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Guy D, Bagnall R, Morgan RL, Babatunde I, Nevière A, Friedrich G, Bennetts L, Irfan O, Odame I. Impact of transcranial Doppler screening on stroke prevention in children and adolescents with sickle cell disease: A systematic review and meta-analysis. Blood Rev 2025; 69:101253. [PMID: 39710547 DOI: 10.1016/j.blre.2024.101253] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/07/2024] [Revised: 11/28/2024] [Accepted: 12/07/2024] [Indexed: 12/24/2024]
Abstract
BACKGROUND Children with sickle cell disease (SCD) have increased stroke risk, identifiable by elevated velocities on transcranial Doppler (TCD). This review assessed the impact of TCD screening on stroke, mortality, quality of life and morbidity in children with SCD. METHODS A systematic search of MEDLINE, PubMed, Cochrane libraries, and trial registries was conducted from inception to 28th February 2023. Randomised controlled trials (RCTs) and non-randomised studies (NRS) were included. A meta-analysis and narrative synthesis were performed. FINDINGS Nine studies were included in the review. In one RCT, initiating chronic blood transfusion in children with abnormal TCD velocities reduced stroke risk by 92 %, while no deaths were reported. Pooled results from three NRS indicated TCD screening leads to four fewer strokes per 1000 patients annually. No studies analysing morbidity nor quality of life were identified. INTERPRETATION TCD screening may decrease the risk of stroke in patients with SCD.
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Affiliation(s)
- Danielle Guy
- Amaris Heath Economics and Market Access, Barcelona, Catalunya, Spain
| | - Robert Bagnall
- Amaris Heath Economics and Market Access, Barcelona, Catalunya, Spain.
| | - Rebecca L Morgan
- Department of Health Research Methods, Evidence, and Impact, McMaster University, Hamilton, Ontario, Canada; School of Medicine, Case Western Reserve University, Cleveland, OH, USA.
| | - Ifeoluwa Babatunde
- School of Medicine, Case Western Reserve University, Cleveland, OH, USA.
| | - Agathe Nevière
- Amaris Health Economics and Market Access, Nantes, France.
| | | | - Liga Bennetts
- Amaris Health Economics and Market Access, Montreal, Quebec, Canada.
| | - Omar Irfan
- Amaris Health Economics and Market Access, Toronto, Ontario, Canada
| | - Isaac Odame
- Division of Haematology/Oncology, The Hospital for Sick Children, Toronto, Ontario, Canada; Departments of Paediatrics and Medicine, University of Toronto, Ontario, Canada.
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2
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Rawanduzy CA, Earl E, Mayer G, Lucke-Wold B. Pediatric Stroke: A Review of Common Etiologies and Management Strategies. Biomedicines 2022; 11:2. [PMID: 36672510 PMCID: PMC9856134 DOI: 10.3390/biomedicines11010002] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/09/2022] [Revised: 12/12/2022] [Accepted: 12/15/2022] [Indexed: 12/24/2022] Open
Abstract
Pediatric stroke is an important cause of mortality and morbidity in children. There is a paucity of clinical trials pertaining to pediatric stroke management, and solidified universal guidelines are not established for children the way they are for the adult population. Diagnosis of pediatric stroke can be challenging, and it is often delayed or mischaracterized, which can result in worse outcomes. Understanding risks and appropriate therapy is paramount to improving care.
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Affiliation(s)
| | - Emma Earl
- School of Medicine, University of Utah, Salt Lake City, UT 84112, USA
| | - Greg Mayer
- School of Medicine, University of Utah, Salt Lake City, UT 84112, USA
| | - Brandon Lucke-Wold
- Department of Neurosurgery, University of Florida, Gainesville, FL 32608, USA
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3
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Reeves SL, Freed GL, Madden B, Wu M, Miller L, Cogan L, Anders D, Creary SE, McCormick J, Dombkowski KJ. Trends in quality of care among children with sickle cell anemia. Pediatr Blood Cancer 2022; 69:e29446. [PMID: 34854548 PMCID: PMC9367210 DOI: 10.1002/pbc.29446] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/21/2021] [Revised: 09/07/2021] [Accepted: 09/23/2021] [Indexed: 02/03/2023]
Abstract
INTRODUCTION For decades, it has been recommended that children with sickle cell anemia (SCA) receive antibiotic prophylaxis to prevent serious infections and undergo transcranial Doppler (TCD) screening to identify those at highest risk of overt stroke. We assessed recent temporal trends in antibiotic prophylaxis prescription fills and TCD screening among children with SCA using validated quality measures. PROCEDURE Using validated claims-based definitions, we identified children with SCA who were enrolled in Michigan or New York State (NYS) Medicaid programs (2011-2018). Among recommended age groups, two outcomes were assessed yearly: (a) filling of ≥300 days of antibiotics, and (b) receipt of greater than or equal to one TCD. The proportion of children with each outcome was calculated by state. Temporal trends in each preventive service were assessed using generalized linear models. RESULTS A total of 1784 children were eligible for antibiotic prophylaxis (Michigan: 384; NYS: 1400), contributing 3322 person-years. Annual rates of filling ≥300 days of antibiotics ranged from 16% to 22% and were similar by state. There was no change in rates of antibiotic filling over time in Michigan (p-value: .10), but there was a decrease in NYS (p-value: .02). A total of 3439 children with SCA were eligible for TCD screening (Michigan: 710; NYS: 2729), contributing 10,012 person-years. Annual rates of TCD screening ranged from 39% to 45%, were similar by state, and did not change over time (p-values >.05). CONCLUSIONS Most children with SCA do not receive recommended antibiotic prophylaxis and/or TCD screening. New, sustainable, and coordinated interventions across preventive services are urgently needed.
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Affiliation(s)
- Sarah L Reeves
- Susan B Meister Child Health Evaluation and Research Center, Department of Pediatrics, University of Michigan, Ann Arbor, Michigan, USA
- Department of Epidemiology, University of Michigan, Ann Arbor, Michigan, USA
| | - Gary L Freed
- Susan B Meister Child Health Evaluation and Research Center, Department of Pediatrics, University of Michigan, Ann Arbor, Michigan, USA
| | - Brian Madden
- Susan B Meister Child Health Evaluation and Research Center, Department of Pediatrics, University of Michigan, Ann Arbor, Michigan, USA
| | - Meng Wu
- New York State Department of Health, Albany, New York, USA
| | - Lauren Miller
- New York State Department of Health, Albany, New York, USA
| | - Lindsay Cogan
- New York State Department of Health, Albany, New York, USA
| | - David Anders
- New York State Department of Health, Albany, New York, USA
| | - Susan E Creary
- Department of Pediatrics, Nationwide Children's Hospital, Columbus, Ohio, USA
| | - Julie McCormick
- Susan B Meister Child Health Evaluation and Research Center, Department of Pediatrics, University of Michigan, Ann Arbor, Michigan, USA
| | - Kevin J Dombkowski
- Susan B Meister Child Health Evaluation and Research Center, Department of Pediatrics, University of Michigan, Ann Arbor, Michigan, USA
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4
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Kanter J, Phillips S, Schlenz A, Mueller M, Dooley M, Sirline L, Nickel R, Brown RC, Hilliard L, Melvin C, Adams R. Transcranial Doppler Screening in a Current Cohort of Children With Sickle Cell Anemia: Results From the DISPLACE Study. J Pediatr Hematol Oncol 2021; 43:e1062-e1068. [PMID: 33625093 PMCID: PMC8481351 DOI: 10.1097/mph.0000000000002103] [Citation(s) in RCA: 23] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/28/2020] [Accepted: 01/08/2021] [Indexed: 11/26/2022]
Abstract
Stroke prevention guidelines for sickle cell anemia (SCA) recommend transcranial Doppler (TCD) screening to identify children at stroke risk; however, TCD screening implementation remains poor. This report describes results from Part 1 of the 28-site DISPLACE (Dissemination and Implementation of Stroke Prevention Looking at the Care Environment) study, a baseline assessment of TCD implementation rates. This report describes TCD implementation by consortium site characteristics; characteristics of TCDs completed; and TCD results based on age. The cohort included 5247 children with SCA, of whom 5116 were eligible for TCD implementation assessment for at least 1 study year. The majority of children were African American or Black, non-Hispanic and received Medicaid. Mean age at first recorded TCD was 5.9 and 10.5 years at study end. Observed TCD screening rates were unsatisfactory across geographic regions (mean 49.9%; range: 30.9% to 74.7%) independent of size, institution type, or previous stroke prevention trial participation. The abnormal TCD rate was 2.9%, with a median age of 6.3 years for first abnormal TCD result. Findings highlight real-world TCD screening practices and results from the largest SCA cohort to date. Data informed the part 3 implementation study for improving stroke screening and findings may inform clinical practice improvements.
