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Two New Drugs Help Relieve Sickle-Cell Disease. But Who Will Pay?

The Food and Drug Administration recently approved two transformative new treatments for sickle-cell disease, the first in 20 years. But the drugs are wildly expensive, renewing troubling questions about access to cutting-edge medicines. 

Adakveo, made by Novartis, can prevent episodes of nearly unbearable painthat occur when malformed blood cells get stuck in blood vessels. Approved only for patients aged 16 and over, it is delivered as an infusion once a month.

Oxbryta,made by Global Blood Therapeutics, can prevent severe anemia from the diseasethat can lead to permanent damage to the brain and other organs. A daily pill, the drug is approved for patients ages 12 and older. 

Each treatment is priced at around $100,000 a year and must be taken for life. While it is not uncommon for a drug treating a rare disease to carry such a high price, there are 100,000 people with sickle-cell disease in the United States, and millions more around the world.

ASH and FDA Unveil New Recommendations to Guide Clinical Development of SCD Therapies  

The American Society of Hematology (ASH) has released the most comprehensive set of recommendations to date, aimed at establishing uniformity and global standards for clinical trial endpoints used to evaluate new therapies for sickle cell disease (SCD). The new recommendations – published in two companion papers in the current issue of Blood Advances– are the result of seven expert and patient led panels convened by ASH and the U.S. Food and Drug Administration (FDA) to improve the design of clinical trials for new SCD therapies, including promoting broader use of patient reported outcomes and biomarkers as clinical endpoints.


Papers in Blood Advances:

• End points for sickle cell disease clinical trials: patient-reported outcomes, pain, and the brain

• End points for sickle cell disease clinical trials: renal and cardiopulmonary, cure, and low-resource settings

ASH’s New Clinical Practice Guideline on Cardiopulmonary and Kidney Disease in SCD

In 2016, the American Society of Hematology (ASH) initiated an effort to develop clinical practice guidelines on sickle cell disease (SCD). ASH appointed 61 clinical experts, five methodologists and 10 patient representatives to review evidence and form recommendations on SCD. The recommendations address treatment of both adult and pediatric SCD and the systematic review of evidence was led by the Mayo Clinic Evidence-Based Practice Center. ASH has published the first chapter of the SCD guidelines on: cardiopulmonary and kidney disease in SCD. In total, five chapters will be published with the remaining four chapters scheduled to be published in the first quarter of 2020. Learn more about these guidelines, the development process, and find additional resources by visiting hematology.org/SCDguidelines

ASH’s 61st Annual Meeting Recap
The American Society of Hematology (ASH)’s 61st Annual Meeting and Exposition took place December 7-10, 2019, in Orlando, Florida. The meeting provided an invaluable educational experience and the opportunity to review thousands of scientific abstracts, highlighting updates and exciting developments in the hottest topics in hematology, including sickle cell disease (SCD). In addition to sessions and abstracts, this year’s meeting featured a SCD Kiosk where attendees could view ASH’s SCD curriculum for fellows, learn about ASH’s SCD initiative, hear five minute rapid fire SCD presentations on ASH’s new SCD Guidelines,and sign up for ASH’s Find a Hematologist portal – a tool designed to help patients locate hematologists in their area. For a SCD roundup at the ASH Meeting, click here. For those who missed a session or two, they are now available for purchase on ASH on Demand.  Additionally, three studies presented during the Meetinghighlighted efforts to offer better treatments and more comprehensive care for people living with SCD. An overview of these studies and the late breaking abstract on encouraging results seen with a novel approach to gene therapy for SCD, will be published in easy to understand language in a future SCDC Update

First Industry Datasets Submitted to ASH Research Collaborative Data Hub
The ASH Research Collaborative (ASH RC) has collaborated with two industry leaders, Novartis and Amgen, to include de-identified patient data from three separate studies of nearly 500 patients living with Sickle Cell Disease (SCD) and more than 1,000 patients with multiple myeloma as part of an unprecedented data sharing initiative. Novartis and Amgen are the first two pharmaceutical companies to provide datasets to the growing collection of data in the ASH RC Data Hub, a platform designed to accelerate scientific discovery by gathering clinical data on rare blood diseases. Click herefor more information. 

