Monday, May 25, 2015

Sickle Cell News for June 2015

June 19 – World Sickle Cell Day - World Sickle Cell Day 2015: How Rare Disease Awareness Leads To Quality Care, Treatment http://www.medicaldaily.com/world-sickle-cell-day-2015-how-rare-disease-awareness-leads-quality-care-treatment-338846

http://www.huffingtonpost.com/edda-collins-coleman/world-sickle-cell-day-why_b_7617714.html

New Book for Patients and Family Members - Breaking Silence: Living With Sickle Cell Anemia  by James Griffin III

James Griffin III was diagnosed at the age of two with Sickle Cell Disease. Since then he has been determined to make a difference in his life and others by raising awareness about sickle cell anemia. This book reveals many aspects that patients face daily and is current and referenced.

http://www.amazon.com/Breaking-Silence-Living-Sickle-Anemia/dp/1500858005/ref=sr_1_3?ie=UTF8&qid=1435685668&sr=8-3&keywords=living+with+sickle+cell

New Web Resource - Super Moms with Sickle Cell and we're here to spread awareness in our own unique way and to help mothers.. Mothers with sickle cell go through so much more than a typical carrier. www.SuperMomswithSickleCell.com and email supermomswithsicklecell@yahoo.com

FDA- Sickle Cell and Clinical Trials Page - http://www.fda.gov/ForConsumers/ByAudience/MinorityHealth/ucm451865.htm

Video Resource –June 24 – 25, 2015  NHLBI Sickle Cell Disease Forum Engaging the Community: Developing Solutions (Day 1 and Day 2) http://videocast.nih.gov/summary.asp?Live=16351&bhcp=1

http://videocast.nih.gov/Summary.asp?File=19087&bhcp=1

High School Scholarship - Inspiring More Minds, Inc. presents the $500.00 2015 Paradise ScholarshipThis scholarship has been created to financially assist an eligible High School senior pursuing college or any other continued educational program. The Paradise Scholarship has been named in memory of Paradise Vaughn, a vibrant individual who passed away at the age of 19 due to complications from Sickle Cell Disease. Eligibility to apply      

-Current High School Senior   - Have Sickle Cell Disease - Acceptance into a program of higher educationTwo scholarship recipients will be selected.

Application deadline is July 5, 2015For Application go to www.InspiringMoreMinds.com( click on the FORMS tab )

Track  the new bill in Congress - H.R. 1807 Sickle Cell Disease Research, Surveillance, Prevention, and Treatment Act of 2015 at https://popvox.com/bills/us/114/hr1807 or https://www.govtrack.us/congress/bills/114/hr1807


Tuesday, May 5, 2015

Sickle cell in the Medical Literature | May 2015

1.
Cochrane Database Syst Rev. 2015 May 8;5:CD001916. [Epub ahead of print]
Abstract
BACKGROUND:
Sickle cell disease comprises a group of genetic blood disorders. It occurs when the sickle haemoglobin gene is inherited from both parents. The effects of the condition are: varying degrees of anaemia which, if severe, can reduce mobility; a tendency for small blood capillaries to become blocked causing pain in muscle and bone commonly known as 'crises'; damage to major organs such as the spleen, liver, kidneys, and lungs; and increased vulnerability to severe infections. There are both medical and non-medical complications, and treatment is usually symptomatic and palliative in nature. Psychological interventions for individuals with sickle cell disease might complement current medical treatment, and studies of their efficacy have yielded encouraging results. This is an update of a previously published Cochrane Review.
OBJECTIVES:
To examine the evidence that psychological interventions improve the ability of people with sickle cell disease to cope with their condition.
SEARCH METHODS:
We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Haemoglobinopathies Trials Register, which comprises references identified from comprehensive electronic database searches and the Internet, handsearches of relevant journals and abstract books of conference proceedings.Date of the most recent search of the Group's Haemoglobinopathies Trials Register: 17 February 2015.
SELECTION CRITERIA:
All randomised or quasi-randomised controlled trials comparing psychological interventions with no (psychological) intervention in people with sickle cell disease.
DATA COLLECTION AND ANALYSIS:
Both authors independently extracted data and assessed the risk of bias of the included studies.
MAIN RESULTS:
Twelve studies were identified in the searches and seven of these were eligible for inclusion in the review. Five studies, involving 260 participants, provided data for analysis. One study showed that cognitive behaviour therapy significantly reduced the affective component of pain (feelings about pain), mean difference -0.99 (95% confidence interval -1.62 to -0.36), but not the sensory component (pain intensity), mean difference 0.00 (95% confidence interval -9.39 to 9.39). One study of family psycho-education was not associated with a reduction in depression. Another study evaluating cognitive behavioural therapy had inconclusive results for the assessment of coping strategies, and showed no difference between groups assessed on health service utilisation. In addition, family home-based cognitive behavioural therapy did not show any difference compared to disease education. One study of patient education on health beliefs showed a significant improvement in attitudes towards health workers, mean difference -4.39 (95% CI -6.45 to -2.33) and medication, mean difference -1.74 (95% CI -2.98 to -0.50). Nonetheless, these results may not apply across all ages, severity of sickle cell disease, types of pain (acute or chronic), or setting.
AUTHORS' CONCLUSIONS:
Evidence for the efficacy of psychological therapies in sickle cell disease is currently limited. This systematic review has clearly identified the need for well-designed, adequately-powered, multicentre randomised controlled trials assessing the effectiveness of specific interventions in sickle cell disease.