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Affiliation(s)
- Julie Kanter
- Division of Hematology & Oncology, University of Alabama Birmingham
| | | | - Alyssa Schlenz
- Department of Pediatrics, University of Colorado School of Medicine
| | - Martina Mueller
- College of Nursing, Medical University of South Carolina
- Department of Public Health Sciences, Medical University of South Carolina
| | - Mary Dooley
- College of Nursing, Medical University of South Carolina
| | - Logan Sirline
- Department of Public Health Sciences, Medical University of South Carolina
| | - Robert Nickel
- Divison of Hematology-Oncology, Children’s National Medical Center
| | - R. Clark Brown
- Aflac Cancer and Blood Disorder Center, Emory University
| | | | - Cathy Melvin
- Department of Public Health Sciences, Medical University of South Carolina
| | - Robert Adams
- Department of Neurology and Neurosurgery, Medical University of South Carolina
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5
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Phillips SM, Schlenz AM, Mueller M, Melvin CL, Adams RJ, Kanter J. Identified barriers and facilitators to stroke risk screening in children with sickle cell anemia: results from the DISPLACE consortium. Implement Sci Commun 2021; 2:87. [PMID: 34376249 PMCID: PMC8353775 DOI: 10.1186/s43058-021-00192-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/03/2020] [Accepted: 07/25/2021] [Indexed: 11/10/2022] Open
Abstract
Background Children with sickle cell anemia are at risk for stroke. Ischemic stroke risk can be identified among children ages 2–16 years with sickle cell anemia using transcranial Doppler ultrasound. Despite strong recommendations for transcranial Doppler screening in guidelines released by the National Heart, Lung, and Blood Institute, implementation of transcranial Doppler screening in sickle cell anemia remains suboptimal. The purpose of this study was to identify barriers and facilitators to transcranial Doppler screening in a large national consortium to inform subsequent implementation interventions. Methods A qualitative descriptive approach was used to conduct 52 semi-structured interviews with a sample of patients with sickle cell anemia, their parents or primary caregivers, and healthcare providers dispersed across the United States. Interviews took place from September 2018 through March 2019. Directed content analysis was conducted with an adapted version of the Multilevel Ecological Model of Health as an initial coding framework, completed July 2019. Frequency analysis was conducted to determine predominant barrier and facilitator themes. Results Fourteen barrier themes and 12 facilitator themes emerged representing all levels of the ecological framework. Two barrier themes (Logistical Difficulties and Competing Life Demands and Gaps in Scheduling and Coordination), and 5 facilitator themes (Coordination, Scheduling and Reminders; Education and Information; Provider and Staff Investment and Assistance; Positive Patient Experience; and Convenient Location) were predominant. Conclusions Barriers and facilitators to transcranial Doppler screening in children with sickle cell anemia are complex and occur across multiple ecological levels. One barrier theme and 3 facilitator themes were found to be optimal to address in subsequent implementation interventions. Supplementary Information The online version contains supplementary material available at 10.1186/s43058-021-00192-z.
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Affiliation(s)
- Shannon M Phillips
- College of Nursing, Medical University of South Carolina, 99 Jonathan Lucas St, Charleston, USA.
| | - Alyssa M Schlenz
- Department of Pediatrics, Medical University of South Carolina, Charleston, USA.,Department of Pediatrics, University of Colorado School of Medicine, 1800 Grant St. Suite 800, Denver, CO, 80203, USA
| | - Martina Mueller
- College of Nursing, Medical University of South Carolina, 99 Jonathan Lucas St, Charleston, USA.,Department of Public Health Sciences, Medical University of South Carolina, Charleston, USA
| | - Cathy L Melvin
- Department of Public Health Sciences, Medical University of South Carolina, Charleston, USA
| | - Robert J Adams
- Department of Neurology, Medical University of South Carolina, Charleston, SC, 29425, USA
| | - Julie Kanter
- Division of Hematology & Oncology, University of Alabama at Birmingham, 1720 2nd Ave. South, Birmingham, AL, 35294, USA
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6
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Odame I. Sickle cell disease in Germany: Early insights from a national registry. Pediatr Blood Cancer 2020; 67:e28168. [PMID: 31904164 DOI: 10.1002/pbc.28168] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/23/2019] [Accepted: 12/24/2019] [Indexed: 11/09/2022]
Affiliation(s)
- Isaac Odame
- Division of Haematology/Oncology, Hospital for Sick, Children & Department of Paediatrics, University of Toronto, Toronto, Ontario, Canada
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7
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Kunz JB, Lobitz S, Grosse R, Oevermann L, Hakimeh D, Jarisch A, Cario H, Beier R, Schenk D, Schneider D, Groß-Wieltsch U, Prokop A, Heine S, Khurana C, Erlacher M, Dürken M, Linke C, Frühwald M, Corbacioglu S, Claviez A, Metzler M, Ebinger M, Full H, Wiesel T, Eberl W, Reinhard H, Tagliaferri L, Allard P, Karapanagiotou-Schenkel I, Rother LM, Beck D, Le Cornet L, Kulozik AE. Sickle cell disease in Germany: Results from a national registry. Pediatr Blood Cancer 2020; 67:e28130. [PMID: 31867835 DOI: 10.1002/pbc.28130] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/06/2019] [Revised: 11/27/2019] [Accepted: 11/27/2019] [Indexed: 11/06/2022]
Abstract
BACKGROUND Limited data on the prevalence and medical care of sickle cell disease (SCD) in Germany are available. Here, we make use of a patient registry to characterize the burden of disease and the treatment modalities for patients with SCD in Germany. PROCEDURE A nationwide German registry for patients with SCD documents basic data on diagnosis and patient history retrospectively at the time of registration. A prospective annual documentation provides more details on complications and treatment of SCD. For the current analyses, data of 439 patients were available. RESULTS Most patients had homozygous SCD (HbSS 75.1%, HbS/β-thalassemia 13.2%, and HbSC 11.3%). The median age at diagnosis was 1.9 years (interquartile range, 0.6-4.4 years), most patients were diagnosed when characteristic symptoms occurred. Sepsis and stroke had affected 3.2% and 4.2% of patients, respectively. During the first year of observation, 48.3% of patients were admitted to a hospital and 10.1% required intensive care. Prophylactic penicillin was prescribed to 95.6% of patients with homozygous SCD or HbS/β thalassemia below the age of six and hydroxycarbamide to 90.4% of patients above the age of two years. At least one annual transcranial Doppler ultrasound was documented for 74.8% of patients between 2 and 18 years. CONCLUSION With an estimated number of at least 2000, the prevalence of SCD in Germany remains low. Prospectively, we expect that the quality of care for children with SCD will be further improved by an earlier diagnosis after the anticipated introduction of a newborn screening program for SCD.
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Affiliation(s)
- Joachim B Kunz
- Department of Pediatric Oncology, Hematology and Immunology, Hopp-Children's Cancer Center (KiTZ) Heidelberg, University of Heidelberg, Heidelberg, Germany.,GPOH Konsortium Sichelzellkrankheit, Germany
| | - Stephan Lobitz
- GPOH Konsortium Sichelzellkrankheit, Germany.,Gemeinschaftsklinikum Mittelrhein, Kemperhof, Pädiatrische Hämatologie und Onkologie, Koblenz, Germany
| | - Regine Grosse
- GPOH Konsortium Sichelzellkrankheit, Germany.,Universitätsklinikum Hamburg-Eppendorf, Zentrum für Geburtshilfe, Kinder- und Jugendmedizin, Klinik und Poliklinik für Pädiatrische Hämatologie und Onkologie, Hamburg, Germany
| | - Lena Oevermann
- GPOH Konsortium Sichelzellkrankheit, Germany.,Charité - Universitätsmedizin Berlin, Campus Virchow-Klinikum, Klinik für Pädiatrie m.S. Onkologie/Hämatologie/KMT, Berlin, Germany
| | - Dani Hakimeh
- GPOH Konsortium Sichelzellkrankheit, Germany.,Charité - Universitätsmedizin Berlin, Campus Virchow-Klinikum, Klinik für Pädiatrie m.S. Onkologie/Hämatologie/KMT, Berlin, Germany
| | - Andrea Jarisch
- GPOH Konsortium Sichelzellkrankheit, Germany.,Klinikum der Johann-Wolfgang-Goethe-Universität, Zentrum für Kinder- und Jugendmedizin, Schwerpunkt Stammzelltransplantation und Immunologie, Frankfurt am Main, Germany
| | - Holger Cario
- GPOH Konsortium Sichelzellkrankheit, Germany.,Universitätsklinikum Ulm, Klinik für Kinder- und Jugendmedizin, Pädiatrische Hämatologie und Onkologie, Ulm, Germany
| | - Rita Beier
- University Hospital Essen, Pediatric Haematology and Oncology, Essen, Germany
| | - Daniela Schenk
- Department of Pediatrics and Children's Cancer Research Center, Kinderklinik München Schwabing, Klinikum rechts der Isar, Fakultät für Medizin, Technische Universität München, Munich, Germany
| | - Dominik Schneider
- Clinic of Pediatrics, Dortmund Municipal Hospital, Dortmund, Germany
| | - Ute Groß-Wieltsch
- Pediatrics 5 (Oncology, Hematology, Immunology), Center for Pediatric, Adolescent and Women's Medicine, Klinikum Stuttgart - Olgahospital, Stuttgart, Germany
| | - Aram Prokop
- Children's Hospital Amsterdamer Straße Cologne, Clinic for Children and Youth Medicine, Paediatric Oncology/Haematology, Cologne, Germany
| | - Sabine Heine
- Department of Pediatric Hematology and Oncology, Saarland University Hospital, Homburg, Saar, Germany
| | - Claudia Khurana
- Klinik für Kinder- und Jugendmedizin, Evangelisches Klinikum Bethel, Bielefeld, Germany
| | - Miriam Erlacher
- Department of Pediatrics and Adolescent Medicine, Division of Pediatric Hematology and Oncology, University Medical Center Freiburg, Faculty of Medicine, University of Freiburg, Breisgau, Germany
| | - Matthias Dürken
- Department of Pediatric Hematology and Oncology, University of Mannheim, Mannheim, Germany
| | - Christina Linke
- Universitätsklinikum Münster, Klinik für Kinder- und Jugendmedizin - Pädiatrische Hämatologie und Onkologie, Münster, Germany
| | - Michael Frühwald
- University Children's Hospital Augsburg, University Hospital Augsburg, Augsburg, Germany
| | - Selim Corbacioglu
- Department of Pediatric Hematology, Oncology and Stem Cell Transplantation, Franz-Josef-Strauss-Allee 11, University Hospital of Regensburg, Regensburg, Germany
| | - Alexander Claviez
- Klinik für Kinder- und Jugendmedizin I, Pädiatrische Onkologie, Hämatologie, Stammzelltransplantation, Universitätsklinikum Schleswig-Holstein, Kiel, Germany
| | - Markus Metzler
- Pediatric Oncology and Hematology, Department of Pediatrics and Adolescent Medicine, University Hospital Erlangen, Erlangen, Germany
| | - Martin Ebinger
- Universitätsklinikum Tübingen, Klinik für Kinder- und Jugendmedizin, Tübingen, Germany
| | | | - Thomas Wiesel
- Children's Hospital, Vestische Youth Hospital, University of Witten/Herdecke, Datteln, Germany
| | - Wolfgang Eberl
