Sickle Cell News from Allan Platt

Sickle Cell News for August 2014

MONTHLY BLOOD TRANSFUSIONS REDUCE SICKLE CELL ANEMIA-RELATED BRAIN INJURY IN CHILDREN

NIH-funded study provides hope for children with disease-related brain damage

Regular blood transfusions prevent recurrent blockage of brain blood vessels, a serious neurological side effect that occurs in one third of children with sickle cell anemia, according to a study funded by the National Institutes of Health. The findings appear in the August 21 issue of the New England Journal of Medicine. 

In the United States, approximately 100,000 people, primarily African-Americans, live with sickle cell anemia, a genetic disorder in which red blood cells, which should be round, can take on abnormal, crescent-like shapes. These sickle cells are stickier than regular cells and can block blood flow, resulting in pain, organ damage and strokes.

Cerebral infarcts occur when blood vessels in the brain get blocked. Silent cerebral infarcts do not cause any obvious symptoms, so people are unaware that something is wrong. The only way to detect a silent stroke is with magnetic resonance imaging (MRI) scans of the brain, which are not routinely conducted in people with sickle cell anemia. Silent infarcts in children with sickle cell disease are known to be associated with long-term cognitive problems and poor academic performance.

"If scientists detect silent strokes early, young children can benefit from a wide array of educational interventions and can get support from federally mandated educational assistance programs to keep them from falling behind in school," said Michael R. DeBaun, M.D., from Vanderbilt University, Nashville, the lead author and principal investigator for the trial.

Previous studies have demonstrated that blood transfusions may help prevent stroke in patients with sickle cell anemia. Transfusions of healthy blood increase the number of normal red blood cells and make the occurrence of blocked blood vessels less likely. In the current study, Dr. DeBaun and his colleagues investigated whether monthly blood transfusions would help prevent recurrence of silent cerebral infarcts in children with sickle cell anemia who had evidence of a previous incident.

In this multi-center international clinical trial, 1,074 children had MRI scans and 35 percent had silent infarcts. The 196 children with sickle cell anemia who exhibited infarct-like lesions on brain scans were randomized to receive regular blood transfusions or standard medical care. The blood transfusions were administered every month for three years.

The investigators' results show that receiving blood transfusions on a regular basis prevented the recurrence of silent strokes. In the standard medical care group, 14.4 percent of patients experienced a stroke or new silent cerebral infarcts. Among patients who received regular blood transfusions, only 6.1 percent experienced a stroke or new silent cerebral infarct.

"The study provides clear evidence that we may be able to decrease the progression of silent strokes, which occur in 30 percent of children with sickle cell anemia. These results suggest that children who have this disease should be screened early for silent strokes, at least by the time they begin elementary school, to help them manage the disease and to ensure minimal impact on school performance," said Dr. DeBaun. 

The researchers noted that this trial included a very intense regimen for the patients, who were as young as 5 years old, and for their families. "One of the reasons we conducted this study was to check if the burden of the blood transfusion therapy, such as monthly doctor's visits, was worth the potential benefits," said Deborah Hirtz, M.D., program director at the NIH's National Institute of Neurological Disorders and Stroke, which provided funding for the study. Some risks linked to blood transfusions include severe allergic reactions and high levels of iron throughout the body.

"The commitment of the children and their parents, many of whom were working poor families, was quite impressive.  Despite the burden of a three-year intensive trial, 86 percent of the participants completed all aspects of the trial including 36 months of transfusion therapy, three non-sedated MRI scans, multiple neurology evaluations, two two-hour cognitive testing sessions, and two quality of life assessments," said Dr. DeBaun.

An unexpected result, according to the researchers, was that intelligence measures were not different between the two study groups. Previous studies from this trial and others have shown that silent strokes are associated with a five-point reduction in IQ. This issue will be further explored by the investigators.

"The study indicates that screening for silent strokes in children starting school can lead to early detection and prevention of recurrences as well as reduction in other complications of sickle cell anemia such as acute episodes of pain and acute chest syndrome. The results of this trial will make a difference to children with sickle cell anemia and their families," said Dr. Hirtz.

This work was supported by grants from the NINDS (NS042804) and the NIH's National Heart Lung and Blood Institute (HL091759).

The National Institutes of Health awarded Delaware State University and the Nemours Center for Cancer and Blood Disorders with a $10.2 million research grant to conduct comprehensive genetic research on sickle cell disease.

Officials have touted the project, which will establish the Delaware Comprehensive Sickle Cell Research Center, as historic and innovative since it will focus on identifying a genetic mutation to further treatment and care, symptom prevention, fostering strong psychological support for families and ensuring quality of care.

Sickle cell disease is a genetic disorder that attacks the red blood cells, causing them to break down prematurely. That breakdown can lead to anemia (low number of blood cells), infection, pain and eventual organ damage. It is most common among individuals with diverse backgrounds, with ancestors from Africa, the Arabian Peninsula, India and Mediterranean countries or those with Hispanic descent.

Nemours will use $8.4 million of the grant to implement new research training, data recording, conduct clinical trials on pain and inflammation relief using n-3 omega fatty acids and modify a psychosocial assessment tool used to screen children for sickle cell disease.

Additionally, a portion of Nemours' grant will be used to create a three-year pilot study that will vet the children most at risk for developing chronic kidney disease caused by sickle cell.

Down in Dover at DSU, professors received $1.8 million to conduct gene editing research to correct the abnormal hemoglobin causing sickle cells, without harming other cell functions. Another project will also involve growing hematopoietic stem cells on synthetic nanofiber scaffolds to stimulate healthy cell growth. http://www.delawareonline.com/story/news/health/2014/08/14/nemours-dsu-sickle-cell-grant/14058833/

Sickle cell in the Medical Literature

1.

Pediatrics. 2014 Aug 25. pii: peds.2014-0917. [Epub ahead of print]

Hydroxyurea and Growth in Young Children With Sickle Cell Disease.

Rana S1, Houston PE2, Wang WC3, Iyer RV4, Goldsmith J5, Casella JF6, Reed CK2, Rogers ZR7, Waclawiw MA5, Thompson B8; for the BABY HUG Investigators.

Author information:
1Department of Pediatrics and Child Health, Howard University, Washington, District of Columbia; srana@howard.edu.
2Department of Pediatrics and Child Health, Howard University, Washington, District of Columbia;
3St. Jude Children's Research Hospital, Memphis, Tennessee;
4University of Mississippi Medical Center, Jackson, Mississippi;
5National Heart, Lung, and Blood Institute, Bethesda, Maryland;
6Division of Hematology, Department of Pediatrics, Johns Hopkins University, Baltimore, Maryland;
7UT Southwestern Medical Center, Dallas, Texas; and.
8Clinical Trials & Surveys Corporation, Owings Mills, Maryland.

Abstract

BACKGROUND:

Growth impairment is a known complication of sickle cell disease. Effects of hydroxyurea (HU) on growth in very young children are not known.

METHODS:

Height, weight, BMI, and head circumference (HC) were compared with World Health Organization (WHO) standards in BABY HUG, a multicenter, randomized, double-blinded, placebo-controlled 2-year clinical trial of HU in 193 children 9 to 18 months of age. Anthropometric data were closely monitored and converted to z scores by using WHO standardized algorithms for descriptive analyses. The treatment and placebo groups were compared longitudinally by using a mixed model analysis.

RESULTS:

At entry, the z scores of BABY HUG children were higher than WHO norms. After 2 years of HU or placebo treatment, there were no significant differences between the groups, except for the mean HC z scores at study exit (HU: +0.8 versus placebo: +1.0, P = .05). Baseline z scores were the best predictors of z scores at study exit. The absolute neutrophil count, absolute reticulocyte count, and total white blood cell count had significant negative correlations with growth measures.

CONCLUSIONS:

Both groups had normal or near normal anthropometric measures during the study. The HC z scores at study entry and exit were slightly greater than WHO norms. Higher baseline white blood cell count, absolute reticulocyte count, and absolute neutrophil count were associated with poorer growth. The significance of the slightly lower HC in the treatment group at study exit is not clear. Trends toward normalization of weight and height and effects on HC will be monitored in ongoing BABY HUG follow-up studies.

Copyright © 2014 by the American Academy of Pediatrics.


PMID: 25157002 [PubMed - as supplied by publisher]


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2.

Br J Haematol. 2014 Aug 22. doi: 10.1111/bjh.13093. [Epub ahead of print]

Hydroxycarbamide treatment in sickle cell disease: estimates of possible leukaemia risk and of hospitalization survival benefit.

Castro O1, Nouraie M, Oneal P.

Author information:
1Center for Sickle Cell Disease, Howard University, Washington, DC, USA.

Abstract

Using health insurance claims databases we compared the frequency/incidence of acute myeloid leukaemia (AML) and inpatient mortality in sickle cell disease (SCD) subjects taking (n = 1051), or not taking (n = 9203) hydroxycarbamide (HC). Patients taking HC were older (median 19 vs. 17 years of age), had a higher proportion of males (53% vs. 38%), and their median hospitalizations per year was five times greater than in SCD patients not on HC (all P < 0·001). No new AML cases occurred in HC-treated paediatric SCD patients. For adults, the new AML incidence with HC exposure was 10·7/10 000 patient years, vs. 4·0/10 000 patient years in subjects not on HC (P = 0·2), a possible AML risk ratio of 3·18. Adjustment for a probable database bias for AML diagnosis/ascertainment lowered the risk ratio to 0·94 (95% confidence interval = 0·16-5·47). Despite their greater disease severity, the inpatient mortality in SCD adults prescribed HC (0·29%) was lower than that of patients not taking the drug (0·42%, P = 0·032). In this SCD population we find no increased risk for AML with HC treatment. If such a risk is eventually proven, it will probably be lower than that for drugs with known AML association. By contrast, HC treatment appears to confer a survival benefit.

© 2014 John Wiley & Sons Ltd.


PMID: 25146244 [PubMed - as supplied by publisher]


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3.

Health Qual Life Outcomes. 2014 Aug 22;12(1):125. [Epub ahead of print]

Patient reports of health outcome for adults living with sickle cell disease: development and testing of ASCQ-Me item banks.

Keller S, Yang M, Treadwell MJ, Werner EM, Hassell KL.

Abstract

BackgroundProviders and patients have called for improved understanding of the health care requirements of adults with sickle cell disease (SCD) and have identified the need for a systematic, reliable and valid method to document the patient-reported outcomes (PRO) of adult SCD care. To address this need, the Adult Sickle Cell Quality of Life Measurement System (ASCQ-Me) was designed to complement the Patient Reported Outcome Measurement Information System (PROMIS®). Here we describe methods and results of the psychometric evaluation of ASCQ-Me item banks (IBs).MethodsAt seven geographically-disbursed clinics within the US, 556 patients responded to questions generated to assess cognitive, emotional, physical and social impacts of SCD. We evaluated the construct validity of the hypothesized domains using exploratory factor analysis (EFA), parallel analysis (PA), and bi-factor analysis (Item Response Theory Graded Response Model, IRT-GRM). We used IRT-GRM and the Wald method to identify bias in responses across gender and age. We used IRT and Cronbach¿s alpha coefficient to evaluate the reliability of the IBs and then tested the ability of summary scores based on IRT calibrations to discriminate among tertiles of respondents defined by SCD severity.ResultsOf the original 140 questions tested, we eliminated 48 that either did not form clean factors or provided biased measurement across subgroups defined by age and gender. Via EFA and PA, we identified three subfactors within physical impact: sleep, pain and stiffness impacts. Analysis of the resulting six item sets (sleep, pain, stiffness, cognitive, emotional and social impacts of SCD) supported their essential unidimensionality. With the exception of the cognitive impact IB, these item sets also were highly reliable across a broad range of values and highly significantly related to SCD disease severity.ConclusionASCQ-Me pain, sleep, stiffness, emotional and social SCD impact IBs demonstrated exceptional measurement properties using modern and classical psychometric methods of evaluation. Further development of the cognitive impact IB is required to improve its sensitivity to differences in SCD disease severity. Future research will evaluate the sensitivity of the ASCQ-Me IBs to change in SCD disease severity over time due to health interventions.


PMID: 25146160 [PubMed - as supplied by publisher]


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4.

ScientificWorldJournal. 2013;2013:193252. Epub 2013 Sep 19.

Sickle Cell Disease: New Opportunities and Challenges in Africa.

Makani J1, Ofori-Acquah SF2, Nnodu O3, Wonkam A4, Ohene-Frempong K5.

Author information:
1Department of Haematology and Blood Transfusion, Muhimbili University of Health and Allied Sciences, P.O. Box 65001, Dar es Salaam, Tanzania ; Nuffield Department of Medicine, University of Oxford, Oxford, UK.
2Department of Pediatrics, Emory University School of Medicine, Atlanta, GA, USA ; School of Allied Health Sciences, College of Health Sciences, University of Ghana, Ghana.
3Department of Haematology and Blood Transfusion, College of Health Sciences, University of Abuja, Abuja, Nigeria.
4Division of Human Genetics, Faculty of Heath Sciences, University of Cape Town, South Africa ; Faculty of Medicine and Biomedical Sciences, University of Yaoundé I, Cameroon.
5Children's Hospital of Philadelphia, Philadelphia, PA, USA.

Abstract

Sickle cell disease (SCD) is one of the most common genetic causes of illness and death in the world. This is a review of SCD in Africa, which bears the highest burden of disease. The first section provides an introduction to the molecular basis of SCD and the pathophysiological mechanism of selected clinical events. The second section discusses the epidemiology of the disease (prevalence, morbidity, and mortality), at global level and within Africa. The third section discusses the laboratory diagnosis and management of SCD, emphasizing strategies that been have proven to be effective in areas with limited resources. Throughout the review, specific activities that require evidence to guide healthcare in Africa, as well as strategic areas for further research, will be highlighted.


PMID: 25143960 [PubMed - as supplied by publisher]


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5.

N Engl J Med. 2014 Aug 21;371(8):699-710. doi: 10.1056/NEJMoa1401731.

Controlled trial of transfusions for silent cerebral infarcts in sickle cell anemia.

DeBaun MR1, 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, Casella JF.

Author information:
1From the Department of Pediatrics, Division of Hematology-Oncology, Vanderbilt-Meharry Center of Excellence in Sickle Cell Disease, Vanderbilt University School of Medicine, Nashville (M.R.D.); Department of Ophthalmology and Visual Sciences, Division of Biostatistics (M.G.), Departments of Radiology and Pediatrics (R.C.M.), Neurology and Pediatrics (M.J.N.), and Psychology (D.A.W.), the Program in Occupational Therapy and Department of Pediatrics Hematology-Oncology (A.A.K.), and the Division of Biostatistics and Department of Internal Medicine (J.P.M.), Washington University School of Medicine, St. Louis; Department of Pediatrics, Division of Hematology-Oncology, Wayne State University, Detroit (S.A.S.); Center for Cancer and Blood Disorders, Children's National Medical Center, Department of Pediatrics, George Washington University Medical Center (E.R.M.), and Department of Pediatrics, Division of Hematology-Oncology, Georgetown University Hospital (C.E.G.) - all in Washington, DC; Department of Pediatrics, Division of Hematology-Oncology, University of Alabama at Birmingham, Birmingham (T.H.H.); Department of Pediatrics, Division of Hematology-Oncology, University of Mississippi Medical Center, Jackson (S.M.); Department of Paediatrics, Evelina Children's Hospital, St. Thomas' Hospital NHS Trust (B.P.D.I.), Department of Pediatric Hematology, Royal London Hospital, Barts Health NHS Trust (P.T.T.), and the Neurosciences Unit, Institute of Child Health, University College London (F.J.K.) - all in London; Hospital for Sick Children, Department of Paediatrics, Haematology-Oncology, University of Toronto, Toronto (M.K.-A.); Division of Hematology-Oncology, Department of Pediatrics, UT Southwestern Medical Center, Dallas (T.L.M.C.); Département Pédiatrie, Hôpital Intercommunal de Creteil, Creteil, France (A.K.); Department of Pediatrics, Division of Hematology-Oncology, Baylor College of Medicine, Houston (G.A.); Department of Pediatrics, Hematology-Oncology, Univer

Comment in

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.).


PMID: 25140956 [PubMed - in process]


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6.

Platelets. 2014 Aug 20:1-6. [Epub ahead of print]

The effect of prasugrel on ADP-stimulated markers of platelet activation in patients with sickle cell disease.

Jakubowski JA1, Zhou C, Winters KJ, Lachno DR, Howard J, Payne CD, Mant T, Jurcevic S, Frelinger AL 3rd.

Author information:
1Lilly Research Laboratories, Eli Lilly and Company, Indianapolis , IN , USA .

Abstract

Abstract Platelets of patients with sickle cell disease (SCD) show evidence of mild activation in the non-crisis steady state and greater activation during vaso-occlusive crises (VOC). Prasugrel, a potent inhibitor of ADP-mediated platelet activation and aggregation, may be useful in attenuating VOC. We compared platelet responses to ADP stimulation in patients with SCD and healthy subjects before and after treatment with prasugrel. In a phase 1 study, platelet biomarker levels were assessed in 12 adult patients with SCD and 13 healthy subjects before and after 12 ± 2 days of 5.0 or 7.5 mg/day prasugrel. The following were determined in whole blood samples stimulated with 20 µM ADP: (i) percentages of monocytes and neutrophils with adherent platelets (cell-platelet aggregates); (ii) the relative number (mass) of platelets associated with each monocyte and neutrophil as reported by CD61 mean fluorescence intensity (MFI) of the monocyte-platelet and neutrophil-platelet aggregates; (iii) the percentages of platelets positive for surface expression of CD40 ligand (CD40L), P-selectin (CD62p) and activated glycoprotein IIb-IIIa (GPIIb-IIIa); and (iv) the percentages of platelets and monocyte-platelet aggregates positive for surface tissue factor (TF) expression. At baseline, there were no significant differences between cohorts in the percentages of platelets expressing activation biomarkers. Following 12 days of prasugrel administration, the percentages of platelets expressing activation biomarkers following ADP stimulation were reduced in both cohorts, and there were no significant differences between groups. Both patients with SCD and healthy subjects had significant reductions in the monocyte-platelet and neutrophil-platelet aggregate MFI and the percentage of platelets expressing P-selectin and activated GPIIb-IIIa (all p < 0.05). Healthy subjects also had significant reductions in monocyte-platelet aggregate percentages (p = 0.004), neutrophil-platelet aggregate percentages (p = 0.011) and the percentage of CD40L-positive platelets (p = 0.044) that were not observed in patients with SCD. Prasugrel administration to SCD patients attenuates ex vivo ADP-stimulated platelet activation as measured by the percentage of platelets positive for P-selectin and GPIIb-IIIa, thus reducing the proportion of platelets that may participate in aggregates. Furthermore, prasugrel decreases ex vivo ADP-stimulated platelet aggregation with monocytes and neutrophils as measured by the monocyte-platelet and neutrophil-platelet aggregate MFI. This implies that in the presence of prasugrel, fewer platelets adhere to monocytes and neutrophils, which may result in reducing cell-platelet aggregate size. Therefore, reduced platelet reactivity and decreased size of leukocyte-platelet aggregates suggest additional mechanisms by which prasugrel may provide benefit to patients with SCD and support further investigation of possible therapeutic benefits of prasugrel in this population.


PMID: 25140584 [PubMed - as supplied by publisher]


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7.

Stroke. 2014 Aug 19. pii: STROKEAHA.114.006110. [Epub ahead of print]

Sickle Cell Trait and Incident Ischemic Stroke in the Atherosclerosis Risk in Communities Study.

Caughey MC1, Loehr LR2, Key NS2, Derebail VK2, Gottesman RF2, Kshirsagar AV2, Grove ML2, Heiss G2.

Author information:
1From the Departments of Medicine (M.C.C., N.S.K., V.K.D., A.V.K.) and Epidemiology (M.C.C., L.R.L., G.H.), University of North Carolina at Chapel Hill; Department of Neurology, Johns Hopkins University School of Medicine; Baltimore, MD (R.F.G.); and School of Public Health, Human Genetics Center, The University of Texas Health Science Center, Houston (M.L.G.). caughey@med.unc.edu.
2From the Departments of Medicine (M.C.C., N.S.K., V.K.D., A.V.K.) and Epidemiology (M.C.C., L.R.L., G.H.), University of North Carolina at Chapel Hill; Department of Neurology, Johns Hopkins University School of Medicine; Baltimore, MD (R.F.G.); and School of Public Health, Human Genetics Center, The University of Texas Health Science Center, Houston (M.L.G.).

Abstract

BACKGROUND AND PURPOSE:

Numerous case reports describe stroke in individuals with sickle cell trait (SCT) in the absence of traditional risk factors for cerebrovascular disease. To date, no prospective epidemiological studies have investigated this association.

METHODS:

A population-based sample of blacks (n=3497; mean age=54 years; female=62%) was followed from 1987 to 2011 in the Atherosclerosis Risk in Communities (ARIC) study, contributing a total of 65 371 person-years. Hazard ratios and incidence rate differences for ischemic stroke were estimated, contrasting SCT to homozygous hemoglobin A. Models were adjusted for age, sex, smoking, diabetes mellitus, hypertension, total cholesterol, atrial fibrillation, and coronary heart disease.

RESULTS:

SCT was identified in 223 (6.4%) participants. During a median follow-up of 22 years, 401 subjects experienced incident stroke (89% ischemic). Incident ischemic stroke was more frequent among those with SCT (13%) than those with homozygous hemoglobin A (10%). SCT was associated with an ischemic stroke hazard ratio of 1.4 (1.0-2.0) and an incidence rate difference amounting to 1.9 (0.4-3.8) extra strokes per 1000 person-years.

CONCLUSIONS:

We observed an increased risk of ischemic stroke in blacks with SCT. Further investigation of the incidence and pathophysiology of stroke in patients with SCT is warranted.

© 2014 American Heart Association, Inc.


PMID: 25139879 [PubMed - as supplied by publisher]


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8.

Eur J Haematol. 2014 Aug 19. doi: 10.1111/ejh.12435. [Epub ahead of print]

Deferasirox For Iron Chelation In Multi-Transfused Children With Sickle Cell Disease; Long-Term Experience In The East London Clinical Haemoglobinopathy Network.

Tsouana E1, Kaya B, Gadong N, Hemmaway C, Newell H, Simmons A, Whitmarsh S, Telfer P.

Author information:
1Department of Paediatric Haematology, Royal London Hospital, London.

Abstract

Deferasirox (DFX) has been licensed for iron chelation in patients with sickle cell disease (SCD), but there is limited data on its long-term efficacy and safety in children. This retrospective study included 62 regularly transfused children managed in the East London and Essex Clinical Haemoglobinopathy Network (mean age 9.2 ±3.2 years). Efficacy measurements consisted of monthly serum ferritin (SF) and annual R2 MRI-estimated liver iron concentration (LIC), and safety markers included serum creatinine and alanine aminotransferase (ALT). The mean duration of DFX treatment was 2.5±1.4 years, and mean dose at 36 months was 25 mg/kg/day. Mean SF at initiation of treatment was 2542±952ng/ml and increased to 4691±2255ng/ml at 36 months (p=0.05). Mean LIC on first scan was 10.3mg/g dry weight, and did not decrease significantly on follow-up scans. There was a significant correlation between relative change in LIC and in SF (R2 =0.66, p<0.001). Reversible transaminitis episodes, probably due to drug-induced hepatitis, were noted in 53% of patients. Responses to an adherence and acceptability questionnaire indicated that more than 50% of children had difficulties in taking DFX, commonly because of unpleasant taste. Our results show that more than 50% of children with SCD have inadequate control of iron overload with DFX. It is not clear whether this is because of frequent dose interruptions, poor tolerability and adherence, or poor efficacy of the drug. We recommend further studies to confirm these findings and to optimize iron chelation in this population. This article is protected by copyright. All rights reserved.

This article is protected by copyright. All rights reserved.


PMID: 25138173 [PubMed - as supplied by publisher]


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9.

Hematology. 2014 Aug 18. [Epub ahead of print]

A pilot study of manual chronic partial exchange transfusion in children with sickle disease.

Aloni MN, Lê PQ, Heijmans C, Huybrechts S, Devalck C, Azzi N, Ngalula-Mujinga M, Ferster A.

Abstract

Objective Red cell exchange transfusion is frequently used in the management of patients with sickle cell disease (SCD) either electively or chronically to maintain hemoglobin S (HbS) <30%. The purpose of this retrospective study was to evaluate the results of manual chronic partial exchange transfusion (MCPET) on level of Hb and HbS, on iron load and on the need for chelation, on risk of immunization, monitoring transfusion-transmitted viral infection, and clinical outcome. Methods We reviewed the long-term effect of MCPET in 10 children (six men and four women) with SCD and evaluated the iron balance during a median follow-up of 20 months (range: 6-36) in which 248 exchanges were performed. Results The pre-exchange median Hb value was 9.5 g/dl (range: 7.7-10.9 g/dl) and the median post-exchange value was 9.4 g/dl (range: 8.4-11.1 g/dl).The majority of patients reached an HbS of <50% with a median HbS value of 40.04% (range: 30-54). At start of the MCPET program, the median ferritin was 439 ng/ml (range: 80-1704 ng/ml). In the final evaluation, the median value of ferritin was 531 ng/ml (range: 84-3840 ng/ml). The annual calculated iron balance was 0. 28 ± 0.08 mg/kg/day. MCPET was well tolerated, and adverse effects were limited. Discussion MCPET in children with SCD is safe to prevent iron overload, and is effective and easy to use in our cohort. Conclusion Indication for chronic exchange blood transfusion is essential for patients with SCD with recurrent and frequent crises who do not respond to hydroxyurea. However, there is no consensual study for the period at which chronic transfusion can safely be stopped and further research in large population of patients with SCD will need to clarify this question.


PMID: 25133935 [PubMed - as supplied by publisher]


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10.

Pediatr Blood Cancer. 2014 Aug 17. doi: 10.1002/pbc.25177. [Epub ahead of print]

Improved hydroxyurea effect with the use of text messaging in children with sickle cell anemia.

Estepp JH1, Winter B, Johnson M, Smeltzer MP, Howard SC, Hankins JS.

Author information:
1Departments of Hematology, St. Jude Children's Research Hospital, Memphis, Tennessee.

Abstract

BACKGROUND:

In children with sickle cell anemia (SCA), hydroxyurea reduces morbidity, but adherence is frequently suboptimal. Because most families of children with SCA have access to cellular telephone services, we assessed the impact of text messaged reminders as a tool to improve adherence to hydroxyurea.

PROCEDURE:

All patients <19 years of age with HbSS or HbSβ0 thalassemia who were treated with hydroxyurea at a maximal tolerated dosage (MTD) at St. Jude Children's Research Hospital Comprehensive Pediatric Sickle Cell Program and who received automated text message reminders (SIMON®) were retrospectively identified. Laboratory parameters, hospitalizations, and medication possession ratios (MPR) prior to and after initiation of SIMON® were compared to assess the impact of SIMON®.

RESULTS:

Of the 97.3% of families with access to a cell phone, 91% elected to receive text message reminders. Among 55 children receiving hydroxyurea at MTD, laboratory parameters reflected waning medication compliance during the 12 months prior to SIMON®. Following initiation of SIMON®, children had higher mean corpuscular volumes, hemoglobin levels and fetal hemoglobin percentages and lower absolute reticulocyte counts and bilirubin levels, suggesting improved medication adherence. Hospitalizations were uncommon before and after SIMON®, and medication possession ratios (MPRs) were high before and after SIMON®, neither was significantly changed.

CONCLUSIONS:

SIMON® was feasible and improved hematologic parameters in children with SCA receiving hydroxyurea at a MTD. Future work will include extension of this technology to children with other chronic medical conditions who require daily use of medication. Pediatric Blood Cancer © 2014 Wiley Periodicals, Inc.

© 2014 Wiley Periodicals, Inc.


PMID: 25132074 [PubMed - as supplied by publisher]


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11.

J Clin Psychol Med Settings. 2014 Aug 13. [Epub ahead of print]

Predictors of Health-Related Quality of Life over Time Among Adolescents and Young Adults with Sickle Cell Disease.

Jackson JL1, Lemanek KL, Clough-Paabo E, Rhodes M.

Author information:
1Center for Biobehavioral Health, Nationwide Children's Hospital, Columbus, OH, USA.

Abstract

Little is known about what factors affect the health-related quality of life (HRQoL) of adolescents and young adults (AYAs) with sickle cell disease (SCD), and how their HRQoL changes over time. This re

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www.SCInfo.org

Where’s The Celebrity Support? The Unusual Business Of Standing Up For Sickle Cell Anemia - See more at: http://madamenoire.com/451495/wheres-celebrity-support-unusual-business-standing-sickle-cell-anemia/#sthash.qhNwYQjn.dpuf

Jimi Olaghere said sickle cell anemia has given him “a lifetime of pain,” but has also pointed his company in a fresh direction.

Olaghere knew his business needed a change after a recent sickle cell-related trip to the emergency room. While he waited for treatment, he saw #teamsicklecell scroll by on his Instagram page. The tech entrepreneur and owner of Geek Supply Company said it was then that he decided to use his tech skills to help combat issues surrounding his debilitating disease.

“After stumbling across the #teamsicklecell hashtag, I was engaged and I was excited. I wanted to build upon that and create awareness,” Olaghere said. “Right now there is really no one out there talking about [sickle cell] and I think we need to broadcast the message that it is okay to talk about it. As a child I was not encouraged to speak about how it affected me and even as an adult I have been afraid to talk about it because I didn’t want people to think that I couldn’t work or do regular things. We need to change how people think.”

At the time, the Newark resident was co-running Brick City Tech and owned the startup Geek Cook USA. Geek Cook brought design products in from China through New York and New Jersey and had air, road and rail distribution.

While his product line remains largely the same, his company name changed to Geek Supply Company and he has been donating 10 percent of its profits to the Martin Center Sickle Cell Initiative in Indianapolis since this past Spring. The changes to Geek Supply Co. have taken form over the last year, and while Olaghere said the feedback so far has been “a bit slow,” he is confident that over time his efforts will pay off.

“I switched from a business-to-business [model] to a business- to-consumer [model] and now a portion of my profits will go to sickle cell charities,” Olaghere said. “I’ve never run a charity and I wasn’t sure how to create and encourage research so the Initiative really stepped in and outlined how they would spend and improve funds received from us and how this money can improve the lives of those suffering from sickle cell.”

While there are several U.S. and global organizations that help create awareness and education for sickle cell, patients can certainly use any help they can get. According to The Ultimate Health Disparity, a research paper written by Gary A. Gibson, sickle cell is one of the most common genetically transmitted diseases, with two million people worldwide and approximately 100,000 in the United States carrying the disease. While sickle cell is not racially motivated, it does occur most frequently in people who live in or have descended from Africa, South and Central America, the Caribbean, and the Middle East. Every year 1,400 U.S. children are born with this disease, while in Ghana there are 14,000. In Nigeria the number jumps further to 150,000. Without a cure for sickle cell, children and adults around the globe continue to suffer with little more than ibuprofen to ease their pain.

Dr. Michael DeBaun, director at Vanderbilt-Miharry Center for Excellence in Sickle Cell Disease, weighed in on the discussion and said that while the disease does affect a percentage of those of Caucasian descent, the ailment “disproportionately affects people of color.” With symptoms that affect every organ and bone in the body, the disease can cause an immense amount of pain in child and adult patients alike. With treatment and health care options dwindling for adults with sickle cell in the U.S. and around the world, DeBaun said the problems related to this disease have “become more of a humanitarian issue.”

“Part of the challenge is that sickle cell disproportionately affects African Americans. No one is rallying against this disease. You don’t have entertainers stepping forward to educate the community on this issue. I have tried for 20 years to approach some of the biggest names in our community about doing what Jerry Louis did for the Muscular Dystrophy Associations of America. There has been a resounding deaf ear,” DeBaun said.

“Why is it that our entertainment leaders with so much discretionary income choose not to embrace this disease that disproportionately affects African Americans? While I do think it is a complex issue, I believe there are people that can make a difference in the lives of those living with this disease and could channel money to leverage a greater outcome – and they choose not to.”

DeBaun himself has been a pioneer in the battle against sickle cell and has held a camp in the Midwest region where patients and parents could learn more about the disease and how to manage pain and emotional stress. Most recently, he also started “Sickle Cell Sabbath” in St. Louis and Nashville, where Black congregations are educated about blood donations and trait testing.

“We started Sickle Cell Sabbath to encourage people to donate blood. We have found that most don’t donate because they haven’t been asked and told about the true benefit of savinghttp://images.intellitxt.com/ast/adTypes/icon1.png others. Once they know, they donate willingly and repeatedly,” DeBaun said. “We also supply sickle cell trait testing because individuals that are at risk to have children with sickle cell should be empowered with information. We have to try to take charge and make a difference. This has to start today if we want to have an impact 20 years from now.”

Olaghere agreed and said that through his philanthropy and donations, there is hope that others will join his initiative and make big changes for the future of the disease.

“At the end of the day I just felt like I had to do something. All my life I have been so frustrated by my lack of care and I have always felt so misunderstood. I spent part of my life living in Nigeria – and it’s even harder to get care there,” he said. “I want to build a community around this disease and create awareness. The conversation starts with us and hopefully if businesses see us doing this, they will also come on board. I know that if we all can come together there is hope that we can help change some of these practical problems – one business at a time.”

- See more at: http://madamenoire.com/451495/wheres-celebrity-support-unusual-business-standing-sickle-cell-anemia/#sthash.qhNwYQjn.dpuf

Nonmyeloablative Allogeneic HSCT for Sickle Cell Disease

Myeloablative allogeneic hematopoietic stem cell transplantation (HSCT) is curative for children with sickle cell disease, but toxicity may be prohibitive in adults. In a study that involved 30 patients aged 16 to 65 years with severe sickle cell disease or thalassemia, Hsieh and colleagues assessed the efficacy and safety of a low-intensity, nonmyeloablative regimen and HSCT from human leukocyte antigen–matched siblings. The authors report that at a median follow-up of 3.4 years, 29 patients were alive and 26 patients had long-term stable donor engraftment and normalized hemoglobin. In an Editorial, King and DiPersio discuss the potential to cure sickle cell disease in adults.

Editorial and Related Article

Author Video Interview

Congressmen Davis and Burgess Introduce the Sickle Cell Treatment Reauthorization Act of 2014

Congressman Danny K. Davis and Michael C. Burgess support Sickle Cell Treatment Reauthorization Act of 2014! The bill helps to ensure the nation's programs continue to improve life, provide treatment and educate all about sickle cell disease. It also calls for 25 fully funded Sickle Cell Treatment Centers throughout the US.

Baltimore, MD, July 25, 2014 --(PR.com)-- Representatives Danny K. Davis (D-IL) and Michael C. Burgess (R-TX) revealed bipartisan legislation to renew the nation’s programs for research, surveillance, prevention and treatment of Sickle Cell Disease (SCD) for another four years.

Sickle Cell Newborn Screening Program Update

We would like to invite you to join us for a community forum to discuss the Sickle Cell Disease Newborn Screening Program. During this session, you will learn HRSA’s vision for the direction of the program and have the opportunity to provide your feedback.
We will host the same session on two occasions; you are welcome to attend either or both sessions; however, the presentation will be the same. Below and attached are additional details.

 Webinar Information

Date: Wednesday, July 30 and Wednesday, August 6, 2014

Time: 3:00-4:30pm (ET)

Location: Online Webinar: [log in information available when registering]

 If you have any questions, please contact me at smerchant@nichq.org

New Video link – Be the Match for Sickle Cell Disease

Link from CBS CW 46 in Atlanta https://vimeo.com/99527982

Sickle cell in the Medical Literature

1.

Care coordination and unmet specialty care among children with special health care needs.

Boudreau AAPerrin JMGoodman EKurowski DCooley WCKuhlthau K.

Abstract

OBJECTIVES:

Care coordination and the medical home may ensure access to specialty care. Children with special health care needs (CSHCN) have higher rates of specialty care use and unmet need compared with the general pediatric population. We hypothesized that care coordination, regardless of whether it was provided in a medical home, would decrease unmet specialty care needs among CSHCN and that the effect of care coordination would be greater among low-income families.

METHODS:

Secondary data analysis of participants in the 2009–2010 National Survey of CSHCN who reported unmet specialty care needs and for whom care coordination and medical home status could be determined (n = 18 905). Logistic regression models explored the association of unmet need with care coordination and medical home status adjusting for household income.

RESULTS:

Approximately 9% of CSHCN reported having unmet specialty care needs. Care coordination was associated with reduced odds of unmet specialty care need (without a medical home, odds ratio: 0.63, 95% confidence interval: 0.47–0.86; within a medical home, odds ratio: 0.22, 95% confidence interval: 0.16–0.29) with a greater reduction among those receiving care coordination within a medical home versus those receiving care coordination without a medical home. We did not find differences in the impact of care coordination by percentage of the federal poverty level.

CONCLUSIONS:

Care coordination is associated with family report of decreased unmet specialty care needs among CSHCN independent of household income. The effect of care coordination is greater when care is received in a medical home.

 decreased avoidable hospitalizations. Pediatr Blood Cancer © 2014 Wiley Periodicals, Inc.

© 2014 Wiley Periodicals, Inc.

PMID: 24962217 [PubMed - as supplied by publisher]

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1.

Emerg Med Clin North Am. 2014 Aug;32(3):629-647. doi: 10.1016/j.emc.2014.04.011. Epub 2014 Jun 7.

Sickle Cell Disease in the Emergency Department.

Lovett PB1Sule HP2Lopez BL1.

Abstract

Acute painful episodes are the most common reason for emergency department visits among patients with sickle cell disease (SCD). Early and aggressive pain management is a priority. Emergency providers (EPs) must also diagnose other emergent diagnoses in patients with SCD and differentiate them from vaso-occlusive crisis. EPs should be aware of cognitive biases that may misdirect the diagnostic process. Administration of intravenous fluids should be used judiciously. Blood transfusion may be considered. Coordination of care with hematology is an important part of the effective emergency department and long-term management of patients with SCD.

Copyright © 2014 Elsevier Inc. All rights reserved.

PMID: 25060254 [PubMed - as supplied by publisher]

 

2.

JAMA. 2014 Jul 2;312(1):48-56. doi: 10.1001/jama.2014.7192.

Nonmyeloablative HLA-Matched Sibling Allogeneic Hematopoietic Stem Cell Transplantation for Severe Sickle Cell Phenotype.

Hsieh MM1Fitzhugh CD1Weitzel RP1Link ME1Coles WA1Zhao X2Rodgers GP1Powell JD3Tisdale JF1.

Abstract

IMPORTANCE:

Myeloablative allogeneic hematopoietic stem cell transplantation (HSCT) is curative for children with severe sickle cell disease, but toxicity may be prohibitive for adults. Nonmyeloablative transplantation has been attempted with degrees of preparative regimen intensity, but graft rejection and graft-vs-host disease remain significant.

OBJECTIVE:

To determine the efficacy, safety, and outcome on end-organ function with this low-intensity regimen for sickle cell phenotype with or without thalassemia.

DESIGN, SETTING, AND PARTICIPANTS:

From July 16, 2004, to October 25, 2013, 30 patients aged 16-65 years with severe disease enrolled in this nonmyeloablative transplant study, consisting of alemtuzumab (1 mg/kg in divided doses), total-body irradiation (300 cGy), sirolimus, and infusion of unmanipulated filgrastim mobilized peripheral blood stem cells (5.5-31.7 × 106 cells/kg) from human leukocyte antigen-matched siblings.

MAIN OUTCOMES AND MEASURES:

The primary end point was treatment success at 1 year after the transplant, defined as a full donor-type hemoglobin for patients with sickle cell disease and transfusion independence for patients with thalassemia. The secondary end points were the level of donor leukocyte chimerism; incidence of acute and chronic graft-vs-host disease; and sickle cell-thalassemia disease-free survival, immunologic recovery, and changes in organ function, assessed by annual brain imaging, pulmonary function, echocardiographic image, and laboratory testing.

RESULTS:

Twenty-nine patients survived a median 3.4 years (range, 1-8.6), with no nonrelapse mortality. One patient died from intracranial bleeding after relapse. As of October 25, 2013, 26 patients (87%) had long-term stable donor engraftment without acute or chronic graft-vs-host disease. The mean donor T-cell level was 48% (95% CI, 34%-62%); the myeloid chimerism levels, 86% (95% CI, 70%-100%). Fifteen engrafted patients discontinued immunosuppression medication with continued stable donor chimerism and no graft-vs-host disease. The normalized hemoglobin and resolution of hemolysis among engrafted patients were accompanied by stabilization in brain imaging, a reduction of echocardiographic estimates of pulmonary pressure, and allowed for phlebotomy to reduce hepatic iron. The mean annual hospitalization rate was 3.23 (95% CI, 1.83-4.63) the year before, 0.63 (95% CI, 0.26-1.01) the first year after, 0.19 (95% CI, 0-0.45) the second year after, and 0.11 (95% CI, 0.04-0.19) the third year after transplant. For patients taking long-term narcotics, the mean use per week was 639 mg (95% CI, 220-1058) of intravenous morphine-equivalent dose the week of their transplants and 140 mg (95% CI, 56-225) 6 months after transplant. There were 38 serious adverse events: pain and related management, infections, abdominal events, and sirolimus related toxic effects.

