group, 0.312 (SD 0.174) in the placebo group, p = .072, below the p-value of .10 often used to justify subsequent phase III investigations. Serious adverse events related to study procedures occurred in 3/41 MRIs performed, all related to sedation. These results suggest that hydroxyurea may have profound neuroprotective effect in children with SCD and support a definitive phase III study to encourage the early use of hydroxyurea in all infants with SCD.

Association of elevated tricuspid regurgitation velocity with cerebrovascular and kidney disease in children with sickle cell disease.

BACKGROUND: Tricuspid regurgitation velocity (TRV), measured by echocardiography, is a surrogate marker for pulmonary hypertension. Limited pediatric studies have considered the association between TRV and surrogate markers of end-organ disease. METHODS: We conducted a cross-sectional study that evaluated the prevalence of elevated TRV ≥2.5 m/s and its associations with renal and cerebrovascular outcomes in children with sickle cell disease (SCD) 1-21 years of age in two large sickle cell cohorts, the University of Alabama at Birmingham (UAB) sickle cell cohort, and the Sickle Cell Clinical Research and Intervention Program (SCCRIP) cohort at St. Jude Children's Research Hospital. We hypothesized that patients with SCD and elevated TRV would have higher odds of having either persistent albuminuria or cerebrovascular disease. RESULTS: We identified 166 children from the UAB cohort (mean age: 13.49 ± 4.47 years) and 325 children from the SCCRIP cohort (mean age: 13.41 ± 3.99 years) with echocardiograms. The prevalence of an elevated TRV was 21% in both UAB and SCCRIP cohorts. Elevated TRV was significantly associated with cerebrovascular disease (odds ratio [OR] 1.88, 95% confidence interval [CI]: 1.12-3.15; p = .017) and persistent albuminuria (OR 1.81, 95% CI: 1.07-3.06; p = .028) after adjusting for age, sex, treatment, and site. CONCLUSION: This cross-sectional, multicenter study identifies associations between surrogate markers of pulmonary hypertension with kidney disease and cerebrovascular disease. A prospective study should be performed to evaluate the longitudinal outcomes for patients with multiple surrogate markers of end-organ disease.

Kidney failure outcomes in children and young adults with sickle cell disease in the United States Renal Data System.

BACKGROUND: Children and young adults with sickle cell disease (SCD) develop kidney disease early in childhood, with some patients progressing to require dialysis and kidney transplantation. The prevalence and outcomes of children with kidney failure (chronic kidney disease stage 5) due to SCD are not well described. This study aimed to assess the outcome of children and young adults with SCD with kidney failure compared to matched children and young adults without SCD with kidney failure in a large national database. METHODS: Utilizing the United States Renal Data System (USRDS), we retrospectively examined kidney failure outcomes in children and young adults with SCD from 1998 to 2019. RESULTS: We identified 97 patients with SCD who developed kidney failure and identified 96 matched controls with a median age of 19 years (IQR 17, 21) at the time of kidney failure diagnosis. SCD patients had significantly shorter survival (8.4 years vs. 14.0 years, p < 0.001) and had a longer waiting time for their first transplant when compared to matched non-SCD kidney failure patients (12.1 years vs. 7.3 years, p < 0.001). CONCLUSIONS: Children and young adults with SCD kidney failure have significantly higher mortality when matched to non-SCD kidney failure children and experience a longer mean time to kidney transplant.

Outcomes of Referrals in Pediatric Patients With Peripheral Lymphadenopathy.

