Sickle Cell News from Allan Platt

Sickle Cell News for March 2014

 

 

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]

Related citations

Icon for Journal of Clinical Investigation

 

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]

Related citations

Icon for Journal of Clinical Investigation

 

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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Icon for Lippincott Williams & Wilkins

 

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]

Related citations

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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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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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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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Icon for HighWire

 

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]


Related citations



 

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]


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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]


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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]


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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]


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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]


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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]


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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]


Related citations



 

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]


Related citations



 

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]

Related citations

 

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]

Related citations

 

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]

Related citations


 

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]

Related citations

 

 

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]


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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]


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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]


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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]


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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-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 April

 

1.

J Pediatr Hematol Oncol. 2013 Apr 24. [Epub ahead of print]

Cytochrome P450 2D6 Polymorphisms and Predicted Opioid Metabolism in African American Children With Sickle Cell Disease.

Yee MMJosephson CHill CEHarrington RCastillejo MIRamjit ROsunkwo I.

*Aflac Cancer and Blood Disorders Center, Children's Healthcare of Atlanta Departments of †Pediatrics, Hematology/Oncology ‡Pathology and Laboratory Medicine, Emory University §Emory University School of Medicine, Atlanta, GA.

Abstract

The opioid medications codeine and hydrocodone, commonly prescribed in sickle cell disease (SCD), require metabolic conversion by cytochrome P450 2D6 (CYP2D6) to morphine and hydromorphone, respectively, to exert their analgesic effects. The CYP2D6 gene is highly polymorphic, with variant alleles that result in decreased, absent, or ultrarapid enzyme activity. Seventy-five children with SCD were tested for CYP2D6 polymorphisms, and metabolic phenotypes were inferred from the genotypes. The most common variant alleles were CYP2D6*2 (normal activity, 28.7%), CYP2D6*17 (reduced activity, 17.3%), CYP2D6*5 (gene deletion, 8.7%), and CYP2D6*4 (absent function, 8.0%). Normal/extensive metabolizer genotypes were found in 28/75 (37.5%), intermediate metabolism in 33/75 (44.0%), poor metabolism in 4/75 (5.3%), ultrarapid metabolism in 3/75 (4.0%), indeterminate in 6/75 (8.0%). Allele frequencies did not vary significantly among different hemoglobin genotypes. Identification of variant CYP2D6 genotypes may identify individuals with altered metabolism and therefore altered analgesic response to codeine and hydrocodone, thus providing a personalized medicine approach to treatment of pain in SCD. Further pharmacokinetic and pharmacodynamic studies are needed to define the relationship of CYP2D6 and other gene polymorphisms to individual opioid effect in SCD.


PMID: 23619115 [PubMed - as supplied by publisher]


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2.

J Pediatr Hematol Oncol. 2013 Apr 24. [Epub ahead of print]

Hyperhemolysis in Sickle Cell Disease.

Aragona EKelly MJ.

*Division of Hospitalist Medicine, Children's National Medical Center, The George Washington University School of Medicine and Health Sciences, Washington, DC †Division of Pediatric Hematology Oncology, The Floating Hospital for Children at Tufts Medical Center, Tufts University School of Medicine, Boston, MA.

Abstract

An 18-year-old female with sickle cell disease presented with thigh pain, dark urine, and hematuria within 72 hours of receiving a blood transfusion. Her clinical picture was consistent with hemolysis. Subsequent laboratory workup, however, demonstrated reticulocytopenia without evidence of an antibody-mediated transfusion reaction. As her hemoglobin continued to decrease, she was treated with IVIG and steroids for presumed hyperhemolysis. Clinicians should have a high index of suspicion for hyperhemolysis in sickle cell patients with evidence of hemolysis after a recent transfusion. Differentiating hyperhemolysis from other hemolytic syndromes is critical; transfusions in a hyperhemolytic episode can accelerate hemolysis causing life-threatening anemia.


PMID: 23619113 [PubMed - as supplied by publisher]


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3.

J Pediatr Hematol Oncol. 2013 May;35(4):289-298.

Barriers to Hematopoietic Cell Transplantation Clinical Trial Participation of African American and Black Youth With Sickle Cell Disease and Their Parents.

Omondi NAFerguson SEMajhail NSDenzen EMBuchanan GRHaight AE,Labotka RJRizzo JDMurphy EA.

*National Marrow Donor Program †Center for International Blood and Marrow Transplant Research and University of Minnesota, Minneapolis, MN ‡The University of Texas Southwestern Medical Center, Children's Medical Center, Dallas, TX §Children's Healthcare of Atlanta, Emory University School of Medicine, Atlanta, GA ∥Chicago Sickle Cell Center, University of Illinois, Chicago, IL ¶Center for International Blood and Marrow Transplant Research, Medical College of Wisconsin Clinical Cancer Center, Milwaukee, WI.

Abstract

African Americans and Blacks have low participation rates in clinical trials and reduced access to aggressive medical therapies. Hematopoietic cell transplantation (HCT) is a high-risk but potentially curative therapy for sickle cell disease (SCD), a disorder predominantly seen in African Americans. We conducted focus groups to better understand participation barriers to HCT clinical trials for SCD. Nine focus groups of youth with SCD (n=10) and parents (n=41) were conducted at 3 sites representing the Midwest, South Atlantic, and West South Central US. Main barriers to clinical trial participation included gaps in knowledge about SCD, limited access to SCD/HCT trial information, and mistrust of medical professionals. For education about SCD/HCT trials, participants highly preferred one-on-one interactions with medical professionals and electronic media as a supplement. Providers can engage with sickle cell camps to provide information on SCD/HCT clinical trials to youth and local health fairs for parents/families. Youth reported learning about SCD through computer games; investigators may find this medium useful for clinical trial/HCT education. African Americans affected by SCD face unique barriers to clinical trial participation and have unmet HCT clinical studies education needs. Greater recognition of these barriers will allow targeted interventions in this community to increase their access to HCT.


PMID: 23612380 [PubMed - as supplied by publisher]


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4.

J Pediatr Hematol Oncol. 2013 May;35(4):329-30. doi: 10.1097/MPH.0b013e318290c5f3.

Sickle Cell-related Bone Marrow Complications: The Utility of Diffusion-weighted Magnetic Resonance Imaging.

Pratesi AMedici ABresci RMicheli ABarni SPratesi C.

Misericordia e Dolce Hospital, Prato, Tuscany, Italy.

Abstract

In sickle cell disease diffusion-weighted imaging (DWI) are helpful, costeffective, and promising techniques for differentiating bone marrow involvements. So we suggest to consider a MR diffusion panoramic study (whole-body diffusion MR) when multiple follow-up imaging is required in young patients who are at high risk for chronic radiation damage, so that alternatives to PET study may be taken into consideration.


PMID: 23612384 [PubMed - in process]


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5.

Eur Cytokine Netw. 2013 Apr 19. [Epub ahead of print]

Altered levels of pro-inflammatory cytokines in sickle cell disease patients during vaso-occlusive crises and the steady state condition.

Keikhaei BMohseni ARNorouzirad RAlinejadi MGhanbari SShiravi FSolgi G.

Thalassemia & Hemoglobinopathy research center, Ahvaz Joundishapur University of Medical Science, Ahvaz, Iran.

Abstract

Objective: This study aimed to evaluate serum levels of pro-inflammatory cytokines and TGF-β in sickle cell disease (SCD) patients, and to compare the results during vaso-occlusive crisis (VOC) or steady state (StSt) conditions. Methods: 54 SCD patients (37HbSS and 17Sβ+Thal) were enrolled in the study and evaluated in two groups as follows; group A consisted of 39 VOC patients and group B comprised 15 StSt patients. Nineteen healthy volunteers were included as controls. Circulating levels of IL-1, IL-6, IL-8, IL-17,TNF-α and TGF-β were measured using ELISA. Results: Patients in VOC showed higher mean levels of all cytokines than those found in steady-state patients, but this was only marginally significant for IL-8 levels (P = 0.08). Increased levels of TGF-β and IL-17 were found in StSt patients versus normal controls (P = 0.004 and P<0.0001 respectively). A positive correlation was observed between IL-8 and IL-17 in both groups of patients (P = 0.002 and P = 0.005 respectively). Decreased levels of TNF-α, IL-1β and IL-17 were found in hydroxyurea-treated patients. Additionally, significantly higher levels of IL-6 and IL-8 were observed in hydroxyurea-treated and untreated patients than in controls respectively (P = 0.04 and P = 0.01). Conclusions: Our findings indicate that pro-inflammatory cytokines, especially IL-8 and IL-17, could be used as related markers for assessing disease severity, and consequently therapeutic intervention.


PMID: 23608554 [PubMed - as supplied by publisher]


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6.

Am J Hematol. 2013 Apr 20. doi: 10.1002/ajh.23457. [Epub ahead of print]

Genetic modifiers of sickle cell anemia in the BABY HUG cohort: Influence on laboratory and clinical phenotypes.

Sheehan VALuo ZFlanagan JMHoward TAThompson BWWang WCKutlar AWare REBABY HUG Investigators.

Hematology Center, Department of Pediatrics, Baylor College of Medicine, Houston, TX.

Abstract

The recently completed BABY HUG trial investigated the safety and efficacy of hydroxyurea in infants with sickle cell anemia (SCA). To investigate the effects of known genetic modifiers, genomic DNA on 190 randomized subjects was analyzed for alpha thalassemia, beta-globin haplotype, polymorphisms affecting endogenous fetal hemoglobin (HbF) levels (XmnI, BCL11A, and HBS1L-MYB), UGT1A1 promoter polymorphisms, and the common G6PD A- mutation. At study entry, infants with alpha thalassemia trait had significantly lower MCV, total bilirubin, and absolute reticulocyte count. Beta-globin haplotypes associated with milder disease had significantly higher hemoglobin and %HbF. BCL11A and XmnI polymorphisms had significant effects on baseline HbF, while UGT1A1 promoter polymorphisms significantly influenced baseline serum bilirubin. At study exit, subjects randomized to placebo still exhibited laboratory effects of alpha thalassemia and other modifiers, while those assigned hydroxyurea had treatment effects that exceeded most genetic influences. The pain phenotype was influenced by HbF modifiers in both treatment groups. These data document that genetic polymorphisms do modify laboratory and clinical phenotypes even in very young patients with SCA. The hydroxyurea effects are more potent, however, indicating that treatment criteria should not be limited to certain genetic subsets, and supporting the use of hydroxyurea for all young patients with SCA.

Copyright © 2013 Wiley Periodicals, Inc., A Wiley Company.


PMID: 23606168 [PubMed - as supplied by publisher]


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News for March 2013

New Treatment for Sickle Cell Brings Hope and a Cure to Chicago Area Patients

Source Newsroom: University of Illinois at Chicago

Newswise — Two brothers have been cured of their sickle cell disease at the University of Illinois Hospital & Health Sciences System using a relatively uncommon type of stem cell transplant that is performed without chemotherapy.

Their transplants were possible thanks to a third brother who was a match for both, against long odds.

Julius and Desmond Means never imagined life without sickle cell. The brothers, ages 25 and 19, have spent their lives in and out of hospitals, each suffering from different complications of the disease.

Growing up, they tired easily and couldn't keep up with their friends. As they grew older, the disease caused bone damage and affected Julius's lungs. Desmond's organs were also being damaged, and he was jaundiced.

For either young man to receive a transplant, a healthy sibling who is a compatible donor was needed. An acceptable match requires that at least eight of 10 known human leukocyte antigen (H.L.A.) genes be identical between donor and recipient.

Julius and Desmond's healthy older brother Clifford, 27, matched 10 of 10 H.L.A. genes with both of them -- an occurrence of "extremely low" likelihood, according to Dr. Damiano Rondelli, director of stem-cell transplantation at UI Health. The men's mother, Beverly Means, also noted the good fortune.

"I had won the lottery of health," she said.

In preparation for the transplant, Clifford was given medication to increase the number of stems cells released from the bone marrow into the bloodstream. His blood was then processed through a machine that collects white cells, including stem cells. The stem cells were frozen until the transplants.

Last May, Julius received his transplant at UI Hospital. He was given medication to suppress his immune system and one small dose of total body radiation right before the transplant. Then the frozen bags of stem cells were thawed and hung by IV pole for infusion into him.

Then in September, Desmond received his stem cell transplant.

Now several months since the transplants, both Julius and Desmond no longer have sickle cell disease. Their bone marrow is producing healthy red blood cells.

"Being cured, I feel like we can do anything," says Julius, who composed a rap about his transplant while recovering in the hospital. The brothers are pursuing their interests in rap music and dance and plan to attend college.

The chemotherapy-free stem cell transplant is a new procedure and is much better-tolerated by patients with aggressive sickle cell disease, who often have underlying organ damage and other complications.

UI Health is the first center in the Chicago area to offer this treatment, and one other patient has been successfully transplanted here. The efficacy and safety of the pre-transplant medication regimen are currently being studied at UI Health.

About 30 adults have received chemotherapy-free stem cell transplants for sickle cell disease at the National Institutes of Health in Bethesda, Md. Approximately 85 percent have been cured.

NSIGHT: Cyclists for sickle cell unite in Dar es Salaam Tanzania

http://thecitizen.co.tz/business/-/29878-insight-cyclists-for-sickle-cell-unite-in-dar-es-salaam

In one of the biggest cycling charity events the city has yet seen, around 400 people, of an astonishing range of ages and physical abilities, donned orange reflector vests emblazoned with ‘Cycle for Sickle Cell’, to join the event to raise funds for a new Sickle Cell Centre at Muhimbili National Hospital, (MNH) and awareness into a disease that is one of the biggest causes of childhood mortality in Tanzania.

Sickle cell disease is an inherited blood disorder that causes significant illness and death and Tanzania’s burden of the disease ranks fourth in the world, with the highest number of SCD births a year (up to 11,000), after Nigeria, India and Democratic Republic of Congo. If untreated, up to 90 per cent of these children will die in childhood. One of the main challenges is that awareness of this inherited disease is considerably low in Tanzania. Many children go undiagnosed and lives are lost. Research scientists, doctors and other healthcare workers are working hard, hand in hand, to change this.

The Government of Tanzania has recognized the public health burden of sickle cell disease and dedicated sickle cell services have been provided at Muhimbili National Hospital since the 1980s.

In 2004, a systematic framework for comprehensive healthcare was established at Muhimbili (http://www.muhas.ac.tz and http://www.mnh.or.tz/), which is the main clinical, academic and research centre in the country.

In 2009, the ministry of Health and Social Welfare included sickle cell disease as a priority condition in the national strategy for non-communicable diseases and Tanzania intends to introduce new-born screening and strengthen sickle cell services in health facilities at primary, secondary and tertiary level.

In order to develop a platform for advocacy, the Sickle Cell Foundation of Tanzania was launched in 2010. Tanzania has established a biomedical research programme in SCD to find interventions that are locally appropriate and have global significance.

With local and global partnerships, it has developed a systematic framework for comprehensive research with prospective surveillance of over 2,500 SCD patients.

Tech update – Novartis develops two Smartphone apps for Android and  iPhone

The Sickle Cell Disease Resource Locator uses your location to connect you with health resources relevant to sickle cell disease and a Sickle Cell Disease Tracker to help  with iron overload.

 

New Video - 2/28: Disparities in Sickle Cell Disease Care: Disentangling the Roles of Race, Place, and Disease State

Dr. Carlton Haywood Jr., Johns Hopkins University

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

3/28: Strategies to Improve Implementation of Hydroxyurea

     Dr. Courtney Thornburg, Duke Pediatric Sickle Cell Clinic

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  

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-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 Pediatr Hematol Oncol. 2013 Apr;35(3):165-9. doi: 10.1097/MPH.0b013e3182847483.

Systematic review of transition from adolescent to adult care in patients with sickle cell disease.

Jordan LSwerdlow PCoates TD.

*The Sickle Cell Disease Association of America Inc., Baltimore, MD †Department of Epidemiology and Public Health, University of Miami, Miller School of Medicine, Miami, FL ‡Barbara Ann Karmanos Cancer Institute, Wayne State University, Detroit, MI §Children's Hospital Los Angeles, Los Angeles, CA.

Abstract

Awareness and practice of appropriate treatment for childhood sickle cell disease (SCD) has improved, and survival rates have increased significantly. Today, most patients will eventually require treatment in the adult-care setting. Adolescents who are transferred out from successful pediatric programs face numerous challenges regarding continuity of care, and mortality rates remain high in this age group. Here, we describe a systematic literature review conducted to examine the barriers to and approaches for successful transition of patients with SCD from adolescent to adult care. Articles were primarily located through the US National Library of Medicine (Pubmed.gov) and were omitted if their principal focus was not SCD transition treatment. A secondary search of 5 additional sources was conducted regarding relevant guidelines or meta-analyses. Current publications describe barriers to continuity of care in this group, proposals for improving the transition process, and contemporary models for SCD care transition. Clinical recommendations include development of a flexible, patient-centric transition plan and education for health care providers.


PMID: 23511487 [PubMed - in process]


Related citations

 


 

2.

Pediatr Blood Cancer. 2013 Mar 18. doi: 10.1002/pbc.24473. [Epub ahead of print]

Stroke with intracranial stenosis is associated with increased platelet activation in sickle cell anemia.

Majumdar SWebb SNorcross EMannam VAhmad NLirette SIyer R.

Department of Pediatrics, University of Mississippi Medical Center, Jackson, Mississippi. smajumdar@umc.edu.

Abstract

BACKGROUND:

Overt stroke in sickle cell anemia (SCA) is associated with intracranial stenosis and thrombus formation. Platelet activation is critical for thrombus formation.

PROCEDURE:

Platelet activation studies were performed in 50 subjects: 18 SCA patients with history of stroke or abnormal transcranial Doppler (TCD) and intracranial stenosis seen by magnetic resonance angiogram (MRA), 7 SCA patients with history of stroke or abnormal TCD but no intracranial stenosis, 13 SCA patients with no history of stroke or abnormal TCD, and 12 healthy African-Americans.

RESULTS:

Of the 18 patients with intracranial stenosis, 11 (61%) had evidence of the moyo-moya phenomenon on MRA. SCA children with intracranial stenosis had a significantly greater total white cell count compared to both healthy African-American controls and SCA patients in the steady-state (P < 0.001). In addition, SCA patients with history of stroke or abnormal TCD had a significantly higher platelet count compared to healthy African-American controls (P < 0.002). The percentage of platelet surface P-selectin expression was significantly greater in patients with intracranial stenosis compared to the other groups (P < 0.05), particularly in individuals that did not have the moya-moya phenomenon seen on MRA.

CONCLUSION:

Stroke with intracranial stenosis is associated with increased platelet activation in sickle cell anemia, and further investigation is needed on the role of anti-platelet agents in this high-risk population. Pediatr Blood Cancer © 2013 Wiley Periodicals, Inc.

Copyright © 2013 Wiley Periodicals, Inc.


PMID: 23509099 [PubMed - as supplied by publisher]


Related citations



 

3.

Pediatr Blood Cancer. 2013 Mar 18. doi: 10.1002/pbc.24530. [Epub ahead of print]

Alloimmunization in Sickle Cell Anemia in the Era of Extended Red Cell Typing.

O'Suoji CLiem RIMack AKKingsberry PRamsey GThompson AA.

Division of Hematology, Oncology and Stem Cell Transplant, Ann and Robert H. Lurie Children's Hospital of Chicago, Department of Pediatrics, Northwestern University Feinberg School of Medicine, Chicago, Illinois.

Abstract

BACKGROUND:

Red blood cell (RBC) transfusion remains an essential part of the management of patients with sickle cell disease (SCD). Alloimmunization is a major complication of transfusions. Extended RBC typing is advocated as a means to reduce alloimmunization in SCD. Our goal was to assess alloimmunization among individuals with SCD at our center since implementing extended RBC typing.

MATERIALS AND METHODS:

We reviewed electronic medical records of all patients with SCD (N = 641) in our comprehensive SCD Program to determine transfusion histories. Cross-referencing with our blood bank database, we extracted data such as antibodies identified, detection date and genotyping in specific cases. Transfusion sources were determined for those with C, E, and Kell antibodies.

RESULTS:

Of 180 patients transfused from 2002 to 2011, 26 developed at least one new antibody. The majority of alloimmunized patients (14/26) received episodic transfusions only. The most common antibodies formed were against C and E antigens. Of the 16 patients who developed C, E, Kell antibodies, nine had one or more documented transfusions at an outside hospital. Five patients had Rh variants undetectable on routine phenotyping including two novel e alleles related to ceAR and ceS (733G).

CONCLUSION:

Despite extended RBC typing, alloimmunization may still occur due to RBC variants that are not detected on routine screening and transfusions at institutions where extended RBC typing is not done. Extended RBC typing should be the standard of care for patients with SCD. Prospective genotyping may reduce allosensitization to rare variants not detected on routine screening. Pediatr Blood Cancer 2013;9999:XX-XX. © 2013 Wiley Periodicals, Inc.

Copyright © 2013 Wiley Periodicals, Inc.


PMID: 23508932 [PubMed - as supplied by publisher]


Related citations

 


 

4.

Eur J Haematol. 2013 Mar 14. doi: 10.1111/ejh.12103. [Epub ahead of print]

Optimizing Hydroxyurea Use In Children With Sickle Cell Disease: Low Regimen Dose Is Effective.

Sharef SWAl-Hajri MBeshlawi IAl-Shahrabally AElshinawy MZachariah M,Mevada STBashir WRawas ATaqi AAl-Lamki ZWali Y.

Departments of Child Health, Sultan Qaboos University Hospital, Oman.

Abstract

BACKGROUND AND OBJECTIVES:

Hydroxyurea (HU) is the standard treatment for severely affected children with sickle cell disease (SCD). Starting dose is 15-20 mg/kg/day that can be escalated up to 35 mg/kg/day. Ethnic neutropenia is common in this area of the world that requires judicious usage of myelosuppressive drugs. Aim was to assess the efficacy of a lower initial dose of HU and cautious dose escalation regimen in patients with SCD.

METHODS:

We assessed 161 patients with SCD on HU, at Sultan Qaboos University Hospital (SQUH), Muscat, Oman, retrospectively from 1998-2008 and prospectively from 2009-2011. Starting dose of HU was 10-12 mg/kg/day, adjusted based on response or side-effects. Patients were divided into two groups according to the dose of HU (10-15.9 mg/kg/day, and 16-26 mg/kg/day).

RESULTS:

Nineteen patients were excluded for various reasons. Forty four children were in the low dose group, and 98 were in the high dose group. There was significant reduction in the annual number of admissions due to vaso-occlusive crisis in both groups (P <0.001). However, the difference between the two groups was statistically insignificant (P > 0.05). In addition, there was an observed clinical improvement regarding the acute chest syndrome (ACS). Both groups had comparable significant improvements in their laboratory markers (e.g.; Hb, MCV, and ANC). All 142 patients tolerated the treatment well. Reversible toxicities occurred in both low and high dose groups.

CONCLUSION:

In SCD patients, low dose regimen of HU is a feasible option that ensured safety and yet did not affect efficacy. © 2013 John Wiley & Sons A/S.

© 2013 John Wiley & Sons A/S.


PMID: 23489171 [PubMed - as supplied by publisher]


Related citations



 

5.

Platelets. 2013 Mar 7. [Epub ahead of print]

Platelet Activation and Inhibition iN Sickle cell disease (PAINS) study.

Frelinger AL 3rdJakubowski JABrooks JKCarmichael SLBerny-Lang MABarnard MRHeeney MMMichelson AD.

Center for Platelet Research Studies, Division of Hematology/Oncology, Boston Children's Hospital, Dana-Farber Cancer Institute, Harvard Medical School , Boston, MA , USA.

Abstract

Platelet activation/aggregation in sickle cell disease (SCD) may promote tissue ischemia, suggesting that antiplatelet therapy may be useful. However, the assessment of platelet function and the effect of antiplatelet therapy in blood from SCD patients may be confounded by hemolysis with the release of adenosine 5'-diphosphate (ADP). Here we evaluate the levels of platelet activation markers in SCD adolescents vs. normal controls and compare, by multiple methods, the effect of in vitro blockade of the platelet ADP receptor P2Y12 by prasugrel's active metabolite, R-138727. Platelet activation markers in blood from SCD adolescents (n = 15) and healthy adults (n = 10), and the effect of R-138727 (0.1-10 µM) added in vitro, were evaluated with and without ADP stimulation. The circulating levels of platelet-monocyte and platelet-neutrophil aggregates were significantly higher (p < 0.01) in SCD patients than in healthy controls. R-138727, in a concentration-dependent manner, inhibited platelet function in both SCD patients and healthy subjects as judged by ADP-stimulated light transmission aggregation, VerifyNow® P2Y12 assay, multiple electrode aggregometry, and flow cytometric analysis of platelet vasodilator-stimulated phosphoprotein, activated GPIIb-IIIa and P-selectin. The R-138727 IC50s for each assay were not significantly different in SCD vs. healthy subjects. In summary: (1) The high circulating levels of platelet-monocyte and platelet-neutrophil aggregates demonstrate in vivo platelet activation in SCD and may be useful as markers of the in vivo pharmacodynamic efficacy of antiplatelet therapy in SCD. (2) The similar in vitro R-138727 IC50s in SCD and healthy subjects suggest that the prasugrel dose-dependence for platelet inhibition in SCD patients will be similar to that previously observed in healthy subjects.


PMID: 23469943 [PubMed - as supplied by publisher]


Related citations



 

6.

Pediatrics. 2013 Mar 4. [Epub ahead of print]

Weight Status of Children With Sickle Cell Disease.

Chawla ASprinz PGWelch JHeeney MUsmani NPashankar FKavanagh P.

Hasbro Children's Hospital, Providence, Rhode Island;

Abstract

OBJECTIVE:Historically, many children and adolescents with sickle cell disease (SCD) were underweight. Treatment advances like hydroxyurea have been associated with improved growth. We hypothesized that increased hemoglobin (Hb) levels would be associated with increased weight status of children with SCD.METHODS:Investigators at 6 institutions conducted a retrospective chart review of all patients aged 2 to 19 years of age for the calendar years 2007-2009. Height, weight, baseline Hb levels, demographic information, and select comorbidities were recorded from the most recent clinic visit. Overweight and obesity were defined as ≥85th and ≥95th BMI percentiles for age and gender, respectively, and underweight was defined as <5th BMI percentile.RESULTS:Data were collected on 675 children and adolescents in 3 New England states. In this sample, 22.4% were overweight or obese, whereas only 6.7% were underweight. Overweight or obese status was associated with sickle genotypes other than Hb SS or Hb Sβ0 disease, and were associated with higher baseline Hb levels. Underweight individuals were more likely to be male, older, and have had at least 1 SCD-related complication. After adjusting for demographic factors, any SCD-related complication, SCD-directed treatments, and obesity-related conditions, there was a 36% increased odds of overweight/obesity for each 1 g/dL increase in baseline Hb levels.CONCLUSIONS:Nearly one-quarter of children and adolescents with SCD in New England are overweight or obese. Longitudinal studies are needed to determine the impact of elevated BMI on the morbidity and mortality of both children and adults with SCD.


PMID: 23460681 [PubMed - as supplied by publisher]


Related citations



 

7.

Pain Res Manag. 2013 Jan-Feb;18(1):33-8.

Daily changes in pain, mood and physical function in children hospitalized for sickle cell disease pain.

Zempsky WTPalermo TMCorsi JMLewandowski ASZhou CCasella JF.

Connecticut Children's Medical Center, Hartford, Connecticut 06106, USA.wzempsk@ccmckids.org

Abstract

BACKGROUND:

Youth with sickle cell disease (SCD) are commonly hospitalized for treatment of painful vaso-occlusive episodes (VOE). However, limited data are available concerning the course of hospitalization for these children and adolescents and, in particular, whether daily changes occur in pain, emotional status and physical function.