SCD Training and Mentoring Program (STAMP)

Many adults living with sickle cell disease (SCD) have challenges accessing care due to a national shortage of SCD-trained hematologists. To help address this gap, the Health Resources and Services Administration is collaborating with the U.S. Department of Health and Human Services’ Office of Minority Health to deliver a new telehealth series for primary care providers called STAMP, the SCD Training and Mentoring Program. This series, taught by hematologists using a case study-based, tele-mentoring approach, will cover the basics of SCD care, such as pain management, hydroxyurea, and preventive services. Participating primary care providers will also be eligible to request on-demand consultative services from hematologists to further support patient care. The next trainings are scheduled for January 2020. Learn more here


CDC’s Sickle Cell Data Collection (SCDC) Program Announcements

• SCDC Data Brief: Hydroxyurea Use Among Medicaid Beneficiaries with Sickle Cell Disease in California and Georgia, 2006–2016: shows that during an 11-year period, the use of hydroxyurea (HU) among Medicaid beneficiaries with sickle cell disease (SCD) who lived in California or Georgia increased. However, many beneficiaries with severe complications of SCD do not use HU.

• SCDC Brief: Access to Care for Children: examines geographical access to specialized care, based upon a one-hour drive radius to either daily or periodic specialty care clinics.

• MAPS: The Geography of Sickle Cell Disease in Georgia: maps that allow users to hover over an area or marker for data on SCD births in Georgia, 2004-2016.

• CDC’s new videos feature people with SCD of diverse backgrounds who share that SCD can affect anyone, no matter what you look like or where your family comes from: 
          • “Sickle Cell Has Many Faces.” (for a general audience)”
          • A Message for Healthcare Providers: Sickle Cell Has Many Faces.
 

• Mimi’s Story: mentions that throughout her life, healthcare providers have doubted Mimi when she told them she has SCD. This has caused delays in Mimi getting the treatment she needs. 

2019 Year-End ASH Advocacy Efforts Related to SCD 

The American Society of Hematology (ASH) continues to work with federal agencies and the U.S. Congress to help enhance and expand government activities in sickle cell disease (SCD) research, training, and services. ASH is working with congressional champions to raise awareness for SCD on Capitol Hill and to have legislation introduced to strengthen current federal SCD programs. ASH and the Society’s advocates took a number of steps in 2019 to advance the Society’s SCD-focused advocacy agenda. For more information, click here.
Funding Opportunity on Improving Transition Care
A new Funding Opportunity Announcement (FOA) from Agency for Healthcare Research & Quality will test promising health information technology solutions to improve communication and care coordination during care transitions. Poorly managed transitions can lead to costly, unsafe, and low-quality care. This FOA: PA-20-068 “Improving Quality of Care and Patient Outcomes During Care Transitions (R01),” focuses on improving care transitions between multiple providers and different institutional care settings with a focus on patients, their families, and communities. Applications will be accepted on a rolling basis; the first due date is February 5. Learn more, here.  


Cure Sickle Cell Initiative 

The Cure Sickle Cell Initiative (CureSCi) was created by the National Institute of Health (NIH)’s National Heart, Lung and Blood Institute (NHLBI) in 2017 and was formally launched in September 2018 to accelerate the development of curative genetic therapies for sickle cell disease (SCD) within the next 5-10 years. The Initiative’s membership is comprised of NIH and NHLBI stakeholders, members of the patient and advocacy communities, industry, academia, and other federal partners. CureSCi is approaching the challenge of finding a cure through multiple avenues, one of which is by establishing common data elements (CDEs) in cooperation with the CureSCi’s Data Consortium and other investigators/partners that have been working in this space for some time. By reviewing and curating the data elements from previous SCD clinical studies with consideration for common endpoints and outcomes, the Initiative is seeking to establish “common data elements” (CDEs). Once defined, these CDEs will be included in future NHLBI funded clinical trials. This approach will promote consistency in future data collection and improve data harmonization for cross-study comparisons and analysis. It will also speed investigators’ timelines to be able to focus on the significant questions and to better leverage knowledge from prior studies. Further information is available at the Initiative’s website: https://curesickle.org/.
  