PMID: 25966336 [PubMed - as supplied by publisher]


2.
Am J Hematol. 2015 May 11. doi: 10.1002/ajh.24051. [Epub ahead of print]
Abstract
Red blood cell (RBC) alloimmunization is a significant clinical complication of sickle cell disease (SCD). It can lead to difficulty with cross-matching for future transfusions and may sometimes trigger life-threatening delayed hemolytic transfusion reactions. We conducted a retrospective study to explore the association of clinical complications and age of red blood cells (RBC) with alloimmunization in patients with SCD followed at a single institution from 2005-2011. One hundred and sixty six patients with a total of 488 RBC transfusions were evaluated. Nineteen patients (11%) developed new alloantibodies following blood transfusions during the period of review. The median age of RBC units was 20 days (interquartile range: 14-27 days). RBC antibody formation was significantly associated with the age of RBC units (p = 0.002), with a hazard ratio of 3.5 (95% CI: 1.71-7.11) for a RBC unit that was 7 days old and 9.8 (95% CI: 2.66-35.97) for a unit that was 35 days old, 28 days after the blood transfusion. No association was observed between RBC alloimmunization and acute vaso-occlusive complications. Although increased echocardiography-derived tricuspid regurgitant jet velocity (TRV) was associated with the presence of RBC alloantibodies (p = 0.02), TRV was not significantly associated with alloimmunization when adjusted for patient age and number of transfused RBC units. Our study suggests that RBC antibody formation is significantly associated with older age of RBCs at the time of transfusion. Prospective studies in patients with SCD are required to confirm this finding. This article is protected by copyright. All rights reserved.
© 2015 Wiley Periodicals, Inc.

PMID: 25963831 [PubMed - as supplied by publisher]


3.
Br J Haematol. 2015 May 5. doi: 10.1111/bjh.13477. [Epub ahead of print]
Abstract
Sickle cell disease induces specific brain alterations that involve both the macrocirculation and the microcirculation. The main overt neurovascular complications in children are infarctive stroke, transient ischaemic attack and cerebral haemorrhage. Silent cerebral infarction, cognitive dysfunction and recurrent headache are also common. Cerebrovascular disease selectively affects children with the HbSS or HbS-β0genotypes (i.e. sickle cell anaemia). The incidence of stroke peaks between 2 and 5 years of age (1·02/100 patient-years) and increases with the severity of the anaemia. Most strokes can be prevented by annual transcranial Doppler screening from 2 to 16 years of age and providing chronic blood transfusion when this investigation shows elevated blood-flow velocities. The role for hydroxycarbamide in children with abnormal transcranial Doppler findings is under investigation. After a stroke, chronic blood transfusion is very strongly recommended, unless haematopoietic stem cell transplantation can be performed. Routine magnetic resonance imaging shows that more than one-third of children have silent cerebral infarction, which is associated with cognitive impairments. Screening for silent infarcts seems legitimate, since their presence may lead to supportive treatments. The role for more aggressive interventions such as hydroxycarbamide or chronic blood transfusion is debated.
© 2015 John Wiley & Sons Ltd.

PMID: 25944412 [PubMed - as supplied by publisher]


