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  • 1
    In: British Journal of Haematology, Wiley, Vol. 192, No. 6 ( 2021-03), p. 1082-1091
    Abstract: Neurocognitive deficits in sickle cell disease (SCD) may impair adult care engagement. We investigated the relationship between neurocognitive functioning and socio‐environmental factors with healthcare transition outcomes. Adolescents aged 15–18 years who had neurocognitive testing and completed a visit with an adult provider were included. Transition outcomes included transfer interval from paediatric to adult care and retention in adult care at 12 and 24 months. Eighty adolescents (59% male, 64% HbSS/HbSβ 0 ‐thalassaemia) were included. Mean age at adult care transfer was 18·0 (±0·3) years and transfer interval was 2·0 (±2·3) months. Higher IQ ( P  = 0·02; P FDR  = 0·05) and higher verbal comprehension ( P  = 0·008; P FDR  = 0·024) were associated with 〈 2 and 〈 6 month transfer intervals respectively. Better performance on measures of attention was associated with higher adult care retention at 12 and 24 months ( P  = 0·009; P FDR  = 0·05 and P  = 0·04; P FDR  = 0·12 respectively). Transfer intervals 〈 6 months were associated with smaller households ( P  = 0·02; P FDR  = 0·06) and households with fewer children ( P  = 0·02; P FDR  = 0·06). Having a working parent was associated with less retention in adult care at 12 and 24 months ( P  = 0·01; P  = 0·02 respectively). Lower IQ, verbal comprehension, attention difficulties and environmental factors may negatively impact transition outcomes. Neurocognitive function should be considered in transition planning for youth with SCD.
    Type of Medium: Online Resource
    ISSN: 0007-1048 , 1365-2141
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    Language: English
    Publisher: Wiley
    Publication Date: 2021
    detail.hit.zdb_id: 1475751-5
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  • 2
    In: Pediatric Blood & Cancer, Wiley, Vol. 65, No. 9 ( 2018-09)
    Abstract: Previous natural history studies have advanced the understanding of sickle cell disease (SCD), but generally have not included sufficient lifespan data or investigation of the role of genetics in clinical outcomes, and have often occurred before the widespread use of disease‐modifying therapies, such as hydroxyurea and chronic erythrocyte transfusions. To further advance knowledge of SCD, St. Jude Children's Research Hospital established the Sickle Cell Clinical Research and Intervention Program (SCCRIP), to conduct research in a clinically evaluated cohort of individuals with SCD across their lifetime. Procedures Initiated in 2014, the SCCRIP study prospectively recruits patients diagnosed with SCD and includes retrospective and longitudinal collection of clinical, neurocognitive, geospatial, psychosocial, and health outcomes data. Biological samples are banked for future genomics and proteomics studies. The organizational structure of SCCRIP is based upon organ/system‐specific working groups and is opened to the research community for partnerships. Results As of August 2017, 1,044 (92.3% of eligible) patients with SCD have enrolled in the study (860 children and 184 adults), with 11,915 person‐years of observation. Population demographics included mean age at last visit of 11.3 years (range 0.7–30.1), 49.8% females, 57.7% treated with hydroxyurea, 8.5% treated with monthly transfusions, and 62.9% hemoglobin (Hb) SS or HbSB 0 ‐thalassemia, 25.7% HbSC, 8.4% HbsB + ‐Thalassemia, 1.7% HbS/HPFH, and 1.2% other. Conclusions The SCCRIP cohort will provide a rich resource for the conduct of high impact multidisciplinary research in SCD.