Help Raise Awareness for Blood Donation in January

January is National Blood Donor Month, a month to focus on celebrating those blood donors who save lives and to inspire friends and family to become blood donors. Blood transfusions are one of the most critical treatments for the 100,000 Americans living with sickle cell disease. It is essential to have a robust supply of compatible red cells ready; the best supply source has been found to come from those of similar race and ethnic backgrounds. However, only five percent of blood donors are of African ancestry. It is time for this to change.  How can you help in January? Share these marketing materials and resourcesfrom Association of Donor Relations Professionals, an International Division of America’s Blood Centers, throughout the month of January and encourage your constituents to spread awareness of the need for blood. Blood has an expiration date and needs to be continuously donated to ensure a robust supply is maintained.

Articles in the medical literature

Prevalence of Bacteremia in Febrile Patients With Sickle Cell Disease: Meta-Analysis of Observational Studies Pediatr Emerg Care 2019 Dec 16[Online ahead of print]Authors Natasha Bala  1 Jennifer Chao  2 Delna John  2 Richard Sinert  2 Abstract Objective: Pneumococcal vaccination has decreased the bacteremia rate in both the general pediatric and sickle cell disease (SCD) populations. Despite this decrease, and an increasing concern for antibiotic resistance, it remains standard practice to obtain blood cultures and administer antibiotics in all febrile (>38.5°C) patients with SCD. We conducted a systematic review and meta-analysis of the available studies of the prevalence of bacteremia in febrile patients with SCD. Methods: We searched the medical literature up to November 2018 in PUBMED, EMBASE, and Web of Science with terms epidemiology, prevalence, bacteremia, and sickle cell anemia. We only included studies with patients after 2000, when the pneumococcal 7-valent conjugate (PCV7) vaccine became widely available. The prevalence of bacteremia [95% confidence interval (CI)] was calculated by dividing the number of positive blood cultures by the number of febrile episodes. The I statistic measured heterogeneity between prevalence estimates. Bias in our studies was quantified by the Newcastle-Ottawa Quality Assessment Scale. Results: Our search identified 228 citations with 10 studies meeting our inclusion/exclusion criteria. The weighted prevalence of bacteremia across all studies was 1.9% (95% CI, 1.22%-2.73%), and for Streptococcus pneumoniae bacteremia, it was 0.31% (95% CI, 0.16%-0.50%). Risks for bacteremia except central lines could not be determined because of the low prevalence of the outcome. Conclusions: There appears to be a need to develop a risk stratification strategy to guide physicians to manage febrile patients with SCD based on factors including, but not limited to, history and clinical examination, vaccination status, use of prophylactic antibiotics, laboratory values, likely source of infection, and accessibility to health care. Full-text links  Wolters Kluwer 
3. Emerging Drugs in Randomized Controlled Trials for Sickle Cell Disease: Are We on the Brink of a New Era in Research and Treatment? Expert Opin Investig Drugs 2019 Dec 17[Online ahead of print]Authors Alessandro Matte  1 Maria Domenica Cappellini  2 Achille Iolascon  3 Federti Enrica  1 Lucia De Franceschi  1 Abstract Introduction: Sickle cell disease (SCD) is caused by a mutation in the HBB gene which is key for making a component of hemoglobin. The mutation leads to the formation of an abnormal hemoglobin molecule called sickle hemoglobin (HbS). SCD is a chronic, complex disease with a multiplicity of pathophysiological targets; it has high morbidity and mortality.Hydroxyurea has for many years been the only approved drug for SCD; hence the development of new therapeutics is critical.Areas covered: This article offers an overview of the key studies of new therapeutic options for SCD. We searched the PubMed database and Cochrane Database of Systemic Reviews for agents in early phase clinic trials and preclinical development.Expert Opinion: Although knowledge of SCD has progressed, patient survival and quality of life must be improved. Phase II and III clinical trials investigating pathophysiology-based novel agents show promising results in the clinical management of SCD acute events. The design of long-term clinical studies is necessary to fully understand the clinical impact of these new therapeutics on the natural history of the disease. Furthermore, the building of global collaborations will enhance the clinical management of SCD and the design of primary outcomes of future clinical trials. Keywords: haemoglobinopathies; inflammatory vasculopathy; new treatment; sickle cell disease. Full-text links  Taylor & Francis 