CONCLUSIONS AND RELEVANCE:

Among 30 patients with sickle cell phenotype with or without thalassemia who underwent nonmyeloablative allogeneic HSCT, the rate of stable mixed-donor chimerism was high and allowed for complete replacement with circulating donor red blood cells among engrafted participants. Further accrual and follow-up are required to assess longer-term clinical outcomes, adverse events, and transplant tolerance.

TRIAL REGISTRATION:

clinicaltrials.gov Identifier: NCT00061568.

PMID: 25058217 [PubMed - in process]

Related citations

 

3.

J Pain Symptom Manage. 2014 Jul 21. pii: S0885-3924(14)00361-3. doi: 10.1016/j.jpainsymman.2014.06.007. [Epub ahead of print]

Sickle Cell Disease Patients With and Without Extremely High Hospital Use: Pain, Opioids, and Coping.

Brown SE1Weisberg D2Balf-Soran G2Sledge W2.

Abstract

CONTEXT:

Patients with sickle cell disease (SCD) and extremely high hospital use (EHHU) encounter significant challenges in pain management because of opioid medication use for pain and providers' concerns about addiction.

OBJECTIVES:

To characterize engagement with the health care system surrounding opioid pain management among SCD patients with EHHU by comparing their experiences with low hospital-utilizing patients and their medical providers' perspectives.

METHODS:

One-on-one, semi-structured qualitative interviews with patients and medical providers were audiotaped and transcribed. Participants were eight SCD patients with EHHU, matched by age, gender, and hemoglobinopathy type with eight SCD patients with low hospital use, and five providers identified by patients with EHHU as important to their care. A multidisciplinary team conducted chart review, created narrative summaries from the interviews and used qualitative software to code transcripts based on themes.

RESULTS:

High and low hospital-utilizing patients had similar descriptions of their experience of pain and pain management with opioids. Patients and medical providers shared concerns about addiction. Low hospital-utilizing patients described themselves as allies using specific interpersonal and symptom-related strategies, whereas high hospital-utilizing patients took a defensive and reactive stance toward their providers, who were similarly defensive about their care.

CONCLUSION:

The prescription of opioid medications for SCD pain management exacerbates issues of distrust in the patient-provider relationship. Such issues dominate patient care in patients with EHHU. Patients with EHHU and providers may learn from the proactive nature of low hospital-utilizing patients' engagement with the health care system as further research and interventions are designed for EHHU.

Copyright © 2014 U.S. Cancer Pain Relief Committee. Published by Elsevier Inc. All rights reserved.

PMID: 25057985 [PubMed - as supplied by publisher]

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4.

Pain Manag Nurs. 2014 Jul 18. pii: S1524-9042(14)00095-2. doi: 10.1016/j.pmn.2014.06.001. [Epub ahead of print]

Self-Efficacy, Transition, and Patient Outcomes in the Sickle Cell Disease Population.

Molter BL1Abrahamson K2.

.

Abstract

Severe pain is a common symptom of sickle cell disease (SCD). Transitions between adult and pediatric care are a point of particular vulnerability for patients, increasing the risk for poor pain management. The purpose of this literature review was to investigate the relationships among self-efficacy, transition, and SCD health outcomes. A systematic literature search was performed within CINAHL, Academic Search Premier, MEDLINE, and PubMed on published papers between 2003 and 2013. After applying exclusion criteria, 20 articles were used in the final review. Few studies were identified that directly tested the relationship between self-efficacy and SCD outcomes. Although there are few studies on this topic, most demonstrated positive correlations between self-efficacy during transition and positive patient outcomes in the SCD population. Additional studies are needed to support causation. Studies were commonly limited by small sample sizes and attrition. Furthermore, there is a large gap in the literature regarding how self-efficacy can be increased in these patients. Interventions that promote self-efficacy have the potential to improve SCD pain outcomes, but more research is needed to develop interventions to increase these adolescents' self-efficacy. If providers can identify individuals in this population with low self-efficacy, they may be able to intervene early to improve patient outcomes. Most identified studies point to the positive correlation between self-efficacy and positive health outcomes in adolescents with SCD. Self-efficacy has the potential to guide self-care interventions and further research with the SCD population.

Copyright © 2014 American Society for Pain Management Nursing. Published by Elsevier Inc. All rights reserved.

PMID: 25047808 [PubMed - as supplied by publisher]

Related citations

 

5.

BMC Psychiatry. 2014 Jul 21;14(1):207. [Epub ahead of print]

Sleep disturbance, depression and pain in adults with sickle cell disease.

Wallen GRMinniti CPKrumlauf MEckes EAllen DOguhebe ASeamon CDarbari DSHildesheim MYang L,Schulden JDKato GJTaylor JG 6th.

Abstract

BACKGROUND:

Sleep disturbance and depression are commonly encountered in primary care. In sickle cell disease, depression is associated with pain, poor treatment compliance, and lower quality of life. The prevalence of sleep disturbance and its effect upon quality of life in adults with sickle cell disease is unknown. The goal of this study was to determine the prevalence of sleep disturbance and if it is associated with pain and depression in sickle cell disease.

METHODS:

Three hundred twenty eight adults with sickle cell disease enrolled on the Bethesda Sickle Cell Cohort Study were assessed using the Pittsburgh Sleep Quality Index and Beck Depression Inventory II screening measures as a cross-sectional survey. Scores greater than 5 (Pittsburgh Sleep Quality Index) and 16 (Beck Depression Inventory II) defined sleep disturbance and depression, respectively. Clinical and laboratory parameters were also assessed.

RESULTS:

The mean Pittsburgh Sleep Quality Index score was 8.4 (SD +/- 4.2) indicating a 71.2% prevalence of sleep disturbance. The mean Beck Depression Inventory II score was 8.0 (SD +/- 8.9). Sixty five (20.6%) participants had a score indicating depression, and half of these (10.0%) had thoughts of suicide. Both Pittsburgh Sleep Quality Index and Beck Depression Inventory II scores were significantly correlated (p < .001). The number of days with mild/moderate pain (p = .001) and a history of headaches (p = .005) were independently associated with depression by multivariate regression analysis. Patients with sleep disturbance were older (p = .002), had higher body mass index (p = .011), had more days of pain (p = .003) and more frequent severe acute painful events (emergency room visits and hospitalizations) during the previous 12 months (p < .001).

CONCLUSIONS:

More than 70 percent of adults with sickle cell disease had sleep disturbance, while 21 percent showed evidence of clinical depression. Sleep disturbance and depression were correlated, and were most common among those with more frequent pain. Providers caring for adults with sickle cell disease and frequent pain should consider screening for these common co-morbidities. Additional study is needed to confirm these findings and to determine if treatments for pain, depression or sleep disturbances will improve quality of life measures in this patient population.Trial registration: ClinicalTrials.gov identifier: NCT00011648.

Free Article

PMID: 25047658 [PubMed - as supplied by publisher]

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6.

Pediatr Pulmonol. 2014 Jul 10. doi: 10.1002/ppul.23074. [Epub ahead of print]

Sleep pathology characterization in sickle cell disease: Case-control study.

Mascarenhas MI1Loureiro HCFerreira TDias A.

.

Abstract

BACKGROUND:

Children and adolescents with sickle cell disease (SCD) have a higher incidence of sleep pathology and obstructive sleep apnea syndrome (OSAS). The nocturnal hypoxemia is a risk to vaso-occlusive crisis among other SCD morbidities. Our aim was to compare polysomnography (PSG) results in a sample of children with SCD with a sample of children with suspected OSAS without SCD.

DESIGN AND METHODS:

A retrospective study compared clinical and PSG parameters. A descriptive analysis and t-test were done considering P < 0.05 as significant.

RESULTS:

PSG was done in 65 children with SCD and 65 control-children. Control sample was selected to be equal to SCD sample considering gender (53.8% were male), age (mean age was 9.4 years (SD ± 4.6) and AHI (mean 3.57 events/hr). Mean efficiency, latency and percentage of sleep phases in both groups showed no statistically significant differences. Mean SpO2 and minimum SpO2 were lower in SCD group and it was statistically significant (P < 0.01). Enuresis was more frequent in the SCD children group (35.4% vs. 6.2%, P < 0.01).

CONCLUSION:

Comparing children with and without SCD, sleep architecture was similar in both groups and minimum SpO2 was significantly lower in SCD children although both groups had a similar AHI. This is an important issue in these children, so it is essential to have a sleep evaluation in order to prevent complications and co-morbidities. Pediatr Pulmonol. © 2014 Wiley Periodicals, Inc.

© 2014 Wiley Periodicals, Inc.

PMID: 25045078 [PubMed - as supplied by publisher]

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Icon for John Wiley & Sons, Inc. 

 

7.

Br J Haematol. 2014 Jul 14. doi: 10.1111/bjh.13031. [Epub ahead of print]

Regular automated red cell exchange transfusion in the management of pulmonary hypertension in sickle cell disease.

Tsitsikas DA1Seligman HSirigireddy BOdeh LNzouakou RAmos RJ.

Author information: 
1Haemoglobinopathy Service, Department of Haematology, Homerton University Hospital NHS Foundation Trust, London, UK. Dimitris.Tsitsikas@homerton.nhs.uk.

PMID: 25041505 [PubMed - as supplied by publisher]

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8.

J Law Med Ethics. 2014 Jun;42(2):139-46. doi: 10.1111/jlme.12129.

Treating pain in sickle cell disease with opioids: clinical advances, ethical pitfalls.

Smith WR.

Author information: 
Professor in the Division of General Internal Medicine and the Principal Investigator for the VCU Basic and Translational Research Program in Sickle Cell Disease at the VCU Sickle Cell Disease Outcomes Research Center, SCD Clinical Research Network.

Abstract

This article explores the ethical principles of prescribing in Sickle Cell Disease. The first two sections of the article provide detailed scientific justification for the last section of the manuscript, which explores and discusses the ethical principles.

© 2014 American Society of Law, Medicine & Ethics, Inc.

PMID: 25040377 [PubMed - in process]

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Icon for Blackwell Publishing 

 

9.

J Law Med Ethics. 2014 Jun;42(2):135-8. doi: 10.1111/jlme.12128.

Prevention of stroke in sickle cell anemia.

Adams RJ.

Author information: 
University Eminent Scholar, Professor of Neuroscience, and SmartState Endowed Chair at the South Carolina Center for Economic Excellence in Stroke at the Medical University of South Carolina in Charleston, SC.

Abstract

The risk of stroke for a child with SCD is many times greater than that of a healthy child without SCD or heart disease. There is a technique that allows the identification of the children with SCD who have high risk even within this relatively high-risk group. And there is a highly effective preventive treatment. While this would on the surface appear to be a straightforward medical decision, it is not. One must weigh the benefits of preventing permanent brain damage against the risks of infection from transfused blood, iron overload, which is the result of the frequent transfusions, and rare transfusion reactions.

© 2014 American Society of Law, Medicine & Ethics, Inc.

PMID: 25040376 [PubMed - in process]

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Icon for Blackwell Publishing 

 

10.

Eur J Haematol. 2014 Jul 10. doi: 10.1111/ejh.12411. [Epub ahead of print]

Sickle Cell Disease in children: chronic complications and search of predictive factors for adverse outcomes.

Silva IV1Reis AFPalaré MJFerrão ARodrigues TMorais A.

Author information: 
1Department of Paediatrics, Hospital Vila Franca de Xira, Portugal.

Abstract

BACKGROUND:

Sickle cell disease (SCD) has extremely variable phenotypes and several factors have been associated with the severity of the disease OBJECTIVES: To analyse the chronic complications of SCD and look for predictive risk factors for increased severity and number of complications METHODS: Retrospective study including all children followed for SCD in the Paediatric Haematology Unit of a tertiary hospital in Portugal, who completed 17 years old between the years 2004 to 2013 RESULTS: We identified 44 patients, 55% female and 98% black. Chronic complications occurred in 80% of cases. Slight dilatation of the left ventricle was the most frequent complication (47.7%), followed by respiratory function disturbs (43.2%), microlithiasis or cholelithiasis (40.9%), increased flow velocity of cerebral arteries (31.8%), enuresis, delayed puberty and bone abnormalities (6.8% each), sickle cell retinopathy and leg ulcer (4.6% each) and recurrent priapism (2.3%). We identified a statistically significant association between leukocytes >15000/μL and a higher number of hospitalizations (p<0.001) and chronic complications of the disease (p=0.035). The occurrence of dactylitis in first year of life was also significantly associated with a higher number of hospitalizations (p=0.004) and chronic complications (p=0.018). The presence of α-thalassemia was associated with a lower number of chronic complications (p=0.036) CONCLUSIONS: Leucocytosis and dactylitis in the first year of life can be predictors of SCD severity while the presence of α-thalassemia can be protective. The determination of early predictors of chronic complications of SCD may improve the comprehensive care of these patients. This article is protected by copyright. All rights reserved.

This article is protected by copyright. All rights reserved.

PMID: 25039473 [PubMed - as supplied by publisher]

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Sickle Cell News for June 2014

Incorporation of Patient Perspective on Disease and Treatment Options Critical in Drug Development and Review

06.18.14 | By Kristin Van Goor http://www.phrma.org/catalyst/first-technology-pilot-program-shares-perspective-of-sickle-cell-disease-community-with-fda

For the first Patient-Focused Drug Development pilot project, Genetic Alliance, in collaboration with PhRMA, partnered with four community-based organizations concerned with patient experience and their needs and treatment goals for sickle cell disease: North Alabama Sickle Cell Foundation, Inc.; Sickle Cell Disease Association of America Southern Connecticut; William E. Proudford Sickle Cell Fund; and Citizens for Quality Sickle Cell Care

Sickle cell disease, a genetic disease, affects approximately 100,000 Americans and millions of people throughout the world.  Sickle cell disease is a major public health concern and the need for innovative medicines to treat this disease is great.  It is hoped that the information provided by patients and their families and gathered by Genetic Alliance, in partnership with the community-based groups, will further the understanding of sickle cell disease, the daily experience of and challenges for patients with the disease, and the patient perspective on the need for new treatment options.

Using the PEER system, we were able to engage a diverse group of individuals with sickle cell disease and their families.  The PEER system allows each participant to select who can access their data and allows them to modify the access over time as their preferences change.   In addition, participants were able to not only address the questions put forward by the Food and Drug Administration (FDA) but also able to propose new questions and issues that are important to the community.

The information gathering process engaged more than 120 individuals across the country.  The top two symptoms experienced by the participants included pain and fatigue or tiredness.  More than half of those surveyed reported that symptoms affected their ability to sleep through the night, to participate in physical activity, and to withstand weather changes.  Symptoms also impacted the ability to complete tasks at home, enjoy life, and/or attend work or school.  On an individual’s worst days, any type of physical activity or activity related to cognition was affected.  Of note, because individuals do not see themselves as sickle cell patients per se, respondents focused more on how treatments affect them, rather than how the disease affects them.

Nearly half of participants reported fatigue as a side effect of their treatment plan that negatively impacts their daily life the most, followed by pain, constipation and insomnia.  Participants indicated that being treated like a drug seeker was the most common problem when trying to comply with their prescribed treatment plan.  Individuals also noted the frequent clinic visits and blood draws as problems. 

A great majority (89%) of individuals would either agree or possibly agree to participate in a clinical trial even if the trial would not directly benefit themselves.  However, if participation in the clinical trial required the individual to stop their current treatment, the willingness to join a clinical trial drops by approximately ten per cent.  Factors that would improve clinical trial participation included being matched with another trial participant for support (87%), a clear explanation of the value of the trial (77%), receiving a summary of the outcome (65%), and frequent communications about trial milestones (56%).

The sickle cell disease community is passionate about finding efficacious treatments for sickle cell disease. They are committed to working with industry and federal agencies, such as FDA and the National Institutes of Health, to achieve that goal within a participatory and patient–centered framework achieved through partnerships with individuals affected by the specific disease being targeted for drug development. Toward that end, they are willing to share clinical data about themselves and their disease.  However, our work shows that they want to participate fully in the data collection in a dynamic manner that is mindful of privacy.

- See more at: http://www.phrma.org/catalyst/first-technology-pilot-program-shares-perspective-of-sickle-cell-disease-community-with-fda#sthash.NHY418uq.dpuf

The survey is available through the websites of Sickle Cell Disease Advocacy organizations:  http://www.scdaaofsouthernct.org/

The Sickle Cell Disease Association of America is kicking off a new campaign to build participation in World Sickle Cell Awareness Day which takes place on June 19, 2014.  See the PDF link by clicking here

A new sickle cell disease clinic at the University of Mississippi Medical Center will help patients get swift, specialized care to relieve their chronic and often excruciating pain - http://www.clarionledger.com/story/news/2014/06/22/ummc-opens-clinic-sickle-cell-patients/11247285/

Young Soccer Fan With Sickle Cell Anemia Goes to World Cup, Thanks to Make-a-Wish http://www.nbcnewyork.com/news/local/Brooklyn-Soccer-Fan-Sickle-Cell-Anemia-World-Cup-Brazil-Make-a-Wish-264066041.html

Free content from across BMJ to mark World Sickle Cell Day

We've selected a number of our products to showcase for the rest of the month to mark World Sickle Cell Day. Read on for free access to journal content, the latest haematology jobs from BMJ Careers and information on our Sickle cell anaemia monograph. See the link http://journals.bmj.com/site/marketing/landing-pages/Sicklecellday_2014.xhtml

New Audio Link -  Educate And Ask: Key To Living With Sickle Cell Disease http://wvpublic.org/post/educate-and-ask-key-living-sickle-cell-disease

 

New Video link – Be the Match for Sickle Cell Disease

Link from CBS CW 46 in Atlanta https://vimeo.com/99527982

 

Sickle cell in the Medical Literature

1.

Pediatr Blood Cancer. 2014 Jun 24. doi: 10.1002/pbc.25024. [Epub ahead of print]

Impact of individualized pain plan on the emergency management of children with sickle cell disease.

Krishnamurti L1, Smith-Packard B, Gupta A, Campbell M, Gunawardena S, Saladino R.

Author information:
1Division of Hematology/Oncology Children's Hospital of Pittsburgh of UPMC, Pittsburgh, Pennsylvania.

Abstract

BACKGROUND:

Vaso-occlusive crisis (VOC) the hallmark of sickle cell disease (SCD) is often treated inadequately in the emergency department (ED). We hypothesized that pain management plans individualized for each patient can improve pain management and lead to high levels of patient satisfaction.

PROCEDURE:

Starting in 2002, we treated all patients with SCD reporting to Children's Hospital of Pittsburgh (CHP) ED with VOC using a structured algorithm. We recorded regimens used successfully for each patient as an "individualized pain plan" and implemented it during subsequent VOC visits and adjusted it to patient response. We compared rates of hospitalization following an ED visit with VOC and readmission within 1 week after discharge for CHP with that of four comparable hospitals from Pediatric Health Information (PHIS) database. Patients and parents completed surveys of satisfaction with pain management and with care.

RESULTS:

Between 2002 and 2008 there was a greater decline in the rate of admission of patients presenting to the ED at CHP (78% to 52%) as compared to PHIS (71% to 68%), (P < 0.05) and readmission rates at CHP (7.3% to 3.2%) as compared to PHIS (6.5% to 5.1%) (P < 0.05). Improvement in pain score during ED management was 2.0 or more on a Wong Baker scale of 0-5 (P < 0.01). Participants on average, rated quality of pain management as very good or higher.

CONCLUSION:

Individualized pain management plans in the ED are effective in delivering high quality management of VOC and are associated with a high level of patient satisfaction and decreased avoidable hospitalizations. Pediatr Blood Cancer © 2014 Wiley Periodicals, Inc.

© 2014 Wiley Periodicals, Inc.

PMID: 24962217 [PubMed - as supplied by publisher]

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2.

Hemoglobin. 2014 Jun 18:1-8. [Epub ahead of print]

Comparison of Patients from Nigeria and the USA Highlights Modifiable Risk Factors for Sickle Cell Anemia Complications.

Akingbola TS1, Tayo BO, Salako B, Layden JE, Hsu LL, Cooper RS, Gordeuk VR, Saraf SL.

Author information:
1Department of Haematology, University of Ibadan , Ibadan, Oyo , Nigeria .

Abstract

Abstract To identify factors that affect manifestations of sickle cell anemia we compared patients 11-30 years of age from University of Ibadan, Ibadan, Oyo, Nigeria (n = 214) and University of Illinois at Chicago, Chicago, IL, USA (n = 209). Paralleling findings in the general populations of the two countries, the Chicago patients were more often overweight or obese as defined by the Centers for Disease Control and Prevention (Atlanta, GA, USA) guidelines, and more often had elevated blood pressure (BP) as defined by the National Heart, Lung, and Blood Institute (NHLBI), Bethesda, MD, USA guidelines. The Ibadan patients did not receive the pneumococcal vaccine or hydroxyurea (HU) therapy as frequently as the Chicago patients. Consistent with lower rates of elevated BP and increased body mass index (BMI), stroke history was less frequent in the Ibadan patients ≥18 years old. Furthermore, in combined analyses, systolic and diastolic BP directly correlated with BMI, and elevated weight status independently associated with history of stroke. Our findings are consistent with the possibility that higher values for BMI and BP in Chicago sickle cell anemia patients may contribute to an increased risk of stroke and highlights the need for measures to reduce these risk factors. On the other hand, lower pneumococcal vaccination and HU therapy rates in Ibadan patients highlights the need for more improved vaccination coverage and for studies to define the role of HU therapy in Africa.

PMID: 24941131 [PubMed - as supplied by publisher]

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3.

Blood. 2014 Jun 9. pii: blood-2013-12-545186. [Epub ahead of print]

Magnetic resonance imaging/angiography and transcranial Doppler velocities in sickle cell anemia: results from the SWiTCH trial.

Helton KJ1, Adams RJ2, Kesler KL3, Lockhart A3, Aygun B4, Driscoll C5, Heeney MM6, Jackson SM2, Krishnamurti L7, Miller ST8, Sarnaik SA9, Schultz WH10, Ware RE10.

Author information:
1St. Jude Children's Research Hospital, Memphis, TN, United States; kathleen.helton@stjude.org.
2Medical University of South Carolina, Charleston, SC, United States;
3Rho Inc., Chapel Hill, NC, United States;
4Cohen Children's Medical Center, New Hyde Park, NY, United States;
5Montefiore Medical Center, New York, NY, United States;
6Children's Hospital Boston, Boston, MA, United States;
7Pittsburgh Children's Hospital, Pittsburgh, PA, United States;
8SUNY-Downstate, Brooklyn, NY, United States;
9Wayne State University, Detroit, MI, United States;
10Cincinnati Children's Hospital, Cincinnati, OH, United States.

Abstract

Stroke With Transfusions Changing to Hydroxyurea (SWiTCH) compared standard (transfusions/chelation) to alternative (hydroxyurea/phlebotomy) treatment to prevent recurrent stroke and manage iron overload in children chronically transfused over seven years before enrollment. Standardized brain magnetic resonance imaging/ angiography (MRI/MRA) and transcranial Doppler (TCD) exams were performed at entry and exit with central blinded review. A novel MRA vasculopathy grading scale demonstrated frequent severe baseline left/right vessel stenosis (53%/41% ≥Grade 4); 31% had no vessel stenosis on either side. Baseline parenchymal injury was prevalent (85%/79% subcortical, 53%/37% cortical, 50%/35% subcortical and cortical). Most children had low or uninterpretable baseline middle cerebral artery TCD velocities, which were associated with worse stenoses (IRR=5.1, p=<0.0001 and IRR=4.1, p<0.0001) than normal velocities; only 2-12% had any conditional/abnormal velocity. Adjudicated stroke (7) and TIA (19 in 11 Standard/8 Alternative Arm subjects) had substantial parenchymal injury/vessel stenosis. At exit, one child (Alternative Arm) had a new silent infarct, another had worse stenosis. SWiTCH neuroimaging data document severe parenchymal and vascular abnormalities in children with SCA and stroke, and support concerns about chronic transfusions lacking effectiveness for preventing progressive cerebrovascular injury. The novel SWiTCH vasculopathy grading scale warrants validation testing and consideration for use in future clinical trials. This study was registered at clinicaltrials.gov, identifier: NCT 00122980.

Copyright © 2014 American Society of Hematology.

PMID: 24914136 [PubMed - as supplied by publisher]

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4.

Br J Haematol. 2014 Jan;164(1):124-30. doi: 10.1111/bjh.12594. Epub 2013 Oct 8.

Moderate endurance exercise in patients with sickle cell anaemia: effects on oxidative stress and endothelial activation.

Faes C1, Balayssac-Siransy E, Connes P, Hivert L, Danho C, Bogui P, Martin C, Pialoux V.

Author information:
1CRIS EA647, Université de Lyon 1, Villeurbanne, France.

Abstract

Very few studies have investigated the effects of exercise on the biological parameters involved in vaso-occlusive events in sickle cell anaemia (SCA). The aim of this study was to test how a mild-moderate endurance exercise modulates oxidative stress, nitric oxide bioavailability and endothelial activation in SCA patients and healthy individuals. Eleven patients with SCA and 15 healthy subjects completed a 20-min duration submaximal cycling exercise at ≈45 Watts. Plasma markers of oxidative stress, antioxidant activity, endothelial activation and nitric oxide bioavailability were investigated before and after the exercise. Nitric oxide levels, anti-oxidant capacity, soluble (s)E-selectin and sP-selectin did not change in response to this exercise. Except for the malondialdehyde levels, which increased in the two groups, the other markers of oxidative stress remained unchanged in both groups in response to exercise. Soluble vascular cell adhesion molecule 1 levels were increased at the end of exercise in both groups. sL-selectin decreased and soluble intercellular adhesion molecule 1 increased with exercise in SCA patients only. The present data suggest that patients with SCA may undertake mild-moderate physical activities without any acute clinical complications, but care should be taken because oxidative stress and endothelial activation significantly increased in some patients.

© 2013 John Wiley & Sons Ltd.

PMID: 24903630 [PubMed - in process]

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5.

Am J Hematol. 2014 May 31. doi: 10.1002/ajh.23777. [Epub ahead of print]

Reticulocytosis and anemia are associated with an increased risk of death and stroke in the newborn cohort of the Cooperative Study of Sickle Cell Disease.

Meier ER1, Wright EC, Miller JL.

Author information:
1Molecular Medicine Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland, 20892; Center for Cancer and Blood Disorders, Children's National Medical Center, Washington, D.C., 20010; Department of Pediatrics, The George Washington University School of Medicine and Health Sciences, Washington, D.C., 20037.

Abstract

Prior analyses of the Cooperative Study of Sickle Cell Disease (CSSCD) newborn cohort identified elevated white blood cell (WBC) count, low baseline hemoglobin and dactylitis between the ages of 1 and 2 years as markers of severe disease. Reticulocytosis was also associated with severe disease. Here, we further analyzed data collected on enrolled CSSCD infants for the predictive value of those markers for stroke and death later in life. Three hundred fifty-four CSSCD subjects were identified who had absolute reticulocyte counts (ARC) measured during infancy (2 to 6 months of age). Infants with higher ARC had significantly increased risk of stroke or death during childhood; lower hemoglobin levels also increased the risk but to a lesser degree than ARC. WBC levels and dactylitis were not predictive of death or stroke. These data suggest that reticulocytosis among asymptomatic infants with sickle cell anemia is associated with an increased risk of death or stroke during childhood. Am. J. Hematol., 2014. © 2014 Wiley Periodicals, Inc.

Copyright © 2014 Wiley Periodicals, Inc.

PMID: 24891147 [PubMed - as supplied by publisher]

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6.

PLoS One. 2014 May 30;9(5):e97462. doi: 10.1371/journal.pone.0097462. eCollection 2014.

Severe nocturnal and postexercise hypoxia in children and adolescents with sickle cell disease.

Halphen I1, Elie C2, Brousse V3, Le Bourgeois M4, Allali S3, Bonnet D5, de Montalembert M6.

Author information:
1Pediatric Emergency Department, Hospital Necker, APHP, Paris, France.
2Paris Descartes University, Paris, France; Department of Biostatistics, Hospital Necker, APHP, Paris, France.
3Pediatrics Department and Sickle Cell Clinic, Hospital Necker, AP-HP, Paris, France.
4Pediatric Pneumology and Allergology Department, Hospital Necker, APHP, Paris, France.
5Paris Descartes University, Paris, France; Pediatric Cardiology Department, M3C-Necker, AP-HP, Paris, Paris Descartes University, France.
6Paris Descartes University, Paris, France; Pediatrics Department and Sickle Cell Clinic, Hospital Necker, AP-HP, Paris, France.

Abstract

Hypoxia is a common feature in children with sickle cell disease (SCD) that is inconsistently associated with painful crises and acute chest syndrome. To assess the prevalence and risk factors of hypoxia, we recorded daytime, nocturnal, and postexercise pulse oximetry (SpO2) values in 39 SCD patients with a median age of 10.8 years. Median daytime SpO2 was 97% (range, 89%-100%), and 36% of patients had daytime hypoxia defined as SpO2<96%. Median nocturnal SpO2 was 94.7% (range, 87.7%-99.5%), 50% of patients had nocturnal hypoxia defined as SpO2≤93%, and 11(37%) patients spent more than 10% of their total sleep time with SpO2<90%. Median postexercise SpO2 was 94% (range, 72%-100%) and 44.7% of patients had postexercise hypoxia defined as an SpO2 decrease ≥3% after a 6-minute walk test. Among patients with normal daytime SpO2, 35% had nocturnal and 42% postexercise hypoxia. Compared to 9 patients without daytime, nocturnal, or postexercise hypoxia, 25 patients with hypoxia under at least one of these three conditions had greater anemia severity (P = 0.01), lower HbF levels (P = 0.04), and higher aspartate aminotransferase levels (P = 0.03). Males predominated among patients with postexercise hypoxia (P = 0.004). Hypoxia correlated neither with painful crises nor with acute chest syndrome. Of 32 evaluable patients, 6 (18.8%) had a tricuspid regurgitation velocity ≥2.6 m/s, and this feature was associated with anemia (P = 0.044). Median percentage of the predicted distance covered during a 6-minute walk test was 86% [46-120]; the distance was negatively associated with LDH (P = 0.044) and with a past history of acute chest syndrome (P = 0.009). In conclusion, severe episodes of nocturnal and postexercise hypoxia are common in children with SCD, even those with normal daytime SpO2.

PMCID: PMC4039516 Free PMC Article

PMID: 24878576 [PubMed - in process]

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7.

Br J Haematol. 2014 May 26. doi: 10.1111/bjh.12950. [Epub ahead of print]

The spleen and sickle cell disease: the sick(led) spleen.

Brousse V1, Buffet P, Rees D.

Author information:
1Department of Paediatrics, Reference Centre for Sickle Cell Disease, Hôpital Universitaire Necker-Enfants Malades, APHP, Paris, France; Université Paris Descartes, Paris, France; Laboratory of Excellence GR-Ex, Paris, France.

Abstract

The spleen has a combined function of immune defence and quality control of senescent or altered red cells. It is the first organ injured in sickle cell anaemia (SCA) with evidence of hyposplenism present before 12 months in the majority of children. Repeated splenic vaso-occlusion leads to fibrosis and progressive atrophy of the organ (autosplenectomy), which is generally complete by 5 years in SCA. The precise sequence of pathogenic events leading to hyposplenism is unknown. Splenic injury is generally silent and progressive. It can be clinically overt with acute splenic sequestration of red cells, an unpredictable and life-threatening complication in infants. Splenomegaly, with or without hypersplenism, can also occur and can coexist with loss of function. Hyposplenism increases the susceptibility of SCA children to infection with encapsulated bacteria, which is notably reduced by penicillin prophylaxis and immunization. Whether hyposplenism indirectly increases the risk of vaso-occlusion or other circulatory complications remains to be determined.

© 2014 John Wiley & Sons Ltd.

PMID: 24862308 [PubMed - as supplied by publisher]

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8.

Eur J Haematol. 2014 May 3. doi: 10.1111/ejh.12361. [Epub ahead of print]

Predictors of splenic function preservation in children with sickle cell anemia treated with hydroxyurea.

Nottage KA1, Ware RE, Winter B, Smeltzer M, Wang WC, Hankins JS, Dertinger SD, Shulkin B, Aygun B.

Author information:
1Department of Hematology, St. Jude Children's Research Hospital, Memphis, TN, USA.

Abstract

BACKGROUND:

More than 90% of children with sickle cell anemia (SCA) lose splenic function by the age of 2 yrs. Splenic function may improve with hydroxyurea, but previous studies are conflicting. We prospectively evaluated the effect of hydroxyurea on splenic filtrative function.

METHODS:

Children with SCA enrolled in the Hydroxyurea Study of Long-Term Effects (HUSTLE-NCT00305175) underwent clinical evaluations including Tc99 m liver-spleen (LS) scans before hydroxyurea initiation and after 3 yrs of treatment to maximum tolerated dose (MTD). LS scans were classified as follows: no uptake, <10% uptake, decreased but ≥10% uptake, and normal.

RESULTS:

Mean age (N = 40) was 9.1 yrs, range 2.3-17.0. After 3 yrs of treatment, 13 (33%) had uptake on LS scan. These 13 children were younger (median age 6.0 vs. 10.6 yrs, P = 0.008), had a higher HbF at baseline (mean 10.2% vs. 5.8%, P = 0.004) and after 3 yrs (22.9% vs. 13.9%, P < 0.001), achieved MTD more rapidly (median 288 vs. 358 d, P = 0.021), and were more likely to have baseline splenic uptake (P < 0.001).

CONCLUSIONS:

Hydroxyurea at MTD is associated with preserved or improved splenic filtrative function, with 33% demonstrating LS scan uptake after 3 yrs. Younger age, higher %HbF, and baseline splenic function are associated with a favorable outcome.

© 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

PMID: 24796940 [PubMed - as supplied by publisher]

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9.

J Public Health (Oxf). 2014 May 5. [Epub ahead of print]

A retrospective analysis of the cost of hospitalizations for sickle cell disease with crisis in England, 2010/11.

Pizzo E1, Laverty AA, Phekoo KJ, Aljuburi G, Green SA, Bell D, Majeed A.

Author information:
1Business School, Imperial College, London SW72AZ, UK.

Abstract

BACKGROUND:

Sickle cell disease (SCD) is an inherited blood disorder which may result in a broad range of complications including recurring and severe episodes of pain-sickle 'crises'-which require frequent hospitalizations. We assessed the cost of hospitalizations associated with SCD with crisis in England.

METHODS:

Hospital Episodes Statistics data for all hospital episodes in England between 2010 and 2011 recording Sickle Cell Anaemia with Crisis as primary diagnosis were used. The total cost of admissions and exceeded length of stay due to SCD were assessed using Healthcare Resource Groups tariffs. The impact of patients' characteristics on SCD admissions costs and the likelihood of incurring extra bed days were also examined.

RESULTS:

In 2010-11, England had 6077 admissions associated with SCD with crisis as primary diagnosis. The total cost for these admissions for commissioners was £18 798 255. The cost of admissions increases with age (children admissions costs 50% less than adults). Patients between 10 and 19 years old are more likely to stay longer in hospital compared with others.

CONCLUSION:

SCD represents a significant cost for commissioners and the NHS. Further work is required to assess how best to manage patients in the community, which could potentially lead to a reduction in hospital admissions and length of stay, and their associated costs.

PMID: 24796312 [PubMed - as supplied by publisher]

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Sickle Cell Conferences and Events

 

  

Global Sickle Cell Diseases Network Conference: Rio De Janeiro, Brazil, 2014 website www.globalsicklecelldisease.org  the planned April 9-11 meeting of GSCDN and WISSH in Rio de Janeiro has been postponed to November 11-14, 2014The postponement is to enable the GSCDN and WISSH meetings to be held in conjunction with the 2nd Global Congress on Sickle Cell Disease.  Also, there was concern that the April date would be in partial conflict with the 8th  Annual SCD Research and Education Symposium and National Sickle Cell Disease Scientific Meeting in Florida, US on April 11-14, which will for the first time have a major international component. See www.wissh.net  for information as it becomes available.

 

Event: Sickle Cell in Focus (SCiF) Date: Monday 15 – Tuesday 16 September 2014

Venue: National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, Maryland, Washington, USA

This year we have been invited by the National Heart, Lung and Blood Institute (NHLBI) to hold SCiF the National Institutes of Health campus in Bethesda, Maryland USA. This is a fantastic opportunity to visit such a prestigious institution and our plan is to alternate the location yearly between King’s College London and NHLBI. 

SCiF is now in its 8th year the event has become a world-class educational update for sickle cell disease. Over two intensive days we will focus on the treatment and management of sickle cell disease and provide a comprehensive update on recent research news.  It attracts a wide audience of clinicians, academics and other healthcare professionals involved in the disease from around the world.  

To book: Online booking will be open soon.  If you would like to be kept up-to-date, please join the STSTN mailing list by sending an email to: info@ststn.co.uk

Contact details: info@ststn.co.uk / + 44 (0) 20 7848 5441www.ststn.co.uk

 

September 19-20 2014, Duke-UNCConference 2nd Annual Engaging Providers and Families to Improve Care for Individuals with Sickle Cell Conference. Save the dates. More information to follow.

15th Atlanta Annual Sickle Cell Education Day Date:       September 27, 2014 Theme:  Sickle Cell – Let’s Talk!  Time:       Registration    9:00 am – 10:00  am Program10:00 am – 3:00 pm  Location:  Courtyard by Marriott  Decatur  Downtown/Emory  130 Clairemont Avenue Decatur, GA 30030

Sickle Cell News for May 2014

Walsall pop star hails brave teenager battling sickle cell anaemia who recorded Culture Club classic http://www.birminghammail.co.uk/whats-on/music-nightlife-news/boy-george-backing-leesha-macs-7102068

A stroke survivor who is also battling sickle cell anaemia is finally living her dream to become a singer – with the help of Boy George.Leesha McIntosh had to re-learn how to walk and talk after she suffered a stroke when she was just 12 years old.

Now aged 22 Leesha she has just recorded her first song which she has dedicated to sickle-cell sufferers, after her close friend Imani passed away from the genetic blood disorder.And Leesha’s debut record New Love – a re-working of the 1980s Culture Club hit I Want to Be Loved – is being backed by lead singer Boy George.

The internationally acclaimed star took time out from his USA tour to back Leesha’s song.“I wish Lisa all the luck in the world and can’t wait to hear her version of the Culture Club song,” said 52 year-old Boy George, who lived in Walsall as a teenager and sold shoes on Birmingham’s Rag Market.

Leesha, from Handsworth, Birmingham, continues to have monthly blood transfusions to prevent another stroke and she has treatment for the genetic blood disorder sickle cell anaemia.Her illness often leaves her extremely tired and in pain. Her song has become a smash hit in her community after she raised the roof while performing it to more than 250 people at the Drum nightclub recently.She has already been asked to sing there again.“I feel uplifted when I sing,” said Leesha. “It makes me feel that there is hope in the world for Sicklers.

“This single is dedicated to all Sickle Cell and Thalassemia sufferers. I am a sicklier and grateful to God that I’m alive and living proof that we can live with this dreadful disease and still achieve so much in life. I never thought I’d accomplish my dream of becoming the singer I’d always wanted to be.”Leesha was rushed to Birmingham Children’s Hospital when she suffered a stroke in 2004.

She was left unable to walk and talk and her family feared she would never recover. Dad Trevor, 54 said: “She dedicated the song to all the people who suffer with sickle-cell anaemia.

Like Howard University, interim President Wayne A.I. Frederick has faced tough times  http://www.washingtonpost.com/local/interim-president-wayne-ai-frederick-seeks-to-improve-health-of-howard-university/2014/05/20/7db99416-e058-11e3-810f-764fe508b82d_story.html

 

Wayne A.I. Frederick was 16 when he arrived at Howard University from Trinidad in 1988. Bespectacled and frail from a life-and-death struggle with sickle cell anemia, the freshman stood 5 foot 6 and weighed only 88 pounds. And yet, by age 22, he’d not only earned a bachelor’s degree in zoology but also completed medical school. He went on to become associate dean of the medical college. In 2011, he earned a master’s degree in business. Last October, at age 42, the “triple alum” was appointed interim president of his alma mater.

It is a résumé and life journey that seems tailor-made for the challenges he faces.

The prognosis for Howard University is dire, to hear some tell it. A ranking member of the board of trustees warned a year ago that without more intensive care — especially more attention to the flow of money, the school’s life blood — Howard would be dead within three years.

Enter Frederick — a cancer surgeon with an MBA.

