33 results on '"Debaun, Michael R."'
Search Results
2. Initiating adjunct low-dose hydroxyurea therapy for stroke prevention in children with SCA during the COVID-19 pandemic.
- Author
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DeBaun MR
- Subjects
- Anemia, Sickle Cell complications, Blood Donors supply & distribution, Blood Safety, COVID-19, Child, Child, Preschool, Humans, Pandemics, Risk Factors, Secondary Prevention, Stroke etiology, Anemia, Sickle Cell therapy, Antisickling Agents therapeutic use, Blood Transfusion, Coronavirus Infections epidemiology, Hydroxyurea therapeutic use, Pneumonia, Viral epidemiology, Stroke prevention & control
- Published
- 2020
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3. Differential cerebral hemometabolic responses to blood transfusions in adults and children with sickle cell anemia.
- Author
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Juttukonda MR, Lee CA, Patel NJ, Davis LT, Waddle SL, Gindville MC, Pruthi S, Kassim AA, DeBaun MR, Donahue MJ, and Jordan LC
- Subjects
- Adolescent, Adult, Age Factors, Brain metabolism, Child, Female, Hematocrit, Hemodynamics, Humans, Longitudinal Studies, Magnetic Resonance Imaging, Male, Oximetry, Oxygen metabolism, Oxygen Consumption, Pain Management, Prospective Studies, Recurrence, Stroke, Young Adult, Anemia, Sickle Cell diagnostic imaging, Blood Transfusion, Cerebrovascular Circulation
- Abstract
Background: Blood transfusions are administered to children and adults with sickle cell anemia (SCA) for secondary stroke prevention, or as treatment for recurrent pain crises or acute anemia, but transfusion effects on cerebral hemodynamics and metabolism are not well-characterized., Purpose: To compare blood transfusion-induced changes in hemometabolic parameters, including oxygen extraction fraction (OEF) and cerebral blood flow (CBF), within and between adults and children with SCA., Study Type: Prospective, longitudinal study., Subjects: Adults with SCA (n = 16) receiving simple (n = 7) or exchange (n = 9) transfusions and children with SCA (n = 11) receiving exchange transfusions were scanned once when hematocrit was near nadir and again within 7 days of transfusion. Adult controls without SCA or sickle trait (n = 7) were scanned twice on separate days., Field Strength/sequence: 3.0T T
1 -weighted, T2 -weighted, and T2 -relaxation-under-spin-tagging (TRUST) imaging, and phase contrast angiography., Assessment: Global OEF was computed as the relative difference between venous oxygenation (from TRUST) and arterial oxygenation (from pulse oximetry). Global CBF was computed as total blood flow to the brain normalized by intracranial tissue volume., Statistical Tests: Hemometabolic variables were compared using two-sided Wilcoxon signed-rank tests; associations were analyzed using two-sided Spearman's correlation testing., Results: In adults with SCA, posttransfusion OEF = 0.38 ± 0.05 was lower (P = 0.001) than pretransfusion OEF = 0.45 ± 0.09. A change in OEF was correlated with increases in hematocrit (P = 0.02; rho = -0.62) and with pretransfusion hematocrit (P = 0.02; rho = 0.65). OEF changes after transfusion were greater (P = 0.002) in adults receiving simple versus exchange transfusions. Posttransfusion CBF = 77.7 ± 26.4 ml/100g/min was not different (P = 0.27) from pretransfusion CBF = 82.3 ± 30.2 ml/100g/min. In children with SCA, both posttransfusion OEF = 0.28 ± 0.04 and CBF = 76.4 ± 26.4 were lower than pretransfusion OEF = 0.36 ± 0.06 (P = 0.004) and CBF = 96.4 ± 16.5 (P = 0.004)., Data Conclusion: Cerebral OEF reduces following transfusions in adults and children with SCA. CBF reduces following transfusions more often in children compared to adults, indicating that vascular reserve capacity may remain near exhaustion posttransfusion in many adults., Level of Evidence: 2 Technical Efficacy Stage 5 J. Magn. Reson. Imaging 2019;49:466-477., (© 2018 International Society for Magnetic Resonance in Medicine.)- Published
- 2019
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4. Chronic transfusion therapy for stroke in sickle cell disease.
- Author
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DeBaun MR and Quirolo K
- Subjects
- Adolescent, Child, Humans, Procedures and Techniques Utilization, Stroke etiology, Young Adult, Anemia, Sickle Cell complications, Blood Transfusion, Stroke therapy
- Published
- 2017
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5. New option for primary stroke prevention in sickle cell anaemia.
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DeBaun MR and Kirkham FJ
- Subjects
- Female, Humans, Male, Anemia, Sickle Cell drug therapy, Antisickling Agents therapeutic use, Blood Transfusion methods, Hydroxyurea therapeutic use
- Published
- 2016
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6. Evolution of sickle cell disease from a life-threatening disease of children to a chronic disease of adults: The last 40 years.
- Author
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Chaturvedi S and DeBaun MR
- Subjects
- Adult, Anemia, Sickle Cell complications, Anemia, Sickle Cell mortality, Anemia, Sickle Cell prevention & control, Anti-Bacterial Agents administration & dosage, Antibiotic Prophylaxis, Antisickling Agents administration & dosage, Child, Child, Preschool, Chronic Disease, Humans, Hydroxyurea therapeutic use, Infant, Infant, Newborn, Mortality trends, Neonatal Screening, Penicillins therapeutic use, Stroke etiology, Stroke prevention & control, Anemia, Sickle Cell therapy, Anti-Bacterial Agents therapeutic use, Antisickling Agents therapeutic use, Blood Transfusion, Hematopoietic Stem Cell Transplantation
- Abstract
Over the past 40 years, public health measures such as universal newborn screening, penicillin prophylaxis, vaccinations, and hydroxyurea therapy have led to an impressive decline in sickle cell disease (SCD)-related childhood mortality and SCD-related morbidity in high-income countries. We remain cautiously optimistic that the next 40 years will be focused on meeting current challenges in SCD by addressing chronic complications of SCD to reduce mortality and improve quality of life in a growing population of adults with SCD in high-income countries, while simultaneously decreasing the disparity of medical care between high and low-income countries., (© 2015 Wiley Periodicals, Inc.)
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- 2016
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7. Health-related quality of life in children with sickle cell anemia: impact of blood transfusion therapy.