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4.
Lancet Haematol. 2014 Dec 1;1(3):e95-e103.
Abstract
BACKGROUND:
Well-tolerated and effective treatments are needed for chronic leg ulcers in sickle cell anaemia. Topical sodium nitrite, a known nitric oxide donor, enhances blood flow in ulcers and has known bacteriostatic effects. We aimed to assess the safety, tolerability, and pharmacokinetics of topical sodium nitrite in patients with sickle cell disease and chronic leg ulcers.
METHODS:
We enrolled adult patients from an ambulatory clinic at the National Institutes of Health (Bethesda, MD, USA) with sickle cell anaemia with leg ulcers (with a surface area of 2.5-100 cm2) persisting for at least 4 weeks into a safety and tolerability phase 1 dose-escalation trial of topical sodium nitrite. Increasing concentrations of sodium nitrite cream were applied twice weekly for 4 weeks to one ulcer per patient at five dose levels (0.5%, 1%, 1.5%, 1.8%, and 2%). The primary endpoints were safety and tolerability, with secondary endpoints of pharmacokinetics, blood flow, and wound healing. Pain relief was analysed post hoc. Endpoints were analysed over time for the whole study population and according to dose level. This study is registered with ClinicalTrials.gov, number NCT01316796.
FINDINGS:
Between April 4, 2011, and March 19, 2013, we enrolled 18 adult patients with sickle cell anaemia and leg ulcers into our trial. We assigned three patients into each cohort, and each cohort was treated with a different concentration of sodium nitrite cream (cohort 1: 0.5%, cohort 2: 1.0%, cohort 3: 1.5%, and cohort 4: 2.0%). Patients were not enrolled into the next cohort dose until we were able to establish that no dose-limiting toxicities were observed. An additional six patients were enrolled to cohort 3a: 1.8%, after two patients in cohort 4 had asymptomatic drops in diastolic blood pressure. No grade 3-4 adverse events were observed, and there were no serious adverse events or dose-limiting side-effects. Pharmacokinetic analysis showed that systemic absorption of sodium nitrite was very low. Application of topical sodium nitrite was associated with a significant increase in peri-wound cutaneous blood flow measured by laser speckle contrast imaging (p=0.0002), corroborated by increased peri-wound skin temperature by infrared thermography (p=0.0119). We recorded a dose-dependent decrease in leg ulcer size (p=0.0012) and pain (p<0.0001). Ulcers healed completely in three patients who received the highest concentrations of topical sodium nitrite (the 1.8% and 2% cream). In our post-hoc analysis of pain, brief pain inventory scores improved in pain severity (p=0.0048) and pain interference (p=0.0013).
INTERPRETATION:
Our results indicate that topical sodium nitrite 2% cream is suitable for additional clinical trials in adults with sickle cell anaemia to promote healing of leg ulcers.
FUNDING:
National Heart, Lung and Blood Institute Division of Intramural Research (National Institutes of Health).
PMCID: PMC4415859 Free PMC Article 

PMID: 25938131 [PubMed]


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5.
Pediatr Blood Cancer. 2015 Apr 30. doi: 10.1002/pbc.25563. [Epub ahead of print]
Author information:
  1Department of Community Health and Psychiatry, University of the West Indies, Mona, Kingston, Jamaica.
Abstract
We undertook a cost effectiveness analysis (CEA) of hydroxyurea (HU) in preventing stroke recurrence and/or death. We followed 43 children with sickle cell disease from 2000 to 2009 after having a first clinical stroke, of whom 10 opted for HU therapy. HU use led to decreased stroke recurrence and death without significantly increasing the annual cost of care per patient (J$83,250 vs. J$76,901, P = 0.491). The incremental cost effectiveness ratio (ICER) for prevention of stroke recurrence amounted to J$169,238 (US$1,900), while that for death prevention equalled J$635,843 (US$7,140). HU may be recommended when safe and affordable transfusion therapy is not feasible. Pediatr Blood Cancer © 2015 Wiley Periodicals, Inc.
© 2015 Wiley Periodicals, Inc.

PMID: 25929458 [PubMed - as supplied by publisher]


Icon for John Wiley & Sons, Inc.
6.
J Pediatr. 2015 May;166(5):1226-32. doi: 10.1016/j.jpeds.2015.01.054.
Abstract
OBJECTIVE:
To assess the rates and types of complications associated with deep sedation in children with sickle cell disease (SCD) and to explore potential risk factors.
STUDY DESIGN:
This was a retrospective cohort study of children with SCD and a comparison group of children without SCD who underwent magnetic resonance imaging with deep sedation. The rates of general and SCD-associated sedation complications were calculated, and potential associated clinical and laboratory variables were assessed.
RESULTS:
A total of 162 sedation records in 94 subjects with SCD and 324 sedation records in 321 subjects without SCD were assessed (mean age, 4.3 years in both groups). Pentobarbital, fentanyl, and midazolam were used in the majority of sedation episodes without routine presedation transfusion. Sedation-related complication rates did not differ significantly between the SCD and comparison groups. Within 1 month after the sedation procedure, 17 children (10%) experienced a vaso-occlusive pain episode (VOE), and 2 children (1.2%) developed acute chest syndrome. Preprocedure and postprocedure rates of these complications did not differ significantly. Subjects who developed VOE after sedation had a significantly higher VOE rate before sedation, but no other significant clinical or laboratory risk factors were identified.
CONCLUSION:
Deep sedation in young children with SCD using a standard protocol is safe, with a sedation-related complication rate comparable to that of the general pediatric population. The observed rate of VOE, although not significantly higher than expected, warrants further investigation.
Copyright © 2015 Elsevier Inc. All rights reserved.