Frederick balks at being cast in a doctor-patient relationship with Howard. Nevertheless, during a recent interview, there was no doubt that a physician was on call.

“It’s important for me to be a calm voice in the room, bring my mind to rest in order to make the best decisions,” Frederick said, referring to the challenges posed by the fiscal crisis and political turmoil that had consumed his predecessor, Sidney Ribeau. “When things are going haywire in the operating room, I don’t get to lose my cool, or else I could lose my patient.”

Frederick, who was provost for academic affairs, was prepared to step up when Ribeau stepped down. He’d spent years studying “the anatomy of the university,” as he put it, the way he’d study the human body.

“You have to look at how one part affects the other,” he said. While serving as associate dean of the medical college in 2009, Frederick enrolled in Howard’s MBA program. Being a “consumer” of university services as a student and overhearing classmates speak about their experiences was akin to taking a patient’s pulse and listening to the heartbeat.

“One of the first things we had to do was become more operationally efficient,” Frederick said. “So the long lines and long waits for students to get help in the administration building don’t exist anymore. That has taken away some of the students’ frustrations.”

Probably did wonders for their blood pressure, too.

From a window in the president’s office, Frederick can see the remaining bleachers on “the Yard,” the green acreage at the center of the campus where commencement ceremonies were held earlier this month. More than 2,500 students had graduated — including 105 who received PhDs, the largest doctoral class in Howard’s history.

“I’m obsessed with the educational journey that the students and their families make to get here and where they go after they leave,” Frederick said. He noted the decisive role of Howard lawyers in the landmark Brown v. Board of Education school desegregation case 60 years ago. “Howard students don’t just get a degree. We expect them to use that degree to provide a service to the world and bring that degree to life.”

Just as his mother expected of him.

“What I brought on my journey to Howard was a life of love and support from a mother who had a dream,” he said. “She wanted to become a physician, but at that time her dad didn’t feel that women should become physicians. So she became a nurse. I believe my sickle cell intersected with her dream and made me want to become a physician.”

Frederick was the commencement speaker for the medical school graduation, a kind of 20th-year reunion for him. His mother, Frances Tyson, who is marking her 50th year as a nurse, had flown in from Trinidad for the occasion.

To help Howard students realize their dreams, Frederick believes, Howard needs a more rigorous curriculum and stronger career counseling.

“We’re bringing in professional academic advisers who can monitor a student’s transcripts for strengths and deficits related to what they are trying to accomplish,” he said.

And just because someone has a doctorate in a subject doesn’t mean he or she can teach the subject, he added. So Howard is hiring more faculty members who understand the “technical aspects of teaching,” he said, especially to a new generation of students.

“We have to meet the demands of an increasingly competitive workforce,” Frederick said. “Our students will be seeking jobs and careers where African Americans are underrepresented, where there will be fewer people to advocate on their behalf. So they need a very strong academic environment, the kind of preparation that Charles Drew meant when he said excellence of performance will transcend all boundaries created by man.”

That’s a tall order — especially for a historically black university trying to improve its credit rating on Wall Street and restore its good name, a school that some have all but declared brain-dead.

Then again, Frederick is a doctor. Perhaps more important, he knows what it’s like to be deathly ill, then not only survive but thrive.

“When you’re sick and you’re told that you won’t live to see your eighth birthday, then told you won’t make it to 16, you can get depressed — or you can get motivated,” he said. No doubt about his response.

 

New Web link

Nutrition for the Child with Sickle Cell Anemia at http://www.eatright.org/kids/article.aspx?id=6442480398

 

Sickle Cell Disease Treatment Demonstration Program Frequently Asked Questions the Sickle Cell Disease Treatment Demonstration Program You can find the Grants.gov and the FOA number is HRSA-14-078.  You can also find more information about the FOA athttp://www.hrsa.gov/grants/apply/assistance/sicklecell/

 1.        Can an organization or foundation with a contract with a medical center that meets the eligibility requirements apply to the SCDTDP FOA based on the contract with the medical center?

 

The authorizing legislation is very specific as to its eligible applicants.  Under section (1)(A), the Administrator may make grants “to up to 40 eligible entities,” and under section (5)(B), eligible entities are defined as being:

 

Any Federally-qualified health center, nonprofit hospital or clinic, or university health center that provides primary health care that:

 

(i) has a collaborative agreement with a community-based Sickle Cell Disease organization or a nonprofit entity with experience in working with individuals who have Sickle Cell Disease; and

(ii) demonstrates to the Administrator that either the Federally-qualified health center, the nonprofit hospital or clinic, the university health center, the organization or entity described in clause (i), or the experts described in paragraph (2)(C), has at least 5 years of experience in working with individuals who have Sickle Cell Disease.

 

Given this specificity in the statutory language, a collaborating nonprofit organization is not eligible to apply in its own right unless it meets the criterion of being a “Federally-qualified health center, nonprofit hospital or clinic, or university health center that provides primary health care…” and meets the additional criteria in subsections (i) and (ii).

 

The FOA describes the eligibility requirements, but it is up to the organization to decide whether or not it believes that it satisfies the FOA requirements.  The organization needs to decide whether or not it wishes to submit an application on the basis of its own judgment, and HRSA will make eligibility determinations upon reviewing the information provided by the applicants.

 

2.         Can the primary grantee place a cap on the Indirect cost amount for sub-awards?

 

No, the primary applicant cannot put a cap on the Indirect cost for sub-awards.  The applicant may wish to see if they can negotiate with the sub-awardee to see if they will use the same rate as the grantee, but, if they have a negotiated rate and want to use it, they can.

 

3.         Does the primary applicant need to submit the itemized budget and the CV’s/resumes of the sub-awardees?

 

Yes, the applicant will need to submit the itemized budget and the CV’s/resumes of all of the sub-awardees to HRSA.   Applicants should keep in mind that they will not be penalized if they do not have all of their sub-award agreements in place by the time of the application submission.  The FOA states that the applicant will make sub-awards (agreements) or demonstrate the ability to make sub-awards.  Therefore, if your application demonstrates that you can make the partnership within a reasonable amount of time, then you will not be penalized.   You must make a good faith effort to provide assistance to every state in your region as the regional center. 

 

"What is PCORI and what does it have to do with sickle cell disease”

PCORI is Patient Centered Outcomes Research Institute, a new organization funded by US government to promote a new sense that healthcare should focus on what patients and community stakeholders say.   PCORI is trying to design research and healthcare that are centered on the needs voiced by patients, not just on life expectancy or lab tests or costs for the healthcare industry. This an active areas of healthcare change.

This is the time for the sickle cell community to help healthcare and health research to recognize the needs of sickle cell disease. This is the chance for the  voices and opinions of sickle cell patients to be heard beyond the realm of YouTube statements and Patient Forum discussions that are "preaching to the choir" during sickle cell meetings, and move to forums that can influence the national and regional agenda. 

There are several ways that sickle cell community can get involved in this active area of healthcare change.   Here is a link about signing up to get involved in PCORI   http://www.pcori.org/get-involved/landing/    Attached is a guide to some of the roles in PCORI.  

 In many academic medical centers, the Clinical Research Center funded by NIH has additional roles for patients and families in the Community Engagement Center or Patient Advisory Council. These have very similar goals as PCORI. 

The FDA is looking at sickle cell disease in their program on Patient-Focused Drug Development. A Public Meeting was held in February 7, followed by 2 months of surveys on websites.     Institutional Review Boards (IRB) are always looking for community members to help review medical research protocols.

Sickle cell in the Medical Literature

1.

J Fam Plann Reprod Health Care. 2014 May 23. pii: jfprhc-2013-100763. doi: 10.1136/jfprhc-2013-100763. [Epub ahead of print]

Trends in family planning and counselling for women with sickle cell disease in the UK over two decades.

Eissa AA1Tuck SM2Rantell K3Stott D4.

Abstract

BACKGROUND:

Pregnancies in women with sickle cell disease (SCD) are known to have high rates of maternal and fetal mortality and morbidity. Given these pregnancy-associated problems for women with SCD, advice both about pregnancy planning and about effective contraception are of paramount importance. This study sought to discover the contraception methods used by women with SCD, what complications women with SCD encounter with contraception, and their experiences of pre-pregnancy counselling and pregnancy planning, and how such issues may have changed over the past two decades.

METHOD:

The study was a multicentre, interview-based, cross-sectional study. Interviews were carried out with 102 women with SCD, in north and central London during 2010, concerning their current and previous contraceptive use, their pregnancy history, their menstrual history, and the advice they received concerning pregnancy planning and contraception. Patient information was anonymised and ethical approval was obtained. These data were compared with data from a similar study undertaken in 1993.

RESULTS:

There were significant differences in a number of key areas: the number of unplanned pregnancies decreased from 64% in 1993 to 53% in 2010. The number of women with SCD who were advised not to become pregnant also fell, from 36% to 15%. The use of combined oral contraceptive pills declined, from 45% of the women in 1993 to 31% in 2010. Conversely the use of depot medroxyprogesterone acetate contraception (DMPA) and the levonorgestrel intrauterine system (LNG-IUS) both increased.

CONCLUSIONS:

Significant changes in the contraceptive methods used by women with SCD are demonstrated in the London population. LNG-IUS use in SCD has not been investigated before. There has been an encouraging decrease in the number of women with SCD who are advised not to become pregnant, perhaps reflecting an improvement in their overall health. Although the number of unplanned pregnancies has fallen, it remains high - emphasising the continuing need for women with SCD to have access to informed advice about pregnancy-associated issues and contraception.

Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

PMID: 24860151 [PubMed - as supplied by publisher]

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2.

Am J Hematol. 2014 May 20. doi: 10.1002/ajh.23762. [Epub ahead of print]

The Glomerulopathy of Sickle Cell Disease.

Ataga KI1Derebail VKArcher DR.

Author information: 
1Division of Hematology/Oncology, University of North Carolina, Chapel Hill.

Abstract

Sickle cell disease (SCD) produces many structural and functional abnormalities in the kidney, including glomerular abnormalities. Albuminuria is the most common manifestation of glomerular damage, with a prevalence between 26% and 68% in adult patients. The pathophysiology of albuminuria in SCD is likely multifactorial, with contributions from hyperfiltration, glomerular hypertension, ischemia-reperfusion injury, oxidative stress, decreased NO bioavailability and endothelial dysfunction. Although its natural history in SCD remains inadequately defined, albuminuria is associated with increased echocardiography-derived tricuspid regurgitant jet velocity, systemic blood pressure and hypertension, as well as history of stroke, suggesting a shared vasculopathic pathophysiology. While most patients with albuminuria are treated with angiotensin converting enzyme inhibitors/angiotensin receptor blockers, there are no published long-term data on the efficacy of these agents. With the improved patient survival following kidney transplantation, SCD patients with end-stage renal disease should be considered for this treatment modality. Given the high prevalence of albuminuria and its association with multiple SCD-related clinical complications, additional studies are needed to answer several clinically important questions in a bid to adequately elucidate its pathophysiology, natural history and treatment.

Copyright © 2014 Wiley Periodicals, Inc., A Wiley Company.

PMID: 24840607 [PubMed - as supplied by publisher]

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3.

Cell Host Microbe. 2014 May 14;15(5):587-99. doi: 10.1016/j.chom.2014.04.005.

Genomic analyses of pneumococci from children with sickle cell disease expose host-specific bacterial adaptations and deficits in current interventions.

Carter R1Wolf J2van Opijnen T3Muller M2Obert C2Burnham C2Mann B2Li Y4Hayden RT5Pestina T6Persons D6Camilli A7Flynn PM2Tuomanen EI2Rosch JW8.

Abstract

Sickle cell disease (SCD) patients are at high risk of contracting pneumococcal infection. To address this risk, they receive pneumococcal vaccines, and antibiotic prophylaxis and treatment. To assess the impact of SCD and these interventions on pneumococcal genetic architecture, we examined the genomes of more than 300 pneumococcal isolates from SCD patients over 20 years. Modern SCD strains retained invasive capacity but shifted away from the serotypes used in vaccines. These strains had specific genetic changes related to antibiotic resistance, capsule biosynthesis, metabolism, and metal transport. A murine SCD model coupled with Tn-seq mutagenesis identified 60 noncapsular pneumococcal genes under differential selective pressure in SCD, which correlated with aspects of SCD pathophysiology. Further, virulence determinants in the SCD context were distinct from the general population, and protective capacity of potential antigens was lost over time in SCD. This highlights the importance of understanding bacterial pathogenesis in the context of high-risk individuals.

Copyright © 2014 Elsevier Inc. All rights reserved.

PMID: 24832453 [PubMed - in process]

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4.

Int J Low Extrem Wounds. 2014 May 13. pii: 1534734614534979. [Epub ahead of print]

Autologous Platelet Gel: Five Cases Illustrating Use on Sickle Cell Disease Ulcers.

Gilli SC1Oliveira SA2Saad ST2.

Author information: 
1University of Campinas-UNICAMP, INCT do Sangue, Campinas, São Paulo, Brazilmona@unicamp.br.
2University of Campinas-UNICAMP, INCT do Sangue, Campinas, São Paulo, Brazil.

Abstract

Leg ulcers represent a particularly disabling complication in patients with sickle cell disease (SCD). Platelet gel (PG) is a novel therapeutic strategy used for accelerating wound healing of a wide range of tissues through the continuous release of platelet growth factors. Here, we describe the use of PG preparation according to Anitua's PRGF (preparations rich in growth factors) protocol for treating chronic nonhealing ulcers in patients with SCD. A positive response occurred in 3 patients with an area reduction of 85.7% to 100%, which occurred within 7 to 10 weeks, and a 35.2% and 20.5% of area reduction in 2 other patients, who however, had large ulcers. After calcium chloride addition, the platelet-rich plasmas demonstrated enhanced platelet-derived growth factors-BB (P < .001), transforming growth factor-β1 (P = .015), vascular endothelial growth factors (P = .03), and hepatocyte growth factors (nonsignificant) secretion. Furthermore, calcium chloride addition induced a significant decrease in platelet number (P = .0134) and there was no leukocyte detection in the PG product. These results demonstrate that PG treatment might impact the healing of leg ulcers in sickle cell disease, especially in patients with small ulcers.

© The Author(s) 2014.

PMID: 24827464 [PubMed - as supplied by publisher]

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5.

Hemoglobin. 2014;38(3):221-3. doi: 10.3109/03630269.2014.911748.

Low-molecular-weight heparins for managing vasoocclusive crises in people with sickle cell disease: a summary of a cochrane systematic review.

van Zuuren EJ1Fedorowicz Z.

Author information: 
1Department of Dermatology, Leiden University Medical Centre , Leiden , The Netherlands .

Abstract

Abstract We summarize a Cochrane systematic review that was conducted to assess the effects of low-molecular-weight heparins (LMWH) for managing vasoocclusive crises (VOC) in people with sickle cell disease. Sickle cell disease is one of the most common and severe genetic disorders in the world. It can be divided into three broadly distinct clinical phenotypes characterized by either hemolysis, pain syndromes or organ damage. Pain is the most prominent symptom of vasoocclusion, and hypercoagulability is a well-established pathogenic phenomenon in people with sickle cell disease. Searches included the Cochrane Cystic Fibrosis and Genetic Disorders Group Haemoglobinopathies Trials Register, abstract books of conference proceedings and several online trials registries (December 2012). One study (with an overall unclear to high risk of bias) comprising 253 participants was included. This study provided limited data, but concluded that tinzaparin resulted in a more rapid resolution of pain, and in a statistically significant lower number of hospitalization days compared to a placebo. Two minor bleeding events were reported as adverse events in the tinzaparin group. Based on the results from this single study, there is incomplete evidence to either support or refute the effectiveness of LMWH in people with sickle cell disease.

PMID: 24826795 [PubMed - in process]

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6.

Blood Cells Mol Dis. 2014 May 7. pii: S1079-9796(14)00032-1. doi: 10.1016/j.bcmd.2014.04.004. [Epub ahead of print]

Deferiprone versus Deferoxamine in Sickle Cell Disease: Results from a 5-year long-term Italian multi-center randomized clinical trial.

Calvaruso G1Vitrano A2Di Maggio R1Ballas S3Steinberg MH4Rigano P1Sacco M1Telfer P5Renda D1Barone R1Maggio A6The Investigators of the Multicenter Randomized Clinical Trial of Deferiprone versus Deferoxamine in Sickle-Cell-Disease.

Author information: 
1Unita'Operativa Complessa Ematologia II, A.O.R. Villa Sofia-V. Cervello, Palermo, Italy.
2Dipartimento di Scienze Economiche, Aziendali e Statistiche, Università di Palermo, Palermo, Italy.
3Division of Hematology/Cardeza Foundation, Department of Medicine, Jefferson Medical College, Thomas Jefferson University, Philadelphia, PA, USA.
4Center of Excellence in Sickle Cell Disease, Department of Pediatrics, Pathology and Laboratory Medicine, Boston Medical Center, Boston, MA, USA.
5Department of Hematology, The Royal London Hospital, London, United Kingdom.
6Unita'Operativa Complessa Ematologia II, A.O.R. Villa Sofia-V. Cervello, Palermo, Italy. Electronic address: md.amaggio@gmail.it.

Abstract

Blood transfusion and iron chelation currently represent a supportive therapy to manage anemia, vasculopathy and vaso-occlusion crises in Sickle-Cell-Disease. Here we describe the first 5-year long-term randomized clinical trial comparing Deferiprone versus Deferoxamine in patients with Sickle-Cell-Disease. The results of this study show that Deferiprone has the same effectiveness as Deferoxamine in decreasing body iron burden, measured as repeated measurements of serum ferritin concentrations on the same patient over 5-years and analyzed according to the linear mixed-effects model (LMM) (p=0.822). Both chelators are able to decrease, significantly, serum ferritin concentrations, during 5-years, without any effect on safety (p=0.005). Moreover, although the basal serum ferritin levels were higher in transfused compared with non-transfused group (p=0.031), the changes over time in serum ferritin levels were not statistically significantly different between transfused and non-transfused cohort of patients (p=0.389). Kaplan-Meier curve, during 5-years of study, suggests that Deferiprone does not alter survival in comparison with Deferoxamine (p=0.38). In conclusion, long-term iron chelation therapy with Deferiprone was associated with efficacy and safety similar to that of Deferoxamine. Therefore, in patients with Sickle-Cell-Disease, Deferiprone may represent an effective long-term treatment option.

Copyright © 2014. Published by Elsevier Inc.

PMID: 24814618 [PubMed - as supplied by publisher]

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7.

PLoS One. 2014 May 8;9(5):e96561. doi: 10.1371/journal.pone.0096561. eCollection 2014.

Renal function in children suffering from sickle cell disease: challenge of early detection in highly resource-scarce settings.

Aloni MN1Ngiyulu RM1Gini-Ehungu JL1Nsibu CN2Ekila MB3Lepira FB4Nseka NM4.

Author information: 
1Division of Hemato-oncology and Nephrology, Department of Pediatrics, University Hospital of Kinshasa, School of Medicine, University of Kinshasa, Kinshasa, Democratic Republic of Congo.
2Intensive Care Division, Department of Pediatrics, University Hospital of Kinshasa, School of Medicine, University of Kinshasa, Kinshasa, Democratic Republic of Congo.
3Department of Internal Medicine, University Hospital of Kinshasa, School of Medicine, University of Kinshasa, Kinshasa, Democratic Republic of Congo.
4Division of Nephrology and Dialysis, Department of Internal Medicine, University Hospital of Kinshasa, School of Medicine, University of Kinshasa, Kinshasa, Democratic Republic of Congo.

Abstract

BACKGROUND:

The prevalence of Sickle cell disease is extremely high in Democratic Republic of Congo. Despite this high prevalence of the disease, data on renal abnormalities in children are rare.

METHOD:

The study proposed to assess blood pressure, glomerular function, urea and uric acid levels in 65 steady state Congolese children with homozygous sickle cell disease and 67 normal controls.

RESULTS:

In Hb-SS group, blood pressure level tended to be lower than Hb-AA groups but there was no statistically significant difference (p>0.05) between the two groups. The absolute values for GFR corrected for BSA were significantly higher in Hb-SS group compared to Hb-AA group (130.5±34.1 ml/min/1.73 m2 vs 113.7±24.5 ml/min/1.73 m2; p = 0.004). Children with Hb-SS were more likely to hyperfiltrate (30.8% of subjects) than children with Hb-AA (6.1% of subjects). Proteinuria was found in 4 (6.2%) children with Hb-SS. Uric acid level was significantly increased in children with Hb-SS compared to corresponding values in control group (4.4±1.3 mg/dl vs 3.5±1.1 mg/dl; p<0.001). Urea level was significantly decreased compared to corresponding values in Hb-AA group (15.3±8.3 mg/dl vs 22.9±10.1 mg/dl; p<0.001).

CONCLUSION:

Hyperfiltration, low creatinine, lower urea and high uric acid are more common in children with sickle cell disease than in normal controls.

PMCID: PMC4014510 Free PMC Article

PMID: 24810610 [PubMed - in process]

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8.

J Pediatr Hematol Oncol. 2014 May 6. [Epub ahead of print]

Patient-centered Approach to Designing Sickle Cell Transition Education.

Williams CP1Smith CHOsborn KBemrich-Stolz CJHilliard LMHoward THLebensburger JD.

Author information: 
1*Division of Pediatric Hematology Oncology †Lister Hill Library of Health Sciences, University of Alabama at Birmingham, Birmingham, AL.

Abstract

INTRODUCTION::

It is vital to engage patients with sickle cell disease (SCD) in the transition process from pediatric to adult care. To better understand the patient perspective during the time of transition, we conducted this research with the goal of incorporating patient comprehension and desires for transition education.

MATERIALS AND METHODS::

We surveyed 37 adolescent patients with SCD about their understanding of SCD and transition education preferences. In addition, patient responses were analyzed to understand differences among urban and rural patients.

RESULTS::

The mean age of surveyed participants was 14.9 years (SD=2.1). Forty-three percent of participants responded that the topic of transition had been introduced to them, and only 21% responded that they received education about transition. Despite the poor awareness about transition, almost all participants were interested in learning more about the transition process through a technology-based transition education platform where individual health topics could be explored.

DISCUSSION::

Despite a didactic teaching approach to transition education, we identified that sickle cell participants had poor recognition of receiving transition education and poor understanding of their basic medical history. However, patients can identify specific health topics that should be addressed during an individualized transition education program.

PMID: 24807007 [PubMed - as supplied by publisher]

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9.

Pediatr Blood Cancer. 2014 May 7. doi: 10.1002/pbc.25085. [Epub ahead of print]

Combined umbilical cord blood and bone marrow from HLA-identical sibling donors for hematopoietic stem cell transplantation in children with hemoglobinopathies.

Soni S1Boulad FCowan MJScaradavou ADahake JEdwards SWalters MC.

Author information: 
1Nationwide Children's Hospital, The Ohio State University, Columbus, Ohio.

Abstract

BACKGROUND:

It is well established that umbilical cord blood and bone marrow are biologically different stem cell sources.

PATIENTS AND METHODS:

We analyzed the feasibility and outcome of hematopoietic stem cell transplantation (HSCT) in 13 children (median age 5.9 years) with hemoglobinopathies after the co- infusion of cord blood (CB) and bone marrow (BM) from the same human leucocyte antigen (HLA) identical sibling donor. We also compared outcomes of children with co-transplantation to outcomes in children with hemoglobinopathies who had received a BM (n = 21) or CB (n = 22) transplant alone.

RESULTS:

Compared to CB transplant (CBT) recipients, the co-transplant group had more rapid neutrophil (17 vs. 25 days, P = 0.013) and platelet (29 vs. 48 days, P = 0.009) recovery and less transplant related mortality. Patients who received a co-transplant had a lower incidence of ≥grade II acute (0% vs. 26.3%) and chronic (0% vs. 21%) graft versus host disease (GVHD) compared to BM transplant (BMT) recipients (P = 0.055 and 0.045, respectively). With a median follow-up of >60 months in each treatment group, the 5-year probability of event free survival (EFS) was 100% in the co-transplant group, 90% after BMT and 86% after CBT (P = 0.42).

CONCLUSION:

Co-transplantation of CB and BM from HLA-identical sibling donors appears to be a feasible and effective strategy to further optimize outcomes of HSCT for hemoglobinopathies. Pediatr Blood Cancer © 2014 Wiley Periodicals, Inc.

© 2014 Wiley Periodicals, Inc.

PMID: 24803091 [PubMed - as supplied by publisher]







Sickle Cell News for April 2014

New tool helps young adults with sickle cell disease in the transition to adult care Child and adolescent hematologists at Boston Medical Center (BMC) have developed a tool to gauge how ready young adults with sickle cell disease are for a transition into adult care. In a new article for the Journal of Pediatric Hematology/Oncology, Amy Sobota, MD, MPH, and her collaborators have shown that a questionnaire geared to the needs of young adults with sickle cell disease can pinpoint areas of need before the patient goes into an adult clinic.

BMC's sickle cell disease transition clinic, which is unique in Boston, was established in 2008 and serves approximately 45 patients. Sickle cell disease is a hemoglobin disorder, the molecule in red blood cells that carries oxygen to the tissues. Due to a genetic mutation, sickle cell patients make red blood cells that are shaped like a crescent or "sickle." These patients are often anemic and can get bouts of extreme pain when sickled red blood cells become caught in small vessels of the body. Sickle cell disease traditionally has had a high mortality rate; however, children with sickle cell disease are now living longer, healthier lives thanks to early diagnosis and effective treatment.

These welcome changes have given new importance to the young patient's point of transition into adult care. Previous studies have shown that patients with SCD who are transitioning from pediatric to adult care have more admissions and emergency department visits. "We saw that these patients had specific needs, and that is why we started the transition clinic at BMC," said Sobota, who is an attending in pediatric hematology/oncology at BMC and an assistant professor of pediatrics at Boston University School of Medicine.

To determine the tool's efficacy, the researchers looked at the answers provided by 33 patients between the ages of 18 and 22 who completed the assessment. A majority, 97 percent, of the respondents said they could explain sickle cell disease to another person and that they understood "how they got" the genetic disease, and 94 percent understood that sickle cell disease might be passed on to their children.

All of the patients said that they planned to attend college or obtain post-high-school training, but only 70 percent knew where to find information about job training and opportunities. Sixty four percent of transitioning patients said they understood the various types of health insurance available to them, but only 13 percent had drawn up a portable medical history form that they could give to adult healthcare providers. Encouragingly, 97 percent of young sickle cell patients claimed a good social support system.

Finally, patients were asked about their ability to manage independent living and 73 percent of the patients had some job experience, full- or part-time. Although all of the patients were 18 and over, only 79 percent said they were already going to doctor's appointments on their own. However, few mentioned that they had anxiety about transitioning to adult care.

"Our study indicates that this assessment tool – the only one of its kind – provides important information to physicians of patients with sickle cell disease who are transitioning from pediatric to adult care," said Sobota. "Caregivers can use this information from patients in order to effectively tailor and guide their treatment and education through this transition."

Sickle cell disease: The forgotten survivors  See the story athttp://america.aljazeera.com/features/2014/4/sickle-cell-diseasetheforgottensurvivors.html

Funding Opportunity Announcement for the Sickle Cell Disease Treatment Demonstration Program has been released.  You can find the Grants.gov and the FOA number is HRSA-14-078.  You can also find more information about the FOA athttp://www.hrsa.gov/grants/apply/assistance/sicklecell/

 

There will be a informational webinar  regarding this funding opportunity on Monday, May 12 at 3:00pm Eastern Standard Time.

 

Please share this information as widely as possible.  If you have any questions regarding the FOA, please submit your question to me by email, so that I may address the question for the entire pool of potential applicants.  Please do not call me to ask questions regarding the FOA, as I will just ask you to submit your question by email.

 

Thank you,

 

Edward Donnell Ivy, MD, MPH

Medical Officer, Genetics Services Branch

Division of Services for Children with Special Health Needs

Maternal and Child Health Bureau

5600 Fishers Lane. Rm 18-A-19

Rockville, MD 20857

301-480-1312-fax

301-443-9775-phone

eivy@hrsa.gov

 

Sickle cell in the Medical Literature

1.

Blood. 2014 Apr 24. [Epub ahead of print]

How I treat renal complications in sickle cell disease.

Sharpe CC1Thein SL.

Author information: 
1Department of Renal Medicine, King's College London, London, United Kingdom;

Abstract

Renal disease is one of the most frequent and severe complications experienced by patients with sickle cell disease; its prevalence is likely to increase as the patient population ages. We recommend regular monitoring for early signs of renal involvement and a low threshold for the use of hydroxyurea as preventative measures for end stage renal disease. Once renal complications are detected, a careful assessment of the patient is required to rule out other causes of renal disease. Proteinuria and hypertension should be managed aggressively and the patient referred to a specialist nephrology center when progressive decline in renal function noted. For the few patients who develop advanced chronic kidney disease, timely planning for dialysis and transplantation can significantly improve outcome and we recommend an exchange blood transfusion policy for all patients on the transplant waiting list and for those with a functioning graft. Alongside the invasive treatment regimes, it is important to remember that renal failure in conjunction with sickle cell disease does carry a significant burden of morbidity, and that focusing on symptom control has to be central to good patient care.


PMID: 24764565 [PubMed - as supplied by publisher]


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2.

Thromb Res. 2014 May;133 Suppl 1:S52-3. doi: 10.1016/j.thromres.2014.03.021.

Red blood cells and thrombin generation in sickle cell disease.

Whelihan MF1Lim MY1Key NS2.

Author information: 
1Division of Hematology/Oncology, Department of Medicine, University of NC at Chapel Hill, USA.
2Division of Hematology/Oncology, Department of Medicine, University of NC at Chapel Hill, USA. Electronic address:nigel_key@med.unc.edu.

Abstract

The prothrombotic nature of sickle cell disease (SCD) is evidenced by the chronically elevated levels of almost all coagulation activation biomarkers, and an increased incidence of certain thrombotic events, including venous thromboembolism. Numerous studies have attempted to define the extent and elucidate the mechanism of the observed increase in thrombin generation in SCD patients in vivo. In general, these studies were performed using thrombin generation assays in platelet poor or platelet rich plasma and showed little difference in endogenous thrombin potential between the SCD cohort and healthy matched controls. In SCD, erythrocytes and monocytes have been demonstrated to exhibit procoagulant characteristics. Thus, the absence of these cellular components in standard thrombin generation assays may fail to reflect global hypercoagulability in the whole blood of patients with SCD. We were therefore surprised to see no difference in net thrombin generation in tissue factor-initiated initiated clotting of whole blood from patients with SCD. However, we are continuing to reconcile these seemingly disparate observations by slight modifications of the whole blood model that include alternative coagulation triggers and a re-examination of the net thrombin generation when the protein/protein S system is simultaneously interrogated.

Copyright © 2014 Elsevier Ltd. All rights reserved.


PMID: 24759144 [PubMed - in process]


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3.

Br J Health Psychol. 2014 Apr 23. doi: 10.1111/bjhp.12099. [Epub ahead of print]

Assessing the quality of life of children with sickle cell anaemia using self-, parent-proxy, and health care professional-proxy reports.

Constantinou C1Payne NInusa B.

Author information: 
1Psychology Department, Middlesex University, London, UK.

Abstract

OBJECTIVES:

The quality of life (QoL) of children with sickle cell anaemia (SCA) in the United Kingdom has not been examined, and a discrepancy measure based on Gap theory has rarely been used. This study investigated whether (1) child self-reports of QoL using a discrepancy measure (the Generic Children's QoL Measure; GCQ) are lower than those from healthy children, (2) proxy reports from parents and health care professionals are lower than child self-reports, and (3) demographic and disease severity indicators are related to QoL.

DESIGN AND METHODS:

An interdependent groups, cross-sectional design was implemented. Seventy-four children with SCA, their parent, and members of their health care team completed the GCQ. Demographic and disease severity indicators were recorded. GCQ data from healthy children were obtained from the UK Data Archive.

RESULTS:

Contrary to past research, when examining generic discrepancy QoL, children with SCA did not report a lower QoL than healthy children, and parent- and health care professional-proxy reports were not lower than child self-reports. Few of the demographic and disease severity indicators were related to QoL.

CONCLUSIONS:

Proxy reports may be used to gain a more complete picture of QoL, but should not be a substitute for self-reports. The explanation for the relatively high levels of QoL reported is not clear, but children with SCA may have realistic expectations about their ideal-self, place greater emphasis on aspects other than health in shaping their QoL, and define achievements within the limits of their illness. Future research should focus on psychological factors in explaining QoL. Statement of contribution What is already known on this subject? Children with sickle cell disease (SCD) generally have a reduced QoL compared with healthy children, but there appears to be no research measuring QoL in paediatric SCD in the United Kingdom. Proxy QoL reports from parents are often lower than child self-reports, but there is less research examining proxy reports from health care professionals. Previous research has measured paediatric QoL using measures of current health-related QoL, but this is not in line with the WHO's definition of QoL as the discrepancy between current state and expectations. What does this study add? Children with Sickle cell anaemia do not have an impaired discrepancy QoL; they may have realistic expectations about their ideal-self and define achievements within the limits of their illness. Health care professionals are able to gauge a SCA child's discrepancy QoL better than parents. The GCQ (a generic discrepancy measure of QoL) takes into account expectations about ideal QoL and does not emphasize health; it may be of use to Psychologists working with SCA children.

© 2014 The British Psychological Society.


PMID: 24758574 [PubMed - as supplied by publisher]


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4.

Br J Haematol. 2014 Apr 18. doi: 10.1111/bjh.12879. [Epub ahead of print]

Management of the acute painful crisis in sickle cell disease- a re-evaluation of the use of opioids in adult patients.

Telfer P1Bahal NLo AChallands J.

Author information: 
1Department of Haematology, Royal London Hospital, Barts Health NHS Trust, London, UK.

Abstract

Management of the acute painful crisis (APC) of sickle cell disease (SCD) remains unsatisfactory despite advances in the understanding and management of acute pain in other clinical settings. One reason for this is an unsophisticated approach to the use of opioid analgesics for pain management. This applies to haematologists who are responsible for developing acute sickle pain management protocols for their patients, and to health care staff in the acute care setting. The objective of this article is to evaluate the evidence for use of opioids in APC management. We have highlighted the possibilities for improving management by using alternatives to morphine, and intranasal (IN) or transmucosal routes of administration for rapid onset of analgesia in the emergency department (ED). We suggest how experience gained in managing acute sickle pain in children could be extrapolated to adolescents and young adults. We have also questioned whether patients given strong opioids in the acute setting are being safely monitored and what resources are required to ensure efficacy, safety and patient satisfaction. We also identify aspects of care where there are significant differences of opinion, which require further study by randomized controlled trial.

© 2014 John Wiley & Sons Ltd.


PMID: 24750050 [PubMed - as supplied by publisher]


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5.

Lancet Glob Health. 2014 Feb;2(2):e80-e89.

Global migration and the changing distribution of sickle haemoglobin: a quantitative study of temporal trends between 1960 and 2000.

Piel FB1Tatem AJ2Huang Z3Gupta S4Williams TN5Weatherall DJ6.

Author information: 
1Evolutionary Ecology of Infectious Disease Group, Tinbergen Building, Department of Zoology, University of Oxford, Oxford, UK ; Global Sickle Cell Disease Network, Toronto, ON, Canada.
2Department of Geography and Environment, University of Southampton, Southampton, UK ; Fogarty International Center, National Institutes of Health, Bethesda, MD, USA.
3Center for Infectious Disease Dynamics and Department of Biology, Pennsylvania State University, PA, USA.
4Evolutionary Ecology of Infectious Disease Group, Tinbergen Building, Department of Zoology, University of Oxford, Oxford, UK.
5Global Sickle Cell Disease Network, Toronto, ON, Canada ; Kenya Medical Research Institute-Wellcome Trust Programme, Centre for Geographic Medicine Research-Coast, Kilifi District Hospital, Kilifi, Kenya ; Department of Medicine, Imperial College, St Mary's Hospital, London, UK.
6Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, UK.

Abstract

BACKGROUND:

Changes in the geographical distribution of genetic disorders are often thought to happen slowly, especially when compared with infectious diseases. Whereas mutations, genetic drift, and natural selection take place over many generations, epidemics can spread through large populations within a few days or weeks. Nevertheless, population movements can interfere with these processes, and few studies have been done of their effect on genetic disorders. We aimed to investigate the effect of global migration on the distribution of the sickle-cell gene-the most common and clinically significant haemoglobin structural variant.

METHODS:

For each country, we extracted data from the World Bank's Global Bilateral Migration Database about international human migrations between 1960 and 2000. We combined this information with evidence-based estimates of national HbS allele frequencies, generated within a Bayesian geostatistical framework, to analyse temporal changes in the net numbers of migrants, and classified countries with an index summarising these temporal trends.

FINDINGS:

The number of international migrants increased from 92·6 million in 1960, to 165·2 million in 2000. The estimated global number of migrants with HbS increased from about 1·6 million in 1960, to 3·6 million in 2000. This increase was largely due to an increase in the number of migrants from countries with HbS allele frequencies higher than 10%, from 3·1 million in 1960, to 14·2 million in 2000. Additionally, the mean number of countries of origin for each destination country increased from 70 (SE 46) in 1960, to 98 (48) in 2000, showing an increasing diversity in the network of international migrations between countries. Our index of change map shows a patchy distribution of the magnitude of temporal changes, with the highest positive and negative values scattered across all continents.

INTERPRETATION:

Global human population movements have had a substantial effect on the distribution of the HbS gene. Population movements can create a long-term burden on health-care systems. Our findings, which emphasise countries in which migration fluxes are changing the most, should increase awareness about the global burden of haemoglobinopathies and encourage policy makers to implement specific public health interventions, such as screening programmes and genetic counselling.

FUNDING:

Wellcome Trust, European Research Council, Bill & Melinda Gates Foundation, National Institute of Allergy and Infectious Diseases-National Institutes of Health, the Research and Policy for Infectious Disease Dynamics program, Fogarty International Center.

PMCID: PMC3986033 Free PMC Article


PMID: 24748392 [PubMed]


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6.

J Pain Symptom Manage. 2014 Apr 14. pii: S0885-3924(14)00182-1. doi: 10.1016/j.jpainsymman.2014.02.002. [Epub ahead of print]

Perceived Discrimination in Health Care is Associated with a Greater Burden of Pain in Sickle Cell Disease.

Haywood C Jr1Diener-West M2Strouse J3Carroll CP3Bediako S4Lanzkron S3Haythornthwaite J3Onojobi G5Beach MC3;IMPORT Investigators.

Author information: 
1The Johns Hopkins School of Medicine. Electronic address:chaywoodjr@jhu.edu.
2The Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland.
3The Johns Hopkins School of Medicine.
4The University of Maryland, Baltimore County, Baltimore, Maryland.
5The Howard University Hospital, Washington, DC, USA.

Abstract

CONTEXT:

Perceived discriminatory experiences in society have been associated with a higher burden of pain among some minority patient populations.

OBJECTIVES:

To describe the extent to which patients with sickle cell disease (SCD) perceive discrimination from health care providers, and to examine the association of these experiences with the burden of chronic SCD pain.

METHODS:

Cross-sectional analysis of data collected at baseline of a prospective cohort study of SCD patient experiences of care (n = 291). Perceived race-based and disease-based discrimination from health care providers were measured using subscales adapted from the Interpersonal Processes of Care Survey. Discrimination scores were examined for their association with patient characteristics and measures of pain burden using descriptive, bivariate, and multivariate analytic techniques.

RESULTS:

Respondents reported a greater burden of race-based discrimination from health care providers than has been previously reported by African Americans, and they reported a greater amount of disease-based versus race-based discrimination. While age and having difficulty persuading providers about pain were the only patient characteristics independently associated with race-based discrimination, older age, greater emergency room utilization, having difficulty persuading providers about pain, daily chronic pain, fewer "good days" during a week, and a higher severity of pain on their "good days" were independently associated with greater disease-based discrimination.

CONCLUSION:

Perceived disease-based, but not race-based, discrimination was found to be associated with a greater range of self-reported pain among patients with SCD. If causal, this finding could signal an important new approach to mitigating the burden of pain experienced by persons with SCD.

Copyright © 2014 U.S. Cancer Pain Relief Committee. Published by Elsevier Inc. All rights reserved.


PMID: 24742787 [PubMed - as supplied by publisher]


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7.

Pediatr Blood Cancer. 2014 Apr 17. doi: 10.1002/pbc.25059. [Epub ahead of print]

Outcomes of matched sibling donor hematopoietic stem cell transplantation for severe sickle cell disease with myeloablative conditioning and intermediate-dose of rabbit anti-thymocyte globulin.

Soni S1Gross TGRangarajan HBaker KSSturm MRhodes M.

Author information: 
1Division of Hematology/Oncology/BMT, Nationwide Children's Hospital and Department of Pediatrics, The Ohio State University, Columbus, Ohio.