- Institute for Clinical Transfusion Medicine and Children's Hospital, Klinikum Braunschweig GmbH, Germany
| | - Harald Reinhard
- Asklepios Kinderklinik Sankt Augustin, St. Augustin, Germany
| | - Laura Tagliaferri
- Department of Pediatric Oncology, Hematology and Immunology, Hopp-Children's Cancer Center (KiTZ) Heidelberg, University of Heidelberg, Heidelberg, Germany.,GPOH Konsortium Sichelzellkrankheit, Germany
| | - Pierre Allard
- Department of Pediatric Oncology, Hematology and Immunology, Hopp-Children's Cancer Center (KiTZ) Heidelberg, University of Heidelberg, Heidelberg, Germany
| | - Irini Karapanagiotou-Schenkel
- NCT Trial Center, National Center for Tumor Diseases (NCT) Heidelberg, German Cancer Research Center (dkfz), Heidelberg, Germany
| | - Lisa-Marie Rother
- NCT Trial Center, National Center for Tumor Diseases (NCT) Heidelberg, German Cancer Research Center (dkfz), Heidelberg, Germany
| | - Dorothea Beck
- NCT Trial Center, National Center for Tumor Diseases (NCT) Heidelberg, German Cancer Research Center (dkfz), Heidelberg, Germany
| | - Lucian Le Cornet
- NCT Trial Center, National Center for Tumor Diseases (NCT) Heidelberg, German Cancer Research Center (dkfz), Heidelberg, Germany
| | - Andreas E Kulozik
- Department of Pediatric Oncology, Hematology and Immunology, Hopp-Children's Cancer Center (KiTZ) Heidelberg, University of Heidelberg, Heidelberg, Germany.,GPOH Konsortium Sichelzellkrankheit, Germany
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Franco JM, Borges CCL, Ansaloni MA, Mauro RDDL, Souza YCDC, Braga JAP. Chronic transfusion therapy effectiveness as primary stroke prophylaxis in sickle cell disease patients. Hematol Transfus Cell Ther 2019; 42:12-17. [PMID: 31791880 PMCID: PMC7031109 DOI: 10.1016/j.htct.2018.05.015] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/08/2018] [Revised: 05/24/2018] [Accepted: 05/28/2018] [Indexed: 12/26/2022] Open
Abstract
Introduction About 10% of sickle cell anemia patients will have ischemic stroke. Adams showed stroke incidence reduction in children receiving monthly erythrocyte transfusions by reducing transcranial Doppler (TCD) velocities. Since then, chronic transfusion is recommended as primary stroke prophylaxis. This study aims to assess the effectiveness of chronic transfusions as stroke prophylaxis. Method Retrospective study, reviewing medical records from 15 sickle cell anemia patients undergoing chronic transfusion. Data collected were age, sex, adverse reactions, stroke, hemoglobin, reticulocytes, ferritin, HbS and TCD values (baseline, after 12 and 24 months of treatment). Results The mean age was 118.67 ± 41.40 months; six patients experienced allergic reactions. No stroke was recorded. One patient had alloimmunization. There was a decrease in the HbS rate and an increase in hemoglobin values in the first 12 months. Values were maintained after 24 months, but with no improvement of data. Before treatment, the mean HbS rate was 75.18%±11.69; after 12 months, 41.63 ± 14.99 and after 24 months, 43.78 ± 10.6. Thirteen patients initiated chelation after 12 months from the beginning of chronic transfusions and ferritin decline after 24 months. Pre-transfusional TCD velocities were 204.28 ± 9.41 cm/s (right) and 198.85 ± 33.37 cm/s (left). After a 12-month treatment, these values were 158.5 ± 28.89 cm/s and 157.62 ± 34.43 cm/s, respectively, and this reduction was statistically significant (p = 0.002 right and p = 0.02 left). After 24 months, these values were 149.63 ± 26.95 cm/s (right) and 143.7 ± 32.27 cm/s (left). Conclusion Significant reduction of TCD velocity occurred after treatment with chronic transfusion in sickle cell anemia patients, leading to a normal or conditional test and reducing stroke risk in all but one patient.
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9
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Evaluation of Outcomes and Quality of Care in Children with Sickle Cell Disease Diagnosed by Newborn Screening: A Real-World Nation-Wide Study in France. J Clin Med 2019; 8:jcm8101594. [PMID: 31581727 PMCID: PMC6832704 DOI: 10.3390/jcm8101594] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/19/2019] [Revised: 09/19/2019] [Accepted: 09/23/2019] [Indexed: 12/30/2022] Open
Abstract
This study's objective was to assess, on a national scale, residual risks of death, major disease-related events, and quality of care during the first five years in children diagnosed at birth with sickle cell disease (SCD). Data were retrospectively collected from medical files of all children with SCD born between 2006-2010 in France. Out of 1792 eligible subjects, 1620 patients (71.8% SS or S/beta°-thalassemia -SB°-) had available follow-up data, across 69 centers. Overall probability of survival by five years was 98.9%, with 12/18 deaths related to SCD. Probability of overt stroke by five years in SS/SB° patients was 1.1%, while transcranial Doppler (TCD) was performed in 81% before three years of age. A total of 26 patients had meningitis/septicemia (pneumococcal in eight cases). Prophylactic penicillin was started at a median age of 2.2 months and 87% of children had received appropriate conjugate pneumococcal vaccination at one year. By five years, the probability of survival without SCD-related events was 10.7% for SS/SB° patients. In contrast, hydroxyurea was prescribed in 13.7% and bone marrow transplant performed in nine patients only. In this study, residual risks of severe complications were low, probably resulting from a good national TCD, vaccination, and healthcare system coverage. Nonetheless, burden of disease remained high, stressing the need for disease-modifying or curative therapy.
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10
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Hamm J, Hilliard L, Howard T, Lebensburger J. Maintaining High Level of Care at Satellite Sickle Cell Clinics. J Health Care Poor Underserved 2018; 27:280-292. [PMID: 27763470 DOI: 10.1353/hpu.2016.0004] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/05/2023]
Abstract
Traveling to and from university-based clinics is a major health care barrier for children with sickle cell disease in Alabama. To reduce this barrier, the University of Alabama at Birmingham (UAB) developed satellite clinics. This study seeks to determine if these satellite clinics provide a similar level of comprehensive care when compared with the university-based clinic using four surrogate markers: 1) attendance rates, 2) percentage of patients on hydroxyurea, 3) percentage of screening MRIs obtained, and 4) percentage of transcranial dopplers (TCD) completed. A retrospective review of sickle cell visits from June 1, 2012 to May 31, 2013 demonstrated that satellite clinics can provide levels of medical care for children with sickle cell disease similar to those provided by university-based clinics.
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11
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Belisário AR, Silva CM, Velloso-Rodrigues C, Viana MB. Genetic, laboratory and clinical risk factors in the development of overt ischemic stroke in children with sickle cell disease. Hematol Transfus Cell Ther 2018; 40:166-181. [PMID: 30057991 PMCID: PMC6003005 DOI: 10.1016/j.bjhh.2017.08.008] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/25/2016] [Accepted: 08/30/2017] [Indexed: 12/22/2022] Open
Abstract
Cerebrovascular disease, particularly stroke, is one of the most severe clinical complications associated with sickle cell disease and is a significant cause of morbidity in both children and adults. Over the past two decades, considerable advances have been made in the understanding of its natural history and enabled early identification and treatment of children at the highest risk. Transcranial Doppler screening and regular blood transfusions have markedly reduced the risk of stroke in children. However, transcranial Doppler has a limited positive predictive value and the pathophysiology of cerebrovascular disease is not completely understood. In this review, we will focus on the current state of knowledge about risk factors associated with ischemic stroke in patients with sickle cell disease. A search of PubMed was performed to identify studies. Full texts of the included articles were reviewed and data were summarized in a table. The coinheritance of alpha-thalassemia plays a protective role against ischemic stroke. The influence of other genetic risk factors is controversial, still preliminary, and requires confirmatory studies. Recent advances have established the reticulocyte count as the most important laboratory risk factor. Clinical features associated with acute hypoxemia as well as silent infarcts seem to influence the development of strokes in children. However, transcranial Doppler remains the only available clinical prognostic tool to have been validated. If our understanding of the many risk factors associated with stroke advances further, it may be possible to develop useful tools to detect patients at the highest risk early, improving the selection of children requiring intensification therapy.
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Affiliation(s)
- André Rolim Belisário
- Centro de Tecidos Biológicos de Minas Gerais, Fundação Hemominas, Lagoa Santa, MG, Brazil
- Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, MG, Brazil
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Neumayr L, Vichinsky E. Stroke recurrence in adult sickle cell patients: it is time for action! Transfusion 2018; 56:1001-4. [PMID: 27167352 DOI: 10.1111/trf.13614] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/15/2016] [Accepted: 03/15/2016] [Indexed: 12/23/2022]
Affiliation(s)
- Lynne Neumayr
- UCSF Benioff Children's Hospital Oakland, Oakland, CA
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13
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Pediatric arterial ischemic stroke: Epidemiology, risk factors, and management. Blood Cells Mol Dis 2017; 67:23-33. [PMID: 28336156 DOI: 10.1016/j.bcmd.2017.03.003] [Citation(s) in RCA: 88] [Impact Index Per Article: 11.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/11/2016] [Revised: 03/06/2017] [Accepted: 03/06/2017] [Indexed: 12/17/2022]
Abstract
Pediatric arterial ischemic stroke (AIS) is an uncommon but important cause of neurologic morbidity in neonates and children, with consequences including hemiparesis, intellectual disabilities, and epilepsy. The causes of pediatric AIS are unique to those typically associated with stroke in adults. Familiarity with the risk factors for AIS in children will help with efficient diagnosis, which is unfortunately frequently delayed. Here we review the epidemiology and risk factors for AIS in neonates and children. We also outline consensus-based practices in the evaluation and management of pediatric AIS. Finally we discuss the outcomes observed in this population. While much has been learned in recent decades, many uncertainties sill persist in regard to pediatric AIS. The ongoing development of specialized centers and investigators dedicated to pediatric stroke will continue to answer such questions and improve our ability to effectively care for these patients.