    Type of Medium: Online Resource
    ISSN: 1545-5009 , 1545-5017
    URL: Issue
    Language: English
    Publisher: Wiley
    Publication Date: 2018
    detail.hit.zdb_id: 2130978-4
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  • 3
    In: British Journal of Haematology, Wiley, Vol. 189, No. 6 ( 2020-06), p. 1192-1203
    Abstract: Patients with sickle cell disease (SCD) are at increased risk for neurocognitive impairments. While disease‐modifying treatment, such as hydroxycarbamide (hydroxyurea), may decrease this risk, it has not been systematically investigated in children with SCD. We screened neurocognitive functioning in 103 adolescents with SCD (16–17 years, 50% female) and compared outcomes between patients with a history of exposure to hydroxycarbamide ( n  = 12 HbSC/HbSβ + thalassaemia; n  = 52 HbSS/HbSβ 0 thalassaemia) and those never treated with hydroxycarbamide ( n  = 31 HbSC/HbSβ + thalassaemia; n  = 8 HbSS/HbSβ 0 thalassaemia). Demographic distributions were similar between the groups. After adjusting for socioeconomic status, the hydroxycarbamide group had significantly higher scores on nonverbal IQ (HbSC/HbSβ thalassaemia: P  = 0·036, effect size [ d ] = 0·65), reaction speed (HbSS/HbSβ 0 thalassaemia: P  = 0·002, d  = 1·70), sustained attention (HbSS/HbSβ 0 thalassaemia: P  = 0·014, d  = 1·30), working memory (HbSC/HbSβ + thalassaemia: P  = 0·034, d  = 0·71) and verbal memory (HbSC/HbSβ + thalassaemia: P  = 0·038, d  = 0·84) when compared to those who did not receive hydroxycarbamide. In patients with HbSS/HbSβ 0 thalassaemia, longer treatment duration with hydroxycarbamide was associated with better verbal memory ( P  = 0·009) and reading ( P  = 0·002). Markers of hydroxycarbamide effect, including higher fetal haemoglobin (HbF), higher mean corpuscular volume (MCV) and lower white blood cell count (WBC), were associated with better verbal fluency (HbF: P  = 0·014, MCV: P  = 0·006, WBC: P  = 0·047) and reading (MCV: P  = 0·021, WBC: P  = 0·037). Cognitive impairment may be mitigated by exposure to hydroxycarbamide in adolescents with SCD.
    Type of Medium: Online Resource
    ISSN: 0007-1048 , 1365-2141
    URL: Issue
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    Language: English
    Publisher: Wiley
    Publication Date: 2020
    detail.hit.zdb_id: 1475751-5
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  • 4
    In: British Journal of Haematology, Wiley, Vol. 200, No. 3 ( 2023-02), p. 358-366
    Abstract: Children diagnosed with sickle cell disease (SCD) are at risk of the development of neurobehavioural problems early in life. Specific impairments in executive function skills, including working memory, have been documented in school‐aged children with SCD. These executive skills are known to strongly contribute to early academic skills and preparedness for entering kindergarten. This study examined working memory and school readiness in preschool children with SCD compared to a healthy control group matched for race, sex and parent education. A total of 84 patients diagnosed with SCD (61.9% haemoglobin [Hb]SS/HbSβ 0 ‐thalassaemia) and 168 controls completed testing. The mean (SD) ages of patients and controls at testing were 4.53 (0.38) and 4.44 (0.65) years respectively. The SCD group performed worse than controls on measures of executive function, working memory and school readiness ( p   〈  0.01; Cohen's D range: 0.32–0.39). Measures of working memory were associated with school readiness after accounting for early adaptive development. Multiple linear regression models among patients diagnosed with SCD revealed that college education of the primary caregiver was positively associated with school readiness ( p   〈  0.001) after controlling for sex, genotype, age and early adaptive development. These results highlight the need to implement school readiness interventions in young children diagnosed with SCD emphasising executive function skills.