Abstract

BACKGROUND:

Allogeneic hematopoietic stem cell transplantation (HSCT) is a curative therapy for sickle cell disease (SCD) in children. Despite excellent outcomes of matched sibling donor (MSD) HSCT, there is still 5-10% chance of rejection and transplant related mortality (TRM) with 12-23% incidence of graft versus host disease (GVHD). We postulated that an intermediate dose of rabbit anti-thymocyte globulin (r-ATG, 10 mg/kg cumulative) would be effective in preventing both rejection and GVHD.

PATIENTS AND METHODS:

Fifteen patients, median age 5 (range 1.5-18) years, underwent MSD HSCT using busulfan (≥12.8 mg/kg with first dose pharmacokinetics), cyclophosphamide (total 200 mg/kg) and r-ATG. Bone marrow was the stem cell source; tacrolimus and methotrexate were given for GVHD prophylaxis.

RESULTS:

All patients achieved donor engraftment and there was no TRM. One patient rejected donor cells at 2 months post-transplant. Majority of the patients had high and sustained level of donor chimerism. None of the patients developed ≥Grade II GVHD. Incidence of CMV (10%) and EBV (9%) reactivations was low with rapid immune-reconstitution. Overall survival was 100% with event free survival of 93%.

CONCLUSIONS:

Eliminating the risks of TRM and GVHD by optimizing the regimen may lead to further acceptance of HSCT for SCD. Pediatr Blood Cancer © 2014 Wiley Periodicals, Inc.

© 2014 Wiley Periodicals, Inc.


PMID: 24740582 [PubMed - as supplied by publisher]


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8.

PLoS One. 2014 Apr 16;9(4):e94387. doi: 10.1371/journal.pone.0094387. eCollection 2014.

Outcomes of acute chest syndrome in adult patients with sickle cell disease: predictors of mortality.

Allareddy V1Roy A2Lee MK3Nalliah RP4Rampa S5Allareddy V6Rotta AT7.

Author information: 
1Assistant Professor of Pediatrics, Pediatric Critical Care, Rainbow Babies and Children's Hospital, Cleveland, Ohio, United States of America.
2Fellow, Pediatric Critical Care Medicine, Rainbow Babies and Children's Hospital, Cleveland, Ohio, United States of America.
3Developmental Biology, Harvard School of Dental Medicine, Boston, Massachusetts, United States of America.
4Instructor, Dental Medicine, Harvard University, Boston, Massachusetts, United States of America.
5Advanced Graduate Student, Texas A & M University, College station, Texas, United States of America.
6Associate Professor, Department of Orthodontics, University of Iowa; Iowa, United States of America.
7Professor of Pediatrics, Pediatric Critical Care, Rainbow Babies and Children's Hospital, Cleveland, Ohio, United States of America.

Abstract

Adults with sickle cell disease(SCD) are a growing population. Recent national estimates of outcomes in acute chest syndrome(ACS) among adults with SCD are lacking. We describe the incidence, outcomes and predictors of mortality in ACS in adults. We hypothesize that any need for mechanical ventilation is an independent predictor of mortality.

METHODS:

We performed a retrospective analysis of the Nationwide Inpatient Sample(2004-2010),the largest all payer inpatient database in United States, to estimate the incidence and outcomes of ACS needing mechanical ventilation(MV) and exchange transfusion(ET) in patients >21 years. The effects of MV and ET on outcomes including length of stay(LOS) and in-hospital mortality(IHM) were examined using multivariable linear and logistic regression models respectively. The effects of age, sex, race, type of sickle cell crisis, race, co-morbid burden, insurance status, type of admission, and hospital characteristics were adjusted in the regression models.

RESULTS:

Of the 24,699 hospitalizations, 4.6% needed MV(2.7% for <96 hours, 1.9% for ≥96 hours), 6% had ET, with a mean length of stay(LOS) of 7.8 days and an in-hospital mortality rate(IHM) of 1.6%. There was a gradual yearly increase in ACS hospitalizations that needed MV(2.6% in 2004 to 5.8% in 2010). Hb-SS disease was the phenotype in 84.3% of all hospitalizations. After adjusting for a multitude of patient and hospital related factors, patients who had MV for <96 hours(OR = 67.53,p<0.01) or those who had MV for ≥96 hours(OR = 8.73,p<0.01) were associated with a significantly higher odds for IHM when compared to their counterparts. Patients who had MV for ≥96 hours and those who had ET had a significantly longer LOS in-hospitals(p<0.001).

CONCLUSION:

In this large cohort of hospitalized adults with SCD patients with ACS, the need for mechanical ventilation predicted higher mortality rates and increased hospital resource utilization. Identification of risk factors may enable optimization of outcomes.

PMCID: PMC3989222 Free PMC Article


PMID: 24740290 [PubMed - in process]


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9.

Eur J Haematol. 2014 Apr 15. doi: 10.1111/ejh.12340. [Epub ahead of print]

Thinking beyond sickling to better understand pain in sickle cell disease.

Darbari DS1Ballas SClauw DJ.

Author information: 
1Division of Hematology, Center for Cancer and Blood Disorders, Children's National Medical Center, Department of Pediatrics, George Washington University, Washington, DC.

Abstract

Painful vaso-occlusive crises (VOCs) are the hallmark of sickle cell disease (SCD) however many patients experience frequent daily pain that does not follow the pattern of typical VOCs. This pain of variable severity also referred as persistent pain in the SCD literature, contributes to significant morbidity and poor quality of life and often fails to respond adequately to standard SCD therapies. In this article we briefly describe types of pain encountered in SCD with a special emphasis on persistent pain. We discuss altered pain processing as a potential contributing mechanism which may lead to development and maintenance of persistent pain. We describe advances in the non-SCD pain field that may help improve the understanding of SCD pain. We highlight the need for further investigation in this area since some of these patients with persistent pain may benefit from receiving adjuvant mechanism based therapies used successfully in other non-SCD chronic pain conditions. This article is protected by copyright. All rights reserved.

This article is protected by copyright. All ri

 

 

Sickle cell disease once meant a short and painful life, but now there’s growing hope http://www.washingtonpost.com/national/health-science/sickle-cell-disease-once-meant-a-short-and-painful-life-but-now-theres-growing-hope/2014/03/03/d964d318-6275-11e3-91b3-f2bb96304e34_story.html

New research and better and more aggressive treatment have begun to change sickle cell disease from an inherited condition that often condemned children to painful and short lives into a condition that can be managed with less pain and has a better life expectancy.

Man with sickle cell disease, not expected to live past 40, celebrates 70th birthday http://www.nydailynews.com/life-style/health/man-sickle-cell-disease-celebrates-70th-birthday-article-1.1723095

The average life span of people with the inherited disease is 42 years for men. Richard Mitchell's doctors now say he may be the oldest patient who is currently living with the disease.


Program Update: Sickle Cell Disease Treatment Demonstration

 Dear Colleagues,

HRSA’s Sickle Cell Disease Treatment Demonstration Grant Program supports the creation of systemic mechanisms to improve the prevention and treatment of Sickle Cell Disease, including the coordination of service delivery for individuals with Sickle Cell Disease. 

This year the program is expanding its reach by transitioning to a regional model.  The new program structure will require grantees to develop multi-state partnerships. 

The proposed regional structure for the HRSA Sickle Cell Regional Collaborative regions is as follows:

 

SCDTDP Region                                 HRSA Regions                                   States

North Atlantic Region                     HRSA Region 1                                   CT, MA, ME, NH, RI, VT

Northeast Region                            HRSA Regions 2 and 3                     DC, DE, MD, NY, NJ, PA, PR, VA, WV, VI

Southeast Region                            HRSA Region 4                                   AL, FL, GA, KY,  MS, NC, SC, TN

Midwest Region                               HRSA Region 5                                   IL, IN, MI, MN, OH, WI

Southwest Region                           HRSA Region 6                                   AR, LA, NM, OK, TX

Heartland Region                             HRSA Region 7                                   IA, KS, MO, NE,

Prairie Region                                    HRSA Region 8                                   CO, MT, NDSD, UT, WY

Pacific Region                                    HRSA Regions 9 and 10                  AK, AZ, CA, HI, ID, NV, OR, WA, Pacific Basin

 

We will continue to keep you informed of program updates.

 

Best regards,

 

Edward Donnell Ivy, MD, MPH

Medical Officer, Division of Services for Children with Special Health Needs

Maternal and Child Health Bureau

Health Resources and Services Administration (HRSA)

U.S. Department of Health and Human Services

New Web Resource _ Emergency Department Sickle Cell Disease from Duke University athttp://sickleemergency.duke.edu/

This website is designed as an educational resource to support emergency clinicians in their care of children and adults living with Sickle Cell Disease (SCD) There are pain management guidelines and case presentations.

New Book for Sickle Cell Providers - IASP Publishes Sickle Cell Pain

A new second edition published by the International Association for the Study of Pain will interest researchers and clinicians focused on sickle cell disease. Sickle Cell PainSecond Edition, by Samir K. Ballas, is a panoramic, in-depth exploration of every scientific, human, and social dimension of this cruel disease. This comprehensive, definitive work is unique in that it is the only book devoted to sickle cell pain, as opposed to general aspects of the disease.

The 752-page book links sickle cell pain to basic, clinical, and translational research, addressing various aspects of sickle pain from molecular biology to the psychosocial aspects of the disease. Supplemented with patient narratives, case studies, and visual art, Sickle Cell Pain’s scientific rigor extends through its discussion of analgesic pharmacology, including abuse-deterrent formulations. The book also addresses in great detail inequities in access to care, stereotyping and stigmatization of patients, the implications of rapidly evolving models of care, and recent legislation and litigation and their consequences.

Qualified reviewers may request complimentary review copies in digital format throughiaspdesk@iasp-pain.org. The book’s table of contents is available on the IASP website. At http://www.iasp-pain.org/PublicationsNews/ProductDetail.aspx?ItemNumber=3153

 

CDC Web based Sickle Cell Resources

 “Public Health Webinar Series on Hemoglobinopathies”

New Video 

2/27: The history of sickle cell disease

Dr. Todd Savitt, Brody School of Medicine at East Carolina University

mms://realaudio.service.emory.edu/SOM/PA/PLATT/SICKLE/CDC022714.wmv

 

Hosted by: The Division of Blood Disorders, National Center on Birth Defects and Developmental Disabilities (NCBDDD),

Centers for Disease Control and Prevention (CDC)

4th Thursday of every month from 2:00PM – 3:00PM ET

Hemoglobinopathy Webinar recordings and slide presentations are archived at

http://scinfo.org under the “webinars” toolbar

 

The purpose of this webinar series is to offer a hemoglobinopathies

learning collaborative platform for providers, consumers, educators, and scientists.

 

To Join The Webinar

Copy this address and paste it into your web browser: https://www.livemeeting.com/cc/cdc/join

Copy and paste the required meeting ID: 84QK2D and click “join”.

First Time Users: To save time before the meeting, check your system to make sure it is ready to use Microsoft Office Live Meeting.

 

To hear the presentation you must call in to the number below. 

 

For Audio

Dial 1-877-953-6706 and enter participant code: 9706616

If you are unable to join us on the internet for viewing, you are welcome to call in for audio access only.

Participants outside the United States must be able to access 800 numbers to the US.

 

Hemoglobinopathies Webinar Schedule 2014

 

 

3/27: Global initiatives in sickle cell disease

Dr. Kwaku Ohene-Frempong, Sickle Cell Foundation of Ghana

 

4/24: Sickle cell disease in Georgia, from newborn screening to transition

Dr. Peter Lane, Children’s Healthcare of Atlanta

 

5/22: The global burden of sickle cell disease

Dr. Fred Piel, University of Oxford

 

6/26: Quality of life measurement for the hemoglobinopathies

Dr. Marsha Treadwell, Children’s Hospital Oakland Research Institute

 

7/24: Topic TBD

Dr. Rakhi Naik, Johns Hopkins Medicine

 

8/28: Pregnancy and thalassemia

Dr. Alexis Thompson, Northwestern University

 

9/25: Sickle cell trait and neonatal hematologic screening

Dr. Zora Rogers, University of Texas Southwestern Medical Center

 

10/23: Transition of care for children and young adults living with sickle cell disease

Dr. Ify Osunkwo, Levine Cancer Institute/Carolinas HealthCare System

 

November and December: --- No Webinar ---

 

If you have ideas on topics for future webinars, or have any questions or comments about this series please submit them to Shae Pope spope@cdc.gov .

CDC’s YouTube Link: http://www.youtube.com/watch?v=gnrvYsZWR1c&list=UUiMg06DjcUk5FRiM3g5sqoQ&index=2&feature=plpp_video

 CDC Video Archive (http://scinfo.org/world-wide-resources/cdc-webinars-hemoglobinopathies-and-public-health

 CDC Sickle Cell Disease Webpage: http://wwwdev.cdc.gov/NCBDDD/sicklecell/video.html  

Articles in the Medical Literature for March

1.

J Clin Invest. 2014 Mar 18. pii: 72305. doi: 10.1172/JCI72305. [Epub ahead of print]

Neutrophil AKT2 regulates heterotypic cell-cell interactions during vascular inflammation.

Li JKim KHahm EMolokie RHay NGordeuk VRDu XCho J.

Abstract

Interactions between platelets, leukocytes, and activated endothelial cells are important during microvascular occlusion; however, the regulatory mechanisms of these heterotypic cell-cell interactions remain unclear. Here, using intravital microscopy to evaluate mice lacking specific isoforms of the serine/threonine kinase AKT and bone marrow chimeras, we found that hematopoietic cell-associated AKT2 is important for neutrophil adhesion and crawling and neutrophil-platelet interactions on activated endothelial cells during TNF-α-induced venular inflammation. Studies with an AKT2-specific inhibitor and cells isolated from WT and Akt KO mice revealed that platelet- and neutrophil-associated AKT2 regulates heterotypic neutrophil-platelet aggregation under shear conditions. In particular, neutrophil AKT2 was critical for membrane translocation of αMβ2 integrin, β2-talin1 interaction, and intracellular Ca2+ mobilization. We found that the basal phosphorylation levels of AKT isoforms were markedly increased in neutrophils and platelets isolated from patients with sickle cell disease (SCD), an inherited hematological disorder associated with vascular inflammation and occlusion. AKT2 inhibition reduced heterotypic aggregation of neutrophils and platelets isolated from SCD patients and diminished neutrophil adhesion and neutrophil-platelet aggregation in SCD mice, thereby improving blood flow rates. Our results provide evidence that neutrophil AKT2 regulates αMβ2 integrin function and suggest that AKT2 is important for neutrophil recruitment and neutrophil-platelet interactions under thromboinflammatory conditions such as SCD.

PMID: 24642468 [PubMed - as supplied by publisher]

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2.

J Clin Invest. 2014 Mar 18:1-4. doi: 10.1172/JCI75238. [Epub ahead of print]

Not simply misshapen red cells: multimolecular and cellular events in sickle vaso-occlusion.

Vercellotti GMBelcher JD.

Abstract

Thromboinflammatory diseases result from the interactions of vascular endothelial cells, inflammatory cells, and platelets with cellular adhesion molecules, plasma proteins, and lipids. Tipping the balance toward a prothrombotic, proinflammatory phenotype results from multicellular activation signals. In this issue of the JCI, Li et al. explore the regulation of heterotypic neutrophil-platelet contacts in response to TNF-α-induced venular inflammation with relevance to sickle cell disease (SCD).

PMID: 24642460 [PubMed - as supplied by publisher]

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3.

J Pain Symptom Manage. 2014 Mar 15. pii: S0885-3924(14)00043-8. doi: 10.1016/j.jpainsymman.2013.08.020. [Epub ahead of print]

Outpatient Pain Predicts Subsequent One-Year Acute Health Care Utilization Among Adults With Sickle Cell Disease.

Ezenwa MO1Molokie RE2Wang ZJ3Yao Y4Suarez ML4Angulo V4Wilkie DJ5.

Author information: 
1Department of Biobehavioral Health Science, University of Illinois at Chicago College of Nursing, Chicago, Illinois, USA; Comprehensive Sickle Cell Center, University of Illinois Hospital & Health Sciences System, Chicago, Illinois, USA.
2Comprehensive Sickle Cell Center, University of Illinois Hospital & Health Sciences System, Chicago, Illinois, USA; Division of Hematology/Oncology, Department of Medicine, University of Illinois at Chicago College of Medicine, Chicago, Illinois, USA; Department of Biopharmaceutical Sciences, University of Illinois at Chicago College of Pharmacy, Jesse Brown VA Medical Center (R.E.M.), Chicago, Illinois, USA.
3Department of Biopharmaceutical Sciences, University of Illinois at Chicago College of Pharmacy, Jesse Brown VA Medical Center (R.E.M.), Chicago, Illinois, USA.
4Department of Biobehavioral Health Science, University of Illinois at Chicago College of Nursing, Chicago, Illinois, USA.
5Department of Biobehavioral Health Science, University of Illinois at Chicago College of Nursing, Chicago, Illinois, USA. Electronic address: diwilkie@uic.edu.

Abstract

CONTEXT:

Patient demographic and clinical factors have known associations with acute health care utilization (AHCU) among patients with sickle cell disease (SCD), but it is unknown if pain measured predominantly in an outpatient setting is a predictor of future AHCU in patients with SCD.

OBJECTIVES:

To determine whether multidimensional pain scores obtained predominantly in an outpatient setting predicted subsequent 1-year AHCU by 137 adults with SCD and whether the pain measured at a second visit also predicted AHCU.

METHODS:

Pain data included the Composite Pain Index (CPI), a single score representative of a multidimensional pain experience (number of pain sites, intensity, quality, and pattern). Based on the distribution of AHCU events, we divided patients into three groups: 1) zero events (zero), 2) 1 to 3 events (low), or 3) 4 to 23 events (high).

RESULTS:

The initial CPI scores differed significantly by the three groups (F(2,134) = 7.38, P = 0.001). Post hoc comparisons showed that the zero group had lower CPI scores than both the low (P < 0.01) and high (P < 0.001) groups. In multivariate overdispersed Poisson regression analyses, age and CPI scores (at both measurement times) were statistically significant predictors of utilization events. Pain intensity scores at both measurement times were significant predictors of utilization, but other pain scores (number of pain sites, quality, and pattern) were not.

CONCLUSION:

Findings support use of outpatient CPI scores or pain intensity and age to identify at-risk young adults with SCD who are likely to benefit from improved outpatient pain management plans.

Copyright © 2014 U.S. Cancer Pain Relief Committee. Published by Elsevier Inc. All rights reserved.

PMID: 24636960 [PubMed - as supplied by publisher]

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4.

Haematologica. 2014 Mar 14. [Epub ahead of print]

Impaired blood rheology plays a role in the chronic disorders associated with sickle cell-hemoglobin C disease.

Lemonne N1Lamarre YRomana MHardy-Dessources MDLionnet FWaltz XTarer VMougenel DTressières BLalanne-Mistrih MLEtienne-Julan MConnes P.

Author information: 
1Guadeloupe;

Abstract

-

Free Article

PMID: 24633868 [PubMed - as supplied by publisher]

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5.

J Pediatr Hematol Oncol. 2014 Mar 13. [Epub ahead of print]

Prodromal Illness Before Acute Chest Syndrome in Pediatric Patients With Sickle Cell Disease.

Creary SE1Krishnamurti L.

Author information: 
1*Division of Pediatric Hematology/Oncology, Nationwide Children's Hospital, Columbus, OH †Division of Pediatric Hematology/Oncology, Children's Hospital of Pittsburgh of UPMC, Pittsburgh, PA.

Abstract

BACKGROUND::

Acute chest syndrome (ACS) is associated with morbidity and mortality in children with sickle cell disease. We hypothesize that children with sickle cell disease have a distinct prodromal illness before their ACS episode.

MATERIALS AND METHODS::

We performed a chart review of ICD-9-CM identified ACS episodes at a pediatric hospital from 2005 to 2010. Prodromal visits were defined as acute visits that resulted in a discharge from care and occurred within 2 weeks of a hospitalization that included ACS. We reviewed the documented history, examination, laboratory studies, and radiographs for each prodromal visit.

RESULTS::

We identified 196 ACS episodes. Children received prodromal care in 29% of the ACS episodes. Painful vaso-occlusive crisis was a common reason for seeking this care (61%) and was commonly located in the chest or back (81%). We also observed that patients were hypoxic (53%), tachypneic (29%), had a history of asthma (39%) or ACS (80%), and presented during the winter months (38%).

CONCLUSIONS::

These data suggest that nearly one third of patients who develop ACS seek care for a prodromal illness. Further research is needed to confirm and better define an ACS prodromal illness that may help to identify patients at high risk for developing ACS.

PMID: 24633302 [PubMed - as supplied by publisher]

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6.

J Pediatr Hematol Oncol. 2014 Mar 13. [Epub ahead of print]

Pediatric Hematology Providers on Referral for Transplant Evaluation for Sickle Cell Disease: A Regional Perspective.

Mikles B1Bhatia MOyeku SOJin ZGreen NS.

Author information: 
1*Department of Pediatric Hematology/Oncology, Naval Medical Center Portsmouth, Portsmouth, VA †Pediatric Hematology, Oncology and Stem Cell Transplantation §Department of Biostatistics, Mailman School of Public Health, Columbia University Medical Center ‡Department of Pediatrics, Division of General Pediatrics, Albert Einstein College of Medicine, Montefiore Medical Center, New York, NY.

Abstract

Hematology referral for evaluation is a key step for hematopoietic stem cell transplantation for sickle cell disease (SCD). Pediatric SCD providers in the US Northeast (New York-Mid-Atlantic and New England regions) were surveyed anonymously for perspectives and practices regarding transplant referral and compared by whether they practiced at SCD transplant centers. Data were analyzed using the Fisher exact test, χ test, and logistic regression. Half of the respondents practiced primarily at transplant sites. Most (79%) were enthusiastic about transplant for SCD and 78% had recently referred ≥1 child for evaluation. Overall, 77% limited referral to certain sickle hemoglobinopathies and 44% preferred referral for β-thalassemia to SCD. Indications selected for referral resembled current transplant criteria, plus family request or poor response to therapy. Referral for children on chronic transfusions predicted enthusiasm and prior referral. Many (66%) referred children with multiple SCD complications, even without matched sibling donors, 37% with sibling donors despite limited disease. Practitioners at transplant centers more commonly accepted event-free survival rates of ≤90% (P=0.002). Northeastern providers expressed varying enthusiasm for referral for evaluation based on eligibility, donor availability, and acceptable risk, with modestly more interest from practitioners at transplant centers. Differing provider perspectives may affect patient referral for transplant consideration.

PMID: 24633300 [PubMed - as supplied by publisher]

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7.

Am J Nurs. 2014 Mar 13. [Epub ahead of print]

Using Guided Imagery to Manage Pain in Young Children with Sickle Cell Disease.

Dobson CE1Byrne MW.

Author information: 
1Cassandra Elaine Dobson is an assistant professor of nursing at Lehman College, the City University of New York, in New York City. Mary Woods Byrne is the Stone Foundation and Elise D. Fish Professor in Clinical Health Care for the Underserved at the Columbia University School of Nursing in New York City. The authors acknowledge Meghan D. Kelly, MSEd, CCLS, for providing training in guided imagery for child participants at the Children's Hospital at Montefiore Medical Center in New York City, and Songs of Love, a nonprofit organization, for creating and donating the original music CDs given to each child at the end of the study. Contact author: Cassandra Elaine Dobson,cassandra.dobson@lehman.cuny.edu. The authors and planners have disclosed no potential conflicts of interest, financial or otherwise.

Abstract

: Findings show the technique can be readily taught to and used effectively by this population.

BACKGROUND:

Despite innovations in treatment, disease-related pain is still the primary cause of hospitalization for children with sickle cell disease. Pharmacologic pain management relieves pain temporarily, but adverse effects are increasingly a concern. Cognitive behavioral therapies, which include the use of guided imagery, have shown promise in changing pain perception and coping patterns in people with chronic illnesses. Few studies have been done in children with sickle cell disease.

OBJECTIVES:

The purposes of this study were to test the effects of guided imagery training on school-age children who had been diagnosed with sickle cell disease, and to describe changes in pain perception, analgesic use, self-efficacy, and imaging ability from the month before to the month after training.

METHODS:

A quasi-experimental interrupted time-series design was used with a purposive sample of 20 children ages six to 11 years enrolled from one sickle cell disease clinic, where they had been treated for at least one year. Children completed pain diaries daily for two months, and investigators measured baseline and end-of-treatment imaging ability and self-efficacy.

RESULTS:

After training in the use of guided imagery, participants reported significant increases in self-efficacy and reductions in pain intensity, and use of analgesics decreased as well.

CONCLUSIONS:

Guided imagery is an effective technique for managing and limiting sickle cell disease-related pain in a pediatric population.

PMID: 24632887 [PubMed - as supplied by publisher]

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8.

Blood. 2014 Mar 11. [Epub ahead of print]

Heme-induced neutrophil extracellular traps contribute to the pathogenesis of sickle cell disease.

Chen G1Zhang DFuchs TAWagner DDFrenette PS.

Author information: 
1Ruth L. and David S. Gottesman Institute for Stem Cell and Regenerative Medicine Research, Albert Einstein College of Medicine, Bronx, NY, United States;

Abstract

Sickle cell disease (SCD) is characterized by recurring episodes of vascular occlusion in which neutrophil activation plays a major role. The disease is associated with chronic hemolysis with elevated cell-free hemoglobin and heme. The ensuing depletion of heme scavenger proteins leads to non-specific heme uptake and heme-catalyzed generation of reactive oxygen species (ROS). Here, we have identified a novel role for heme in the induction of neutrophil extracellular trap (NET) formation in SCD. NETs are decondensed chromatin decorated by granular enzymes and are released by activated neutrophils. In humanized SCD mice, we have detected NETs in the lungs and soluble NET components in plasma. The presence of NETs was associated with hypothermia and death of these mice, which could be prevented and delayed, respectively, by dismantling NETs with DNase I treatment. We have identified heme as the plasma factor that stimulates neutrophils to release NETs in vitro and in vivo. Increasing or decreasing plasma heme concentrations can induce or prevent, respectively, in vivo NET formation, indicating that heme plays a crucial role in stimulating NET release in SCD. Our results thus suggest that NETs significantly contribute to SCD pathogenesis, and can serve as a therapeutic target for treating SCD.

PMID: 24620350 [PubMed - as supplied by publisher]

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Sickle Cell News for January 2014

UAMS opens statewide sickle cell treatment program in Little Rock Ark. http://www.sfgate.com/news/article/UAMS-opens-statewide-sickle-cell-treatment-program-5162744.php

Page 1 of 1

Adult sickle cell patients across the state will have better access to treatment under a new clinic launched Tuesday by the University of Arkansas for Medical Sciences.About 1,300 adults and children in Arkansas suffer from the hereditary disease, which causes painful episodes that often bring complications, such as bone infections, stroke and kidney disease.

Sickle cell patients living in medically underserved rural areas will particularly benefit from the new clinic, which is operating in partnership with UAMS' distance health center so patients can have consultations via the Internet. The program is led by Dr. Robin Devan, a palliative care physician at UAMS.

"Sickle cell is a chronic, high-maintenance disease, because as a blood disease it affects every organ in the body," Devan said in a news release. Patients with severe forms of the disease can live into their 40s, she said. The disease used to kill patients at an early age. With sickle cell patients living longer, more is needed to provide for their care.

"People in their 20s and 30s may present with kidney failure, liver failure, strokes, retinopathy, and other life-threatening conditions," Devan said.

In 2011, a bill by state Rep. Reginald Murdock, D-Marianna, provided $400,000 to start the clinic. It now draws funding from the Legislature and the state Medicaid program. The program has nurses available around the clock to assist patients who call 855-742-2355. It also features a transition clinic, which helps patients make the transition from child to adult care. A patient registry will track adult patients who give consent so the clinic can monitor morbidity and mortality trends.

Duluth girl battles sickle cell anemia with help from little sister Gwinnettdailypost.com  http://www.gwinnettdailypost.com/news/2014/jan/04/duluth-girl-battles-sickle-cell-anemia-with-help/

After an emotional and challenging 2013, Vanessa Gissel is looking forward to the new year.The 11-year-old girl from Duluth endured long stints away from home after undergoing a bone marrow transplant to treat her sickle cell anemia. It was a difficult journey — 39 straight days in the Aflac Cancer Center of Children’s Healthcare of Atlanta followed by 32 nights in the Atlanta Ronald McDonald House — but one made easier by the love and support of her family.

Four million Nigerians are currently suffering from Sickle Cell Disease (SCD)  http://dailypost.com.ng/2014/01/24/four-million-nigerians-living-sickle-cell/

  A Professor of Haematology and President, Sickle Cell Hope Alive Foundation (SCHAF), Adeyinka Falusi has said that about four million Nigerians are currently suffering from Sickle Cell Disease (SCD). Adeyinka who disclosed this at the Achievers Private University in Owo during its 7th matriculation lecture, also said over 40 million Nigerians have AS genotypes, while 66 to 72 per cent of the country’s population is AA.

She said it disease was one of the problematic issues facing the nation, blaming the federal government for poor sensitization exercise. Falusi warned that the population of SCD patients would continue to rise as long as the 40million AS people continue to marry each other. The Professor said “today’s discussion centres on SCD because it is the most prevalent disease in Nigeria with 2-3 per cent of 167 million people affected (about 4million). It is the most problematic disorder for several reasons as will be enumerated. Over 150,000 SCD children are born annually and 100,000 children and adult are affected die annually.

“At least 40 million Nigerians have sickle cell trait and if they continue to inter-marry, with all caution thrown to the wind, then the chicken will come home to roost with many more Nigerians bearing the burden of SCD. Falusi observed that Nigeria is one of the countries in the world that has the largest number of SCD patients, adding that the population grows due to what she described as government’s nonchalant attitude towards those patients and inability to encourage parents to check the status of their children at the age of six months.

She said “our government does not bother on how to tackle this problem. Look at Ghana, they are far from us on this. There is an amount of fund budgeted for this health disease. There are some countries in the world whose population of SCD patient is like ours, but today, they have been able to reduce this population. In Nigeria, there is nothing like that, government should rise up and ensure it fight against this disease”.

“I am advising the government to have a comprehensive SCD prevention program that benefits from the full range of up-to-date scientific information concerning inheritance patterns, prevention approaches, and structured management of the disease. They also need to embark on sensitization, particularly for the people in rural areas. Also, the NGOs should facilitate training of trainers workshops for students, artisan and professional groups.

Student's ordeal raises sickle cell awareness USA Today http://www.usatoday.com/story/news/nation/2014/01/16/students-ordeal-raises-sickle-cell-awareness/4551007/

Honoring James Eckman, MD http://emorymedicinemagazine.emory.edu/issues/2014/winter/class_notes/eckmansdevotion/index.html

New Video Resource

"Across the Lifespan of Women and Girls with Blood Disorders: Adolescence to Menopause"

This is a recorded version of FWGBD's Friday Satellite Symposium "Across the Lifespan of Women and Girls with Blood Disorders: Adolescence to Menopause" that preceded the 55th American Society of Hematology's (ASH) Annual Meeting on December 6, 2013 in New Orleans, LA. There are six 25- to 35-minute presentations followed by a Q & A after each topic area. Each session may be viewed individually and at your own pace. Presentations and speakers are as follows:

  • Adolescents, Sickle Cell Disease and Reproductive Lifespan Issues (Kim Smith-Whitley, MD)
  • Girls with Bone Marrow Failure: Challenges with Menarche and Beyond (Adrianna Vlachos, MD)
  • Red Cell Alloimmunization in Pregnancy: Diagnosis and Management (Kenneth Moise, Jr., MD)
  • Platlet Alloimmunization in Pregnancy (Terry Gernsheimer, MD)
  • Growing Older with von Willebrand Disease (Barbara Konkle, MD)
  • Menopause Life-Stage Challenges for Women with a History of Thrombosis (JoAnn Pinkerton, MD)

View Presentations at www.fwgbd.org

FDA’s Sickle Cell Patient-Focused Drug Development  Meeting:

This is a reminder about the upcoming public meeting on sickle cell disease, as part of FDA’s Patient-Focused Drug Development initiative. The purpose of the meeting is to hear patient perspectives on the health effects of sickle cell disease and on treating sickle cell disease. This meeting is free and open to the public.  

Meeting information:Date: February 7, 2014 Time: 10:00 am – 4:00 pm Location: FDA White Oak campus Building 31 (Great Room) 10903 New Hampshire Avenue  Silver Spring, MD 20993 

Attendees can register through January 27, 2014 herehttp://patientfocusedsicklecell.eventbrite.com/.

Contribute to the meeting dialogue!The meeting format maximizes patient participation. For each discussion topic, a small panel of patients or caretakers will prove brief comments to start the dialogue. The panel comments will be followed by a facilitated discussion with others in the audience. Patients or caregivers who would like to be considered for an opening panel can indicate that as part of registration. They will be asked to send a short summary of their responses to the discussion questions (posted on our registration site) toPatientFocused@fda.hhs.gov 

Live Webcast: A live webcast will be available for those unable to attend in person. Web participants will be able to submit comments as part of the discussion through the webcast. Please register for the webcast at http://patientfocusedsicklecell.eventbrite.com/. Send in Comments: Patients and anyone else who is interested can also share their perspectives by submitting a comment to FDA.  Click here to send comments: http://www.regulations.gov/#!documentDetail;D=FDA-2013-N-1328-0001.     

For more information:Please visit the FDA website: http://www.fda.gov/ForIndustry/UserFees/PrescriptionDrugUserFee/ucm370867.htm.  This website also includes a series ofbackground webinars on FDA and Patient-Focused Drug Development.

 

CDC Web based Sickle Cell Resources

“Public Health Webinar Series on Hemoglobinopathies”

Hosted by: The Division of Blood Disorders, National Center on Birth Defects and Developmental Disabilities (NCBDDD),

Centers for Disease Control and Prevention (CDC)

4th Thursday of every month from 2:00PM – 3:00PM ET

Hemoglobinopathy Webinar recordings and slide presentations are archived at

http://scinfo.org under the “webinars” toolbar

 

The purpose of this webinar series is to offer a hemoglobinopathies

learning collaborative platform for providers, consumers, educators, and scientists.

 

To Join The Webinar

Copy this address and paste it into your web browser: https://www.livemeeting.com/cc/cdc/join

Copy and paste the required meeting ID: 84QK2D and click “join”.

First Time Users: To save time before the meeting, check your system to make sure it is ready to use Microsoft Office Live Meeting.

 

To hear the presentation you must call in to the number below.

 

For Audio

Dial 1-877-953-6706 and enter participant code: 9706616

If you are unable to join us on the internet for viewing, you are welcome to call in for audio access only.

Participants outside the United States must be able to access 800 numbers to the US.

 

Hemoglobinopathies Webinar Schedule 2014

 New Video available at  mms://realaudio.service.emory.edu/SOM/PA/PLATT/SICKLE/CDC012314.wmv

For 1/23: An overview of sickle cell disease activities in Angola

Dr. Russell Ware and Dr. Patrick McGann, Cincinnati Children's Hospital Medical Center

 

2/27: The history of sickle cell disease

Dr. Todd Savitt, Brody School of Medicine at East Carolina University

 

3/27: Global initiatives in sickle cell disease

Dr. Kwaku Ohene-Frempong, Sickle Cell Foundation of Ghana

 

4/24: Sickle cell disease in Georgia, from newborn screening to transition

Dr. Peter Lane, Children’s Healthcare of Atlanta

 

5/22: The global burden of sickle cell disease

Dr. Fred Piel, University of Oxford

 

6/26: Quality of life measurement for the hemoglobinopathies

Dr. Marsha Treadwell, Children’s Hospital Oakland Research Institute

 

7/24: Topic TBD

Dr. Rakhi Naik, Johns Hopkins Medicine

 

8/28: Pregnancy and thalassemia

Dr. Alexis Thompson, Northwestern University

 

9/25: Sickle cell trait and neonatal hematologic screening

Dr. Zora Rogers, University of Texas Southwestern Medical Center

 

10/23: Transition of care for children and young adults living with sickle cell disease

Dr. Ify Osunkwo, Levine Cancer Institute/Carolinas HealthCare System

 

November and December: --- No Webinar ---

 

If you have ideas on topics for future webinars, or have any questions or comments about this series please submit them to Shae Pope spope@cdc.gov .

CDC’s YouTube Link: http://www.youtube.com/watch?v=gnrvYsZWR1c&list=UUiMg06DjcUk5FRiM3g5sqoQ&index=2&feature=plpp_video

 CDC Video Archive (http://scinfo.org/world-wide-resources/cdc-webinars-hemoglobinopathies-and-public-health

 CDC Sickle Cell Disease Webpage: http://wwwdev.cdc.gov/NCBDDD/sicklecell/video.html  

Articles in the Medical Literature for January

1.

Paediatr Respir Rev. 2013 Dec 21. pii: S1526-0542(13)00157-7. doi: 10.1016/j.prrv.2013.12.004. [Epub ahead of print]

Hypoxemia in Sickle Cell Disease: Significance And Management.

Caboot JB1Allen JL2.

Abstract

Hypoxemia is common in SCD and likely exacerbates SCD vasculopathy. Pulse oximeter correlation with arterial oxygen tension in patients with SCD may at times be poor and arterial blood gas confirmation is required in hypoxic patients. Supplemental oxygen should be administered for the correction of hypoxemia, which if untreated creates a risk of multi-organ failure. Transfusion and hydroxyurea can improve oxygen delivery to tissues and organs. The role of supplemental oxygen therapy in preventing or reversing SCD vasculopathy is controversial. Nitric oxide therapy for VOC pain has not fulfilled promise to date. On the other hand, lung distension (CPAP, incentive spirometry, PEP therapy) are promising treatments requiring further study.

Published by Elsevier Ltd.


PMID: 24461342 [PubMed - as supplied by publisher]


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2.

Clin J Am Soc Nephrol. 2014 Jan 23. [Epub ahead of print]

Prevalence and Correlates of Metabolic Acidosis among Patients with Homozygous Sickle Cell Disease.

Maurel SStankovic Stojanovic KAvellino VGirshovich ALetavernier EGrateau GBaud LGirot RLionnet FHaymann JP.

 

BACKGROUND AND OBJECTIVES:

Very few studies report acid base disorders in homozygous patients with sickle cell anemia (SCA) and describe incomplete renal acidosis rather than true metabolic acidosis, the prevalence of which is unknown and presumably low. This study aimed to assess the prevalence of metabolic acidosis and to identify its risk factors and mechanisms.

DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS:

This study retrospectively analyzed 411 homozygous patients with SCA with a GFR≥60 ml/min per 1.73 m2, referred in a single center between 2007 and 2012. Acidosis and nonacidosis groups were compared for clinical and biologic data including SCA complications and hemolytic parameters. A subgroup of 65 patients with SCA, referred for a measured GFR evaluation in the setting of sickle cell-associated nephropathy, was further analyzed in order to better characterize metabolic acidosis.

RESULTS:

Metabolic acidosis was encountered in 42% of patients with SCA, with a higher prevalence in women (52% versus 27% in men; P<0.001). Several hemolytic biomarkers, such as lactate dehydrogenase, were different between the acidosis and nonacidosis groups (P=0.02 and P=0.03 in men and women, respectively), suggesting higher hemolytic activity in the former group. To note, fasting urine osmolality was low in the whole study population and was significantly lower in men with SCA in the acidosis group (392 versus 427 mOsm/kg; P=0.01). SCA subgroup analysis confirmed metabolic acidosis with a normal anion gap in 14 patients, characterized by a lower urinary pH (P<0.02) and no increase in urinary ammonium. Serum potassium, plasma renin, and aldosterone were similar between the two groups and thus could not explain impaired urinary ammonium excretion.

CONCLUSIONS:

These results suggest that the prevalence of metabolic acidosis in patients with SCA is underestimated and related to impaired ammonium availability possibly due to an altered corticopapillary gradient. Future studies should evaluate whether chronic metabolic acidosis correction may be beneficial in this population, especially in bone remodeling.


PMID: 24458070 [PubMed - as supplied by publisher]


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Sickle Cell News for December  2013

Flipping a Gene Switch Reactivates Fetal Hemoglobin, May Reverse Sickle Cell Diseasehttp://www.sciencedaily.com/releases/2013/12/131208133646.htm

Dec. 8, 2013 — Hematology researchers at The Children's Hospital of Philadelphia have manipulated key biological events in adult blood cells to produce a form of hemoglobin normally absent after the newborn period. Because this fetal hemoglobin is unaffected by the genetic defect in sickle cell disease (SCD), the cell culture findings may open the door to a new therapy for the debilitating blood disorder.

"Our study shows the power of a technique called forced chromatin looping in reprogramming gene expression in blood-forming cells," said hematology researcher Jeremy W. Rupon, M.D., Ph.D., of The Children's Hospital of Philadelphia. "If we can translate this approach to humans, we may enable new treatment options for patients."

