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Silent cerebral infarcts and cerebral aneurysms are prevalent in adults with sickle cell anemia.
Kassim AA, Pruthi S, Day M, Rodeghier M, Gindville MC, Brodsky MA, DeBaun MR, Jordan LC
(2016) Blood 127: 2038-40
MeSH Terms: Adolescent, Adult, Anemia, Sickle Cell, Asymptomatic Diseases, Cerebral Infarction, Child, Child, Preschool, Cross-Sectional Studies, Female, Humans, Infant, Intracranial Aneurysm, Male, Prevalence, Young Adult
Added July 20, 2016
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15 MeSH Terms
Transfusions for silent cerebral infarcts in sickle cell anemia.
DeBaun MR, Casella JF
(2014) N Engl J Med 371: 1841-2
MeSH Terms: Anemia, Sickle Cell, Blood Transfusion, Cerebral Infarction, Female, Humans, Male
Added March 19, 2015
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6 MeSH Terms
Health-related quality of life in children with sickle cell anemia: impact of blood transfusion therapy.
Beverung LM, Strouse JJ, Hulbert ML, Neville K, Liem RI, Inusa B, Fuh B, King A, Meier ER, Casella J, DeBaun MR, Panepinto JA, SIT trial investigators
(2015) Am J Hematol 90: 139-43
MeSH Terms: Adolescent, Anemia, Sickle Cell, Blood Transfusion, Cerebral Infarction, Child, Child, Preschool, Female, Humans, Male, Patient-Centered Care, Quality of Life, Severity of Illness Index, Surveys and Questionnaires, Treatment Outcome
Show Abstract · Added March 19, 2015
The completion of the Multicenter Silent Infarct Transfusion Trial demonstrated that children with pre-existing silent cerebral infarct and sickle cell anemia (SCA) who received regular blood transfusion therapy had a 58% relative risk reduction of infarct recurrence when compared to observation. However, the total benefit of blood transfusion therapy, as assessed by the parents, was not measured against the burden of monthly blood transfusion therapy. In this planned ancillary study, we tested the hypothesis that a patient centered outcome, health-related quality of life (HRQL), would be greater in participants randomly assigned to the blood transfusion therapy group than the observation group. A total of 89% (175 of 196) of the randomly allocated participants had evaluable entry and exit HRQL evaluations. The increase in Change in Health, measured as the child's health being better, was significantly greater for the transfusion group than the observation group (difference estimate = -0.54, P ≤ 0.001). This study provides the first evidence that children with SCA who received regular blood transfusion therapy felt better and had better overall HRQL than those who did not receive transfusion therapy.
© 2014 Wiley Periodicals, Inc.
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14 MeSH Terms
Controlled trial of transfusions for silent cerebral infarcts in sickle cell anemia.
DeBaun MR, Gordon M, McKinstry RC, Noetzel MJ, White DA, Sarnaik SA, Meier ER, Howard TH, Majumdar S, Inusa BP, Telfer PT, Kirby-Allen M, McCavit TL, Kamdem A, Airewele G, Woods GM, Berman B, Panepinto JA, Fuh BR, Kwiatkowski JL, King AA, Fixler JM, Rhodes MM, Thompson AA, Heiny ME, Redding-Lallinger RC, Kirkham FJ, Dixon N, Gonzalez CE, Kalinyak KA, Quinn CT, Strouse JJ, Miller JP, Lehmann H, Kraut MA, Ball WS, Hirtz D, Casella JF
(2014) N Engl J Med 371: 699-710
MeSH Terms: Adolescent, Anemia, Sickle Cell, Blood Transfusion, Cerebral Infarction, Child, Child, Preschool, Female, Ferritins, Hemoglobin, Sickle, Humans, Intelligence, Intention to Treat Analysis, Male, Secondary Prevention, Single-Blind Method, Transfusion Reaction
Show Abstract · Added October 7, 2014
BACKGROUND - Silent cerebral infarcts are the most common neurologic injury in children with sickle cell anemia and are associated with the recurrence of an infarct (stroke or silent cerebral infarct). We tested the hypothesis that the incidence of the recurrence of an infarct would be lower among children who underwent regular blood-transfusion therapy than among those who received standard care.