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Rodrigues DLG, Adegoke SA, Campos RDSM, Braga JAP, Figueiredo MS, Silva GS. Patients with sickle cell disease are frequently excluded from the benefits of transcranial doppler screening for the risk of stroke despite extensive and compelling evidence. ARQUIVOS DE NEURO-PSIQUIATRIA 2017; 75:15-19. [DOI: 10.1590/0004-282x20160175] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/18/2016] [Accepted: 09/01/2016] [Indexed: 11/22/2022]
Abstract
ABSTRACT Transcranial doppler (TCD) is a strategic component of primary stroke prevention in children with sickle cell disease (SCD). This study was conducted to examine the TCD characteristics of children with SCD in nine different medical centers in Brazil. Methods: Transcranial doppler was performed in accordance with the Stroke Prevention Trial in Sickle Cell Anemia Protocol. Results: Of the 396 patients, 69.5% had homozygous SS hemoglobin. The TCD result was abnormal in 4.8%, conditional in 12.6%, inadequate in 4.3% and abnormally low in 1% of patients. The highest mean flow velocities were 121±23.83cm/s and 124±27.21cm/s in the left and right middle cerebral artery respectively. A total of 28.8% patients (mean age 9.19±5.92 years) were evaluated with TCD for the first time. Conclusions: The SCD patients were evaluated with TCD at an older age, representing an important missed opportunity for stroke prevention. Since TCD screening in patients with SCD is important to detect those at high risk for stroke, it is recommended that this screening should be made more readily available.
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Affiliation(s)
| | | | | | | | | | - Gisele Sampaio Silva
- Universidade Federal de São Paulo, Brasil; Hospital Israelita Albert Einstein, Brasil
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15
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Transcranial Doppler in the evaluation of infants treated with retrograde ventriculosinus shunt. Childs Nerv Syst 2016; 32:2133-2142. [PMID: 27638718 DOI: 10.1007/s00381-016-3237-5] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/13/2016] [Accepted: 08/30/2016] [Indexed: 12/20/2022]
Abstract
INTRODUCTION Hydrocephalus is a prevalent condition among infants. Retrograde ventriculosinus shunt (RVSS) proposes a feasible option to treat hydrocephalus according to the principles presented by El-Shafei. In this essay, we analyze nuances and application of transcranial Doppler (TCD) in patients submitted to RVSS. METHODS We consecutively enrolled patients diagnosed with hydrocephalus after surgical repair of myelomeningocele from January 2010 to January 2012, users of Hospital das Clinicas, University of Sao Paulo. They were treated with RVSS. Patients enrolled to the study were consecutively evaluated in an outpatient basis with TCD in preoperative, immediate postoperative period, and late postoperative period (1 year). RESULTS Except for patient 3, there was an increase in mean flow velocity, decreased pulsatility index, and decreased resistance index in all vessels analyzed. DISCUSSION In our sample, transcranial Doppler could be used as a diagnostic and follow-up tool to evaluate hemodynamics and hydrodynamics in the preoperative and postoperative phases of RVSS. It was technically feasible in all patients, had close relation with other clinical and image parameters, and was sensitive to identify system malfunction.
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Reeves SL, Fullerton HJ, Cohn LM, Dombkowski KJ, Boulton ML, Braun TM, Lisabeth LD. Missed Opportunities for Transcranial Doppler Screening Among Children With Sickle Cell Disease. Clin Pediatr (Phila) 2016; 55:1093-9. [PMID: 26538586 DOI: 10.1177/0009922815614351] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
Abstract
Transcranial Doppler (TCD) screening rates remain low among children with sickle cell disease (SCD). We assessed TCD screening rates and missed opportunities for TCD screening. Children 2 to 16 years old with SCD enrolled in Michigan Medicaid for ≥1 year (2007-2011) were identified through newborn screening. Receipt of TCD screening and presence of a missed opportunity (≥1 SCD-related outpatient visit, no TCD screening) were identified through administrative claims. Potential correlates of missed opportunities included SCD-related health services, comorbidities, and demographics. Logistic regression with generalized estimating equations modeled associations between a missed opportunity and correlates. Overall, 353 children contributed 1066 person-years. TCD screening was low yearly (10%-32%); missed opportunities occurred in 73% of the person-years. Increasing age (odds ratio [OR] = 1.11; confidence interval CI = 1.07, 1.15), previous TCD screening (OR = 0.26; CI = 0.16, 0.41), and 4 to 5 (OR = 0.48; CI = 0.26, 0.87) or ≥6 outpatient visits (OR = 0.26; CI = 0.14, 0.49) were associated with a missed opportunity. Reduction of missed opportunities is a potential strategy to increase TCD screening rates.
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Affiliation(s)
- Sarah L Reeves
- University of Michigan School of Public Health, Ann Arbor, MI, USA University of Michigan, Department of Pediatrics, Ann Arbor, MI, USA
| | | | - Lisa M Cohn
- University of Michigan, Department of Pediatrics, Ann Arbor, MI, USA
| | | | | | - Thomas M Braun
- University of Michigan School of Public Health, Ann Arbor, MI, USA
| | - Lynda D Lisabeth
- University of Michigan School of Public Health, Ann Arbor, MI, USA University of Michigan, Department of Neurology, Ann arbor, MI, USA
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17
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Transcranial Doppler Screening in a Regional Care Network for Sickle Cell Disease in the United Kingdom. J Pediatr Hematol Oncol 2016; 38:517-24. [PMID: 27379529 DOI: 10.1097/mph.0000000000000633] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
The risk of stroke in children screened with transcranial Doppler ultrasound in the United Kingdom is not known. We evaluated a clinician-led program using a risk assessment modified from the STOP protocol. High-risk classification included abnormal velocities in the anterior cerebral artery, and single abnormal scan if initial velocity >220 cm/s (high abnormal) or if preceded by at least 2 conditional scans. In total, 1653 scans were performed in 542 children, followed for 2235 patient-years. Fifty-eight (10.7%) high-risk subjects were identified, including 18 (31%) with high abnormal, and 15 (26%) with previous conditional scans. In 2 (3%), abnormal velocity was restricted to the anterior cerebral artery. The estimated proportion of children at high risk, scanned before 6 years of age was >20%. There were 4 cases of acute ischemic stroke (AIS) and 2 of acute hemorrhagic stroke. The incidence of all stroke, AIS, and acute hemorrhagic stroke were 0.27, 0.18, and 0.09 per 100 patient-years, respectively. The proportion of children at high risk is higher than most previous estimates, partly as a result of our modified risk assessment. About 2 children per 1000 screened with transcranial Doppler ultrasound progress to AIS.
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18
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Bush AM, Borzage MT, Choi S, Václavů L, Tamrazi B, Nederveen AJ, Coates TD, Wood JC. Determinants of resting cerebral blood flow in sickle cell disease. Am J Hematol 2016; 91:912-7. [PMID: 27263497 DOI: 10.1002/ajh.24441] [Citation(s) in RCA: 71] [Impact Index Per Article: 7.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/26/2016] [Revised: 05/31/2016] [Accepted: 06/01/2016] [Indexed: 11/11/2022]
Abstract
Stroke is common in children with sickle cell disease and results from an imbalance in oxygen supply and demand. Cerebral blood flow (CBF) is increased in patients with sickle cell disease to compensate for their anemia, but adequacy of their oxygen delivery has not been systematically demonstrated. This study examined the physiological determinants of CBF in 37 patients with sickle cell disease, 38 ethnicity matched control subjects and 16 patients with anemia of non-sickle origin. Cerebral blood flow was measured using phase contrast MRI of the carotid and vertebral arteries. CBF increased inversely to oxygen content (r(2) = 0.69, P < 0.0001). Brain oxygen delivery, the product of CBF and oxygen content, was normal in all groups. Brain composition, specifically the relative amounts of grey and white matter, was the next strongest CBF predictor, presumably by influencing cerebral metabolic rate. Grey matter/white matter ratio and CBF declined monotonically until the age of 25 in all subjects, consistent with known maturational changes in brain composition. Further CBF reductions were observed with age in subjects older than 35 years of age, likely reflecting microvascular aging. On multivariate regression, CBF was independent of disease state, hemoglobin S, hemoglobin F, reticulocyte count and cell free hemoglobin, suggesting that it is regulated similarly in patients and control subjects. In conclusion, sickle cell disease patients had sufficient oxygen delivery at rest, but accomplish this only by marked increases in their resting CBF, potentially limiting their ability to further augment flow in response to stress. Am. J. Hematol. 91:912-917, 2016. © 2016 Wiley Periodicals, Inc.