Rupon presented the team's findings today at a press conference during the annual meeting of the American Society of Hematology (ASH) in New Orleans. Rupon worked in collaboration with a former postdoctoral fellow, Wulan Deng, Ph.D., in the laboratory of Gerd Blobel, M.D., Ph.D.

Hematologists have long sought to reactivate fetal hemoglobin as a treatment for children and adults with SCD, the painful, sometimes life-threatening genetic disorder that deforms red blood cells and disrupts normal circulation.

In the normal course of development, a biological switch flips during the production of hemoglobin, the oxygen-carrying component of red blood cells. Regulatory elements in DNA shift the body from producing the fetal form of hemoglobin to producing the adult form instead. This transition occurs shortly after birth. When patients with SCD undergo this transition, their inherited gene mutation distorts adult hemoglobin, forcing red blood cells to assume a sickled shape.

In the current study, Rupon and Blobel reprogrammed gene expression to reverse the biological switch, causing cells to resume producing fetal hemoglobin, which is not affected by the SCD mutation, and produces normally shaped red blood cells.

The scientists built on previous work by Blobel's team showing that chromatin looping, a tightly regulated interaction between widely separated DNA sequences, drives gene transcription -- the conversion of DNA code into RNA messages to carry out biological processes.

In the current study, the researchers used a specialized tool, a genetically engineered zinc finger (ZF) protein, which they custom-designed to latch onto a specific DNA site carrying the code for fetal hemoglobin. They attached the ZF to another protein that forced a chromatin loop to form. The loop then activated gene expression that produced embryonic hemoglobin in blood-forming cells from adult mice. The team obtained similar results in human adult red blood cells, forcing the cells to produce fetal hemoglobin.

Rupon and Blobel will continue investigations aimed at moving their research toward clinical application. Rupon added that the approach may also prove useful in treating other diseases of hemoglobin, such as thalassemia.

Living with Sickle Cell Disease  http://www.wric.com/story/24263562/positively-richmond-living-with-sickle-cell-disease

RICHMOND (WRIC)—More than 100,000 people across the country suffer from sickle cell disease, a disorder that's more common in African-American families. In Virginia, one in 325 babies is born with the disease. Doctor visits at VCU Medical Center are just a normal part of life for Francis Churchill. He's been living with sickle cell disease for more than 47 years and has one word to describe it: chaos. 

The disease keeps Churchill in constant pain. He's had dozens of surgeries, including four on his leg after developing an ulcer."I've had operations on almost every part of my body, especially my joints, because that's where sickle cell attacks—your joints," Churchill said. Sickle cell disease is an inherited blood disorder, and its main symptom is pain.

"Pain that causes hospitalization, pain that requires morphine and narcotics, pain that's unremitting—days, weeks at a time," said Dr. Wally Smith, director of the VCU Health Systems Adult Sickle Cell Program.

Search for sickle cell cure  http://www.koaa.com/news/search-for-sickle-cell-cure/

Sickle cell disease is a hereditary blood disorder caused by a single genetic mutation The disease occurs more commonly among people whose ancestors lived in tropical and sub-tropical sub-saharan regions where malaria is or was common. Doctors researching the condition have been given a multi-million dollar grant to advance our knowledge of the illness.   For those like the Overstreet family, the Aflac Cancer Center of Children's Healthcare of Atlanta is home away from home. Both children Madison and Landon Overstreet have sickle cell disease. The inherited blood disorder that changes the way blood circulates causes patients to sometimes have blockages that lead to inflammation, infections and severe pain. When Landon was still a baby he started having pain crisis, a debilitating hallmark of the disease.When Madison was three, a common cold virus quickly progressed to acute chest syndrome in which the blood starts to accumulate in the lungs making it hard to breathe. This potentially life-threatening complication is the focus of a new research grant just awarded to the Aflac Center. Researchers are trying to find the target that triggers acute chest syndrome. 

FDA’s Sickle Cell Patient-Focused Drug Development  Meeting:

This is a reminder about the upcoming public meeting on sickle cell disease, as part of FDA’s Patient-Focused Drug Development initiative. The purpose of the meeting is to hear patient perspectives on the health effects of sickle cell disease and on treating sickle cell disease. This meeting is free and open to the public.  

Please help us reach patients and caregivers! This is an important opportunity to bring the sickle cell disease patient’s voice to FDA; therefore, patient participation is essential. Please help us make this meeting a success by reaching out and encouraging patients, parents and other caregivers to attend   Meeting information:Date:      February 7, 2014 Time:      10:00 am – 4:00 pm Location: FDA White Oak campus Building 31 (Great Room) 10903 New Hampshire Avenue  Silver Spring, MD 20993 

Attendees can register through January 27, 2014 herehttp://patientfocusedsicklecell.eventbrite.com/.

Contribute to the meeting dialogue!The meeting format maximizes patient participation. For each discussion topic, a small panel of patients or caretakers will prove brief comments to start the dialogue. The panel comments will be followed by a facilitated discussion with others in the audience. Patients or caregivers who would like to be considered for an opening panel can indicate that as part of registration. They will be asked to send a short summary of their responses to the discussion questions (posted on our registration site) toPatientFocused@fda.hhs.gov 

Live Webcast: A live webcast will be available for those unable to attend in person. Web participants will be able to submit comments as part of the discussion through the webcast. Please register for the webcast at http://patientfocusedsicklecell.eventbrite.com/. Send in Comments: Patients and anyone else who is interested can also share their perspectives by submitting a comment to FDA.  Click here to send comments:http://www.regulations.gov/#!documentDetail;D=FDA-2013-N-1328-0001.     


For more information:
Please visit the FDA website: http://www.fda.gov/ForIndustry/UserFees/PrescriptionDrugUserFee/ucm370867.htm.  This website also includes a series of background webinars on FDA and Patient-Focused Drug Development. Questions?  Please contact Graham Thompson at 301-796-5003 or atGraham.Thompson@fda.hhs.gov.                                                                                                                                                              &nbs! p;                                                                                                                          


Sickle Cell News for November  2013

 

CDC Web based Sickle Cell Resources

CDC’s YouTube Link: http://www.youtube.com/watch?v=gnrvYsZWR1c&list=UUiMg06DjcUk5FRiM3g5sqoQ&index=2&feature=plpp_video

 CDC Video Archive (http://scinfo.org/world-wide-resources/cdc-webinars-hemoglobinopathies-and-public-health

 CDC Sickle Cell Disease Webpage: http://wwwdev.cdc.gov/NCBDDD/sicklecell/video.html  

Articles in the Medical Literature for December

 


Thromb Res. 2013 Dec 7. pii: S0049-3848(13)00573-2. doi: 10.1016/j.thromres.2013.12.008. [Epub ahead of print]

A phase 1 study of prasugrel in patients with sickle cell disease: Effects on biomarkers of platelet activation and coagulation.

Jakubowski JA1Zhou C2Jurcevic S3Winters KJ2Lachno DR4Frelinger AL 3rd5Gupta N2Howard J6Payne CD4Mant TG7.

Abstract

INTRODUCTION:

Prasugrel, a P2Y12 adenosine diphosphate (ADP) receptor antagonist effectively inhibits ADP-mediated platelet activation and aggregation, and may be useful in reducing vaso-occlusive crises in sickle cell disease (SCD). In this study, we assess the effect of prasugrel on biomarkers of platelet activation and coagulation in patients with SCD.

MATERIALS AND METHODS:

Twelve adult patients with SCD and 13 healthy subjects were examined before and after 12±2days of 5.0 or 7.5mg/day oral prasugrel. Assessed cellular biomarkers included monocyte- and neutrophil-platelet aggregates, activated glycoprotein IIb-IIIa (GPIIbIIIa), P-selectin, CD40 ligand (CD40L), tissue factor (TF) expression on circulating platelets and on monocyte-platelet aggregates, and platelet-erythrocyte aggregates. Soluble biomarkers included CD40L, prothrombin fragment 1.2 (F1.2), thromboxane B2 (TXB2), P-selectin, and TF.

RESULTS:

Patients with SCD had increased platelet baseline activation compared to healthy subjects, as measured by percentages of monocyte-platelet aggregates, neutrophil-platelet aggregates, and platelets expressing CD40L. Likewise, baseline levels of soluble F1.2 and TXB2 were elevated in patients with SCD compared to healthy subjects. After 12days of prasugrel, patients with SCD had a significant reduction in platelet-monocyte aggregates that was not observed in healthy subjects. Following prasugrel administration, those with SCD maintained higher levels of monocyte-platelet aggregates and soluble F1.2, but had lower levels of platelet-erythrocyte aggregates and soluble TF compared to healthy subjects.

CONCLUSIONS:

These results provide evidence for chronic platelet activation in the SCD steady state, activation that was in part attenuated by prasugrel, thereby suggesting that ADP may mediate platelet activation in SCD.


PMID: 24368019 [PubMed - as supplied by publisher]


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2.

Handb Clin Neurol. 2014;120:1015-25. doi: 10.1016/B978-0-7020-4087-0.00068-1.

Neurologic complications of sickle cell disease.

Venkataraman A1Adams RJ2.

Abstract

Sickle cell disease (SCD) is a group of genetic blood disorders that vary in severity, but the most severe forms, primarily homozygous sickle cell anemia, are associated with neurologic complications. Over the last 90 years it has become established that some patients will develop severe arterial disease of the intracranial brain arteries and suffer brain infarction. Smaller infarctions and brain atrophy may also be seen and over time there appear to be negative cognitive effects in some patients, with or without abnormal brain imaging. Focal mononeuropathies and pneumococcal meningitis are also more common in these patients. Brain infarction in children can largely be prevented screening children beginning at age 2 years and instituting regular blood transfusion when the Doppler indicates high stroke risk (>200cm/sec). Iron overload and the uncertain duration of transfusion are disadvantages but overall this approach, tested in a randomized clinical trial, reduced first stroke by over 90%. Secondary stroke prevention has not been subjected to a randomized controlled trial except for one recently stopped comparison of regular transfusions compared to hydroxuyrea (results favored transfusion). The usual stroke prevention agents (such as aspirin or warfarin) have not been rigorously tested. Magnetic resonance imaging and positron emission tomography give evidence of subtle and sometimes overt brain injury due to stroke in many adults, but a preventive strategy for adults with SCD has not been developed. Bone marrow transplantation is the only cure, but some non-neurologic symptoms can be controlled in adults with hydroxuyrea.

© 2014 Elsevier B.V. All rights reserved.


PMID: 24365368 [PubMed - in process]


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3.

Mediterr J Hematol Infect Dis. 2013 Nov 7;5(1):e2013069. doi: 10.4084/MJHID.2013.069.

Iron Deficiency Anaemia among Pre-School Children with Sickle Cell Anaemia: Still a Rare Diagnosis?

Akodu SOKehinde OADiaku-Akinwumi INNjokanma OF.

Abstract

BACKGROUND:

The frequent need for blood transfusion in children with SCA creates the impression that IDA is rare in this class of children.

OBJECTIVES:

The objective of the study is to determine the prevalence of IDA in a population of under-five children with SCA in Lagos, Nigeria.

METHODOLOGY:

Serum iron, total iron binding capacity, transferrin saturation and serum ferritin were assayed in 97 under-five children with SCAand 97 age/sex matched controls. THE DIAGNOSIS OF IDA WAS ESTABLISHED BASED ON THE FOLLOWING CRITERIA: haemoglobin <11.0 g/dl plus two or more of the following: MCV <70fl, transferrin saturation (Ts) <16% or serum ferritin (SF) <25ng/dL.

RESULTS:

Overall prevalence of IDA was significantly higher among AA controls. In the younger age group, the prevalence of IDA was significantly higher among HbAA controls while in the older age group the odds of having IDA was three times higher among HbSS subjects but the difference was not statistically significant. Two of the three SCA children with IDA have history of previous blood transfusion.

CONCLUSION:

IDA is uncommon in pre-school aged children with SCA. A multi-centre study is necessary to yield large number of transfused subjects to examine the effects of blood transfusion on prevalence of IDA.

PMCID: PMC3867223 Free PMC Article


PMID: 24363884 [PubMed]


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Icon for PubMed Central

 

4.

Mediterr J Hematol Infect Dis. 2013 Nov 4;5(1):e2013062. doi: 10.4084/MJHID.2013.062.

Sickle cell disease: management options and challenges in developing countries.

Ansong D1Akoto AO1Ocloo D2Ohene-Frempong K3.

Abstract

Sickle Cell Disease (SCD) is the most common genetic disorder of haemoglobin in sub-Saharan Africa. This commentary focuses on the management options available and the challenges that health care professionals in developing countries face in caring for patients with SCD. In a developing countries like Ghana, new-born screening is now about to be implemented on a national scale. Common and important morbidities associated with SCD are vaso-occlusive episodes, infections, Acute Chest Syndrome (ACS), Stroke and hip necrosis. Approaches to the management of these morbidities are far advanced in the developed countries. The differences in setting and resource limitations in developing countries bring challenges that have a major influence in management options in developing countries. Obviously clinicians in developing countries face challenges in managing SCD patients. However understanding the disease, its progression, and instituting the appropriate preventive methods are paramount in its management. Emphasis should be placed on early counselling, new-born screening, anti-microbial prophylaxis, vaccination against infections, and training of healthcare workers, patients and caregivers. These interventions are affordable in developing countries.

PMCID: PMC3867228 Free PMC Article


PMID: 24363877 [PubMed]


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Icon for PubMed Central

 

5.

Paediatr Respir Rev. 2013 Nov 15. pii: S1526-0542(13)00145-0. doi: 10.1016/j.prrv.2013.11.003. [Epub ahead of print]

Differences in the clinical and genotypic presentation of sickle cell disease around the world.

Saraf SL1Molokie RE2Nouraie M3Sable CA4Luchtman-Jones L5Ensing GJ6Campbell AD7,Rana SR8Niu XM3Machado RF9Gladwin MT10Gordeuk VR11.

Abstract

Sickle cell disease (SCD), caused by a mutation in the β-globin gene HBB, is widely distributed in malaria endemic regions. Cardiopulmonary complications are major causes of morbidity and mortality. Hemoglobin SS (Hb SS) represents a large proportion of SCD in the Americas, United Kingdom, and certain regions of Africa while higher proportions of hemoglobin SC are observed in Burkina Faso and hemoglobin Sβ-thalassemia in Greece and India. Coinheritance of α-thalassemia and persistence of hemoglobin F production are observed in highest

Scientists Use Light to Uncover the Cause of Sickle Cell Disease

Nov. 5, 2013 — In sickle cell disease, hemoglobin -- the oxygen-carrying component of blood -- forms fibers that stiffen red blood cells and cause life-threatening symptoms. Using light-scattering techniques to study the detailed thermodynamics of this process, researchers reporting in the November 5 issue of the Biophysical Journal, a Cell Press publication, have determined the strength of the forces that hold these fibers intact. The information could be used to design therapies that interfere with the sickling process.

Red blood cells resemble beanbags whose contents are molecules of hemoglobin that give the cells their "squishiness" by slipping past one another rather than sticking together. This is no easy feat, because the molecules have positive and negative charges spread around their surfaces, as well as oily patches that repel water and thus provide natural partners. Yet it's thought that when two places of mutual attraction meet, locations of repulsion also come together and keep the net sum of attraction at zero.

In rare cases, such as sickle cell disease, a mutation in hemoglobin disrupts this delicate cancellation of attractive spots, and large stiff fibers, or polymers, of hemoglobin form inside normally pliable red blood cells.

Dr. Frank Ferrone, of Drexel University in Philadelphia, and Dr. Yihua Wang, currently at the Mayo Clinic in Rochester, discovered that the cancellation is not as perfect as previously thought, however. In fact, hemoglobin molecules do indeed associate, especially when the temperature is high or when hemoglobin solutions are concentrated. "This is true for normal hemoglobin, and even more pronounced for sickle hemoglobin," says Dr. Ferrone. His team found that under physiological conditions, sickle cell hemoglobin molecules are more likely to be found in pairs than as solitary molecules.

The researchers made these discoveries while conducting experiments with light-scattering techniques: they measured how rays of light are deflected by sickle hemoglobin fibers in order to calibrate the strength of the connections that hold them together. "By comparing the propensity of molecules of sickle hemoglobin to associate into pairs with the propensity of normal hemoglobin to do so, the relative strengths of the two major bonds within the sickle polymer were determined. The sickle cell mutation site was far stronger," Dr. Ferrone explains. "This makes the sickle hemoglobin polymers behave much like long tiny coil springs and helps us to understand their stiffness, which causes so much difficulty for affected individuals."

The findings could lead to new drug therapies that target the regions of hemoglobin that are responsible for polymer formation

Arginine therapy shows promise for sickle cell pain

Arginine therapy may be a safe and inexpensive treatment for acute pain episodes in patients with sickle cell disease, according to results of a recent clinical study. The study was the first randomized placebo-controlled study to demonstrate benefits of arginine therapy in children with sickle cell disease hospitalized for severe pain. Sickle cell disease is an inherited condition in which the body makes red blood cells containing abnormal hemoglobin, the protein that carries oxygen from the lungs to other cells in the body. This abnormal hemoglobin (hemoglobin S) causes red blood cells to distort into a sickle, or crescent shape that often blocks blood flow in small blood vessels, leading to pain and organ damage.

An acute deficiency of nitric oxide in sickled red blood cells contributes to the episodes of blocked vessels and pain. Since the amino acid arginine is a building block of nitric oxide, researchers hypothesized that arginine could be a beneficial treatment for pain related to sickle cell disease.

Previous research found that a single dose of arginine given to sickle cell patients with acute pain episodes resulted in a significant dose-dependent increase in plasma nitric oxide. Building on that knowledge, the current research study was a randomized, double blind clinical trial of 38 children with sickle cell disease hospitalized for 56 episodes of pain. The research team discovered a 54 percent reduction in the use of pain medication and significantly lower pain scores at hospital discharge in those treated with arginine over those receiving placebo.

The results were published in the journal Haematologica. First author was Claudia R. Morris, MD, assistant professor of pediatrics at Emory University School of Medicine. She conducted the study while in her previous position at Children’s Hospital and Research Center in Oakland, CA, with senior author Elliott P. Vichinsky, MD.

“Episodes of pain due to vaso-occlusion are the leading cause of hospital admission and emergency room visits and are associated with increased mortality, yet there is no effective therapy targeting the underlying cause,” says Morris. “Treatment consists only of symptom relief with pain medicines and hydration. There is an urgent need for new therapies for acute sickle cell pain, and a greater than 50 percent reduction in use of pain medication was a remarkable finding.”

The study found no problems with safety in the use of arginine therapy. Although the treatment did not result in a significantly shorter length of stay in the hospital, the researchers believe delivering the study drug as early as possible in the emergency department or clinic may have a greater impact on length of stay, since many patients received their first dose of medication more than 24 hours after presenting at the hospital. A large, multi-center trial is warranted in order to confirm these observations and test the effects of delivering the therapy sooner, they note in the published paper. Full text article at http://www.haematologica.org/content/98/9/1375.full.pdf+html

The St. Jude Children’s Research Hospital-led national BABY HUG trial linked hydroxyurea to a 21 percent reduction in annual medical costs for young children with sickle cell anemia; savings expected to grow

A drug proven effective for treatment of adults and children with sickle cell anemia reduced hospitalizations and cut annual estimated medical costs by 21 percent for affected infants and toddlers, according to an analysis led by St. Jude Children’s Research Hospital. The report appears in the advance online edition of the journal Pediatrics.

The study is the largest ever focusing on the economic impact of the drug hydroxyurea in children with the inherited blood disorder. The result supports expanded use of the drug to extend the length and quality of life for sickle cell anemia patients of all ages, said Winfred Wang, M.D., a member of the St. Jude Department of Hematology and principal investigator of the multicenter federally funded trial known as BABY HUG.

“We estimate that hydroxyurea cut overall annual medical expenses about $3,000 for each patient by helping patients avoid disease complications that require inpatient hospital care,” said Wang, who is first and corresponding author of the Pediatrics study. “We expect those savings will grow along with patients, whose symptoms often increase in severity and frequency as they age.”

About 100,000 individuals in the U.S. and millions worldwide have sickle cell disease, which leaves them at risk for premature death and disability. The disease is the most common genetic disorder affecting African-American individuals, but those from other ethnic and racial backgrounds also inherit mutations in the hemoglobin gene. The mutations result in blood cells that are prone to assuming the sickled shape that gives the disease its name and that leave patients at increased risk for episodes of acute pain, stroke, organ damage and other complications.

The analysis comes two years after Wang and his colleagues reported that hydroxyurea reduced episodes of acute pain and pneumonia-like illness, eased other symptoms, reduced the need for blood transfusions and cut hospitalizations for infants and toddlers with sickle cell anemia. Sickle cell anemia is the most common and severe form of sickle cell disease.

Earlier studies had demonstrated that adults and adolescents with the disease benefited from hydroxyurea. BABY HUG showed the drug, which is inexpensive and easy to administer, was safe and effective for young children. The study involved 193 children who were 9 to 18 months old when they enrolled at one of the 13 participating medical centers. The children were randomly assigned to receive either a daily dose of hydroxyurea for two years or an inactive look-alike.

Continued concern about U.S. health care spending prompted BABY HUG researchers to retrospectively assess hydroxyurea’s impact on treatment costs. Investigators used a national database of Medicaid expenditures to estimate the 2009 cost of caring for BABY HUG participants. Medicaid is the state-federal health insurance program that covers lower income and disabled children and adults. The six-year BABY HUG study ended in 2009.

The results showed that hydroxyurea was associated with higher outpatient costs, but lowered overall expenditures. Children who received the drug were hospitalized 232 times during the study, compared to 324 hospitalizations for those in the placebo group. The estimated annual treatment cost $11,072 for children who received hydroxyurea compared to $13,962 for children who received the placebo.

Wang said actual savings associated with hydroxyurea treatment are likely greater, since medical costs are roughly 25 percent less for children enrolled in Medicaid than for those with private health insurance. The analysis was unable to capture all treatment-related costs. “The analysis also could not capture the anxiety patients and family experience when children must be hospitalized,” Wang said.

Hydroxyurea was developed in the 1960s as a possible anti-cancer agent. It won approval for treatment of adults and later adolescents with sickle cell anemia in 1998 following evidence that the drug reduced episodes of severe pain and improved patient quality of life.

The drug works by increasing production of fetal hemoglobin, a form of the oxygen-carrying protein that is unaffected by the mutations that cause sickle cell disease. Fetal hemoglobin normally drops dramatically after birth. Hydroxyurea, however, increases production of red blood cells that contain that form of hemoglobin.

The drug remains an underutilized treatment for sickle cell anemia. Wang estimated the drug is prescribed to about 30 percent of pediatric patients nationwide and an even smaller percentage of adults. Work is underway at St. Jude and other medical centers to identify and address barriers to more widespread use of the drug, including lingering concerns about possible long-term toxicity.

New Bone Marrow Transplant  Web Resources for Patients and Providers _ Haplo Bone Marrow Transplant for Sickle Cell Disease Consortium http://www.sicklecelltransplantconsortium.org

 This recently formed multi-institutional group offers curative transplants to children and adolescents with severe sickle cell disease who do not have HLA-matched donors.  The approach uses a family (usually preferably mother) haplo-identical donor.  The donor stem cell product then undergoes T-cell depletion via CD34 selection to remove allo-reactive cells that could cause graft versus host disease (GVHD).

Currently two patients with sickle cell disease have been successfully transplanted using this approach.  Both of these patients are doing well approximately 1 year from their transplant and have no GVHD.  Other patients are in the process of starting the conditioning regimen.

Families and patients who are interested in learning more about this exciting cure should be referred to one of the participating clinical sites  http://www.sicklecelltransplantconsortium.org/clinical-sites.html or call Sandi Foley at 914-594-4333.  For information please also see  http://clinicaltrials.gov/show/NCT01461837 .

Community Forum on Future Directions for Sickle Cell Disease Treatment Demonstration Program

NICHQ, together with the Health Resources and Services Administration (HRSA), will be hosting a community forum to discuss the Sickle Cell Disease Treatment Demonstration Program. Please join us to hear HRSA’s vision for the direction of the program and to provide your feedback.

Healthcare Professionals Webinar Information

DateWednesday, December 18

Time3:00-4:30pm (ET)

Location: Online Webinar: [call in information available when registering]

You can REGISTER for the webinar here: http://www.cvent.com/d/j4qkk9

 

Patients and Families Webinar Information

DateThursday, December 12

Time3:00-4:30pm (ET)

Location: Online Webinar: [call in information available when registering]

You can REGISTER for the webinar here: http://www.cvent.com/d/j4qkk9

Background and Mission of the SCD Treatment Demonstration Program

 In 2004, Congress enacted PL 108-357, which included the authorization of the SCDTDP

 The stated purpose of this program was to develop and implement “systemic mechanisms” to enhance treatment of sickle cell disease to:  Improve coordination and service delivery for individuals with sickle cell disease and trait

 Improve access to services

 Improve and expand patient and provider education

 

 Mission: To improve care and outcomes for persons with Sickle Cell Disease

 

This event will be hosted by NICHQ, a non-profit dedicated to improving the systems that deliver health care to children and families. For more information about NICHQ, please visit www.nichq.org.

                                                                                                                                                                                                                                                                                                     

New Videos   

 

James R. Eckman, MD Sickle Cell Scientific Symposium Saturday, November 16, 2013

Period

These are the video lectures from the symposium. PDF handouts will be available at http://scinfo.org/world-wide-resources/james-r-eckman-md-sickle-cell-scientific-symposium

Words of Thanks to Dr. James Eckman Christian Larsen, MD, DPhil J. William Eley, MD,MPH

Welcome/Introductions Fadlo Khuri, MD and Ruth O’Regan, MD

The Georgia Comprehensive Sickle Cell Center at Grady Health Sysytem A Medical Home for Sickle Cell Disease Allan F. Platt, PA-C, MMScmms://realaudio.service.emory.edu/SOM/PA/PLATT/SICKLE/Eckman/Eckmanintro.wmv

 

Mechanisms for SCD Neurocognitive Impairment and Options forTreatment: Look What Comes from Talking About Things to Include in the Discussion Section of a Paper

F. Daniel Armstrong, PhD

mms://realaudio.service.emory.edu/SOM/PA/PLATT/SICKLE/Eckman/armstrong.wmv

 

Water, Water Everywhere, and Still the Cells Did Shrink…Red Cell Dehydration in Sickle Cell Disease Clinton Joiner, MD, PhD

mms://realaudio.service.emory.edu/SOM/PA/PLATT/SICKLE/Eckman/Joiner.wmv

 

Renal Complications of Sickle Cell Disease:Progress and Promise Antonio Guasch, MD

mms://realaudio.service.emory.edu/SOM/PA/PLATT/SICKLE/Eckman/Guasch.wmv

 

Sickle Cell Disease: Lessons Learned in the Past Four Decades Abdullah Kutlar, MD mms://realaudio.service.emory.edu/SOM/PA/PLATT/SICKLE/Eckman/Kutlar.wmv

 

Clinical Aspects of Sickle Cell Disease: A Coat of Many Colors Kathryn Hassell, MD mms://realaudio.service.emory.edu/SOM/PA/PLATT/SICKLE/Eckman/Hassell.wmv

 

Hematopoietic Cell Transplantation for Sickle Cell Disease Mark Walters, MD mms://realaudio.service.emory.edu/SOM/PA/PLATT/SICKLE/Eckman/Walters.wmv

 

Transfusion Consequences: Good, Bad and?? Cage Johnson, MD mms://realaudio.service.emory.edu/SOM/PA/PLATT/SICKLE/Eckman/Johnson.wmv

 

Microvascular Flow Dynamics: A 'Sticky' Problem in Sickle Cell Disease Timothy Wick, PhD mms://realaudio.service.emory.edu/SOM/PA/PLATT/SICKLE/Eckman/Wick.wmv

 

Closing Remarks and Special Presentations James Eckman, MD mms://realaudio.service.emory.edu/SOM/PA/PLATT/SICKLE/Eckman/Closingremarks.wmv

 

Oct 24, 2013: Current Data on Efficacy and Effectiveness of Hydroxyurea in Children with Sickle Cell Disease

Dr. Winfred Wang, St. Jude Children’s Research Hospital

mms://realaudio.service.emory.edu/SOM/PA/PLATT/SICKLE/CDC102913.wmv

Nov 7, 2013: Improved Survival of Children and Adolescents with Sickle Cell Disease

Dr. Charles Quinn, Cincinnati Children's Hospital Medical Center

mms://realaudio.service.emory.edu/SOM/PA/PLATT/SICKLE/CDC111313.wmv

...


 

CDC Web based Sickle Cell Resources

CDC’s YouTube Link: http://www.youtube.com/watch?v=gnrvYsZWR1c&list=UUiMg06DjcUk5FRiM3g5sqoQ&index=2&feature=plpp_video

 CDC Video Archive (http://scinfo.org/world-wide-resources/cdc-webinars-hemoglobinopathies-and-public-health

 CDC Sickle Cell Disease Webpage: http://wwwdev.cdc.gov/NCBDDD/sicklecell/video.html  

Articles in the Medical Literature for November

 

1.

Pediatr Blood Cancer. 2013 Nov 19. doi: 10.1002/pbc.24864. [Epub ahead of print]

Use of a clinical pathway to improve the acute management of vaso-occlusive crisis pain in pediatric sickle cell disease.

Ender KLKrajewski JABabineau JTresgallo MSchechter WSaroyan JM,Kharbanda A.

Department of Pediatrics, Division of Pediatric Hematology, Oncology, and Stem Cell Transplant, Columbia University, Medical Center, New York, New York.

Abstract

BACKGROUND:

The most common, debilitating morbidity of sickle cell disease (SCD) is vaso-occlusive crisis (VOC) pain. Although guidelines exist for its management, they are generally not well-followed, and research in other pediatric diseases has shown that clinical pathways improve care. The purpose of our study was to determine whether a clinical pathway improves the acute management of sickle cell vaso-occlusive crisis (VOC) pain in the pediatric emergency department (PED).

PROCEDURE:

Pain management practices were prospectively investigated before and after the initiation of a clinical pathway in the PED of an urban, tertiary care center with 50,000 ED visits per year and approximately 200 active sickle cell patients. The pathway included instructions for triage, monitoring, medication administration, and timing of assessments and interventions. Data were eligible from 35 pre-pathway and 33 post-pathway visits. Primary outcome was time interval to administration of first analgesic medication. Statistical analysis was by Student's t-test, using natural-log-transformed data for outcomes with skewed distribution curves.

RESULTS:

Time interval to first analgesic improved from 74 to 42 minutes (P = 0.012) and to first opioid from 94 to 46 minutes (P = 0.013). The percentage of patients who received ketorolac increased from 57% to 82% (P = 0.03). Decrease in time interval to subsequent pain score assessment was not statistically significant (110 to 72 minutes (P = 0.07)), and change in pain score was not different (P = 0.25).

CONCLUSIONS:

The use of a clinical pathway for sickle cell VOC in the PED can improve important aspects of pain management and merits further investigation and implementation. Pediatr Blood Cancer 2013;9999:1-4. © 2013 Wiley Periodicals, Inc.

© 2013 Wiley Periodicals, Inc.


PMID: 24249617 [PubMed - as supplied by publisher]


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2.

J Clin Gastroenterol. 2013 Nov 15. [Epub ahead of print]

Abdominal Pain in Children With Sickle Cell Disease.

Rhodes MMBates DGAndrews TAdkins LThornton JDenham JM.

*Nationwide Children's Hospital †Department of Pediatrics, The Ohio State University, Columbus, OH.

Abstract

The differential diagnosis of abdominal pain is broad in any child, and further complicated in children with sickle cell disease (SCD). Acute causes of abdominal pain may require emergent surgery, such as for appendicitis or obstruction caused by a bezoar. Rapid intervention is necessary and life-saving in children with SCD and acute splenic or hepatic sequestration. The majority of children with SCD presenting to the physician's office or emergency department will have subacute reasons for their abdominal pain, including but not limited to constipation, urinary tract infection, peptic ulcer disease, and cholecystitis. Vaso-occlusive pain often presents in children as abdominal pain, but is a diagnosis of exclusion. The case of a 10-year-old girl with intermittent abdominal pain is used as a starting point to review the pathophysiology, diagnosis, and treatment of the most acute and common causes of abdominal pain in children with SCD.


PMID: 24247814 [PubMed - as supplied by publisher]


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3.

Cochrane Database Syst Rev. 2013 Nov 14;11:CD003146. [Epub ahead of print]

Blood transfusion for preventing primary and secondary stroke in people with sickle cell disease.

Wang WCDwan K.

Department of Hematology, St Jude Children's Research Hospital, 262 Danny Thomas Place, Mail Stop 800, Memphis, Tennessee 38105, USA.

Abstract

BACKGROUND:

In sickle cell disease, a common inherited haemoglobin disorder, abnormal haemoglobin distorts red blood cells, causing anaemia, vaso-occlusion and dysfunction in most body organs. Without intervention, stroke affects around 10% of children with sickle cell anaemia (HbSS) and recurrence is likely. Chronic blood transfusion dilutes the sickled red blood cells, reducing the risk of vaso-occlusion and stroke. However, side effects can be severe.

OBJECTIVES:

To assess risks and benefits of chronic blood transfusion regimens in people with sickle cell disease to prevent first stroke or recurrences.

SEARCH METHODS:

We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register, comprising references identified from comprehensive electronic database searches and handsearches of relevant journals and conference proceedings.Date of the latest search of the Group's Haemoglobinopathies Trials Register: 28 January 2013.

SELECTION CRITERIA:

Randomised and quasi-randomised controlled trials comparing blood transfusion as prophylaxis for stroke in people with sickle cell disease to alternative or no treatment.

DATA COLLECTION AND ANALYSIS:

Both authors independently assessed the risk of bias of the included trials and extracted data.

MAIN RESULTS:

Searches identified three eligible randomised trials (n = 342). The first two trials addressed the use of chronic transfusion to prevent primary stroke; the third utilized the drug hydroxycarbamide (hydroxyurea) and phlebotomy to prevent both recurrent (secondary) stroke and iron overload in patients who had already experienced an initial stroke. In the first trial (STOP) a chronic transfusion regimen for maintaining sickle haemoglobin lower than 30% was compared with standard care in 130 children with sickle cell disease judged (through transcranial Doppler ultrasonography) as high-risk for first stroke. During the trial, 11 children in the standard care group suffered a stroke compared to one in the transfusion group, odds ratio 0.08 (95% confidence interval 0.01 to 0.66). This meant the trial was terminated early. The transfusion group had a high complications rate, including iron overload, alloimmunisation, and transfusion reactions. The second trial (STOP II) investigated risk of stroke when transfusion was stopped after at least 30 months in this population. The trial closed early due to a significant difference in risk of stroke between participants who stopped transfusion and those who continued as measured by reoccurrence of abnormal velocities on Doppler examination or the occurrence of overt stroke in the group that stopped transfusion. The third trial (SWiTCH) was a non-inferiority trial comparing transfusion and iron chelation (standard management) with hydroxyurea and phlebotomy (alternative treatment) with the combination endpoint of prevention of stroke recurrence and reduction of iron overload. This trial was stopped early after enrolment and follow up of 133 children because of analysis showing futility in reaching the composite primary endpoint. The stroke rate (seven strokes on hydroxyurea and phlebotomy, none on transfusion and chelation, odds ratio 16.49 (95% confidence interval 0.92 to 294.84)) was within the non-inferiority margin, but the liver iron content was not better in the alternative arm.

AUTHORS' CONCLUSIONS:

The STOP trial demonstrated a significantly reduced risk of stroke in participants with abnormal transcranial Doppler ultrasonography velocities receiving regular blood transfusions. The follow-up trial (STOP 2) indicated that individuals may revert to former risk status if transfusion is discontinued. The degree of risk must be balanced against the burden of chronic transfusions. The combination of hydroxyurea and phlebotomy is not as effective as "standard" transfusion and chelation in preventing secondary stroke and iron overload. Ongoing multicentre trials are investigating the use of chronic transfusion to prevent silent infarcts, the use of hydroxyurea as an alternative to transfusion in children with abnormal transcranial Doppler ultrasonography velocities, and the use of hydroxyurea to prevent conversion of transcranial Doppler ultrasonography velocities from conditional (borderline) to abnormal values.


PMID: 24226646 [PubMed - as supplied by publisher]


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Sickle Cell News for October 2013

Children's-Emory receive $10M grant for sickle cell research

Children’s Healthcare of Atlanta and Emory University have received a grant of almost $10 million to target lung damage that causes death in children with sickle cell disease.

Sickle Cell Disease is the most common single-gene disorder in the nation, affecting about 100,000 Americans, according to a statement.

The National Heart Lung and Blood Institute grant will provide about $2 million in funding annually over five years, is aimed at helping find a treatment that could stem a complication of sickle cell disease called “acute chest syndrome.”

Acute chest syndrome damages the lungs, causing them to fill with fluid and sometimes resulting in respiratory failure.

Specifically, the grant calls for Emory and the Aflac Cancer and Blood Disorders Center of Children’s Healthcare of Atlanta to accomplish two key goals — find a drug that would protect, stop or stem lung damage in sickle cell patients; and develop innovative therapies for sickle cell and its complications.

The Aflac Cancer Center was a frontrunner for the grant because it treats the largest population of sickle cell patients in the nation and focuses on acute chest syndrome.

Emory won the grant because of its research on a receptor called the Toll-like receptor #4 or TLR-4.

This receptor is tied to the often-deadly process that occurs in sickle cell patients, in which heme, released from hemoglobin when sickle red blood cells are fragmented in the circulation, triggers a toxic inflammatory response by TLR-4 that damages the lungs. This creates a vicious cycle of more heme being released, and more lung damage occurring, sometimes until the patient dies.

The grant aims to prove that the TLR-4 receptor is the key to acute chest syndrome; and to find a drug, or a biological agent that could block the TLR-4 from performing its deadly task, the statement noted.

 

New Study Findings: Invasive Pneumococcal Disease among Children with and without Sickle Cell Disease in the United States, 1998-2009

 The journal Pediatric Infectious Diseases recently published a CDC study “Invasive Pneumococcal Disease among Children with and without Sickle Cell Disease in the United States, 1998-2009.” A summary of the key findings from this article is shown in the screen capture below.  To review these findings and their implications, please click here.

 

From the American Academy of Pediatrics - Need affordable health insurance for your family?  http://aapnews.aappublications.org/content/34/10/40.5.full.pdf+html

By January 1, almost all Americans must have health insurance. If you do not have health insurance, you may have to pay a fee. The requirement is part of the Affordable Care Act, the health care law signed by President Obama in 2010. Now is a good time to see what health insurance benefits are best for your family and whether you qualify for a lower cost plan. If your family already has health insurance through an employer, thereis no need to change anything. Children under age 26 can be covered on their parents’ health plan. If you do not have health insurance, you can find options through yourstate’s Health Insurance Marketplace. You can sign up for an insurance plan during the open enrollment period, Oct. 1 through March 31. After March 31, you can make changes to your insurance if there is a life change, such as a new baby, a change in income or job change/loss.
Families who have used Medicaid or a Children’s Health Insurance Program state-funded plan should make sure they still are able to get the same benefits. Under the new health insurance options, for example, some families may have children who will stay on Medicaid while parents buy their own health insurance through the Health Insurance Marketplace, an insurance company or a broker.
If your family needs health insurance, here’s what to do:Step 1: Visit the American Academy of Pediatrics’ Healthy Children website, www.healthychildren.org/ACAmarketplace,
which explains the Affordable Care Act and the Health Insurance Marketplace. Look for the map and click on your state to find out where to get help. You also can go to http://www.healthcare.gov/or call 800-318-2596 to get information on choosing
and enrolling in a plan.
Step 2: Is your child’s primary care doctor a pediatrician? Your pediatrician knows what care your child should get and when. New insurance plans now cover the cost of preventive care (checkups). Anyone 19 years old or younger with a preexisting
condition must be insured, by law. People age 26 and younger who were in foster care at age 18 can sign up to be insured by Medicaid starting on Jan. 1.
Step 3: Look at all options and prices. When deciding whether to use a marketplace plan or private insurance, consider that the marketplace price is based on family size and income. Choose what is best for your family
.

From the SCDAA - How does the ACA protect you as an individual living with sickle cell disease? SCDAA wants to point out how ACA can improve the healthcare of people with sickle cell disease.

1. Insurers can no longer deny coverage to anyone with a chronic or pre-existing health condition such as sickle cell disease. Children and adults are now able to get insurance that covers treatment of their illnesses.

2. Lifetime caps on coverage have been removed and insurers have to set annual limits on essential health services at a minimum of $750,000.

What does this mean? This means that health insurance companies cannot deny coverage to anyone with a chronic health condition such as sickle cell disease. Furthermore, your health insurance company can no longer set a limit on how much of your health care costs they will pay forever, this is known as "lifetime cap".