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Beverung LM, Strouse JJ, Hulbert ML, Neville K, Liem RI, Inusa B, Fuh B, King A, Meier ER, Casella J, DeBaun MR, and Panepinto JA
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- Adolescent, Anemia, Sickle Cell complications, Anemia, Sickle Cell physiopathology, Anemia, Sickle Cell therapy, Cerebral Infarction complications, Cerebral Infarction physiopathology, Cerebral Infarction therapy, Child, Child, Preschool, Female, Humans, Male, Patient-Centered Care, Severity of Illness Index, Surveys and Questionnaires, Treatment Outcome, Anemia, Sickle Cell psychology, Blood Transfusion, Cerebral Infarction psychology, Quality of Life
- Abstract
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.)
- Published
- 2015
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8. Transfusions for silent cerebral infarcts in sickle cell anemia.
- Author
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DeBaun MR and Casella JF
- Subjects
- Female, Humans, Male, Anemia, Sickle Cell therapy, Blood Transfusion, Cerebral Infarction prevention & control
- Published
- 2014
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9. The challenge of creating an evidence-based guideline for sickle cell disease.
- Author
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DeBaun MR
- Subjects
- Humans, Anemia, Sickle Cell therapy, Blood Transfusion, Hydroxyurea therapeutic use
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- 2014
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10. Randomization is not associated with socio-economic and demographic factors in a multi-center clinical trial of children with sickle cell anemia.
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Roberts DO, Covert B, Rodeghier MJ, Parmar N, DeBaun MR, Thompson AA, and Liem RI
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- Adolescent, Child, Child, Preschool, Demography, Female, Follow-Up Studies, Humans, Male, Prognosis, Socioeconomic Factors, Anemia, Sickle Cell therapy, Blood Transfusion, Cerebral Infarction therapy
- Abstract
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.)
- Published
- 2014
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11. Controlled trial of transfusions for silent cerebral infarcts in sickle cell anemia.
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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 Jr, Hirtz D, and Casella JF
- Subjects
- Adolescent, Anemia, Sickle Cell complications, Cerebral Infarction etiology, Child, Child, Preschool, Female, Ferritins blood, Hemoglobin, Sickle analysis, Humans, Intelligence, Intention to Treat Analysis, Male, Secondary Prevention, Single-Blind Method, Transfusion Reaction, Anemia, Sickle Cell therapy, Blood Transfusion, Cerebral Infarction prevention & control
- Abstract
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.).
- Published
- 2014
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12. The case for and against initiating either hydroxyurea therapy, blood transfusion therapy or hematopoietic stem cell transplant in asymptomatic children with sickle cell disease.
- Author
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Kassim AA and DeBaun MR
- Subjects
- Anemia, Sickle Cell diagnosis, Anemia, Sickle Cell physiopathology, Chest Pain prevention & control, Child, Humans, Models, Statistical, Pain prevention & control, Stroke prevention & control, Anemia, Sickle Cell therapy, Antisickling Agents therapeutic use, Blood Transfusion, Hematopoietic Stem Cell Transplantation, Hydroxyurea therapeutic use
- Abstract
Introduction: The perception of an asymptomatic sickle cell disease (SCD) state is a misnomer. Children without overt symptoms, likely have subclinical disease beginning in infancy with progression into adulthood. Predictive models of SCD severity are unable to predict a subgroup of asymptomatic children likely to develop severe SCD. The introduction of penicillin prophylaxis, conjugated pneumococcal and Haemophilus influenzae type B vaccines have dramatically decreased the rate of life-threatening infections, while use of hydroxyurea in children has decreased pain and acute chest syndrome events. Use of transcranial Doppler coupled with regular blood transfusion therapy has decreased the rate of overt strokes and premature death associated with strokes. Currently, therapy for asymptomatic children includes hydroxyurea, regular blood transfusion or allogeneic hematopoietic stem cell transplant (allo-HSCT)., Areas Covered: The pros and cons of initiating hydroxyurea, regular blood transfusion or allo-HSCT in asymptomatic children with SCD., Expert Opinion: Emerging evidence from observational studies indicates that hydroxyurea prolongs survival in children and adults with sickle cell anemia. Regular blood transfusions reduce incidence of strokes, acute chest and pain episodes, but is associated with the burden of monthly visits and excessive iron stores. Although curative, the perceived risk:benefit ratio associated with allo-HSCT limits its use in asymptomatic children.
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- 2014
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13. Associated risk factors for silent cerebral infarcts in sickle cell anemia: low baseline hemoglobin, sex, and relative high systolic blood pressure.
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DeBaun MR, Sarnaik SA, Rodeghier MJ, Minniti CP, Howard TH, Iyer RV, Inusa B, Telfer PT, Kirby-Allen M, Quinn CT, Bernaudin F, Airewele G, Woods GM, Panepinto JA, Fuh B, Kwiatkowski JK, King AA, Rhodes MM, Thompson AA, Heiny ME, Redding-Lallinger RC, Kirkham FJ, Sabio H, Gonzalez CE, Saccente SL, Kalinyak KA, Strouse JJ, Fixler JM, Gordon MO, Miller JP, Noetzel MJ, Ichord RN, and Casella JF
- Subjects
- Adolescent, Anemia, Sickle Cell blood, Asymptomatic Diseases epidemiology, Cerebral Infarction blood, Cerebral Infarction pathology, Child, Child, Preschool, Cross-Sectional Studies, Female, Hemoglobin, Sickle metabolism, Humans, Magnetic Resonance Imaging, Male, Multivariate Analysis, Risk Factors, Sex Distribution, beta-Thalassemia blood, Anemia, Sickle Cell epidemiology, Anemia, Sickle Cell therapy, Blood Pressure, Blood Transfusion, Cerebral Infarction epidemiology, beta-Thalassemia epidemiology
- Abstract
The most common form of neurologic injury in sickle cell anemia (SCA) is silent cerebral infarction (SCI). In the Silent Cerebral Infarct Multi-Center Clinical Trial, we sought to identify risk factors associated with SCI. In this cross-sectional study, we evaluated the clinical history and baseline laboratory values and performed magnetic resonance imaging of the brain in participants with SCA (HbSS or HbSβ° thalassemia) between the ages of 5 and 15 years with no history of overt stroke or seizures. Neuroradiology and neurology committees adjudicated the presence of SCI. SCIs were diagnosed in 30.8% (251 of 814) participants who completed all evaluations and had valid data on all prespecified demographic and clinical covariates. The mean age of the participants was 9.1 years, with 413 males (50.7%). In a multivariable logistic regression analysis, lower baseline hemoglobin concentration (P < .001), higher baseline systolic blood pressure (P = .018), and male sex (P = .030) were statistically significantly associated with an increased risk of an SCI. Hemoglobin concentration and systolic blood pressure are risk factors for SCI in children with SCA and may be therapeutic targets for decreasing the risk of SCI. This study is registered at www.clinicaltrials.gov as #NCT00072761.