    Type of Medium: Online Resource
    ISSN: 0007-1048 , 1365-2141
    URL: Issue
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    Language: English
    Publisher: Wiley
    Publication Date: 2023
    detail.hit.zdb_id: 1475751-5
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  • 5
    In: Pediatric Blood & Cancer, Wiley, Vol. 68, No. 10 ( 2021-10)
    Abstract: Sickle cell anemia (SCA) results in numerous adverse effects on the brain, including neurocognitive dysfunction. Hydroxyurea has been utilized extensively for management of SCA, but its effects on brain function have not been established. Methods We examined prospectively the effects of 1 year of treatment with hydroxyurea on brain function in children with SCA (HbSS/HbSβ 0 ‐thalassemia) by baseline and exit evaluations, including comprehensive neurocognitive testing, transcranial Doppler ultrasound (TCD), and brain MRI (silent cerebral infarcts [SCI], gray matter cerebral blood flow [GM‐CBF] , and blood oxygen level‐dependent [BOLD] signal from visual stimulation). Results Nineteen patients with SCA, mean age 12.4 years (range 7.2–17.8), were evaluated. At baseline, subjects had these mean values: full‐scale IQ (FSIQ) 82.8, TCD velocity 133 cm/s, GM‐CBF 64.4 ml/100 g/min, BOLD signal 2.34% increase, and frequency of SCI 47%. After 1 year of hydroxyurea, there were increases in FSIQ (+2, p  = .059) and reading passage comprehension (+4, p  = .033), a significant decrease in TCD velocity (−11 cm/s, p  = .007), and no significant changes in GM‐CBF, BOLD, or SCI frequency. Hemoglobin F (HbF) was associated with passage comprehension, hemoglobin with lower TCD velocity, and lower GM‐CBF with greater working memory. Higher BOLD signal was associated with higher processing speed and lower TCD velocity with higher math fluency. Discussion Improvements in neurocognition and decreased TCD velocity following 1 year of treatment support hydroxyurea use for improving neurocognitive outcomes in SCA. Understanding the mechanisms of benefit, as indicated by relationships of neurocognitive function with HbF, hemoglobin, and CBF, requires further evaluation.
    Type of Medium: Online Resource
    ISSN: 1545-5009 , 1545-5017
    URL: Issue
    Language: English
    Publisher: Wiley
    Publication Date: 2021
    detail.hit.zdb_id: 2130978-4
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  • 6
    In: Blood, American Society of Hematology, Vol. 138, No. Supplement 1 ( 2021-11-05), p. 2987-2987
    Abstract: Background: The costs associated with the treatment of sickle cell disease (SCD) are understudied in low and middle-income countries (LMIC), where resources are scarcer and policy decisions about resource allocation rely on detailed cost data. Few studies have investigated the cost-savings of disease-modifying therapies in SCD in real-world setting. We evaluated the cost of treating SCD-related acute complications and the potential cost-savings of hydroxyurea therapy at HEMORIO, a specialized tertiary hematology center in Brazil. Methods: The costs (US dollars) of emergency department (ED) and hospitalizations from SCD-related complications between 01.01.2018 and 06.30.2018 were ascertained using absorption and micro-costing approaches. ED costs are presented as cost per each ED event and hospital admission costs are presented as cost per each admission event. ED and admission costs (separated and combined) were determined and compartmentalized into several inputs by fixed and variable categories for all patients over the period of the study [Falk JA et al, Atlas 2001]. The cause of ED or hospital admission visit was verified by a physician and abstracted via medical record review. All hospital admissions were evaluated in the ED. If an ED encounter resulted in an admission, the encounter was counted as an admission event only. The causes related to SCD were grouped and classified according to the discharge diagnosis: 1) VOC (acute pain crisis, priapism or dactylitis); 2) Infection (fever, sepsis, or acute chest syndrome); 3) Anemia exacerbation (acute hemolytic crisis, transient aplastic crisis, or acute splenic sequestration); 4) Chronic organ damage (overt stroke, chronic kidney disease, chronic liver disease or organ failure. Hydroxyurea adherence was estimated by medication possession ratio (MPR) during the study period [Shah N, et al. Health and quality of life outcomes. 