PMID: 25919732 [PubMed - in process]


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7.
J Adv Nurs. 2015 Apr 27. doi: 10.1111/jan.12678. [Epub ahead of print]
Abstract
AIMS:
To examine the relationship between pain and satisfaction in patients with sickle cell disease.
BACKGROUND:
Frequency and severity of unrelieved sickle cell pain are positively associated with mortality. Yet, information is scarce on whether sickle cell patients are satisfied with their pain level.
DESIGN:
A cross-sectional, correlational analysis of baseline data from a randomized clinical trial.
METHODS:
A randomized sample of adult outpatients was recruited between February 2007-March 2011. Patients completed the PAINReportIt® , containing measures of pain, satisfaction and socio-demographics. We analysed data using Kendall's rank correlations, analysis of variance, Tukey-Kramer post hoc tests, Fisher's tests and proportional odds logistic regression.
RESULTS:
There were statistically significant correlations between pain outcomes and satisfaction with pain level, but average pain intensity more strongly discriminated groups based on satisfaction with pain level. Among pain variables bivariately associated with patient satisfaction with pain level, only pain expectation maintained its significant relationship with satisfaction with pain level when average pain intensity was controlled. A smaller percentage of our sickle cell patients reported moderate to severe pain intensity (28%) or high composite pain index (39%), while reporting being satisfied with pain their level than reported in earlier studies using different measures and populations (70-94%).
CONCLUSION:
Satisfaction with pain level was an unambiguous measure of patient satisfaction and a promising indicator of pain that did not show the paradoxical relationship between satisfaction and pain seen with past measures.
© 2015 John Wiley & Sons Ltd.

PMID: 25916256 [PubMed - as supplied by publisher]


Icon for Blackwell Publishing
8.
Transfusion. 2015 Apr 23. doi: 10.1111/trf.13134. [Epub ahead of print]
Author information:
  1Department of Physics.
Abstract
BACKGROUND:
Sickle cell disease (SCD) is characterized by hemoglobin polymerization upon deoxygenation. Polymerization causes the sickle cells to become rigid and misshapen (sickling). Red blood cell (RBC) dehydration greatly increases polymerization. Cycles of sickling and unsickling cause an influx of calcium that leads to loss of potassium via the calcium-activated Gardos channel, which dehydrates the cells leading to increased polymerization. In this study the effects of nitric oxide (NO) and its congeners on RBC deformability were examined, focusing on sickle RBCs (sRBCs).
STUDY DESIGN AND METHODS:
RBCs from patients with SCD and from nonpatients were exposed to various compounds that release NO or its congeners. Intracellular calcium was increased using a calcium ionophore or cycling of oxygen tension for sRBCs. Deformability was measured by laser-assisted osmotic gradient ektacytometry.
RESULTS:
Consistent with a previous report, sodium nitroprusside (SNP) was found to protect against calcium-induced loss of deformability in normal RBCs, but (contrary to some previous reports) no effect of any NO donors was observed when calcium influx was not induced. Importantly, in studies of deoxygenation-induced dehydration of sRBCs, SNP resulted in substantial improvements in deformability (p = 0.036) and hydration (p = 0.024). Sodium nitrite showed similar trends. SNP was shown to have no effect on calcium influx, but reduced potassium efflux.
CONCLUSION:
These data suggest that SNP and perhaps certain nitrogen oxides (like nitrite) inhibit the Gardos channel and may be able to protect sickle cells from dehydration and thereby improve outcome in the disease.
© 2015 AABB.

PMID: 25912054 [PubMed - as supplied by publisher]