OBJECTIVES:

To characterize changes in daily pain intensity, physical function and mood over the course of hospitalization, and to determine whether specific clinical characteristics were associated with these changes.

METHODS:

Daily ratings of pain (0 to 10 numerical rating scale) and mood (Positive and Negative Affect Scale for Children) were completed by 25 youth (11 to 20 years of age) with SCD over a total of 152 days (mean [± SD] = 6.7±5.6 days) of hospitalization. Trained raters determined each youth's daily physical function.

RESULTS:

Sickle Cell News for February  2013

Could an old antidepressant treat sickle cell disease?

Tests in mice & human blood cells look promisinghttp://www.eurekalert.org/pub_releases/2013-02/uomh-cao021913.php

An antidepressant drug used since the 1960s may also hold promise for treating sickle cell disease, according to a surprising new finding made in mice and human red blood cells by a team from the University of Michigan Medical School.

The discovery that tranylcypromine, or TCP, can essentially reverse the effects of sickle cell disease was made by U-M scientists who have spent more than three decades studying the basic biology of the condition, with funding from the National Institutes of Health.

Their findings, published in Nature Medicine, pave the way for a clinical trial now being planned for adult patients who have the life-threatening condition. The discovery may also lead to other treatments for the disease, which leads misshapen red blood cells to cause vascular damage and premature death.

But the researchers caution it is too soon for the drug to be used in routine treatment of sickle cell anemia, an inherited genetic disease that affects tens of thousands of Americans and millions of others worldwide.

The climax of a decade of discovery

In the new paper, the researchers describe a painstaking effort to test TCP's effect on the body's production of a particular form of hemoglobin – the key protein that allows red blood cells to carry oxygen.

The drug acts on a molecule inside red blood cells called LSD1, which is involved in blocking the production of the fetal form of hemoglobin. The U-M team zeroed in on the importance of LSD1 as a drug target after many years of research.

Then, they literally did a Google search to find drugs that act on LSD1. That's how they found TCP, which since 1960 has been used to treat severe depression.

In the new paper, they describe how TCP blocked LSD1 and boosted the production of fetal hemoglobin -- offsetting the devastating impact of the abnormal "adult" form of hemoglobin that sickle cell patients make.

"This is the first time that fetal hemoglobin synthesis was re-activated both in human blood cells and in mice to such a high level using a drug, and it demonstrates that once you understand the basic biological mechanism underlying a disease, you can develop drugs to treat it," says Doug Engel, Ph.D., senior author of the study and chair of U-M's Department of Cell & Developmental Biology. "This grew out of an effort to discover the details of how hemoglobin is made during development, not with an immediate focus on curing sickle cell anemia, but just toward understanding it."

Engel credits the dedication and persistence of his team, including a former research assistant professor, Osamu Tanabe, M.D., Ph.D., now at Japan's Tohoku University, U-M postdoctoral fellow, Lihong Shi, Ph.D., first author of the study, and research instructor Shuaiying Cui, Ph.D..

Together, they have identified LSD1's crucial role, and its epigenetic interaction with two nuclear receptors in the nuclei of red blood cell precursors called TR2 and TR4. Working in tandem, they repress the expression of the gene that makes fetal hemoglobin – an effect called gene silencing. So, interfering with this repression allows the fetal hemoglobin subunits to be made.

Treatment with TCP caused fetal hemoglobin to be produced at such high abundance that it made up 30 percent of all hemoglobin in cultured human blood cells – a finding Engel called "startling." TCP is FDA-approved, though patients taking it need to follow strict dietary guidelines to avoid drug interactions with certain naturally occurring chemicals in some foods.

Reference: Nature Medicinehttp://dx.doi.org/10.1038/nm.3101

NFL Twins to Tackle Sickle Cell Disease

http://newbrunswick.patch.com/articles/nfl-twins-to-tackle-sickle-cell-disease

NFL defensive backs and twin brothers Jason McCourty of the Tennessee Titans and Devin McCourty of the New England Patriots will visit Robert Wood Johnson University Hospital on Saturday, Feb. 23 for a campaign against sickle cell disease.

The McCourtys, along with the Embrace Kids Foundation, Robert Wood Johnson University Hospital, and the New York Blood Center are working together on the “Tackle Sickle Cell” campaign, which intends to educate and raise monetary and blood donors to fight against the disease.

Anyone who registers through TackleSickleCell.org and donates will receive a $10 restaurant gift card, and will be entered in a drawing for a signed football helmet and a $100 restaurant gift card, according to the hospital.

For more information, visit TackleSickleCell.org or Facebook.com/TackleSickleCell.

Treatment of sickle cell disease largely involves long-term disease management.

http://myfox8.com/2013/02/22/house-call-sickle-cell-disease-adult-disease-management/

Proper lifestyle modifications are essential to avoiding sickle cell disease-related symptomatic episodes and health conditions, which involve maintaining a well-balanced diet, avoiding smoking and alcohol consumption, limiting caffeine intake, and staying hydrated. Long-term sickle cell disease management also involves proper dental, foot, eye and skin/wound care.

Sickle news from Tanzania.  Sickle Cell Disease: What can Africa contribute? 13 February 2013. 

http://videocast.nih.gov/Summary.asp?File=17804&bhcp=1 part of NIH Wednesday Afternoon Lecture Series. http://wals.od.nih.gov/

Improving Sickle Cell Disease Care Beyond the Clinic

From text reminders to self-monitoring pill bottles, healthcare providers in the Working to Improve Sickle Cell Healthcare (WISCH) project using technology to improve care for patients with sickle cell disease when they leave the doctor’s office.

http://www.nichq.org/resources/SickleCellTech-Feb2013.html

Books

Telfair, J. and Crosby, L. (2013) Disparities in the delivery of health care and pain management for persons with sickle cell disease. In Incayawar, M and Todd, K (EDs) CULTURE, BRAIN AND ANALGESIA: Understanding and Managing Pain in Diverse Populations  New York, NY: Oxford University Press (Chapter 17), 198-204.

Sickle Cell Art

by 
Hertz Nazaire

World famous sickle cell artist Hertz Nazaire is selling his art to raise sickle cell awareness. Much of his work goes unpaid, but he needs support also:

“I don't mind not getting paid for my work as long as it helps others understand our pain but I don't think the community knows how hard my life has been while these images have been on slides and spread out all over the world.”

“I only sold 20 items in 6 years online mostly the postage stamps that canvas is new, just created this week. I turn 40 years old this year my pain is still very annoying but I am glad that my art has been loved by so many.  Thank You for your support”

His latest work, avery large wrapped canvas print ready to hang for an office is available at: http://www.zazzle.com/need_not_suffer_alone_sickle_cell_art_canvas_g-192431769758790410?gl=nazaire&rf=238198779154864644

Hertz online store address is http://www.zazzle.com/nazaire

Happy birthday Hertz and many more

 

Video Resources

505 LIVING WITH ILLNESS ( with Discussion Guide)

In the Mix is the Emmy award winning PBS series for young adults. One program addresses sickle cell anemia and is available as an educational DVD. A special discount of $20 off the usual $70 can be received by using the code 20Off and listing that on the P.O. For more information and a transcript, visit www.inthemix.org

This program addresses the most critical issues and problems concerning school, friends and family that challenge young people who are coping with serious and/or chronic conditions. Teens speak frankly from their experiences, sharing their concerns and advice with insight and humor. A boy describes his ways of dealing with Crohn’s; a girl copes with Juvenile Diabetes; and several teens who are living with sickle cell anemia describe their conditions and dispel misconceptions. They all stress that they want to be treated as normal teenagers.Young Adult Library Services Association “Selected Videos” list. Winner of the CINE Golden Eagle Award

The well-spoken adolescents, who represent a variety of backgrounds, openly share their experiences and discuss the impact of their afflictions on their lives. Including information on treatments and side effects, this video takes an honest and insightful look at a topic not often discussed among teens.” – Booklist

New video posted - Managing and Monitoring Transfusional Iron Overload

by Dr. Thomas Coates on 1/25/13

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

2/28: Disparities in Sickle Cell Disease Care: Disentangling the Roles of Race, Place, and Disease State

     Dr. Carlton Haywood Jr., Johns Hopkins University

3/28: Strategies to Improve Implementation of Hydroxyurea

     Dr. Courtney Thornburg, Duke Pediatric Sickle Cell Clinic

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  

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-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.

Lab Chip. 2013 Feb 22. [Epub ahead of print]

A simple, rapid, low-cost diagnostic test for sickle cell disease.

Yang XKanter JPiety NZBenton MSVignes SMShevkoplyas SS.

Department of Biomedical Engineering, Tulane University, New Orleans, LA 70118. shevkop@tulane.edu.

Abstract

This communication describes a very simple, rapid and inexpensive point-of-care diagnostic test for sickle cell disease (SCD) that can conclusively differentiate between blood samples from normal healthy individuals, sickle cell trait carriers and SCD patients using the characteristic blood stain patterns produced by each sample on paper.


PMID: 23429713 [PubMed - as supplied by publisher]



 

2.

Pediatr Neurol. 2013 Mar;48(3):188-99. doi: 10.1016/j.pediatrneurol.2012.12.004.

Cerebral blood flow abnormalities in children with sickle cell disease: a systematic review.

Behpour AMShah PSMikulis DJKassner A.

Department of Diagnostic Imaging, Hospital for Sick Children, Toronto, Ontario, Canada; Department of Medical Imaging, University of Toronto, Toronto, Ontario, Canada.

Abstract

A systematic review was performed to assess whether cerebral blood flow with different imaging modalities could identify brain abnormalities in children with sickle cell disease where structural magnetic resonance imaging and transcranial Doppler velocity appeared normal. A total of 11 studies were identified which reported cerebral blood flow abnormalities alongside structural magnetic resonance imaging or transcranial Doppler velocity abnormalities in patients with sickle cell disease. Potential for bias was assessed with the quality assessment of diagnostic accuracy studies scale in addition to treatment bias. Subjects of each study were categorized into patients with and without stroke. The prevalence of abnormalities for each modality was then separately calculated in each group. The included studies had mostly moderate degrees of bias. The prevalence of blood flow abnormalities compared with structural magnetic resonance imaging abnormalities was equal to or lower in patients with stroke and equal to or greater in patients without stroke. Blood flow abnormalities were more prevalent than transcranial Doppler abnormalities in four studies of patients without stroke and in one study of patients with stroke. The studies suggest that the assessment of cerebral blood flow in sickle cell disease can be of potential value in addressing brain abnormalities at the tissue level; however, further studies are warranted.

Copyright © 2013 Elsevier Inc. All rights reserved.


PMID: 23419469 [PubMed - in process]



 

3.

Pediatr Blood Cancer. 2013 Feb 15. doi: 10.1002/pbc.24486. [Epub ahead of print]

Exploring barriers and facilitators to clinical trial enrollment in the context of sickle cell anemia and hydroxyurea.

Lebensburger JDSidonio RFDebaun MRSafford MMHoward THScarinci IC.

Department of Pediatrics, University of Alabama at Birmingham, Birmingham, Alabama. jlebensburger@peds.uab.edu.

Abstract

BACKGROUND:

Several sickle cell clinical trials have closed due to inability to enroll patients. To limit the early cessation of a proposed clinical trial due to low accrual rates, we sought to better understand barriers and facilitators to enrolling parents of children with sickle cell anemia (SCD) into clinical trials.

PROCEDURE:

Focus groups (n = 3) were conducted with parents/guardians (n = 14) who had not previously been recruited for a clinical trial and were not administering hydroxyurea to their children.

RESULTS:

Three main themes related to barriers to clinical trial enrollment were identified during analysis of focus groups: general barriers to health related research (general mistrust of research studies, emotional and practical concerns), barriers to trial design (randomization), and barriers to hydroxyurea (long term unknown risks, cancer, myelosuppressive effects). Facilitators identified were need for more education, including request for peer education, and improved explanation of clinical trials or study rationale.

CONCLUSION:

Engagement of parents/guardians of children with SCD in identifying barriers and facilitators to clinical trial enrollment may be critical to the development of strategies to enhance SCD trial completion. Pediatr Blood Cancer © 2013 Wiley Periodicals, Inc.

Copyright © 2013 Wiley Periodicals, Inc.


PMID: 23418000 [PubMed - as supplied by publisher]



 

4.

Biol Blood Marrow Transplant. 2013 Feb 14. pii: S1083-8791(13)00082-7. doi: 10.1016/j.bbmt.2013.02.010. [Epub ahead of print]

Long Term Outcome and Evaluation of Organ Function in Pediatric Patients Undergoing Haploidentical and Matched Related Hematopoietic Cell Transplantation for Sickle Cell Disease.

Dallas MTriplett BShook DHartford CSrinivasan ALaver J,Ware RLeung W.

Departmentof BoneMarrowTransplantationand CellularTherapy,St. JudeChildren's Research Hospital; Departmentof Pediatrics,Universityof TennesseeHealthScienceCenter, College of Medicine, Memphis, Tennessee. Electronic address: mari.dallas@stjude.org.

Abstract

Human leukocyte antigen (HLA) matched related donor (MRD) hematopoietic stem cell transplant (HSCT) for patients with sickle cell disease (SCD) has been well established, however experience using alternative donors, including haploidentical donors for treatment of SCD is limited. We report the long-term outcome of 22 pediatric patients who underwent a related donor HSCT for SCD at St. Jude Children's Research Hospital. Patients received a myeloablative MRD from a sibling (14) or reduced intensity parental haploidentical (8) HSCT. The medianageforthe patients who underwent a MRD and haploidentical donor HSCT were11.0±3.9 yrs. and9.0±5.0 yrs., respectively. The median time to follow up for the MRD cohort was 9.0 ± 2.3 yrs. withan overallsurvival (OS) of93%andrecurrence/graftfailureof0%. The median follow up for the haploidentical donor cohort was 7.4 ± 2.4 years with an OSof75%, disease free survival of 38%anddisease recurrence of 38%. We report the long-term hematological response and organ function in patients undergoing a MRD and haploidentical donor HSCT for severe SCD. Our data demonstrate long-term hematologic improvements after HSCT for our patients with sustained engraftment. In summary, our dataconfirmsthatHSCT offerslong--termprotectionfromcomplicationsthat commonlydevelopinpatientswithSCDsuchasstroke,pulmonaryhypertension, acutechest and nephropathy, regardless of donor source.

Copyright © 2013 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.


PMID: 23416852 [PubMed - as supplied by publisher]

 

 

 

5.

J Hematol Oncol. 2013 Feb 17;6(1):17. [Epub ahead of print]

A double-blind, randomized, multicenter phase 2 study of prasugrel versus placebo in adult patients with sickle cell disease.

Wun TSoulieres DFrelinger ALKrishnamurti LNovelli EM,Kutlar AAtaga KIKnupp CLMcMahon LEStrouse JJZhou C,Heath LENwachuku CEJakubowski JARiesmeyer JSWinters KJ.

Abstract

ABSTRACT:

BACKGROUND: Platelet activation has been implicated in the pathogenesis of sickle cell disease (SCD) suggesting antiplatelet agents may be therapeutic. To evaluate the safety of prasugrel, a thienopyridine antiplatelet agent, in adult patients with SCD, we conducted a double-blind, randomized, placebo-controlled study.

METHODS:

The primary endpoint, safety, was measured by hemorrhagic events requiring medical intervention. Patients were randomized to prasugrel 5 mg daily (n = 41) or placebo (n = 21) for 30 days. Platelet function by VerifyNow(R) P2Y12 and vasodilator-stimulated phosphoprotein assays at days 10 and 30 were significantly inhibited in prasugrel- compared with placebo-treated SCD patients.

RESULTS:

There were no hemorrhagic events requiring medical intervention in either study arm. Mean pain rate (percentage of days with pain) and intensity in the prasugrel arm were decreased compared with placebo. However, these decreases did not reach statistical significance. Platelet surface P-selectin and plasma soluble P-selectin, biomarkers of in vivo platelet activation, were significantly reduced in SCD patients receiving prasugrel compared with placebo. In sum, prasugrel was well tolerated and not associated with serious hemorrhagic events.

CONCLUSIONS:

Despite the small size and short duration of this study, there was a decrease in platelet activation biomarkers and a trend toward decreased pain.

Free Article


PMID: 23414938 [PubMed - as supplied by publisher]





 

6.

J Health Psychol. 2013 Feb 13. [Epub ahead of print]

Psychological aspects and hospitalization for pain crises.

Tsao JJacob ESeidman LLewis MAZeltzer L.

University of California, Los Angeles, USA.

Abstract

Sickle-cell disease is a genetic disorder characterized by severe pain episodes or "vaso-occlusive crises" that may require hospitalization. This study examined the associations among emotion regulation, somatization, positive and negative affect, and hospitalizations for pain crises in youth with sickle-cell disease. Multivariate analyses indicated that emotional suppression and somatization were significantly associated with more frequent hospitalizations for pain crises in the previous year after controlling for sickle-cell disease type and pain. These results suggest that efforts to reduce emotional suppression and somatization may assist in decreasing the frequency of hospitalizations for pain crises among youth with sickle-cell disease.


PMID: 23407129 [PubMed - as supplied by publisher]


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7.

Am J Emerg Med. 2013 Feb 1. pii: S0735-6757(12)00568-2. doi: 10.1016/j.ajem.2012.11.005. [Epub ahead of print]

The impact of race and disease on sickle cell patient wait times in the emergency department.

Haywood C JrTanabe PNaik RBeach MCLanzkron S.

Department of Medicine, Division of Hematology, The Johns Hopkins School of Medicine, Baltimore, MD 21205, USA; The Johns Hopkins Berman Institute of Bioethics, Baltimore, MD 21205, USA. Electronic address: chaywoodjr@jhu.edu.

Abstract

STUDY OBJECTIVE:

To determine whether patients with sickle cell disease (SCD) experience longer wait times to see a physician after arrival to an emergency department (ED) compared to patients with long bone fracture and patients presenting with all other possible conditions (General Patient Sample), and to attempt to disentangle the effects of race and disease status on any observed differences.

METHODS:

A cross-sectional, comparative analysis of year 2003 through 2008 data from the National Hospital Ambulatory Medical Care Survey, a nationally representative sample of nonfederal emergency department visits in the United States. Our primary outcome was wait time (in minutes) to see a physician after arrival to an ED. A generalized linear model was used to examine ratios of wait times comparing SCD visits to the two comparison groups.

RESULTS:

SCD patients experienced wait times 25% longer than the General Patient Sample, though this difference was explained by the African-American race of the SCD patients. SCD patients waited 50% longer than did patients with long bone fracture even after accounting for race and assigned triage priority.

CONCLUSIONS:

Patients with SCD presenting to an ED for care experience longer wait times than other groups, even after accounting for assigned triage level. The African-American race of the SCD patients, and their status as having SCD itself, both appear to contribute to longer wait times for these pati

Sickle Cell News for January 2013

Sickle Cell Test Gets NCAA OK Despite Docs

The National Collegiate Athletic Association (NCAA) has approved mandatory confirmation of sickle cell trait status in Division III student athletes, despite the objections of the American Society of Hematology (ASH).

NCAA delegates voted 254 to 200 in favor of the measure at the 2013 NCAA convention over the weekend. Confirmation of sickle cell status will be required of all incoming student athletes in the 2013-2014 school year and for all athletes by 2014-2015. Mandatory sickle cell screening is already required by the NCAA in Division I and Division II athletes.

Last year, ASH challenged the NCAA, declaring that athletes need not be tested for or disclose sickle cell trait status before participating in sporting events. In a statement released over the weekend, ASH said the "NCAA policy is medically groundless – perhaps even dangerous – and is focused more on protecting the NCAA from legal liability than protecting the health of student athletes." http://www.medpagetoday.com/Orthopedics/SportsMedicine/36947 also see

http://www.ncaa.org/wps/wcm/connect/public/NCAA/Health+and+Safety/Sickle+Cell/Sickle+Cell+Landing+Page

Fighting Painful Misconceptions About Sickle Cell Disease In The ER

When sickle cell patients arrive at emergency rooms, they often have great difficulty getting the treatment they need. Paula Tanabe, an associate professor at the Duke University School of Nursing, is making it her mission to change that.

http://www.kaiserhealthnews.org/Stories/2013/January/24/sickle-cell-misconceptions-and-the-ER.aspx

 

Bahrain to Host International Conference on Sickle Cell Disease, Management and Prevention http://www.bna.bh/portal/en/news/542546

 

Bahrain is hoping to benefit from international experience when it hosts a global conference about sickle cell disease. Hundreds of patients and doctors are expected to attend the event, taking place at the Ritz-Carlton Bahrain, Hotel and Spa from February 5 to 7. The International Conference on Sickle Cell Disease, Management and Prevention is being organised by the Health Ministry and held under the patronage of His Royal Highness Prime Minister Prince Khalifa bin Salman Al Khalifa.

 

"Prominent speakers from around the world, the Middle East and GCC as well as from Bahrain have already confirmed their participation," said National Committee to Combat Genetic Diseases and students screening programme head Dr Shaikha Al Arrayed.

 

"The conference will also provide an interactive forum for participants to discuss important and emerging health issues," she said. "The event will be an opportunity to strengthen communication and networking and to share best practices and improve the health of blood disorder populations."This is the time to unite to fight these diseases and protect the new generation." Dr Al Arrayed said emerging health issues, protocols for pain management, prevention and treatment of opiate addiction, avoidance of causes of death in patients and avoidance of complications such as acute chest syndrome, stroke, renal failure and vascular necrosis would be discussed at the event. Participants will also learn about alternative forms of treatment.

 

Sickle Cells Show Potential to Attack Aggressive Cancer Tumors

 

Reporting in the Jan. 9, 2013, edition of the on-line journal PLOS ONE, the researchers describe a process of exploiting sickle-shaped red blood cells to selectively target oxygen deprived cancer tumors in mice and block the blood vessels that surround them.

"Sickle cells appear to be a potent way to attack hypoxic (oxygen-starved) solid tumors, which are notable for their resistance to existing cancer chemotherapy agents and radiation," said senior author Mark W. Dewhirst, DVM, PhD, a radiation oncologist and director of Duke's Tumor Microcirculation Laboratory. "This is an exciting finding that suggests a potential new approach to fighting tumors that are currently associated with aggressive disease." http://www.sciencedaily.com/releases/2013/01/130109185852.htm

 

Greensboro's Cone Health To Open Sickle Cell Center

The center will be the second round-the-clock sickle cell center in the southeast.http://www.digtriad.com/video/default.aspx?bctid=2081955080001

 

5-year-old twin rappers battling sickle cell anemia

Marcus and Marlon Davis are identical 5-year-old twins who could be the next big rappers to hail from Houston. But first, they'll have to overcome an obstacle bigger than those typically faced by singers seeking fame in the rap game. Their group -- The Official Two Times Two -- is out with their new single called, "I'ma Act Bad."The twins were four when they started rapping, but they're moving up quickly.

Marcus and Marlon recently had their first live performance at a small downtown venue. "It was fantastic. I thought they were going to be nervous but they weren't," said their mother, Felicia Pollard. Their mother is nervous for another reason.The twins have a severe case of sickle cell anemia.

"They've been hospitalized 36 times, both of them," Pollard said. "Marlon, we almost lost him before Thanksgiving,” said their aunt and manager, Linda Marshall. Doctors have told the family that the twins may not live to see the age of 21. Sickle cell causes the boys' red blood cells to collapse into a crescent shape. This can lead to organ damage. It always leads to excruciating pain. In between hospital stays, Marcus and Marlon enjoy sessions in the studio. "It keeps 'em focused, you know, keeps their mind off their pain," Marshall said. Their next goal is to appear on "The Ellen DeGeneres Show." http://www.khou.com/news/health/Young-Houston-rappers-battle-sickle-cell-anemia--185480032.html

 

Video Resources

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

2013 Dates: 1/24, 2/28, 3/28, 4/25, 5/23, 6/27, 7/25, 8/22, 9/26, 10/24   

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 January

 

1.

Blood. 2013 Jan 24. [Epub ahead of print]

Erythrocyte NADPH oxidase activity modulated by Rac GTPases, PKC, and plasma cytokines contributes to oxidative stress in sickle cell disease.

George APushkaran SKonstantinidis DGKoochaki SMalik P,Mohandas NZheng YJoiner CHKalfa TA.

Texas Children's Hematology Center, Texas Children's Hospital, Houston, TX, United States;

Abstract

Chronic inflammation has emerged as an important pathogenic mechanism in sickle cell disease (SCD). One component of this inflammatory response is oxidant stress mediated by reactive oxygen species (ROS) generated by leukocytes, endothelial cells, plasma enzymes, and sickle red blood cells (RBC). Sickle RBC ROS generation has been attributed to sickle hemoglobin auto-oxidation and Fenton chemistry reactions catalyzed by denatured heme moieties bound to the RBC membrane. In this study, we demonstrate that a significant part of ROS production in sickle cells is mediated enzymatically by NADPH oxidase, which is regulated by protein kinase C, Rac GTPase and intracellular Ca(2+) signaling within the sickle RBC. Moreover, plasma from patients with SCD and isolated cytokines, such as TGFβ1 and ET1, enhance RBC NADPH oxidase activity and increase ROS generation. ROS-mediated damage to RBC membrane components is known to contribute to erythrocyte rigidity and fragility in SCD. Erythrocyte ROS generation, hemolysis, vaso-occlusion, and the inflammatory response to tissue damage may therefore act in a positive feedback loop to drive the pathophysiology of sickle cell disease. These findings suggest a novel pathogenic mechanism in SCD and may offer new therapeutic targets to counteract inflammation and RBC rigidity and fragility in sickle cell disease.


PMID: 23349388 [PubMed - as supplied by publisher]


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2.

Am J Respir Crit Care Med. 2013 Jan 24. [Epub ahead of print]

Hemodynamic Predictors of Mortality in Adults with Sickle Cell Disease.

Mehari AAlam STian XCuttica MJBarnett CFMiles GXu D,Seamon CAdams-Graves PCastro OLMinniti CPSachdev V,Taylor Vi JGKato GJMachado RF.

Cardiovascular and Pulmonary Branch, National Heart, Lung, and Blool Institute, Bethesda, Maryland, United States.

Abstract

BACKGROUND:

Pulmonary hypertension (PH) in adults with sickle cell disease (SCD) is associated with early mortality, but no prior studies have evaluated quantitative relationships of mortality to physiological measures of pre- and post-capillary PH.

OBJECTIVE:

To identify risk factors associated with mortality and to estimate the expected survival in a cohort of patients with SCD with PH documented by right heart catheterization.

METHODS:

Nine year follow-up data (median 4.7 years) from the NIH SCD PH screening study are reported. Five hundred twenty-nine adults with SCD were screened by echocardiography between 2001 and 2010 with no exclusion criteria. Hemodynamic data were collected from 84 patients. PH was defined as mean pulmonary artery pressure (PAP) ≥25 mmHg. Survival rates were estimated by the Kaplan-Meier method and mortality risk factors were analyzed by the Cox proportional hazards regression.

MEASUREMENTS AND MAIN RESULTS:

Specific hemodynamic variables were independently related to mortality: mean PAP (HR 1.61, 95% CI 1.05- 2.45, per 10 mmHg increase, P=0.027), diastolic PAP (HR 1.83, 95% CI 1.09-3.08, per 10 mmHg increase, P=0.022), diastolic PAP - pulmonary capillary wedge pressure (HR 2.19, 95% CI 1.23-3.89, per 10 mmHg increase, P=0.008), transpulmonary gradient (HR 1.78, 95% CI 1.14-2.79 per 10 mmHg increase, P=0.011), pulmonary vascular resistance (HR 1.44 , 95% CI 1.09-1.89 per Wood unit increase, P=0.009 ) as risk factors for mortality.