2019] . The one-sample proportions test with continuity correction compared the differences in frequency of ED or admissions across discharge diagnoses and the Wilcoxon rank sum test with continuity correction was used to compare cost differences across the groups. Results: In total, 1144 patients, median age 17 years (range 0-70), 903 (78.9%) with HbSS/HbSβ 0-thalassemia, 441 (38.5%) prescribed hydroxyurea, visited the ED, of whom 381 (33%) were admitted. VOC accounted for 64% of all ED visits and 60% of all admissions (Table 1). Anemia exacerbation was the most expensive reason for ED visit ($321.87/visit), while chronic organ damage carried the highest admission cost ($2,176.40/visit) (Figure 1). Compared with other genotypes, individuals with HbSS/HbSβ 0-thalassemia were admitted more often (79% versus 21%, p & lt;0.0001), and their admission costs were higher ($1,677.18 versus $1,224.47/visit, p=0.0001). Antibiotics and analgesics accounted for 43% and 42% of the total ED costs, respectively, while housing accounted for 46% of the total admission costs (Figure 2). In a regression tree analysis, costs of ED visits were lower among HbSS/HbSβ 0-thalassemia individuals with hydroxyurea MPR ≥65% compared with those with MPR & lt;65% or untreated ($182.46 versus $98.16/visit, p=0.0007). No difference in admission costs were observed relative to hydroxyurea use. Discussion: It is estimated that between 60,000 to 100,000 individuals live with SCD in Brazil today [Lobo CL, et al. Pediatric blood & cancer. 2014]. In a LMIC hematology-specialized center, VOCs accounted for most acute visits from patients with SCD, but costs were highest due to anemia exacerbation. Analgesics, antibiotics, and housing drove most expenses. Our results confirm the lower acute health care resource utilization with hydroxyurea therapy (fewer ED visits and admissions among those prescribed this medication). Hydroxyurea therapy reduced ED costs among individuals with HbSS/HbSβ 0-thalassemia, however, was dependent on adherence level. A cost analysis of individuals with SCD has never been performed in Brazil previously. Our study will facilitate appropriate planning of allocation of funds and development of health policies for individuals with SCD and may serve as the benchmark against which new SCD disease-modifying therapies may be compared for cost-effectiveness and cost-savings estimation in LMIC, such as Brazil. Figure 1 Figure 1. Disclosures Lobo: Novartis: Consultancy. Hankins: Global Blood Therapeutics: Consultancy; UpToDate: Consultancy; Vindico Medical Education: Consultancy; Bluebird Bio: Consultancy.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2021
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
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  • 7
    In: BMC Health Services Research, Springer Science and Business Media LLC, Vol. 22, No. 1 ( 2022-12)
    Abstract: The costs associated with the treatment of sickle cell disease (SCD) are understudied in low and middle-income countries (LMIC). We evaluated the cost of treating SCD-related acute complications and the potential cost-savings of hydroxyurea in a specialized hematology center in Brazil. Methods The costs (US dollars) of emergency department (ED) and hospitalizations from SCD-related complications between 01.01.2018 and 06.30.2018 were ascertained using absorption and micro-costing approaches. The reasons for acute hospital visits were grouped as: 1) vaso-occlusive (VOC) pain, 2) infection, 3) anemia exacerbation, and 4) chronic organ damage complications. Hydroxyurea adherence was estimated by medication possession ratio (MPR) during the study period. Results In total, 1144 patients, median age 17 years (range 0–70), 903 (78.9%) with HbSS/HbSβ 0 -thalassemia, 441 (38.5%) prescribed hydroxyurea, visited the ED, of whom 381 (33%) were admitted. VOC accounted for 64% of all ED visits and 60% of all admissions. Anemia exacerbation was the most expensive reason for ED visit ($321.87/visit), while chronic organ damage carried the highest admission cost ($2176.40/visit). Compared with other genotypes, individuals with HbSS/HbSβ 0 -thalassemia were admitted more often (79% versus 21%, p   〈  0.0001), and their admission costs were higher ($1677.18 versus $1224.47/visit, p  = 0.0001). Antibiotics and analgesics accounted for 43% and 42% of the total ED costs, respectively, while housing accounted for 46% of the total admission costs. Costs of ED visits not resulting in admissions were lower among HbSS/HbSβ 0 -thalassemia individuals with hydroxyurea MPR ≥65% compared with visits by patients with MPR  〈 65% ($98.16/visit versus $182.46/visit, p  = 0.0007). No difference in admission costs were observed relative to hydroxyurea use. Discussion In a LMIC hematology-specialized center, VOCs accounted for most acute visits from patients with SCD, but costs were highest due to anemia exacerbation. Analgesics, antibiotics, and housing drove most expenses. Hydroxyurea may reduce ED costs among individuals with HbSS/HbSβ 0 -thalassemia but is dependent on adherence level.