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9.
J Emerg Med. 2015 Apr 21. pii: S0736-4679(15)00053-0. doi: 10.1016/j.jemermed.2014.12.080. [Epub ahead of print]
Abstract
BACKGROUND:
Emergency Department Reliance (EDR: total emergency department [ED] visits/total ambulatory [outpatient + ED] visits) differentiates acute episodic ED users from those who may not have adequate access to outpatient care.
OBJECTIVE:
This study's aim was to investigate age-related patterns of EDR and associated health-care costs in pediatric patients with sickle cell disease (SCD) and those transitioning from pediatric to adult care.
METHODS:
State Medicaid data were used for this study. Patients with two or more SCD diagnoses and one or more blood transfusion were included. Quarterly rates of ED visits, EDR, SCD complications associated with ED visits, and ED visits resulting in hospitalization were evaluated. Risk factors associated with high EDR and the association between high EDR and health-care costs were explored through regression analyses.
RESULTS:
A total of 3208 patients were included. The most common SCD complications associated with ED visits were pain, infection, and pneumonia. Beginning at the age of 15 years, EDR rose from 0.17 to 0.29 visits per quarter at age 22 years, and remained high throughout adulthood. Regression analyses indicated that patients were most likely to have high EDR during the post-transition period and when experiencing an SCD complication. Patients with high EDR incurred statistically significantly higher inpatient and ED costs, resulting in significantly higher total health-care costs.
CONCLUSIONS:
Compared to children, patients transitioning to adulthood relied more on the ED for their care. In addition, patients with high EDR incurred more days in the hospital and significantly higher health-care costs, highlighting the need to improve transition-related support, including better access to primary care and increased engagement with patients with SCD.
10.
Am J Hematol. 2015 May;90(5):376-80. doi: 10.1002/ajh.23961. Epub 2015 Feb 25.

Abstract
Most adults with sickle cell disease (SCD) receive care for their acute painful episodes in an emergency department (ED) setting. The purpose of this article is to describe the impact of opening a dedicated treatment center for adults with SCD [Sickle Cell Infusion Clinic (SCIC)] on patient outcomes and on hospital discharges for SCD. Descriptive data including demographics, time to first dose of narcotic, and pain scores were collected on patients presenting to the SCIC and ED. Maryland hospital discharge data were obtained from the Maryland Health Services Cost Review Commission. Analyses were conducted using T tests, χ(2) tests, and simple generalized estimating equation regression models accounting for the clustered nature of observations, as appropriate. There were 3,874 visits to the SCIC by 361 unique patients; 85% of those visits resulted in the patient being sent home. During the same time period, there were 3,408 visits to the ED by 558 unique patients with SCD. The overall admission rate from the ED for these patients was 35.9% but decreased significantly over the time period with a rate of 20% in December 2011. There was a significant decrease in readmissions over time for the entire Baltimore Metro area with the likelihood of readmission decreasing by 7% over time. The SCIC model provides adults with SCD access to high quality care that decreases the need for hospital admission. Further research needs to be done to evaluate the cost effectiveness of this model. Am. J. Hematol. 90:376-380, 2015. © 2015 Wiley Periodicals, Inc.
© 2015 Wiley Periodicals, Inc.
PMCID: PMC4409504 [Available on 2016-05-01]

PMID: 25639822 [PubMed - in process]


Icon for John Wiley & Sons, Inc.
11.
Blood. 2015 Mar 31. pii: blood-2014-07-589283. [Epub ahead of print]
Abstract
Intravascular hemolysis describes the relocalization of heme and hemoglobin from erythrocytes to plasma. We investigated the concept that erythrocyte membrane microparticles (MP) concentrate cell-free heme in human hemolytic diseases, and that heme-laden MP have a physiopathological impact. Up to one third of cell-free heme in plasma from 47 patients with sickle cell disease (SCD) was sequestered in circulating MP. Erythrocyte vesiculation in vitro produced MP loaded with heme. In silico analysis predicted that externalized phosphatidylserine in MP may associate with and help retain heme at the cell surface. Immunohistology identified hemoglobin-laden MP adherent to capillary endothelium in kidney biopsies from hyperalbuminuric SCD patients. In addition, heme-laden erythrocyte MP adhered and transferred heme to cultured endothelial cells, inducing oxidative stress and apoptosis. In transgenic SAD mice, infusion of heme-laden MP triggered rapid vaso-occlusions in kidneys, and compromised microvascular dilation ex vivo. These vascular effects were largely blocked by heme-scavenging hemopexin and by the phosphatidylserine antagonist annexin-a5, in vitro and in vivo. Adversely remodeled MP carrying heme may thus be a source of oxidant stress for the endothelium, linking hemolysis to vascular injury. This pathway might provide new targets for the therapeutic preservation of vascular function in SCD.
Copyright © 2015 American Society of Hematology.

PMID: 25827830 [PubMed - as supplied by publisher]


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12.
Am J Hematol. 2015 May;90(5):381-5. doi: 10.1002/ajh.23956. Epub 2015 Apr 1.
Abstract
Intravenous immunoglobulin (IVIG) decreases neutrophil adhesion to endothelium and red blood cell-neutrophil interactions in sickle cell mice undergoing vaso-occlusion. In this Phase I clinical trial of sickle cell anemia (SCA) patients admitted with pain crisis, we evaluated the status of adhesion molecules on neutrophils in control and IVIG-treated subjects pre- and post-infusion up to 800 mg/kg, the same dose used in murine studies. Mac-1 function significantly decreased from baseline in the low-dose IVIG (200-400 mg/kg) cohorts. IVIG-related adverse events may have occurred in the high-dose (600-800 mg/kg) cohorts. There were no significant increases in neutrophil and leukocyte counts, suggesting that IVIG may more selectively inhibit Mac-1 function as opposed to neutrophil adhesion. This study provides the first in-human validation of pre-clinical murine studies that IVIG can decrease Mac-1 function. Am. J. Hematol. 90:381-385, 2015. © 2015 Wiley Periodicals, Inc. 
© 2015 Wiley Periodicals, Inc.
PMCID: PMC4409477 [Available on 2016-05-01]