CONCLUSION:

Mortality in adults with SCD and PH is proportional to the physiological severity of pre-capillary PH, demonstrating its prognostic and clinical relevance despite anemia-induced high cardiac output and less severely elevated pulmonary vascular resistance.


PMID: 23348978 [PubMed - as supplied by publisher]


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3.

Nephrol Dial Transplant. 2013 Jan 22. [Epub ahead of print]

Improved survival among sickle cell kidney transplant recipients in the recent era.

Huang EParke CMehrnia AKamgar MPham PTDanovitch G,Bunnapradist S.

1Division of Nephrology, Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, CA, USA.

Abstract

BackgroundStudies from older cohorts of kidney recipients have observed that recipients with sickle cell disease (SCD) have lower patient survival compared with age- and race-matched controls. We examined whether survival has improved among SCD recipients in the current era.MethodsUsing Organ Procurement and Transplantation Network/United Network for Organ Sharing data, all black/African-American kidney recipients were stratified according to transplant year into an early (1988-99) and recent era (2000-11). Patient and allograft survival among SCD recipients and those with other diagnoses were compared (early era: SCD n = 67, others n = 20 694; recent era: SCD n = 106, others n = 34 428). A secondary-matched cohort analysis compared patient and allograft survival between SCD recipients matched to recipients with other diagnoses based on recipient and donor age, gender and donor type (deceased versus living).ResultsPatient survival at 6 years was lower among SCD recipients in the early era compared with other diagnoses (55.7 versus 78.0%; P < 0.001). Six-year patient survival among sickle cell recipients improved in the recent era (69.8%; P versus early era = 0.04), although still trended toward lower survival compared with other diagnoses (80.0%; P = 0.07). Multivariate Cox proportional hazard models revealed an increased mortality risk with SCD in both eras [early: hazard ratio (HR) = 3.12; 95% confidence interval (CI): 2.15-4.54; recent: HR: 2.03; 95% CI: 1.31-3.16]. Patient survival among matched SCD recipients in the recent era was comparable to diabetic recipients (SCD: 73.1%, diabetes: 74.1%; P = 0.44).ConclusionsPatient survival has improved among contemporary sickle cell recipients compared with an earlier cohort and is comparable to a matched cohort of diabetic kidney recipients. Appropriately selected SCD patients may receive kidney transplants with reasonable survival outcome.


PMID: 23345624 [PubMed - as supplied by publisher]


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4.

Pain Manag Nurs. 2013 Jan 21. pii: S1524-9042(12)00175-0. doi: 10.1016/j.pmn.2012.10.007. [Epub ahead of print]

Care Seeking for Pain in Young Adults with Sickle Cell Disease.

Jenerette CMBrewer CAAtaga KI.

School of Nursing, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina. Electronic address:coretta.jenerette@unc.edu.

Abstract

In individuals with sickle cell disease (SCD), recognizing the cues to an acute pain episode and responding appropriately are important. The purpose of this mixed-methods pilot study is to identify preliminary factors that influence care seeking for pain in young adults with SCD. Responses were received from 69 young adults with SCD, age 18-35 years. The majority of respondents (88%) wait until the pain intensity is an average of 8.7 (± 1.2) on a scale of 1 to 10 before seeking care. Prominent themes influencing care seeking for pain include: trying to treat pain at home, avoiding the emergency department because of past treatment experiences, the desire to avoid admission to the hospital, and the importance of time in the lives of the young adults with SCD. Young adults with SCD need additional support from family and healthcare providers in order to make timely, appropriate decisions regarding care seeking.

Copyright © 2013 American Society for Pain Management Nursing. Published by Elsevier Inc. All rights reserved.


PMID: 23343879 [PubMed - as supplied by publisher]


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5.

J Natl Med Assoc. 2012 Sep-Oct;104(9-10):449-54.

Sickle cell disease patients' perceptions of emergency department pain management.

Porter JFeinglass JArtz NHafner JTanabe P.

St. Jude Children's Research Hospital, Department of Psychology, Memphis, TN 38105, USA.

Abstract

Patients with sickle cell disease (SCD) experience painful crises that often require admission to the emergency department (ED) for pain management. Factors such as ED overcrowding and negative perception and stigmatization of SCD may impact patients' perceptions of the quality of pain management in the ED. Data from a multisite prospective cohort study was assessed to determine whether demographic (age and sex), clinical (time to administration of initial analgesia, number of analgesic doses, discharge disposition, and clinical site), or interpersonal factors (separately measured perceptions of being treated with trust and respect by ED triage nurses, nurses, and physicians) were associated with patient ratings of their pain management in the ED. Patients were adults with SCD seen at 3 EDs (2 urban and 1 rural). Demographic and clinical information was derived from medical record review; interpersonal and ED pain management ratings were derived from interviews conducted 1 week post ED visit. A total of 209 interviews by 98 patients were analyzed. Results indicated significant differences among the ED sites on the demographic, clinical, and interpersonal factors. Overall, patients reported being treated with trust and respect by ED clinicians. Adjusted logistic regression analyses indicated that ED clinical site 1 (odds ratio [OR], 10.42; 95% confidence interval [Cl], 1.44-7.36) and being treated with trust and respect by the ED physician (OR, 25.53; 95% CI, 2.07-314.96) predicted good ED pain management ratings. Interpersonal health care experiences may be an important indicator of patient satisfaction and quality of care received by patients with SCD in the ED.


PMID: 23342819 [PubMed - in process]


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6.

Pediatr Infect Dis J. 2013 Jan 21. [Epub ahead of print]

Epidemiology of Bloodstream Infections in Children with Sickle Cell Disease.

Ellison AMOta KVMcGowan KLSmith-Whitley K.

From the Divisions of 1Emergency Medicine and 3Hematology, Department of Pediatrics, The Children's Hospital of Philadelphia, Perelman School of Medicine at the University of Pennsylvania; 2 the Department of Pathology and Laboratory Medicine, The Children's Hospital of Philadelphia, Perelman School of Medicine at the University of Pennsylvania.

Abstract

The incidence of invasive Streptococcus pneumoniae and Haemophilus influenzae type b infections in the sickle cell disease (SCD) population has declined. In this report, we determine the predominant organisms responsible for bloodstream infections (BSIs) and associated foci of infection in a pediatric SCD population during the post heptavalent conjugate (PCV7) vaccine era. Central venous access device associated infections are a new burden to efforts aimed at preventing BSIs in this population.


PMID: 23340560 [PubMed - as supplied by publisher]


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7.

Transl Res. 2013 Jan 18. pii: S1931-5244(12)00447-1. doi: 10.1016/j.trsl.2012.12.011. [Epub ahead of print]

Gene therapy for hemoglobinopathies: progress and challenge.

Dong ARivella SBreda L.

Weill Cornell Medical College, Department of Pediatrics, Division of Hematology-Oncology, New York, NY.

Abstract

Hemoglobinopathies are genetic inherited conditions that originate from the lack or malfunction of the hemoglobin protein. Sickle cell disease (SCD) and thalassemia are the most common forms of these conditions. The severe anemia combined with complications that arise in the most affected patients raises the necessity for a cure to restore hemoglobin function. The current routine therapies for these conditions, namely transfusion and iron chelation, have significantly improved the quality of life in patients over the years, but still fail to address the underlying cause of the diseases. A curative option, allogeneic bone marrow transplantation is available, but limited by the availability of suitable donors and graft-vs-host disease. Gene therapy offers an alternative approach to cure patients with hemoglobinopathies and aims at the direct recovery of the hemoglobin function via globin gene transfer. In the last 2 decades, gene transfer tools based on lentiviral vector development have been significantly improved and proven curative in several animal models for SCD and thalassemia. As a result, clinical trials are in progress and 1 patient has been successfully treated with this approach. However, there are still frontiers to explore that might improve this approach: the stoichiometry between the transgenic hemoglobin and endogenous hemoglobin with respect to the different globin genetic mutations; donor cell sourcing, such as the use of induced pluripotent stem cells (iPSCs); and the use of safer gene insertion methods to prevent oncogenesis. With this review we will provide insights about (1) the different lentiviral gene therapy approaches in mouse models and human cells; (2) current and planned clinical trials; (3).hurdles to overcome for clinical trials, such as myeloablation toxicity, insertional oncogenesis, and high vector expression; and (4) future perspectives for gene therapy, including safe harbors and iPSCs technology.

Copyright © 2012 Mosby, Inc. All rights reserved.


PMID: 23337292 [PubMed - as supplied by publisher]


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8.

Pediatr Blood Cancer. 2013 Jan 17. doi: 10.1002/pbc.24459. [Epub ahead of print]

Age-related treatment patterns in sickle cell disease patients and the associated sickle cell complications and healthcare costs.

Blinder MAVekeman FSasane MTrahey APaley CDuh MS.

Department of Medicine and Department of Pathology & Immunology, Washington University in St. Louis, St. Louis, Missouri.mblinder@dom.wustl.edu.

Abstract

BACKGROUND:

This study explored the blood transfusion patterns, SCD complications, utilization of iron chelation therapies (ICT), healthcare resource use, and costs in pediatric, transitioning (18 years old) and adult p


Sickle Cell News for December 2012

Q&A with Dr. Kwaku Ohene-Frempong about the importance of sickle cell screening and disparities between the US and abroad To mark the 50th anniversary of newborn screening, we did an interview with Dr. Kwaku Ohene-Frempong about screening for SCD and trait. Dr. Ohene-Frempong is the Director Emeritus of the Comprehensive Sickle Cell Center at Children’s Hospital of Philadelphia, President of the Sickle Cell Foundation of Ghana, and a NICHQ faculty member. Link http://www.nichq.org/resources/Sickle-Cell-Frempong-QA-Dec2012.html
 
Into Adulthood, Sickle Cell Patients Rely on ER
Patients with sickle cell disease rely more on the emergency room as they move from pediatric to adult health care, according to researchers at Washington University School of Medicine in St. Louis.  Link http://www.infozine.com/news/stories/op/storiesView/sid/54200/
Sickle cell patient refuses to let disease define her
 Marquita Gaines is a college student living with sickle cell disease. She was diagnosed at birth and first presented symptoms at a young age. She currently receives regular blood cell transfusions administered by registered nurses from the American Red Cross to treat and prevent complications from the disease Link http://www.cnn.com/2012/12/13/us/iyw-blood-donor-gaines/
Ask The Experts
Q: What is the best diet to give a 8 year old with sickle cell disease (Hb SS)
A: Thank you for your question. Diet in sickle cell disease is the subject of active research, but the studies are far from complete or conclusive. Researchers have not tried to demonstrate a what a "Sickle Cell Diet" should be. Here are some bits of information:
 
(1) Sickle hemoglobin and breakdown of sickle red blood cells place the body under high oxidant stress, so that taking anti-oxidants supplements seem like a good idea. 
(2) Blood chemistries in people with sickle cell are slightly abnormal in multiple different ways.  Supplementing for the deficiencies seem like a good idea.
(3)  Studies have been designed to examine single-ingredient supplements such as vitamins ( folic acid, tetrahydrobiopterin, vitamin D, vitamin C, vitamin E), minerals ( zinc, magnesium), amino acids ( glutamine, arginine, citrulline), anti-oxidants, nitrite, nitrate, or fish oil.  I don't remember seeing studies designed as head-to-head comparions to show what ingredient(s) are the most important. 
(4) We do think that extra iron supplements are not necessary for sickle cell disease, unless somebody has lost a lot of blood or has demonstrated unusual barriers to iron absorption. 
(5) Probably the only advice we can give is to eat a generally balanced diet as recommended for most American families in the general population: plenty of fruits & vegetables, balanced protein intake (meats, dairy, nuts & beans), drink plenty of fluids, eat dietary fiber, and avoid excessive amounts of sugary or fried snacks.  This nutritional advice is based on dietary research on reduce the risks of diabetes, heart attacks, stroke, and some cancers.
 
Sincerely,
 
Lewis Hsu, MD
Pediatric Hematologist
 
Video Resources
SAVE THE DATESFellow 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 EST2013 Dates: 1/24, 2/28, 3/28, 4/25, 5/23, 6/27, 7/25, 8/22, 9/26, 10/24  
The purpose of this webinar series is to offer a hemoglobinopathies learning collaborative platform for providers, consumers, educators, and scientists.
January’s webinar will take place on Thursday, January 24th from 2:00pm – 3:00pm EST, featuring
Dr. Thomas Coates’ presentation on “Monitoring and Management of Transfusional Iron Overload”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  would appreciate your feedback on this year’s “Public Health Webinar Series on Hemoglobinopathies” hosted by the Division of Blood Disorders, CDCby completing a brief online survey: http://www.surveymonkey.com/s/M986NWM Please forward the survey link to colleagues who participated on this webinar series as a group.Your feedback is valuable and will help us improve the series for 2013.
Thank you for your participation!
 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 (you can get the video code from this site and embed the video on another webpage, or download it): http://www.cdc.gov/NCBDDD/video/SickleCell/index.html  CDC Sickle Cell Disease Webpage: http://wwwdev.cdc.gov/NCBDDD/sicklecell/video.html  Articles in the Medical Literature for November
 
1. Blood. 2012 Dec 20. [Epub ahead of print]
Hemolysis and free hemoglobin revisited: exploring hemoglobin and hemin scavengers as a novel class of therapeutic proteins.
Schaer DJ, Buehler PW, Alayash AI, Belcher JD, Vercellotti GM.
Division of Internal Medicine, University Hospital, Zurich, Switzerland;
Abstract
Hemolysis occurs in many hematologic and non-hematologic diseases. Extracellular hemoglobin (Hb) has been recognized to trigger specific pathophysiologies that are associated with ad

verse clinical outcomes in patients with hemolysis, such as acute and chronic vascular disease, inflammation, thrombosis and renal impairment. Among the molecular characteristics of extracellular Hb, translocation of the molecule into the extravascular space, oxidative and nitric oxide reactions, hemin release and molecular signaling effects of hemin appear to be the most critical. Limited clinical experience with a plasma-derived haptoglobin product in Japan and more recent preclinical animal studies suggest that the natural Hb and hemin scavenger proteins haptoglobin (Hp) and hemopexin (Hpx) have a strong potential to neutralize the adverse physiologic effects of Hb and hemin. This includes conditions that are as diverse as red blood cell transfusion, sickle cell disease, sepsis and extracorporeal circulation. This perspective reviews the principal mechanisms of Hb and hemin toxicity in different disease states, updates how the natural scavengers efficiently control these toxic moieties, and explores critical issues in the development of human plasma-derived Hp and Hpx as therapeutics for patients with excessive intravascular hemolysis.
PMID: 23264591 [PubMed - as supplied by publisher]

 
2. Transfus Apher Sci. 2012 Dec 17. pii: S1473-0502(12)00234-0. doi: 10.1016/j.transci.2012.09.002. [Epub ahead of print]
Long-term red blood cell exchange in children with sickle cell disease: Manual or automatic?
Duclos C, Merlin E, Paillard C, Thuret I, Demeocq F, Michel G, Kanold J.
CHU Bordeaux Hôpital Haut-Lévêque, Service hématologie, 33600 Pessac, France. Electronic address: cedric.duclos@chu-bordeaux.fr.
Abstract
Little information is available on erythrocytapheresis in children with sickle cell disease, and no comparison has ever been made with manual exchanges in a long-term blood exchange program. We matched a historical cohort of five patients who received 60 erythrocytapheresis procedures with five who received 124 manual exchanges. Long-term erythrocytapheresis was feasible and well-tolerated even in children of low weight. In a long-term approach, automated exchanges were more efficient in maintaining a low HbS level, and exchanges could be spaced out. This approach appears especially useful in the cases where the HbS level must be maintained below 30%.
Copyright © 2012 Elsevier Ltd. All rights reserved.
PMID: 23257506 [PubMed - as supplied by publisher]

 
3. Am J Hematol. 2012 Nov 17. doi: 10.1002/ajh.23365. [Epub ahead of print]
Hydroxyurea treatment decreases glomerular hyperfiltration in children with sickle cell anemia.
Aygun B, Mortier NA, Smeltzer MP, Shulkin BL, Hankins JS, Ware RE.
Department of Hematology, St. Jude Children's Research Hospital, Memphis, Tennessee. baygun@nshs.edu.
Abstract
Glomerular hyperfiltration and microalbuminuria/proteinuria are early manifestations of sickle nephropathy. The effects of hydroxyurea therapy on these renal manifestations of sickle cell anemia (SCA) are not well defined. Our objective was to investigate the effects of hydroxyurea on glomerular filtration rate (GFR) measured by (99m) Tc-DTPA clearance, and on microalbuminuria/proteinuria in children with SCA. Hydroxyurea study of long-term effects (HUSTLE) is a prospective study (NCT00305175) with the goal of describing the long-term cellular, molecular, and clinical effects of hydroxyurea therapy in SCA. Glomerular filtration rate, urine microalbumin, and serum cystatin C were measured before initiating hydroxyurea therapy and then repeated after 3 years. Baseline and Year 3 values for HUSTLE subjects were compared using the Wilcoxon Signed Rank test. Associations between continuous variables were evaluated using Spearman correlation coefficient. Twenty-three children with SCA (median age 7.5 years, range, 2.5-14.0 years) received hydroxyurea at maximum tolerated dose (MTD, 24.4 ± 4.5 mg/kg/day, range, 15.3-30.6 mg/kg/day). After 3 years of treatment, GFR measured by (99m) Tc-DTPA decreased significantly from 167 ± 46 mL/min/1.73 m(2) to 145 ± 27 mL/min/1.73 m(2) (P = 0.016). This decrease in GFR was significantly associated with increase in fetal hemoglobin (P = 0.042) and decrease in lactate dehydrogenase levels (P = 0.035). Urine microalbumin and cystatin C levels did not change significantly. Hydroxyurea at MTD is associated with a decrease in hyperfiltration in young children with SCA.Am. J. Hematol., 2012. © 2012 Wiley Periodicals, Inc.
Copyright © 2012 Wiley Periodicals, Inc.
PMID: 23255310 [PubMed - as supplied by publisher]

 
4. Pediatr Blood Cancer. 2012 Dec 19. doi: 10.1002/pbc.24413. [Epub ahead of print]
High rates of recurrent biliary tract obstruction in children with sickle cell disease.
Amoako MO, Casella JF, Strouse JJ.
Johns Hopkins University School of Medicine, Baltimore, Maryland.
Abstract
BACKGROUND:
Individuals with sickle cell disease (SCD) have an increased risk of cholelithiasis from bilirubin stones. Symptomatic biliary tract disease (BTD) includes acute and chronic cholecystitis, obstruction of the common bile duct (CBD), cholangitis, and gallstone pancreatitis. Cholecystectomy is the main treatment strategy for symptomatic patients; however, the prevalence of recurrent BTD following cholecystectomy has not been systematically evaluated. We conducted a retrospective cohort study to describe the recurrence of BTD after cholecystectomy and characterize risk factors for recurrent disease.
PROCEDURE:
We identified patients <22 years of age who presented to the Johns Hopkins Children Center with symptomatic BTD from July 1993 to June 2008.
RESULTS:
We identified 56 patients with a total of 76 episodes of symptomatic BTD (median age at first event 15.9, range 4.6-21.5 years). Eleven of the 56 patients (19.6%) had at least one episode of recurrent symptomatic BTD (median follow-up of 5.3 years). Baseline characteristics were similar between the patients with a single episode of BTD and those with recurrent BTD.
CONCLUSIONS:
These results demonstrate that recurrent BTD is a frequent complication of SCD (20% by age 4 years) and often presents as CBD obstruction by stone, despite cholecystectomy. In our cohort, recurrence was not associated with age at first episode, baseline total bilirubin, gender, or genotype of SCD. Pediatr Blood Cancer © 2012 Wiley Periodicals, Inc.
Copyright © 2012 Wiley Periodicals, Inc.
PMID: 23255346 [PubMed - as supplied by publisher]

 
5. Clin Transl Sci. 2012 Dec;5(6):437-44. doi: 10.1111/cts.12005. Epub 2012 Oct 17.
Effect of propranolol as antiadhesive therapy in sickle cell disease.
De Castro LM, Zennadi R, Jonassaint JC, Batchvarova M, Telen MJ.
Duke Comprehensive Sickle Cell Center, Division of Hematology, Department of Medicine, Duke University, Durham, North Carolina, USA.
Abstract
Sickle red blood cells (SSRBCs) adhere to both endothelial cells (ECs) and the extracellular matrix. Epinephrine elevates cyclic adenosine monophosphate in SSRBCs and increases adhesion of SSRBCs to ECs in a β-adrenergic receptor and protein kinase A-dependent manner. Studies in vitro as well as in vivo have suggested that adrenergic stimuli like epinephrine may contribute to vaso-occlusion associated with physiologic stress. We conducted both animal studies and a Phase I dose-escalation study in sickle cell disease (SCD) patients to investigate whether systemically administered propranolol inhibits SSRBC adhesion and to document the safety of propranolol in SCD. Systemically administered propranolol prevented SSRBC adhesion and associated vaso-occlusion in a mouse model. In patients receiving a single oral dose of 10, 20, or 40 mg propranolol, SSRBC adhesion to ECs was studied before and after propranolol, with and without stimulation with epinephrine. Propranolol administration significantly reduced epinephrine-stimulated SSRBC adhesion in a dose dependent manner (p = 0.03), with maximum inhibition achieved at 40 mg. Adverse events were not severe, did not show dose dependence, and were likely unrelated to drug. No significant heart rate changes occurred. These results imply that β-blockers may have a role as antiadhesive therapy for SCD. Clin Trans Sci 2012; Volume 5: 437-444.
© 2012 Wiley Periodicals, Inc.
PMID: 23253664 [PubMed - in process]

 
6. Platelets. 2012 Dec 18. [Epub ahead of print]
Circulating platelet and erythrocyte microparticles in young children and adolescents with sickle cell disease: Relation to cardiovascular complications.
Tantawy AA, Adly AA, Ismail EA, Habeeb NM, Farouk A.
Pediatrics Department, Faculty of Medicine, Ain Shams University , Cairo , Egypt.
Abstract
Sickle cell disease (SCD) is characterized by a complex vasculopathy, consisting of endothelial dysfunction and increased arterial stiffness, with a global effect on cardiovascular function. The hypercoagulable state may result from chronic hemolysis and circulating cell-derived microparticles (MPs) originating mainly from activated platelets and erythrocytes. We measured the levels of platelet and erythrocyte-derived MPs (PMPs and ErMPs) in 50 young SCD patients compared with 40 age- and sex-matched healthy controls and assessed their relation to clinicopathological characteristics and aortic elastic properties. Patients were studied stressing on the occurrence of sickling crisis, transfusion history, hydroxyurea therapy, hematological, and coagulation profile as well as flow cytometric expression of PMPs (CD41b(+)) and ErMPs (glycophorin A(+)). Echocardiography was performed to assess aortic stiffness and distensibility, left ventricular function and pulmonary artery pressure. Both PMPs and ErMPs were significantly elevated in SCD patients compared with control group (p < 0.001). SCD patients had significantly elevated D-dimer and von Willebrand factor antigen (vWF Ag) levels with lower antithrombin III compared with controls (p < 0.001). Aortic stiffness index and pulmonary artery pressure were significantly higher in SCD (p < 0.001), whereas aortic strain and aortic distensibility were significantly lower (p < 0.001) compared with controls. MPs levels were significantly increased in SCD patients with pulmonary hypertension, acute chest syndrome, and stroke as well as those who had history of thrombosis or splenectomy (p < 0.001). Also, patients in sickling crisis during the study had higher PMPs and ErMPs levels than those in steady state (p < 0.001). Patients on hydroxyurea therapy had lower MPs levels than untreated patients (p < 0.001). PMPs and ErMPs were positively correlated with disease duration, transfusion index, white blood cell count, HbS, markers of hemolysis, serum ferritin, D-dimer, and vWF Ag, whereas negatively correlated with hemoglobin and HbF levels (p < 0.05). Both PMPs and ErMPs levels were positively correlated with aortic stiffness, pulmonary artery pressure, and tricuspid regurgitant velocity (p < 0.05) while negatively correlated with aortic distensibility. We suggest that PMPs and ErMPs overproduction may be considered a potential biological marker for vascular dysfunction and disease severity in SCD and may be implicated in the pathogenesis of coagulation abnormalities encountered in those patients. Their levels are closely related to sickling crisis, pulmonary hypertension, markers of hemolysis, fibrinolysis, and iron overload. Therefore, quantification of MPs in SCD may provide utility for identifying patients who are at increased risk of thrombotic events or cardiovascular abnormalities and would help to monitor response to hydroxyurea therapy.
PMID: 23249216 [PubMed - as supplied by publisher]

 
7. Clin J Pain. 2012 Dec 14. [Epub ahead of print]
A Preliminary Study of Psychiatric, Familial, and Medical Characteristics of High-utilizing Sickle Cell Disease Patients.
Carroll PC, Haywood C Jr, Hoot MR, Lanzkron S.
*Department of Psychiatry and Behavioral Sciences †Department of Medicine, Division of Hematology, The Johns Hopkins School of Medicine ‡The Johns Hopkins Berman Institute of Bioethics, Baltimore, MA.
Abstract
OBJECTIVES:: To identify demographic, medical, and psychosocial characteristics that distinguished sickle cell disease (SCD) patients who were frequent utilizers of urgent or emergent care resources from low-utilizing patients. METHODS:: Patients at a large urban comprehensive SCD treatment center were recruited from clinic or during urgent care visits. Participants who were high utilizers, defined as having >4 acute or emergency care visits in the prior 12 months, were compared with patients with more typical utilization patterns on lifetime complications of SCD, family background, psychiatric history, occupational function, coping, depressive symptoms, and personality. RESULTS:: High utilizers were nearly a decade younger on average; despite this they had a similar lifetime history of SCD complications. High-utilizing patients' parents seemed to have greater educational achievement overall. High utilizers reported a nearly 3-fold greater prevalence of psychiatric illness in family members than low utilizers. On other measures, including coping strategies, social support, and personality, the 2 groups were comparable. DISCUSSION:: The study strengthens emerging evidence that disease severity, familial factors related to greater parental education, and psychiatric illness are important factors in high care utilization in patients with SCD.
PMID: 23246997 [PubMed - as supplied by publisher]

 
8. Cochrane Database Syst Rev. 2012 Dec 12;12:CD007175. doi: 10.1002/14651858.CD007175.pub3.
Antibiotics for treating osteomyelitis in people with sickle cell disease.
Martí-Carvajal AJ, Agreda-Pérez LH.
Facultad de Ciencias de la Salud Eugenio Espejo, Universidad Tecnológica Equinoccial, Quito, Ecuador.
Abstract
BACKGROUND:
Osteomyelitis (both acute and chronic) is one of the most common infectious complications in people with sickle cell disease. There is no standardized approach to antibiotic therapy and treatment is likely to vary from country to country. Thus, there is a need to identify the efficacy and safety of different antibiotic treatment approaches for people with sickle cell disease suffering from osteomyelitis.
OBJECTIVES:
To determine whether an empirical antibiotic treatment approach (monotherapy or combination therapy) is effective and safe as compared to pathogen-directed antibiotic treatment and whether this effectiveness and safety is dependent on different treatment regimens, age or setting.
SEARCH METHODS:
We searched The Group's Haemoglobinopathies Trials Register, which comprises references identified from comprehensive electronic database searches and handsearching of relevant journals and abstract books of conference proceedings. We also searched the LILACS database (1982 to 2 November 2012), African Index Medicus (3 November 2012), ISI Web of Knowledge (3 November 2012) and World Health Organization International Clinical Trials Registry Platform (3 November 2012).Date of most recent search of the Group's Haemoglobinopathies Trials Register: 29 October 2012.
SELECTION CRITERIA:
We searched for published or unpublished randomised and quasi-randomised controlled trials.
DATA COLLECTION AND ANALYSIS:
Each author intended to independently extract data and assess trial quality by standard Cochrane Collaboration methodologies, but no eligible randomised controlled trials were identified.
MAIN RESULTS:
This update was unable to find any randomised or quasi-randomised controlled trials on antibiotic treatment approaches for osteomyelitis in people with sickle cell disease.
AUTHORS' CONCLUSIONS:
We were unable to identify any relevant trials on the efficacy and safety of the antibiotic treatment approaches for people with sickle cell disease suffering from osteomyelitis. Randomised controlled trials are needed to establish the optimum antibiotic treatment for this condition.
PMID: 23235640 [PubMed - in process]
 