 

Tanzania Marks Sickle Cell Awareness Month

This September, Tanzania marked the Sickle Cell Awareness Month- September through various activities conducted with the main aim of raising awareness of the disease and improving lives. On 23rd September 2013, Dr. Stella, Head of Clinical Haematology at the Muhimbili National Hospital together with the Honeymoon Aljabri, Director of Motion Arts Production Tanzania (MAPTz) held a press conference at the Maelezo House in Dar-es-salaam to talk about the disease and various activities to be done for the Sickle Cell Awareness Month. They went on to appear at two big television stations in the country; TBC and EATV and give talks on national radio stations; TBC FM and East Africa Radio.  Their appearances were also to give health education to the general public about the disease and urged individuals to get tested at the Muhimbili National Hospital. This is the national referral hospital which has a Sickle Cell Disease (SCD) cohort

 

On 28th September 2013, MAPTz organized and orchestrated a 5Km walk for Sickle Cell in Dar-es-salaam, Tanzania. Participants walked from The National Stadium, then along Kilwa Road and back to the stadium. The motto of the walk was “Fight Sickle Cell Out of Tanzania” a message meant to inspire people to get tested with their families In order to prevent mortality from SCD. Dr. Stella of Muhimbili National Hospital once again talked about the disease but also mentioned challenges currently incurred by health care professionals in SCD Management.

Leading up to the campaign, Motion Arts Production Tanzania conducting a “Fight Sickle Cell Out of Africa Campaign” in Houston, Texas. More about this can be found on: http://www.newafricatv.com/tv-shows/fight-sickle-cell-out-of-africa

 

Linking Screening and Support for Sickle Cell –A report from Georgia

                                                                                                                                                                                                                                                                                                     

New Videos   

Sept 26, 2013: The Road to the Evidence Based Management of Sickle Cell Disease: Expert Panel Report

mms://realaudio.service.emory.edu/SOM/PA/PLATT/SICKLE/CDC092613.wmv

...

 

CDC Web based Sickle Cell Resources

CDC’s YouTube Link: http://www.youtube.com/watch?v=gnrvYsZWR1c&list=UUiMg06DjcUk5FRiM3g5sqoQ&index=2&feature=plpp_video

 CDC Video Archive (http://scinfo.org/world-wide-resources/cdc-webinars-hemoglobinopathies-and-public-health

 CDC Sickle Cell Disease Webpage: http://wwwdev.cdc.gov/NCBDDD/sicklecell/video.html  

Articles in the Medical Literature for October

 

1.

J Public Health (Oxf). 2013 Oct 29. [Epub ahead of print]

Socio-economic deprivation and risk of emergency readmission and inpatient mortality in people with sickle cell disease in England: observational study.

Aljuburi GLaverty AAGreen SAPhekoo KJBell DMajeed A.

Department of Primary Care and Public Health, Imperial College London, London W6 8RP, UK.

Abstract

BACKGROUND:

Sickle cell disease (SCD) is a cause of frequent emergency readmissions. We examined trends in SCD emergency readmissions and inpatient mortality in England in relation to socio-economic status.

METHODS:

Data from Hospital Episode Statistics were extracted for all SCD patients admitted in 2005/06. The financial year 2005/06 was taken as the index year for analysis. We calculated readmission rates and inpatient mortality for patients admitted with a primary or secondary diagnosis of sickle cell anaemia with crisis and without crisis in the index year during the subsequent 5 years (2006/07-2010/11). Charlson Score was used to measure comorbidity. Using Cox proportional hazards models, we also examined the relationship between patient characteristics and both emergency readmissions and inpatient mortality.

RESULTS:

In 2005/06, there were 7679 SCD index admissions. Over the subsequent 5-year period, patients living in the most socio-economically deprived areas were at highest risk of readmission (54.2% readmitted over the study period compared with 28% of the least deprived group). Inpatient mortality amongst readmissions was highest in patients living in the most deprived areas [hazard ratio (HR) 2.34, 95% CI 1.41-3.90].

CONCLUSION:

SCD patients from the most socio-economically deprived areas and with comorbidities are at highest risk of both SCD readmissions and in-hospital mortality, suggesting that there are inequalities in healthcare access and health outcomes amongst people with SCD.


PMID: 24169414 [PubMed - as supplied by publisher]


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2.

Pediatrics. 2013 Oct 28. [Epub ahead of print]

Association of Hospital and Provider Types on Sickle Cell Disease Outcomes.

Jan SSlap GSmith-Whitley KDai DKeren RRubin DM.

Department of Medicine, and.

Abstract

OBJECTIVES:Adolescents and young adults (A/YA) with sickle cell disease (SCD) are hospitalized in both children's and general hospitals. We determined the effect of hospital type and provider specialty on outcomes of hospitalized A/YA with SCD and acute chest syndrome (ACS).METHODS:This retrospective cohort study used the 2007-2009 Premier Database, a large multi-institutional database, to identify 1476 patients ages 16 to 25 years with 2299 admissions with SCD and ACS discharged from 256 US hospitals from 2007 to 2009. Multilevel logistic regression and zero-truncated negative binomial regression were performed after adjustment for patient demographic, clinical, and hospital characteristics to test the association of hospital type and provider specialty on death, endotracheal intubation, simple or exchange transfusion, length of stay (LOS), and 30-day readmission.RESULTS:Of all admissions, 14 died and 45% were intubated. General hospitals had 13 deaths and were associated with higher intubation rates (predicted probability [PP], 48% [95% confidence interval (CI), 43%-52%]) and longer LOS (predicted mean LOS, 7.6 days [95% CI, 7.2-7.9]) compared with children's hospitals (PP of intubation, 24% [95% CI, 5%-42%]; and predicted mean LOS, 6.8 days [95% CI, 5.6-5.8]). There was no difference by hospital type or provider specialty in PP of simple or exchange transfusion, or 30-day readmission.CONCLUSIONS:General hospitals carry higher intubation risks for A/YA with SCD and ACS compared with children's hospitals. We need to better understand the drivers of these differences, including the role of staff expertise, hospital volume, and quality of ongoing SCD care.


PMID: 24167173 [PubMed - as supplied by publisher]


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3.

Pediatr Blood Cancer. 2013 Oct 26. doi: 10.1002/pbc.24838. [Epub ahead of print]

Neuropathic pain in patients with sickle cell disease.

Brandow AMFarley RAPanepinto JA.

Section of Pediatric Hematology/Oncology, Milwaukee, Wisconsin; Medical College of Wisconsin, Milwaukee, Wisconsin; Children's Research Institute of the Children's Hospital of Wisconsin, Milwaukee, Wisconsin.

Abstract

BACKGROUND:

Despite the suggestion of a neuropathic component to sickle cell disease (SCD) pain, there are minimal data on the systematic assessment of neuropathic pain in patients with SCD. Neuropathic pain is defined as pain primarily initiated by dysfunction of the peripheral or central nervous system.

PROCEDURE:

In a cross-sectional study, we used the painDETECT questionnaire, a one-page validated neuropathic pain screening tool, to determine the presence of neuropathic pain in patients with SCD and to evaluate the relationship between neuropathic pain, age, and gender. We hypothesized that 20% of patients with SCD will experience neuropathic pain and that neuropathic pain will be associated with older age and female gender. The completed painDETECT questionnaire yields a total score between 0 and 38 (≥19 = definite neuropathic pain, 13-18 = probable neuropathic pain, ≤12 = no neuropathic pain). Scores ≥13 were designated as having evidence of neuropathic pain.

RESULTS:

A total of 56 patients participated. Median age was 20.3 years and 77% were female. We found 37% of patients had evidence of neuropathic pain. Age was positively correlated with total score (r = 0.43; P = 0.001) suggesting older patients experience more neuropathic pain. Females had higher mean total scores (13 vs. 8.4; P = 0.04). Significantly more patients with neuropathic pain were taking hydroxyurea (90% vs. 59%; P = 0.015). Despite 37% of patients experiencing neuropathic pain, only 5% were taking a neuropathic pain drug.

CONCLUSIONS:

Neuropathic pain exists in SCD. Valid screening tools can identify patients that would benefit from existing and future neuropathic pain therapies and could determine the impact of these therapies. Pediatr Blood Cancer © 2013 Wiley Periodicals, Inc.

© 2013 Wiley Periodicals, Inc.


PMID: 24167104 [PubMed - as supplied by publisher]


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4.

Clin Chem. 2013 Oct 24. [Epub ahead of print]

Newborn Blood Spot Screening for Sickle Cell Disease by Using Tandem Mass Spectrometry: Implementation of a Protocol to Identify Only the Disease States of Sickle Cell Disease.

Moat SJRees DKing LIfederu AHarvey KHall KLloyd GMorell CHillier S.

Wales Newborn Screening Laboratory, Department of Medical Biochemistry, Immunology & Toxicology, and.

Abstract

BACKGROUND:

The currently recommended technologies of HPLC and isoelectric focusing for newborn blood spot screening for sickle cell disease (SCD) identify both the disease and carrier states, resulting in large numbers of infants being followed up unnecessarily. Analysis of blood spot tryptic peptides performed by using tandem mass spectrometry (MS/MS) is an alternative technology to detect hemoglobin (Hb) variant disorders.METHODS: We analyzed 2154 residual newborn blood spots and 675 newborn blood spots from infants with Hb variants by using MS/MS after trypsin digestion. Screening cutoffs were developed by using the ratio between the variant peptide-to-wild-type peptide abundance for HbS, C, DPunjab, OArab, Lepore, and E peptides. A postanalytical data analysis protocol was developed using these cutoffs to detect only the disease states of SCD and not to identify carrier states. A parallel study of 13 249 newborn blood spots from a high-prevalence SCD area were analyzed by both MS/MS and HPLC.RESULTS: Screening cutoffs developed distinguished the infants with the disease states of SCD, infants who were carriers of SCD, and infants with normal Hb. In the parallel study no false-negative results were identified, and all clinically relevant cases were correctly identified using the MS/MS protocol. Unblinding the data revealed a total of 328 carrier infants that were successfully excluded by the protocol.CONCLUSIONS: The screening protocol developed correctly identified infants with the disease states of SCD. Furthermore, large numbers of sickle cell carrier infants were successfully not identified, thereby avoiding unnecessary follow-up testing and referral for genetic counseling.


PMID: 24158758 [PubMed - as supplied by publisher]


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5.

Curr Opin Endocrinol Diabetes Obes. 2013 Oct 21. [Epub ahead of print]

An update on the recent literature on sickle cell bone disease.

Osunkwo I.

Children's Healthcare of Atlanta and The Department of Pediatrics Emory University, Atlanta, Georgia, USA.

Abstract

PURPOSE OF REVIEW:

To summarize the findings of the recent publications on sickle cell bone disease (SBD).

RECENT FINDINGS:

Individuals with sickle cell disease (SCD) are living longer and develop progressive organ damage including SBD with age. Recent studies suggest alternative radiological diagnostics such as ultrasound and scintigraphy can detect and differentiate between different forms of SBD. MRI with or without diffusion-weighted sequences remains the gold standard. Case reports of cranio-orofacial SBD highlight the rarity of this presentation. Vitamin D deficiency is highly prevalent at all ages, but may not be an independent risk factor for avascular necrosis (AVN). Gene polymorphisms of the Annexin A gene may predict AVN in SCD. A recent study demonstrated reduced days with pain and improved physical activity quality of life following high-dose vitamin D therapy. The high rates of osteopenia and osteoporosis in SCD support the need for research addressing this rising public health problem. Lastly, results of total hip arthroplasty for AVN in SCD has improved significantly over time with the use of cementless prosthetic material and improved supportive care.

SUMMARY:

SBD remains poorly studied. Prospective randomized studies targeting predictors, diagnostics, prevention, and treatment options for SBD are sorely needed.


PMID: 24150191 [PubMed - as supplied by publisher]


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6.

Medsurg Nurs. 2013 Jul-Aug;22(4):255-7.

Optimizing adolescent transition to adult care for sickle cell disease.

Cerns SMcCracken CRich C.

Inpatient Medicine/Hematology-Oncology/Palliative Care Unit, Froedtert Hospital, Milwaukee, WI, USA.

Abstract

Transitioning health care from a pediatric to an adult environment in a patient with sickle cell disease presents challenges. A program developed to assist with transition is described.


PMID: 24147324 [PubMed - in process]


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7.

J Med Screen. 2013 Oct 21. [Epub ahead of print]

Universal newborn screening for haemoglobinopathies in Guadeloupe (French West Indies): A 27-year experience.

September is Sickle Cell Month

 

 Drug reduces hospitalizations and cost of treating young children with sickle cell anemia

The St. Jude Children’s Research Hospital-led national BABY HUG trial linked hydroxyurea to a 21 percent reduction in annual medical costs for young children with sickle cell anemia; savings expected to grow. A drug proven effective for treatment of adults and children with sickle cell anemia reduced hospitalizations and cut annual estimated medical costs by 21 percent for affected infants and toddlers, according to an analysis led by St. Jude Children’s Research Hospital. The report appears today in the advance online edition of the journal Pediatrics.

The study is the largest ever focusing on the economic impact of the drug hydroxyurea in children with the inherited blood disorder. The result supports expanded use of the drug to extend the length and quality of life for sickle cell anemia patients of all ages, said Winfred Wang, M.D., a member of the St. Jude Department of Hematology and principal investigator of the multicenter federally funded trial known as BABY HUG.

“We estimate that hydroxyurea cut overall annual medical expenses about $3,000 for each patient by helping patients avoid disease complications that require inpatient hospital care,” said Wang, who is first and corresponding author of the Pediatrics study. “We expect those savings will grow along with patients, whose symptoms often increase in severity and frequency as they age.”

About 100,000 individuals in the U.S. and millions worldwide have sickle cell disease, which leaves them at risk for premature death and disability. The disease is the most common genetic disorder affecting African-American individuals, but those from other ethnic and racial backgrounds also inherit mutations in the hemoglobin gene. The mutations result in blood cells that are prone to assuming the sickled shape that gives the disease its name and that leave patients at increased risk for episodes of acute pain, stroke, organ damage and other complications.

The analysis comes two years after Wang and his colleagues reported that hydroxyurea reduced episodes of acute pain and pneumonia-like illness, eased other symptoms, reduced the need for blood transfusions and cut hospitalizations for infants and toddlers with sickle cell anemia. Sickle cell anemia is the most common and severe form of sickle cell disease.

Earlier studies had demonstrated that adults and adolescents with the disease benefited from hydroxyurea. BABY HUG showed the drug, which is inexpensive and easy to administer, was safe and effective for young children. The study involved 193 children who were 9 to 18 months old when they enrolled at one of the 13 participating medical centers. The children were randomly assigned to receive either a daily dose of hydroxyurea for two years or an inactive look-alike.

Continued concern about U.S. health care spending prompted BABY HUG researchers to retrospectively assess hydroxyurea’s impact on treatment costs. Investigators used a national database of Medicaid expenditures to estimate the 2009 cost of caring for BABY HUG participants. Medicaid is the state-federal health insurance program that covers lower income and disabled children and adults. The six-year BABY HUG study ended in 2009.

The results showed that hydroxyurea was associated with higher outpatient costs, but lowered overall expenditures. Children who received the drug were hospitalized 232 times during the study, compared to 324 hospitalizations for those in the placebo group. The estimated annual treatment cost $11,072 for children who received hydroxyurea compared to $13,962 for children who received the placebo.

Wang said actual savings associated with hydroxyurea treatment are likely greater, since medical costs are roughly 25 percent less for children enrolled in Medicaid than for those with private health insurance. The analysis was unable to capture all treatment-related costs. “The analysis also could not capture the anxiety patients and family experience when children must be hospitalized,” Wang said.

Hydroxyurea was developed in the 1960s as a possible anti-cancer agent. It won approval for treatment of adults and later adolescents with sickle cell anemia in 1998 following evidence that the drug reduced episodes of severe pain and improved patient quality of life.

The drug works by increasing production of fetal hemoglobin, a form of the oxygen-carrying protein that is unaffected by the mutations that cause sickle cell disease. Fetal hemoglobin normally drops dramatically after birth. Hydroxyurea, however, increases production of red blood cells that contain that form of hemoglobin.

The drug remains an underutilized treatment for sickle cell anemia. Wang estimated the drug is prescribed to about 30 percent of pediatric patients nationwide and an even smaller percentage of adults. Work is underway at St. Jude and other medical centers to identify and address barriers to more widespread use of the drug, including lingering concerns about possible long-term toxicity.

 Sickle Cell News for September 2013

SCDAA Receives $250,000 Research Gift

SCDAA is proud to announce that we have received a $250,000 donation to further research programming. The award will be used to expand SCDAA’s overall research agenda. SCDAA Chief Medical Officer Dr. Kim Smith-Whitley says this gift is an important opportunity. “We are so grateful for this gift. It is a great opportunity for SCDAA to expand our research program efforts,” she says.

University of Pittsburgh and UPMC are developing better treatments for children and adults with sickle cell disease (SCD).

Their ultimate goal is to find a cure. Pittsburgh Steelers captain Ryan Clark, who has personally been affected by SCD, supports their work. As a sickle cell trait carrier, he experienced a life-threatening crisis—brought on by altitude—while playing a game in Denver. Sadly, he also lost his sister-in-law to complications from SCD. She was only 27.

“After my ordeal in Denver, and following Kim’s death, my wife and I prayed daily for guidance about what to do next. I didn’t just want to lend my name to a cause; I wanted to get involved in a big way. That’s when we approached the University of Pittsburgh and UPMC about our idea of creating Ryan Clark’s Cure League,” Clark says.

UPMC, in a push to achieve advances in sickle cell research and treatment, has recruited three national leaders in the disease, the medical center announced this week.

"It is pretty unprecedented to have this many people focused on sickle cell come together in one place, so it is very exciting," said Mark Gladwin, director of the Pittsburgh Heart, Lung, Blood and Vascular Medicine Institute.

Solomon Ofori-Acquah from Emory University in Atlanta and Gregory Kato from the National Heart, Lung and Blood Institute at the National Institutes of Health are already here. Laura DeCastro will come to Pittsburgh from Duke University in January.

The will help UPMC in "creating a critical mass" to make progress against the disease, Dr. Gladwin said. The new hires, together with existing researchers and doctors at UPMC, represent an "impressive scope of experience," said Dr. Kato, that extends "from bench to bedside."

 

New Book Resource for Adolescent Sickle Cell Patients

Hope and Destiny Jr. ISBN 978-0-9764449-1-2 Hilton Publishing,

Adolescence transition to adulthood in sickle cell is an important and a high-risk period. This book aims to address some of the needs of the adolescent preparing for transition.  It is intended to:

  • Emphasize patient-centered topics, like delayed puberty.
  • Counsel like an experienced sickle cell doctor in the office, but with more pictures.
  • Connect to peers with real stories from teens and children with sickle cell
  • Provide inspiration / role models for career & education

A recent review of sickle cell adolescent transition  (Jordan L, Swerdlow P, Coates TD.Systematic review of transition from adolescent  to adult care in patients with sickle cell disease. Pediatr Hematol Oncol. 2013 Apr;35(3):165-9.) includes recommendations for age-appropriate educational materials, education that anticipates common fears and concerns of teens.

Hilton Publishing's #1 bestselling book to the general market is now available in a book just for children and adolescents! Hope and Destinyremains the only comprehensive, culturally sensitive book on sickle cell disease on the market and now children have a book, with many pictures and a game, which they can read themselves to learn about their special disease.

Hope and Destiny Jr. is the best resource available for young patients and families impacted by sickle cell disease. It is the only comprehensive book on the market especially for children that tackles all aspects of the disease. The book discusses:

  • How did I get sickle cell, and is it contagious?
  • What can and can't I do because I have sickle cell?
  • The most current treatment options
  • Symptoms of sickle cell and how to reduce them
  • The unique changes and challenges faced by children with sickle cell
  • Pain assessment and management that children can do better on their own.
  • Strategies to lower the likelihood of pain episodes
  • How to communicate frustrations and emotions associated with sickle cell

Authors: Lewis L. Hsu, MD, PhD is the director of the pediatric sickle cell program and a professor of pediatric hematology-oncology at Children's Hospital University of Illinois.

Silvia R. Brandalise, MD is the pediatric hematology-oncology service coordinator at the Medical Science of Campinas (UNICAMP), São Paulo, Brazil, and is the general secretary of the Latin American Society of Pediatric Oncology (SLAOP).

Carmen C.M. Rodrigues, RN, is a graduate of the State University of Campinas (UNICAMP) with a master's degree focusing on sickle cell disease and is a member of the technical advisory group on sickle cell disease at the Ministry of Health, São Paulo, Brazil.  Seehttp://www.hiltonpub.com/bookstore/products/56026-hope-and-destiny-jr.aspx Bulk pricing available. For more information, or to place an order, contact Daniel at dderousseau@hiltonpub.com or 219-922-4868.

New Videos

Aug 22, 2013: Mental Health and Learning Needs in children with Sickle Cell Disease Dr. Patricia Kavanagh, Boston University School of Medicine/Boston Medical Center

 mms://realaudio.service.emory.edu/SOM/PA/PLATT/SICKLE/CDC072513.wmv

SAVE THE DATES

Fellow colleagues, you are invited to participate in the“Public Health Webinar Series on Hemoglobinopathies” Hosted by: The Division of Blood Disorders, CDC

4th Thursday of every month from 2:00PM – 3:00PM EST

9/26: NHLBI Sickle Cell Disease Guidelines

     Dr. Joylene John-Sowah, National Heart Lung and Blood Institute, NIH   

10/24: Current Data on Efficacy and Effectiveness of Hydroxyurea in Children with Sickle Cell Disease

     Dr. Winfred Wang, St. Jude Children’s Research Hospital 

November/December: --- No Webinars---

If you have ideas on topics for future webinars, or have any questions or comments about this series please submit them to Shae Pope spope@cdc.gov .

The purpose of this webinar series is to offer a hemoglobinopathies learning collaborative platform for providers, consumers, educators, and scientists. 

 

CDC Web based Sickle Cell Resources

CDC’s YouTube Link: http://www.youtube.com/watch?v=gnrvYsZWR1c&list=UUiMg06DjcUk5FRiM3g5sqoQ&index=2&feature=plpp_video

 CDC Video Archive (http://scinfo.org/world-wide-resources/cdc-webinars-hemoglobinopathies-and-public-health

 CDC Sickle Cell Disease Webpage: http://wwwdev.cdc.gov/NCBDDD/sicklecell/video.html  

Articles in the Medical Literature for September

 

 

1.

Pediatr Blood Cancer. 2013 Sep 4. doi: 10.1002/pbc.24711. [Epub ahead of print]

Newborn screening program for hemoglobinopathies in Rio de Janeiro, Brazil.

de Castro Lobo CLBallas SKDomingos ACMoura PGdo Nascimento EMCardoso GPde Carvalho SM.

Clinical Hematology Division, Instituto de Hematologia Arthur de Siqueira Cavalcanti-HEMORIO, Rio de Janeiro, RJ, Brazil.

Abstract

BACKGROUND:

Newborn screening for hemoglobinopathy in Brazil has been decentralized until 2001 when the Health Ministry of Brazil established the National Newborn Hemoglobinopathy Screening Program. The State of Rio de Janeiro started a program in collaboration with the State Health Department and the Institute of Hematology in Rio (HEMORIO). The goal of this study was to evaluate the effectiveness of the first 10 years of the Newborn Hemoglobinopathy Screening Program in identifying and managing infants with Sickle cell disease (SCD) in the State of Rio de Janeiro.

PROCEDURE:

Blood samples from 1,217,833 neonates were analyzed by High Performance Liquid Chromatography. Infants with SCD were enrolled in comprehensive treatment programs.

RESULTS:

Data showed that 4.87% of the newborns were heterozygous for a hemoglobin variant, 0.08% were homozygous or doubly heterozygous for abnormal hemoglobins and 95.02% had normal hemoglobin. All the 912 newborns with SCD were referred for treatment at HEMORIO, 34 (3.7%) of these died due to acute chest syndrome, sepsis or splenic sequestration. Four more children died of unknown causes. The implementation of the Rio de Janeiro Newborn Screening Program gradually increased the area of the State covered by the program.

CONCLUSION:

Data collected during the 10 years of the program showed reduction in mortality of patients with SCD in comparison to available historical statistical data before the implementation of the national screening program. This 10-year study showed that early diagnosis and treatment of newborns was associated with improved survival and quality of life of Brazilian children with SCD. Pediatr Blood Cancer © 2013 Wiley Periodicals, Inc.

© 2013 Wiley Periodicals, Inc.


PMID: 24038856 [PubMed - as supplied by publisher]


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2.

Pediatr Blood Cancer. 2013 Sep 2. doi: 10.1002/pbc.24744. [Epub ahead of print]

Comparison of automated red cell exchange transfusion and simple transfusion for the treatment of children with sickle cell disease acute chest syndrome.

Saylors RLWatkins BSaccente STang X.

Division of Pediatric Hematology and Oncology, Arkansas Children's Hospital and University of Arkansas for Medical Sciences, Little Rock, Arkansas.

Abstract

BACKGROUND:

Both simple transfusion (ST) of packed red blood cells and automated red cell exchange (RCE) are used in the treatment of acute chest syndrome (ACS). We report our experience using each of these modalities for the treatment of ACS.

METHODS:

Retrospective chart review of patients with ACS treated with ST only (51 episodes, ST group) or RCE performed either at diagnosis (U-RCE group, 15 episodes) or after ST (ST + RCE group, 15 episodes).

RESULTS:

The mean clinical respiratory score (CRS) at diagnosis was significantly higher in the U-RCE group than in the ST group, but there were no significant differences among the other groups. The CRS and WBC each decreased significantly after simple transfusion in the ST group and after RCE in the U-RCE group, but both the CRS and WBC increased significantly, and the mean platelet count fell significantly, after simple transfusion in the ST + RCE group. Only patients in the ST + RCE group required mechanical ventilation. There were no significant differences in length of stay (LOS) or total hospital charges among any of the groups, probably due to the small sample size.

CONCLUSIONS:

We conclude that the CRS identifies the patients who are most severely affected with ACS, and that upfront RCE is a safe and effective treatment for these patients. Additional work is needed to develop a method to predict which of the apparently less severely affected patients will fail to improve after simple transfusion and should receive upfront RCE. Pediatr Blood Cancer © 2013 Wiley Periodicals, Inc.

© 2013 Wiley Periodicals, Inc.


PMID: 24000077 [PubMed - as supplied by publisher]


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3.

Pediatrics. 2013 Sep 2. [Epub ahead of print]

Hydroxyurea Is Associated With Lower Costs of Care of Young Children With Sickle Cell Anemia.

Wang WCOyeku SOLuo ZBoulet SLMiller STCasella JFFish BThompson BWGrosse SDfor the BABY HUG Investigators.

Department of Hematology, St Jude Children's Research Hospital, Memphis, Tennessee;

Abstract

BACKGROUND AND OBJECTIVE:In the BABY HUG trial, young children with sickle cell anemia randomized to receive hydroxyurea had fewer episodes of pain, hospitalization, and transfusions. With anticipated broader use of hydroxyurea in this population, we sought to estimate medical costs of care in treated versus untreated children.METHODS:The BABY HUG database was used to compare inpatient events in subjects receiving hydroxyurea with those receiving placebo. Unit costs were estimated from the 2009 MarketScan Multi-state Medicaid Database for children with sickle cell disease, aged 1 to 3 years. Inpatient costs were based on length of hospital stay, modified by the occurrence of acute chest syndrome, splenic sequestration, or transfusion. Outpatient expenses were based on the schedule required for BABY HUG and a "standard" schedule for 1- to 3-year-olds with sickle cell anemia.RESULTS:There were 232 hospitalizations in the subjects receiving hydroxyurea and 324 in those on placebo; length of hospital stay was similar in the 2 groups. Estimated outpatient expenses were greater in those receiving hydroxyurea, but these were overshadowed by inpatient costs. The total estimated annual cost for those on hydroxyurea ($11 072) was 21% less than the cost of those on placebo ($13 962; P = .038).CONCLUSIONS:Savings on inpatient care resulted in a significantly lower overall estimated medical care cost for young children with sickle cell anemia who were receiving hydroxyurea compared with those receiving placebo. Because cost savings are likely to increase with age, these data provide additional support for broad use of hydroxyurea treatment in this population.


PMID: 23999955 [PubMed - as supplied by publisher]


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4.

Am J Hematol. 2013 Aug 31. doi: 10.1002/ajh.23586. [Epub ahead of print]

Frequent red cell transfusions reduced vascular endothelial activation and thrombogenicity in children with sickle cell anemia and high stroke risk.

Hyacinth HIAdams RJVoeks JHHibbert JMGee BE.

Stroke Center, Department of Neuroscience, Medical University of South Carolina, Charleston, SC; Department of Microbiology, Biochemistry and Immunology, Morehouse School of Medicine, Atlanta, Georgia.

Abstract

Stroke is one of the most disabling complications of sickle cell anemia (SCA). The molecular mechanisms leading to stroke in SCA or by which packed red blood cell (PRBC) transfusion prevents strokes are not understood. We investigated the effects of PRBC transfusion on serum biomarkers in children with SCA who were at high-risk for stroke. Serum samples from 80 subjects were analyzed, including baseline, study exit time point and 1 year after study exit. Forty of the 80 samples were from subjects randomized to standard care and 40 from transfusion arm. Samples were assayed for levels of BDNF, sVCAM-1, sICAM-1, MPO, Cathepsin-D, PDGF-AA, PDGF-AB/BB, RANTES (CCL5), tPAI-1 and NCAM-1 using antibody immobilized bead assay. Significantly lower mean serum levels of sVCAM-1 (2.2X106 ±0.8X106 pg/ml vs. 3.1X106±0.9X106 pg/ml, p<0.0001), Cathepsin-D (0.5X106 ±0.1X106 pg/ml vs. 0.7X106 ±0.2X106 pg/ml, p<0.0001), PDGF-AA (10556±4033pg/ml vs. 14173±4631pg/ml, p=0.0008), RANTES (0.1X106 ±0.07X106 pg/ml vs. 0.2X106 ±0.06X106 pg/ml, p<0.006), and NCAM-1 (0.7X106 ±0.2X106 pg/ml vs. 0.8X106 ±0.1X106pg/ml, p<0.0006) were observed among participants who received PRBC transfusion, compared to those who received standard care. Twenty or more PRBC transfusion over 4 years was associated with lower serum levels of sVCAM-1 (p<0.001), PDGF-AA (p=0.025) and RANTES (p=0.048). Low baseline level of BDNF (p=0.025), sVCAM-1 (p=0.025), PDGF-AA (p=0.01), t-PAI-1 (p=0.025) and sICAM-1 (p=0.022) was associated with higher probability of stroke free survival. Beyond improving hemoglobin levels, our results suggest that the protective effects of PRBC transfusion on reducing stroke in SCD may result from reduced thrombogenesis and vascular remodeling.

Copyright © 2013 Wiley Periodicals, Inc., A Wiley Company.


PMID: 23996496 [PubMed - as supplied by publisher]


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5.

Arch Dis Child. 2013 Aug 30. doi: 10.1136/archdischild-2012-302387. [Epub ahead of print]

Evidence review of hydroxyurea for the prevention of sickle cell complications in low-income countries.

Mulaku MOpiyo NKarumbi JKitonyi GThoithi GEnglish M.

School of Pharmacy, University of Nairobi, , Nairobi, Kenya.

Abstract

Hydroxyurea is widely used in high-income countries for the management of sickle cell disease (SCD) in children. In Kenyan clinical guidelines, hydroxyurea is only recommended for adults with SCD. Yet many deaths from SCD occur in early childhood, deaths that might be prevented by an effective, disease modifying intervention. The aim of this review was to summarise the available evidence on the efficacy, effectiveness and safety of hydroxyurea in the management of SCD in children below 5 years of age to support guideline development in Kenya. We undertook a systematic review and used the Grading of Recommendations Assessment, Development and Evaluation system to appraise the quality of identified evidence. Overall, available evidence from 1 systematic review (n=26 studies), 2 randomised controlled trials (n=354 children), 14 observational studies and 2 National Institute of Health reports suggest that hydroxyurea may be associated with improved fetal haemoglobin levels, reduced rates of hospitalisation, reduced episodes of acute chest syndrome and decreased frequency of pain events in children with SCD. However, it is associated with adverse events (eg, neutropenia) when high to maximum tolerated doses are used. Evidence is lacking on whether hydroxyurea improves survival if given to young children. Majority of the included studies were of low quality and mainly from high-income countries. Overall, available limited evidence suggests that hydroxyurea may improve morbidity and haematological outcomes in SCD in children aged below 5 years and appears safe in settings able to provide consistent haematological monitoring.

Free Article


PMID: 23995076 [PubMed - as supplied by publisher]


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August 2013

James Eckman MD, Director of the 24 hour Georgia Comprehensive Sickle Cell Center to Retire – Symposium in his honor on November 16, 2013at Emory University in Atlanta Georgia

Prior to 1984, patients presenting with sickle cell pain crisis were seen in Atlanta area emergency rooms, placed low on triage lists, evaluation procedures were erratic and continuity of care usually absent.

Dr. James Eckman arrived in Atlanta from the University of Minnesota Medical School to establish a sickle cell program at Grady Memorial Hospital and Emory University School of Medicine. With very little resources, Dr. Eckman obtained grant funding to support the salaries of a genetics nurse, a social worker and a clinical nurse specialist in psychiatry as the beginning of a multidisciplinary team. Dr. Eckman, with an intense lobbying effort by the Sickle Cell Patient/Parent Group, and hospital administration, convinced members of the Georgia General Assembly of the need for a specialized clinic in the state of Georgia.  In 1984 the Georgia General Assembly provided the original state grant of $550,000 to Grady Memorial Hospital to fund the world’s first 24-hour comprehensive acute care, sickle cell center.

Having established the clinic on this foundation, during the past 27 years, under the leadership of Dr. Eckman, the center has cared for more than 4,000 patients, expanded its scope of services, and become a medical home model in the care of sickle cell patients. This has occurred through the development of the Problem Oriented Clinical Guidelines for Sickle Syndromes, authored by Dr. Eckman, first published with a Maternal and Child Health grant and distributed for free world-wide in 1991. These guidelines are continually updated and are available on the World Wide Web for all providers to access at the Sickle Cell Information Center web site at  http://www.SCInfo.org.

The clinical success of the center, led by Dr. Eckman, with a dedicated staff of hematologists, physician assistants, nurse practitioners, nurses, clinic assistants, social workers and clinical nurse specialists in psychiatry, allowed the staff to apply for Federal research funding.  In 1993, the National Institutes of Health awarded Dr. Eckman and Emory University $7 million over five years in research funding for projects to discover new treatments and prevention of complications. Emory is now the leading center out of twenty-five national centers, providing bone marrow transplants to cure sickle cell disease in the United States. Emory provided the first unrelated cord blood stem cell transplant. There are new treatments, such as fish oil or N3 fatty acids that prevent pain events with little or no side effects, new psychosocial interventions, new educational materials on computer-based CD-ROM and Internet technology, new understanding of the pathology of pain events and kidney damage that will lead to new treatments.

 

Dr. Eckman has championed newborn screening for sickle cell in many states nationally and internationally. Through his public health efforts, the infant mortality related to sickle cell disease decreased in Georgia. This has saved the lives of many sickle cell children who would have died from pneumococcal sepsis if timely preventive care with oral penicillin prophylaxis was not started. It was through his efforts that Georgia instituted universal mandatory sickle cell screening for newborns in October of 1998.

As a Professor of Medicine and Adjunct Professor of Pediatrics, Dr. Eckman teaches medical students, residents, and fellows the Art and science of patient care. He spends countless hours preparing stimulating lectures with practical handouts and visually pleasing slides. He teaches at the bedside as a role model for housestaff, showing them how to deliver compassionate and expert care. With all of his duties and responsibilities, he is available to comfort a patient with a reassuring word or answer a family’s question. He has published extensively on sickle cell disease management, new treatments, newborn screening, pain assessment and pain treatment. He is co-author of the bestselling lay sickle cell education book Hope and Destiny, The Patient and Parent’s Guide to Sickle Cell Disease and Sickle Cell Trait  (Hilton Publishing 2011)

Dr. Eckman has been committed to attending to the psychosocial needs of the patients and their families. To this end, he has supported the provision of mental health services to individuals across their life span with sickle cell disease. These services have included psychology services from psychology interns, postdoctoral fellows, and faculty. Psychology trainees and faculty frequently comment on the value Dr. Eckman places on a biopsychosocial approach  to care and the ways in which this enhances the quality of life of the patients served at the Center. Since most psychology trainees and faculty have received minimal, if any, training in sickle cell disease, Dr. Eckman has been invested in educating them about the disease. He offers multiple training opportunities to non-medical professionals through didactics, informal teaching, multimedia educational materials (e.g., CD-ROM, videos, Web based and internet information), and the coordination of conferences. In his teaching, he is very respectful of the knowledge base and training of those he is educating, shares his extensive knowledge base openly and effectively, and is always approachable. He clearly loves to teach and views educating others as a way to ultimately enhance the quality of the care offered to the patients. In addition to teaching other professionals, the families at the Center have tremendous admiration and respect for what he has taught them.

On behalf of the Department of Hematology and Medical Oncology at Emory University School of Medicine, you are cordially invited to join us in celebrating the long anddistinguished career of James R. Eckman, MD at the Sickle Cell Scientific Symposium and Reception on Saturday, November 16, 2013.  This educational program will be held on Emory University’s campus and will feature world renowned authorities in sickle cell disease, all of whom are longtime friends and colleagues of Dr. Eckman.   If you would like to attend, please feel free to RSVP now as the program plans are developing.  Please contact: Chris Terry-Carter at cterryc@emory.edu or Joél Anthony atjantho3@emory.edu

Healthy People 2020 Blood Disorders and Blood Safety Objectives http://www.healthypeople.gov/2020/topicsobjectives2020/overview.aspx?topicid=4 

Sickle Cell disease objectives and recommendations are a part of Healthy Perople 2020

New Videos

2013-07-25 - Dr. Coretta Jenerette, International Association of Sickle Cell Nurses and Physician Assistants

Nurses’ Impact on the Stigmatization of Individuals with Sickle Cell: Challenges and Recommendations

 mms://realaudio.service.emory.edu/SOM/PA/PLATT/SICKLE/CDC072513.wmv

SAVE THE DATES

Fellow colleagues, you are invited to participate in the“Public Health Webinar Series on Hemoglobinopathies” Hosted by: The Division of Blood Disorders, CDC

4th Thursday of every month from 2:00PM – 3:00PM EST

9/26: NHLBI Sickle Cell Disease Guidelines

Dr. Joylene John-Sowah, National Heart Lung and Blood Institute, NIH   

10/24: Current Data on Efficacy and Effectiveness of Hydroxyurea in Children with Sickle Cell Disease

Dr. Winfred Wang, St. Jude Children’s Research Hospital 

November/December: --- No Webinars---  

If you have ideas on topics for future webinars, or have any questions or comments about this series please submit them to Shae Popespope@cdc.gov .

The purpose of this webinar series is to offer a hemoglobinopathies learning collaborative platform for providers, consumers, educators, and scientists. 


 

CDC Web based Sickle Cell Resources

CDC’s YouTube Link: http://www.youtube.com/watch?v=gnrvYsZWR1c&list=UUiMg06DjcUk5FRiM3g5sqoQ&index=2&feature=plpp_video

 CDC Video Archive (http://scinfo.org/world-wide-resources/cdc-webinars-hemoglobinopathies-and-public-health

 CDC Sickle Cell Disease Webpage:http://wwwdev.cdc.gov/NCBDDD/sicklecell/video.html  

Articles in the Medical Literature for June

 

 

1.

PLoS One. 2013 Aug 14;8(8):e72077. doi: 10.1371/journal.pone.0072077. eCollection 2013.

Hydroxyurea use and hospitalization trends in a comprehensive pediatric sickle cell program.

Nottage KAHankins JSSmeltzer MMzayek F,Wang WCAygun BGurney JG.

Department of Hematology, St. Jude Children's Research Hospital, Memphis, Tennessee, United States of America.

Abstract

BACKGROUND:

A decline in hospitalizations and pain episodes among those with sickle cell disease (SCD) who take hydroxyurea (HU) has been shown when compared to pre-HU patterns but paradoxically, when compared to those who have never been treated, HU recipients often have more frequent hospitalizations. This analysis evaluates the impact of increasing usage of HU on trends in hospitalizations and blood transfusions within a large SCD treatment program.

METHODS:

Eligibility was restricted to patients with Hb SS or Hb Sβ(0)-thalassemia who were 2-18 years old between 2006-2010 and received care at St. Jude Children's Research Hospital (N = 508). Hospitalizations and blood transfusions were calculated for each of the years under study for those exposed and never exposed to HU. Differences in number of hospitalizations before and after HU initiation were compared.