- Published
- 2012
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14. Silent cerebral infarcts occur despite regular blood transfusion therapy after first strokes in children with sickle cell disease.
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Hulbert ML, McKinstry RC, Lacey JL, Moran CJ, Panepinto JA, Thompson AA, Sarnaik SA, Woods GM, Casella JF, Inusa B, Howard J, Kirkham FJ, Anie KA, Mullin JE, Ichord R, Noetzel M, Yan Y, Rodeghier M, and Debaun MR
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- Anemia, Sickle Cell complications, Brain blood supply, Brain pathology, Cerebral Infarction complications, Cerebral Revascularization, Child, Child, Preschool, Cohort Studies, Disease-Free Survival, Humans, Magnetic Resonance Angiography, Magnetic Resonance Imaging, Stroke complications, Time Factors, Anemia, Sickle Cell therapy, Blood Transfusion methods, Cerebral Infarction prevention & control, Stroke prevention & control
- Abstract
Children with sickle cell disease (SCD) and strokes receive blood transfusion therapy for secondary stroke prevention; despite this, approximately 20% experience second overt strokes. Given this rate of second overt strokes and the clinical significance of silent cerebral infarcts, we tested the hypothesis that silent cerebral infarcts occur among children with SCD being transfused for secondary stroke prevention. A prospective cohort enrolled children with SCD and overt strokes at 7 academic centers. Magnetic resonance imaging and magnetic resonance angiography of the brain were scheduled approximately every 1 to 2 years; studies were reviewed by a panel of neuroradiologists. Eligibility criteria included regularly scheduled blood transfusion therapy. Forty children were included; mean pretransfusion hemoglobin S concentration was 29%. Progressive cerebral infarcts occurred in 45% (18 of 40 children) while receiving chronic blood transfusion therapy; 7 had second overt strokes and 11 had new silent cerebral infarcts. Worsening cerebral vasculopathy was associated with new cerebral infarction (overt or silent; relative risk = 12.7; 95% confidence interval, 2.65-60.5, P = .001). Children with SCD and overt strokes receiving regular blood transfusion therapy experience silent cerebral infarcts at a higher rate than previously recognized. Additional therapies are needed for secondary stroke prevention in children with SCD.
- Published
- 2011
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15. Design of the silent cerebral infarct transfusion (SIT) trial.
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Casella JF, King AA, Barton B, White DA, Noetzel MJ, Ichord RN, Terrill C, Hirtz D, McKinstry RC, Strouse JJ, Howard TH, Coates TD, Minniti CP, Campbell AD, Vendt BA, Lehmann H, and Debaun MR
- Subjects
- Cerebral Infarction prevention & control, Child, Humans, Magnetic Resonance Imaging, Research Design, Stroke complications, Stroke prevention & control, Stroke therapy, Anemia, Sickle Cell complications, Blood Transfusion, Cerebral Infarction complications, Cerebral Infarction therapy
- Abstract
Background: Silent cerebral infarct (SCI) is the most common cause of serious neurological disease in sickle cell anemia (SCA), affecting approximately 22% of children. The goal of this trial is to determine whether blood transfusion therapy will reduce further neurological morbidity in children with SCI, and if so, the magnitude of this benefit., Procedure: The Silent Cerebral Infarct Transfusion (SIT) Trial includes 29 clinical sites and 3 subsites, a Clinical Coordinating Center, and a Statistical and Data Coordinating Center, to test the following hypothesis: prophylactic blood transfusion therapy in children with SCI will result in at least an 86% reduction in the rate of subsequent overt strokes or new or progressive cerebral infarcts as defined by magnetic resonance imaging (MRI) of the brain. The intervention is blood transfusion versus observation. Two hundred and four participants (102 in each treatment assignment) will ensure 85% power to detect the effect necessary to recommend transfusion therapy (86% reduction), after accounting for 10% drop out and 19% crossover rates. MRI examination of the brain is done at screening, immediately before randomization and study exit. Each randomly assigned participant receives a cognitive test battery at study entry, 12-18 months later, and study exit and an annual neurological examination. Blood is obtained from all screened participants for a biologic repository containing serum and a renewable source of DNA., Conclusion: The SIT Trial could lead to a change in standard care practices for children affected with SCA and SCI, with a consequent reduction in neurological morbidity.
- Published
- 2010
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16. Mailing of a sickle cell disease educational packet increases blood donors within an African American community.
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Price CL, Boyd JH, Watkins AR, Fleming F, and DeBaun MR
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- Adolescent, Adult, Audiovisual Aids, Child, Child, Preschool, Humans, Postal Service, Prospective Studies, Black or African American education, Anemia, Sickle Cell therapy, Blood Donors education, Blood Transfusion, Health Education
- Abstract
Background: Low blood donor rates among African American persons are recognized; however, few strategies exist to increase these numbers., Study Design and Methods: A 1-year, prospective, ecologic study performed before and after an educational intervention designed to test the hypothesis that increased education about the importance of blood donation for children with sickle cell disease (SCD) would result in an increase in total blood donors among African American persons., Results: Approximately 5000 videos were mailed to 50 percent of the households in a zip code where 98 percent of the residents are African American. In the first 6-month interval after mailing the video packet, there was a 75 percent (217 vs. 124; p = 0.05) increase in the total number of presenting donors and a 64 percent (126 vs. 77; p = 0.02) increase in the total number of first-time donors from the same 6-month period in the previous year. During the second 6-month interval, the total number of first-time donors declined. No significant increase in donor activity was noted during the two 6-month periods after the intervention in the surrounding zip codes., Conclusion: A mass mailing directed toward educating African American persons about the importance of blood donation for children with SCD may increase the number of total African American donors.
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- 2006
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17. Chronic blood transfusion therapy practices to treat strokes in children with sickle cell disease.