9. Cochrane Database Syst Rev. 2012 Dec 12;12:CD003968. doi: 10.1002/14651858.CD003968.pub3.
Psychological therapies for the management of chronic and recurrent pain in children and adolescents.
Eccleston C, Palermo TM, Williams AC, Lewandowski A, Morley S, Fisher E, Law E.
Centre for Pain Research, The University of Bath, Claverton Down, Bath, UK, BA2 7AY.
Abstract
BACKGROUND:
Chronic pain affects many children, who report severe pain, distressed mood, and disability. Psychological therapies are emerging as effective interventions to treat children with chronic or recurrent pain. This update adds recently published randomised controlled trials (RCTs) to the review published in 2009.
OBJECTIVES:
To assess the effectiveness of psychological therapies, principally cognitive behavioural therapy and behavioural therapy, for reducing pain, disability, and improving mood in children and adolescents with recurrent, episodic, or persistent pain. We also assessed the risk of bias and methodological quality of the included studies.
SEARCH METHODS:
Searches were undertaken of MEDLINE, EMBASE, and PsycLIT. We searched for RCTs in references of all identified studies, meta-analyses and reviews. Date of most recent search: March 2012.
SELECTION CRITERIA:
RCTs with at least 10 participants in each arm post-treatment comparing psychological therapies with active treatment were eligible for inclusion (waiting list or standard medical care) for children or adolescents with episodic, recurrent or persistent pain.
DATA COLLECTION AND ANALYSIS:
All included studies were analysed and the quality of the studies recorded. All treatments were combined into one class: psychological treatments; headache and non-headache outcomes were separately analysed on three outcomes: pain, disability, and mood. Data were extracted at two time points; post-treatment (immediately or the earliest data available following end of treatment) and at follow-up (at least three months after the post-treatment assessment point, but not more than 12 months).
MAIN RESULTS:
Eight studies were added in this update of the review, giving a total of 37 studies. The total number of participants completing treatments was 1938. Twenty-one studies addressed treatments for headache (including migraine); seven for abdominal pain; four included mixed pain conditions including headache pain, two for fibromyalgia, two for pain associated with sickle cell disease, and one for juvenile idiopathic arthritis. Analyses revealed five significant effects. Pain was found to improve for headache and non-headache groups at post-treatment, and for the headache group at follow-up. Mood significantly improved for the headache group at follow-up, although, this should be interpreted with caution as there were only two small studies entered into the analysis. Finally, disability significantly improved in the non-headache group at post-treatment. There were no other significant effects.
AUTHORS' CONCLUSIONS:
Psychological treatments are effective in reducing pain intensity for children and adolescents (<18 years) with headache and benefits from therapy appear to be maintained. Psychological treatments also improve pain and disability for children with non-headache pain. There is limited evidence available to estimate the effects of psychological therapies on mood for children and adolescents with headache and non-headache pain. There is also limited evidence to estimate the effects on disability in children with headache. These conclusions replicate and add to those of the previous review which found psychological therapies were effective in reducing pain intensity for children with headache and non-headache pain conditions, and these effects were maintained at follow-up.
PMID: 23235601 [PubMed - in process]

 
10. Hematology Am Soc Hematol Educ Program. 2012;2012:290-1. doi: 10.1182/asheducation-2012.1.290.
What is the evidence that hydroxyurea improves health-related quality of life in patients with sickle cell disease?
Darbari DS, Panepinto JA.
1Division of Hematology, Center for Cancer and Blood Disorders, Children's National Medical Center, Washington, DC; and.
Abstract
A 10-year-old male patient with homozygous sickle cell disease presents for a follow-up clinic visit after a recent hospitalization for a painful vasoocclusive event. His parents mention that in the past year he has had 4 hospitalizations for vasoocclusive events, 2 of which were complicated by the development of acute chest syndrome that resulted in transfer to the intensive care unit. He has missed many school days and may be retained a grade this year. He feels particularly sad about missing the school field trip that occurred during his last hospitalization. He also reports that he is not able to keep up with his friends when participating in physical activities at school. The child's parents are worried that he may be depressed. You as the provider discuss the option of hydroxyurea therapy. His parents ask if hydroxyurea would improve his overall well-being and functioning.
Free Article
PMID: 23233594 [PubMed - in process]

11. Hematology Am Soc Hematol Educ Program. 2012;2012:284-9. doi: 10.1182/asheducation-2012.1.284.
Health-related quality of life in patients with hemoglobinopathies.
Panepinto JA.
1Department of Pediatrics, Section of Hematology/Oncology/Bone Marrow Transplantation, Children's Hospital of Wisconsin/Medical College of Wisconsin, Milwaukee, WI.
Abstract
The use of patient-reported outcomes to measure the health and well-being of patients from their perspective has become an acceptable method to determine the impact of a disease and its treatment on patients. In patients with hemoglobinopathies, prior work has demonstrated that patients experience significant impairment in health-related quality of life (HRQL, a type of patient-reported outcome). This work has provided a better understanding of the burden that these patients experience and the factors that are associated with worse HRQL. The recent development of disease-specific HRQL instruments in sickle cell disease heralds new opportunities to explore the impact of the disease and its treatment on patients. The standards necessary to incorporate the measurement of HRQL into clinical trials are now well outlined by regulatory agencies. Measuring HRQL within a clinical practice setting and outside of the healthcare setting while the patient is at home are now possible and present new opportunities to understand the health and well-being of patients with hemoglobinopathies.
Free Article
PMID: 23233593 [PubMed - in process]

 

 12. Hematology Am Soc Hematol Educ Program. 2012;2012:276-83. doi: 10.1182/asheducation-2012.1.276.
Advances in stem cell transplantation and gene therapy in the β-hemoglobinopathies.
Payen E, Leboulch P.
1Commissariat a l'Energie Atomique, Institute of Emerging Diseases and Innovative Therapies, Fontenay aux Roses, France;
Abstract
High-level production of β-globin, γ-globin, or therapeutic mutant globins in the RBC lineage by hematopoietic stem cell gene therapy ameliorates or cures the hemoglobinopathies sickle cell disease and beta thalassemia, which are major causes of morbidity and mortality worldwide. Considerable efforts have been made in the last 2 decades in devising suitable gene-transfer vectors and protocols to achieve this goal. Five years ago, the first β(E)/β(0)-thalassemia major (transfusion-dependent) patient was treated by globin lentiviral gene therapy without injection of backup cells. This patient has become completely transfusion independent for the past 4 years and has global amelioration of the thalassemic phenotype. Partial clonal dominance for an intragenic site (HMGA2) of chromosomal integration of the vector was observed in this patient without a loss of hematopoietic homeostasis. Other patients are now receiving transplantations while researchers are carefully weighing the benefit/risk ratio and continuing the development of further modified vectors and protocols to improve outcomes further with respect to safety and efficacy.
Free Article
PMID: 23233592 [PubMed - in process]

13. Hematology Am Soc Hematol Educ Program. 2012;2012:271-5. doi: 10.1182/asheducation-2012.1.271.
Emerging 'A' therapies in hemoglobinopathies: agonists, antagonists, antioxidants, and arginine.
Vichinsky E.
1Hematology/Oncology, Children's Hospital and Research Center Oakland, Oakland, CA.
Abstract
Sickle cell disease and thalassemia have distinctly different mutations, but both share common complications from a chronic vasculopathy. In the past, fetal hemoglobin-modulating drugs have been the main focus of new therapy, but the increased understanding of the complex pathophysiology of these diseases has led to the development of novel agents targeting multiple pathways that cause vascular injury. This review explores the pathophysiology of hemoglobinopathies and novel drugs that have reached phase 1 and 2 clinical trials. Therapies that alter cellular adhesion to endothelium, inflammation, nitric oxide dysregulation, oxidative injury, altered iron metabolism, and hematopoiesis will be highlighted. To evaluate these therapies optimally, recommendations for improving clinical trial design in hemoglobinopathies are discussed.
Free Article
PMID: 23233591 [PubMed - in process]

14. Hematology Am Soc Hematol Educ Program. 2012;2012:208-14. doi: 10.1182/asheducation-2012.1.208.
Baby on board: what you need to know about pregnancy in the hemoglobinopathies.
Naik RP, Lanzkron S.
1Department of Medicine, Division of Hematology, Johns Hopkins University, Baltimore, MD.
Abstract
Pregnancy poses a unique challenge to patients with sickle cell disease and β-thalassemia, who often have exacerbations of hemolysis or anemia during the gestational period, experience higher rates of obstetric and fetal complications, and may have distinct underlying comorbidities related to vasculopathy and iron overload that can endanger maternal health. Optimal management of pregnant women with hemoglobinopathies requires both an understanding of the physiologic demands of pregnancy and the pathophysiology of disease-specific complications of inherited blood disorders. A multidisciplinary team of expert hematologists and high-risk obstetricians is therefore essential to ensuring appropriate antenatal maternal screening, adequate fetal surveillance, and early recognition of complications. Fortunately, with integrated and targeted care, most women with sickle cell disease and β-thalassemia can achieve successful pregnancy outcomes.
Free Article
PMID: 23233583 [PubMed - in process]

 

 
15. Hemoglobin. 2012 Dec 7. [Epub ahead of print]
Safety And Efficacy Of 4 Years Of Deferasirox Treatment For Sickle Cell Disease Patients.
Vlachaki E, Mainou M, Bekiari E, Vetsiou E, Tsapas A.
Thalassemia Unit, Second Medical Department, Hippokratio General Hospital, Aristotle University Thessaloniki , Greece.
Abstract
Deferasirox (DFRA) is a novel oral chelator agent for treatment of iron overload. Although well established in the treatment of β-thalassemia major (β-TM), it has not yet been fully investigated in patients with sickle cell disease. The aim of this report is to present the preliminary results of a pilot study assessing the effect of 4 years of DFRA treatment in six patients with sickle cell disease who are in need of recurrent transfusions. Our results show a significant reduction of ferritin levels and improvement of liver hemosiderosis, assessed by means of magnetic resonance imaging T2* (MRI T2*). None of the patients presented any serious adverse effects and the treatment was well tolerated. These results are in accordance with previous studies about the use of DFRA in sickle cell disease.
PMID: 23215738 [PubMed - as supplied by publisher]

 
16. J Pediatr Hematol Oncol. 2012 Nov 30. [Epub ahead of print]
The Other Side of Abnormal: A Case Series of Low Transcranial Doppler Velocities Associated With Stroke in Children With Sickle Cell Disease.
Buchanan ID, James-Herry A, Osunkwo I.
*Morehouse School of Medicine, Department of Pediatrics ‡Division of Hematology/Oncology, Department of Pediatrics, Emory University §Aflac Cancer Center and Blood Disorder Services of Children Healthcare of Atlanta †Sickle Cell Consortium, Atlanta, GA.
Abstract
The prevalence of cerebrovascular events in sickle cell disease (SCD) can be as low as 10% by the age of 18 for overt cerebral infarction or strokes, up to 35% for silent cerebral infarction, and as high as 43/100 patient years for acute silent cerebral ischemic events. These events typically occur during childhood with a peak incidence between the age of 4 and 7 years. The cumulative risk of central nervous system events in SCD increases with age. Transcranial Doppler (TCD) ultrasonography is an established screening tool for detecting children with SCD at highest risk for stroke by measuring the flow velocity in the large intracranial vessels. Velocities are considered abnormal with readings >200 cm/s and chronic red cell transfusions are recommended to reduce further risk or progression. Red cell transfusions have reduced the rate of cerebrovascular accidents by 90%. We describe the case of 5 children with sickle cell anemia, whose antecedent screening TCD velocities were measured to be ≤70 cm/s in the study. All patients developed some form of cerebral insults, an overt cerebral infarctions, silent stroke or transient ischemic attack, and are now receiving chronic transfusion to prevent further progression. On the basis of these cases, low TCD velocities may identify another group of children at risk for cerebrovascular disease. We suggest TCD velocities <70 cm/s in major vessels (MCA, ACA, and ICA) be considered another type of "abnormal," prompting more sensitive evaluations (such as a brain MRI and MRA) for the presence of central nervous system disease, and, if negative, decrease intervals between subsequent TCD assessments.
PMID: 23211694 [PubMed - as supplied by publisher]
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17. Pediatr Blood Cancer. 2012 Nov 28. doi: 10.1002/pbc.24395. [Epub ahead of print]

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Sickle Cell News for November 2012

Sickle cell anemia: maps and newborn estimates In 2010 around 300,000 babies were born with sickle cell anaemia, a serious blood disorder which can be fatal if untreated, and 5.5 million newborns inherited the sickle cell gene, a new study suggests. The 5.5 million who only inherit the gene will usually not present any clinical complications, these individuals could still pass this gene on to their offspring and give birth to babies suffering from sickle cell anaemia. Accurate estimates of the numbers and geographical distribution of those affected is vital for effective prevention and treatment policies to be put in place.

The research by the Malaria Atlas Project (MAP; http://www.map.ox.ac.uk), a multinational team of researchers funded mainly by the Wellcome Trust, maps the geographical contemporary distribution of sickle haemoglobin - a genetic disorder causing sickle cell anaemia. It also estimates the number of newborns affected by this condition.Historically, the sickle cell gene (haemoglobin S or HbS) was common in people of African, Mediterranean and Indian origin but, following human migrations, it is now much more widespread. The MAP team's estimates suggest that about half of the affected newborns are born in Nigeria, the Democratic Republic of the Congo, and India, but important uncertainties remain in large parts of these countries due to a lack of data.
An image showing areas with high predicted frequencies of sickle haemoglobin [credit: MAP]

Dr Fred Piel from Oxford University's Department of Zoology, who led the research, said: "Sickle cell disease has now been studied intensively for more than a hundred years but our knowledge about its current distribution and burden is really poor. Our aim was to use available evidence-based epidemiological data from the literature combined with modern mapping and modelling methods to come up with the best maps and estimates. In the future, we hope that accessing additional data, including from national screening programmes, would help further refine these results."

This study provides the first rigorous assessment of the contemporary distribution of this disorder and uses state-of-the-art methodology to estimate the number of newborns affected globally, regionally and nationally. The team was inspired by work conducted by Frank B Livingstone, in the 1970s and 80s. Although ageing, his global database on inherited blood disorder frequencies still represents a unique resource. There is growing awareness about the burden of genetic blood disorders, sickle cell disease in particular, and it is crucial for public health policy makers to access evidence-based quantitative epidemiological data allowing the assessment of the current situation and to measure changes in the future. The data will be released in open access on the MAP website (www.map.ox.ac.uk).Professor Sir David Weatherall, who has shared his unique expertise in the field and provided exceptional support to this project, said: "The inherited haemoglobin disorders, notably sickle cell disease and the different forms of thalassaemia, are by far the commonest monogenic diseases and the vast majority of births affected occur in low or middle income countries. Previous work suggested that their distribution varied considerably even within short geographical distances and data regarding their true frequency is extremely difficult to obtain. Hitherto, they have been largely ignored by the international health community and it is absolutely vital that better information is obtained regarding their true frequency so that their control and better management can be achieved, particularly in the developing countries where they are so common. The impressive work described in this paper provides an invaluable base for future work of this kind."

For further information visit http://www.map.ox.ac.uk or contact Dr Fred Piel of Oxford University on +44 (0)1865 271 132 or email fred.piel@zoo.ox.ac.uk or Professor Simon Hay of Oxford University on +44 (0)1865 271 243 or email simon.hay@zoo.ox.ac.uk. Sickle Cell Transplants Could See Wider UseNY Times article - CDC committee recommends HibMenCY for infantsThe Centers for Disease Control and Prevention’s Advisory Committee for Immunization Practices voted on October 24 to recommend a meningococcal vaccination for infants at increased risk of contracting the disease.The committee recommended that infants with anatomic or functional asplenia, including sickle cell disease, or with recognized persistent complement pathway deficiencies receive the HibMenCY meningococcal vaccine. The recommended vaccination practice includes four doses of the vaccine at two, four, six and 12 through 15 months.The vaccine can be used in infants ages two through 18 months who live in communities with serogroup Y and C meningococcal disease outbreaks.“The ACIP meningococcal vaccine working group concluded that the recently licensed HibMenCY infant vaccine should be routinely given to those infants at high risk for meningococcal disease due to certain immunocompromising conditions,” Alison Patti, a representative with the CDC, said. “Now that this vaccine is available, it made clinical and public health sense to routinely administer it to high risk infants. Before HibMenCY, no infant meningococcal vaccine was available.”ACIP’s recommendations were forwarded to the CDC’s director for approval. If approved, the recommendations will represent the official CDC recommendations for U.S. immunizations. Until that time, the recommendations are considered provisional.Meningococcal disease is a vaccine-preventable and serious bacterial infection caused by Neisseria meningitis bacteria. The two most common illnesses caused by the bacteria include bloodstream infections and meningitis. Infants with medical conditions like a complement component deficiency or sickle cell disease are at increased meningococcal disease risk.“It’s estimated that 5,000 kids per year will get HibMenCY vaccine through this high risk recommendation,” Patti said. “Most of these children are at lifelong risk for meningococcal disease, so they can now be protected younger than ever before.”Video ResourcesNew Webinar Posted for November10/25/12 Webinar - Strategies from the Field – Data Collection and Harmonization CDC’s Division of Blood Disorders and RuSH Project StatesThe video link is mms://realaudio.service.emory.edu/SOM/PA/PLATT/SICKLE/CDCdatacollection.wmvSee all the previous CDC Sickle Cell Webinars and instructions to view or listen to future events see:  http://scinfo.org/world-wide-resources/cdc-webinars-hemoglobinopathies-and-public-healthWe would appreciate your feedback on this year’s “Public Health Webinar Series on Hemoglobinopathies” hosted by the Division of Blood Disorders, CDCby completing a brief online survey: http://www.surveymonkey.com/s/M986NWM Please forward the survey link to colleagues who participated on this webinar series as a group.Your feedback is valuable and will help us improve the series for 2013.Thank you for your participation! CDC Web based Sickle Cell ResourcesCDC’s YouTube Link: http://www.youtube.com/watch?v=gnrvYsZWR1c&list=UUiMg06DjcUk5FRiM3g5sqoQ&index=2&feature=plpp_video  CDC Video Archive (you can get the video code from this site and embed the video on another webpage, or download it): http://www.cdc.gov/NCBDDD/video/SickleCell/index.html  CDC Sickle Cell Disease Webpage: http://wwwdev.cdc.gov/NCBDDD/sicklecell/video.html  Articles in the Medical Literature for November1. Mediterr J Hematol Infect Dis. 2012;4(1):e2012065. doi: 10.4084/MJHID.2012.065. Epub 2012 Oct 3.Sickle cell anaemia and malaria.Luzzatto L.Honorary Professor of Haematology, University of Florence, Scientific Director, Istituto Toscano Tumori. Firenze. Italy.AbstractSickle cell anaemia is a major chapter within haemolytic anaemias; at the same time, its epidemiology is a remarkable signature of the past and present world distribution of Plasmodium falciparum malaria. In this brief review, in keeping with the theme of this journal, we focus on the close and complex relationship betweeen this blood disease and this infectious disease. On one hand, heterozygotes for the sickle gene (AS) are relatively protected against the danger of dying of malaria, as now firmly established through a number of clinical field studies from different parts of Africa. In addition, experimental work is consistent with a plausibile mechanism: namely, that in AS heterozygotes P falciparum-infected red cells sickle preferentially and are then removed by macrophages. On the other hand, patients who are homozygous for the sickle gene and therefore suffer from sickle cell anaemia (SCA) are highly susceptible to the lethal effects of malaria. The simplest explanation of this fact is that malaria makes the anaemia of SCA more severe; in addition, in SCA there is often hyposplenism, which reduces clearance of parasites. From the point of view of public health it is important that in malaria-endemic countries patients with SCA, and particularly children, be protected from malaria by appropriate prophylaxis.PMCID: PMC3499995 Free PMC Article

PMID: 23170194 [PubMed - in process]

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2. J Hosp Med. 2012 Nov 20. doi: 10.1002/jhm.1987. [Epub ahead of print]"I'm Talking About Pain": Sickle cell disease patients with extremely high hospital use.Weisberg D, Balf-Soran G, Becker W, Brown SE, Sledge W.Department of Psychiatry, Yale University School of Medicine, New Haven, Connecticut.AbstractBACKGROUND: A small minority of sickle cell disease patients accounts for the majority of inpatient hospital days. Admitted as often as several times a month, over successive years, this cohort of patients has not been studied in depth despite their disproportionate contribution to inpatient hospital costs in sickle cell disease.OBJECTIVE: To characterize the subjective experience of extremely high hospital use in patients with sickle cell disease, and generate hypotheses about the antecedents and consequences of this phenomenon.DESIGN: Qualitative study involving in-depth, open-ended interviews using a standardized interview guide.SETTING: A single urban academic medical center.PARTICIPANTS: Eight individuals, of varying age and gender, identified as the sickle cell disease patients who are among the highest hospital use patients over a 3-year period.RESULTS: A common narrative emerged from the interview transcripts. Participants were exposed to the hospital environment and intravenous (IV) opioids at a young age, and this exposure was associated with extremely high hospital use in adulthood, evident in descriptions of multiple dimensions of their lives: pain and opioid medication use, interpersonal relationships, and personal development.CONCLUSIONS: Our results suggest a systematic, self-reinforcing process of isolation from mainstream society, support structures, and caregivers, based on increasing hospitalization, growing dependency on opioid medications, as well as missed developmental milestones. Further study and interventions should be geared towards breaking this spiraling cycle with long-term strategies in disease management and social integration. Journal of Hospital Medicine 2012; © 2012 Society of Hospital Medicine.Copyright © 2012 Society of Hospital Medicine.

PMID: 23169484 [PubMed - as supplied by publisher]

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 3. Cochrane Database Syst Rev. 2012 Nov 14;11:CD008394. doi: 10.1002/14651858.CD008394.pub2.Interventions for treating leg ulcers in people with sickle cell disease.Martí-Carvajal AJ, Knight-Madden JM, Martinez-Zapata MJ.Facultad de Ciencias de la Salud Eugenio Espejo, Universidad Tecnológica Equinoccial, Quito, Ecuador.AbstractBACKGROUND: The frequency of skin ulceration makes it an important contributor to the morbidity burden in people with sickle cell disease. Many treatment options are available to the healthcare professional, although it is uncertain which treatments have been assessed for effectiveness in people with sickle cell disease.OBJECTIVES: To assess the clinical effectiveness and safety of interventions for treating leg ulcers in people with sickle cell disease.SEARCH METHODS: We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group's Haemoglobinopathies Trials Register.We searched LILACS (1982 to August 2012), the African Index Medicus (up to August 2012), ISI Web of Knowledge (1985 to August 2012), and the Clinical Trials Search Portal of the World Health Organization (August 2012). We checked the reference lists of all the trials identified. We also contacted those groups or individuals who may have completed relevant randomised trials in this area.Date of the last search of the Group's Haemoglobinopathies Trials Register: 25 May 2012.SELECTION CRITERIA: Randomised controlled trials of interventions for treating leg ulcers in people with sickle cell disease compared to placebo or an alternative treatment.DATA COLLECTION AND ANALYSIS: Two authors independently selected studies for inclusion. All three authors independently assessed the risk of bias of the included studies and extracted data.MAIN RESULTS: Six studies met the inclusion criteria (198 participants with 250 ulcers). Each trial investigated a different intervention and within this review we have grouped these as systemic pharmaceutical interventions (L-cartinine, arginine butyrate, isoxsuprine) and topical pharmaceutical interventions (Solcoseryl(®) cream, RGD peptide dressing, topical antibiotics). Three interventions reported on the change in ulcer size (arginine butyrate, RGD peptide, L-cartinine). Of these, RGD peptide matrix significantly reduced ulcer size compared with a control group, mean reduction 6.60cm(2) (95% CI 5.51 to 7.69). Three trials reported on the incidence of complete closure (isoxsuprine, arginine butyrate, RGD peptide matrix). None reported a significant effect. No trial reported on: the time to complete ulcer healing; ulcer-free survival following treatment for sickle cell leg ulcers; quality of life measures; or incidence of amputation. There was no reported information on the safety of these interventions.AUTHORS' CONCLUSIONS: There is evidence that a topical intervention (RGD peptide matrix) reduced ulcer size in treated participants compared to controls. This evidence of efficacy is limited by the generally high risk of bias associated with these reports.We planned to analyse results according to general groups: pharmaceutical interventions (systemic and topical); and non-pharmaceutical interventions (surgical and non-surgical). However, we were unable to pool findings due to the heterogeneity in outcome definitions, and inconsistency between the unit of randomisation and the unit of analysis. This heterogeneity, along with a paucity of identified trials, prevented us performing any meta-analyses.This Cochrane review provides some evidence for the effectiveness of one topical intervention - RGD peptide matrix. However, this intervention was assessed as having a high risk of bias due to inadequacies in the single trial report. Other included studies were also assessed as having a high risk of bias. We recommend that readers interpret the trial results with caution. The safety profile of the all interventions was inconclusive.

PMID: 23152256 [PubMed - in process]

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 4. Cochrane Database Syst Rev. 2012 Nov 14;11:CD007652. doi: 10.1002/14651858.CD007652.pub3.Gene therapy for sickle cell disease.Olowoyeye A, Okwundu CI.Lagos University Teaching Hospital, P.O.Box 8893 Marina, Lagos, Nigeria.AbstractBACKGROUND: Sickle cell disease encompasses a group of genetic disorders characterized by the presence of at least one hemoglobin S (Hb S) allele, and a second abnormal allele that could allow abnormal hemoglobin polymerisation leading to a symptomatic disorder.Autosomal recessive disorders (such as sickle cell disease) are good candidates for gene therapy because a normal phenotype can be restored in diseased cells with only a single normal copy of the mutant gene.OBJECTIVES: The objectives of this review are:- to determine whether gene therapy can improve survival and prevent symptoms and complications associated with sickle cell disease;- to examine the risks of gene therapy against the potential long-term gain for people with sickle cell disease.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 searching relevant journals and abstract books of conference proceedings.Date of the most recent search of the Group's Haemoglobinopathies Trials Register: 21 June 2012.SELECTION CRITERIA: All randomised or quasi-randomised clinical trials (including any relevant phase 1, 2 or 3 trials) of gene therapy for all individuals with sickle cell disease, regardless of age or setting.DATA COLLECTION AND ANALYSIS: No trials of gene therapy for sickle cell disease were found.MAIN RESULTS: No trials of gene therapy for sickle cell disease were reported.AUTHORS' CONCLUSIONS: No randomised or quasi-randomised clinical trials of gene therapy for sickle cell disease were reported. Thus, no objective conclusions or recommendations in practice can be made on gene therapy for sickle cell disease. This systematic review has identified the need for well-designed, randomised controlled trials to assess the benefits and risks of gene therapy for sickle cell disease.