Lymphadenopathy is a common reason for referral to a subspecialist, which may result in significant anxiety for parents. Understanding which patients require a subspecialty referral for lymphadenopathy is key to streamlining health care utilization for this common clinical entity. This is an IRB-approved retrospective study examining pediatric patients consecutively referred to pediatric hematology oncology, otolaryngology, or surgery for lymphadenopathy from 2012 to 2021 at a free-standing tertiary-care children's hospital. Logistic regression was fitted to examine the association between the maximum size of the lymph nodes (LN) and a diagnosis of malignancy. The odds ratio, area under the receiver operator curve, sensitivity, and specificity were estimated. We found a significant association between LN size and cancer diagnosis. For every centimeter increase in the maximal dimension of LN, there was an estimated 2.3 times increase in the odds of malignancy (OR=2.3, 95% CI: 1.65-3.11; P<0.0001). The estimated area under the curve (0.84, 95% CI: 0.78-0.90) indicated that LN size correlated well with cancer diagnosis. A LN cut-off size of 2 cm resulted in an estimated sensitivity of 1.0 (95% CI: 0.87-1.00) and specificity of 0.54 (95% CI: 0.46-0.61). Maximum LN size may be a predictor of malignancy among pediatric patients with lymphadenopathy.

Peroxiredoxin-2 recycling is slower in denser and pediatric sickle cell red cells.

Peroxiredoxin-2 (Prx-2) is a critical antioxidant protein in red blood cells (RBC). Prx-2 is oxidized to a disulfide covalently-bound dimer by H2 O2 , and then reduced back by the NADPH-dependent thioredoxin-thioredoxin reductase system. The reduction of oxidized Prx-2 is relatively slow in RBCs. Since Prx-2 is highly abundant, Prx-2s' peroxidase catalytic cycle is not considered to be limiting under normal conditions. However, whether Prx-2 recycling becomes limiting when RBCs are exposed to stress is not known. Using three different model systems characterized by increased oxidative damage to RBCs spanning the physiologic (endogenous RBCs of different ages), therapeutic (cold-stored RBCs in blood banks) and pathologic (RBCs from sickle cell disease (SCD) patients and humanized SCD mice) spectrum, basal levels of Prx-2 oxidation and Prx-2 recycling kinetics after addition of H2 O2 were determined. The reduction of oxidized Prx-2 was significantly slower in older versuin older versus younger RBCs, in RBCs stored for 4-5 weeks compared to 1 week, and in RBC from pediatric SCD patients compared to RBCs from control non-SCD patients. Similarly, the rate of Prx-2 recycling was slower in humanized SCD mice compared to WT mice. Treatment of RBC with carbon monoxide (CO) to limit heme-peroxidase activity had no effect on Prx-2 recycling kinetics. Treatment with glucose attenuated slowed Prx-2 recycling in older RBCs and SCD RBCs, but not stored RBCs. In conclusion, the reduction of oxidized Prx-2 can be further slowed in RBCs, which may limit the protection afforded by this antioxidant protein in settings associated with erythrocyte stress.

Assessing barriers and facilitators to transition in sickle cell disease care prior to implementation of a formalized program.

Over 95% of children with sickle cell disease (SCD) survive into adulthood in the United States. However, early mortality remains a problem, especially in persons between the ages of 18 and 35. One possible explanation for the increased mortality rate in young adults is difficulties in engaging in care during the transition from a heavily contiguous pediatric healthcare model to a more self-reliant adult healthcare model. The goal of this study was to identify potential facilitators and barriers to a successful transfer in care from the pediatric to adult SCD program before the formation of a formal transition program. This is a retrospective cohort study of transition outcomes for 472 individuals with SCD (all genotypes) treated at the University of Alabama at Birmingham (UAB) sickle cell clinic (aged 18-24). The primary outcome was whether the patient continued care in (any) adult SCD program (defined as being seen at least once in an adult hematology/SCD clinic). One hundred eighty-eight (45%) transition age patients successfully transferred to adult care. Facilitators to successful transfer in care included being treated at the same hospital for both pediatric and adult programs, having the genotype HbSS, and/or receiving an SCD-modifying therapy at the time of transition (hydroxyurea and/or red cell transfusion therapy). Of primary interest, many of the patients who failed to transition to an adult clinic were lost to follow-up prior to 15 years of age. Importantly, these patients who had previously been labeled as "transition failures," were lost to follow-up long before the transition age. Early engagement is needed for this population.