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Affiliation(s)
- Adam M. Bush
- Department of Biomedical Engineering; University of Southern California; California
| | - Matthew T. Borzage
- Division of Neonatology and Radiology; Children's Hospital Los Angeles; California
| | - Soyoung Choi
- Neurosciences Program; University of Southern California; California
| | - Lena Václavů
- Department of Radiology; Academic Medical Center; Amsterdam
| | - Benita Tamrazi
- Department of Radiology; Children's Hospital Los Angeles; California
| | | | - Thomas D. Coates
- Section of Hematology; Children's Hospital Los Angeles; California
| | - John C. Wood
- Department of Radiology; Children's Hospital Los Angeles; California
- Division of Cardiology; Children's Hospital Los Angeles; California
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Belisário AR, Sales RR, Toledo NE, Muniz MBDSR, Velloso-Rodrigues C, Silva CM, Viana MB. Reticulocyte count is the most important predictor of acute cerebral ischemia and high-risk transcranial Doppler in a newborn cohort of 395 children with sickle cell anemia. Ann Hematol 2016; 95:1869-80. [PMID: 27520094 DOI: 10.1007/s00277-016-2789-5] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/29/2016] [Accepted: 08/05/2016] [Indexed: 10/21/2022]
Abstract
Stroke is a severe clinical manifestation of sickle cell anemia (SCA). Despite the prognostic relevance of transcranial Doppler (TCD), more accurate tools to assess stroke risk in children with SCA are required. Here, we describe the effect of clinical, laboratory, and molecular features on the risk of stroke and high-risk TCD in children from the newborn cohort of Minas Gerais, Brazil. Outcomes studied were acute cerebral ischemia and high-risk TCD. Clinical and hematological data were retrieved from children's records. Genetic markers, which were known for their association with stroke risk, were genotyped by polymerase chain reaction/restriction fragment length polymorphism and sequencing. The cumulative incidence of acute cerebral ischemia by the age of 8 years was 7.4 % and that of high-risk TCD by the age of 11.5 years was 14.2 %. The final multivariate model for acute cerebral ischemia risk included high white blood cell count and reticulocyte count, acute chest syndrome rate, and the single nucleotide polymorphisms (SNPs) TEK rs489347 and TNF-α rs1800629. The model for high-risk TCD included high reticulocyte count and the SNPs TEK rs489347 and TGFBR3 rs284875. Children with risk factors should be considered for intensive risk monitoring and for intervention therapy.
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Affiliation(s)
- André Rolim Belisário
- Centro de Tecidos Biológicos de Minas Gerais, Fundação Hemominas, Rua das Goiabeiras, 779, Lagoa Santa, Minas Gerais, 33400-000, Brazil. .,Faculdade de Medicina/NUPAD, Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, Minas Gerais, Brazil.
| | | | | | | | - Cibele Velloso-Rodrigues
- Departamento Básico-Área de Saúde, Universidade Federal de Juiz de Fora (UFJF), Governador Valadares, Minas Gerais, Brazil
| | - Célia Maria Silva
- Serviço de Pesquisa, Fundação Hemominas, Belo Horizonte, Minas Gerais, Brazil
| | - Marcos Borato Viana
- Faculdade de Medicina/NUPAD, Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, Minas Gerais, Brazil
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Neunert CE, Gibson RW, Lane PA, Verma-Bhatnagar P, Barry V, Zhou M, Snyder A. Determining Adherence to Quality Indicators in Sickle Cell Anemia Using Multiple Data Sources. Am J Prev Med 2016; 51:S24-30. [PMID: 27320461 PMCID: PMC4918094 DOI: 10.1016/j.amepre.2016.02.011] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/02/2015] [Revised: 01/22/2016] [Accepted: 02/09/2016] [Indexed: 10/21/2022]
Abstract
INTRODUCTION Advances in primary prophylaxis have resulted in improved outcomes for patients with sickle cell anemia (SCA; i.e., hemoglobin SS- and Sβ(0)-thalassemia). Standard prophylactic measures include a first pneumococcal polysaccharide vaccine (PPV) and transcranial Doppler ultrasound (TCD) at age 2 years. Though efficacious, evidence suggests that delivery of these interventions is suboptimal. This study reports adherence to these measures and examines concordance across various data sources, using Registry and Surveillance for Hemoglobinopathies project data. METHODS Retrospective database and SCA center chart review identified children with SCA aged 24-36 months between January 1, 2004, and December 31, 2008. PPV and TCD administration were determined through Medicaid and Children's Health Insurance Program administrative claims data, medical record review, and Georgia Registry of Immunization Transaction and Services. Analysis was conducted in 2015. RESULTS A total of 125 children met inclusion criteria. Forty-five (36.0%) children had documentation of both interventions, whereas 19 (15.2%) had no documentation of either intervention. Sixty-one (48.8%) children obtained only one intervention. Of these, more were likely to have had PPV than TCD (77.0% vs 23.0%, respectively, p<0.001). Agreement between claims data and medical record review was moderate for PPV (κ=0.55) and substantial for TCD (κ=0.74). CONCLUSIONS No single, reliable data source for tracking standard of care for children with SCA statewide was found. According to study data, prophylaxis measures were not universally implemented during the surveillance period. Further research is needed to adequately track changes over time, determine risk groups, and develop methods of evaluating important metrics.
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Affiliation(s)
- Cindy E Neunert
- Department of Pediatrics, Columbia University Medical Center and Morgan Stanley Children's Hospital, New York, New York
| | - Robert W Gibson
- Department of Emergency Medicine, Georgia Regents University, Augusta, Georgia
| | - Peter A Lane
- Aflac Cancer and Blood Disorders Center, Children's Healthcare of Atlanta, Atlanta, Georgia; Department of Pediatrics, Emory University School of Medicine, Atlanta, Georgia
| | - Pragya Verma-Bhatnagar
- Department of Pediatrics and Preventive Medicine, Quality of Life Health Services, Inc., Gadsden, Alabama
| | - Vaughn Barry
- Aflac Cancer and Blood Disorders Center, Children's Healthcare of Atlanta, Atlanta, Georgia; Department of Pediatrics, Emory University School of Medicine, Atlanta, Georgia
| | - Mei Zhou
- Georgia Health Policy Center, Andrew Young School of Policy Studies, Georgia State University, Atlanta, Georgia
| | - Angela Snyder
- Georgia Health Policy Center, Andrew Young School of Policy Studies, Georgia State University, Atlanta, Georgia; Department of Public Management and Policy, Andrew Young School of Policy Studies, Georgia State University, Atlanta, Georgia.
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21
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Reeves SL, Madden B, Freed GL, Dombkowski KJ. Transcranial Doppler Screening Among Children and Adolescents With Sickle Cell Anemia. JAMA Pediatr 2016; 170:550-6. [PMID: 27064406 PMCID: PMC7111507 DOI: 10.1001/jamapediatrics.2015.4859] [Citation(s) in RCA: 47] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/31/2023]
Abstract
IMPORTANCE With transcranial Doppler (TCD) screening, we can identify children and adolescents with sickle cell anemia who are at the highest risk of stroke. An accurate claims-based method for identifying children and adolescents with sickle cell anemia was recently developed and validated that establishes the necessary groundwork to enable large population-based assessments of health services utilization among children and adolescents with sickle cell anemia using administrative claims data. OBJECTIVE To assess the feasibility of using administrative claims data to identify and describe the receipt of TCD screening among children and adolescents with sickle cell anemia and to characterize opportunities for intervention. DESIGN, SETTING, AND PARTICIPANTS Retrospective cross-sectional study using Medicaid claims data from 2005 to 2010. Medicaid claims data were obtained from the following states: Florida, Illinois, Louisiana, Michigan, South Carolina, and Texas. Children and adolescents 2 to 16 years of age with sickle cell anemia were identified by the presence of 3 or more Medicaid claims with a diagnosis of sickle cell anemia within a calendar year (2005-2010). A total of 4775 children and adolescents contributed 10 787 person-years throughout the study period. Data were analyzed in 2015. A subset of children and adolescents enrolled for 2 or more consecutive years was identified to examine potential predictors of TCD screening, which included age, sex, previous receipt of TCD screening, state of residence, and health services utilization (well-child visits, outpatient visits, emergency department visits, and inpatient visits). MAIN OUTCOMES AND MEASURES Receipt of TCD screening was assessed by year and state. Using logistic regression with generalized estimating equations, we included associated predictors in a multivariable model to estimate odds of TCD screening. RESULTS For a total of 4775 children and adolescents 2 to 16 years of age, TCD screening rates increased over the 6-year study period from 22% to 44% (P < .001); rates varied substantially across states. A subset of 2388 children and adolescents with sickle cell anemia (50%) was enrolled for 2 or more consecutive years. Each year of increasing age was associated with 3% lower odds of TCD screening (odds ratio, 0.97 [95% CI, 0.95-0.98]; P = .002). Previous receipt of TCD screening (odds ratio, 2.44 [95% CI, 2.11-2.81]; P < .001) and well-child visits (odds ratio, 1.10 [95% CI, 1.03-1.18]; P = .007) were associated with higher odds of receiving a TCD screening. CONCLUSIONS AND RELEVANCE Despite national recommendations, TCD screening rates remain low. Successful strategies to improve TCD screening rates may capitalize on the numerous health care interactions among children and adolescents with sickle cell anemia.