PMID: 23152248 [PubMed - in process]

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 5. Pediatr Blood Cancer. 2012 Nov 14. doi: 10.1002/pbc.24394. [Epub ahead of print]Mental health disorders influence admission rates for pain in children with sickle cell disease.Myrvik MP, Burks LM, Hoffman RG, Dasgupta M, Panepinto JA.Department of Pediatrics, Hematology/Oncology/Bone Marrow Transplantation, Children's Research Institute/Medical College of Wisconsin, Milwaukee, Wisconsin. mmyrvik@mcw.edu.AbstractBACKGROUND: Patients with sickle cell disease (SCD) experience a broad range of mental health disorders placing them at risk for more complicated hospitalizations for pain. The current study examined the impact of mental health disorders on admission rates and hospital length of stay (LOS) for vaso-occlusive pain events (VOE) in pediatric patients with SCD.PROCEDURE: Patients (5-18 years old) with a primary discharge diagnosis of SCD with crisis were acquired through the Pediatric Health Information System and categorized by history of mental health disorders (mood disorder, anxiety disorder, disruptive behavior disorder, and substance use disorder). Using a retrospective cohort design, hospital admission rates for VOE were examined as the primary outcome and LOS as a secondary outcome.RESULTS: A total of 5,825 patients accounted for 23,561 admissions for SCD with crisis with approximately 8% of the patients having a mental health diagnosis. Longer LOS was found among patients with a history of any mental health diagnosis (P < 0.0001) and within the mood disorder (P < 0.0001), anxiety disorder (P < 0.0001), and substance use disorder (P = 0.01) subtypes. Hospital admissions rates for VOE were higher among patients with a history of any mental health diagnosis (P < 0.0001) and within the mood disorder (P < 0.0001), anxiety disorder (P < 0.0001), disruptive behavior disorder (P = 0.002), and substance use disorder (P < 0.0001) subtypes.CONCLUSIONS: Pediatric patients with SCD and a history of a mental health diagnosis have longer LOS and higher admission rates for management of VOE. Ultimately, these findings suggest that mental health pose a challenge to the management of sickle cell pain. Pediatr Blood Cancer © 2012 Wiley Periodicals, Inc.Copyright © 2012 Wiley Periodicals, Inc.

PMID: 23151972 [PubMed - as supplied by publisher]

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 6. Pediatr Blood Cancer. 2012 Nov 14. doi: 10.1002/pbc.24392. [Epub ahead of print]National trends in incidence rates of hospitalization for stroke in children with sickle cell disease.McCavit TL, Xuan L, Zhang S, Flores G, Quinn CT.Division of Pediatric Hematology-Oncology, University of Texas Southwestern Medical Center at Dallas, Dallas, Texas; Children's Medical Center Dallas, Dallas, Texas. tim.mccavit@childrens.com.AbstractBACKGROUND: The success of primary stroke prevention for children with sickle cell disease (SCD) throughout the United States is unknown. Therefore, we aimed to generate national incidence rates of hospitalization for stroke in children with sickle cell disease (SCD) before and after publication of the Stroke Prevention Trial in Sickle Cell Anemia (STOP trial) in 1998.PROCEDURE: We performed a retrospective trend analysis of the 1993-2009 Nationwide Inpatient Sample and Kids' Inpatient Databases. Hospitalizations for SCD patients 0-18 years old with stroke were identified by ICD-9CM code. The primary outcome, the trend in annual incidence rate of hospitalization for stroke in children with SCD, was analyzed by linear regression. Incidence rates of hospitalization for stroke before and after 1998 were compared by the Wilcoxon rank-sum test.RESULTS: From 1993 to 2009, 2,024 hospitalizations were identified for stroke. Using the mean annual incidence rate of hospitalization for stroke from 1993 to 1998 as the baseline, the rate decreased from 1993 to 2009 (point estimate = -0.022/100 patient years [95% CI, -0.039, -0.005], P = 0.027). The mean annual incidence rate of hospitalization stroke decreased by 45% from 0.51 per 100 patient years in 1993-1998 to 0.28 per 100 patient years in 1999-2009 (P = 0.008). Total hospital days and charges attributed to stroke also decreased by 45% and 24%, respectively.CONCLUSIONS: After publication of the STOP trial and hydroxyurea licensure in 1998, the incidence of hospitalization for stroke in children with SCD decreased across the United States, suggesting that primary stroke prevention has been effective nationwide, but opportunity for improvement remains. Pediatr Blood Cancer © 2012 Wiley Periodicals, Inc.Copyright © 2012 Wiley Periodicals, Inc.

PMID: 23151905 [PubMed - as supplied by publisher]

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Sickle Cell News for October  2012

 

Researchers identify painful symptoms of sickle cell disease

Researchers at Drexel University have identified the physical forces in red blood cells and blood vessels underlying the painful symptoms of sickle cell disease. Their experiment, the first to answer a scientific question about sickle cell disease using microfluidics engineering methods, may help future researchers better determine who is at greatest risk of harm from the disease. They report their findings in Cell Press'sBiophysical Journal today.

Like many scientific questions, this discovery began with a mystery. Normal, healthy red blood cells are extremely flexible, squeezing and slipping through blood vessels with ease, even passing through the smallest capillaries that are narrower than the red blood cells themselves. But in sickle cell disease, red blood cells are prone to deforming and turning rigid while flowing through the body. A seemingly logical explanation for sickle cell disease was that its symptoms - painful episodes and organ damage caused by oxygen deprivation - resulted from the rigid sickle cells forming inside narrow capillaries and then getting stuck there.

In fact, sickle cells do not get stuck inside capillaries. The symptoms of sickle cell disease come from partial obstructions in slightly wider blood vessels farther downstream-vessels wide enough that sickle cells should be wide enough to flow through. The mystery, then, was why? How do wide, rigid cells regularly pass through the narrowest channels without getting stuck?http://www.news-medical.net/news/20121018/Researchers-identify-painful-symptoms-of-sickle-cell-disease.aspx

 

1% Of Kuwait Population Has Sickle Cell Disease

DESPITE its being one of the most commonly inherited genetic disorders on earth, there is a far-reaching lack of awareness of Sickle Cell Disease and its effects, in a case where awareness may be all it takes to for the prevention of potentially tragic results. Moreover, being that SCD is common around tropics where malaria is prevalent, the Arabian Peninsula is one of the areas commonly afflicted with SCD, with a rate of approximately 1% of the Kuwait population suffering -- in many cases unknowingly -- from the disease.

New Day Hospital in UK

After years of planning, Thursday 18 October sees the opening of a day care centre at Homerton Hospital for sufferers of both Sickle Cell Anemia and Thassalmania.

It’s the most serious of inherited conditions in the UK, yet it is the least known about and Homerton Hospital already manages over 300 local patients with the condition, while providing advice and support for those who aren’t themselves affected but ‘carry’ the condition, and could pass it on to their children.  In England alone, there are approximately 12,500 people who suffer from this disease and an estimated 240,000 carriers of sickle cell in England  http://www.hackneyhive.co.uk/index/2012/10/homerton-hospital-to-open-sickle-cell-day-care-centre/

New Sickle Cell Clinic in Missouri

University of Missouri Health Care is opening a new clinic to treat patients with sickle cell disease.  The clinic will be open the second and fourth Thursdays of every month.

Sickle cell is a genetic disease where red blood cells are in short supply.  According to Children’s Mercy Hospital, most of the treatment centers are aimed toward children. Elizabeth Gunier, a sickle cell coordinator at Women's and Children's Hospital's blood disorder and cancer unit, says the new clinic is specifically for adults.

“This is the first time since I’ve been here that we are able to set up an adult clinic, just specifically for them," she says. "It’s something that’s been in the works, something that everybody’s wanted to do.”

The clinic is set to open at Ellis Fischel Cancer Center on Oct. 25, 2012.  It is the first such clinic in Columbia.  Others are located in St. Louis and Kansas City

Tionne "T-Boz" Watkins, a member of the 1990s R&B trio TLC, is getting her own reality show, TMZ reports.

The show, called Totally T-Boz, will showcase Watkins juggling being a single mom with attempting to re-launch her music career, sources tell TMZ . The show will air on (what else?) TLC, which has reportedly ordered four episodes.

Watkins was diagnosed with sickle-cell anemia as a child and is a spokesperson for the Sickle Cell Disease Association of America. In 2006, she discovered that she had a potentially fatal brain tumor, which was removed in 2009. After the surgery, Watkins underwent therapy to re-learn how to walk and talk, according to TMZ.

Watkins filed for bankruptcy protection twice in 2011, but TLC recently announced plans for a reunion tour that will feature a hologram of Lisa "Left-Eye" Lopes, who died in a car accident in 2002.

http://www.tvguide.com/News/TLCs-Boz-Reality-Show-1054028.aspx

 

 

 

Video Resources

New Webinar Posted for October

:Improving Quality of Care for Sickle Cell Pediatrics in the Emergency Department Dr. James Moses, Boston Medical Center 9/27/12

The video link is mms://realaudio.service.emory.edu/SOM/PA/PLATT/SICKLE/CDCMoses.wmv

Schedule of  Free CDC 2012 Webinars

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

Hemoglobinopathy Webinars are archived at http://scinfo.org

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. Otherwise, please RSVP the location and number of participants for alternative international conference line access.

10/25: Strategies from the Field – Data Collection and HarmonizationCDC’s Division of Blood Disorders and RuSH Project States 

November/December: --- No Webinars---

See all the previous CDC Sickle Cell Webinars and instructions to view or listen to future events see:  http://scinfo.org/world-wide-resources/cdc-webinars-hemoglobinopathies-and-public-health

New Web Resource

NHS Sickle Cell and Thalassaemia Screening Programme Resources

Adult Carrier Leaflets:

Adults who attend antenatal screening will  receive an Adult Carrier Leaflet with information about being a carrier of a significant haemoglobin variant to assist them in their understanding of their haemoglobin carrier status.  These leaflets can be used in an antenatal setting as well as in other settings such as in a GP surgery or other healthcare centres.  

The leaflets cover the carrier states Hb AS, Hb AC, Hb AD, Hb AE, Beta Thalassaemia, Delta beta thalassaemia, O Arab, and Hb Lepore and can be downloaded at sct.screening.nhs.uk/adultcarrierleaflets 

NICE Guidelines:

The Sickle Cell Acute Painful Episode are published and are available on the National Institute for Health and Clinical Excellence (NICE) websitehttp://www.nice.org.uk/CG143   

You can find the consultation comments and responses on this page:http://guidance.nice.org.uk/CG/Wave24/6

 See all the publications at http://sct.screening.nhs.uk/

 

 

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 (you can get the video code from this site and embed the video on another webpage, or download it):http://www.cdc.gov/NCBDDD/video/SickleCell/index.html

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

Articles in the Medical Literature for October

1.

Bone. 2012 Oct 13. pii: S8756-3282(12)01312-9. doi: 10.1016/j.bone.2012.10.005. [Epub ahead of print]

Relationship between vitamin D deficiency and bone fragility in sickle cell disease: A cohort study of 56 adults.

Arlet JBCourbebaisse MChatellier GEladari DSouberbielle JC,Friedlander Gde Montalembert MPrié DPouchot JRibeil JA.

Source

Service de médecine interne, Faculté de médecine Paris Descartes, Sorbonne Paris-Cité et Assistance publique - hôpitaux de Paris, hôpital européen Georges Pompidou, 75908 Paris, France. Electronic address:jean-benoit.arlet@egp.aphp.fr.

Abstract

BACKGROUND:

Recent studies suggest that patients with sickle cell disease (SCD) have profound vitamin D (VD) deficiency. Limited data exist on the effect of VD deficiency on bone fragility in these patients.

OBJECTIVES:

To assess the prevalence of VD deficiency in adults with SCD and its consequences on bone metabolism and fragility.

METHODS:

This prospective study included 56 SCD adult patients (mean age 29.8±9.5years), in a clinically steady state. Clinical and laboratory data were recorded. Bone mineral density (BMD) was measured using dual X-ray absorptiometry. Fracture history, BMD, avascular osteonecrosis, H-shaped vertebra and markers of mineral metabolism were compared between two groups of patients presenting very low (≤6ng/ml, n=26) (group 1) and low (>6ng/ml, n=26) (group 2) 25(OH)D concentration, respectively.

RESULTS:

Median 25(OH)D concentration was 6ng/mL. VD deficiency (25(OH)D <10ng/mL) was found in 42 out of 56 patients (75%) and secondary hyperparathyroidism in 40 (71.4%). History of fracture was documented in 17 patients (30.3%), osteopenia and/or ospeoporosis in 39.6% of patients. Overall, patients of group 1 were more likely to have sustained a fracture (42.8%) compared to patients of group 2 (17.8%) (p=0.04). These patients had also lower body mass index and significantly higher parathyroid hormone, C-terminal telopeptides of type I-collagen and bone-specific alkaline phosphatase serum levels. There was no difference between group for BMD, avascular osteonecrosis history, H-shaped vertebra, and disease severity markers.

CONCLUSION:

This study suggests that VD deficiency is a key feature in SCD-bone disease. It is highly prevalent and associated with hyperparathyroidism, bone resorption markers, and history of fracture. The optimal supplementation regimen remains to be determined.

Copyright © 2012. Published by Elsevier Inc.

PMID: 23072921 [PubMed - as supplied by publisher]

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2.

Am J Epidemiol. 2012 Oct 1;176 Suppl 7:S175-85. doi: 10.1093/aje/kws323.

Sickle Cell Trait Protects Against Plasmodium falciparum Infection.

Billo MAJohnson ESDoumbia SOPoudiougou BSagara IDiawara SIDiakité MDiallo MDoumbo OKTounkara ARice JJames MA,Krogstad DJ.

Abstract

Although sickle cell trait protects against severe disease due to Plasmodium falciparum, it has not been clear whether sickle trait also protects against asymptomatic infection (parasitemia). To address this question, the authors identified 171 persistently smear-negative children and 450 asymptomatic persistently smear-positive children in Bancoumana, Mali (June 1996 to June 1998). They then followed both groups for 2 years using a cohort-based strategy. Among the 171 children with persistently negative smears, the median time for conversion to smear-positive was longer for children with sickle trait than for children without (274 vs. 108 days, P < 0.001; Cox hazard ratio = 0.56, 95% confidence interval: 0.33, 0.96; P = 0.036). Similar differences were found in the median times to reinfection after spontaneous clearance without treatment (365 days vs. 184 days; P = 0.01). Alternatively, among the 450 asymptomatic children with persistently positive smears, the median time for conversion to smear-negative (spontaneous clearance) was shorter for children with sickle trait than for children without (190 vs. 365 days; P = 0.02). These protective effects of sickle trait against asymptomatic P. falciparum infection under conditions of natural transmission were demonstrable using a cohort-based approach but not when the same data were examined using a cross-sectional approach.

PMID: 23035141 [PubMed - in process]

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3.

J Blood Med. 2012;3:105-12. doi: 10.2147/JBM.S32588. Epub 2012 Sep 19.

Barriers in transition from pediatrics to adult medicine in sickle cell anemia.

Lebensburger JDBemrich-Stolz CJHoward TH.

Source

Department of Pediatrics, University of Alabama at Birmingham, Birmingham, AL, USA.

Abstract

Transition of care from pediatric to adult providers is an essential step in the care of young adults with sickle cell anemia. Transition programs should be developed by individual institutions to systematically enhance the transition process for their patients. Prior to transfer, patients must be educated about their disease and personal medical history and develop skill sets required to navigate the adult health care setting. The objective of this literature review is to identify key concepts associated with transition of care for patients with sickle cell anemia. First, transition programs should be developed so that education about transition can begin at an early age. The readiness of patients and families should be assessed and education tailored to meet individual patient needs. Finally, the emotions and fears about transition should be recognized and addressed prior to transition.

PMCID: PMC3460672 Free PMC Article

PMID: 23055784 [PubMed]

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4.

Rev Bras Hematol Hemoter. 2012;34(4):270-4. doi: 10.5581/1516-8484.20120070.

The burden and quality of life of caregivers of sickle cell anemia patients taking hydroxyurea versus those not taking hydroxyurea.

da Silva LBIvo MLde Souza ASPontes ERPinto AMde Araujo OM.

Source

Universidade Federal de Mato Grosso do Sul - UFMS, Campo Grande, MS, Brazil.

Abstract

OBJECTIVE:

To assess the burden and quality of life of caregivers of patients with sickle cell anemia taking hydroxyurea versus those of patients not taking hydroxyurea.

METHODS:

A cross-sectional study was performed of caregivers of outpatients with sickle cell anemia in two public hospitals in Campo Grande, MS, from January through June 2010. The World Health Organization Quality of Life-BREF Scale and the Caregiver Burden Scale were used.

RESULTS:

Of the 37 caregivers in this study, 81.1% were women, 73.0% were mothers, 59.5% were married, 54.1%were mulattos, 48.6% were housewives, 54.1% had family incomes of up to one minimum wage and 75.7% had onlycompleted elementary education. The mean duration of care provided (time after diagnosis) was 16.08 ± 9.88 yearsand 89.2% reported that they provided 24-hour care. Regarding health, 27.0% of study participants reported having physical and 13.5% emotional problems. There were no significant relationships between these variables either with the different domains or the total score of the WHOQOL-BREF comparing caregivers of patients taking hydroxyurea versusthose of patients not taking hydroxyurea. There was a moderate negative linear correlation between the WHOQOL-BREF and the Caregiver Burden Scale scores (linear correlation test of Pearson: p-value = 0.003, r = -0.477). The burden of caregivers of patients who did not take hydroxyurea was significantly higher than those of patients who took the medication in terms of general tension, disappointment, environment and total score (student t-test: p-value < 0.05).

CONCLUSION:

In the perception of the caregiver, looking after sickle cell anemia patients represents a moderate negative burden.

PMCID: PMC3460397 Free PMC Article

PMID: 23049439 [PubMed]

Related citations

 

5.

Rev Bras Hematol Hemoter. 2012;34(3):178-9. doi: 10.5581/1516-8484.20120042.

Is sickle cell disease the same everywhere?

Hankins J.

Source

St. Jude Children's Research Hospital Memphis, TN, USA.

PMCID: PMC3459638 Free PMC Article

PMID: 23049412 [PubMed - in process]

Related citations

 

6.

Rev Bras Hematol Hemoter. 2012;34(3):175-7. doi: 10.5581/1516-8484.20120041.

Sickle cell disease: looking back but towards the future.

Cançado RD.

Source

Faculdade de Ciências Médicas da Santa Casa de São Paulo - FCMSCSP, SP, Brazil.

PMCID: PMC3459630 Free PMC Article

PMID: 23049411 [PubMed - in process]

Related citations

 

7.

Curr Opin Ophthalmol. 2012 Nov;23(6):533-6. doi: 10.1097/ICU.0b013e328358b921.

Ophthalmic manifestations of sickle cell disease: update of the latest findings.

Lim JI.

Source

Department of Ophthalmology, University of Illinois at Chicago, Chicago, Illinois, USA.

Abstract

PURPOSE OF REVIEW:

Recent developments in the diagnosis and management of sickle cell ocular manifestations are reviewed to enable the clinician to better manage the ophthalmic care of these patients.

RECENT FINDINGS:

Research over the past year has focused upon systemic and ocular clues to the presence of sickle cell retinopathy. In addition, newer imaging modalities, such as spectral domain optical coherence tomography and wide-field imaging, have resulted in the detection of subclinical retinopathy related to sickle cell disease. Decreased retinal function (via microperimetry testing) has also been detected in association with areas of retinal thinning. Identification of these ocular and systemic factors that are associated with sickle cell retinopathy will help identify those patients who most need to be screened for sickle cell retinopathy.

SUMMARY:

The awareness of subclinical disease as well as the identification of systemic factors associated with higher prevalence of sickle cell retinopathy will aid the clinician in identifying those patients who are at higher risk of retinopathy.

PMID: 23047170 [PubMed - in process]

Related citations

 

8.

Br J Haematol. 2012 Oct 4. doi: 10.1111/bjh.12061. [Epub ahead of print]

Challenges of alloimmunization in patients with haemoglobinopathies.

Chou STLiem RIThompson AA.

Source

Children's Hospital of Philadelphia, Philadelphia, PA, USA.

Abstract

Red blood cell (RBC) transfusions can be life-sustaining in chronic inherited anaemias, such as thalassaemia, and the indications for blood transfusions in patients with sickle cell disease continue to expand. Complications of transfusions, such as allosensitization, can create significant medical challenges in the management of patients with haemoglobinopathies. This review summarizes key findings from the medical literature related to alloimmunization in haemoglobinopathies and examines potential measures to mitigate these risks. Areas where future studies are needed are also addressed.

© 2012 Blackwell Publishing Ltd.

PMID: 23034087 [PubMed - as supplied by publisher]

Related citations

 

9.

J Fam Pract. 2012 Sep;61(9 Suppl):S5-8.

Chronic Pain Perspectives: Sickle cell disease: Gaining control over the pain.

Gregory TB.

Source

Department of Pharmacy, Truman Medical Centers, Kansas City, MO, USA.

Abstract

Ongoing adjustments to the medication regimen and careful attention to lifestyle and support systems are critical to helping patients manage the pain of sickle cell disease.

PMID: 23000669 [PubMed - in process]

Related citations

 

10.

Pediatrics. 2012 Oct 1. [Epub ahead of print]

Transition and Sickle Cell Disease.

Debaun MRTelfair J.

Source

Department of Pediatrics, Vanderbilt University School of Medicine and Monroe Carell Jr. Children's Hospital at Vanderbilt, Nashville, Tennessee; and.

Abstract

Sickle cell disease (SCD), the most common genetic disease screened for in the newborn period, occurs in ∼1 in 2400 newborns in the general population and 1 in 400 individuals of African descent in the United States. Despite the relative high prevalence and low pediatric mortality rate of SCD when compared with other genetic diseases or chronic diseases in pediatrics, few evidence-based guidelines have been developed to facilitate the transition from pediatrics to an internal medicine or family practice environment. As with any pediatric transition program, common educational, social, and health systems themes exist to prepare for the next phase of health care; however, unique features characterizing the experience of adolescents with SCD must also be addressed. These challenges include, but are not limited to, a higher proportion of SCD adolescents receiving public health insurance when compared with any other pediatric genetic or chronic diseases; the high proportion of overt strokes or silent cerebral infarcts (∼30%) affecting cognition; risk of low high school graduation; and a high rate of comorbid disease, including asthma. Young adults with SCD are living longer; consequently, the importance of transitioning from a pediatric primary care provider to adult primary care physician has become a critical step in the health care management plan. We identify how the primary care physicians in tandem with the pediatric specialist can enhance transition interventions for children and adolescents with SCD.

PMID: 23027174 [PubMed - as supplied by publisher]

 

Sickle Cell Conferences and Events

West Coast Sickle Cell Nurses Conference Friday, October 26, 2012Presented by 
Children's Hospital Los Angeles
 -Improving Outcomes for Children and Adults 
with Sickle Cell Disease Location: John Stauffer Conference Room  Children's Hospital Los Angeles  Registration fee: $45.00  5 CEU's Lunch provided

Please note, this is a NURSES ONLY conference.  

For adults and parents, please provide this information     to your nurse or health care provider.     For more information, contact  Trish Peterson attpeterson@chla.usc.edu 
or Debbie Harris at dharris@chla.usc.edu 

Caribbean Sickle Cell Conference in Saint Lucia from October 26 to 28, 2012, at the Bay Gardens Hotel

The Caribbean Organization of Sickle Cell Associations (COSCA), with the Saint Lucia Sickle Cell Association, the Saint Lucia Medical and Dental Association, and the University of the West Indies Medical School (Cave Hill), will be hosting the eighth Caribbean Sickle Cell Conference in Saint Lucia from October 26 to 28, 2012, at the Bay Gardens Hotel.  
 
In attendance will be medical practitioners, government representatives, sickle cell patients and support personnel from the region and internationally. Speakers will come from Canada, the United States, Jamaica, Martinique, Guadeloupe and Saint Lucia.  
 
Several topics will be discussed, including the prevention of sickle cell disease, research on bone marrow transplant, stroke prevention and management, the socio- economic and policy impact of sickle cell disease (SCD), the Sick Kids Caribbean haematology-oncology outreach programme, Caribbean sickle cell experience, pain management, ethical dilemmas and social issues. 

the Cuban Society of Hematology VII National Congress for the Spring of 2013 (May 20-24) at the Havana International Conference Center, under the name of HEMATOLOGIA 2013. Toghether with this event, we will be celebrating the III Caribbean Conference on Sickle Cell Disease (from CAREST), as well as the IX Latinamerican Meeting on Hematology, Immunology and Transfusion Medicine, the IV International Workshop on Hemophilia, and the III Internatioal Symposium of Regenerative Medicine.

 

emails: hematologia2013@infomed.sld.cu, mailto:ihi@infomed.sld.cu,aliciagarcia@palco.cu

 

 

7th Annual Sickle Cell Disease Research and Educational Symposium & Annual National Sickle Cell Disease Scientific meeting April 12 – 17, 2013 Miami, FL  http://www.florida-sickle.org/

Sickle Cell News for September  2012

September is Sickle Cell Month

WISCH (Working to Improve Sickle Cell Healthcare)

WISCH (Working to Improve Sickle Cell Healthcare) is NICHQ’s portfolio of projects focused on improving the quality of care for individuals with sickle cell disease across the lifespan. These projects include the Sickle Cell Disease Newborn Screening Program and the Sickle Cell Disease Treatment Demonstration Program, both of which are funded through the Health Resources and Services Administration (HRSA).

NICHQ is working with 15 grantee sites through two HRSA-funded projects to improve systems of detection and care for people living with SCD. Teams made up of healthcare providers, patients, hematologists, nurses and others are using quality improvement techniques to implement:

 

  • Timely acute care management
  • Better coordination of care
  • Better transition from pediatric to adult care
  • Improved screening, counseling, and education for individuals with SCD and trait
  • Enhanced education for providers on treating, assessing and monitoring SCD

WISCH Overview Video at  https://vimeo.com/49602847

 

Q&A with Lynnie Reid, NICHQ’s Senior Manager of Patient and Family Partnerships

Lynnie Reid went from being a young mother who knew nothing about sickle cell disease to becoming a passionate champion for people affected by the blood disorder.

"Hemoglobinopathy Learning Collaborative: Using Quality Improvement (QI) to Achieve Equity in Health Care Quality, Coordination, and Outcomes for Sickle Cell Disease" [Journal Article]

This journal article centers on NICHQ's Working to Improve Sickle Cell Healthcare (WISCH) project, which seeks to improve outcomes and care across the life course through improvement science for individuals living with sickle cell disease (SCD). 

The authors would like to acknowledge the contribution of improvement teams who participated in the expert panel meeting to review and rate indicators and to provide feedback on the feasibility of collecting data for project indicators.

 

  • Note: The full text of this article is being shared with the permission of Meharry Medical College and the Journal of Health Care for the Poor and Underserved (JHCPU).
  • Citation: Oyeku SO, Wang JC, Scoville R, Vanderkruik R, Clermont E, McPherson ME, Adams WG, and Homer CJ. "Hemoglobinopathy Learning Collaborative: Using Quality Improvement (QI) to Achieve Equity in Health Care Quality, Coordination, and Outcomes for Sickle Cell Disease." Journal of Health Care for the Poor and Underserved. Volume 23 (2012): 34–48.
  • Access the full article from the Journal of Health Care for the Poor and Underserved.

Treating Pain More Quickly for Children with Sickle Cell Disease at Boston Medical Center Hospital uses quality improvement techniques to cut the wait to pain medications in half.

New Tennessee Center Offers Affordable Care to Sickle Cell Patients A team of healthcare specialists is working to coordinate care, reduce ER visits, and spread awareness

Partially-matched bone marrow transplants can eliminate sickle cell disease in some patients

In a preliminary clinical trial, investigators at Johns Hopkins have shown that even partially-matched bone marrow transplantscan eliminate sickle cell disease in some patients, ridding them of painful and debilitating symptoms, and the need for a lifetime of pain medications and blood transfusions.  The researchers say the use of such marrow could potentially help makebone marrow transplants accessible to a majority of sickle cell patients who need them.