    Type of Medium: Online Resource
    ISSN: 1472-6963
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2022
    detail.hit.zdb_id: 2050434-2
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  • 8
    In: Blood, American Society of Hematology, Vol. 130, No. Suppl_1 ( 2017-12-07), p. 760-760
    Abstract: Background: Sickle cell anemia is associated with progressive compromise of neurocognitive function exacerbated by stroke or silent cerebral infarction. Despite decades of experience with chronic transfusion, hematopoietic stem cell transplantation, and HU, improvement in neurocognitive performance from these interventions has not been clearly demonstrated; only one study has reported improvement in global cognitive index from HU (Puffer, Child Neuropsychology, 2007). As part of a comprehensive prospective evaluation of the effects of HU treatment on the central nervous system, we evaluated neuropsychological performance in school-age children with sickle cell anemia. Methods: Subjects had HbSS/Sβ0 thalassemia and no history of previous central nervous system (CNS) events and were 7-18 years old. After informed consent, baseline evaluations included the Wechsler Intelligence Scale for Children, 4th edition (WISC-IV) and the Woodcock-Johnson Achievement Test Version III (WJ-III). Treated patients received HU beginning at 20 mg/kg/d with gradual escalation to maximum tolerated dose (MTD) within one year. They were evaluated with the same CNS studies after 12 months. A control group who declined HU treatment was matched by diagnosis and age and was also evaluated at baseline and after one year. Summary statistics of WISC and WJ-III scores were reported for each time point and for their change between two time points in each group and were compared using the Wilcoxon rank sum and Wilcoxon signed rank tests, respectively. Results: Age and gender distributions in HU-treated (n=21) and untreated control patients (n=11) were comparable. In HU-treated patients, but not in controls, there was significant improvement in mean full scale IQ (FSIQ) after one year (Table 1). In treated subjects, mean WISC subscale scores were all higher after one year, although none were statistically significant. Among controls, FSIQ and all subscales, except working memory, showed a numerical decrease in mean scores, with the greatest decline in perceptual reasoning. Subtest scores from the WJ-III Achievement test in HU-treated patients showed significant improvement in comprehension of word passages. Among controls, WJ-III Achievement subtest scores showed no significant changes. When mean changes in WISC scores from baseline to one-year follow-up were compared (Table 2), treated patients showed greater positive changes than controls, but differences were not significant. Changes in WJ-III scores for treated and control subjects also were not significant. Conclusions: In children with sickle cell anemia, HU treatment over a one year period was associated with a significant improvement in the Wechsler Full Scale IQ; subscales showed small to medium positive changes although the differences were not statistically significant. By contrast, in the untreated control group, most scores were lower after one year and mean changes in scores from baseline were less positive than those in the HU group. In measures of achievement, the treated group demonstrated improved passage (reading) comprehension, a skill related to executive function. Overall, these results suggest that HU may improve cognitive function or prevent decline. Correlation of standard and functional MR neuroimaging in these subjects with neurocognitive performance is pending. Future trials are needed to examine the impact of other interventions (e.g., memory training, multisensory reading intervention), possibly in conjunction with HU. Disclosures No relevant conflicts of interest to declare.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    RVK:
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2017