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Lindsey T, Watts-Tate N, Southwood E, Routhieaux J, Beatty J, Diane C, Phillips M, Lea G, Brown E, and DeBaun MR
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- Attitude of Health Personnel, Child, Chronic Disease, Cytapheresis methods, Evidence-Based Medicine, Exchange Transfusion, Whole Blood methods, Health Services Needs and Demand, Humans, Long-Term Care, Nurse Practitioners organization & administration, Nurse Practitioners psychology, Nursing Evaluation Research, Nursing Methodology Research, Nursing Staff, Hospital organization & administration, Nursing Staff, Hospital psychology, Pediatric Nursing organization & administration, Practice Guidelines as Topic, Surveys and Questionnaires, Time Factors, Total Quality Management, Transfusion Reaction, Washington, Anemia, Sickle Cell complications, Blood Transfusion methods, Blood Transfusion nursing, Blood Transfusion standards, Stroke etiology, Stroke therapy
- Abstract
Purpose: To identify variations in practices used by nurses for pediatric patients with sickle cell disease (SCD) receiving chronic blood transfusion therapy for strokes., Data Sources: Descriptive study of a convenience sample of 11 nurses who care for children with SCD from nine institutions completed a closed-ended questionnaire consisting of 37 items. Responses reflected practice experience with a total of 189 transfused patients with SCD., Conclusions: A wide range of nursing practices exists for blood transfusion therapy for children with SCD and strokes. Manual partial exchange transfusion (66%) was the most commonly used method for blood transfusion in children with strokes reported among the nurses surveyed. Simple transfusions and erythrocytapheresis account for 21% and 13% of the practices reported. Opportunities exist to establish evidence-based nursing care guidelines to improve the care of children with strokes receiving blood transfusion therapy., Implications for Practice: A wide range of local standard care guidelines for blood transfusion therapy exists. The results of this survey indicate that partial manual exchange transfusion is the most commonly used method of chronic blood transfusion therapy in children with SCD and stroke despite the fact that the magnitude of benefit in comparison with simple transfusion has not been established. Factors such as peripheral venous access, compliance with current chelation regimen, and the presence of antibodies are important considerations in the choice of method.
- Published
- 2005
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18. Risk of recurrent stroke in children with sickle cell disease receiving blood transfusion therapy for at least five years after initial stroke.
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Scothorn DJ, Price C, Schwartz D, Terrill C, Buchanan GR, Shurney W, Sarniak I, Fallon R, Chu JY, Pegelow CH, Wang W, Casella JF, Resar LS, Berman B, Adamkiewicz T, Hsu LL, Ohene-Frempong K, Smith-Whitley K, Mahoney D, Scott JP, Woods GM, Watanabe M, and Debaun MR
- Subjects
- Adolescent, Adult, Child, Comorbidity, Follow-Up Studies, Humans, Incidence, Prevalence, Recurrence, Retrospective Studies, Risk Factors, Stroke epidemiology, Anemia, Sickle Cell complications, Anemia, Sickle Cell therapy, Blood Transfusion, Stroke etiology
- Abstract
Objective: To test the hypothesis that children with sickle cell disease (SCD) who have an initial stroke temporally unrelated to another medical event are at higher risk for recurrent stroke than are children who had strokes temporally related to medical events., Methods: A retrospective cohort study of children with SCD and stroke who received regularly scheduled blood transfusions for a minimum of 5 years was conducted. Medical records were examined for the documentation of antecedent or concurrent medical events (hypertension, acute chest syndrome, aplastic crisis, fever associated with infection, exchange transfusion) associated with physician contact within 14 days before the initial stroke., Results: A total of 137 pediatric patients from 14 centers were studied. Mean age at first stroke was 6.3 years (1.4 to 14.0 years) with mean follow-up of 10.1 years (5 to 24 years). Thirty-one (22%) patients had a second stroke (2.2 per 100 patient years); 26 patients had an identified medical or concurrent event associated with their initial stroke. None of these patients had recurrent stroke 2 or more years after the initial event. The remaining 111 patients had an ongoing risk of recurrent stroke (1.9 per 100 patient-years) despite long-term transfusions (P =.038)., Conclusions: The absence of an antecedent or concurrent medical event associated with an initial stroke is a major risk factor for subsequent stroke while receiving regular transfusions.
- Published
- 2002
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19. Effect of Blood Transfusion on Cerebral Hemodynamics and Vascular Topology Described by Computational Fluid Dynamics in Sickle Cell Disease Patients.
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Sawyer, Russell P., Pun, Sirjana, Karkoska, Kristine A., Clendinen, Cherita A., DeBaun, Michael R., Gutmark, Ephraim, Barrile, Riccardo, and Hyacinth, Hyacinth I.
- Subjects
COMPUTATIONAL fluid dynamics ,SICKLE cell anemia ,INTERNAL carotid artery ,BLOOD transfusion ,POSTERIOR cerebral artery - Abstract
The main objective of this study was to demonstrate that computational fluid dynamics (CFD) modeling can be used to study the contribution of covert and overt vascular architecture to the risk for cerebrovascular disease in sickle cell disease (SCD) and to determine the mechanisms of response to therapy such as chronic red blood cell (cRBC) transfusions. We analyzed baseline (screening), pre-randomization and study exit magnetic resonance angiogram (MRA) images from 10 (5 each from the transfusion and observation arms) pediatric sickle SCD participants in the silent cerebral infarct transfusion (SIT) trial using CFD modeling. We reconstructed the intracranial portion of the internal carotid artery and branches and extracted the geometry using 3D Slicer. We cut specific portions of the large intracranial artery to include segments of the internal carotid, middle, anterior, and posterior cerebral arteries such that the vessel segment analyzed extended from the intracranial beginning of the internal carotid artery up to immediately after (~0.25 inches) the middle cerebral artery branching point. Cut models were imported into Ansys 2021R2/2022R1 and laminar and time-dependent flow simulation was performed. Change in time averaged mean velocity, wall shear stress, and vessel tortuosity were compared between the observation and cRBC arms. We did not observe a correlation between time averaged mean velocity (TAMV) and mean transcranial Doppler (TCD) velocity at study entry. There was also no difference in change in time average mean velocity, wall shear stress (WSS), and vessel tortuosity between the observation and cRBC transfusion arms. WSS and TAMV were abnormal for 2 (developed TIA) out of the 3 participants (one participant had silent cerebral infarctions) that developed neurovascular outcomes. CFD approaches allow for the evaluation of vascular topology and hemodynamics in SCD using MRA images. In this proof of principle study, we show that CFD could be a useful tool and we intend to carry out future studies with a larger sample to enable more robust conclusions. [ABSTRACT FROM AUTHOR]
- Published
- 2022
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20. Primary Prevention of Stroke in Children With Sickle Cell Anemia in Nigeria: Protocol for a Mixed Methods Implementation Study in a Community Hospital.