After a median follow-up of two years, the transplants successfully eliminated sickle cell disease in 11 of 17 patients.  Three were fully matched to their donors and eight received half-matched donor marrow.  All 11 patients are free of painful sickle cell crises and 10 no longer have anemia.  There were no deaths and no unexpected toxicities.

Six of the 11 patients (all half-matched) have stopped taking immunosuppressive drugs, although some still require narcotics for chronic pain because of sickle cell-related organ damage.  Blood tests on the six patients show that their red cells are now completely derived from their donor’s marrow.

Patients with severe sickle cell disease (SCD) face shortened life spans, intractable pain and eventual organ damage as a result of their disease, an inherited disorder caused by a mistake in the oxygen-carrying hemoglobin molecules in red blood cells.  The flawed genetic code stiffens red cells, and shapes them into a pronged “sickle” that clump and stick into blood vessel walls, cutting off blood and oxygen to tissues and organs throughout the body.

SCD occurs in approximately one in 400 African Americans, and rarely in Caucasians. An estimated 100,000 people are currently living with sickle cell disease in the U.S.

Most patients die before age 50, and many suffer poor quality of life with frequent episodes of “off-the-charts” pain, and an increased risk for kidney failurestrokedeep-vein thrombosis, and lung disease.

Treatments include blood transfusions and a drug, hydroxyurea.  Many patients use narcotics to control severe pain and have repeat hospitalizations. Bone marrow transplants have been successful in curing some cases, but matching donors are rare and the procedure itself poses risk.

In the current study, 17 patients at the Johns Hopkins Hospital were offered bone marrow transplant options, including the use of half-matched donor marrow to try and replace their “sickled” blood cells with new, healthy ones. The transplants were successful in 11 of the patients, of whom eight were only half-matches. Results of the trial were published in the Sept. 6 early online edition of Blood.

“We’re trying to reformat the blood system and give patients new blood cells to replace the diseased ones, much like you would replace a computer’s circuitry with an entirely new hard drive,” says Robert Brodsky, M.D., director of the Division ofHematology at Johns Hopkins and The Johns Hopkins Family Professor of Medicine and Oncology. “While bone marrow transplants have long been known to cure sickle cell disease, only a small percentage of patients have fully matched, eligible donors.”

National registries often are of little help in finding donors for sickle cell patients, because most of those in need are African American and other minorities who are vastly underrepresented in registries, say the Johns Hopkins researchers.

To overcome the shortage of donors, investigators at Johns Hopkins developed techniques, recently tested in leukemia andlymphoma patients, to transplant with bone marrow that is half-identical or “haploidentical” to the patient’s tissue type.  Half-matched bone marrow can be obtained from parents, children and most siblings, and is extracted by needle from the hip bone.

For the study, the Johns Hopkins team screened 19 patients to find bone marrow donors with either half-identical or fully matched tissue. Each transplant candidate had experienced many severe pain crises, significant organ problems, or had failed hydroxyruea, the only drug known to curtail sickle cell symptoms.  The team found donors for 17 of the 19 patients: 14 were half-identical and three were fully matched siblings.  The youngest patient was 15; the oldest 46.

Novartis has taken an option to buy a novel drug for sickle cell disease, as well as the US biotech company that developed it, in a deal valued at up to $665m in upfront, acquisition and milestone payments.

Oklahoma-based Selexys Pharmaceuticals has just completed a $23m equity financing to help fund the next stage of development of the drug, which is an anti-P-selectin antibody called SelG1.

And Novartis has taken an exclusive option to acquire Selexys and SelG1 after the completion of a phase II study in patients with sickle cell disease, a condition in which red blood cells form an abnormal sickle or crescent shape.

The deformation of the red blood cells causes them to stiffen so they cannot pass through small blood vessels so easily, which in turn prevents oxygen from being delivered to tissues. In severe episodes - known as vaso-occlusive crises - the blood vessels become obstructed leading to ischaemia, pain and organ damage.

"Patients with sickle cell disease endure great suffering and frequent hospitalisation due to painful vaso-occlusive crises," said Selexys' president and chief executive Dr Scott Rollins.

The company developed SelG1 based on the idea that blocking P-selectin - an adhesion molecule that causes cells to clump together - may help avert vaso-occlusive crises in sickle cell patients.

A recently-completed phase I trial supported the antibody's safety in human volunteers and the company is now pressing ahead with a phase II evaluation in patients with the disease.

Rollins said the financing will help Selexys fund not only the SelG1 trial but also a phase I study of a second antibody candidate which targets PSGL-1 and could have activity in the treatment of inflammatory bowel diseases such as Crohn's.

Sickle cell disease is currently treated using a handful of pharmacological therapies. The only drug specifically approved to treat the underlying pathology in the disease is hydroxyurea, with other drugs used to treat symptoms such as pain.

Another drug in trials for sickle cell is Emmaus Medical's L-glutamine, which is currently in phase III testing and has been designated an orphan drug by the US FDA.

 

Biotechnology company honored for work in development of clinical drug candidate for the potential treatment of vaso-occlusive crisis of sickle cell disease

GlycoMimetics, Inc., a clinical-stage biotechnology company developing a new class of glycobiology-based therapies for a broad range of indications, announced today that the William E. Proudford Sickle Cell Fund presented the company with its 2012 Unsung Hero Award last night. The award was presented during the organization's 7th Annual "Rockin' the Red" Fundraiser which was held at the Legg Mason World Headquarters, in Baltimore, Maryland.

The Unsung Hero Award is bestowed to individuals and organizations that have helped to raise awareness about sickle cell disease and sickle cell trait. Each year, a different segment of the community is chosen in an effort to emphasize that a community-wide effort is needed to help combat sickle cell disease. Previous Unsung Hero awardees have included United States Senator Thomas Carper, Maryland State Delegate Shirley Nathan-Pulliam, Dr. Sophie Lanzkron with Johns Hopkins, and Ms. Jean R. Wadman with Nemours duPont Hospital for Children.

"We are extremely honored to be recognized for our research of treatment options for people living with sickle cell disease by such a remarkable organization," said Chief Executive Officer Rachel K. King. "Receiving this award bolsters our company's efforts to advance our lead drug candidate, GMI-1070, which is currently in a Phase 2 clinical trial of patients experiencing sickle cell crisis. We hope this drug can make a difference for people living with sickle cell disease."

GlycoMimetics is studying vaso-occlusive crisis (VOC) of sickle cell disease, one of the most debilitating effects of sickle cell disease, where changes in blood protein cause red blood cells to become rigid and stick inside small blood vessels, causing blockages in blood flow and pain. Researchers are studying the potential of GlycoMimetics' lead drug candidate, GMI-1070, to treat VOC by reducing the cell adhesion and inflammation that is believed to contribute to blood flow blockages.

 

Enrollment complete in Gamida Cell’s NiCord Phase I/II trial for hematological problems

NiCord is in development as an experimental treatment for a series of indications that potentially could be cured with a bone marrow transplantation including hematological malignancies (blood cancer), sickle cell diseasethalassemia, severeautoimmune diseases and metabolic diseases. The clinical trial announced today (clinicaltrials.gov identifier NCT01221857) is studying NiCord as an alternative investigational treatment for hematological malignancies (HM). A combined total of 11 patients were transplanted at Duke University Medical Center and at Loyola University Medical Center. Dr. Mitchell E. Horwitz of Duke University Medical Center is the principal investigator. Final results of the Phase I/II study are expected within 6 months. The company is also actively enrolling for a Phase I/II study of NiCord as an experimental treatment for sickle cell, a genetic blood disease (clinicaltrials.gov identifier NCT01590628).

NiCord is an expanded cell graft derived from an entire unit of umbilical cord blood enriched with stem cells. NiCord was developed based on Gamida Cell's proprietary NAM technology. As the Phase I/II trial for HM is a first in man safety andefficacy study, for this stage, NiCord was transplanted with a second un-manipulated cord blood unit in a double cord blood configuration.

 

 

Steelers' Clark launches sickle cell campaign

safety Ryan Clark is teaming up with a Pittsburgh hospital to help raise awareness for those who suffer from sickle cell blood disorder.

Clark and UPMC launched the ''Cure League'' on Tuesday, hoping to bring more attention to sickle cell disease. Clark is one an estimated 2 million Americans who suffer from the disorder. He had to have his spleen removed after the disease was aggravated playing at high elevation in Denver in 2007. He eventually lost 35 pounds and was forced to miss the rest of the season. He will travel but not play for the Steelers on Sunday night when they hit the road to face the Broncos to open the 2012 campaign.

This initiative focuses on education, donations and support that will enable researchers to learn how to provide better care and hopefully help lead to a cure.

On the Web: www.CureLeague.org.

 

 

Video Resources

Schedule of  Free CDC 2012 Webinars

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

Hemoglobinopathy Webinars are archived at http://scinfo.org

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. Otherwise, please RSVP the location and number of participants for alternative international conference line access.

9/27: Improving Quality of Care for Sickle Cell Pediatrics in the Emergency Department Dr. James Moses, Boston Medical Center 

10/25: Strategies from the Field – Data Collection and Harmonization CDC’s Division of Blood Disorders and RuSH Project States 

November/December: --- No Webinars---

See all the previous CDC Sickle Cell Webinars and instructions to view or listen to future events see: http://scinfo.org/world-wide-resources/cdc-webinars-hemoglobinopathies-and-public-health

New Web Resource

NHS Sickle Cell and Thalassaemia Screening Programme Training Modules

Standards are key in the delivery of an expert antenatal and newborn screening programme.  The NHS Sickle Cell and Thalassaemia Screening Programme has invested in a laboratory module where laboratory personnel can participate in online training which tests them on the basic heterozygous conditions which must be detected by the antenatal screening programme.

The module has been designed to incorporate the standards of the Screening Programme’s Laboratory Handbook

See all the publications at http://sct.screening.nhs.uk/

 

Articles in the Medical Literature for September

1.

J Pediatr Oncol Nurs. 2012 Sep 19. [Epub ahead of print]

Exploring Family Communication About Sickle Cell Disease in Adolescence.

Graff JCHankins JGraves RJRobitaille KYRoberts RCejda KHardy BTJohnson MPorter JS.

Source

College of Nursing, University of Tennessee Health Science Center, Memphis, TN, USA.

Abstract

Sickle cell disease (SCD) is a lifelong disorder that involves progressive organ damage and requires ongoing medical attention to prevent and treat episodic acute complications. Children with SCD need ongoing monitoring and extra attention that may be stressful to family members. Communication within families can help resolve family stress and may be associated with medical follow-up and management of SCD. Focus groups were conducted with 12 African American families to explore the communication that occurred within and outside of the family from the perspectives of adolescents with SCD, siblings, and parents. Factors that influence family communication were explored. The extended family was an important social network and resource to adolescents, siblings, and parents. Family member knowledge of SCD was an important factor that influenced communication about SCD; adolescents and parents communicated more easily than siblings and also reported having more knowledge of SCD than siblings. Future research focusing on the knowledge of immediate and extended family members and their recognition of their contribution to the child with SCD is recommended.


PMID: 22992426 [PubMed - as supplied by publisher]


Related citations



 

2.

Haematologica. 2012 Sep 14. [Epub ahead of print]

The relationship between the severity of hemolysis, clinical manifestations and risk of death in 415 patients with sickle cell anemia in the US and Europe.

Nouraie MLee JSZhang YKanias TZhao XXiong ZOriss TBZeng QKato GJGibbs JS,Hildesheim MESachdev VBarst RMachado RHassell KLLittle JASchraufnagel DE,Krishnamurti LNovelli EGirgis REMorris CRosenzweig EBBadesch DBLanzkron SCastro OGoldsmith JCGordeuk VGladwin MT.

Source

Howard University, USA;

Abstract

Background The intensity of hemolytic anemia has been proposed as an independent risk factor for the development of certain clinical complications of sickle cell disease, such as pulmonary hypertension, hypoxemia and cutaneous leg ulceration. A composite variable derived from several individual markers of hemolysis could facilitate studies of the underlying mechanisms of hemolysis. In this study we assessed the association of hemolysis with outcomes in sickle cell disease anemia. Design and Methods A hemolytic component was calculated by principal component analysis from reticulocyte count, serum lactate dehydrogenase, aspartate aminotransferase and total bilirubin concentrations in 415 hemoglobin SS patients. Association of this component with direct markers of hemolysis and clinical outcomes was assessed. Results As primary validation, both plasma red blood cell microparticles and cell-free hemoglobin concentration were higher in the highest hemolytic component quartile compared to the lowest quartile (p≤0.0001 for both analyses). The hemolytic component was lower with hydroxyurea therapy, higher hemoglobin F, and alpha-thalassemia (p≤0.0005); it was higher with higher systemic pulse pressure, lower oxygen saturation, and greater values for tricuspid regurgitation velocity, left ventricular diastolic dimension and left ventricular mass (all p<0.0001). Two-year follow-up analysis showed that a high hemolytic component was associated with an increased risk of death (hazard ratio of 3.44; 95% CI=1.2-9.5; p = 0.02). Conclusion The hemolytic component reflects direct markers of intravascular hemolysis in patients with sickle cell disease and allows for adjusted analysis of associations between hemolytic severity and clinical outcomes. These results confirm associations between hemolytic rate and pulse pressure, oxygen saturation, increases in Doppler-estimated pulmonary systolic pressures and mortality (Clinicaltrials.gov identifier: NCT00492531). Key words: Sickle Cell Anemia, hemolysis, validation study, RBC Microparticles, Cell-Free Plasma Hemoglobin.

Free Article


PMID: 22983573 [PubMed - as supplied by publisher]


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3.

J Natl Med Assoc. 2012 May-Jun;104(5-6):299-304.

Identification and management of sickle cell trait by young physicians.

Koopmans JRoss LF.

Source

Pediatric Emergency Medicine, Ann & Robert H. Lurie Children's Hospital of Chicago, Northwestern University, Illinois, USA.

Abstract

BACKGROUND:

Sickle cell disease (SCD) is found in many ethnic groups, with the highest prevalence of heterozygote ' carriers (sickle cell trait [SCT]) in African Americans. SCT is associated with an increased risk of fatal exertional heat illness, renal papillary necrosis, and splenic infarction. Since 2006, all infants born in the United States are required to be screened for hemoglobinopathies as part of newborn screening (NBS). In 2010, as part of a legal settlement, the National Collegiate Athletic Association (NCAA) implemented SCT screening in division I athletes.

METHODS:

Members of the American Academy of Pediatrics (AAP) Section on Young Physicians were sent up to 4 e-mail survey requests to evaluate SCT education during residency, current NBS follow-up practice, and awareness of the NCAA policy. Descriptive statistics and chi2 analyses were performed.

RESULTS:

Of 871 eligible participants, 355 (41%) completed the survey. Respondents were 70% female, 71% white, and 79% general pediatricians. Most had experience with SCD during residency and had been taught about the medical and reproductive implications of SCT. Virtually all pediatricians report SCT to families when identified during NBS, but only 59% order confirmatory testing (e.g., hemoglobin electrophoresis) to verify status. While 93% counsel about reproductive implications of SCT, only 71% counsel about other medical implications. Only 27% were aware of the NCAA policy.

DISCUSSION:

Despite formal SCT education, a significant number of pediatricians do not verify NBS results or counsel about the medical implications of SCT. More comprehensive AAP guidelines about SCT are needed and must be incorporated into residency education.


PMID: 22973679 [PubMed - in process]


Related citations



 

4.

Cochrane Database Syst Rev. 2012 Sep 12;9:CD003427.

Prophylactic antibiotics for preventing pneumococcal infection in children with sickle cell disease.

Hirst COwusu-Ofori S.

Source

AstraZeneca, Parklands (90HW2Q1), Alderley Park, Cheshire, UK, SK10 4TG.

Abstract

BACKGROUND:

People with sickle cell disease are particularly susceptible to infection. Infants and very young children are especially vulnerable, and the 'Co-operative Study of Sickle Cell Disease' observed an incidence rate of 10 per 100 patient years of pneumococcal septicaemia in children under the age of three. Vaccines, including customary pneumococcal vaccines, may be of limited use in this age group. Therefore, prophylactic penicillin regimens may be advisable for this population.

OBJECTIVES:

To assess the effects of prophylactic antibiotic regimens for preventing pneumococcal infection in children with sickle cell disease.

SEARCH METHODS:

We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Haemoglobinopathies Trials Register, which is comprised of references identified from comprehensive electronic database searches and hand searches of relevant journals and abstract books of conference proceedings. Date of the most recent search: 28 March 2012.

SELECTION CRITERIA:

All randomised or quasi-randomised controlled trials comparing prophylactic antibiotics to prevent pneumococcal infection in children with sickle cell disease with placebo, no treatment or a comparator drug.

DATA COLLECTION AND ANALYSIS:

Both authors independently extracted data and assessed trial quality.

MAIN RESULTS:

Five trials were identified by the initial search, of which three trials met the inclusion criteria. All of the included trials showed a reduced incidence of infection in children with sickle cell disease (SS or Sβ0Thal) receiving prophylactic penicillin. In trials which investigated initiation of penicillin on risk of pneumococcal infection, the odds ratio was 0.37 (95% CI 0.16 to 0.86), while for withdrawal the odds ratio was 0.49 (95% CI 0.09 to 2.71). Adverse drug effects were rare and minor. Rates of pneumococcal infection were found to be relatively low in children over the age of five.

AUTHORS' CONCLUSIONS:

Prophylactic penicillin significantly reduces risk of pneumococcal infection in children with homozygous sickle cell disease, and is associated with minimal adverse reactions. Further research may help to determine the ideal age to safely withdraw penicillin.


PMID: 22972063 [PubMed - in process]


Related citations

 

Sickle Cell News for August  2012

September is Sickle Cell Month – see all the events at the end of the newsletter Living Well with Sickle CellForty-eight-year-old Ayoola Olajide is living well with sickle cell anaemia (SS). Olajide, the Editor of African Sickle Cell News and World Report, and author of Menace In My Blood- my affliction with sickle cell anaemia is married to a woman with the AA genotype (without the SS trait) and they have three boys (AS, without anaemia but are carriers). Olajide, a journalist, is on a crusade to address the genetic disorder through aggressive public enlightenment.. He said Nigerians with sickle cell could live well into old age if they have the right information and others could avoid having children with the condition by making the right choices. http://www.ngrguardiannews.com/index.php?option=com_content&view=article&id=96379:living-well-with-sickle-cell-anaemia-for-48-years&catid=44:natural-health&Itemid=599 Affordable Care Act (ACA) by the United States Supreme Court -  SCDAA Summary at http://www.sicklecelldisease.org/index.cfm?page=chief-medical-officer-newsThe Sickle Cell Disease Association of America, Inc. (SCDAA) applauds the upholding of many of the provisions of the Affordable Care Act (ACA) by the United States Supreme Court. The ACA represents a significant victory for individuals with chronic diseases such as sickle cell disease. Fear of moving from your pediatric doctor to an adult doctor because you may not have insurance may be unnecessary under the ACA. 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". Currently, the limit on how much they will pay for your heath care in each year has been set at $750,000. The long-term goal of ACA is to eliminate annual limits that are currently practiced by insurance companies from imposing any annual limits at all. SCDAA will closely monitor and report to you and our member organizations as to the progress the ACA law makes in removing these annual limits completely.  Video ResourcesNew  CDC  Videos PostedTranslating Research to Policy Dr. Shawn Bediako, University of Maryland, Baltimore County  at  mms://realaudio.service.emory.edu/SOM/PA/PLATT/SICKLE/CDCBediako.wmvSchedule of  Free CDC 2012 Webinars “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 The purpose of this webinar series is to offer a hemoglobinopathies learning collaborative platform for providers, consumers, educators, and scientists. Hemoglobinopathy Webinars are archived at http://scinfo.org 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. Otherwise, please RSVP the location and number of participants for alternative international conference line access. 9/27: Improving Quality of Care for Sickle Cell Pediatrics in the Emergency Department Dr. James Moses, Boston Medical Center 10/25: Strategies from the Field – Data Collection and Harmonization CDC’s Division of Blood Disorders and RuSH Project States November/December: --- No Webinars---See all the previous CDC Sickle Cell Webinars and instructions to view or listen to future events see:  http://scinfo.org/world-wide-resources/cdc-webinars-hemoglobinopathies-and-public-healthNew Web ResourceNHS Sickle Cell and Thalassaemia Screening Programme Training ModulesStandards are key in the delivery of an expert antenatal and newborn screening programme.  The NHS Sickle Cell and Thalassaemia Screening Programme has invested in a laboratory module where laboratory personnel can participate in online training which tests them on the basic heterozygous conditions which must be detected by the antenatal screening programme.The module has been designed to incorporate the standards of the Screening Programme’s Laboratory Handbook See all the publications at http://sct.screening.nhs.uk/ Articles in the Medical Literature for August1. Br J Haematol. 2012 Aug 28. doi: 10.1111/bjh.12019. [Epub ahead of print]High dose vitamin D therapy for chronic pain in children and adolescents with sickle cell disease: results of a randomized double blind pilot study.Osunkwo I, Ziegler TR, Alvarez J, McCracken C, Cherry K, Osunkwo CE, Ofori-Acquah SF, Ghosh S, Ogunbobode A, Rhodes J, Eckman JR, Dampier C, Tangpricha V.SourceAflac Cancer and Blood Disorders Center of Children's Healthcare of Atlanta, Atlanta, GA, USA; Department of Pediatrics, Emory University School of Medicine, Atlanta, GA, USA.AbstractWe report results of a pilot study of high-dose vitamin D in sickle cell disease (SCD). Subjects were given a 6-week course of oral high-dose cholecalciferol (4000-100 000 IU per week) or placebo and monitored prospectively for a period of six months. Vitamin D insufficiency and deficiency was present at baseline in 82·5% and 52·5% of subjects, respectively. Subjects who received high-dose vitamin D achieved higher serum 25-hydroxyvitamin D, experienced fewer pain days per week, and had higher physical activity quality-of-life scores. These findings suggest a potential benefit of vitamin D in reducing the number of pain days in SCD. Larger prospective studies with longer duration are needed to confirm these effects.© 2012 Blackwell Publishing Ltd.

PMID: 22924607 [PubMed - as supplied by publisher]

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 2. ScientificWorldJournal. 2012;2012:949535. Epub 2012 Aug 1.Beyond the definitions of the phenotypic complications of sickle cell disease: an update on management.Ballas SK, Kesen MR, Goldberg MF, Lutty GA, Dampier C, Osunkwo I, Wang WC, Hoppe C, Hagar W, Darbari DS, Malik P.SourceCardeza Foundation and Department of Medicine, Thomas Jefferson University, 1015 Walnut Street, Philadelphia, PA 19107, USA.AbstractThe sickle hemoglobin is an abnormal hemoglobin due to point mutation (GAG → GTG) in exon 1 of the β globin gene resulting in the substitution of glutamic acid by valine at position 6 of the β globin polypeptide chain. Although the molecular lesion is a single-point mutation, the sickle gene is pleiotropic in nature causing multiple phenotypic expressions that constitute the various complications of sickle cell disease in general and sickle cell anemia in particular. The disease itself is chronic in nature but many of its complications are acute such as the recurrent acute painful crises (its hallmark), acute chest syndrome, and priapism. These complications vary considerably among patients, in the same patient with time, among countries and with age and sex. To date, there is no well-established consensus among providers on the management of the complications of sickle cell disease due in part to lack of evidence and in part to differences in the experience of providers. It is the aim of this paper to review available current approaches to manage the major complications of sickle cell disease. We hope that this will establish another preliminary forum among providers that may eventually lead the way to better outcomes.PMCID: PMC3415156 Free Article

PMID: 22924029 [PubMed - in process]

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 3. Blood. 2012 Aug 24. [Epub ahead of print]Sickle cell pain: a critical reappraisal.Ballas SK, Gupta K, Adams-Graves P.SourceCardeza Foundation, Department of Medicine, Jefferson Medical College, Thomas Jefferson University, Philadephia, PA, United States;AbstractSickle cell pain includes three types: acute recurrent painful crises, chronic pain syndromes and neuropathic pain. The acute painful crisis is the hallmark of the disease and the most common cause of hospitalization and treatment in the Emergency Department. It evolves through four phases: prodromal, initial, established and resolving. Each acute painful episode is associated with inflammation that worsens with recurrent episodes, often culminating in serious complications and organ damage such as acute chest syndrome, multi-organ failure and sudden death. Three pathophysiologic events operate in unison during the prodromal phase of the crisis: vaso-occlusion, inflammation and nociception. Aborting the acute painful episode at the prodromal phase could potentially prevent or minimize tissue damage. Our hypothesis is that managing these events with hydration, anti-inflammatory drugs, aggressive analgesia and possibly vasodilators could abort the crisis and prevent or minimize further damage. Chronic pain syndromes are associated with or accompany avascular necrosis and leg ulcers. Neuropathic pain is not well studied in patients with sickle cell disease but has been modeled in the transgenic sickle mouse. Management of sickle cell pain should be based on its own pathophysiologic mechanisms rather than borrowing guidelines from other non-sickle pain syndromes.

PMID: 22923496 [PubMed - as supplied by publisher]

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 4. Chest. 2012 Aug 20. doi: 10.1378/chest.12-0611. [Epub ahead of print]The impact of Sickle Cell Disease on exercise capacity in children.Chaudry12 RA, Bush1 A, Rosenthal1 M, Crowley2 S.AbstractABSTRACTBACKGROUND: Little is known about pulmonary vascular complications in children with Sickle Cell Disease (SCD). We hypothesised that transfer factor (DLco) may be used as a surrogate for the size of the pulmonary vascular bed, and that pulmonary vascular abnormalities in SCD children may limit exercise capacity.METHODS: 50 stable SCD patients aged10 to-18 years and 50 healthy controls matched for race and age were recruited. Incremental ergometer cardiopulmonary exercise testing (CPET) was performed using respiratory mass spectrometry (RMS) for exhaled gas analysis. A rebreathing manoeuvre was used to measure functional residual capacity (FRC), effective pulmonary blood flow (Qpeff) and DLCO, and helium dilution was used to calculate minute ventilation (VE), oxygen consumption (VO2) and carbon dioxide production (CO2).RESULTS: In the 89 evaluable subjects, there were no ventilatory differences between SCD and controls. Qpeff was consistently 15-20% greater in SCD than controls at all stages but Dlco corrected for both surface area and haemoglobin was only about 7-10% greater in SCD at all stages As a result the Dlco/Qpeff ratio was considerably lower in SCD at all stages. Arteriovenous oxygen content difference was about one third less in SCD at all stages.CONCLUSIONS: Contrary to our hypothesis, failure to maintain a sufficient Qpeff to compensate for anaemia led to exercise limitation. The ratio of Pulmonary capillary blood volume to flow is reduced throughout, implying subtle pulmonary vascular disease; however this was not a factor limiting exercise.1Royal Brompton Hospital, London, United Kingdom.2St Georges' Hospital, London, United Kingdom.Corresponding author's details (also author for reprint requests): Dr Mark Rosenthal, Department of Paediatric Respiratory Medicine, Royal Brompton Hospital, London SW3 6NP Email: M. Rosenthal@rbht.nhs.uk.