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
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  • 9
    In: Pediatric Blood & Cancer, Wiley, Vol. 69, No. 11 ( 2022-11)
    Abstract: Transcranial doppler (TCD) ultrasonography can be used to identify stroke risk in children with sickle cell anemia. Previous studies have reported mixed findings on neurocognitive outcomes in children with elevated TCD. This study examined associations between TCD velocity and neurocognitive outcomes in children and adolescents without prior history of stroke. Procedure Participants were selected from the Sickle Cell Clinical Research Intervention Program cohort. The highest recorded mean maximum TCD velocity was selected for analysis, along with participant's most recent data from serial neurocognitive surveillance. Results A total of 200 children with sickle cell anemia completed neurocognitive testing (109 males, 91 females; mean age 12.7 years [SD = 3.56]). Most participants were prescribed hydroxyurea (72%) at the time of neurocognitive testing and nearly 16% had a history of chronic transfusions prior to neurocognitive evaluation. Mean age at time of highest TCD value was 6.6 years (SD = 2.5) and 13.5% of screenings were abnormal (≥200 cm/s). Mean interval between TCD and most recent neurocognitive evaluation was 6.1 years (±3.5). There were no significant differences in the interval between TCD and neurocognitive testing across normal, conditional, and abnormal groups. Maximum TCD velocity was not significantly associated with neurocognitive outcomes in multivariate models. Conclusions History of elevated TCD in the absence of overt stroke should not be considered a risk factor for poor neurocognitive outcomes in children and adolescents with sickle cell anemia on modern disease‐modifying therapy.
    Type of Medium: Online Resource
    ISSN: 1545-5009 , 1545-5017
    URL: Issue
    Language: English
    Publisher: Wiley
    Publication Date: 2022
    detail.hit.zdb_id: 2130978-4
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  • 10
    In: British Journal of Haematology, Wiley, Vol. 195, No. 2 ( 2021-10), p. 256-266
    Abstract: Neurocognitive impairment is common in sickle cell disease (SCD) and is associated with significant functional limitations. In a cross‐sectional analysis, we examined the association between hydroxyurea (HU) treatment and neurocognitive functioning from school‐age to young adulthood in individuals with SCD. A total of 215 patients with HbSS/HbSβ 0 ‐thalassaemia (71% HU treated) and 149 patients with HbSC/HbSβ + ‐thalassaemia (20% HU treated) completed neurocognitive measures at one of four developmental stages: school‐age (age 8–9 years), early adolescence (age 12–13 years), late adolescence (age 16–17 years) and young adulthood (ages 19–24 years). For participants with multiple assessments, only the most recent evaluation was included. In multivariable analysis adjusted for social vulnerability, HU treatment and sex, older age was associated with a reduction in overall intelligence quotient (IQ) of 0·55 points per year of life [standard error (SE) = 0·18, false discovery rate adjusted P value ( PFDR ) = 0.01] for patients with HbSS/HbSβ 0 ‐thalassaemia. Earlier initiation of HU ( n  = 152) in HbSS/HbSβ 0 ‐thalassaemia was associated with higher scores on neurocognitive measures across most domains, including IQ [estimate (SE) 0·77 (0·25)/year, PFDR =  0·01], after adjusting for social vulnerability, sex and treatment duration. These results support the early use of HU to limit the detrimental neurocognitive effects of SCD, while highlighting the need for additional measures to further mitigate neurocognitive deterioration.
    Type of Medium: Online Resource
    ISSN: 0007-1048 , 1365-2141
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    RVK:
    Language: English
    Publisher: Wiley
    Publication Date: 2021
    detail.hit.zdb_id: 1475751-5
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