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Affiliation(s)
- Sarah L Reeves
- Child Health Evaluation and Research Unit, Department of Pediatrics, University of Michigan, Ann Arbor
| | - Brian Madden
- Child Health Evaluation and Research Unit, Department of Pediatrics, University of Michigan, Ann Arbor
| | - Gary L Freed
- Child Health Evaluation and Research Unit, Department of Pediatrics, University of Michigan, Ann Arbor
| | - Kevin J Dombkowski
- Child Health Evaluation and Research Unit, Department of Pediatrics, University of Michigan, Ann Arbor
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Bundy DG, Muschelli J, Clemens GD, Strouse JJ, Thompson RE, Casella JF, Miller MR. Preventive Care Delivery to Young Children With Sickle Cell Disease. J Pediatr Hematol Oncol 2016; 38:294-300. [PMID: 26950087 PMCID: PMC4842129 DOI: 10.1097/mph.0000000000000537] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/02/2023]
Abstract
Preventive services can reduce the morbidity of sickle cell disease (SCD) in children but are delivered unreliably. We conducted a retrospective cohort study of children aged 2 to 5 years with SCD, evaluating each child for 14 months and expecting that he/she should receive ≥75% of days covered by antibiotic prophylaxis, ≥1 influenza immunization, and ≥1 transcranial Doppler ultrasound (TCD). We used logistic regression to quantify the relationship between ambulatory generalist and hematologist visits and preventive services delivery. Of 266 children meeting the inclusion criteria, 30% consistently filled prophylactic antibiotic prescriptions. Having ≥2 generalist, non-well child care visits or ≥2 hematologist visits was associated with more reliable antibiotic prophylaxis. Forty-one percent of children received ≥1 influenza immunizations. Children with ≥2 hematologist visits were most likely to be immunized (62% vs. 35% among children without a hematologist visit). Only 25% of children received ≥1 TCD. Children most likely to receive a TCD (42%) were those with ≥2 hematologist visits. One in 20 children received all 3 preventive services. Preventive services delivery to young children with SCD was inconsistent but associated with multiple visits to ambulatory providers. Better connecting children with SCD to hematologists and strengthening preventive care delivery by generalists are both essential.
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Affiliation(s)
- David G. Bundy
- Division of General Pediatrics, Department of Pediatrics, Medical University of South Carolina, Charleston, SC
| | - John Muschelli
- Department of Biostatistics, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD
| | - Gwendolyn D. Clemens
- Department of Biostatistics, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD
| | - John J. Strouse
- Division of Pediatric Hematology, Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, MD
- Division of Hematology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD
| | - Richard E. Thompson
- Department of Biostatistics, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD
| | - James F. Casella
- Division of Pediatric Hematology, Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, MD
| | - Marlene R. Miller
- Division of Quality and Safety, Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, MD
- Department of Health Policy & Management, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD
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24
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Wood JC, Cohen AR, Pressel SL, Aygun B, Imran H, Luchtman-Jones L, Thompson AA, Fuh B, Schultz WH, Davis BR, Ware RE. Organ iron accumulation in chronically transfused children with sickle cell anaemia: baseline results from the TWiTCH trial. Br J Haematol 2015; 172:122-30. [PMID: 26523836 DOI: 10.1111/bjh.13791] [Citation(s) in RCA: 42] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/07/2015] [Accepted: 08/25/2015] [Indexed: 10/22/2022]
Abstract
Transcranial Doppler (TCD) With Transfusions Changing to Hydroxyurea (TWiTCH) trial is a randomized, open-label comparison of hydroxycarbamide (also termed hydroxyurea) versus continued chronic transfusion therapy for primary stroke prevention in patients with sickle cell anaemia (SCA) and abnormal TCD. Severity and location of iron overload is an important secondary outcome measure. We report the baseline findings of abdominal organ iron burden in 121 participants. At enrollment, patients were young (9·8 ± 2·9 years), predominantly female (60:40), and previously treated with transfusions (4·1 ± 2·4 years) and iron chelation (3·1 ± 2·1 years). Liver iron concentration (LIC; 9·0 ± 6·6 mg/g dry weight) and serum ferritin were moderately elevated (2696 ± 1678 μg/l), but transferrin was incompletely saturated (47·2 ± 23·6%). Spleen R2* was 509 ± 399 Hz (splenic iron ~13·9 mg/g) and correlated with LIC (r(2) = 0·14, P = 0·0008). Pancreas R2* was increased in 38·3% of patients but not to levels associated with endocrine toxicity. Kidney R2* was increased in 80·7% of patients; renal iron correlated with markers of intravascular haemolysis and was elevated in patients with increased urine albumin-creatinine ratios. Extra-hepatic iron deposition is common among children with SCA who receive chronic transfusions, and could potentiate oxidative stress caused by reperfusion injury and decellularized haemoglobin.
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Affiliation(s)
- John C Wood
- Department of Cardiology, Childrens Hospital of Los Angeles, Los Angeles, CA, USA
| | - Alan R Cohen
- Department of Pediatrics, The Children's Hospital of Philadelphia, Philadelphia, PA, USA
| | - Sara L Pressel
- Department of Biostatistics, University of Texas Health Science Center, Houston, TX, USA
| | - Banu Aygun
- Department of Pediatrics, Cohen Children's Medical Center of NY, New Hyde Park, NY, USA
| | - Hamayun Imran
- Department of Pediatrics, University of South Alabama, Mobile, AL, USA
| | - Lori Luchtman-Jones
- Department of Pediatrics, Cincinnati Children's Hospital Medical Center, Cincinnnati, OH, USA
| | - Alexis A Thompson
- Department of Pediatrics, Anna and Robert H. Lurie Children's Hospital of Chicago, Chicago, IL, USA
| | - Beng Fuh
- Department of Biostatistics, University of Texas Health Science Center, Houston, TX, USA
| | - William H Schultz
- Department of Pediatrics, Cincinnati Children's Hospital Medical Center, Cincinnnati, OH, USA
| | - Barry R Davis
- Department of Biostatistics, University of Texas Health Science Center, Houston, TX, USA
| | - Russell E Ware
- Department of Pediatrics, Cincinnati Children's Hospital Medical Center, Cincinnnati, OH, USA
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25
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The role of neighborhoods in the receipt of transcranial Doppler screening among children with sickle cell disease. J Pediatr Hematol Oncol 2015; 37:269-73. [PMID: 25265467 DOI: 10.1097/mph.0000000000000266] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
Although transcranial Doppler (TCD) screening assesses the need for stroke prevention efforts among children with sickle cell disease (SCD), screening rates remain low across many parts of the United States. We sought to identify neighborhoods with low TCD screening rates and neighborhood-level factors related to screening to inform the utility of community-level interventions to improve TCD screening. Children ages 2 to 16 years with SCD (HbSS/HbS/β-thalassemia) living in Wayne County, MI, were identified in Michigan Medicaid (2007 to 2011) through newborn screening records. Children were enrolled for ≥ 1 year and could contribute multiple years. We determined receipt of ≥ 1 TCD screening and neighborhood (census tract) each year. The proportion of children receiving TCD in the tract was calculated and investigated for spatial patterns across tracts (Moran's I). Median household income, % unemployment, % black residents, and % less than high school education within each tract were ascertained from the American Community Survey. Logistic regression with generalized estimating equations was used to model associations between TCD screening and neighborhood-level factors. Overall, 329 children contributed 532 person-years and screening rates increased from 7% to 36% from 2007 to 2011. Median screening rate in tracts was 0% (interquartile range = 29%) and there was no spatial pattern of TCD screening across tracts (Moran's I Z-score = -0.94, P-value = 0.35). No associations were found between neighborhood characteristics and receipt of TCD screening in this disadvantaged Michigan county. Additional research is needed to inform interventions to increase TCD screening in this high stroke-risk population.
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Reeves SL, Fullerton HJ, Dombkowski KJ, Boulton ML, Braun TM, Lisabeth LD. Physician attitude, awareness, and knowledge regarding guidelines for transcranial Doppler screening in sickle cell disease. Clin Pediatr (Phila) 2015; 54:336-45. [PMID: 25320061 DOI: 10.1177/0009922814553429] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
Abstract
OBJECTIVE We explored factors that may influence physician adherence to transcranial Doppler (TCD) screening guidelines among children with sickle cell disease. METHODS Pediatric hematologists, neurologists, and primary care physicians (n = 706) responded to a mailed survey in May 2012 exploring factors hypothesized to influence physician adherence to TCD screening guidelines: physician (internal) barriers and physician-perceived external barriers. Responses were compared by specialty using chi-square tests. RESULTS Among 276 physicians (44%), 141 currently treated children with sickle cell disease; 72% recommend screening. Most primary care physicians (66%) did not feel well informed regarding TCD guidelines, in contrast to neurologists (25%) and hematologists (6%, P < .0001). Proportion of correct answers on knowledge questions was low (13%-35%). Distance to a vascular laboratory and low patient adherence were external barriers to receipt of TCD screening. CONCLUSIONS Additional research regarding physicians' lack of self-efficacy and knowledge of recommendations could help clarify their role in recommendation of TCD screening.
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Naffaa LN, Tandon YK, Irani N. Transcranial Doppler screening in sickle cell disease: The implications of using peak systolic criteria. World J Radiol 2015; 7:52-56. [PMID: 25729487 PMCID: PMC4326734 DOI: 10.4329/wjr.v7.i2.52] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/14/2014] [Revised: 12/25/2014] [Accepted: 01/20/2015] [Indexed: 02/06/2023] Open
Abstract
AIM: To compare time average maximum mean velocity (TAMV) and peak systolic velocity (PSV) criteria of Trans Cranial Doppler (TCD) in their ability to predict abnormalities on magnetic resonance imaging (MRI)/magnetic resonance angiogram (MRA) in patients with sickle cell disease.
METHODS: A retrospective evaluation was performed of the outcomes in all patients with a Transcranial Doppler examination at our institution since the implementation of the hospital picture archiving and communication system (PACS) system in January 2003 through December 2012. All ultrasound imaging exams were performed by the same technologist with a 3 MHz transducer. Inclusion criteria was based upon the Transcranial Doppler procedure code in our PACS which had an indication of sickle cell disease in the history. The patient’s age and gender along with the vessel with the highest time averaged mean velocity as well as the highest peak systolic velocity was recorded for analysis. A subset of the study cohort also had subsequent MR imaging and Angiograms performed within 6 mo of the TCD examination. MRI results were categorized as having a disease related abnormality (vessel narrowing, collateral formation/moya-moya, or abnormal fluid attenuation inversion recovery signal in parenchyma indicative of prior stroke) or normal. The MRI results formed the comparison standards for TCD exams in evaluating intracranial injury. Sensitivity and specificity for the two TCD criteria (TAMV and PSV) were calculated to determine which could be a better predictor for intracranial vasculopathy /clinically occult strokes.