4. National Comparative Audit of Blood Transfusion: 2014 Audit of Transfusion Services and Practice in Children and Adults With Sickle Cell Disease Transfus Med 2019 Dec 17[Online ahead of print]Authors Sara Trompeter  1   2 Paula Bolton-Maggs  1 Kate Ryan  3 Farrukh Shah  4 Lise Estcourt  5 Gavin Cho  6 David Rees  7 Derek Lowe  8 Baaba Davis  9 Abstract Objectives: To determine the organisational resources in place; what blood was being transfused, why, how, where, when and by whom; whether laboratory support and policies met standards for patients with sickle cell disease (SCD). Background: SCD affects 14 000 people in the United Kingdom (UK). Standards and guidelines do not cover all aspects of transfusion in SCD and there are no data on their use; people may become very sick without warning presenting to non-specialist hospitals; blood services are increasingly supplying units for transfusion in SCD with little data on their use. Methods: A retrospective audit of transfusion services/practice for people with SCD who had received a transfusion in January-July 2014 in participating hospitals in the UK and Republic of Ireland (ROI). Results: Eighty-four hospitals submitted 1290 cases, 75% of cases came from 18 hospitals submitting 25 or more cases. Transfusions (91.2% [1164/1276]) were administered to patients with HbSS, 60% (732/1227) of patients needed Rh CE negative blood. Transfusion episodes (4528) were recorded, of which 84% were elective. Stroke prevention accounted for 42% of all transfusions; adults received 56% of transfusions of which 50% were automated red cell exchange (RCE), children received 44% of transfusions of which 87% were simple transfusions. Conclusions: There was a paucity of appropriate clinical management protocols, adequately trained staff and network arrangements. The high numbers of children being transfused, disparity in transfusion modality between children and adults and the high frequency of the CE negative Rh phenotype were noted. © 2019 British Blood Transfusion Society. 39 references Full-text links  Wiley 
5. Treatment of Dental Complications in Sickle Cell Disease Cochrane Database Syst Rev , 12, CD011633 2019 Dec 16Authors Priti Mulimani  1 Samir K Ballas  2 Adinegara Bl Abas  3 Laxminarayan Karanth  4 Abstract Background: Sickle cell disease is the most common single gene disorder and the commonest haemoglobinopathy found with high prevalence in many populations across the world. Management of dental complications in people with sickle cell disease requires special consideration for three main reasons. Firstly, dental and oral tissues are affected by the blood disorder resulting in several oro-facial abnormalities. Secondly, living with a haemoglobinopathy and coping with its associated serious consequences may result in individuals neglecting their oral health care. Finally, the treatment of these oral complications must be adapted to the systemic condition and special needs of these individuals, in order not to exacerbate or deteriorate their general health. Guidelines for the treatment of dental complications in this population who require special care are unclear and even unavailable in many aspects. Hence this review was undertaken to provide a basis for clinical care by investigating and analysing the existing evidence in the literature for the treatment of dental complications in people with sickle cell disease. This is an update of a previously published review. Objectives: To assess methods of treating dental complications in people with sickle cell disease. Search methods: We searched the Cochrane Cystic Fibrosis and Genetic Disorders Review Group’s Haemoglobinopathies Trials Register, compiled from electronic database searches and handsearching of journals and conference abstract books. Date of last search: 01 August 2019. Additionally, we searched nine online databases (PubMed, Google Scholar, ClinicalTrials.gov, WHO International Clinical Trials Registry