PMID: 25616042 [PubMed - in process]


Icon for John Wiley & Sons, Inc.
13.
Am J Med. 2015 May;128(5):541-4. doi: 10.1016/j.amjmed.2014.11.020. Epub 2014 Dec 9.
Abstract
BACKGROUND:
The American Pain Society recommends that individuals experiencing sickle cell crisis receive parenteral pain medication within 30 minutes of assessment. We examined factors affecting achievement of this standard at the Johns Hopkins Sickle Cell Infusion Center.
METHODS:
Baseline patient care time intervals and data on variables affecting the ability to achieve the American Pain Society goal were measured. Time to first parenteral opiate administration was modeled using simple and multivariable linear regression.
RESULTS:
Mean time from initial assessment to first dose was initially 41 minutes. Increased nurse to patient ratio decreased time to first dose.
CONCLUSIONS:
Of the factors associated with improved times to first dose, only nurse to patient ratio is amenable to process change, suggesting it as a potential target for future interventions.
Copyright © 2015 Elsevier Inc. All rights reserved.

PMID: 25498167 [PubMed - in process]
J Pediatr Health Care. 2015 Mar 12. pii: S0891-5245(15)00056-5. doi: 10.1016/j.pedhc.2015.01.012. [Epub ahead of print]

The Daily Experiences of Adolescents in Lebanon With Sickle Cell Disease.

Abstract

OBJECTIVES: Despite the psychosocial and physical consequences associated with sickle cell disease (SCD), the daily lived experience of adolescents diagnosed with this disease is a phenomenon rarely described. The objective of this study was to explore the daily lived experience of adolescents with SCD living in Lebanon.

METHOD: Twelve adolescents with SCD between the ages of 12 and 17 years were interviewed with use of a semi-structured interview during a routine follow-up visit after they were assessed as being pain free. Interviews were transcribed verbatim, and thematic analysis was conducted.

RESULTS: Adolescents with SCD experience a layered burden consisting of physical, emotional, and sympathetic pain that affects much of their daily personal and social lives. Nevertheless, they seem to claim normalcy and to downplay their pain and suffering in order to limit their caregivers' distress.

CONCLUSION: These findings can be used to assist health care providers in designing culturally sensitive interventions specifically designed for adolescents with SCD and their families to enable them to better cope with their illness.

J Pediatr Health Care. 2015 Jan-Feb;29(1):54-60. doi: 10.1016/j.pedhc.2014.06.007. Epub 2014 Aug 10.
Educational intervention to improve the health outcomes of children with sickle cell disease.
Abstract
INTRODUCTION: Although sickle cell disease (SCD) is the most common single gene disorder worldwide, caregivers of children do not have adequate knowledge about the illness and its management. The purpose of this study was to assess the efficacy of education along with tailored written materials in changing the behaviors of caregivers to help them provide better care for children with SCD.
METHODS: A preintervention and postintervention quasi-experimental design was used. A convenience sample of 43 caregivers of 57 children were asked to complete a questionnaire related to their knowledge of SCD before and after educational sessions. The educational sessions (the intervention) were provided to caregivers at the Children's Cancer Center in Lebanon by one registered nurse, one certified pediatric nurse practitioner, and one pediatric hematologist. Emergency department (ED) visits and hospitalizations were compared 2 months before and 2 months after the intervention.
RESULTS: A statistically significant increase was found in the knowledge of caregivers about the cause, symptoms, and management of the disease. A statistically significant decrease occurred in the number of hospitalizations before and after the intervention but not in the number of visits to the ED. Multiple regression analysis found that none of the background variables were related to knowledge, ED visits, or hospitalizations.
CLINICAL IMPLICATIONS: Education and written materials written in a simple language that is understood by 5th-graders were beneficial in improving the knowledge of caregivers and in decreasing the number of hospitalizations of children with SCD.









Monday, May 4, 2015

Sickle Cell News | May 2015

Landmark article
1.
Blood. 2015 Apr 23;125(17):2597-604. doi: 10.1182/blood-2014-12-615948. Epub 2015 Mar 2.

Correction of the sickle cell disease mutation in human hematopoietic stem/progenitor cells.