METHODS - In this randomized, single-blind clinical trial, we randomly assigned children with sickle cell anemia to receive regular blood transfusions (transfusion group) or standard care (observation group). Participants were between 5 and 15 years of age, with no history of stroke and with one or more silent cerebral infarcts on magnetic resonance imaging and a neurologic examination showing no abnormalities corresponding to these lesions. The primary end point was the recurrence of an infarct, defined as a stroke or a new or enlarged silent cerebral infarct.
RESULTS - A total of 196 children (mean age, 10 years) were randomly assigned to the observation or transfusion group and were followed for a median of 3 years. In the transfusion group, 6 of 99 children (6%) had an end-point event (1 had a stroke, and 5 had new or enlarged silent cerebral infarcts). In the observation group, 14 of 97 children (14%) had an end-point event (7 had strokes, and 7 had new or enlarged silent cerebral infarcts). The incidence of the primary end point in the transfusion and observation groups was 2.0 and 4.8 events, respectively, per 100 years at risk, corresponding to an incidence rate ratio of 0.41 (95% confidence interval, 0.12 to 0.99; P=0.04).
CONCLUSIONS - Regular blood-transfusion therapy significantly reduced the incidence of the recurrence of cerebral infarct in children with sickle cell anemia. (Funded by the National Institute of Neurological Disorders and Stroke and others; Silent Cerebral Infarct Multi-Center Clinical Trial ClinicalTrials.gov number, NCT00072761, and Current Controlled Trials number, ISRCTN52713285.).
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16 MeSH Terms
Silent cerebral infarction, income, and grade retention among students with sickle cell anemia.
King AA, Rodeghier MJ, Panepinto JA, Strouse JJ, Casella JF, Quinn CT, Dowling MM, Sarnaik SA, Thompson AA, Woods GM, Minniti CP, Redding-Lallinger RC, Kirby-Allen M, Kirkham FJ, McKinstry R, Noetzel MJ, White DA, Kwiatkowski JK, Howard TH, Kalinyak KA, Inusa B, Rhodes MM, Heiny ME, Fuh B, Fixler JM, Gordon MO, DeBaun MR
(2014) Am J Hematol 89: E188-92
MeSH Terms: Adolescent, Anemia, Sickle Cell, Cerebral Infarction, Child, Child, Preschool, Cross-Sectional Studies, Educational Status, Humans, Male, Models, Biological, United States
Show Abstract · Added October 7, 2014
Children with sickle cell anemia have a higher-than-expected prevalence of poor educational attainment. We test two key hypotheses about educational attainment among students with sickle cell anemia, as measured by grade retention and use of special education services: (1) lower household per capita income is associated with lower educational attainment; (2) the presence of a silent cerebral infarct is associated with lower educational attainment. We conducted a multicenter, cross-sectional study of cases from 22 U.S. sites included in the Silent Infarct Transfusion Trial. During screening, parents completed a questionnaire that included sociodemographic information and details of their child's academic status. Of 835 students, 670 were evaluable; 536 had data on all covariates and were used for analysis. The students' mean age was 9.4 years (range: 5-15) with 52.2% male; 17.5% of students were retained one grade level and 18.3% received special education services. A multiple variable logistic regression model identified that lower household per capita income (odds ratio [OR] of quartile 1 = 6.36, OR of quartile 2 = 4.7, OR of quartile 3 = 3.87; P = 0.001 for linear trend), age (OR = 1.3; P < 0.001), and male gender (OR, 2.2; P = 0.001) were associated with grade retention; silent cerebral infarct (P = 0.31) and painful episodes (P = 0.60) were not. Among students with sickle cell anemia, household per capita income is associated with grade retention, whereas the presence of a silent cerebral infarct is not. Future educational interventions will need to address both the medical and socioeconomic issues that affect students with sickle cell anemia.
© 2014 Wiley Periodicals, Inc.
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11 MeSH Terms
Reply: To PMID 24529619.