RESULTS: The study cohort for our institution was 110 patients with a total of 291 TCD examinations. These patients had a mean age of 7.6 years with a range from 2-18 years of age. Sixty-two of the 110 patients (56%) had two or more TCD exams. Thirty-seven patients (34%) had at least one MRI following a TCD examination. Of the 291 TCD examinations, 46 (16%) were conditional or abnormal by TAMV criteria. One hundred and sixteen (40%) were conditional or abnormal by PSV criteria. All studies that were abnormal by TAMV were also abnormal by PSV criteria. Seventy of the 116 (60%) studies which were conditional or abnormal by peak systolic criteria would not have been identified by time averaged mean maximum velocity criteria. The most frequent location of highest velocity measurement was noted to be in the middle cerebral artery regardless of whether it was measured by PSV or TAMV. From the 37 patients having one or more MRIs, 43 MRI exams were performed within 6 mo of a TCD examination. Twenty two (51%) MRIs had a disease related abnormality reported. When evaluating conditional or abnormal exams by PSV criteria against follow-up MRI/MRA, the sensitivity was 73% [16/(16 + 6)] and specificity was 81% [17/(4 + 17)]. When evaluating conditional or abnormal exams by TAMV criteria by follow-up MRI/MRA as the gold standard, the sensitivity was 41% [9/(9 + 13)] and the specificity was 100% [21/(21 + 0)]. In using conditional or abnormal criteria from PSV and TAMV to predict abnormalities on follow-up MRI/MR Angiogram, PSV was more sensitive (73% vs 41%) while TAMV was more specific (100% vs 81%).
CONCLUSION: Based on the data obtained at our institution and using the assumption that the best screening test is the one with the highest sensitivity, the peak systolic velocity could be the measurement of choice for TCD screening.
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Hussain S, Nichols F, Bowman L, Xu H, Neunert C. Implementation of transcranial Doppler ultrasonography screening and primary stroke prevention in urban and rural sickle cell disease populations. Pediatr Blood Cancer 2015; 62:219-223. [PMID: 25381872 DOI: 10.1002/pbc.25306] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/17/2014] [Accepted: 09/18/2014] [Indexed: 11/06/2022]
Abstract
BACKGROUND Transcranial Doppler (TCD) ultrasonography identifies children with sickle cell disease (SCD) at increased risk of stroke. Initiation of chronic transfusions as primary stroke prevention in children with abnormal TCD significantly reduces stroke risk. Here, we report the results describing the implementation of TCD screening and primary stroke prevention in both urban and rural clinical practices. PROCEDURE Retrospective chart review identified children ages 2-16 years with Hgb SS or Sß0 -thalassemia and no history of stroke followed in either the local urban or rural SCD clinics at Georgia Regents University. We defined standard of care (SOC) as having one TCD performed annually between January 2010 and December 2012 starting at age 2 years. RESULTS A total of 195 patients were included in the evaluation of SOC screening, overall 41% achieved SOC. There was no difference in SOC between the two clinics (35% urban and 47.4% rural). The majority of patients with abnormal TCDs are on chronic transfusions (83%), and none have experienced a stroke. Monitoring of effects of transfusion was difficult with 38% and 31% of rural patients lacking documentation of Hgb S% and ferritin levels, respectively, in the past year. CONCLUSIONS We report here data describing primary stroke prophylaxis in rural patients. SOC rates are similar between the two clinical settings. While implementation of primary stroke prevention in rural patients was difficult, rural TCD screening is feasible and can achieve SOC equal to that in an urban setting. This suggests that barriers exist in provided primary stroke prevention to all patients. Pediatr Blood Cancer 2015;62:219-223. © 2014 Wiley Periodicals, Inc.
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Affiliation(s)
- Samiya Hussain
- Medical College of Georgia, Georgia Regents University, Augusta, Georgia
| | - Fenwick Nichols
- Department of Neurology, Georgia Regents University, Augusta, Georgia
| | - Latanya Bowman
- Sickle Cell Center, Georgia Regents University, Augusta, Georgia
| | - Hongyan Xu
- Department of Biostatistics and Epidemiology, Georgia Regents University, Augusta, Georgia
| | - Cindy Neunert
- Cancer Center, Georgia Regents University, Augusta, Georgia.,Department of Pediatrics, Georgia Regents University, Augusta, Georgia
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Bundy DG, Abrams MT, Strouse JJ, Mueller CH, Miller MR, Casella JF. Transcranial Doppler screening of Medicaid-insured children with sickle cell disease. J Pediatr 2015; 166:188-90. [PMID: 25444529 DOI: 10.1016/j.jpeds.2014.09.018] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/29/2014] [Revised: 07/25/2014] [Accepted: 09/09/2014] [Indexed: 02/09/2023]
Abstract
Transcranial Doppler screening reduces the risk of stroke in children with sickle cell disease. We tested the effect of informational letters sent to parents and doctors of Medicaid-insured children on improving screening efficiency. The letters did not improve the low baseline screening rates, suggesting the need for more aggressive outreach. Hematologist visits were correlated with increased screening rates.
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Affiliation(s)
- David G Bundy
- Division of General Pediatrics, Department of Pediatrics, Medical University of South Carolina, Charleston, SC.
| | - Michael T Abrams
- The Hilltop Institute, University of Maryland, Baltimore County, Baltimore, MD
| | - John J Strouse
- Division of Pediatric Hematology, Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, MD; Division of Hematology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD
| | - Carl H Mueller
- The Hilltop Institute, University of Maryland, Baltimore County, Baltimore, MD
| | - Marlene R Miller
- Division of Quality and Safety, Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, MD; Department of Health Policy and Management, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD; Children's Hospital Association, Alexandria, VA
| | - James F Casella
- Division of Pediatric Hematology, Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, MD
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Poisson SN, Schardt TQ, Dingman A, Bernard TJ. Etiology and treatment of arterial ischemic stroke in children and young adults. Curr Treat Options Neurol 2014; 16:315. [PMID: 25227455 DOI: 10.1007/s11940-014-0315-4] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/22/2023]
Abstract
OPINION STATEMENT Stroke is the second leading cause of death worldwide (Go et al. Circulation 129:e28-292, 2014) and is a major cause of morbidity and mortality. Compared with older adults, arterial ischemic stroke (AIS) is relatively uncommon in children and young adults, comprising 5-10 % of all stroke (Biller Nat Rev Cardiol 6:395-97, 2009), but is associated with significant cost. In contrast to the declining overall incidence of stroke, some early studies suggest that the rate of stroke hospitalizations in children and young adults is rising (George et al. Ann Neurol 70:713-21, 2011; Kissela et al. Stroke 41:e224, 2010; Nguyen-Huynh et al. Stroke 43, 2012), emphasizing the importance of understanding the similarities and differences in etiology and treatment of AIS across the age spectrum. Among the most common causes of AIS in children are cardioembolism (often related to congenital heart disease), cervicocephalic arterial dissections, focal arteriopathy of childhood and several genetic and metabolic disorders, such as sickle cell disease (SCD). AIS in young adults is less well understood, but likely overlaps in etiology with both children and older adults. Young adults with AIS often have classic atherosclerotic risk factors similar to older adults, but are also more likely to have thrombophilias, cervicocephalic arterial dissections and cardioembolism, similar to children with AIS. Since little evidence exists regarding both acute treatment and secondary prevention after AIS in children and young adults, standard treatment practices are mainly extrapolated from research done in older adults. In most cases we recommend treating young adults per the guidelines published by the American Heart Association for adults with stroke (Jauch et al. Stroke 44:870-947, 2013; Kernan et al. Stroke 45:2160-2236, 2014) and children per the equivalent guidelines regarding pediatric stroke (Roach et al. Stroke 39:2644-91, 2008). It is also important in children and young adults to consider less common structural, metabolic and genetic risk factors for stroke, which may require more specific treatment. Other standard risk factors for stroke, including hypertension, hyperlipidemia and diabetes mellitus should also be addressed, but are less likely in children and young adults. Given the lack of data and possibility of rare underlying etiologies such as Antiphospholipid Antibody Syndrome or Ehlers-Danlos syndrome, we recommend including multiple specialists in the care of these patients, such as hematologists and vascular neurologists.
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Affiliation(s)
- Sharon N Poisson
- Department of Neurology, University of Colorado Denver, Leprino Building, 12401 E. 17th Ave., Mail Stop L950, Aurora, CO, 80045, USA,
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Arkuszewski M, Krejza J, Chen R, Ichord R, Kwiatkowski JL, Bilello M, Zimmerman R, Ohene-Frempong K, Melhem ER. Sickle cell anemia: intracranial stenosis and silent cerebral infarcts in children with low risk of stroke. Adv Med Sci 2014; 59:108-13. [PMID: 24797985 DOI: 10.1016/j.advms.2013.09.001] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/12/2013] [Accepted: 09/13/2013] [Indexed: 10/25/2022]
Abstract
PURPOSE Children with sickle cell anemia (SCA), who have mean blood flow velocities <170 cm/s in the terminal internal carotid (tICA) or middle cerebral (MCA) arteries on transcranial Doppler ultrasonography (TCD), are considered to be at low risk of stroke. The prevalence of intracranial stenosis, which raises the risk of stroke, is not known in these children. Here, we estimated the prevalence of stenosis and explored its association with silent cerebral infarcts determined based on Magnetic Resonance (MR) scans. PATIENTS/METHODS We studied prospectively a cohort of 67 children with SCA without prior clinically overt stroke or TIA (median age 8.8 years; range limits 2.3-13.1 years; 33 females) and with TCD mean velocity <170 cm/s. They underwent MR imaging of the brain and MR angiography of intracranial arteries. RESULTS In 7 children (10.5%, 95% CI: 4.9-20.3%) we found 10 stenoses, including 4 with isolated left tICA stenosis and 3 with multiple stenoses. We found silent infarcts in 26 children (37.7%, 95% CI: 27.2-49.5%). The median number of infarcts in an affected child was 2 (range limits: 1-9), median volume of infarcts was 171 mm(3) (range limits: 7-1060 mm(3)), and median infarct volume in relation to total brain volume was 0.020% (range limits: 0.001-0.101%). The number and volume of infarcts were significantly higher in children with arterial stenosis (both p=0.023). CONCLUSIONS The prevalence of intracranial arterial stenosis in children with SCA classified as at low risk of stroke by TCD mean velocity <170 cm/s is high. Children with stenosis are at higher risk of brain parenchymal injury as they have more silent cerebral infarcts.