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

BACKGROUND: 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. METHODS: We performed a cross-sectional survey of 105 pediatric patients with SCD aged 8-17 years 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. RESULTS: 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 12 months 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 12 months. 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. CONCLUSION: 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.

Diagnosis and management of isolated neutropenia: A survey of pediatric hematologist oncologists.

BACKGROUND: Isolated neutropenia is a common referral to pediatric hematology oncology (PHO) physicians. There are no established consensus guidelines in the diagnosis and management of patients with isolated, asymptomatic, and incidentally discovered neutropenia. METHODS: A survey was distributed to PHO physicians on the American Society of Pediatric Hematology Oncology member discussion page to determine the common diagnostic and management decisions regarding patients with isolated neutropenia and to explore beliefs regarding the term "benign ethnic neutropenia." RESULTS: One hundred twenty-six PHO attending physicians completed the survey. The most common tests reportedly ordered for this patient population included complete blood cell count (CBC) (98%), peripheral smear (75%), antineutrophil antibody testing (29%), and immunoglobulins (24%). Providers were more likely to order an antineutrophil antibody in toddlers (p = .0085), and antinuclear antibody (ANA) panels in adolescents (p < .001). Half of providers do not request additional CBCs prior to their initial consultation, and most suggest referring patients with mild neutropenia after confirming a declining absolute neutrophil count (ANC) (51%). The three most important factors influencing ongoing follow-up included: history of recurrent/severe infections (98%), family history of blood disorders (98%), and more severe/progressively worsening neutropenia (97%). Seventy percent of respondents have diagnosed patients with "benign ethnic neutropenia," and 75% support replacement of the term to "typical neutrophil count with Fy(a-/b-) status," if confirmed with red cell phenotyping. CONCLUSION: We identified practice patterns of PHO physicians for the diagnosis and management of patients referred for asymptomatic and isolated neutropenia. These data provide the framework to conduct cost-effectiveness studies.

The relationship between nutrition, gut dysbiosis, and pediatric sickle cell pain outcomes: A pilot study.

BACKGROUND: Nutritional deficiencies are prevalent in sickle cell disease (SCD) and may be associated with worse pain outcomes. Gut dysbiosis has been reported in patients with SCD and may contribute to both nutritional deficiencies and pain. OBJECTIVES: We tested the association of nutrition, fat-soluble vitamin (FSV) deficiency, and gut microbiome composition on clinical outcomes in SCD. Second, we measured the association between diet and exocrine pancreatic function on FSV levels. METHODS: Using case control design, we enrolled children with SCD (n = 24) and matched healthy controls (HC; n = 17, age, sex, race/ethnicity). Descriptive statistics summarized demographic and clinical data. Wilcoxson-rank tests compared FSV levels between cohorts. Regression modeling tested the association between FSV levels and SCD status. Welch's t-test with Satterthwaite adjustment evaluated associations between microbiota profiles, SCD status, and pain outcomes. RESULTS: Vitamin A and D levels were significantly decreased in participants with HbSS as compared to HC (vitamin A, p = < .0001, vitamin D, p = .014) independent of nutritional status. FSV correlated with dietary intake in SCD and HC cohorts. Gut microbial diversity was reduced in hemoglobin SS (HbSS) compared to hemoglobin SC (HbSC) and HC, p = .037 and .059, respectively. The phyla Erysipelotrichaceae and Betaproteobacteria were higher in SCD children reporting the highest quality-of-life (QoL) scores (p = .008 and .049, respectively), while Clostridia were higher in those with lower QoL scores (p = .03). CONCLUSION: FSV deficiencies and gut dysbiosis are prevalent in children with SCA. Gut microbial composition is significantly different in children with SCD with low QoL scores.

Gastrointestinal symptoms, diagnostic evaluations, and abdominal pathology in children with sickle cell disease.