DeBaun MR, Dowling MM
(2014) J Pediatr 165: 646
MeSH Terms: Anemia, Sickle Cell, Cerebral Infarction, Female, Headache, Hemoglobins, Humans, Male, Migraine Disorders
Added October 7, 2014
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8 MeSH Terms
Randomization is not associated with socio-economic and demographic factors in a multi-center clinical trial of children with sickle cell anemia.
Roberts DO, Covert B, Rodeghier MJ, Parmar N, DeBaun MR, Thompson AA, Liem RI
(2014) Pediatr Blood Cancer 61: 1529-1535
MeSH Terms: Adolescent, Anemia, Sickle Cell, Blood Transfusion, Cerebral Infarction, Child, Child, Preschool, Demography, Female, Follow-Up Studies, Humans, Male, Prognosis, Socioeconomic Factors
Show Abstract · Added October 7, 2014
BACKGROUND - Few studies have investigated factors influencing participation rates for minority children with a chronic disease in clinical trials. The Silent Cerebral Infarct Multi-Center Clinical (SIT) Trial provides an opportunity to study the impact of demographic and socio-economic factors on randomization in a clinical trial among Black children. Our primary objective was to characterize the factors associated with successful randomization of children with sickle cell disease (SCD) and silent cerebral infarct (SCI) in the SIT Trial after initial consent.
PROCEDURE - Differences in socio-economic and demographic variables, family history and disease-related variables were determined between eligible participants who were successfully randomized and those who were not randomized following initial consent. Head of household educational level and family income were examined separately for US versus non-US sites.
RESULTS - Of 1,176 children enrolled in the SIT Trial, 1,016 (86%) completed screening. Of 208 (20%) children with qualifying SCI on pre-randomization MRI, 196 (94%) were successfully randomized. There were no differences in socio-economic, demographic, or disease-related variables between children who were or were not randomized. Participants from non-US sites were more likely to be randomized (22% vs. 12%, P = 0.011); although, randomization by country was associated with neither head of household education nor family income.
CONCLUSION - In the SIT Trial, acceptance of random allocation was not associated with socio-economic or demographic factors. Although these factors may represent barriers for some participants, they should not bias investigators caring for children with SCD in their approach to recruitment for clinical trial participation.
© 2014 Wiley Periodicals, Inc.
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13 MeSH Terms
Headache and migraine in children with sickle cell disease are associated with lower hemoglobin and higher pain event rates but not silent cerebral infarction.
Dowling MM, Noetzel MJ, Rodeghier MJ, Quinn CT, Hirtz DG, Ichord RN, Kwiatkowski JL, Roach ES, Kirkham FJ, Casella JF, DeBaun MR
(2014) J Pediatr 164: 1175-1180.e1
MeSH Terms: Adolescent, Anemia, Sickle Cell, Biomarkers, Blood Transfusion, Cerebral Infarction, Child, Child, Preschool, Cross-Sectional Studies, Female, Headache, Hemoglobins, Humans, Logistic Models, Magnetic Resonance Imaging, Male, Migraine Disorders, Multivariate Analysis, Pain, Recurrence, Risk Factors, Severity of Illness Index
Show Abstract · Added February 19, 2014
OBJECTIVE - To identify risk factors for headache and migraine in children with sickle cell disease and test the hypothesis that either or both are independently associated with silent cerebral infarcts.
STUDY DESIGN - In this cross-sectional study, we evaluated the health history, laboratory values, and brain magnetic resonance imaging findings of participants with sickle cell disease (hemoglobinSS or hemoglobinSβ°-thalassemia) with no history of overt stroke or seizures. Participants characterized headache severity and quality. Migraine was defined by International Headache Society criteria modified for increased sensitivity in children. Neuroradiology and neurology committees adjudicated the presence of silent cerebral infarction by review of magnetic resonance imaging and standardized examination by pediatric neurologists.
RESULTS - The cohort included 872 children (51.1% males), ranging in age from 5 to 15 years (mean age, 9.1 years). Of these children, 317 (36.4%) reported recurrent headaches, and 132 (15.1%) reported migraines. In multivariable logistic regression analyses, both were associated with lower steady-state hemoglobin (P = .01 for headaches; P < .01 for migraines) and higher pain rate (P < .01 for headaches; P < .01 for migraines), defined as the number of admissions requiring opioids in the previous 3 years. The presence of silent cerebral infarction was not associated with recurrent headaches or migraines. Only 1.9% (6 of 317) of children with recurrent headaches received medication for headache prophylaxis.