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Kassim AA, DeBaun MR. The case for and against initiating either hydroxyurea therapy, blood transfusion therapy or hematopoietic stem cell transplant in asymptomatic children with sickle cell disease. Expert Opin Pharmacother 2014; 15:325-36. [DOI: 10.1517/14656566.2014.868435] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022]
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Abstract
Sickle cell disease (SCD) is a genetic disorder characterised by anaemia and "sickling" of red blood cells, leading to chronic haemolytic anaemia, vascular injury, and organ dysfunction. Although children and adults experience many similar symptoms and problems, complications increase with age, leading to early mortality. Hydroxyurea (hydroxycarbamide), the only US Food and Drug Administration-approved treatment, continues to be under-utilised and other treatments available to children are often inaccessible for adults. Haematopoietic stem-cell transplantation is a curative option, but is limited by a lack of donors and concerns for transplant-related toxicities. Although comprehensive programs exist in paediatrics, affected adults may not have access to preventative and comprehensive healthcare because of a lack of providers or care coordination. They are often forced to rely on urgent care, leading to increased healthcare utilisation costs and inappropriate treatment. This problem highlights the importance of primary care during the transition from paediatrics to adulthood.
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Arkuszewski M, Krejza J, Chen R, Kwiatkowski JL, Ichord R, Zimmerman R, Ohene-Frempong K, Melhem ER. Sickle cell disease in children: accuracy of imaging transcranial Doppler ultrasonography in detection of intracranial arterial stenosis. Neuroradiol J 2012; 25:402-10. [PMID: 24029032 DOI: 10.1177/197140091202500402] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/05/2012] [Accepted: 06/09/2012] [Indexed: 11/17/2022] Open
Abstract
This study aimed to determine the accuracy of imaging transcranial Doppler sonography in detection of intracranial arterial stenosis in children with sickle cell disease using three-dimensional MR angiography as a reference standard. Sixty-one children (mean age 102±39 months, 30 males), who had no history of overt stroke, and were classified as at lowest risk of stroke by mean flow velocity criterion <170 cm/s, underwent conventional and imaging transcranial Doppler ultrasonographic examinations. We employed the area under the receiver operating characteristic curve (AUC) to determine the accuracy of flow velocity measurements obtained with imaging ultrasonography with and without correction for the angle of insonation as well as with conventional ultrasonography. We also established the most efficacious velocity thresholds for detection of the stenosis. We found ten intracranial stenoses in six patients on MR angiography, but we calculated AUC only for detection of stenosis (n=6) of the left intracranial internal carotid artery. The accuracy of flow velocity with angle correction was lower than the accuracy of velocity without angle correction (AUC=0.73, 95% CI, 0.53-0.93 versus AUC=0.87, 95% CI, 0.74-1.00; p=0.017). The accuracy of flow velocity obtained with conventional ultrasonography (AUC=0.82, 95% CI, 0.67-0.97) was not different from the accuracy of flow velocities obtained with imaging ultrasonography. We found that the threshold of 165 cm/s of mean velocity without angle correction is associated with highest efficiency for imaging (92%) and conventional ultrasonography (90%). Velocity measurements without angle-correction provide good accuracy in detection of stenosis of the terminal internal carotid artery, whereas angle-corrected velocities have lower accuracy.
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Affiliation(s)
- M Arkuszewski
- Department of Radiology, Division of Neuroradiology, University of Pennsylvania; Philadelphia, PA, USA - Department of Neurology, Medical University of Silesia; Katowice, Poland -
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Jordan LC, Casella JF, DeBaun MR. Prospects for primary stroke prevention in children with sickle cell anaemia. Br J Haematol 2012; 157:14-25. [PMID: 22224940 DOI: 10.1111/j.1365-2141.2011.09005.x] [Citation(s) in RCA: 35] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/19/2023]
Abstract
This review will focus on the strengths and limitations associated with the current standard of care for primary prevention of ischaemic strokes in children with sickle cell anaemia (SCA) - transcranial Doppler ultrasound (TCD) screening followed by regular blood transfusion therapy when TCD measurement is above a threshold defined by a randomized clinical trial (RCT). The theoretical basis for potential alternative strategies for primary prevention of neurological injury in SCA is also discussed. These strategies will include, but will not be limited to: immunizations to prevent bacterial infections, particularly in low income countries; management of elevated blood pressure; and targeted strategies to increase baseline haemoglobin levels with therapies such as hyroxycarbamide or potentially definitive haematopoietic stem cell transplant.
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Affiliation(s)
- Lori C Jordan
- Department of Neurology, Division of Pediatric Neurology, Vanderbilt University School of Medicine, Nashville, TN 37232, USA
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Co-occurrence of Chiari malformations and sickle cell disease-a diagnostic dilemma: a report of 4 cases and review of literature. J Pediatr Hematol Oncol 2011; 33:624-5. [PMID: 22042280 DOI: 10.1097/mph.0b013e3182346ec3] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
The co-occurrence of sickle cell disease (SCD) and Chiari malformation (CM) poses clinical and diagnostic challenge since symptoms of both conditions may overlap. Although SCD and CM do not have a causal relationship, the overlapping neurologic symptoms may pose a diagnostic dilemma. To the best of our knowledge, the clinical manifestations and long-term consequence of CM in children with SCD has hitherto not been reported in the literature. We describe clinical manifestations of co-occurrence of SCD and CM in a case series of 4 African American children.
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Bollinger LM, Nire KG, Rhodes MM, Chisolm DJ, O'Brien SH. Caregivers' perspectives on barriers to transcranial Doppler screening in children with sickle-cell disease. Pediatr Blood Cancer 2011; 56:99-102. [PMID: 20842753 DOI: 10.1002/pbc.22780] [Citation(s) in RCA: 29] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/18/2009] [Accepted: 07/15/2010] [Indexed: 11/09/2022]
Abstract
BACKGROUND Current guidelines recommend that children with HbSS or HbSβ°thal undergo yearly transcranial Doppler screenings (TCD) to identify those at high risk for stroke. Compliance is low with yearly TCD screenings. Our objective was to describe caregiver experiences and knowledge of TCD screenings as well as barriers that may prevent screening. PROCEDURE Qualitative, in-depth interviews structured around the Health Belief Model were conducted with 36 caregivers of children eligible for annual TCD screenings. Interviews were coded and general themes were extracted. RESULTS Two-thirds (69%) of caregivers believed that stroke occurs sometimes (33%) or frequently (36%) in children with sickle-cell disease (SCD). Lack of knowledge was the most commonly described barrier to annual TCD screening, with 22% of caregivers reporting no knowledge of screening, and 42% unaware that the screen should be performed annually. Lack of self-efficacy and fear of chronic transfusions were other barriers endorsed by caregivers. Barriers less commonly identified (endorsed by <10% of caregivers) included financial barriers, transportation issues, missed appointments, and hours of radiology clinic. Fifty-eight percent of the caregivers' children with SCD had undergone a TCD in the 18 months prior to the study interview. CONCLUSIONS From the caregiver perspective, lack of knowledge and low self-efficacy play a larger role than practical barriers in compliance with annual TCDs. Ongoing education at multiple patient encounters and encouragement of caregivers' empowerment and role in obtaining annual screenings may increase TCD compliance.
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Abstract
Although many underlying diseases have been reported in the setting of childhood arterial ischemic stroke, emerging research demonstrates that non-atherosclerotic intracerebral arteriopathies in otherwise healthy children are prevalent. Minor infections may play a role in arteriopathies that have no other apparent underlying cause. Although stroke in childhood differs in many aspects from adult stroke, few systematic studies specific to pediatrics are available to inform stroke management. Treatment trials of pediatric stroke are required to determine the best strategies for acute treatment and secondary stroke prevention. The high cost of pediatric stroke to children, families, and society demands further study of its risk factors, management, and outcomes. This review focuses on the recent findings in childhood arterial ischemic stroke.
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Affiliation(s)
- Christine K. Fox
- University of California, San Francisco, Box 0114, 505 Parnassus Avenue, Moffitt S798, San Francisco, CA 94143-0114 USA
| | - Heather J. Fullerton
- University of California, San Francisco, Box 0114, 505 Parnassus Avenue, Moffitt S798, San Francisco, CA 94143-0114 USA
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Mallick AA, O'Callaghan FJ. Risk factors and treatment outcomes of childhood stroke. Expert Rev Neurother 2010; 10:1331-1346. [PMID: 20662757 DOI: 10.1586/ern.10.106] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/05/2025]
Abstract
Stroke is an important cause of childhood mortality and morbidity. The risk factors and pathophysiological processes of stroke in children are very different than those in adults. The range of risk factors is very wide, with over 100 presumptive risk factors described. There are a number of clinical guidelines, but despite recent increases in research, the evidence base underpinning these guidelines is sparse. Therefore, treatment is largely based upon expert consensus and extrapolation from adult data. Mortality from childhood stroke is relatively high and at least two-thirds of survivors have neurological impairments. Stroke can affect a wide range of neurocognitive domains and a high proportion of children require additional educational support and have a reduced quality of life.
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