BACKGROUND: Children with sickle cell disease (SCD) frequently present with acute pain. The abdomen, a common site of acute SCD-related pain, may be present in a variety of gastrointestinal (GI) pathologies. Limited data exist on prevalence and workup of abdominal pain in patients with SCD during acute pain events. OBJECTIVES: Determine prevalence of GI symptoms, GI-specific evaluation and risks of hospitalization in children with SCD presenting to the emergency department (ED) or hospitalized with abdominal pain. METHODS: Retrospective study of children less than 21 years presenting to the ED or hospitalized with pain in our center over 2 years. Descriptive statistics were used to report clinical characteristics, frequency of GI symptoms, workup by age (<5 vs. ≥5 years), and genotype (sickle cell anemia [SCA] vs. non-SCA). Logistic regression models were used to identify risks associated with hospitalization. RESULTS: A total of 1279 encounters in 378 patients were analyzed; 23% (n = 291) encounters were associated with abdominal pain. More abdominal pain-associated hospitalizations occurred in older children, SCA, children with lower mean hemoglobin (8.7 ± 1.9 vs. 9.6 ± 1.6 g/dL, p < .001) and higher mean white blood cell (WBC) count (14.9 ± 6.6 vs. 13.2 ± 5.3 × 103 /µL, p = .02). We identified that less than 50% of patients presenting to the ED with abdominal pain received a GI-specific evaluation. CONCLUSION: Children with SCD frequently present with abdominal pain and other GI symptoms, with limited GI evaluations performed. GI-specific evaluation may increase diagnosis of GI pathologies, rule out GI pathologies, and contribute to the limited knowledge of the abdomen as a primary site of SCD pain.

Pediatric refractory immune thrombocytopenia: A systematic review.

Pediatric immune thrombocytopenia (ITP) is an acquired disorder associated with autoimmune destruction and impairment of platelet production in children. Some children exhibit poor or transient response to ITP-directed treatments and are referred to as having refractory ITP (rITP). There is currently no consensus on the definition of rITP, nor evidence-based treatment guidelines for patients with rITP. After a survey of pediatric ITP experts demonstrated lack of consensus on pediatric rITP, we pursued a systematic review to examine the reported clinical phenotypes and treatment outcomes in pediatric rITP. The search identified 253 relevant manuscripts; following review, 11 studies proposed a definition for pediatric rITP with no consensus amongst them. Most definitions included suboptimal response to medical management, while some outlined specific platelet thresholds to define this suboptimal response. Common attributes identified in this study should be used to propose a comprehensive definition, which will facilitate outcome comparisons of future rITP studies.

Consensus definition of essential, optimal, and suggested components of a pediatric sickle cell disease center.

Sickle cell disease (SCD) requires coordinated, specialized medical care for optimal outcomes. There are no United States (US) guidelines that define a pediatric comprehensive SCD program. We report a modified Delphi consensus-seeking process to determine essential, optimal, and suggested elements of a comprehensive pediatric SCD center. Nineteen pediatric SCD specialists participated from the US. Consensus was predefined as 2/3 agreement on each element's categorization. Twenty-six elements were considered essential (required for guideline-based SCD care), 10 were optimal (recommended but not required), and five were suggested. This work lays the foundation for a formal recognition process of pediatric comprehensive SCD centers.

Xanthine Oxidase Drives Hemolysis and Vascular Malfunction in Sickle Cell Disease.

OBJECTIVE: Chronic hemolysis is a hallmark of sickle cell disease (SCD) and a driver of vasculopathy; however, the mechanisms contributing to hemolysis remain incompletely understood. Although XO (xanthine oxidase) activity has been shown to be elevated in SCD, its role remains unknown. XO binds endothelium and generates oxidants as a byproduct of hypoxanthine and xanthine catabolism. We hypothesized that XO inhibition decreases oxidant production leading to less hemolysis. Approach and Results: Wild-type mice were bone marrow transplanted with control (AA) or sickle (SS) Townes bone marrow. After 12 weeks, mice were treated with 10 mg/kg per day of febuxostat (Uloric), Food and Drug Administration-approved XO inhibitor, for 10 weeks. Hematologic analysis demonstrated increased hematocrit, cellular hemoglobin, and red blood cells, with no change in reticulocyte percentage. Significant decreases in cell-free hemoglobin and increases in haptoglobin suggest XO inhibition decreased hemolysis. Myographic studies demonstrated improved pulmonary vascular dilation and blunted constriction, indicating improved pulmonary vasoreactivity, whereas pulmonary pressure and cardiac function were unaffected. The role of hepatic XO in SCD was evaluated by bone marrow transplanting hepatocyte-specific XO knockout mice with SS Townes bone marrow. However, hepatocyte-specific XO knockout, which results in >50% diminution in circulating XO, did not affect hemolysis levels or vascular function, suggesting hepatocyte-derived elevation of circulating XO is not the driver of hemolysis in SCD. CONCLUSIONS: Ten weeks of febuxostat treatment significantly decreased hemolysis and improved pulmonary vasoreactivity in a mouse model of SCD. Although hepatic XO accounts for >50% of circulating XO, it is not the source of XO driving hemolysis in SCD.