PMID: 22922408 [PubMed - as supplied by publisher]

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 5. Blood. 2012 Aug 22. [Epub ahead of print]Impact of hydroxyurea on clinical events in the BABY HUG trial.Thornburg CD, Files BA, Luo Z, Miller ST, Kalpatthi R, Iyer R, Seaman P, Lebensburger J, Alvarez O, Thompson B, Ware RE, Wang WC.SourceDuke University Medical Center, Durham, NC, United States;AbstractBABY HUG was a Phase III multicenter, randomized, double-blind placebo-controlled clinical trial of hydroxyurea in infants (beginning at 9-18 months of age) with sickle cell anemia (SCA). An important secondary objective of this study was to compare clinical events between the hydroxyurea and placebo groups. One hundred and ninety-three subjects were randomized to hydroxyurea (20 mg/kg/day) or placebo; there were 374 patient-years of on-study observation. Hydroxyurea was associated with statistically significantly lower rates of initial and recurrent episodes of pain, dactylitis, ACS and hospitalization; even infants who were asymptomatic at enrollment had less dactylitis as well as fewer hospitalizations and transfusions if treated with hydroxyurea. Despite expected mild myelosuppression, hydroxyurea was not associated with an increased risk of bacteremia or serious infection. These data provide important safety and efficacy information for clinicians considering hydroxyurea therapy for very young children with SCA. This clinical trial is registered with the NIH (NCT00006400, www.clinicaltrials.gov).

PMID: 22915643 [PubMed - as supplied by publisher]

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 6. Adv Skin Wound Care. 2012 Sep;25(9):420-428.Sickle Cell Disease and Leg Ulcers.Ladizinski B, Bazakas A, Mistry N, Alavi A, Sibbald RG, Salcido R.SourceBarry Ladizinski, MD, BS • Clinical Research Fellow • Duke University Medical Center • Durham, North Carolina Andrea Bazakas, BS • Clinical Trials Assistant II • Duke University Medical Center • Durham, North Carolina Nisha Mistry, MD, BSc, FRCPC(Derm), DABD • Community Dermatologist • Mississauga, Ontario, Canada Afsaneh Alavi, MD, FRCPC(Derm) • Dermatologist and Wound Care Consultant • Women's College Hospital • Toronto, Ontario, Canada R. Gary Sibbald, BSc, MD, Med, FRCPC(Med Derm), MACP, FAAD, MAPWCA • Professor of Public Health and Medicine • University of Toronto • Toronto, Ontario, Canada • Director • International Interprofessional Wound Care Course & Masters of Science in Community Health (Prevention & Wound Care) • Dalla Lana School of Public Health • University of Toronto • President World Union of Wound Healing Societies • Clinical Editor • Advances in Skin & Wound Care • Ambler, Pennsylvania Richard Salcido, MD • Editor-in-Chief • Advances in Skin & Wound Care • Ambler, Pennsylvania • Course Director • Annual Clinical Symposium on Advances in Skin & Wound Care • William Erdman Professor • Department of Rehabilitation Medicine • Senior Fellow • Institute on Aging • Associate • Institute of Medicine and Bioengineering • University of Pennsylvania Health System • Philadelphia, Pennsylvania.AbstractPURPOSE:: To enhance the learner's competence with knowledge of sickle cell disease (SCD) and its relationship to leg ulcers. TARGET AUDIENCE:: This continuing education activity is intended for physicians and nurses with an interest in skin and wound care. OBJECTIVES:: After participating in this educational activity, the participant should be better able to:1. Demonstrate knowledge of SCD-associated leg ulcer pathophysiology, symptomatology, diagnostic testing, and risk factors.2. Apply knowledge of pain management and treatment options for SCD-associated leg ulcers to patient care scenarios. ABSTRACT: Sickle cell disease is a genetic disorder of hemoglobin synthesis leading to a deformation of the red blood cell. This disorder is associated with painful, slow-to-heal leg ulcers. This article discusses the wound bed preparation paradigm as a guide to the treatment of sickle cell-associated leg ulcers.

PMID: 22914039 [PubMed - as supplied by publisher]

Sickle Cell News for July 2012.
 
Sickle cell trait can cause sudden cardiac death in black athletes: Why is this controversial? http://www.eurekalert.org/pub_releases/2012-07/mhif-sct072312.phpWhile some published research has hinted at the connection between the sickle cell trait and sudden cardiac death among young, athletic African-American males, which was initially observed in black military recruits 25 years ago, a new study with the first sizeable patient series definitively confirms this risk for these individuals during competitive sports.The sickle cell trait, for which all U.S. African Americans are tested at birth, affects approximately 8 percent of the population. The Minneapolis Heart Institute Foundation maintains a 32-year-old forensic database, the U.S. Sudden Death in Athletes Registry, which researchers interrogated to determine the frequency, epidemiology and clinical profile of sickle cell trait-related deaths in a large population of competitive athletes for the purposes of this study. The findings from this registry show there is "convincing evidence of a causal relationship between the sickle cell trait and the deaths of young, black competitive athletes, especially football players," says the study's senior author Barry J. Maron, MD, director of the Hypertrophic Cardiomyopathy Center at the Minneapolis Heart Institute Foundation. The study will be published in the October edition of the American Journal of Cardiology, but currently is available online.Prior to this registry study, a lawsuit and previous research prompted the National Collegiate Athletic Association (NCAA) to conduct mandatory screening for the sickle cell trait in all division I athletes prior to their participation in college athletics. As of yet, the NCAA has not expanded to the screening program to division II or III athletes, nor has the association shared its data with the medical community. Of the 2,462 athlete deaths in the U.S. Sudden Death in Athletes Registry, which provides the first and largest published record of athletes who died of sudden cardiac death on an athletic field, 23 occurred in association with the sickle cell trait (ages 12 to 22 years): 21 were male and all were African Americans. The deaths most often occurred in college-aged athletes (19-23 years) during football conditioning drills early in the season, and with those exposed to high environmental temperatures."The registry was initially started by Dr. Maron to help the medical community understand why any athlete would collapse on a field," explains the study's lead author Kevin M. Harris, MD, co-director of the Acute Aortic Dissection Program and director of the echocardiography laboratory at the Minneapolis Heart Institute® at Abbott Northwestern Hospital in Minneapolis. "We decided to assess the connection between the sickle cell trait and sudden death within our large registry," Harris continues. "As a result, we have developed the first sizable series of competitive athletes in whom sickle cell trait was associated with otherwise unexplained sudden, unexpected collapse and death."Maron, who has been assessing cardiovascular-related deaths of young athletes for approximately 35 years, is surprised at the level of skepticism he's witnessed regarding the sickle cell trait as a cause of sudden in young, black athletes, even in the scientific medical community. In the study, the researchers concluded that the sickle cell trait "can be associated with largely unpredictable sudden collapse and death and apparent predilection for African American college football players during conditioning. Understanding the risks, mechanisms, and event triggers of the sickle cell trait may allow lifesaving alterations in training methods to be implemented."In order to implement such lifesaving alterations in training methods, particularly due to the unpredictable nature of sickle cell trait events, there needs to be a greater understanding and acceptance of this lethal connection. "To not acknowledge this link between sickle cell trait and sudden death creates the possibility of a failure to fully protect the athlete community," Maron said. http://www.ajconline.org/article/S0002-9149(12)01531-7/abstract

Texas Children's Center for Global Health celebrates 1-year anniversary of successful sickle cell disease screening program in Angola http://www.marketwatch.com/story/texas-childrens-center-for-global-health-celebrates-1-year-anniversary-of-successful-sickle-cell-disease-screening-program-in-angola-2012-07-19Exactly one year after launching the Angolan Sickle Cell Initiative, Texas Children's Center for Global Health is proud to announce that more than 16,000 babies have been screened for this once-overlooked killer of children in Africa. Encouraged by the First Lady of Angola, and aided by the vision and support of Mr. Ali Moshiri, president, Chevron Africa and Latin America Exploration and Production Company and Dr. Mark Kline, physician-in-chief at Texas Children's Hospital and chairman of pediatrics at Baylor College of Medicine (BCM), the Angolan sickle cell initiative was launched in March 2011 by the Texas Children's Center for Global Health. With financial support from Chevron Corporation, and in collaboration with the Ministry of Health of Angola, this bold initiative quickly reached fruition on July 19, 2011, when babies born at Lucrecia Paim Maternity Hospital in the Luanda province became the first Angolan infants to ever receive newborn screening for sickle cell disease. This landmark program in Angola serves as a bold step forward in their efforts to improve healthcare in the country. "Until last year, no newborn infant was tested for sickle cell disease in Angola," explains Dr. Russell E. Ware, Director of the Texas Children's Center for Global Health and a professor of pediatrics at BCM. "Sadly, many die in the first two years of life from preventable infections related to the disease, because they are never properly diagnosed. But after witnessing the success of our first year screening babies for sickle cell in Luanda, we know we can tip the scales and make a sea change of difference for these babies." Angola has one of the highest child mortality rates in the world, and each year, approximately 2 percent of babies (close to 10,000) are born with sickle cell disease. Of these babies, the majority die before they reach 5 years-old. With proper intervention, almost all babies with sickle cell disease will reach adulthood, as has been proven in the United States, where newborn infants are tested soon after birth and given access to proper treatment. Thanks to the Angolan Sickle Cell Initiative, more than 16,000 babies have already been tested, and several hundred babies with sickle cell disease have been identified. "The goal of the Sickle Cell program is to not only provide screening, diagnosis and care for this neglected population of children, but to also develop a training and education program that will be sustainable from within Angola and easily replicated in countries that need it the most," says Meg Ferris, Ph.D., MPH, administrative director Texas Children's Center for Global Health. Angolan obstetrical nurses have been trained to collect the blood samples, Angolan laboratory technicians have become expert in diagnostic testing, and Angolan pediatric nurses and doctors have learned to provide life-saving medical interventions, all important facets to making the program sustainable from within the country. Over the next 12 months, the program will expand to a second Angolan province to screen even more babies and save more lives. In addition, plans are in the works to expand the program into more countries in Africa and South America. For more information http://globalhealth.texaschildrens.org/ . Further information on the Sickle Cell Disease Screening Program can be accessed here: http://www.youtube.com/watch?v=06bmu2HcCGo&list=PL46A8079C258A67D0&index=3 Conference in Bahrain http://www.gulf-daily-news.com/NewsDetails.aspx?storyid=334648 

HUNDREDS of patients and doctors are expected to attend a major conference on sickle cell disease next month at the Gulf Air Club, Salmabad. The Bahrain Society for Sickle Cell Anaemia Patients Care is organising the annual event to spread awareness about the disease.This year's meeting follows a spate of deaths among sickle cell sufferers, with nine patients dying in the space of less than three weeks from June 28 to July 19.The society has so far registered 17 sickle cell deaths this year and hopes to promote its ID card initiative during the meeting on August 1, which starts at 9pm and is expected to be attended by Health Minister Sadiq Al Shehabi and other officials.It is pushing for a scheme in which sickle cell patients are issued ID cards listing details such as blood type, CPR number and other health-related information so they receive proper treatment. The gathering will feature speeches by society members and a special film showcasing the work of sickle cell activist Jehad Rabia, who died last month from the disease.She was among several Bahraini patients who died at Salmaniya Medical Complex (SMC), forcing health authorities to respond to a spate of deaths. "A short film of Jehad's work with the society will be showcased along with another Bahraini film titled Wabel, that highlights the stages of life of a sickle cell patient," said society member Samah Hussain. She said she hoped the fact that it fell in Ramadan would encourage more people to take part in the event."We want more people to know about the disease and those living with it," she added. After several deaths of sickle cell patients in a short period, Mr Al Shehabi this month admitted errors had been made in the treatment of sufferers. He ordered officials to come up with a comprehensive plan to tackle the problem and treat patients.Campaigners have blamed inadequate facilities at SMC and shortage of Intensive Care Unit beds for sickle cell deaths, although officials maintain they have tried their best to provide patients with the best care. The GDN reported on July 20 that as a temporary measure it was planning to treat male sickle cell patients at the Ebrahim Khalil Kanoo Community Medical Centre in Salmaniya.According to ministry figures, 18,000 sickle cell patients receive treatment at SMC. However, society members say the total number of carriers of the disease, excluding those being treated, is about 65,000. A BD2.5 million, four-storey facility that will treat all patients with blood diseases including sickle cell is now being built.The 90-bed facility expected to open early next year will treat all patients with blood diseases, but should be of particular help to those suffering from sickle cell disease. Also see http://www.gulf-daily-news.com/NewsDetails.aspx?storyid=334370Video

ResourcesNew  CDC  Videos PostedNew Posting : Dr. Lanetta Jordan’s presentation on “Sickle Cell Trait – What Every CBO Needs To Know”  at mms://realaudio.service.emory.edu/SOM/PA/PLATT/SICKLE/CDCJordan.wmv2012-05-24 - Dr. Paula Tanabe, Duke UniversityStreaming Video: mms://realaudio.service.emory.edu/SOM/PA/PLATT/SICKLE/CDCertreat.wmvPDF of Presentation Handout: Sickle Cell Disease and Emergency Department Use2012-04-26 - Dr. Kathryn Hassell, University of Colorado Denver Streaming Video: View RecordingPDF of Presentation Handout: Sickle Cell – Adult Providers NetworkSchedule of  Free CDC 2012 Webinars “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 The purpose of this webinar series is to offer a hemoglobinopathies learning collaborative platform for providers, consumers, educators, and scientists. Hemoglobinopathy Webinars are archived at http://scinfo.org   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. Otherwise, please RSVP the location and number of participants for alternative international conference line access. 7/26: -Canciled 8/23:

Translating Research to Policy Dr. Shawn Bediako, University of Maryland, Baltimore County 9/27: Improving Quality of Care for Sickle Cell Pediatrics in the Emergency Department Dr. James Moses, Boston Medical Center 10/25: Strategies from the Field – Data Collection and Harmonization CDC’s Division of Blood Disorders and RuSH Project States November/December: --- No Webinars---See all the previous CDC Sickle Cell Webinars and instructions to view or listen to future events see:  http://scinfo.org/world-wide-resources/cdc-webinars-hemoglobinopathies-and-public-healthNew Web ResourceThe Sickle Cell Society - http://www.sicklecellsociety.org   Newsletter for July. See the news about the Atlanta Blood Disorders conference on page 9 by Iyamide Thomas.http://issuu.com/communityeventsuk/docs/sickle_cell_society_newsletter_july_2012_pages_1-2?mode=window&backgroundColor=%23222222  NHS- UK Sickle Cell Acute Painful Episode Guideline PublicationYou may be interested to know that the clinical guidelines for Sickle Cell Acute Painful Episode were published on Wednesday 27th June and are now available on the NICE website at http://www.nice.org.uk/CG143  You can find the consultation comments and responses on this page: http://guidance.nice.org.uk/CG/Wave24/6 If you have any queries on the Institute’s guideline development process or the progress of a specific guideline, please do not hesitate to contact me.Thank you for your contributions to the development of these guidelines.Many thanks and kind regards, Laura DoneganiClinical Guidelines Coordinator National Institute for Health and Clinical ExcellenceLevel 1A | City Tower | Piccadilly Plaza | Manchester M1 4BT | United Kingdom
Tel: 44 (0)161 870 3147 | Fax: 44 (0)207 061 9755Web: http://nice.org.uk NHS Sickle Cell and Thalassaemia Screening Programme Statement on HbA2 analysis The work that the NHS Sickle Cell and Thalassaemia Screening Programme has been doing with UK NEQAS has shown biases between different analytical platforms for HbA2 [1]. These findings are obviously of concern when there is a national cut off for the diagnosis of beta thalassaemia carriers. The NHS Sickle Cell and Thalassaemia Screening programme is working with the international bodies of the International Federation of Clinical Chemistry and Laboratory Medicine (IFCC ), the International Council for Standardization in Haematology (ICSH) and the World Health Organisation (WHO), who have also recognised the problem and are working with manufacturers. An international standard is in the early stage of preparation and a statement on the use of the current WHO standard is awaited.  Haematology laboratories in the UK should be aware of these problems and ensure they have optimised their methods as much as possible. When considering replacement purchases, haematology laboratories should review all available evidence including the UK NEQAS report. In the meantime laboratories should consider including a statement on this issue in their local risk assessment.  If you have any queries about this issue, please contact the NHS Sickle Cell and Thalassaemia Screening Programme Centre by telephone on 020 7848 6634, or email at the following address: haemscreening@kcl.ac.uk 1.    Batterbee, H., et al., 2010. Evaluation of UK NEQAS (H) Hb A2 and related performance data, Watford: UK NEQAS (H).  The full report is available at http://sct.screening.nhs.uk/cms.php?folder=2419#fileid11145Working to Improve Sickle Cell Healthcare (WISCH) Website at http://www.nichq.org/our_projects/sickle_cell_landing_page.htmlWorking to Improve Sickle Cell Healthcare (WISCH) is NICHQ’s portfolio of projects focused on improving the quality of care for individuals with sickle cell disease across the lifespan. These projects include the Sickle Cell Disease Newborn Screening Program and the Sickle Cell Disease Treatment Demonstration Program, both of which are funded through the Health Resources and Services Administration (HRSA).Free Sickle Cell Pain Fact sheet at http://www.inthefaceofpain.com/content/uploads/2011/09/factsheet_Sickle_Cell.pdf Articles in the Medical Literature for July1. J Pediatr Health Care. 2012 Jul 18. [Epub ahead of print]A Transition Pilot Program for Adolescents With Sickle Cell Disease.Hankins JS, Osarogiagbon R, Adams-Graves P, McHugh L, Steele V, Smeltzer MP, Anderson SM.AbstractINTRODUCTION: Transition from pediatric to adult care is challenging for adolescents with chronic illnesses, including those with sickle cell disease (SCD). We describe a pilot program created to facilitate transition from pediatric to adult care by helping adolescents with SCD identify an adult medical home.METHODS: We investigated the feasibility of this program by evaluation of overall participation, satisfaction, and acceptance. A secondary objective was to compare the proportion of adolescents who fulfilled a first appointment with an adult hematologist among participants and nonparticipants.RESULTS: During the first 18 months of the program, 83 adolescents were invited and 34 (41%) agreed to participate; 25 (74%) completed their first visit within 3 months after leaving the pediatric program, compared with 16 of 49 (33%) of nonparticipants (p = .0002). Overall, 41 of 83 adolescents (49%) completed an appointment with an adult SCD program, regardless of program participation, in contrast with 11 of 75 adolescents (15%) who did so during the 18 months before the program was created (p < .0001).DISCUSSION: This transition pilot program was feasible, and most adolescent participants with SCD established an adult medical home.Copyright © 2012 National Association of Pediatric Nurse Practitioners. Published by Mosby, Inc. All rights reserved.

PMID: 22819193 [PubMed - as supplied by publisher]

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 2. Transfus Clin Biol. 2012 Jul 18. [Epub ahead of print]Relevance of alloimmunization in haemolytic transfusion reaction in sickle cell disease.Noizat-Pirenne F.SourceÉtablissement français du sang Île-de-France, hôpital Henri-Mondor, 51, avenue du Maréchal-de-Lattre-de-Tassigny, 94010 Créteil, France; Inserm U955, hôpital Henri-Mondor, 51, avenue du Maréchal-de-Lattre-de-Tassigny, 94010 Créteil, France.AbstractTransfusion remains a key treatment in sickle cell disease. The occurrence of a delayed haemolytic transfusion reaction is not rare and is a life-threatening event. The main cause of delayed haemolytic transfusion reaction is production of alloantibodies against red blood cell antigens. The high rate of alloimmunization in sickle cell disease patients is mainly due to the differences of red blood groups between patients of African descent, and the frequently Caucasian donors. From an immuno-haematological point of view, delayed haemolytic transfusion reaction in sickle cell disease patients has specific features: classical antibodies known to be haemolytic can be encountered, but otherwise non significant antibodies, autoantibodies and antibodies related to partial and rare blood groups are also frequently found in individuals of African descent. In some cases, there are no detectable antibodies. As alloimmunization remains the main cause of delayed haemolytic transfusion reaction, it is extremely important to promote blood donation by individuals of African ancestry to make appropriate blood available.Copyright © 2012 Elsevier Masson SAS. All rights reserved.

PMID: 22818360 [PubMed - as supplied by publisher]

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 3. J Thromb Haemost. 2012 Jul 20. doi: 10.1111/j.1538-7836.2012.04861.x. [Epub ahead of print]Hydroxyurea is associated with reduction of hypercoagulability markers in sickle cell anemia.Colella MP, de Paula EV, Conran N, Machado-Neto JA, Annicchino-Bizzacchi JM, Costa FF, Saad ST, Traina F.SourceHematology and Hemotherapy Center - University of Campinas/Hemocentro UNICAMP, Instituto Nacional de Ciência e Tecnologia do Sangue, Campinas, São Paulo, Brazil.AbstractSeveral lines of evidence indicate that sickle cell anemia (SCA) is a state of increased hemostatic activation [1-4]. SCA patients present an elevated rate of thrombotic complications including pulmonary embolism, stroke and pregnancy-related venous thromboembolism [5]. Hydroxyurea (hydroxycarbamide) is currently one of the main pillars of SCA management, improving both clinical complications and mortality in SCA [6] and has several well-defined beneficial effects that could contribute to an inhibition of the hypercoagulability state in SCA. These include a reduction of phosphatidylserine exposure by erythrocytes, reduction of adhesive properties of erythrocytes and leukocytes, endothelial activation, nitric oxide depletion, platelet activation and adhesive properties [7-9]. © 2012 International Society on Thrombosis and Haemostasis.© 2012 International Society on Thrombosis and Haemostasis.

PMID: 22817333 [PubMed - as supplied by publisher]

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 4. Med Sci Sports Exerc. 2012 Jul 17. [Epub ahead of print]ACSM and CHAMP Summit on SCT: Mitigating Risks for Warfighters and Athletes.O'Connor FG, Bergeron MF, Cantrell J, Connes P, Harmon KG, Ivy E, Kark J, Klossner D, Lisman P, Meyers BK, O'Brien K, Ohene-Frempong K, Thompson AA, Whitehead J, Deuster PA.Source1Department of Military and Emergency Medicine, Uniformed Services University of the Health Sciences, Bethesda, MD; 2National Institute for Athletic Health and Performance, Sanford USD Medical Center, Sioux Falls, SD; 3Department of Preventive Medicine and Biometrics, Uniformed Services University of the Health Sciences, Bethesda, MD; 4UMR Inserm 665, Universite Antilles-Guyane, Pointe-a-Pitre, Guadeloupe; 5Departments of Family Medicine and Orthopaedics and Sports Medicine, University of Washington, Seattle, WA; 6National Heart, Lung, and Blood Institute, Bethesda, MD; 7Hematology-Oncology Division, Howard University Hospital, Washington, DC; 8National Collegiate Athletic Association, Indianapolis, IN; 9Division of Preventive Medicine, Walter Reed Army Institute of Research, Silver Spring, MD; 10Madigan Army

Sickle Cell News for June 2012
June 19 World Sickle Cell Day celebrated around the world
Read the stories:
http://www.bet.com/news/health/2012/06/19/world-sickle-cell-day-is-today.html
http://www.insidetoronto.com/community/health/article/1379275--malvern-s-taibu-spreads-awareness-on-sickle-cell-disease
http://www.businessdayonline.com/NG/index.php/component/content/article/126-health/39934-sickle-cell-disease-how-well-are-people-informed
http://www.plenglish.com/index.php?option=com_content&task=view&id=518051&Itemid=1
 
Chicago Woman Cured Of Sickle Cell Disease at 33 Chicagoan Ieshea Thomas is the first Midwest patient to receive a successful stem cell transplant to cure her sickle cell disease without chemotherapy in preparation for the transplant. University of Illinois Hospital & Health Sciences System physicians performed the procedure using medication to suppress her immune system and one small dose of total body radiation right before the transplant. The transplant technique is relatively uncommon and is a much more tolerable treatment for patients with aggressive sickle cell disease who often have underlying organ disease and other complications, says Dr. Damiano Rondelli, professor of medicine at UIC, who performed Thomas's transplant. The procedure initially allows a patient's own bone marrow to coexist with that of the donor. Since the patient's bone marrow is not completely destroyed by chemotherapy or radiation prior to transplant, part of the immune defense survives, lessening the risk of infection. The goal is for the transplanted stem cells to gradually take over the bone marrow’s role to produce red blood cells -- normal, healthy ones. Thomas, 33, had her first sickle cell crisis when she was just 8 months old. Her disease became progressively worse as an adult, particularly after the birth of her daughter. She has spent most of her adult life in and out of hospitals with severe pain and has relied on repeated red blood cell transfusions. Her sickle cell disease also caused bone damage requiring two hip replacements. "I just want to be at home with my daughter every day and every night,"said Thomas, who depends on family to help care for her daughter during her frequent hospitalizations. This type of stem cell transplant is only possible for patients who have a healthy sibling who is a compatible donor. Thomas' sister was a match and agreed to donate blood stem cells through a process called leukapheresis. Several days prior to leukapheresis, Thomas' sister was given drugs to increase the number of stem cells released into the bloodstream. Her blood was then processed through a machine that collects white cells, including stem cells. The stem cells were frozen until the transplant. Last Nov. 23, four bags of frozen stem cells were delivered to the hospital's blood and marrow transplant unit. One by one, the bags were thawed and hung on an IV pole for infusion into Thomas. The procedure took approximately one hour. Her 13-year-old daughter, Miayatha, was at her bedside. Six months after the transplant, Thomas is cured of sickle cell disease and no longer requires blood transfusions.  "The donor cells have taken over completely, and blood tests show no sickle cell disease," said Rondelli, director of the blood and marrow transplant program at UI Hospital. Thomas continues to take medication to prevent rejection of the donor stem cells. About 25 adults have received a similar chemotherapy-free stem cell transplant for sickle cell disease in recent years at the National Institutes of Health in Bethesda, Md. Approximately 85 percent have been cured. "Sickle cell disease is devastating -- both emotionally and physically," said Dr. Dennis Levinson, a private rheumatologist in Chicago and clinical associate professor of medicine at UIC, who has taken care of Thomas for the past 16 years. "I've been terribly frustrated with Ieshea's disease over the years, and I've cared for many other sickle cell patients who have died." Levinson says the stem cell transplant provides new hope for patients who often live day-to-day on painkillers and who are often misunderstood by clinicians. As the former chief of medicine at the now closed Michael Reese Hospital, he said he has cared for many patients with sickle cell anemia and was determined to seek out the best treatment option for Thomas. Sickle cell disease primarily affects people of African descent. It is an inherited defect of the red blood cells that causes them to be shaped like a crescent, or sickle. These abnormal cells deliver less oxygen to the body's tissues and can result in severe pain, stroke and organ damage. Approximately one in every 500 African Americans born in the U.S. has sickle cell disease. The disease affects 80,000 Americans of different ethnic backgrounds. The University of Illinois Hospital & Health Sciences System provides comprehensive, life-long care for pediatric and adult sickle cell patients. For more information, visit http://www.hospital.uillinois.edu. [Editor's note: Video report available at http://youtu.be/E89xXeeby-A and photos available at http://newsphoto.lib.uic.edu/v/bone_marrow_transplant/.] Children Stories needed from around the worldThe authors of Hope & Destiny: The Patient and Parent's Guide to Sickle Cell Disease and Sickle Cell Trait are planning a children’s version and would like parents to send a short 1 page story written by their school aged child with sickle cell disease that would encourage a child with sickle cell in another country.. Any selected story  will be published anonymously with the parent’s permission. There is no compensation, only the joy of being published: Send stories with your child’s age and initials to aplatt@emory.edu  New Web resourceNational Center on Birth Defects and Developmental Disabilities, Centers for Disease Control and Prevention2011 Annual Report on Sickle Cell Disease and Thalassemia at  http://www.cdc.gov/ncbddd/AboutUs/blood-disorders-sicklecell.html
 
Video Resources
New  CDC  Videos Posted
2012-05-24 - Dr. Paula Tanabe, Duke University
Streaming Video: mms://realaudio.service.emory.edu/SOM/PA/PLATT/SICKLE/CDCertreat.wmv
PDF of Presentation Handout: Sickle Cell Disease and Emergency Department Use
2012-04-26 - Dr. Kathryn Hassell, University of Colorado Denver
Streaming Video: View Recording
PDF of Presentation Handout: Sickle Cell – Adult Providers NetworkSchedule of  Free CDC 2012 Webinars
“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 The purpose of this webinar series is to offer a hemoglobinopathies learning collaborative platform for providers, consumers, educators, and scientists.
This month’s webinar will take place on Thursday, June 28th from 2:00pm – 3:00pm ET, featuring
Dr. Lanetta Jordan’s presentation on “Sickle Cell Trait – What Every CBO Needs To Know” Hemoglobinopathy Webinars are archived at http://scinfo.org
 
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. Otherwise, please RSVP the location and number of participants for alternative international conference line access.
 