RESULTS:

The proportion of patients receiving HU increased by 4% per year on average. In the HU exposed group, a modest decline in mean per-patient hospitalizations and per-patient hospital days occurred, while those never exposed to HU trended toward a slight increase over time. Rates of blood transfusions declined among those on HU but not in patients never exposed to HU. Patients on HU had a median of one fewer hospital admission in the year after initiation of HU, compared to the year prior. Two deaths occurred in the patient population, both of whom were not exposed to HU.

CONCLUSIONS:

Increasing usage of HU was concurrent with decreased hospitalization rates and blood transfusions. Our results support the utility of HU on decreasing hospitalizations and transfusions for patients with SCD outside of the clinical trial setting.

PMCID: PMC3743768 Free PMC Article


PMID: 23967276 [PubMed - in process]


Related citations



 

2.

J Blood Med. 2013 Aug 5;4:101-10. doi: 10.2147/JBM.S35478. eCollection 2013.

Deferasirox: appraisal of safety and efficacy in long-term therapy.

Chaudhary PPullarkat V.

Jane Ann Nohl Division of Hematology, University of Southern California Keck School of Medicine, Los Angeles, CA, USA.

Abstract

Deferasirox is a once-daily, oral iron chelator that is widely used in the management of patients with transfusional hemosiderosis. Several Phase II trials along with their respective extension studies as well as a Phase III trial have established the efficacy and safety of this novel agent in transfusion-dependent patients with β-thalassemia, sickle-cell disease and bone marrow-failure syndromes, including myelodysplastic syndrome and aplastic anemia. Data from various clinical trials show that a deferasirox dose of 20 mg/kg/day stabilizes serum ferritin levels and liver iron concentration, while a dose of 30-40 mg/kg/day reduces these parameters and achieves negative iron balance in red cell transfusion-dependent patients with iron overload. Across various pivotal clinical trials, deferasirox was well tolerated, with the most common adverse events being gastrointestinal disturbances, skin rash, nonprogressive increases in serum creatinine, and elevations in liver enzyme levels. Longer-term extension studies have also confirmed the efficacy and safety of deferasirox. However, it is essential that patients on deferasirox therapy are monitored regularly to ensure timely management for any adverse events that may occur with long-term therapy.

PMCID: PMC3743529 Free PMC Article


PMID: 23966805 [PubMed]


Related citations


Icon for Dove Medical PressIcon for PubMed Central

 

3.

Popul Health Manag. 2013 Aug 21. [Epub ahead of print]

Characteristics of Acute Care Utilization of a Delaware Adult Sickle Cell Disease Patient Population.

Anderson NBellot JSenu-Oke OBallas SK.

1 Jefferson School of Nursing , Philadelphia, Pennsylvania.

Abstract

Abstract Sickle cell disease (SCD) is an inherited blood disorder that is chronic in nature and manifests itself through many facets of the patient's life. Comprehensive specialty centers have the potential to reduce health care costs and improve the quality of care for patients who have chronic medical conditions such as heart failure and SCD. The purpose of this practice inquiry was to analyze de-identified data for acute care episodes involving SCD in order to create a detailed picture of acute care utilization for adult patients in Delaware with SCD from 2007 to 2009. Gaining a better understanding of acute care utilization for adults with SCD may provide evidence to improve access to high-quality health care services for this vulnerable patient population in the state of Delaware. Population Health Management 20xx;xx:xx-xx.


PMID: 23965046 [PubMed - as supplied by publisher]


Related citations



 

4.

Am J Hematol. 2013 Aug 20. doi: 10.1002/ajh.23575. [Epub ahead of print]

Neuropathy, neuropathic pain and sickle cell disease.

Ballas SKDarbari DS.

Cardeza Foundation, Department of Medicine, Jefferson Medical College, Thomas Jefferson University, Philadelphia, PA.


PMID: 23963922 [PubMed - as supplied by publisher]


Related citations



 

5.

Am J Hematol. 2013 Aug 20. doi: 10.1002/ajh.23571. [Epub ahead of print]

Vasculopathy, inflammation and blood flow in leg ulcers of patients with sickle cell anemia.

Minniti CPDelaney KMGorbach AMXu DLee CCMalik NKoroulakis AAntalek MMaivelett J,Peters-Lawrence MM Novelli ELanzkron SM,Axelrod KCKato GJ.

Hematology Branch, NHLBI, National Institutes of Health, Bethesda, MD, USA.

Abstract

Chronic leg ulcers are frequent and debilitating complications of sickle cell anemia. Inadequate blood supply has been postulated to be an important factor in their occurrence and delayed healing. Little is known about their microcirculatory and histopathological changes. We evaluated the microcirculation of lower extremity ulcers with laser speckle contrast imaging and infrared thermography, and obtained clinical and laboratory characteristics in 18 adults with sickle cell anemia and chronic leg ulcers. Skin biopsies were obtained in four subjects. Subjects had markers of severe disease, anemia, and high degree of hemolysis, inflammation and thrombophilia. Higher blood flow was present in the ulcer bed, lesser in the immediate periwound area, compared to an unaffected control skin area. Microscopic examination showed evidence of venostasis, inflammation, and vasculopathy. Blood vessels were increased in number, had activated endothelium and evidence of thrombosis/recanalization. High blood flow may be due to chronic inflammation, cutaneous vasodilatation, venostasis, and in situ thrombosis. These changes in skin microcirculation are similar to chronic venous ulcers in the non-SCD population, thus suggesting that leg ulcers may be another end-organ complication with endothelial dysfunction that appears in patients with SCD at a younger age and with higher frequency than in the general population.

Copyright © 2013 Wiley Periodicals, Inc., A Wiley Company.


PMID: 23963836 [PubMed - as supplied by publisher]


Related citations



 

6.

Blood. 2013 Aug 20. [Epub ahead of print]

Bone marrow transplantation for thalassemia from alternative related donors: improved outcomes with a new approach.

Gaziev JMarziali MIsgrò ASodani PPaciaroni KGallucci CAndreani MTesti MDe Angelis G,Alfieri CCardarelli LRibersani MArmiento D,Lucarelli G.

International Center for Transplantation in Thalassemia and Sickle Cell Anemia, Mediterranean Institute of Hematology, Policlinico Tor Vergata, Rome, Italy.

Abstract

Bone marrow transplantation performance can be limited by a lack of ideal donors, and the role of alternative donor hematopoietic cell transplantation in thalassemia is not well established. Here we used a new treatment protocol (Pc 26.1) in 16 thalassemia patients to perform BMT using phenotypically HLA-identical or one-antigen mismatched relatives (related donors-RDs). We compared these results with HLA matched sibling (matched sibling donors-MSDs) BMT in 66 patients. The entire RD group and 88% of MSD group had sustained engraftment. Rejection incidence was 0% in the RD and 12% (95% CI, 6-21%) in MSD groups (P = 0.15), with respective thalassemia-free survival (TFS) probabilities of 94% (95% CI, 63-99%) and 82% (95% CI, 70-89%) (P = 0.24). Transplant-related mortality was 6% (95% CI, 1-26%) in the RD group and 8% (95% CI, 3-16%) in the MSD group (P = 0.83). The intensified new protocol was not associated with increased nonhematological toxicity. The present data show that the Pc 26.1 preparative regimen allows thalassemia patients to safely undergo BMT from related donors who are not HLA-matched siblings, with transplant outcomes similar to patients of MSD grafts.


PMID: 23963044 [PubMed - as supplied by publisher]


Related citations



 

7.

PLoS One. 2013 Aug 7;8(8):e70794. doi: 10.1371/journal.pone.0070794. eCollection 2013.

Increased Reticulocytosis during Infancy Is Associated with Increased Hospitalizations in Sickle Cell Anemia Patients during the First Three Years of Life.

Meier ERByrnes CLee YTWright EC,Schechter ANLuban NLMiller JL.

Molecular Medicine Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland, United States of America ; Center for Cancer and Blood Disorders, Children's National Medical Center, Washington, District of Columbia, United States of America ; Department of Pediatrics, The George Washington University Medical Center, Washington, District of Columbia, United States of America.

Abstract

OBJECTIVE:

Among older children with sickle cell anemia, leukocyte counts, hemoglobin, and reticulocytosis have previously been suggested as disease severity markers. Here we explored whether these blood parameters may be useful to predict early childhood disease severity when tested in early infancy, defined as postnatal ages 60-180 days.

STUDY DESIGN:

Data from fifty-nine subjects who were followed at Children's National Medical Center's Sickle Cell Program for at least three years was retrospectively analyzed. Comparisons were made between white blood cell counts, hemoglobin and reticulocyte levels measured at ages 60-180 days and the clinical course of sickle cell anemia during infancy and childhood.

RESULTS:

A majority of subjects had demonstrable anemia with increased reticulocytosis. Only increased absolute reticulocyte levels during early infancy were associated with a significant increase in hospitalization during the first three years of life. Higher absolute reticulocyte counts were also associated with a markedly shorter time to first hospitalizations and a four-fold higher cumulative frequency of clinical manifestations over the first three years of life. No significant increase in white blood cell counts was identified among the infant subjects.

CONCLUSIONS:

These data suggest that during early infancy, increased reticulocytosis among asymptomatic SCA subjects is associated with increased severity of disease in childhood.

PMCID: PMC3737358 Free PMC Article


PMID: 23951011 [PubMed - in process]


Related citations



 

8.

Am J Hematol. 2013 Aug 14. doi: 10.1002/ajh.23569. [Epub ahead of print]

Efficacy and safety of deferasirox compared with deferoxamine in sickle cell disease: 2-year results including pharmacokinetics and concomitant hydroxyurea.

Vichinsky E,

Sickle Cell News for July 2013

UCLA Stem Cell Gene Therapy For Sickle Cell Disease  Advances Toward Clinical Trials
https://www.stemcell.ucla.edu./news/gene-therapy-sickle-cell-disease-advances-toward-clinical-trials - See abstract #5 in this newsletter

Researchers at UCLA’s Eli & Edythe Broad Center of Regenerative Medicine & Stem Cell Research have successfully established the foundation for using hematopoietic (blood-producing) stem cells (HSC) from the bone marrow of patients with sickle cell disease (SCD) to treat the disease. The study was led by Dr. Donald Kohn, professor of pediatrics and microbiology, immunology and molecular genetics in the life sciences.

Kohn introduced an anti-sickling gene into the HSC to capitalize on the self-renewing potential of stem cells and create a continual source of healthy red blood cells that do not sickle. The breakthrough gene therapy technique for sickle cell disease is scheduled to begin clinical trials by early 2014. The study was published online ahead of press today in Journal of Clinical Investigation.

Gene Therapy

Kohn’s gene therapy approach using HSC from patient’s own blood is a revolutionary alternative to current SCD treatments as it creates a self-renewing normal blood cell by inserting a gene that has anti-sickling properties into HSC. This approach also does not rely on the identification of a matched donor, thus avoiding the risk of rejection of donor cells. The anti-sickling HSC will be transplanted back into the patient’s bone marrow and multiplies the corrected cells that make red blood cells without sickling.

“The results demonstrate that our technique of lentiviral transduction is capable of efficient transfer and consistent expression of an effective anti-sickling beta-globin gene in human SCD bone marrow progenitor cells, which improved the physiologic parameters of the resulting red blood cells.” Kohn said.

Kohn and colleagues found that in the laboratory the HSC produced new non-sickled blood cells at a rate sufficient for significant clinical improvement for patients. The new blood cells survive longer than sickled cells, which could also improve treatment outcomes. The success of this technique will allow Kohn to begin clinical trials in patients with SCD by early next year.

Current treatments include transplanting patients with donor HSC, which is a potential cure for SCD, but due to the serious risks of rejection, only a small number of patients have undergone this procedure and it is usually restricted to children with severe symptoms.  This study was supported in part by a Disease Team I Award from the California Institute for Regenerative Medicine (CIRM), the state’s stem cell research agency created by voter initiative in 2004. Other support came from the UCLA Broad Stem Cell Research Center and  Jonsson Comprehensive Cancer Center and the Ruth L. Kirschstein National Research Service Award.

The stem cell center was launched in 2005 with a UCLA commitment of $20 million over five years. A $20 million gift from the Eli and Edythe Broad Foundation in 2007 resulted in the renaming of the center. With more than 200 members, the Eli and Edythe Broad Center of  Regenerative Medicine and Stem Cell Research is committed to a multi-disciplinary, integrated collaboration of scientific, academic and medical disciplines for the purpose of understanding adult and human embryonic stem cells. The center supports innovation, excellence and the highest ethical standards focused on stem cell research with the intent of facilitating basic scientific inquiry directed towards future clinical applications to treat disease. The center is a collaboration of the David Geffen School of Medicine, UCLA’s Jonsson Cancer Center, the Henry Samueli School of Engineering and Applied Science and the UCLA College of Letters and Science. To learn more about the center, visit our web site at http://www.stemcell.ucla.edu.

Please join the discussion about Bone Marrow Transplantation in Sickle Cell Disease at the

NHLBI Annual Sickle Cell Disease Clinical Research Meetings

Bone Marrow Transplantation in Sickle Cell Disease:  A Question of Outcomes.

Monday, August 19, 2013;  1:00 -  5:00 PM, Natcher Conference Center, NIH, Bethesda, MD

New advances to improve outcomes in SCD and to lower the toxicities of BMT in SCD mandate continued and ongoing comparison of the outcomes of SCD patients undergoing BMT with those not transplanted.   This session will explore issues of expanding eligibility criteria for BMT and of developing and standardizing outcomes measures to optimize comparisons of transplanted and non-transplanted patients with SCD.  The meeting is open to all and the audience will be encouraged to participate in the discussion. 

Please register for the meetings (and indicated your choice to attend the session) at:  https://www.cvent.com/events/annual-sickle-cell-disease-clinical-research-meetings/registration-b0cafc512d25422096ef3a6a28095937.aspx

Registration is free.

Johns Hopkins professor: Sickle cell patient, researcher, and advocatehttp://hub.jhu.edu/2013/07/08/carlton-haywood-sickle-cell

Johns Hopkins researcher .understands sickle cell disease in a way few others can—the overwhelming pain that "blossoms into a thunderstorm," the toll it takes on a patient's life, and the paucity of understanding of—or funding for—the condition in the health care community.

Haywood, 37, a faculty member at the Johns Hopkins schools of medicine and public health and at the university's Berman Institute of Bioethics, has lived with the rare disease since birth. He was featured in Saturday's edition of The Baltimore Sun:

In Memory of  Keone Penn, age 27: Medical trailblazer wanted to be a chef http://www.ajc.com/news/news/local-obituaries/keone-penn-27-medical-trailblazer-wanted-to-be-a-c/nYXxF/

Keone Penn’s middle initial — D — actually stood for Denard, but it could have easily been short for determination. When Penn was 12 years old, he was thrust into the medical spotlight as the first person in the world to undergo a groundbreaking stem cell transplant that ultimately cured him of sickle cell disease. It was a painful process but he was determined to beat the disease and the health complications that would follow, his mother, Leslie Brodnex said.

Not long before his 27th birthday, an age his doctors never imagined he’d reach, Penn did something else they said he’d never do: He enrolled in culinary arts school.

 

Listening to Blood Cells http://www.photonics.com/Article.aspx?AID=54334

Red blood cells struck with laser light generate high-frequency sound waves that could help researchers to differentiate normal blood cells from abnormal ones for the diagnosis of blood-related diseases like sickle cell

Dangerous Braids That Tangle in Brains and Veins

By Frank Ferrone | May 30, 2013 at http://blogs.scientificamerican.com/guest-blog/2013/05/30/dangerous-braids-that-tangle-in-brains-and-veins/

 

New Free Publications from the CDC  

The CDC has recently updated their Sickle Cell Disease National Resource Directory. The directory is a listing of national agencies, specialty care centers, and community-based organizations that provide services and resources for people affected by sickle cell disease (SCD). The interactive map of the directory is available at http://www.cdc.gov/ncbddd/sicklecell/map/map-nationalresourcedirectory.html.  The directory is available as a PDF version at http://www.cdc.gov/ncbddd/sicklecell/freematerials.html

 In 2010, in partnership with the National Institutes of Health’s National Heart, Lung, and Blood Institute, the Registry and Surveillance System for Hemoglobinopathies (RuSH) project was launched to collect initial state-specific, information on people with SCD and thalassemia. Factsheets featuring new data on sickle cell disease in the RuSH project states are now available on our website. http://www.cdc.gov/ncbddd/sicklecell/freematerials.html

 The CDC factsheet “What You Should Know About Sickle Cell Trait” is now available in Spanish. http://www.cdc.gov/ncbddd/spanish/sicklecell/freematerials.html. The English version has also been updated: http://www.cdc.gov/ncbddd/sicklecell/freematerials.html  


New Videos

CDC webinar: from April 2013 - 4/25: Building Behavioral and Social Science Databases for the Hemoglobinopathies: Lessons from the Study of Thalassemia Dr. Robert Yamashita, California State University San Marcos  

mms://realaudio.service.emory.edu/SOM/PA/PLATT/SICKLE/CDC042513.wmv

CDC webinar from June 2013 Beta-globin Haplotype Analysis in Children with Sickle Cell Anemia -Dr. Christopher Bean, National Center on Birth Defects and Developmental Disabilities, CDC  mms://realaudio.service.emory.edu/SOM/PA/PLATT/SICKLE/CDC062713.wmv

SAVE THE DATES

Fellow colleagues, you are invited to participate in the“Public Health Webinar Series on Hemoglobinopathies” Hosted by: The Division of Blood Disorders, CDC

4th Thursday of every month from 2:00PM – 3:00PM EST

  8/22: Mental Health and Learning Needs in children with Sickle Cell Disease

Dr. Patricia Kavanagh, Boston University School of Medicine/Boston Medical Center  

9/26: NHLBI Sickle Cell Disease Guidelines

Dr. Joylene John-Sowah, National Heart Lung and Blood Institute, NIH   

10/24: Current Data on Efficacy and Effectiveness of Hydroxyurea in Children with Sickle Cell Disease

Dr. Winfred Wang, St. Jude Children’s Research Hospital 

November/December: --- No Webinars---  

If you have ideas on topics for future webinars, or have any questions or comments about this series please submit them to Shae Pope spope@cdc.gov .

The purpose of this webinar series is to offer a hemoglobinopathies learning collaborative platform for providers, consumers, educators, and scientists. 

 

CDC Web based Sickle Cell Resources

CDC’s YouTube Link: http://www.youtube.com/watch?v=gnrvYsZWR1c&list=UUiMg06DjcUk5FRiM3g5sqoQ&index=2&feature=plpp_video

 CDC Video Archive (http://scinfo.org/world-wide-resources/cdc-webinars-hemoglobinopathies-and-public-health

 CDC Sickle Cell Disease Webpage: http://wwwdev.cdc.gov/NCBDDD/sicklecell/video.html  

Articles in the Medical Literature for June

 


1.

PLoS Med. 2013 Jul;10(7):e1001484. doi: 10.1371/journal.pmed.1001484. Epub 2013 Jul 16.

Global Burden of Sickle Cell Anaemia in Children under Five, 2010-2050: Modelling Based on Demographics, Excess Mortality, and Interventions.

Piel FBHay SIGupta SWeatherall DJWilliams TN.

Evolutionary Ecology of Infectious Disease, Department of Zoology, University of Oxford, Oxford, United Kingdom ; Spatial Ecology and Epidemiology Group, Department of Zoology, University of Oxford, Oxford, United Kingdom ; Global Network for Sickle Cell Disease, Toronto, Ontario, Canada.

Abstract

BACKGROUND:

The global burden of sickle cell anaemia (SCA) is set to rise as a consequence of improved survival in high-prevalence low- and middle-income countries and population migration to higher-income countries. The host of quantitative evidence documenting these changes has not been assembled at the global level. The purpose of this study is to estimate trends in the future number of newborns with SCA and the number of lives that could be saved in under-five children with SCA by the implementation of different levels of health interventions.

METHODS AND FINDINGS:

First, we calculated projected numbers of newborns with SCA for each 5-y interval between 2010 and 2050 by combining estimates of national SCA frequencies with projected demographic data. We then accounted for under-five mortality (U5m) projections and tested different levels of excess mortality for children with SCA, reflecting the benefits of implementing specific health interventions for under-five patients in 2015, to assess the number of lives that could be saved with appropriate health care services. The estimated number of newborns with SCA globally will increase from 305,800 (confidence interval [CI]: 238,400-398,800) in 2010 to 404,200 (CI: 242,500-657,600) in 2050. It is likely that Nigeria (2010: 91,000 newborns with SCA [CI: 77,900-106,100]; 2050: 140,800 [CI: 95,500-200,600]) and the Democratic Republic of the Congo (2010: 39,700 [CI: 32,600-48,800]; 2050: 44,700 [CI: 27,100-70,500]) will remain the countries most in need of policies for the prevention and management of SCA. We predict a decrease in the annual number of newborns with SCA in India (2010: 44,400 [CI: 33,700-59,100]; 2050: 33,900 [CI: 15,900-64,700]). The implementation of basic health interventions (e.g., prenatal diagnosis, penicillin prophylaxis, and vaccination) for SCA in 2015, leading to significant reductions in excess mortality among under-five children with SCA, could, by 2050, prolong the lives of 5,302,900 [CI: 3,174,800-6,699,100] newborns with SCA. Similarly, large-scale universal screening could save the lives of up to 9,806,000 (CI: 6,745,800-14,232,700) newborns with SCA globally, 85% (CI: 81%-88%) of whom will be born in sub-Saharan Africa. The study findings are limited by the uncertainty in the estimates and the assumptions around mortality reductions associated with interventions.

CONCLUSIONS:

Our quantitative approach confirms that the global burden of SCA is increasing, and highlights the need to develop specific national policies for appropriate public health planning, particularly in low- and middle-income countries. Further empirical collaborative epidemiological studies are vital to assess current and future health care needs, especially in Nigeria, the Democratic Republic of the Congo, and India. Please see later in the article for the Editors' Summary.

PMCID: PMC3712914 Free Article


PMID: 23874164 [PubMed - in process]


Related citations



 

2.

PLoS Med. 2013 Jul;10(7):e1001483. doi: 10.1371/journal.pmed.1001483. Epub 2013 Jul 16.

Sickle cell anaemia in a changing world.

Fottrell EOsrin D.

Institute for Global Health, UCL Institute of Child Health, London, United Kingdom ; Umeå Centre for Global Health Research, Umeå University, Umeå, Sweden.

Abstract

David Osrin and Edward Fottrell comment on new research by Frédéric Piel and colleagues on the growing burden of sickle cell anemia, and discuss the need for changing policy and health services in response to epidemiologic transitions in child mortality. Please see later in the article for the Editors' Summary.

PMCID: PMC3712907 Free Article


PMID: 23874163 [PubMed - in process]


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3.

J Control Release. 2013 Jul 17. pii: S0168-3659(13)00401-X. doi: 10.1016/j.jconrel.2013.07.008. [Epub ahead of print]

Drug-Loaded Sickle Cells Programmed ex vivo for Delayed Hemolysis Target Hypoxic Tumor Microvessels and Augment Tumor Drug Delivery.

Choe SWTerman DSRivers AERivera JLottenberg RSorg BS.

Gumi Electronics & Information Technology Research Institute, Gumi, Korea.

Abstract

Selective drug delivery to hypoxic tumor niches remains a significant therapeutic challenge that calls for new conceptual approaches. Sickle red blood cells (SSRBCs) have shown an ability to target such hypoxic niches and induce tumoricidal properties when used together with exogenous pro-oxidants. Here we determine whether the delivery of a model therapeutic encapsulated in murine SSRBCs can be enhanced by ex vivo photosensitization under conditions that delay autohemolysis to a time that coincides with maximal localization of SSRBCs in a hypoxic tumor. Hyperspectral imaging of 4T1 carcinomas shows oxygen saturation levels <10% in a large fraction (commonly 50% or more) of the tumor. Using video microscopy of dorsal skin window chambers implanted with 4T1 tumors, we demonstrate that allogeneic SSRBCs, but not normal RBCs (nRBCs), selectively accumulate in hypoxic 4T1 tumors between 12-24 hours after systemic administration. We further show that ex vivo photo-oxidation can program SSRBCs to postpone hemolysis/release of a model therapeutic to a point that coincides with their maximum sequestration in hypoxic tumor microvessels. Under these conditions, drug-loaded photosensitized SSRBCs show a 3-4 fold greater drug delivery to tumors compared to non-photosensitized SSRBCs, drug-loaded photosensitized nRBCs, and free drug. These results demonstrate that photo-oxidized SSRBCs, but not photo-oxidized nRBCs, sequester and hemolyze in hypoxic tumors and release substantially more drug than photo-oxidized nRBCs and non-photo-oxidized SSRBCs. Photo-oxidation of drug-loaded SSRBCs thus appears to exploit the unique tumor targeting and carrier properties of SSRBCs to optimize drug delivery to hypoxic tumors. Such programmed and drug-loaded SSRBCs therefore represent a novel and useful tool for augmenting drug delivery to hypoxic solid tumors.

© 2013.


PMID: 23871960 [PubMed - as supplied by publisher]


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4.

Pain Manag Nurs. 2013 Jul 16. pii: S1524-9042(13)00032-5. doi: 10.1016/j.pmn.2013.03.002. [Epub ahead of print]

Adolescent Pediatric Pain Tool for Multidimensional Measurement of Pain in Children and Adolescents.

Jacob EMack AKSavedra MVan Cleve LWilkie DJ.

University of California Los Angeles School of Nursing, Los Angeles, California. Electronic address: ejacob@sonnet.ucla.edu.

Abstract

Very few multidimensional tools are available for measurement of pain in children and adolescents. We critically reviewed the scientific literature to examine the psychometrics and utility of the Adolescent Pediatric Pain Tool (APPT), a multidimensional self-report tool that evaluates the intensity, location, and quality (including affective, evaluative, sensory, and temporal) dimensions of pain. The APPT is available in English and Spanish for children and adolescents, and was modeled after the McGill Pain Questionnaire in adults. We found good evidence for construct validity, reliability, and sensitivity of the APPT for the measurement of pediatric pain. The APPT was used to measure pain in children with different conditions, such as cancer, sickle cell disease, orthopedic, traumatic injuries, and allergy testing. Although the APPT was designed to assess the multiple dimensions of pain, the majority of the reports included results only for the intensity ratings. Unlike the numerical and pediatric faces rating scales, which are widely used in clinical practice and research, the APPT is not limited to the single dimension of pain intensity. It measures multiple dimensions, and may be able to discriminate between nociceptive and neuropathic pain. The APPT is one of a few multidimensional pain measures that can help to advance the science of pediatric pain and its management. When the APPT is used in practice or research, the multiple dimensions of pain may be characterized and compared in different painful conditions. It may guide the use of multimodal interventions in children and adolescents with a variety of pain conditions.

Copyright © 2013 American Society for Pain Management Nursing. Published by Elsevier Inc. All rights reserved.


PMID: 23870767 [PubMed - as supplied by publisher]


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5.

J Clin Invest. 2013 Jul 1. pii: 67930. doi: 10.1172/JCI67930. [Epub ahead of print]

β-globin gene transfer to human bone marrow for sickle cell disease.

Romero ZUrbinati FGeiger SCooper ARWherley JKaufman MLHollis RPde Assin RRSenadheera SSahagian AJin X,Gellis AWang XGjertson DDeoliveira SKempert PShupien S,Abdel-Azim HWalters MCMeiselman HJWenby RBGruber T,Marder VCoates TDKohn DB.

Abstract

Autologous hematopoietic stem cell gene therapy is an approach to treating sickle cell disease (SCD) patients that may result in lower morbidity than allogeneic transplantation. We examined the potential of a lentiviral vector (LV) (CCL-βAS3-FB) encoding a human hemoglobin (HBB) gene engineered to impede sickle hemoglobin polymerization (HBBAS3) to transduce human BM CD34+ cells from SCD donors and prevent sickling of red blood cells produced by in vitro differentiation. The CCL-βAS3-FB LV transduced BM CD34+ cells from either healthy or SCD donors at similar levels, based on quantitative PCR and colony-forming unit progenitor analysis. Consistent expression of HBBAS3 mRNA and HbAS3 protein compromised a fourth of the total β-globin-like transcripts and hemoglobin (Hb) tetramers. Upon deoxygenation, a lower percentage of HBBAS3-transduced red blood cells exhibited sickling compared with mock-transduced cells from sickle donors. Transduced BM CD34+ cells were transplanted into immunodeficient mice, and the human cells recovered after 2-3 months were cultured for erythroid differentiation, which showed levels of HBBAS3 mRNA similar to those seen in the CD34+ cells that were directly differentiated in vitro. These results demonstrate that the CCL-βAS3-FB LV is capable of efficient transfer and consistent expression of an effective anti-sickling β-globin gene in human SCD BM CD34+ progenitor cells, improving physiologic parameters of the resulting red blood cells.


PMID: 23863630 [PubMed - as supplied by publisher]


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6.

Am J Hematol. 2013 Jul 16. doi: 10.1002/ajh.23547. [Epub ahead of print]

Pain and other non-neurological adverse events in children with sickle cell anemia and previous stroke who received hydroxyurea and phlebotomy or chronic transfusions and chelation: Results from the SWiTCH clinical trial.

Alvarez OYovetich NAScott JPOwen WMiller ST,

Sickle Cell News for June 2013

June 19 World Sickle Cell Day

orld Sickle Cell Day Education http://www.ippmedia.com/frontend/index.php?l=56137

Sickle cell disease been ranked the biggest killer disease among children under the age of five after malaria, hence the need for the government and stakeholders to put in more efforts to fight it. Over 90 percent of Africans are the most sufferers of the disease followed by Asians and those loving in the Mediterranean area. 

This was revealed yesterday in Dar es Salaam by the Sickle Cell Foundation of Tanzania (SCFT) Chairperson, Grace Rubambey at the World Sickle Cell Day initiated by the World Health Organization (WHO) and celebrated on June 19 annually.

Rubambey said Tanzania ranks fouth in the world, with the highest number of sickle cell disease births a year (up to 11,000), after Nigeria, India and DR Congo, adding that if untreated, up to 90 percent of children may die in childhood. She said Tanzania and Africa in general is in a position of having high rates of the disease due to poverty, as patients need good services like clean water and medical treatment which are still challenges in many countries on the continent.

“Early diagnosis of sickle cell in newborns as well as comprehensive care can effectively improve the situation and reduce mortality rate by 70 percent in some countries,” she noted. She said that low understanding of the disease has been identified as the biggest challenge among Tanzanians as there is a misleading notion that associates sickle cell with HIV/Aids hence leaving many scared of attending clinics.  

However, CSFT launched a campaign on sickle cell called “Cycle for Sickle Cell” which began in October 2012 and turned out successful as it helped raise awareness. 

For his part, sickle cell department coordinator from the Muhimbili National Hospital (MNH), Deogratius Soka said USD2m equivalent to 3bn/- is required to start building a structure for the disease’s centre. He however said as of now awareness among the public has increased whereby the number of patients attending has increased from 800 in 2004 to 4,000 this year.

He said since MNH already has a department dealing with sickle cell, they now focus on reaching other hospitals which don’t have the section by supporting them with experts and facilities.  He added that Tanzania intends to introduce screening for newborns and strengthen sickle cell services in health facilities at all levels.

Soka noted that there are advances in medicine and improved knowledge on the management of sickle cell that can be implemented in Tanzania to reduce mortality and improve the quality of life of people with the disease.

Meanwhile, Kenya Commercial Bank (KCB) branch manager Philipo Pilla said the foundation needs more support from various institutions so that it reaches more people. 

He added that several people are suffering but know nothing about the disease, thus more education is needed to increase awareness.

SICKLE CELL FOUNDATION NIGERIA (SCFN)

www.sicklecellfoundation.com

The SCFN has, arguably, the most comprehensive Sickle Cell Centre in Africa. With donor support, we supervise, in 4 Nigerian States, the running of 6 Sickle Cell Clinics involving a free supply of drugs, some materials and some equipment. More States will be added when financial provision permits. Already, these dedicated clinics have positively impacted the longevity and quality of lives of patients.  Other routine services include an e-library on SCD (membership available); genetic counseling; patient and community education; TCD scanning of children to determine risk of stroke; laboratory diagnosis; leg ulcer treatment; chorionic villus sampling (CVS) for prenatal diagnosis (PND). Access to PND is limited by the cost of having to send samples to England for DNA diagnosis. Our DNA laboratory requires some equipment and materials to enable it attain world standard, complete PND locally and thus improve access to the service.

We also run training courses on Genetic Counseling, Update Seminars for doctors and nurses; Practical training on TCD scanning and on CVS under ultrasound guidance. We invite collaboration on research and office space and accommodation are available for visiting researchers. Our immediate needs are

1. 1 Apheresis machine

2. For DNA analysis

2. 1 Thermocycler (0.2ml tube)

2.2 Nano drop Spectrophotometer

2.3 GeneMapper ®  ID-X v1.2 Software, Full Version for 3500 Genetic analyser

2.4 Gel Tank and Power Pack

Contact: Annette Akinsete    annettea@sicklecellfoundation.com                          

 Olu Akinyanju    oakinyanju@sicklecellfoundation.com   

New Free Publications from the CDC     

All available at http://www.cdc.gov/ncbddd/sicklecell/freematerials.html      

The Registry and Surveillance System for Hemoglobinopathies (RuSH) data for several states    Toolkit for Living Well with Sickle Cell Disease Adobe PDF file      
Fact Sheet: Sickle Cell Disease
 Adobe PDF file
 Sickle Cell Disease National Resource Directory Adobe PDF file
The Sickle Cell Disease National Resource Directory is a compilation of national agencies, state-based health providers, and community-based organizations
that provide services and resources for individuals and families affected by SCD.

New Video

Sickle Cell Disease on the Doctors TV show http://www.thedoctorstv.com/main/show_synopsis/1221?section=synopsis

CDC webinar: from May  Baby on Board: What You Need to Know about Pregnancy in the Hemoglobinopathies

Dr. Sophie Lanzkron, Sickle Cell Center for Adults at Johns Hopkins Hospital

mms://realaudio.service.emory.edu/SOM/PA/PLATT/SICKLE/CDCbabyonboard.wmv

SAVE THE DATES

Fellow colleagues, you are invited to participate in the“Public Health Webinar Series on Hemoglobinopathies” Hosted by: The Division of Blood Disorders, CDC

4th Thursday of every month from 2:00PM – 3:00PM EST

6/27: Beta-globin Haplotype Analysis in Children with Sickle Cell Anemia

Dr. Christopher Bean, National Center on Birth Defects and Developmental Disabilities, CDC  

7/25: Nurses’ Impact on the Stigmatization of Individuals with Sickle Cell: Challenges and Recommendations

Dr. Coretta Jenerette, International Association of Sickle Cell Nurses and Physician Assistants

  8/22: Mental Health and Learning Needs in children with Sickle Cell Disease

Dr. Patricia Kavanagh, Boston University School of Medicine/Boston Medical Center  

9/26: NHLBI Sickle Cell Disease Guidelines

Dr. Joylene John-Sowah, National Heart Lung and Blood Institute, NIH   

10/24: Current Data on Efficacy and Effectiveness of Hydroxyurea in Children with Sickle Cell Disease

Dr. Winfred Wang, St. Jude Children’s Research Hospital 

November/December: --- No Webinars---  

If you have ideas on topics for future webinars, or have any questions or comments about this series please submit them to Shae Pope spope@cdc.gov .

The purpose of this webinar series is to offer a hemoglobinopathies learning collaborative platform for providers, consumers, educators, and scientists. 

 

CDC Web based Sickle Cell Resources

CDC’s YouTube Link: http://www.youtube.com/watch?v=gnrvYsZWR1c&list=UUiMg06DjcUk5FRiM3g5sqoQ&index=2&feature=plpp_video

 CDC Video Archive (http://scinfo.org/world-wide-resources/cdc-webinars-hemoglobinopathies-and-public-health

 CDC Sickle Cell Disease Webpage: http://wwwdev.cdc.gov/NCBDDD/sicklecell/video.html 

Articles in the Medical Literature for June

 

1.

Clin Chim Acta. 2013 Jun 21. pii: S0009-8981(13)00248-9. doi: 10.1016/j.cca.2013.06.007. [Epub ahead of print]

HPLC-ESI-MS/MS analysis of hemoglobin peptides in tryptic digests of dried-blood spot extracts detects HbS, HbC, HbD, HbE, HbO-Arab, and HbG-Philadelphia mutations.

Haynes CAGuerra SLFontana JCDejesús VR.

Biochemical Mass Spectrometry Laboratory, Centers for Disease Control and Prevention, 4770 Buford Hwy. NE, Mail Stop F-19, Atlanta, GA, 30341. Electronic address: cph7@cdc.gov.

Abstract

BACKGROUND:

Hemoglobinopathies are mutations resulting in abnormal globin chain structure; some have clinically significant outcomes such as anemia or reduced lifespan. Five β-globinmutations are (c.20A>T, p.E6V), (c.19G>A, p. E6K),(c.79G>A, p.E26K),(c.364G>C, p.E121Q), and(c.364G>A, p.E121K), resulting in HbS (sickle-cell hemoglobin), HbC, HbE,HbD-Los Angeles, and HbO-Arab, respectively. One α-globin mutation is (c.[207C>G or 207C>A], p.N68K), resulting in HbG-Philadelphia.

METHODS:

HPLC-ESI-MS/MS analysis of dried-blood spot (DBS) punches from newborns extracted with a trypsin-containing solution provides greater than 90% coverage of α-, β-, and γ-globinamino acid sequences. Because the(c.20A>T, p.E6V), (c.19G>A, p. E6K), (c.79G>A, p.E26K), (c.364G>C, p.E121Q), (c.364G>A, p.E121K), and (c.[207C>G or 207C>A], p.N68K)mutations generate globinpeptides with novel amino acid sequences, detecting one of these peptides in DBS extracts is indicative of the presence of ahemoglobinopathy in the newborn.

RESULTS:

The method described here can distinguish normal β-globin peptides from the mutant HbS,HbC, HbE,HbD-Los AngelesandHbO-Arab peptides, as well as normal α-globin peptide from the mutant HbG-Philadelphia peptide, allowing the identification of unaffected heterozygotes such as HbAS, and of compound heterozygotes such as HbASG-Philadelphia.

CONCLUSIONS:

This HPLC-ESI-MS/MS analytical approach provides informationthat is not available from traditional hemoglobin analyses such as isoelectric focusing and HPLC-UV. It is also capable of determining the amino acid sequence of hemoglobinpeptides, potentially allowing the detection of numerous hemoglobinopathiesresulting from point mutations.

Published by Elsevier B.V.

PMID: 23796846 [PubMed - as supplied by publisher]

 

2.

Pediatr Blood Cancer. 2013 Jun 17. doi: 10.1002/pbc.24624. [Epub ahead of print]

Clinically meaningful measurement of pain in children with sickle cell disease.

Myrvik MPBrandow AMDrendel ALYan KHoffmann RGPanepinto JA.

Department of Pediatrics, Medical College of Wisconsin, Milwaukee, Wisconsin; Division of Pediatric Hematology/Oncology/Transplant, Medical College of Wisconsin, Milwaukee, Wisconsin.

Abstract

BACKGROUND:

Limited understanding of the interpretability of patient-reported pain scores may impact pain management. The current study assessed the minimal clinically significant improvement in pain and pain scores signifying patient-reported need for medication and treatment satisfaction in patients with sickle cell disease (SCD).

PROCEDURE:

Patients, 8-18-years-old, with SCD were recruited while receiving treatment for pain. Patients completed initial pain severity ratings using the Visual Analog Scale (VAS) and the Numeric Rating Scale (NRS). Serial assessments of pain severity, pain relief, perceived need for medication, and treatment satisfaction were completed in the emergency department and the hospitalization. Data were used to calculate the minimal clinically significant improvement in pain and pain scores associated with perceived need for pain medication and treatment satisfaction.

RESULTS:

Twenty-eight patients completed 305 assessments during 37 total visits. A decrease in pain severity score of 0.97 cm for the VAS and 0.9 for the NRS was found to be the minimum clinically significant improvement in pain. Pain scores >7.45 cm on the VAS or 7.5 on the NRS were suggestive of patient-reported need for pain medication. Pain scores <7.35 cm on the VAS or 8.5 on the NRS were suggestive of patient-reported treatment satisfaction discrimination.

CONCLUSIONS:

The minimal clinical significant improvement was defined for the VAS and NRS and both scales were able to discriminate between important clinical findings including pain relief, need for pain medication, and treatment satisfaction. Collectively, this study provides data to improve our understanding of pain ratings of pediatric patients with SCD. Pediatr Blood Cancer 2013;9999:1-7. © 2013 Wiley Periodicals, Inc.

Copyright © 2013 Wiley Periodicals, Inc.

PMID: 23776145 [PubMed - as supplied by publisher]

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3.

Pediatr Blood Cancer. 2013 Jun 18. doi: 10.1002/pbc.24630. [Epub ahead of print]

Trends in blood transfusion among hospitalized children with sickle cell disease.

Raphael JLOyeku SOKowalkowski MAMueller BUEllison AM.