CONCLUSION - Recurrent headaches and migraines are common and undertreated in children with sickle cell disease. Low hemoglobin levels and high pain rates are associated with recurrent headaches and migraines; whereas, silent cerebral infarction is not.
Copyright © 2014 Elsevier Inc. All rights reserved.
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21 MeSH Terms
Reproducibility of detecting silent cerebral infarcts in pediatric sickle cell anemia.
Liem RI, Liu J, Gordon MO, Vendt BA, McKinstry RC, Kraut MA, Strouse JJ, Ball WS, DeBaun MR
(2014) J Child Neurol 29: 1685-91
MeSH Terms: Anemia, Sickle Cell, Cerebral Infarction, Child, Female, Humans, Magnetic Resonance Imaging, Male, Reproducibility of Results
Show Abstract · Added February 19, 2014
Detecting silent cerebral infarcts on magnetic resonance images (MRIs) in children with sickle cell anemia is challenging, yet reproducibility of readings has not been examined in this population. We evaluated consensus rating, inter-, and intra-grader agreement associated with detecting silent cerebral infarct on screening MRI in the Silent Infarct Transfusion Trial. Three neuroradiologists provided consensus decisions for 1073 MRIs. A random sample of 53 scans was reanalyzed in blinded fashion. Agreement between first and second consensus ratings was substantial (κ = 0.70, P < .0001), as was overall intergrader agreement (κ = 0.76, P < .0001). In the test-retest sample, intragrader agreement ranged from κ of 0.57 to 0.76. Consensus decisions were more concordant when MRIs contained more than one larger lesions. Routine use of MRI to screen for silent cerebral infarcts in the research setting is reproducible in sickle cell anemia and agreement among neuroradiologists is sufficient.
© The Author(s) 2013.
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8 MeSH Terms
Parent education and biologic factors influence on cognition in sickle cell anemia.
King AA, Strouse JJ, Rodeghier MJ, Compas BE, Casella JF, McKinstry RC, Noetzel MJ, Quinn CT, Ichord R, Dowling MM, Miller JP, Debaun MR
(2014) Am J Hematol 89: 162-7
MeSH Terms: Adolescent, Anemia, Sickle Cell, Cerebral Infarction, Child, Child, Preschool, Cognition Disorders, Cross-Sectional Studies, Female, Hemoglobins, Humans, Magnetic Resonance Imaging, Male, Oxygen Consumption, Prognosis, Risk Factors, Socioeconomic Factors
Show Abstract · Added November 27, 2013
Children with sickle cell anemia have a high prevalence of silent cerebral infarcts (SCIs) that are associated with decreased full-scale intelligence quotient (FSIQ). While the educational attainment of parents is a known strong predictor of the cognitive development of children in general, the role of parental education in sickle cell anemia along with other factors that adversely affect cognitive function (anemia, cerebral infarcts) is not known. We tested the hypothesis that both the presence of SCI and parental education would impact FSIQ in children with sickle cell anemia. A multicenter, cross-sectional study was conducted in 19 US sites of the Silent Infarct Transfusion Trial among children with sickle cell anemia, age 5-15 years. All were screened for SCIs. Participants with and without SCI were administered the Wechsler Abbreviated Scale of Intelligence. A total of 150 participants (107 with and 43 without SCIs) were included in the analysis. In a multivariable linear regression model for FSIQ, the absence of college education for the head of household was associated with a decrease of 6.2 points (P = 0.005); presence of SCI with a 5.2 point decrease (P = 0.017); each $1000 of family income per capita with a 0.33 point increase (P = 0.023); each increase of 1 year in age with a 0.96 point decrease (P = 0.023); and each 1% (absolute) decrease in hemoglobin oxygen saturation with 0.75 point decrease (P = 0.030). In conclusion, FSIQ in children with sickle cell anemia is best accounted for by a multivariate model that includes both biologic and socioenvironmental factors.
Copyright © 2013 Wiley Periodicals, Inc.
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16 MeSH Terms