Abstract

Sickle cell disease (SCD) is characterized by a single point mutation in the seventh codon of the β-globin gene. Site-specific correction of the sickle mutation in hematopoietic stem cells would allow for permanent production of normal red blood cells. Using zinc-finger nucleases (ZFNs) designed to flank the sickle mutation, we demonstrate efficient targeted cleavage at the β-globin locus with minimal off-target modification. By codelivering a homologous donor template (either an integrase-defective lentiviral vector or a DNA oligonucleotide), high levels of gene modification were achieved in CD34(+) hematopoietic stem and progenitor cells. Modified cells maintained their ability to engraft NOD/SCID/IL2rγ(null) mice and to produce cells from multiple lineages, although with a reduction in the modification levels relative to the in vitro samples. Importantly, ZFN-driven gene correction in CD34(+) cells from the bone marrow of patients with SCD resulted in the production of wild-type hemoglobin tetramers. 
Editorial by James Eckman MD:
Sickle cell anemia is the first “molecular disease” defined by Linus Pauling in 1949.1  Considerable progress has been made in understanding this disease and in defining the genetic basis for this and many other diseases.  The human genome project and many other basic studies in molecular genetics have led to development of tools now used to diagnose and treat these genetic disorders.  This month’s Sickle Cell Update highlights an important report from the journal Blood that presents exciting progress in using these new tools to develop a cure for sickle cell disease in the not too distant future. Hoban et al. report the ability to snip out the DNA that contains the sickle mutation and insert the normal DNA sequence, thereby, correcting the mutation in human hematopoietic stem and progenitor cells with relatively high efficiency and excellent specificity. The modified stem cells from bone marrows of individuals with sickle cell anemia are able synthesize normal hemoglobin in culture to a level of about 20%.  They also show that such genetically modified cells are able to be transplanted successfully into immune-deficient mice, although levels of hemoglobin synthesis are not as robust.  The same issue of Blood also contains an excellent editorial that highlights the accomplishments of this research and discusses the limitations of the results in terms of curing sickle cell disease.3
Although there are still many obstacles ahead, it appears that molecular genetic surgery offers promise as a true cure for sickle cell disease.  Increasing the percentage of hematopoietic stem cells corrected and growing them is large enough numbers to use for human bone marrow transplantation remain challenges.  Once these are overcome, marrow could be removed from an individual, stem cells isolated, and the mutation corrected.  These correct stem cells could then be grown to sufficient numbers and used to cure the individual with a marrow transplant using the individual’s own corrected stem cells.  Perhaps in the near future our goal of making sickle cell the first molecular disease cured in all individuals will be realized because of the great advances in molecular genetic research.
References:
1.         Pauling L et al. Sickle cell anemia. A molecular disease. Science 1949;109:443.
2.         Hoban et al. Correction of the sickle cell mutation in human hematopoietic stem/progenitor cells.  Blood 2015;125:2597.
3.         Tolar J. Sickle cell and silent spleen.   Blood 2015;1125:2589.

Proportion of Adults With Sickle Cell Anemia and Pain Crises Receiving Hydroxyurea Nicolas Stettler, MD, MSCE1; Colleen M. McKiernan, MSPH1; Court Q. Melin, BS1; Oluwakayode O. Adejoro, MD, MPH1; Nancy B. Walczak, PhD, FSA1

JAMA. 2015;313(16):1671-1672. doi:10.1001/jama.2015.3075 at http://jama.jamanetwork.com/article.aspx?articleid=2279701

Few American adults with sickle cell anemia are getting a recommended medication that can help them manage pain, breathing problems and other debilitating symptoms, according to a new study. Using a national database, researchers found that less than one-quarter of sickle cell patients who should have been taking a drug called hydroxyurea actually were.

“This is a medication that’s highly beneficial and yet most people aren’t getting it,” said George Buchanan, MD, a sickle cell expert, and a professor at the University of Texas Southwestern Medical Center at Dallas, who was not involved in the new study.

 

Findings from the study were reported in the April 28 issue of the Journal of the American Medical Association.  http://www.theskanner.com/news/health/22714-few-sickle-cell-patients-recieve-beneficial-drug

PhenX Toolkit Seeks Comments

The Toolkit provides standard measures related to complex diseases like sickle cell disease, phenotypic traits and environmental exposures. Use of PhenX measures facilitates combining data from a variety of studies, and makes it easy for investigators to expand a study design beyond the primary research focus. All Toolkit content is available to the public at no cost.

Information about the project is available at www.phenx.org The National Human Genome Research Institute (NHGRI) awarded RTI International a four-year cooperative agreement to expand and enhance the PhenX Toolkit at https://www.phenxtoolkit.org/

An important aim of this grant is to review the measures in the 21 research domains after receiving input from the scientific community.