Department of Pediatrics, Baylor College of Medicine, Houston, Texas.

Abstract

BACKGROUND:

Blood transfusions represent a major therapeutic option in acute management of sickle cell disease (SCD). Few data exist documenting trends in transfusion among children with SCD, particularly during hospitalization.

PROCEDURE:

This was an analysis of cross-sectional data of hospital discharges within the Kid's Inpatient Database (years 1997, 2000, 2003, 2006, 2009). Hospitalizations for children (0-18 years) with a primary or secondary SCD-related diagnosis were examined. The primary outcome was blood transfusion. Trends in transfusion were assessed using weighted multivariate logistic regression in a merged dataset with year as the primary independent variable. Co-variables consisted of child and hospital characteristics. Multivariate logistic regression was conducted for 2009 data to assess child and hospital-level factors associated with transfusion.

RESULTS:

From 1997 to 2009, the percentage of SCD-related hospitalizations with transfusion increased from 14.2% to 28.8% (P < 0.0001). Among all SCD-related hospitalizations, the odds of transfusion increased over 20% for each successive study interval. Hospitalizations with vaso-occlusive pain crisis (OR 1.35, 95% CI 1.27-1.43) or acute chest syndrome/pneumonia (OR 1.24, 95% CI 1.13-1.35) as the primary diagnoses had the highest odds of transfusion for each consecutive study interval. Older age and male gender were associated with higher odds of transfusion.

CONCLUSIONS:

Blood transfusion is increasing over time among hospitalized children with SCD. Further study is warranted to identify indications contributing to the rise in transfusions and if transfusions in the inpatient setting have been used appropriately. Future studies should also assess the impact of rising trends on morbidity, mortality, and other health-related outcomes. Pediatr Blood Cancer © 2013 Wiley Periodicals, Inc.

Copyright © 2013 Wiley Periodicals, Inc.

PMID: 23775719 [PubMed - as supplied by publisher]

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4.

Blood. 2013 Jun 17. [Epub ahead of print]

Mast cell activation contributes to sickle cell pathobiology and pain.

Vincent LVang DNguyen JGupta MLuk KEricson MESimone DAGupta K.

Vascular Biology Center, Division of Hematology, Oncology & Transplantation, Department of Medicine, University of Minnesota, Minneapolis, MN, United States;

Abstract

Sickle cell anemia (SCA) is an inherited disorder associated with severe life-long pain and significant morbidity. The mechanisms of pain in SCA remain poorly understood. We show that mast cell activation/degranulation contributes to sickle pain pathophysiology by promoting neurogenic inflammation and nociceptor activation via the release of substance P in the skin and dorsal root ganglion. Mast cell inhibition with imatinib ameliorated cytokine release from skin biopsies and led to a correlative decrease between GMCSF and white blood cells in sickle mice. Targeting mast cells by genetic mutation or pharmacologic inhibition with imatinib ameliorates tonic hyperalgesia and prevents hypoxia/reoxygenation-induced hyperalgesia in sickle mice. Pre-treatment with the mast cell stabilizer Cromolyn sodium improved analgesia following low doses of morphine that would otherwise be ineffective. Mast cell activation therefore underlies sickle pathophysiology leading to inflammation, vascular dysfunction, pain and requirement for high doses of morphine. Pharmacological targeting of mast cells with imatinib may be a suitable approach to address pain and perhaps treat SCA.

PMID: 23775718 [PubMed - as supplied by publisher]

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5.

Cochrane Database Syst Rev. 2013 Jun 12;6:CD010155. [Epub ahead of print]

Low-molecular-weight heparins for managing vaso-occlusive crises in people with sickle cell disease.

van Zuuren EJFedorowicz Z.

Department of Dermatology, Leiden University Medical Center, PO Box 9600, B1-Q, Leiden, Netherlands, 2300 RC.

Abstract

BACKGROUND:

Sickle cell disease is one of the most common and severe genetic disorders in the world. It can be broadly divided into two distinct clinical phenotypes characterized by either haemolysis or vaso-occlusion. Pain is the most prominent symptom of vaso-occlusion, and hypercoagulability is a well-established pathogenic phenomenon in people with sickle cell disease. Low-molecular-weight heparins might control this hypercoagulable state through their anticoagulant effect.

OBJECTIVES:

To assess the effects of low-molecular-weight heparins for managing vaso-occlusive crises in people with sickle cell disease.

SEARCH METHODS:

We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Haemoglobinopathies Trials Register comprising references identified from comprehensive electronic database searches. We also searched abstract books of conference proceedings and several online trials registries for ongoing trials.Date of the last search of the Cochrane Cystic Fibrosis and Genetic Disorders Group Haemoglobinopathies Trials Register: 6 December 2012.

SELECTION CRITERIA:

Randomised controlled clinical trials and controlled clinical trials that assessed the effects of low-molecular-weight heparins in the management of vaso-occlusive crises in people with sickle cell disease.

DATA COLLECTION AND ANALYSIS:

Study selection, data extraction, assessment of risk of bias and analyses were carried out independently by the two review authors.

MAIN RESULTS:

One study (with an overall unclear to high risk of bias) comprising 253 participants was included. This study, with limited data, reported that pain severity at day two and day three was lower in the tinzaparin group than in the placebo group (P < 0.01, analysis of variance (ANOVA)) and additionally at day 4 (P < 0.05 (ANOVA)). Thus tinzaparin resulted in more rapid resolution of pain, as measured with a numerical pain scale. The mean difference in duration of painful crises was statistically significant at -1.78 days in favour of the tinzaparin group (95% confidence interval -1.94 to -1.62). Participants treated with tinzaparin had statistically significantly fewer hospitalisation days than participants in the group treated with placebo, with a mean difference of -4.98 days (95% confidence interval -5.48 to -4.48). Two minor bleeding events were reported as adverse events in the tinzaparin group, and none were reported in the placebo group.

AUTHORS' CONCLUSIONS:

Based on the results of one study, evidence is incomplete to support or refute the effectiveness of low-molecular-weight heparins in people with sickle cell disease. Vaso-occlusive crises are extremely debilitating for sufferers of sickle cell disease; therefore well-designed placebo-controlled studies with other types of low-molecular-weight heparins, and in participants with different genotypes of sickle cell disease, still need to be carried out to confirm or dismiss the results of this single study.

PMID: 23760785 [PubMed - as supplied by publisher]

Related citations

 

6.

PLoS One. 2013 Jun 6;8(6):e65001. doi: 10.1371/journal.pone.0065001. Print 2013.

Dilemma in Differentiating between Acute Osteomyelitis and Bone Infarction in Children with Sickle Cell Disease: The Role of Ultrasound.

Inusa BPOyewo ABrokke FSanthikumaran GJogeesvaran KH.

Department of Paediatrics, Evelina Children's Hospital, Guy's and St. Thomas' National Health Service (NHS) Foundation Trust, London, United Kingdom.

Abstract

BACKGROUND:

Distinguishing between acute presentations of osteomyelitis (OM) and vaso-occlusive crisis (VOC) bone infarction in children with sickle cell disease (SCD) remains challenging for clinicians, particularly in culture-negative cases. We examined the combined role of ultrasound scan (USS), C - reactive protein and White blood counts (WCC) in aiding early diagnosis in children with SCD presenting acutely with non-specific symptoms such as bone pain, fever or swelling which are common in acute osteomyelitis or VOC.

METHODS:

We reviewed the records of all children with SCD who were discharged from our department from October 2003 to December 2010 with a diagnosis of osteomyelitis based on clinical features and the results of radiological and laboratory investigations. A case control group with VOC who were investigated for OM were identified over the same period.

RESULTS:

In the osteomyelitis group, USS finding of periosteal elevation and/or fluid collection was reported in 76% cases with the first scan (day 0-6). Overall 84% were diagnosed with USS (initial +repeat). 16% had negative USS. With VOC group, USS showed no evidence of fluid collection in 53/58 admissions (91%), none of the repeated USS showed any fluid collection. Mean C-reactive protein (CRP), and white cell count (WCC) were significantly higher in the OM.

CONCLUSION:

The use of Ultrasound in combination with CRP and WCC is a reliable, cost-effective diagnostic tool for differentiating osteomyelitis from VOC bone infarction in SCD. A repeat ultrasound and/or magnetic resonance imaging (MRI) scan may be is necessary to confirm the diagnosis.

PMCID: PMC3675051 Free PMC Article

PMID: 23755165 [PubMed - in process]

Related citations


 

7.

PLoS Negl Trop Dis. 2013 May 30;7(5):e2120. doi: 10.1371/journal.pntd.0002120. Print 2013 May.

Is sickle cell anemia a neglected tropical disease?

Ware RE.

Texas Children's Center for Global Health, Texas Children's Hospital, Houston, Texas, United States of America ; Department of Pediatrics, Baylor College of Medicine, Houston, Texas, United States of America.

PMCID: PMC3671937 Free PMC Article

PMID: 23750287 [PubMed - in process]

Related citations


 

8.

Atherosclerosis. 2013 May 16. pii: S0021-9150(13)00309-2. doi: 10.1016/j.atherosclerosis.2013.05.006. [Epub ahead of print]

Stroke in sickle cell anemia patients: A need for multidisciplinary approaches.

Menaa F.

Center of Hematology and Hemotherapy (Hemocentro), School of Medicine and Medical Sciences (FCM), University of Campinas (UNICAMP), São Paulo, Brazil; Laboratory of Human Molecular Genetics, Center for Molecular Biology and Genetic Engineering (CBMEG), University of Campinas (UNICAMP), São Paulo, Brazil; Department of Nanomedicine and Biochemistry, Fluorotronics, Inc., San Diego, CA, USA. Electronic address: dr.fmenaa@gmail.com.

Abstract

Sickle cell anemia (SCA) is an autosomal recessive disorder, with Mendelian inheritance pattern, caused by a missense mutation in the β-polypeptide chain of the hemoglobin B. SCA preferentially affects populations in countries where malaria was/is present (e.g. Africa, USA, Brazil). Thereby, in USA, the incidence of SCA is relatively high, around 1/500, and the prevalence is about 1/1000. In Brazil, SCA represents a major public health problem with an incidence ranging from 1/2000 to 1/600 depending on the regions. Homozygotic patients present more severe medical conditions and reduced life expectancy than heterozygous individuals who generally are asymptomatic. Eventually, this life-threatening disease displays a complex etiology owing to heterogeneous phenotypes and clinical outcomes, subsequently affecting the management of the patients. One of the most critical complications associated with SCA is stroke, a leading neurologic cause of death and disability. About 24% of SCA patients have a stroke by the age of 45 and 11% by the age of 20. From the general population, twin and familial aggregation studies as well as genome-wide association studies (GWAS), mostly in pediatric populations with ischemic stroke, showed that the risk of stroke has a substantial genetic component. Nevertheless, to fully characterize genomic contributors of stroke and permit reliable personalized medicine, multidisciplinary studies incorporating knowledge from clinical medicine, epidemiology, genetics, and molecular biology, are required. In this manuscript, stroke in SCA patients is extensively reviewed with emphasis to the US and Brazilian populations. Recent advances in genomics analysis of stroke in SCA patients are highlighted.

Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

PMID: 23746538 [PubMed - as supplied by publisher]

Related citations

 

9.

Cochrane Database Syst Rev. 2013 May 31;5:CD007001. doi: 10.1002/14651858.CD007001.pub3.

Hematopoietic stem cell transplantation for people with sickle cell disease.

Oringanje CNemecek EOniyangi O.

Institute of Tropical Disease Research and Prevention, University of Calabar Teaching Hospital, Calabar, Nigeria. chyoma12@yahoo.com.

Update of

Abstract

BACKGROUND:

Sickle cell disease is a genetic disorder involving a defect in the red blood cells due to its sickled hemoglobin. The main therapeutic interventions include preventive and supportive measures. Hematopoietic stem cell transplantations are carried out with the aim of replacing the defective cells and their progenitors (hematopoietic (i.e. blood forming) stem cells) in order to correct the disorder.

OBJECTIVES:

To determine whether stem cell transplantation can improve survival and prevent symptoms and complications associated with sickle cell disease. To examine the risks of stem cell transplantation against the potential long-term gain for people with sickle cell disease.

SEARCH METHODS:

We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Group's Haemoglobinopathies Trials Register complied from electronic searches of the Cochrane Central Register of Controlled Trials (CENTRAL) (updated each new issue of The Cochrane Library) and quarterly searches of MEDLINE.Unpublished work was identified by searching the abstract books of major conference proceedings and we conducted a search of the website: www.ClinicalTrials.gov.Date of the most recent search of the Group's Haemoglobinopathies Trials Register: 16 August 2012.

SELECTION CRITERIA:

Randomized controlled and quasi-randomized studies that compared any method of stem cell transplantation with either each other or with any of the preventive or supportive interventions (e.g. periodic blood transfusion, use of hydroxyurea, antibiotics, pain relievers, supplemental oxygen) in people with sickle cell disease irrespective of the type of sickle cell disease, gender and setting.

DATA COLLECTION AND ANALYSIS:

No relevant trials were identified.

MAIN RESULTS:

Ten trials were identified by the initial search and none for the update. None of these trials were suitable for inclusion in this review.

AUTHORS' CONCLUSIONS:

Reports on the use of hematopoietic stem cell transplantation improving survival and preventing symptoms and complications associated with sickle cell disease are currently limited to observational and other less robust studies. No randomized controlled trial assessing the benefit or risk of hematopoietic stem cell transplantations was found. Thus, this systematic review identifies the need for a multicentre randomized controlled trial assessing the benefits and possible risks of hematopoietic stem cell transplantations comparing sickle status and severity of disease in people with sickle cell disease.

PMID: 23728664 [PubMed - in process]

Related citations

 

10.

Cochrane Database Syst Rev. 2013 May 31;5:CD003425. doi: 10.1002/14651858.CD003425.pub2.

Splenectomy versus conservative management for acute sequestration crises in people with sickle cell disease.

Owusu-Ofori SHirst C.

Transfusion Medicine Unit, Komfo Anokye Teaching Hospital, Kumasi, Ghana.sowusu_ofori@hotmail.com.

Update of

Abstract

BACKGROUND:

Acute splenic sequestration crises are a complication of sickle cell disease, with high mortality rates and frequent recurrence in survivors of first attacks. Splenectomy and blood transfusion, with their consequences, are the mainstay of long-term management used in different parts of the world.

OBJECTIVES:

To assess whether splenectomy (total or partial), to prevent acute splenic sequestration crises in people with sickle cell disease, improved survival and decreased morbidity in people with sickle cell disease, as compared with regular blood transfusions.

SEARCH METHODS:

We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Haemoglobinopathies Trials Register, which comprises of references identified from comprehensive electronic database searches and handsearching relevant journals and abstract books of conference proceedings.Additional trials were sought from the reference lists of the trials and reviews identified by the search strategy.Date of the most recent search: 06 December 2012.

SELECTION CRITERIA:

All randomized or quasi-randomized controlled trials comparing splenectomy (total or partial) to prevent recurrence of acute splenic sequestration crises with no treatment or blood transfusions in people with sickle cell disease.

DATA COLLECTION AND ANALYSIS:

No trials of splenectomy for acute splenic sequestration were found.

MAIN RESULTS:

No trials of splenectomy for acute splenic sequestration were found.

AUTHORS' CONCLUSIONS:

Splenectomy, if full, will prevent further sequestration and if partial, may reduce the recurrence of acute splenic sequestration crises. However, there is a lack of evidence from trials showing that splenectomy improves survival and decreases morbidity in people with sickle cell disease. There is a need for a well-designed, adequately-powered, randomized controlled trial to assess the benefits and risks of splenectomy compared to transfusion programmes, as a means of improving survival and decreasing mortality from acute splenic sequestration in people with sickle cell disease.

PMID: 23728644 [PubMed - in process]

Related citations

 

11.

J Arthroplasty. 2013 May 28. pii: S0883-5403(13)00259-3. doi: 10.1016/j.arth.2013.03.017. [Epub ahead of print]

Excellent Results and Minimal Complications of Total Hip Arthroplasty in Sickle Cell Hemoglobinopathy at Mid-Term Follow-Up Using Cementless Prosthetic Components.

Issa KNaziri QMaheshwari AVRasquinha VJDelanois REMont MA.

Rubin Institute for Advanced Orthopedics, Center for Joint Preservation and Replacement, Sinai Hospital of Baltimore, Baltimore, Maryland.

Abstract

The purpose of this study was to compare the outcomes of cementless primary total hip arthroplasty (THA) in sickle cell patients compared to the remaining cohort of osteonecrosis patients who did not have this disease. Thirty-two sickle cell patients (42 hips) who had a mean age of 37years and mean follow-up of 7.5years (range, 5-11years) were compared to 87 non-sickle cell osteonecrosis patients (102 hips) who had mean age of 43years and mean follow-up of 7years (range, 3-10.5years). Outcomes evaluated included implant survivorship, Harris hip scores, complication rates, radiographic outcomes, and Short Form-(SF-36) health questionnaire. There were no significant differences in aseptic implant survivorship (95 vs. 97%), Harris hip scores (87 vs. 88 points), SF-36 score, or radiographic findings between the two patient cohorts. In light of these findings, we believe that the outcomes of THA improved in sickle cell patients with optimized medical management and the use of cementless prosthetic devices.

Copyright © 2013 Elsevier Inc. All rights reserved.

PMID: 23726348 [PubMed - as supplied by publisher]

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Sickle Cell Conferences and Events

SCDAA 41ST ANNUAL CONVENTION BALTIMORE MD

September 24th - 27th "2013 Moving Forward: Advocating for New Discoveries, Advancements and Breakthroughs"http://www.sicklecelldisease.org/index.cfm?page=annual-convention

ESH Eurocord-Ed Eurocord World Cord Blood Congress IV and Innovative Therapies for Sickle Cell Disease Oct 24 – 27, 2013  Monaco http://www.esh.org/conference/esh-eurocord-ed-eurocord-world-cord-blood-congress-iv/

7th Annual Sickle Cell and Thalassaemia Conference: UK  3-5 October 2013
Improving the quality of life for patients affected with Sickle Cell Disease and Thalassaemia


Now in its seventh year, this annual Sickle Cell Disease and Thalassaemia Conference run by Evelina Children’s Hospital at Guy's and St Thomas' NHS Foundation Trust will take place from3rd to 5th October 2013.Combining theory and clinical practice and drawing on the latest research in the field, this annual Conference is intended for all those health care professionals involved in the diagnosis, treatment and care of patients with Sickle Disease and Thalassaemia.To book or for further information, please visit the website  www.guysandstthomasevents.co.uk

Global Sickle Cell Diseases Network Conference: Rio De Janeiro, Brazil, April 9-11, 2014website www.globalsicklecelldisease.org

Sickle Cell News for May 2013

June 19 World Sickle Cell Day http://worldsicklecellday.webs.com/

The World Health Organization (WHO) has started work to promote a world wide agenda to address hemoglobin dysfunctions.

WHO has made a commitment to:

  • Recognize that sickle cell disease is a major health issue.
  • Increase awareness of the world community regarding sickle cell disease.
  • Eliminate harmful and wrong prejudices associated with sickle cell disease.
  • Urges member countries where sickle cell disease is a public health problem to establish health programs at the national level and operate specialized centers for sickle cell disease and facilitate access to treatment.
  • Promote satisfactory access to medical services to people affected with sickle cell disease.
  • Provide technical support to all countries to prevent and manage sickle cell disease.
  • Promote and help research to improve the lives of people affected with sickle cell disease.

The World Sickle Cell day is celebrated across the globe with special emphasis in African Nations and Asia. The celebrations include a press, media campaigns, music shows, cultural activities, and talk shows.

The main emphasis is hence on educating medical professionals, care givers, and associated personnel about prevention, research, and resources to minimize the complications due to sickle cell disease. Hence June 19th is devoted mainly to spread awareness, through talks, seminars, pamphlets, literature and consultations.

SCDAA Announces Kier "Junior" Spates as Ambassador http://www.sicklecelldisease.org/index.cfm?page=news&id=34

Comedian Kier "Junior" Spates of the Steve Harvey Morning Show is joining the fight against sickle cell disease. Spates signed on as the national celebrity ambassador for the Sickle Cell Disease Association of America, Inc. (SCDAA) after recently speaking out about his struggle with the disease. Together, SCDAA and Spates will launch the "Rise Above" initiative. The campaign will educate and raise awareness about the blood disease across the nation.

Spates, a native of Houston, Texas, boasts an impressive resume that includes television spots on Black Entertainment Television, collaborative efforts on the "Rickey Smiley and Friends" show and his role in Hinton Battle's "Love Lies" stage play. He is most notably known today for his hilarious and high energy commentary on the Steve Harvey Morning Show. "We are excited to work with such a bright talent as Kier. He is the perfect choice for raising awareness about sickle cell disease in addition to spreading joy to those who support our cause," says SCDAA President Sonja Banks.

Spates is also living with sickle cell disease. He hopes to inspire others and increase the support and visibility of the disease through this recent partnership with the SCDAA. Please visitwww.facebook.com/riseabovecampaign for updates about SCDAA's joint "Rise Above" campaign with Spates.

New Video

New Parents hand book and Children’s DVD produced in the UK

The 3rd Edition of, 'A Parents guide to managing Sickle Cell Disease', in English is available on the UK national screening web site www.sct.screening.nhs.ukand on the Brent Centre web site www.sickle-thal.nwlh.nhs.uk. It is being translated into French also and will be available in the summer. A new children's DVD, 'My Sickle Cell Disease and Me', funded by Roald Dhal, aimed at children aged 5 - 11years is available on the Brent Centre web site www.sickle-thal.nwlh.nhs.uk

SAVE THE DATES

Fellow colleagues, you are invited to participate in the“Public Health Webinar Series on Hemoglobinopathies” Hosted by: The Division of Blood Disorders, CDC

4th Thursday of every month from 2:00PM – 3:00PM EST

6/27: Beta-globin Haplotype Analysis in Children with Sickle Cell Anemia

Dr. Christopher Bean, National Center on Birth Defects and Developmental Disabilities, CDC  

7/25: Nurses’ Impact on the Stigmatization of Individuals with Sickle Cell: Challenges and Recommendations

Dr. Coretta Jenerette, International Association of Sickle Cell Nurses and Physician Assistants

  8/22: Mental Health and Learning Needs in children with Sickle Cell Disease

Dr. Patricia Kavanagh, Boston University School of Medicine/Boston Medical Center  

9/26: NHLBI Sickle Cell Disease Guidelines

Dr. Joylene John-Sowah, National Heart Lung and Blood Institute, NIH   

10/24: Current Data on Efficacy and Effectiveness of Hydroxyurea in Children with Sickle Cell Disease

Dr. Winfred Wang, St. Jude Children’s Research Hospital 

November/December: --- No Webinars---  

If you have ideas on topics for future webinars, or have any questions or comments about this series please submit them to Shae Pope spope@cdc.gov .

The purpose of this webinar series is to offer a hemoglobinopathies learning collaborative platform for providers, consumers, educators, and scientists.



 

CDC Web based Sickle Cell Resources

CDC’s YouTube Link: http://www.youtube.com/watch?v=gnrvYsZWR1c&list=UUiMg06DjcUk5FRiM3g5sqoQ&index=2&feature=plpp_video

 CDC Video Archive (http://scinfo.org/world-wide-resources/cdc-webinars-hemoglobinopathies-and-public-health

 CDC Sickle Cell Disease Webpage: http://wwwdev.cdc.gov/NCBDDD/sicklecell/video.html  

Articles in the Medical Literature for May

1.

J Pain. 2013 May 20. pii: S1526-5900(13)00938-3. doi: 10.1016/j.jpain.2013.03.007. [Epub ahead of print]

Validation of the Sickle Cell Disease Pain Burden Interview-Youth.

Zempsky WTO'Hara EASantanelli JPPalermo TMNew TSmith-Whitley KCasella JF.

Division of Pain and Palliative Medicine, Department of Pediatrics, Connecticut Children's Medical Center, Hartford, Connecticut; University of Connecticut School of Medicine, Farmington, Connecticut. Electronic address: wzempsk@ccmckids.org.

Abstract

The purpose of this study was to develop and validate a brief, clinically relevant, multidimensional interview to assess pain burden among children and adolescents with sickle cell disease (SCD). The Sickle Cell Disease Pain Burden Interview-Youth (SCPBI-Y) was developed using a panel of experts, patients, and caregivers. Validation was undertaken with children and youth with SCD, ages 7 to 21 years (N = 129), recruited from 4 urban children's hospitals. Participants were recruited from inpatient (n = 62) and outpatient (n = 67) settings. The SCPBI-Y demonstrated strong internal consistency reliability, cross-informant concordance (child-caregiver), and test-retest reliability (outpatient setting). Moderate construct validity was found with validated measures of functional ability, pain, and quality of life. The SCPBI-Y demonstrated construct validity using a contrasted group approach between youth in inpatient versus outpatient settings and by severity of SCD symptoms, suggesting that youth in inpatient settings and with higher disease severity exhibited greater pain burden. Discriminant validity was found between SCPBI-Y and mood. Our preliminary findings suggest that the SCPBI-Y is a valid and reliable multidimensional interview that can be used in different clinical settings to evaluate pain burden among children and adolescents with SCD. PERSPECTIVE: Multifaceted pain assessments are salient in providing optimal care to children and adolescents with SCD; however, current evaluations are lengthy and cumbersome to administer clinically. The current study introduces and validates a brief, clinically useful multidimensional interview to evaluate pain burden specific to youth with SCD.

Copyright © 2013 American Pain Society. Published by Elsevier Inc. All rights reserved.


PMID: 23701707 [PubMed - as supplied by publisher]


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2.

PLoS Pathog. 2013 May;9(5):e1003327. doi: 10.1371/journal.ppat.1003327. Epub 2013 May 16.

Hemoglobinopathies: Slicing the Gordian Knot of Plasmodium falciparum Malaria Pathogenesis.

Taylor SMCerami CFairhurst RM.

Division of Infectious Diseases and International Health, Duke University Medical Center, Durham, North Carolina, United States of America ; Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, North Carolina, United States of America.

Abstract

Plasmodium falciparum malaria kills over 500,000 children every year and has been a scourge of humans for millennia. Owing to the co-evolution of humans and P. falciparum parasites, the human genome is imprinted with polymorphisms that not only confer innate resistance to falciparum malaria, but also cause hemoglobinopathies. These genetic traits-including hemoglobin S (HbS), hemoglobin C (HbC), and α-thalassemia-are the most common monogenic human disorders and can confer remarkable degrees of protection from severe, life-threatening falciparum malaria in African children: the risk is reduced 70% by homozygous HbC and 90% by heterozygous HbS (sickle-cell trait). Importantly, this protection is principally present for severe disease and largely absent for P. falciparum infection, suggesting that these hemoglobinopathies specifically neutralize the parasite's in vivo mechanisms of pathogenesis. These hemoglobin variants thus represent a "natural experiment" to identify the cellular and molecular mechanisms by which P. falciparum produces clinical morbidity, which remain partially obscured due to the complexity of interactions between this parasite and its human host. Multiple lines of evidence support a restriction of parasite growth by various hemoglobinopathies, and recent data suggest this phenomenon may result from host microRNA interference with parasite metabolism. Multiple hemoglobinopathies mitigate the pathogenic potential of parasites by interfering with the export of P. falciparum erythrocyte membrane protein 1 (PfEMP1) to the surface of the host red blood cell. Few studies have investigated their effects upon the activation of the innate and adaptive immune systems, although recent murine studies suggest a role for heme oxygenase-1 in protection. Ultimately, the identification of mechanisms of protection and pathogenesis can inform future therapeutics and preventive measures. Hemoglobinopathies slice the "Gordian knot" of host and parasite interactions to confer malaria protection, and offer a translational model to identify the most critical mechanisms of P. falciparum pathogenesis.

PMCID: PMC3656091 Free PMC Article


PMID: 23696730 [PubMed - in process]


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3.

Value Health. 2013 May;16(3):A121. doi: 10.1016/j.jval.2013.03.579. Epub 2013 May 3.

Expanding concepts of opioid-taking behavior in sickle cell disease: A multi-phase, mixed methods study.

Alsalman AJLi Wong JKHassan NTSmith WR.

Virginia Commonwealth University, Richmond, VA, USA.


PMID: 23693291 [PubMed - in process]


Related citations



 

4.

Pediatr Blood Cancer. 2013 May 15. doi: 10.1002/pbc.24588. [Epub ahead of print]

Association Between Baseline Fetal Hemoglobin Levels and Incidence of Severe Vaso-Occlusive Pain Episodes in Children With Sickle Cell Anemia.

Bhatnagar PKeefer JRCasella JFBarron-Casella EABean CJHooper CWPayne ABArking DEDebaun MR.

McKusick-Nathans Institute of Genetic Medicine, School of Medicine, Johns Hopkins University, Baltimore, Maryland.

Abstract

The ameliorating effect of high fetal hemoglobin (HbF) levels on the incidence of pain episodes in sickle cell anemia (SCA) is well-known; however, in children this relationship is less clearly established. We hypothesized that higher HbF levels in children with SCA are associated with fewer severe pain episodes. A meta-analysis of data from the Silent Infarct Transfusion Trial (n = 456) and the Cooperative Study of Sickle Cell Disease (n = 764), demonstrated that baseline HbF levels were associated with the incidence of severe pain, commonly defined across studies as an event requiring hospitalization (P-value = 0.02). Pediatr Blood Cancer © 2013 Wiley Periodicals, Inc.

Copyright © 2013 Wiley Periodicals, Inc.


PMID: 23677903 [PubMed - as supplied by publisher]


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5.

J Pediatr Hematol Oncol. 2013 May 9. [Epub ahead of print]

Transcranial Doppler in Sickle Cell Disease.

Sarkar NSharma VK.

*Division of Neurology, National University Hospital †Yong Loo Lin School of Medicine National University of Singapore, Singapore.


PMID: 23669727 [PubMed - as supplied by publisher]


Related citations

 

 

 

6.

Clin J Pain. 2013 May 9. [Epub ahead of print]

Differences in Pain Management Between Hematologists and Hospitalists Caring for Patients With Sickle Cell Disease Hospitalized for Vasoocclusive Crisis.

Shah NRollins MLandi DShah RBae JDe Castro LM.

*Department of Pediatric Hematology/Oncology †Division of Hematology ‡Department of Pediatrics §Division of Oncology ∥Department of Hospital Medicine, Duke University Medical Center, Durham, NC.

Abstract

OBJECTIVES:: Sickle cell disease (SCD) is a chronic disease characterized by multiple vaso-occlusive complications and is increasingly cared for by hospitalists. The purpose of this study is to examine differences in pain management between hematologists and hospitalists. METHODS:: We performed a single-institution, retrospective review of pain management patterns and outcomes in adult SCD patients hospitalized for vaso-occlusive crisis. RESULTS:: Over 26 months, we found a total of 298 patients (120 cared for by the hematologists and 178 by hospitalists), with a mean age of 32 (range 19-58). Patients cared for by hospitalists had a lower total number of hours on a patient controlled analgesia (PCA) device (171 vs. 212 hours, P=0.11). Hospitalists also were significantly more likely to utilize demand only PCA (42% vs. 23%, P=0.002) and had a significantly lower rate of using both continuous and demand PCA (54% vs. 67%, P=0.04). In addition, patients cared for by hospitalists had a significantly shorter hospitalization (8.4 days) compared to hematologists (10 days, P=0.04) with a non-significant difference in 7 and 30 day readmission rates (7.2% vs. 6.7% and 40% vs. 35% respectively). CONCLUSION:: We found patients cared for by hospitalists more frequently utilized home oral pain medication during admission, had shorter lengths of hospitalization, and did not have a significant increase in readmission rates.


PMID: 23669451 [PubMed - as supplied by publisher]


Related citations



 

7.

Clin Pediatr (Phila). 2013 May 9. [Epub ahead of print]

Incidence of Serious Bacterial Infections in Febrile Children With Sickle Cell Disease.

Bansil NHKim TYTieu LBarcega B.

1Loma Linda University, Loma Linda, CA, USA.

Abstract

Objective. To determine the incidence of serious bacterial infections in febrile children with sickle cell disease and to describe the outcomes of children discharged from the pediatric emergency department. Methods. We conducted a retrospective chart review of 188 febrile patients with sickle cell disease presenting to our pediatric emergency department over a 10-year period. Serious bacterial infection was defined as bacteremia, meningitis, urinary tract infection, osteomyelitis, or pneumonia. Results. Our overall incidence rate for serious bacterial infections was 16.0% (95% confidence interval [CI] = 10.8% to 21.2%). Pneumonia had the highest incidence rate of 13.8% (95% CI = 8.8% to 18.8%). This was followed by bacteremia and urinary tract infections, both with incidence rates of 1.1% (95% CI = 0.0% to 2.5%). We had no cases of meningitis or osteomyelitis in our study group. Conclusion. We had an incidence of 16.0% for serious bacterial infections in febrile children with sickle cell disease, with the majority of patients diagnosed with pneumonia.


PMID: 23661790 [PubMed - as supplied by publisher]


Related citations



 

8.

Haematologica. 2013 May 3. [Epub ahead of print]

A randomized, placebo-control trial of arginine therapy for the treatment ofchildren with sickle cell disease hospitalized with vaso-occlusive pain episodes.

Morris CRKuypers FALavrisha LAnsari MSweeters NStewart MGildengorin GNeumayr L,

 

Sickle Cell News for April 2013

Anti-sickling therapies should be focus for sickle cell science

 http://www.eurekalert.org/pub_releases/2013-04/mcog-ats041713.php

Pain is an undeniable focal point for patients with sickle cell disease but it's not the best focus for drug development, says one of the dying breed of physicians specializing in the condition.

Rather scientists need to get back to the crux of the disease affecting 1 in 500 black Americans and find better ways to prevent the hallmark sickling that impedes red blood cells' oxygen delivery, damaging blood vessel walls and organs along the way, said Dr. Abdullah Kutlar, Director of the Sickle Cell Center at the Medical College of Georgia at Georgia Regents University.

"We have one drug that reduces sickling and we need more," said Kutlar, the 2013 Roland B. Scott, M.D., Lecturer for the 7th Annual Sickle Cell Disease Research and Educational Symposium and National Sickle Cell Disease Scientific Meeting April 14-17 in Miami.

"Pain is very important to someone who is suffering, but by using pain as an end point, we are missing opportunities and wasting drugs that could be very helpful," he said. "Moving forward, I suggest we develop new combination therapies that have anti-sickling capabilities at their center," said Kutlar, noting such cocktail approaches have worked well for cancer and HIV.

Kutlar completed an extensive historical review of patient and study outcomes in preparation for the lecture honoring the late Howard University physician who made it his mission to improve the lives of children with sickle cell disease. Scott's contributions include prompting the National Sickle Cell Control Act of 1972, which established the first federally-funded comprehensive sickle cell centers, including the one at MCG led by Dr. Titus H.J. Huisman.

No doubt Scott, Huisman and others have made a tremendous difference to patients, whose average life expectancy has gone from the teens to the 50s in the past 30 years, Kutlar said. Much of that progress grew out of focusing on the basics, including developing hydroxyurea, still the only Food and Drug Administration-approved drug that targets sickling.

Approved 15 years ago, hydroxyurea works by increasing expression of fetal hemoglobin, which can't sickle. However, it's still not widely used – about 35 percent of Kutlar's adult patients take it, for example – probably for a combination of reasons that include a side effect of weight gain and unsubstantiated concerns that it increases cancer risk. He and his colleagues need to do a better job communicating the benefits of this drug in addition to finding new ones, Kutlar said. Reduced sickling means less damage to blood vessels and organs, he said, noting that the major cause of death in adults and children is acute chest syndrome, a severe pneumonia resulting from cumulative lung damage. A handful of new anti-sickling drugs are in various stages of development, including a thalidomide- derivative pioneered by MCG researchers that also enhances fetal hemoglobin expression.

Other good endpoints for drug development include downstream effects of sickling, such as the unnatural adhesion of red blood cells to blood vessel walls, Kutlar said. Unfortunately work was recently halted on a drug that reduced adhesion but not pain, Kutlar said.

Pain needs to be the primary endpoint only for pain medications, he noted. The good news is that many new pain medications are available for these patients, whose pain crises can be severe enough to require hospitalization and whose chronic pain can impair daily living. However, that circles back to the complex causes of pain. The pain initially likely results from tissues crying out for more oxygen and later from nerve and organ damage resulting from ongoing impaired oxygen supplies. Pain control can get even more complex and difficult because regular use of opiates, a common analgesic for sickle cell patients, actually increases pain sensitivity, Kutlar said.

In addition to finding better therapies, physicians who treat sickle cell patients need to help cultivate the next generation of caregivers, Kutlar said. He's in the minority in that he opted to take care of patients with sickle cell disease rather than pursue the more common – and generally more professionally lucrative – hematology path: treating cancer. "We don't have enough hematologists, period," said Kutlar. The problem does have a good cause: the reality that more patients are living longer. However, the number of physicians to treat adult patients is dismal. Helping cultivate the next generation is a focus of a study led by Kutlar and Dr. Robert W. Gibson, a GRU occupational therapist and medical anthropologist. They are reaching out to primary care physicians – who also are in short supply in this country – as a permanent medical home for patients as they reach adulthood. Kutlar and Gibson are co-principal investigators on $7 million, five-year grant from the National Center on Minority Health and Health Disparities of the National Institutes of Health supporting this initiative as well as the search for new drugs and more.

MCG physicians follow about 1,500 adults and children with sickle cell disease.

Clinical Research Forum selects sickle cell project among 'Top 10' clinical research achievements of 2012http://www.news-medical.net/news/20130422/Clinical-Research-Forum-selects-sickle-cell-project-among-Top-10-clinical-research-achievements-of-2012.aspx

Pioneering research led by Johns Hopkins scientists on the use of partially matched bone marrow transplants to wipe out sickle cell disease has been selected as one of the Top 10 Clinical Research Achievements of 2012 by the Clinical Research Forum. The success of a preliminary clinical trial of the so-called haploidentical transplants has the potential to bring curative transplants to a majority of sickle cell patients who need them, eliminating painful and debilitating symptoms and the need for a lifetime of pain medications and blood transfusions.

On behalf of the research team, Robert A. Brodsky, M.D., the Johns Hopkins Family Professor of Medicine in Oncologyand director of the Division of Hematology at the Johns Hopkins University School of Medicine, will receive the award and an additional honor, the Distinguished Clinical Research Achievement Award, at a ceremony on April 18 during the Clinical Research Forum annual meeting in Washington, D.C.

New Web article Sickle Cell Disease Review

Advances in disease management and new treatment models help patients live longer. 1 contact hour of CEU for nurses:

http://nursing.advanceweb.com/Continuing-Education/CE-Articles/Sickle-Cell-Disease.aspx

 

New Video  - Strategies to Improve Implementation of Hydroxyurea

Dr. Courtney Thornburg, Duke Pediatric Sickle Cell Clinic

mms://realaudio.service.emory.edu/SOM/PA/PLATT/SICKLE/CDChydrea313.wmv

SAVE THE DATES

Fellow colleagues, you are invited to participate in the“Public Health Webinar Series on Hemoglobinopathies” Hosted by: The Division of Blood Disorders, CDC

4th Thursday of every month from 2:00PM – 3:00PM EST

5/23: Baby on Board: What You Need to Know about Pregnancy in the Hemoglobinopathies

     Dr. Sophie Lanzkron, Sickle Cell Center for Adults at Johns Hopkins Hospital 

6/27: Beta-globin Haplotype Analysis in Children with Sickle Cell Anemia

     Dr. Christopher Bean, National Center on Birth Defects and Developmental Disabilities, CDC  

7/25: Nurses’ Impact on the Stigmatization of Individuals with Sickle Cell: Challenges and Recommendations

     Dr. Coretta Jenerette, International Association of Sickle Cell Nurses and Physician Assistants

8/22: Mental Health and Learning Needs in children with Sickle Cell Disease

     Dr. Patricia Kavanagh, Boston University School of Medicine/Boston Medical Center  

9/26: NHLBI Sickle Cell Disease Guidelines

     Dr. Joylene John-Sowah, National Heart Lung and Blood Institute, NIH   

10/24: Current Data on Efficacy and Effectiveness of Hydroxyurea in Children with Sickle Cell Disease

     Dr. Winfred Wang, St. Jude Children’s Research Hospital 

November/December: --- No Webinars---  

If you have ideas on topics for future webinars, or have any questions or comments about this series please submit them to Shae Pope spope@cdc.gov .

The purpose of this webinar series is to offer a hemoglobinopathies learning collaborative platform for providers, consumers, educators, and scientists. 

 

CDC Web based Sickle Cell Resources

CDC’s YouTube Link: http://www.youtube.com/watch?v=gnrvYsZWR1c&list=UUiMg06DjcUk5FRiM3g5sqoQ&index=2&feature=plpp_video

 CDC Video Archive (http://scinfo.org/world-wide-