Adverse childhood experiences in children and adolescents with sickle cell disease: A retrospective cohort study.

BACKGROUND: Adverse childhood experiences (ACEs) are linked to poor health outcomes; however, the relationship between ACEs and health outcomes among children and adolescents with sickle cell disease (SCD) has limited documentation in the published literature. PROCEDURE: This retrospective cohort study involved 45 children and 30 adolescents. Participants were screened using the Center for Youth Wellness ACE Questionnaire. Parents completed the questionnaire for children. Adolescents provided self-report. ACEs were treated as continuous and categorical scales: 0-1 verus ≥2 original ACEs (individual and/or familial level); 0-1 versus ≥2 additional ACEs (community level); and 0-3 versus ≥4 expanded ACEs (original + additional). Pain and acute chest syndrome events were compared using Wilcoxon rank-sum tests, and correlated with cumulative ACE scores using Spearman's correlation. Multivariable models were fitted to examine the association between ACEs and pain/acute chest syndrome. RESULTS: The cumulative number of original ACEs positively correlated with acute chest syndrome events (rho = .53, p = .003) and pain (rho = .40, p = .028) among adolescents. Adolescents with ≥2 versus 0-1 original ACEs had a higher number of acute chest syndrome events (4.9 ± 2.6 vs. 1.6 ± 2.2, p = .002); however, this association was confounded by asthma. Acute chest syndrome events and hospitalizations for pain did not differ among child ACE groups. Emergency department (ED) pain visits were higher among children with ≥4 versus 0-3 expanded ACEs (1.6 ± 2.8 vs. 3.3 ± 3.2, p = .042), even after controlling for SCD genotype, asthma, disease-modifying treatment, and follow-up years (p = .027). CONCLUSION: ACEs are linked to increased morbidity among children and adolescents with SCD. Prospective studies are needed to further understand this relationship and test ACE-protective remedies.

Enuresis and Hyperfiltration in Children With Sickle Cell Disease.

Nocturnal enuresis is a common symptom in children with sickle cell disease (SCD). Risk factors for development of enuresis are currently unknown. An early manifestation of SCD-associated kidney damage is glomerular hyperfiltration. We test the hypothesis that in a pediatric SCD cohort, individuals with hyperfiltration are more likely to have nocturnal enuresis when compared to children without hyperfiltration. To assess the relationship between nocturnal enuresis and hyperfiltration, we retrospectively evaluated children with SCD enrolled in the Evaluation of Nocturnal Enuresis and Barriers to Treatment among Pediatric Patients with SCD study and prospectively identified children who reported nocturnal enuresis and were enrolled in the longitudinal cohort study Sickle Cell Clinical Research and Intervention Program. Nocturnal enuresis occurred in 46.5% of Pediatric Patients with Sickle Cell Disease participants and was more frequent in participants with HbSS/HbSß 0 thalassemia and in male participants. We did not identify an association between hyperfiltration from 3 to 5 years of age with the later development of enuresis. Severe SCD genotypes and male sex were associated with nocturnal enuresis after age 5 years. We could not identify additional renal or hematologic predictors associated with the diagnosis of nocturnal enuresis. Future studies should incorporate nonrenal risk factors into studies that predict development of enuresis.