Platform, Literature in the Health Sciences in Latin America and the Caribbean database, African Index Medicus, Index Medicus for South East Asia Region, Index Medicus for the Eastern Mediterranean Region, Indexing of Indian Medical Journals). We also searched the reference lists of relevant articles and reviews and contacted haematologists, experts in fields of dentistry, organizations, pharmaceutical companies and researchers working in this field. Date of last search: 07 November 2019. Selection criteria: We searched for published or unpublished randomised controlled studies of treatments for dental complications in people with sickle cell disease. Data collection and analysis: Two review authors intended to independently extract data and assess the risk of bias of the included studies using standard Cochrane methodologies; however, no studies were identified for inclusion in the review. Main results: No randomised controlled studies were identified. Authors’ conclusions: This Cochrane Review did not identify any randomised controlled studies assessing interventions for the treatment of dental complications in people with sickle cell disease. There is an important need for randomised controlled studies in this area, so as to identify the most effective and safe method for treating dental complications in people with sickle cell disease. Copyright © 2019 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd. Publication types Review Full-text links  Wiley 
6. Health Literacy in Adolescents With Sickle Cell Disease: The Influence of Caregiver Health Literacy J Spec Pediatr Nurs , e12284 2019 Dec 11[Online ahead of print]Author Elizabeth P Caldwell  1  Abstract Purpose: After patients with sickle cell disease (SCD) transfer from pediatric care to adult care, significant morbidity and mortality occurs. There are many possible contributors to the success or failure of this transition. One hypothesis is that health literacy influences this transition from pediatric to adult health care. The purpose of this study was twofold: (a) to examine the relationship between caregiver and adolescent health literacy levels in adolescents with SCD; and (b) to further describe individual traits contributing to health literacy levels in adolescents with SCD as described by pilot data. Design and methods: This cross-sectional, descriptive correlational study included the administration of the newest vital sign (NVS) health literacy instrument to 59 dyads of adolescent patients with SCD and their caregivers in a large, tertiary care center in Dallas, Texas. Convenience sampling was utilized for recruitment. Caregiver health literacy levels, age, current grade level, annual household income, caregiver education level, number of annual healthcare encounters, and adolescent health literacy levels were correlated to determine relationships amongst variables. Results: There was no significant relationship between caregiver and adolescent health literacy levels in this population. Adolescent health literacy NVS scores were positively correlated with adolescent age, r(58) = .468, p < .001, caregiver income, r(46) = .293, p = .023, and caregiver highest education level, r(56) = .318, p = .008. Only adolescent age was a significant predictor of adolescent health literacy NVS scores, β = .485 (standard error [SE] = .109), p = .001. None of the other predictors in the model were significant, including the relationship between caregiver and adolescent health literacy NVS scores, β = .065 (SE = .131), p = .633. In addition, although caregiver income and highest education level were positively correlated with adolescent health literacy NVS scores in the bivariate analysis, these relationships were nonsignificant while controlling for each other, adolescent age, and the other variables in the model. Practice implications: This study gives insight on potential practice and research initiatives to evaluate the health literacy of adolescents, with and without SCD, both now and in the future. Keywords: adolescents; emergency care; health literacy; literacy; sickle cell disease. © 2019 Wiley Periodicals, Inc. Grant support University Research Committee Mid-Range Grant/Baylor University Full-text links  Wiley 