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Bello-Manga, Halima, Haliru, Lawal, Ahmed, Kudrat Abdulkareem, Tabari, Abdulkadir Musa, Farouk, Bilkisu Usman, Bahago, Gloria Yimi, Kazaure, Aisha Shuaibu, Muhammad, Abdulrasheed Sani, Gwarzo, Samira Abubakar, Baumann, Ana A., DeBaun, Michael R., and King, Allison A.
- Subjects
STROKE prevention ,SICKLE cell anemia ,BLOOD transfusion ,HYDROXYUREA - Abstract
Background: In Nigeria, approximately 150,000 children with sickle cell anemia (SCA) are born annually, accounting for more than half of all SCA births worldwide. Without intervention, about 11% of children with SCA will develop a stroke before their 20th birthday. Evidence-based practices for primary stroke prevention include screening for abnormal transcranial Doppler (TCD) measurements coupled with regular blood transfusion therapy for at least one year, followed by hydroxyurea (HU) therapy indefinitely. In high-resource countries, this strategy contributes to a 92% decrease in stroke incidence rates. In 2016, as part of a capacity building objective of the Stroke Prevention Trial in Nigeria (1R01NS094041: SPRING), TCD screening was adopted as standard care at Barau Dikko Teaching Hospital in Kaduna. However, with just 70 radiologists and only 3 certified in TCD screening in the state, just 5.49% (1101/20,040) of eligible children with SCA were screened. Thus, there is a need to explore alternate implementation strategies to ensure children with SCA receive standard care TCD screening to decrease stroke incidence. Objective: This protocol describes a study to create a stroke prevention program in a community hospital in Kaduna through task shifting TCD screening to nurses and training medical officers to initiate and monitor HU utilization for stroke prevention. Methods: This study will be conducted at 2 sites (teaching hospital and community hospital) over a period of 3 years (November 2020 to November 2023), in 3 phases using both quasi-experimental and effectiveness-implementation study designs. In the needs assessment phase, focus groups and structured interviews will be conducted with health care providers and hospital administrators to identify barriers and facilitators to evidence-based stroke prevention practices. Results from the needs assessment will inform intervention strategies and a process plan to fit the needs of the community hospital. In the capacity building phase, nurses and medical officers at the community hospital will be trained on TCD screening and HU initiation and monitoring. In the implementation phase, children with SCA aged 2-16 years will be recruited into a nonrandomized single-arm prospective trial to determine the feasibility of initiating a task-shifted stroke prevention program by recording recruitment, retention, and adherence rates. The Reach and Effectiveness components of the RE-AIM (Reach, Effectiveness, Adoption, Implementation and Maintenance) framework will be used to evaluate implementation outcomes between the community and teaching hospitals. Results: The needs assessment phase of the study was completed in February 2021. Manuscript on findings is currently in preparation. Capacity building is ongoing with TCD training and sickle cell disease and stroke education sessions for nurses and doctors in the community hospital. Recruitment for the implementation trial is expected to commence in July 2022. Conclusions: This study proposes a structured, theory-driven approach to create a stroke prevention program in a community hospital in Kaduna, Nigeria, to decrease stroke incidence among children with SCA. Results will provide preliminary data for a definitive randomized clinical trial in implementation science. [ABSTRACT FROM AUTHOR]
- Published
- 2022
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- View/download PDF
21. Reduction in TCD velocity after regular blood transfusion therapy is associated with a change in hemoglobin S fraction in sickle cell anemia
- Author
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Jordan, Lori C., Rodeghier, Mark, Donahue, Manus J., and DeBaun, Michael R.
- Subjects
Male ,Adolescent ,Ultrasonography, Doppler, Transcranial ,Child, Preschool ,Hemoglobin, Sickle ,Brain ,Humans ,Blood Transfusion ,Female ,Anemia, Sickle Cell ,Child ,Article ,Blood Flow Velocity - Published
- 2020
22. PRIMARY STROKE PREVENTION IN CHILDREN WITH SICKLE CELL ANEMIA LIVING IN AFRICA: THE FALSE CHOICE BETWEEN PATIENT-ORIENTED RESEARCH AND HUMANITARIAN SERVICE--PART II.
- Author
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DEBAUN, MICHAEL R.
- Subjects
SICKLE cell anemia ,STROKE prevention ,BLOOD transfusion ,RANDOMIZED controlled trials - Abstract
In the United States, primary stroke prevention in children with sickle cell anemia (SCA) is the standard of care and includes annual transcranial Doppler ultrasound to detect elevated velocities. For children with velocities >200 cm/sec, initial monthly blood transfusion therapy for at least a year, followed by the option of hydroxyurea therapy, results in a significant decline in the stroke rate. In Africa, no prior strategy exists for primary stroke prevention because regular blood transfusion therapy is not feasible. We completed a randomized controlled trial for primary stroke prevention using initial low- and moderate-dose hydroxyurea as an alternative to blood transfusion therapy. The trial results demonstrated equal primary stroke prevention efficacy with both doses. After the trial, we provided a state-supported stroke screening service and treatment for over 20,000 children in Kano, Nigeria. We will review the strategies implemented to conduct clinical research and provide humanitarian assistance to children with SCA in Nigeria. [ABSTRACT FROM AUTHOR]
- Published
- 2022
23. Differential cerebral hemo-metabolic responses to blood transfusions in adults and children with sickle cell anemia
- Author
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Juttukonda, Meher R., Lee, Chelsea A., Patel, Niral J., Davis, Larry T., Waddle, Spencer L., Gindville, Melissa C., Pruthi, Sumit, Kassim, Adetola A., DeBaun, Michael R., Donahue, Manus J., and Jordan, Lori C.