7/26: Improved Survival of Children and Adolescents with Sickle Cell Disease Dr. Charles Quinn, Cincinnati Children's Hospital Medical Center
8/23: Translating Research to Policy Dr. Shawn Bediako, University of Maryland, Baltimore County
9/27: Improving Quality of Care for Sickle Cell Pediatrics in the Emergency Department Dr. James Moses, Boston Medical Center
10/25: Strategies from the Field – Data Collection and Harmonization CDC’s Division of Blood Disorders and RuSH Project States
November/December: --- No Webinars---
See all the previous CDC Sickle Cell Webinars and instructions to view or listen to future events see:  http://scinfo.org/world-wide-resources/cdc-webinars-hemoglobinopathies-and-public-healthFree ASH webinars  http://hematology.org/Meetings/Webinars/6832.aspx
Pain in Sickle cell disease and  Stroke, Renal Disease, and Treatment with Hydroxyurea in Adults with Sickle Cell Disease
 Articles in the Medical Literature for June
1. Patient Educ Couns. 2012 May 31. [Epub ahead of print]
Use of social support during communication about sickle cell carrier status.
Bradford L, Roedl SJ, Christopher SA, Farrell MH.
Source
Center for Patient Care and Outcomes Research, Medical College of Wisconsin, Milwaukee, WI, USA.
Abstract
OBJECTIVE:
To examine the use of social support behaviors by primary care providers during delivery of positive newborn screening results for Sickle Cell Anemia carrier status.
METHODS:
Transcripts from 125 primary care providers who conveyed Sickle Cell Anemia carrier status to standardized parents were content analyzed using categories derived from Cutrona and Suhr's social support taxonomy. Frequencies and cross-tabulation matrices were calculated to study providers' social support utilization.
RESULTS:
Results showed most primary care providers (80%) incorporate social support behaviors into delivery of Sickle Cell Anemia carrier results and most frequently employed social network (61.6%) and informational support (38.4%) behaviors. Providers used tangible aid (8%), esteem (1.6%), and emotional support (9.6%) behaviors less frequently.
CONCLUSION:
Cutrona and Suhr's taxonomy may be a useful tool for assessing supportive communication during the delivery of Sickle Cell Anemia carrier status and could be incorporated into population scale assessments of communication quality assurance.
PRACTICE IMPLICATIONS:
Primary care providers may need training in how to adapt supportive behaviors to parents' needs during communication of Sickle Cell Anemia carrier status. They also may benefit from specific training about how to use esteem and emotional support.
Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.
PMID: 22658247 [PubMed - as supplied by publisher]
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 2. Anemia. 2012;2012:428137. Epub 2012 May 14.
FK228 Analogues Induce Fetal Hemoglobin in Human Erythroid Progenitors.
Makala L, Di Maro S, Lou TF, Sivanand S, Ahn JM, Pace BS.
Source Department of Pediatrics, Georgia Health Sciences University, Augusta, GA 30912, USA.
Abstract
Fetal hemoglobin (HbF) improves the clinical severity of sickle cell disease (SCD), therefore, research to identify HbF-inducing agents for treatment purposes is desirable. The focus of our study is to investigate the ability of FK228 analogues to induce HbF using a novel KU812 dual-luciferase reporter system. Molecular modeling studies showed that the structure of twenty FK228 analogues with isosteric substitutions did not disturb the global structure of the molecule. Using the dual-luciferase system, a subgroup of FK228 analogues was shown to be inducers of HbF at nanomolar concentrations. To determine the physiological relevance of these compounds, studies in primary erythroid progenitors confirmed that JMA26 and JMA33 activated HbF synthesis at levels comparable to FK228 with low cellular toxicity. These data support our lead compounds as potential therapeutic agents for further development in the treatment of SCD.
PMCID: PMC3359661 Free PMC Article
PMID: 22655179 [PubMed - in process]
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3. Am J Respir Crit Care Med. 2012 Jun 7. [Epub ahead of print]
A Novel Molecular Signature for Elevated Tricuspid Regurgitation Velocity in Sickle Cell Disease.
Desai AA, Zhou T, Ahmad H, Zhang W, Mu W, Trevino S, Wade MS, Raghavachari N, Kato GJ, Peters-Lawrence MH, Thiruvoipati T, Turner K, Artz N, Huang Y, Patel AR, Yuan JX, Gordeuk VR, Lang RM, Garcia JG, Machado RF.
Source
Medicine, University of Illinois at Chicago, Chicago, Illinois, United States.
Abstract
RATIONALE:
Pulmonary hypertension defined by right heart catheterization and an increased tricuspid regurgitation jet velocity (TRV≥2.5m/s) on transthoracic echocardiography both independently confer increased mortality in sickle cell disease.
OBJECTIVE:
We explored the utility of peripheral blood mononuclear cell-derived gene signatures as biomarkers for an elevated tricuspid regurgitation jet velocity in sickle cell disease. Methods &
MEASUREMENTS:
Twenty-seven sickle patients underwent echocardiography and of peripheral blood mononuclear cell isolation for expression profiling and 112 sickle patients were genotyped for SNPs.
MAIN RESULTS:
Genome-wide gene and miRNA expression profiles were correlated against tricuspid regurgitation velocity, yielding 631 transcripts and 12 miRNAs. Support vector machine analysis identified a 10-gene signature including GALNT13 (encoding polypeptide N-acetylgalactosaminyltransferase 13) that discriminates patients with and without increased TRV with 100% accuracy. This finding was then validated in a cohort of sickle patients without (n=10) and with pulmonary hypertension (n=10, 90% accuracy). Increased tricuspid regurgitation velocity-related miRNAs revealed strong in silico binding predictions of miR-301a to GALNT13 corroborated by microarray analyses demonstrating an inverse correlation between their expression. A genetic association study comparing patients with an elevated (n=49) versus normal (n=63) tricuspid regurgitation velocity revealed 5 significant SNPs within GALNT13 (p<0.005), four trans-acting (p<2.1e-07) and one cis-acting (p=0.6e-04) expression quantitative trait loci (eQTLs) upstream of the adenosine-A2B receptor gene (ADORA2B).
CONCLUSION:
These studies validate the clinical utility of genomic signatures as potential biomarkers and highlight ADORA2B and GALNT13 as potential candidate genes in sickle-associated elevated tricuspid regurgitation velocity.
PMID: 22679008 [PubMed - as supplied by publisher]
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4. Hemoglobin. 2012 Jun 19. [Epub ahead of print]
Newborn Screening Shows a High Incidence of Sickle Cell Anemia in Central India.
Jain DL, Sarathi V, Upadhye D, Gulhane R, Nadkarni AH, Ghosh K, Colah RB.
Source Department of Paediatrics, Government Medical College , Nagpur-440009 , India.
Abstract
There is limited data on the incidence of sickle cell anemia in Central India; we therefore conducted a study to estimate the incidence of this disease in Central India. Mothers who delivered a live baby at the Government Medical College, Nagpur, India were screened for the presence of the sickle cell hemoglobin {Hb S: [β6 (A3) Glu →Val, GAG >GTG]} using the solubility test within 48 hours of delivery. Infants of mothers who showed the presence of Hb S then underwent Hb analysis by high performance liquid chromatography (HPLC). A total of 8243 mothers was screened, 1178 of whom were positive. One thousand, one hundred and sixty-two infants of mothers with a positive solubility test underwent Hb analysis by HPLC; 530 infants were normal, while 536 were heterozygous for Hb S (sickle cell trait), 88 babies were homozygous for Hb S (sickle cell anemia), while another eight babies had other Hb abnormalities. The incidence of sickle cell anemia was highest in the Scheduled caste group (1:50). We concluded that the incidence of sickle cell anemia is high in central India.
PMID: 22712682 [PubMed - as supplied by publisher]
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5. Infect Genet Evol. 2012 Jun 12. [Epub ahead of print]
The emergence and maintenance of sickle cell hotspots in the Mediterranean.
Penman BS, Gupta S, Buckee CO.
Source
Department of Zoology, University of Oxford, UK.
Abstract
Genetic disorders of haemoglobin (haemoglobinopathies), including the thalassaemias and sickle cell anemia, abound in historically malarious regions, due to the protection they provide against death from severe malaria. Despite the overall spatial correlation between malaria and these disorders, inter-population differences exist in the precise combinations of haemoglobinopathies observed. Greece and Italy present a particularly interesting case study: their high frequencies of beta thalassaemia speak to a history of intense malaria selection, yet they possess very little of the strongly malaria protective mutation responsible for sickle cell anemia, despite historical migrational links with Africa where high frequencies of sickle cell occur. Twentieth century surveys of beta thalassaemia and sickle cell in Greece, Sicily and Sardinia have revealed striking sickle cell 'hotspots' - places where the frequency of sickle cell approaches that seen in Africa while neighboring populations remain relatively sickle cell free. It remains unclear how these hotspots have been maintained over time without sickle cell spreading throughout the region. Here we use a metapopulation model to show that (i) epistasis between the alpha and beta forms of thalassaemia can restrict the spread of sickle cell through a network of linked subpopulations, and (ii) the emergence of sickle cell hotspots requires relatively low levels of gene flow, but the aforementioned epistasis increases the chances of hotspots forming.
Copyright © 2012. Published by Elsevier B.V.
PMID: 22704979 [PubMed - as supplied by publisher]
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 6. Cytokine. 2012 Jun 14. [Epub ahead of print]
Plasma BDNF and PDGF-AA levels are associated with high TCD velocity and stroke in children with sickle cell anemia.
Hyacinth HI, Gee BE, Adamkiewicz TV, Adams RJ, Kutlar A, Stiles JK, Hibbert JM.
Source Genomics and Hemoglobinopathies Training Program, Department of Microbiology, Biochemistry and Immunology, Morehouse School of Medicine, 720 Westview Drive SW, Atlanta, GA, USA.
Abstract
Sickle cell anemia (SCA) associated cerebrovascular disease includes vascular remodeling, abnormal cerebral blood flow (CBF) and infarction. We studied the relationships between plasma brain derived neurotropic factor (BDNF), platelet derived growth factors (PDGF-AA and -AB/BB) and high trans-cranial Doppler (TCD) velocity as an indication of CBF velocity. Baseline plasma samples from 39 children (19 SCA with abnormal/high TCD [SATCD], 13 SCA with normal TCD [SNTCD] and 7 healthy non-SCA), were assayed for BDNF, PDGF-AA and -AB/BB plus 11 other cytokines. The sensitivity, specificity and usefulness of these biomarkers for stroke prediction was investigated. All subject groups were of similar age and gender distribution. Mean BDNF was significantly higher among SATCD than SNTCD (p=0.004) as was mean PDGF-AA (p=0.001). Similarly, mean PDGF-AA was higher among SCA subjects who developed stroke than those who did not (p=0.012). Elevated BDNF and PDGF-AA were good predictors of the presence of abnormally high CBF velocity and were both associated with severity of anemia. Elevated PDGF-AA predicted risk for stroke development. Stroke incidence and high TCD velocity were associated with elevated BDNF and PDGF-AA. These findings suggest a role for BDNF and PDGF-AA in the patho-physiological mechanism of cerebrovascular disease in SCA.
Copyright © 2012 Elsevier Ltd. All rights reserved.
PMID: 22704695 [PubMed - as supplied by publisher]
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7. Anemia. 2012;2012:492428. Epub 2012 Jun 4.
Integrating interactive web-based technology to assess adherence and clinical outcomes in pediatric sickle cell disease.
Crosby LE, Barach I, McGrady ME, Kalinyak KA, Eastin AR, Mitchell MJ.
Source
College of Medicine, University of Cincinnati, Cincinnati, OH 45221, USA.
Abstract
Research indicates that the quality of the adherence assessment is one of the best predictors for improving clinical outcomes. Newer technologies represent an opportunity for developing high quality standardized assessments to assess clinical outcomes such as patient experience of care but have not been tested systematically in pediatric sickle cell disease (SCD). The goal of the current study was to pilot an interactive web-based tool, the Take-Charge Program, to assess adherence to clinic visits and hydroxyurea (HU), barriers to adherence, solutions to overcome these barriers, and clinical outcomes in 43 patients with SCD age 6-21 years. Results indicate that the web-based tool was successfully integrated into the clinical setting while maintaining high patient satisfaction (>90%). The tool provided data consistent with the medical record, staff report, and/or clinical lab data. Participants reported that forgetting and transportation were major barriers for adherence to both clinic attendance and HU. A greater number of self-reported barriers (P < .01) and older age (P < .05) were associated with poorer clinic attendance and HU adherence. In summary, the tool represents an innovative approach to integrate newer technology to assess adherence and clinical outcomes for pediatric patients with SCD.
PMCID: PMC3372407 Free PMC Article
PMID: 22701785 [PubMed - in process]
Related citations

 
8. Ultrasound Med Biol. 2012 Jun 12. [Epub ahead of print]
Stenosis or Hyperperfusion in Sickle Cell Disease - Ultrasound Assessment of Cerebral Blood Flow Volume.
Doepp F, Kebelmann-Betzing C, Kivi A, Schreiber SJ.
Source
Department of Neurology, University Hospital Charité, Berlin, Germany.
Abstract
Increased blood flow velocity (BFV) in basal cerebral arteries measured by transcranial color-coded sonography (TCCS) is a stroke risk factor in sickle cell disease (SCD). Raised BFV may be caused by vessel narrowing or by hyperperfusion. In 44 SCD patients and 14 controls, intracranial arterial BFVs and global cerebral blood flow (CBF) were analyzed by TCCS and extracranial duplex ultrasound, respectively. Magnetic resonance imaging and magnetic resonance angiography were performed in all patients with pathologic intracranial BFV rise. Intracranial BFVs and CBF in SCD were significantly higher than in controls. CBF in SCD correlated with BFV in all intracranial arteries and correlated inversely with age and hemoglobin values. Magnetic resonance angiography failed to demonstrate any stenosis in our SCD patients, thus raised intracranial BFVs must be interpreted as an anemia-dependent cerebral hyperperfusion. These findings suggest that the pathomechanism of stenosis-derived arterio-arterial embolism might be less relevant in SCD-related ischemic stroke, and other factors like small vessel disease or sickle cell-induced microvascular blood clotting have to be considered.
Copyright © 2012 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.
PMID: 22698503 [PubMed - as supplied by publisher]
Related citations

 
9. Cochrane Database Syst Rev. 2012 Jun 13;6:CD005406.
Fluid replacement therapy for acute episodes of pain in people with sickle cell disease.
Okomo U, Meremikwu MM.
Source
Viral Diseases Programme, Medical Research Council (UK), Atlantic Boulevard, Fajara, Gambia, P.O. Box 273.
Abstract
BACKGROUND:
Treating vaso-occlusive painful crises in people with sickle cell disease is complex and requires multiple interventions. Extra fluids are routinely given as adjunct treatment, regardless of the individual's state of hydration with the aim of slowing or stopping the sickling process and thereby alleviating pain.
OBJECTIVES:
To determine the optimal route, quantity and type of fluid replacement for people with sickle cell disease with acute painful crises.
SEARCH METHODS:
We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register which comprises of references identified from comprehensive electronic database searches and handsearches of relevant journals and abstract books of conference proceedings.We also conducted searches of EMBASE (November 2007), LILACS and www.ClinicalTrials.gov (05 January 2010).Date of most recent search of the Group's Haemoglobinopathies Trials Register: 09 February 2012.
SELECTION CRITERIA:
Randomised and quasi-randomised controlled trials that compared the administration of supplemental fluids adjunctive to analgesics by any route in people with any type of sickle cell disease during an acute painful episode, under medical supervision (inpatient, day care or community).
DATA COLLECTION AND ANALYSIS:
No relevant trials have yet been identified.
MAIN RESULTS:
Sixteen trials were identified by the initial search. Of these, 15 were not suitable for inclusion in this review and one study is awaiting further assessment.
AUTHORS' CONCLUSIONS:
Treating vaso-occlusive crises is complex and requires multiple interventions. Extra fluids, generally oral or intravenous, are routinely administered during acute painful episodes to people with sickle cell disease regardless of the individual's state of hydration. Reports of their use during these acute painful episodes do not state the efficacy of any single route, type or quantity of fluid compared to another. However, there are no randomised controlled trials that have assessed the safety and efficacy of different routes, types or quantities of fluid. This systematic review identifies the need for a multicentre randomised controlled trial assessing the efficacy and possible adverse effects of different routes, types and quantities of fluid administered to people with sickle cell disease during acute painful episodes.
PMID: 22696351 [PubMed - in process]
Related citations

 
10. Acad Emerg Med. 2012 Jun;19(6):664-72. doi: 10.1111/j.1553-2712.2012.01364.x.
Risk Factors for Increased ED Utilization in a Multinational Cohort of Children With Sickle Cell Disease.
Glassberg JA, Wang J, Cohen R, Richardson LD, Debaun MR.
Source
From the Department of Emergency Medicine (JG, LDR) and the Department of Health Evidence and Policy (JW), Mount Sinai School of Medicine, New York, NY; Pediatrics, Drexel University College of Medicine, Division of Pediatrics, and St. Christopher's Hospital for Children (RC), Philadelphia, PA; and the Departments of Pediatrics and Medicine, Vanderbilt Children's Hospital (MRD), Nashville, TN.
Abstract
ACADEMIC EMERGENCY MEDICINE 2012; 19:664-672 © 2012 by the Society for Academic Emergency Medicine ABSTRACT: Objectives: The objective was to identify clinical, social, and environmental risk factors for increased emergency department (ED) use in children with sickle cell disease (SCD). Methods: This study was a secondary analysis of ED utilization data from the international multicenter Silent Cerebral Infarct Transfusion (SIT) trial. Between December 2004 and June 2010, baseline demographic, clinical, and laboratory data were collected from children with SCD participating in the trial. The primary outcome was the frequency of ED visits for pain. A secondary outcome was the frequency of ED visits for acute chest syndrome. Results: The sample included 985 children from the United States, Canada, England, and France, for a total of 2,955 patient-years of data. There were 0.74 ED visits for pain per patient-year. A past medical history of asthma was associated with an increased risk of ED utilization for both pain (rate ratio [RR] = 1.28, 95% confidence interval [CI] = 1.04 to 1.58) and acute chest syndrome (RR = 1.60, 95% CI = 1.03 to 2.49). Exposure to environmental tobacco smoke in the home was associated with 73% more ED visits for acute chest syndrome (RR = 1.73, 95% CI = 1.09 to 2.74). Each $10,000 increase in household income was associated with 5% fewer ED visits for pain (RR = 0.95, 95% CI = 0.91 to 1.00, p = 0.05). The association between low income and ED utilization was not significantly different in the United States versus countries with universal health care (p = 0.51). Conclusions: Asthma and exposure to environmental tobacco smoke are potentially modifiable risk factors for greater ED use in children with SCD. Low income is associated with greater ED use for SCD pain in countries with and without universal health care.
© 2012 by the Society for Academic Emergency Medicine.
PMCID: PMC3375948 [Available on 2013/6/1]
PMID: 22687181 [PubMed - in process]
Related citations

Sickle Cell Conferences and Events

July 5-7, 2012   Venetian / Palazzo Hotel Las Vegas -  Association of Nigerian Physicians in the Americas “The 18th Annual ANPA Convention & Scientific Assembly will be held July 5-7, 2012 at the Venetian / Palazzo Hotel in Las Vegas, Nevada. The theme for this year’s assembly will be “Righting the Wrong in Sickle Cell Disease”, and “Information Technology in Medical Practice”. The ANPA Annual Meeting features three full-day meetings, providing participants’ knowledge related to the challenges facing minority health care providers in the provision of clinical and therapeutic services for diseases and conditions related to a variety of medical specialties. The meeting will feature member lecturers providing state of the art technological advances that will impact the practice of medicine. The annual convention is of great value to our membership and other health care professionals by providing them with opportunities to keep abreast of developments in various areas of health care delivery and also offering continuing medical education (CME) credits. For more information please visit www.anpa.org or call 913.402.7102. “
 
September 25 – 29, 2012  The Sickle Cell Disease Association of America 40th Annual Conference Baltimore MD
The conference will be held September 25 – 29, 2012 at the Baltimore Marriott Waterfront Hotel in Baltimore, MD. We promise that this will be one of the most educational and empowering events to take place within the sickle cell community!  http://www.sicklecelldisease.org/index.cfm?page=annual-convention

May Sickle Cell News

June 19 World Sickle Cell Day

In the year 2008, the General Assembly of the United Nations adopted a resolution which determines sickle cell disease as a public health problem and one of the world’s foremost genetic disease, requiring heightened awareness and activism, diagnosis and management. The result of the resolution was that June 19th was declared as World Sickle Cell to increase awareness of the condition all over the world.

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.

In honor of World Sickle Cell day, Scell Media is offering  afree edition of SICKLE CELL news at http://www.scdjournal.com/free.html
 NIH SELECTS 11 CENTERS OF EXCELLENCE IN PAIN EDUCATIONNIH Pain Consortium partners with selected health professional schools The National Institutes of Health Pain Consortium has selected 11 health professional schools as designated Centers of Excellence in Pain Education (CoEPEs). The CoEPEs will act as hubs for the development, evaluation, and distribution of pain management curriculum resources for medical, dental, nursing and pharmacy schools to enhance and improve how health care professionals are taught about pain and its treatment. Twenty institutes, centers and offices at NIH are involved in the consortium. "Virtually all health professionals are called upon to help patients suffering from pain," said NIH Director Francis S. Collins, M.D., Ph.D. "These new centers will translate current research findings about pain management to fill what have been recognized as gaps in curricula so clinicians in all fields can work with their patients to make better and safer choices about pain treatment."   The new Centers of Excellence in Pain Education were selected by the NIH Pain Consortium <http://painconsortium.nih.gov/index.html> after a contract solicitation process and review. The awardees are the University of Washington, Seattle; the University of Pennsylvania Perelman School of Medicine, Philadelphia; Southern Illinois University, Edwardsville; the University of Rochester, N.Y.; the University of New Mexico, Albuquerque; the Harvard School of Dental Medicine, Boston; the University of Alabama at Birmingham; the Thomas Jefferson University School of Medicine, Philadelphia; the University of California, San Francisco; the University of Maryland, Baltimore; and the University of Pittsburgh. Many of the new CoEPEs will build curricula across several of their health professional schools.  Chronic pain affects approximately 100 million Americans, costing up to $635 billion in medical treatment and lost productivity, and producing immeasurable suffering for people of every age. Yet, pain treatment is not taught extensively in many health professional schools, and clinical approaches can be inconsistent. The curricula developed by the CoEPEs will advance the assessment, diagnosis, and safe treatment of a wide variety of pain conditions while minimizing the abuse of opioid pain relievers. They will include multiple case-based scenarios, many taught in video or electronic formats popularly used in contemporary academic settings. Types of pain of particular interest to the NIH Pain Consortium are rehabilitation pain, arthritis and musculoskeletal pain, neuropathic pain, and headache pain. In addition, the curricula will teach about the pathophysiology and pharmacology of pain and its treatment, the latest research in complementary and integrative pain management, factors that contribute to both under- and over-prescribing of pain medications, and how pain manifests itself differently by gender, in children, in older adults and in diverse populations.    "While opioid pain medications have improved the quality of life for millions who suffer from pain, they can also produce harmful consequences, including addiction," said NIDA Director Nora D. Volkow, M.D., a member of the consortium's executive committee. "These new CoEPEs can help prevent negative outcomes by designing curricula that promote appropriate screening and management of chronic pain patients, along with education about the risks of prescription drug abuse."  NIH supports the full spectrum of pain research from basic understanding of pain mechanisms through translation of discoveries into treatments and prevention strategies. In FY 2011, NIH supported $386 million in research focused on chronic pain, not including the related diseases that often cause chronic pain, such as cancer, arthritis, diabetes, and stroke. The details of individual pain-focused grants are publicly available on the NIH RePORTER website <http://projectreporter.nih.gov/reporter.cfm>. Enhancing education of pain care professionals was highlighted in the June 2011 Institute of Medicine report, "Relieving Pain in America: A Blueprint for Transforming Prevention, Care, Education, and Research."   About the NIH Pain Consortium:  The NIH Pain Consortium was established to enhance pain research and promote collaboration among researchers across the many NIH Institutes and Centers that have programs and activities addressing pain. Its goals include the development of a comprehensive and forward-thinking pain research agenda for the NIH; to identify key opportunities in pain research within NIH and the scientific community; to increase visibility for pain research; and  to pursue the pain research agenda through Public-Private partnerships. For more information on the Pain Consortium, visit <http://painconsortium.nih.gov/index.html>.
 

New Book Resource

 

"Living With Sickle Cell Disease: The Struggle to Survive" A Memoir by Author Judy Gray Johnson with Leroy Williams Jr.

This is a well written self- published  life account of growing up with sickle cell disease in the 1960s and the problems with treatment into 2012. There are many accounts of unfavorable Emergency department encounters commonly shared by those with sickle cell disease. The book is factual and medically accurate.

http://www.judygrayjohnson.com/home.html

http://www.blacknews.com/news/living_with_sickle_cell_disease_judy_gray_johnson101.shtml

 

Video Resources

Schedule of  Free CDC 2012 Webinars

6/28: Sickle Cell Trait – What Every CBO Needs to KnowDr. Lanetta Jordan, Memorial Regional Hospital

7/26: Improved Survival of Children and Adolescents with Sickle Cell DiseaseDr. Charles Quinn, Cincinnati Children's Hospital Medical Center

8/23: Translating Research to PolicyDr. Shawn Bediako, University of Maryland, Baltimore County

9/27: Improving Quality of Care for Sickle Cell Pediatrics in the Emergency DepartmentDr. James Moses, Boston Medical Center

10/25: Strategies from the Field – Data Collection and HarmonizationCDC’s Division of Blood Disorders and RuSH Project States

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

See all the previous CDC Sickle Cell Webinars and instructions to view or listen to future events see: http://scinfo.org/world-wide-resources/cdc-webinars-hemoglobinopathies-and-public-health

Free ASH webinars http://hematology.org/Meetings/Webinars/6832.aspx

Pain in Sickle cell disease and Stroke, Renal Disease, and Treatment with Hydroxyurea in Adults with Sickle Cell Disease

 
Articles in the Medical Literature for May

1. Cochrane Database Syst Rev. 2012 May 16;5:CD004344.

Treatment for avascular necrosis of bone in people with sickle cell disease.

Martí-Carvajal AJ,Solà I,Agreda-Pérez LH.

Source

Universidad de Carabobo and Iberoamerican Cochrane Network, Valencia, Edo. Carabobo, Venezuela.

Abstract

BACKGROUND:

Avascular necrosis of bone is a frequent and severe complication of sickle cell disease and its treatment is not standardised.

OBJECTIVES:

To determine the impact of any surgical procedure compared with other surgical interventions or non-surgical procedures, on avascular necrosis of bone in people with sickle cell disease in terms of efficacy and safety.

SEARCH METHODS:

We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Haemoglobinopathies Trials Register, comprising references identified from comprehensive electronic database searches and handsearches of relevant journals and abstract books of conference proceedings. Additional trials were sought from the reference lists of papers identified by the search strategy.Date of the most recent search of the Group's Haemoglobinopath