The influence of perceived racial bias and health-related stigma on quality of life among children with sickle cell disease.

Objectives: Individuals with sickle cell disease (SCD) experience significant health problems that may result in unpredictable pain episodes and frequent healthcare utilization. Disparities in clinical care may contribute to health-related stigma and racial bias for this majority African-American/Black population. There is less known about the influence of health-related stigma and racial bias on the health-related quality of life (HRQOL) of children with SCD. In the present study, we assessed these relationships and identified differences across demographic factors (i.e. age, gender).Design: Data was collected from African American children with SCD aged 8-16 years (57% male, 63% HbSS). Children completed the Childhood Stigma Scale (adapted for SCD), the Child Perceptions of Racism in Children and Youth scale, and the Pediatric Quality of Life Inventory Sickle Cell Disease Module. Caregivers provided demographic information.Results: In the first regression model, health-related stigma (p = .007) predicted HRQOL, but neither age nor gender were significant predictors. In the second regression model, age (p = .03) predicted HRQOL, but neither gender nor racial bias were significant predictors. Of interest, there was a significant interaction between age, gender, and racial bias (p = .02). Specifically, older girls who reported high levels of perceived racial bias had poorer HRQOL.Conclusions: Our study highlights the need for increased awareness about the effects of health-related stigma and racial bias on HRQOL for children with SCD, particularly for older girls who endorse racial bias. Our findings will guide future stigma and bias reduction interventions that may meet the needs of older girls with SCD.

Generalization of a genetic risk score for time to first albuminuria in children with sickle cell anaemia: SCCRIP cohort study results.

Albuminuria predicts kidney disease progression in individuals with sickle cell anaemia (SCA); however, earlier prediction of kidney disease with introduction of reno-protective therapies prior to the onset of albuminuria may attenuate disease progression. A genetic risk score (GRS) for SCA-related nephropathy may provide an improved one-time test for early identification of high-risk patients. We utilized a GRS from a recent, large, trans-ethnic meta-analysis to identify three single nucleotide polymorphisms that associate individually and in a GRS with time to first albuminuria episode in children with SCA.

Impact of telehealth visits on hydroxyurea response in sickle cell anemia.

BACKGROUND: It is important to ensure access to hydroxyurea (HU) for patients with sickle cell anemia (SCA) living in rural areas. The University of Alabama at Birmingham (UAB) Pediatric Sickle Cell program's satellite clinics reduce the barrier of transportation to the university-based clinic. However, as compared with the university clinic, these satellite clinics do not offer immediate access to HU dosing laboratory results and a nurse clinician calls families with HU dose adjustments after the clinic visit. This study evaluated the impact of telehealth dosing adjustments on HU laboratory and clinical response as compared with university-based patients. METHODS: A one-year retrospective chart review was performed to evaluate HU laboratory and clinical response based on clinic location and socioeconomic status for patients with SCA. We identified the number of clinic and acute care visits for one year and calculated the mean complete blood count and fetal hemoglobin (HbF) values for each patient. RESULTS: We identified 107 academic center participants with SCA-prescribed HU and 65 satellite clinic participants. The mean age of participants was 11 ± 5 years. We identified no difference in HbF (13.3 ± 0.7 vs 11.7 ± 0.8, P = 0.13), Hb (8.46 ± 1.1 vs 8.55 ± 1.1, P = 0.59), mean corpuscular volume (91.0 ± 10.6 vs 91.7 ± 9.5, P = 0.67), or absolute neutrophil count (4.85 ± 2.3 vs 4.87 ± 2.3, P = 0.95) when comparing Birmingham versus satellite clinics. We also identified no difference in hospital admissions (0.99 ± 0.1 versus 0.85 ± 0.2, P = 0.49), based on clinic location. CONCLUSIONS: The use of telehealth did not negatively impact laboratory response to HU. Future studies should identify novel approaches to improve access to HU among patients with SCA living in rural areas.