- Subjects
Adult ,Male ,Adolescent ,Age Factors ,Hemodynamics ,Brain ,Anemia, Sickle Cell ,Magnetic Resonance Imaging ,Article ,Oxygen ,Stroke ,Young Adult ,Oxygen Consumption ,Hematocrit ,Recurrence ,Cerebrovascular Circulation ,Humans ,Pain Management ,Blood Transfusion ,Female ,Longitudinal Studies ,Oximetry ,Prospective Studies ,Child - Abstract
BACKGROUND: Blood transfusions are administered to children and adults with sickle cell anemia (SCA) for secondary stroke prevention, or as treatment for recurrent pain crises or acute anemia, but transfusion effects on cerebral hemodynamics and metabolism are not well-characterized. PURPOSE: To compare blood transfusion-induced changes in hemo-metabolic parameters, including oxygen extraction fraction (OEF) and cerebral blood flow (CBF), within and between adults and children with SCA. STUDY TYPE: Prospective, longitudinal study. SUBJECTS: Adults with SCA (n=16) receiving simple (n=7) or exchange (n=9) transfusions and children with SCA (n=11) receiving exchange transfusions were scanned once when hematocrit was near nadir and again within seven days of transfusion. Adult controls without SCA or sickle trait (n=7) were scanned twice on separate days. FIELD STRENGTH/SEQUENCE: 3.0 Tesla T(1)-weighted, T(2)-weighted, and T(2)-relaxation-under-spin-tagging (TRUST) imaging, and phase contrast angiography. ASSESSMENT: Global OEF was computed as the relative difference between venous oxygenation (from TRUST) and arterial oxygenation (from pulse oximetry). Global CBF was computed as total blood flow to the brain normalized by intracranial tissue volume. STATISTICAL TESTS: Hemo-metabolic variables were compared using two-sided Wilcoxon signed-rank tests; associations were analyzed using two-sided Spearman’s correlation testing. RESULTS: In adults with SCA, post-transfusion OEF=0.38±0.05 was lower (p=0.001) than pre-transfusion OEF=0.45±0.09. Change in OEF was correlated with increases in hematocrit (p=0.02; rho=−0.62) and with pre-transfusion hematocrit (p=0.02; rho=0.65). OEF changes after transfusion were greater (p=0.002) in adults receiving simple versus exchange transfusions. Post-transfusion CBF=77.7±26.4 ml/100g/min was not different (p=0.27) from pre-transfusion CBF=82.3±30.2 ml/100g/min. In children with SCA, both post-transfusion OEF=0.28±0.04 and CBF=76.4±26.4 were lower than pre-transfusion OEF=0.36±0.06 (p=0.004) and CBF=96.4±16.5 (p=0.004). DATA CONCLUSION: Cerebral OEF reduces following transfusions in adults and children with SCA. CBF reduces following transfusions more often in children compared to adults, indicating that vascular reserve capacity may remain near exhaustion post-transfusion in many adults.
- Published
- 2018
24. Children with sickle cell anemia with normal transcranial Doppler ultrasounds and without silent infarcts have a low incidence of new strokes
- Author
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Jordan, Lori C., Roberts Williams, Dionna O., Rodeghier, Mark J., Covert, Brittany, Ponisio, Maria R., Casella, James F., McKinstry, Robert C., Noetzel, Michael J., Kirkham, Fenella J., research, MD, Meier, Emily R., Fuh, Beng, McNaull, Melissa, Sarnaik, Sharada, Majumdar, Suvankar, McCavit, Timothy L., and DeBaun, Michael R.
- Subjects
medicine.medical_specialty ,Blood transfusion ,Adolescent ,Anemia ,Ultrasonography, Doppler, Transcranial ,medicine.medical_treatment ,Anemia, Sickle Cell ,030204 cardiovascular system & hematology ,Article ,03 medical and health sciences ,0302 clinical medicine ,Seizures ,Internal medicine ,medicine ,Humans ,Prospective Studies ,Prospective cohort study ,Child ,Stroke ,Cerebral infarction ,business.industry ,Incidence ,Hazard ratio ,Hematology ,Cerebral Infarction ,medicine.disease ,Sickle cell anemia ,Transcranial Doppler ,Ischemic Attack, Transient ,Child, Preschool ,Cardiology ,cardiovascular system ,business ,030217 neurology & neurosurgery - Abstract
In a prospective cohort study, we tested the hypothesis that children with sickle cell anemia (SCA) with normal transcranial Doppler ultrasound (TCD) velocities and without silent cerebral infarcts (SCIs) would have a lower incidence rate of new neurological events (strokes, seizures or transient ischemic attacks) compared to children with normal TCD measurements and SCIs, not receiving regular blood transfusions. Non-randomized participants from the Silent Cerebral Infarct Transfusion (SIT) Trial who had screening magnetic resonance imaging (MRI) of the brain and normal TCD measurements were included. Follow-up ended at the time of first neurological event, start of regular blood transfusion, or loss to follow-up, whichever came first. The primary endpoint was a new neurological event. Of 421 participants included, 68 had suspected SCIs. Mean follow-up was 3.6 years. Incidence rates of new neurological events in non-transfused participants with normal TCD values with SCIs and without SCIs were 1.71 and 0.47 neurological events per 100 patient-years, respectively, p=0.065. The absence of SCI(s) at baseline was associated with a decreased risk of a new neurological event (hazard ratio 0.231, 95% CI 0.062 - 0.858; p=0.029). Local pediatric neurologists examined 67 of 68 participants with suspected SCIs and identified 2 with overt strokes classified as SCIs by local hematologists; subsequently one had a seizure and the other an ischemic stroke. Children with SCA, without SCIs, and normal TCD measurements have a significantly lower rate of new neurological events when compared to those with SCIs and normal TCD measurements. Pediatric neurology assessment may assist risk stratification. This article is protected by copyright. All rights reserved.
- Published
- 2018
25. Automated exchange compared to manual and simple blood transfusion attenuates rise in ferritin level after 1 year of regular blood transfusion therapy in chronically transfused children with sickle cell disease.
- Author
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Kelly, Shannon, Rodeghier, Mark, and DeBaun, Michael R.