Please take a few minutes to review the measures in these PhenX domains: Demographics, Environmental Exposures, and Social Environments. Your rating (number of stars) should reflect how useful this protocol is to your work and its relevance to the PhenX Toolkit. We tried to make it easy for you to rate the measures you are familiar with; you do not have to rate all of them. Please click Review PhenX Toolkit Measures to rate and comment on these measures.

PhenX will be collecting input on these measures from May 5 - May 18, 2015. Responses collected during this time will be summarized for consideration by an Expert Review Panel.

This is an opportunity to tell PhenX what you like about these measures, what could be better, and suggest improvements!

Comments needed from the Sickle Cell Community from Centers for Medicare and Medicaid Services (CMS)

Early in 2015, the American Society for Blood and Marrow Transplantation (ASBMT) and the National Marrow Donor Program (NMDP) submitted a formal request to the Centers for Medicare and Medicaid Services (CMS) for expansion of the current list of diseases for which Hematopoietic Cell Transplant (HCT) is expressly noted as covered and reimbursable. Several disease categories were included in this request, including Myelofibrosis, Sickle Cell Disease, Lymphoma and Multiple Myeloma.

CMS has agreed to open a National Coverage Analysis (NCA) for two of these disease indications now – Sickle Cell Disease and Myelofibrosis – and they have indicated that they will review the remaining indications sequentially. There is a public comment period open from April 30 – May 30, 2015. Information on how to make a comment is described below.

The NMDP and ASBMT submitted a coverage request for these indications due to an identified barrier to care created by the lack of coverage clarity for these disease indications when treating Medicare patients. Currently, Medicare does not indicate that these indications are either covered or non-covered (with the exception of Myeloma) and does not allow Medicare Administrative Contractors (MACs) to provide pre-authorization for HCT. This lack of a clear national coverage decision places the Medicare beneficiary, and the transplant program treating them, at severe financial risk if the MAC denies the reimbursement claim after the procedure is complete. Our recent experience seeking coverage clarity for HCT for Myelodysplastic Syndromes (MDS) has clearly demonstrated this access barrier and the effect of its removal; the clarity of coverage provided through the Medicare study for MDS has allowed patients to receive the care they need. The request letter submitted by our organizations this January provides additional information on the barriers created by this lack of coverage clarity.

While Medicare primarily serves individuals aged 65 years and older, approximately 15% of those covered are younger adults who have a disabling illness, such as sickle cell disease1. The coverage policies set by Medicare are often used as a benchmark reference for coverage by other payers and insurance plans, including state Medicaid programs.

How you can help: Please visit the Medicare website on this topic, read the materials and follow the instructions on how to submit a comment. You can submit a comment on the CMS website. This system does not accept attachments. If you wish to include an attachment please email it to CAGinquiries@cms.hhs.gov. Please include “NCA for SCT/HCT: CAG-00444R” in the subject line of your email.

Links: http://www.cms.gov/medicare-coverage-database/details/nca-tracking-sheet.aspx?NCAId=280&bc=ACAAAAAAAgAAAA%3d%3d&

Submit Comment link http://www.cms.gov/medicare-coverage-database/details/submit-public-comment.aspx?DocID=280&DocType=nca&DocName=Stem+Cell+Transplantation+%28Sickle+Cell+Disease+and+Myelofibrosis%29&NCAId=280&bc=ACAAAAAAAgEAAA%3d%3d&

Awards

Samir K Ballas, MD, FACP, Emeritus Professor of Medicine,Thomas Jefferson University  was selected as the 2015 recipient of the American Academy of Pain Medicine (AAPM) Patient Advocacy Award. The Award was presented during the AAPM Awards Presentation on Saturday, March 21:

The Patient Advocacy Award recognizes activity of an individual in advocating for appropriate evaluation and treatment of patients suffering from pain. This award was created to honor those healthcare professionals whose deeds reflect their recognition of the importance and impact of the specialty of Pain Medicine. The Academy recognizes only a few individuals for their outstanding contributions to the field of Pain Medicine each year. Dr. Ballas has been a long time advocate for excellent pain management in sickle cell patients.

Lillie Johnson - advocate for sickle cell anemia education in Toronto CA

http://www.insidetoronto.com/news-story/5606609-black-in-toronto-honouring-lillie-johnson-this-mother-s-day-for-her-advocacy-of-sickle-cell-anemia/

Track  the new bill in Congress - H.R. 1807 Sickle Cell Disease Research, Surveillance, Prevention, and Treatment Act of 2015 athttps://popvox.com/bills/us/114/hr1807 or https://www.govtrack.us/congress/bills/114/hr1807