7. Sickle Cell Disease: At the Crossroads of Pulmonary Hypertension and Diastolic Heart Failure Heart 2019 Dec 10[Online ahead of print]Authors Katherine C Wood  1 Mark T Gladwin  2   3 Adam C Straub  2   4  Abstract Sickle cell disease (SCD) is caused by a single point mutation in the gene that codes for beta globin synthesis, causing haemoglobin polymerisation, red blood cell stiffening and haemolysis under low oxygen and pH conditions. Downstream effects include widespread vasculopathy due to recurring vaso-occlusive events and haemolytic anaemia, affecting all organ systems. Cardiopulmonary complications are the leading cause of death in patients with SCD, primarily resulting from diastolic heart failure (HF) and/or pulmonary hypertension (PH). HF in SCD often features biventricular cardiac hypertrophy and left ventricular (LV) diastolic dysfunction. Among HF cases in the general population, approximately half occur with preserved ejection fraction (HFpEF). The insidious evolution of HFpEF differs from the relatively acute evolution of HF with reduced ejection fraction. The PH of SCD has diverse origins, which can be pulmonary arterial (precapillary), pulmonary venous (postcapillary) or pulmonary thromboembolic. It is also appreciated that patients with SCD can develop both precapillary and postcapillary PH, with elevations in LV diastolic pressures, as well as elevations in transpulmonary pressure gradient and pulmonary vascular resistance. Regardless of the cause of PH in SCD, its presence significantly reduces functional capacity and increases mortality. PH that occurs in the presence of HFpEF is usually of postcapillary origin. This review aims to assemble what has been learnt from clinical and animal studies about the manifestation of PH-HFpEF in SCD, specifically the contributions of LV diastolic dysfunction and myocardial fibrosis, in an attempt to gain an understanding of its evolution. Keywords: Heart failure with preserved ejection fraction; myocardial disease basic science; primary pulmonary hypertension; secondary pulmonary hypertension. © Author(s) (or their employer(s)) 2019. No commercial re-use. See rights and permissions. Published by BMJ. Conflict of interest statement Competing interests: AS receives research support from Bayer Pharmaceuticals. MG is listed as a coinventor on an NIH government patent for the use of nitrite salts in cardiovascular diseases and on provisional patents for the use of recombinant neuroglobin and heme-based molecules as antidotes for CO poisoning; the former has been licensed by United Therapeutics and the latter by Globin Solutions, Inc. MG is a coinvestigator in a research collaboration with Bayer Pharmaceuticals to evaluate riociguat as a treatment for patients with SCD.Publication types Review Full-text links  HighWire 
8. International Differences in Outpatient Pain Management: A Survey of Sickle Cell Disease J Clin Med , 8 (12) 2019 Dec 3Authors Nadirah El-Amin  1 Paul Nietert  2 Julie Kanter  3  Abstract Vaso-occlusive pain crises are the hallmark of sickle cell disease (SCD) and the primary reason for health care utilization. Both national and international guidelines recommend aggressive intravenous opioids, intravenous fluids and anti-inflammatory therapy as the mainstay of treatment for acute SCD pain. However, many vaso-occlusive crises are managed at home with oral medication and supportive care. There are no guidelines on home medication management of SCD-related pain, likely due to the lack of well-defined endpoints for acute events and the lack of funding for already approved pain medications. Amplifying this issue is the growing concern for opioid abuse and misuse in the United States (US) and internationally. This study aimed to evaluate differences in opioid prescribing practices among providers treating SCD in the US and internationally. A survey was disseminated electronically to known providers using a combination of purposive and snowball sampling strategy. There were 127 responses and 17 countries represented. US providers were more likely to prescribe opioids (p < 0.001) and were more likely to be “very comfortable” prescribing opioids than non-US prescribers (p < 0.001). US providers also tended to prescribe more tablets per patient of stronger opioids than non-US physicians. US physicians were more likely to be concerned that patients were abusing opioids than non-US physicians (32% vs. 27%, p < 0.05). There are significant variations in how different parts of the world manage pain in the outpatient setting for SCD. Identifying optimal home pain management strategies is necessary to improve care and long-term outcomes in SCD. Keywords: chronic pain; opioid; sickle cell. Conflict of interest statement The authors declare no conflicts of interest.Grant support 1UL1TR001450/TR/NCATS NIH HHS/United States 5U54GM104941/GM/NIGMS NIH HHS/United States Full-text links  Multidisciplinary Digital Publishing Institute (MDPI) 