- Subjects
BLOOD transfusion ,SICKLE cell anemia ,CEREBRAL infarction ,CHELATION therapy ,FERRITIN - Abstract
Background: Optimal strategies for regular blood transfusion therapy are not well defined in sickle cell disease (SCD). This analysis tested the hypothesis that in the first of year of regular transfusions, when chelation therapy use is minimal, automated exchange transfusion would be the superior method for attenuating the rise in ferritin levels compared to simple and manual exchange transfusions. Study design and methods: The Silent Cerebral Infarct Multi‐Center Clinical Trial randomly allocated children with SCD and silent cerebral infarcts to receive standard care or regular transfusions with a target pre‐transfusion HbS concentration ≤ 30% and minimum hemoglobin level > 9.0 g/dL. Participants with at least nine transfusions and sufficient ferritin testing in the first year of the trial were included in a planned secondary analysis. Ferritin levels by the end of the first study year were compared between participants receiving automatic exchange transfusion, manual exchange transfusion, and simple transfusion. Results: A total of 83 participants were analyzed. During the first year of the study, 75.9% of the participants had >80% of transfusions via one transfusion method. At baseline no significant differences in ferritin levels were observed in the three transfusion groups (p = 0.1). After 1 year of transfusions the median (interquartile range) ferritin levels in the simple transfusion (n = 40), manual exchange transfusion (n = 34) and automatic exchange transfusion (n = 9) groups were 1800 ng/mL (1426‐2204 ng/mL), 1530 ng/mL (1205‐1805 ng/mL), and 355 ng/mL (179‐579 ng/mL), respectively (p < 0.001). Conclusion: Automated exchange transfusion, when compared to other transfusion methods, is the optimal transfusion strategy for attenuating increase in ferritin levels in children with SCD. [ABSTRACT FROM AUTHOR]
- Published
- 2020
- Full Text
- View/download PDF
26. Randomization is Not Associated with Socio-economic and Demographic Factors in a Multi-Center Clinical Trial of Children with Sickle Cell Anemia
- Author
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Roberts, Dionna O, Covert, Brittany, Rodeghier, Mark J, Parmar, Nagina, DeBaun, Michael R, Thompson, Alexis A, and Liem, Robert I
- Subjects
Male ,Adolescent ,Anemia, Sickle Cell ,Cerebral Infarction ,Prognosis ,Article ,Socioeconomic Factors ,Child, Preschool ,Medicine and Health Sciences ,Humans ,Blood Transfusion ,Female ,Child ,Demography ,Follow-Up Studies - Abstract
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.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.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.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.
- Published
- 2014
27. Central nervous system complications and management in sickle cell disease.
- Author
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DeBaun, Michael R. and Kirkham, Fenella J.
- Subjects
- *
SICKLE cell anemia treatment , *CENTRAL nervous system diseases , *DISEASE complications , *DISEASE management , *BLOOD transfusion - Abstract
With advances in brain imaging and completion of randomized clinical trials (RCTs) for primary and secondary stroke prevention, the natural history of central nervous system (CNS) complications in sickle cell disease (SCD) is evolving. In order of current prevalence, the primary CNS complications include silent cerebral infarcts (39% by 18 years), headache (both acute and chronic: 36% in children with sickle cell anemia [SCA]), ischemic stroke (as low as 1% in children with SCA with effective screening and prophylaxis, but ∼11% in children with SCA without screening), and hemorrhagic stroke in children and adults with SCA (3% and 10%, respectively). In high-income countries, RCTs (Stroke Prevention in Sickle Cell Anemia [STOP], STOP II) have demonstrated that regular blood transfusion therapy (typically monthly) achieves primary stroke prevention in children with SCA and high transcranial Doppler (TCD) velocities; after at least a year, hydroxycarbamide may be substituted (TCD With Transfusions Changing to Hydroxyurea [TWiTCH]). Also in high-income countries, RCTs have demonstrated that regular blood transfusion is the optimal current therapy for secondary prevention of infarcts for children with SCA and strokes (Stroke With Transfusions Changing to Hydroxyurea [SWiTCH]) or silent cerebral infarcts (Silent Infarct Transfusion [SIT] Trial). For adults with SCD, CNS complications continue to be a major cause of morbidity and mortality, with no evidence-based strategy for prevention. [ABSTRACT FROM AUTHOR]
- Published
- 2016
- Full Text
- View/download PDF
28. Elevation of IgE in children with sickle cell disease is associated with doctor diagnosis of asthma and increased morbidity.
- Author
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An, Ping, Barron-Casella, Emily A., Strunk, Robert C., Hamilton, Robert G., Casella, James F., and DeBaun, Michael R.
- Subjects
IMMUNOGLOBULIN E ,SICKLE cell anemia in children ,ASTHMA diagnosis ,CHEST pain ,ALLERGENS ,CROSS-sectional method ,HEMOGLOBINOPATHY ,BLOOD transfusion - Abstract
Background: A doctor’s diagnosis of asthma is associated with increased morbidity (pain and acute chest syndrome [ACS]) among children with sickle cell disease (SCD). An association between IgE levels and asthma and morbidity has not been investigated in children with SCD. Objective: We tested the hypothesis that elevated total and allergen-specific IgE levels are associated with asthma and SCD morbidity in children with SCD. Methods: A cross-sectional study of children with SCD who participated in the Silent Cerebral Infarct Trial was conducted. Logistic regression and negative binomial regression were used to investigate potential associations of total and allergen-specific IgE levels with asthma diagnosis and SCD morbidity, both confirmed by medical record review. Elevation of total IgE level was defined as age-adjusted and sex-adjusted IgE level exceeding the 90th percentile compared with a nonatopic reference population. IgE antibody positivity to Alternaria alternata (mold), Blattella germanica (cockroach), and Dermatophagoides pteronyssinus (dust mite) was assessed by ImmunoCAP analysis. Results: Children with SCD (140 with asthma; 381 without asthma) were evaluated. Elevations in total IgE level (P = .04) and IgE antibody specific for Alternaria alternata (P = .0003), Blattella germanica (P = .008), and Dermatophagoides pteronyssinus (P = .01) were associated with asthma. ACS (P = .048) but not pain (P = .20) was associated with total IgE level, but neither was associated with specific IgE levels. Conclusion: Significantly increased levels of total and allergen-specific IgE levels are associated with asthma in SCD. High IgE levels are a risk factor for ACS but not pain rates. [ABSTRACT FROM AUTHOR]
- Published
- 2011
- Full Text
- View/download PDF
29. Genome-wide association study identifies genetic variants influencing F-cell levels in sickle-cell patients.
- Author
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Bhatnagar, Pallav, Purvis, Shirley, Barron-Casella, Emily, DeBaun, Michael R, Casella, James F, Arking, Dan E, and Keefer, Jeffrey R
- Subjects
HUMAN genetic variation ,SICKLE cell anemia ,HEMOGLOBINS ,ZINC-finger proteins ,ERYTHROCYTES ,GENETIC polymorphisms ,NUCLEOTIDES ,BLOOD transfusion ,G proteins ,CELL proliferation ,APOPTOSIS ,PATIENTS - Abstract
Fetal hemoglobin (HbF) level has emerged as an important prognostic factor in sickle-cell disease (SCD) and can be measured by the proportion of HbF-containing erythrocytes (F-cells). Recently, BCL11A (zinc-finger protein) was identified as a regulator of HbF, and the strongest association signals were observed either directly for rs766432 or for correlated single-nucleotide polymorphisms (SNPs). To identify additional independently associated genetic variants, we performed a genome-wide association study (GWAS) on the proportion of F-cells in individuals of African ancestry with SCD from the Silent Infarct Transfusion (SIT) Trial cohort. Our study not only confirms the association of rs766432 (P-value <3.32 × 10
−13 ), but also identifies an independent novel intronic SNP, rs7606173, associated with F-cells (P-value <1.81 × 10−15 ). The F-cell variances explained independently by these two SNPs are ∼13% (rs7606173) and ∼11% (rs766432), whereas, together they explain ∼16%. Additionally, in men, we identify a novel locus on chromosome 17, glucagon-like peptide-2 receptor (GLP2R), associated with F-cell regulation (rs12103880; P-value <3.41 × 10−8 ). GLP2R encodes a G protein-coupled receptor and involved in proliferative and anti-apoptotic cellular responses. These findings highlight the importance of denser genetic screens and suggest further exploration of the BCL11A and GLP2R loci to gain additional insight into HbF/F-cell regulation. [ABSTRACT FROM AUTHOR]- Published
- 2011
- Full Text
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30. The Sickle Cell Sabbath: a community program increases first-time blood donors in the African American faith community.
- Author
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Price, Cynthia L., Johnson, Michael T., Lindsay, Terianne, Dalton, Douglas, and DeBaun, Michael R.
- Subjects
SICKLE cell anemia ,AFRICAN American children ,BLOOD donors ,BLOOD transfusion ,RED blood cell transfusion - Abstract
BACKGROUND: Blood transfusion therapy is an established treatment for primary and secondary prevention of strokes in children with sickle cell disease (SCD), a disease that predominantly affects African Americans. African American blood donors are more likely to have compatible minor red blood cell antigens for children with SCD who routinely receive transfusions. This study tested the hypothesis that when informed at church about the importance of blood donation, African Americans will have a higher than expected rate of first-time blood donation compared to the general population. STUDY DESIGN AND METHODS: The Sickle Cell Sabbath Program was developed to increase awareness about SCD and the importance of blood donations within the African American faith community. Church involvement in the program included a 5-minute scripted educational session about SCD that included the importance of blood donations followed by a blood donor drive that was hosted by the church. RESULTS: Thirteen African American churches sponsored 34 blood drives from 2003 through 2006. Each church sponsored at least two blood drives. Approximately 1200 donors participated in the sickle cell blood drives. The majority of the donors were first-time donors and represented a greater than expected first-time donor rate when compared to first-time donors in the metropolitan St Louis area, 60 percent (422 of 699) and 12.2 percent (21,516 of 175,818), respectively (p = 0.001). CONCLUSION: An educational program that engages the African American faith community more than quadruples the rate of expected first-time blood donors when compared to the general community over this 4-year period. [ABSTRACT FROM AUTHOR]
- Published
- 2009
- Full Text
- View/download PDF
31. Perspective: Thinking beyond survival.
- Author
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DeBaun, Michael R.
- Subjects
- *
SICKLE cell anemia in children , *THERAPEUTIC complications , *BRAIN injuries , *BLOOD transfusion , *HIGH-income countries , *THERAPEUTICS - Abstract
The author discusses the quality of life of children treated for sickle cell disease in high-income countries. He mentions the risk of brain injury and academic performance of the children, blood transfusions preventing overt strokes, and issues like organ failure. Routine health checkups and decreasing associated diseases after treatment are mentioned.
- Published
- 2014
- Full Text
- View/download PDF
32. How I treat and manage strokes in sickle cell disease.
- Author
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Kassim, Adetola A., Galadanci, Najibah A., Pruthi, Sumit, and DeBaun, Michael R.
- Subjects
- *
SICKLE cell anemia , *NEUROLOGY , *CLINICAL trials , *BLOOD transfusion , *STEM cell transplantation - Abstract
Neurologic complications are a major cause of morbidity and mortality in sickle cell disease (SCD). In children with sickle cell anemia, routine use of transcranial Doppler screening, coupled with regular blood transfusion therapy, has decreased the prevalence of overt stroke from ~11 % to 1%. Limited evidence is available to guide acute and chronic management of individuals with SCD and strokes. Current management strategies are based primarily on single arm clinical trials and observational studies, coupled with principles of neurology and hematology. Initial management of a focal neurologic deficit includes evaluation by a multidisciplinary team (a hematologist, neurologist, neuroradiologist, and transfusion medicine specialist); prompt neuro-imaging and an initial blood transfusion (simple followed immediately by an exchange transfusion or only exchange transfusion) is recommended if the hemoglobin is >4 gm/dL and <10 gm/dL. Standard therapy for secondary prevention of strokes and silent cerebral infarcts includes regular blood transfusion therapy and in selected cases, hematopoietic stem cell transplantation. A critical component of the medical care following an infarct is cognitive and physical rehabilitation. We will discuss our strategy of acute and long-term management of strokes in SCD. [ABSTRACT FROM AUTHOR]
- Published
- 2015
- Full Text
- View/download PDF
33. Trials in Sickle Cell Disease
- Author
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Kirkham, Fenella J., Lerner, Norma B., Noetzel, Michael, DeBaun, Michael R., Datta, Avijit K., Rees, David C., and Adams, Robert J.
- Subjects
- *
SICKLE cell anemia in children , *BLOOD transfusion , *MAGNETIC resonance imaging , *BLOOD transfusion reaction - Abstract
Children with sickle cell disease are at risk of developing neurologic complications, including stroke, transient ischemic attack, seizures, coma, and a progressive reduction in cognitive function. Transcranial Doppler ultrasound, magnetic resonance imaging, and overnight pulse oximetry appear to predict, making prevention an achievable goal so that there is now a focus on randomized controlled trials. The Stroke Prevention Trial in Sickle Cell Anemia (STOP) reported a reduction in the number of overt clinical strokes experienced by those children with critically high transcranial Doppler velocities (>200 centimeters per second) who were chronically transfused. Two additional Phase III studies and two pilot trials have been funded. STOP II focused on whether it is safe to discontinue blood in prophylactically transfused children when their velocities had remained normal for at least 30 months. The Silent Infarct Transfusion trial is designed to determine whether children with sickle cell anemia and silent cerebal infarcts, approximately 20% of the population, will have a decrease in the progressive neurologic complications after receiving regular blood transfusion therapy. Pilot safety and feasibility trials of low-dose aspirin and overnight respiratory support are also beginning. The collaboration provides an infrastructure for future clinical trials in this vulnerable group of children. [Copyright &y& Elsevier]
- Published
- 2006
- Full Text
- View/download PDF
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