9. Family Resilience From the Perspective of Caregivers of Youth With Sickle Cell Disease J Pediatr Hematol Oncol 2019 Dec 4[Online ahead of print]Authors Steven K Reader  1   2 Ashley Pantaleao  1   3 Colleen N Keeler  1 Nicole M Ruppe  1 Anne E Kazak  1   2 Diana L Rash-Ellis  4 Jean Wadman  4 Robin E Miller  2   4 Janet A Deatrick  5 Abstract Families coping with sickle cell disease (SCD) often face heightened psychosocial risk factors, and research in pediatric SCD has often focused more on this area than resiliency factors. The aim of this study was to gain a better understanding of family resiliency in SCD based on caregiver perspectives. A secondary qualitative analysis was conducted with data from a mixed-methods study of caregivers of youth with SCD (n=22). Qualitative analyses involved coding based on 2 resiliency frameworks, organizing coding categories into themes, and systematically reintegrating these themes into a conceptualization that reflected family resiliency. Themes aligned well with the resiliency frameworks and related to family belief systems and meaning-making around SCD (acceptance of SCD, positive attitude, religious faith), family organization and adaptation (flexibility, stability, social supports), and the importance of communication and problem-solving. Study findings emphasize the importance of assessing resilience in families of youth with SCD and suggest the potential clinical benefits of developing psychosocial interventions based on family strengths. Full-text links  Wolters Kluwer 
10. Kidney Function Decline Among Black Patients With Sickle Cell Trait and Sickle Cell Disease: An Observational Cohort Study J Am Soc Nephrol 2019 Dec 6[Online ahead of print]Authors Kabir O Olaniran  1   2 Andrew S Allegretti  3 Sophia H Zhao  3 Maureen M Achebe  4 Nwamaka D Eneanya  5 Ravi I Thadhani  3   6 Sagar U Nigwekar  3 Sahir Kalim  3 Background: Sickle cell trait and sickle cell disease are thought to be independent risk factors for CKD, but the trajectory and predictors of kidney function decline in patients with these phenotypes are not well understood. Methods: Our multicenter, observational study used registry data (collected January 2005 through June 2018) and included adult black patients with sickle cell trait or disease (exposures) or normal hemoglobin phenotype (reference) status (ascertained by electrophoresis) and at least 1 year of follow-up and three eGFR values. We used linear mixed models to evaluate the difference in the mean change in eGFR per year. Results: We identified 1251 patients with sickle cell trait, 230 with sickle cell disease, and 8729 reference patients, with a median follow-up of 8 years. After adjustment, eGFR declined significantly faster in patients with sickle cell trait or sickle cell disease compared with reference patients; it also declined significantly faster in patients with sickle cell disease than in patients with sickle cell trait. Male sex, diabetes mellitus, and baseline eGFR ≥90 ml/min per 1.73 m2were associated with faster eGFR decline for both phenotypes. In sickle cell trait, low hemoglobin S and elevated hemoglobin A were associated with faster eGFR decline, but elevated hemoglobins F and A2 were renoprotective. Conclusions: Sickle cell trait and disease are associated with faster eGFR decline in black patients, with faster decline in sickle cell disease. Low hemoglobin S was associated with faster eGFR decline in sickle cell trait but may be confounded by concurrent hemoglobinopathies. Prospective and mechanistic studies are needed to develop best practices to attenuate eGFR decline in such patients. Keywords: African American; Sickle cell disease; Sickle cell trait; chronic kidney disease; estimated glomerular filtration rat; kidney function decline. Copyright © 2020 by the American Society of Nephrology. Full-text links  HighWire 
11. Sickle Cell Disease: Current Treatment and Emerging Therapies Am J Manag Care , 25 (18 Suppl), S335-S343 Nov 2019Authors Lynne D NeumayrCarolyn C HoppeClark Brown  1 Abstract Sickle cell disease (SCD) is among the most common genetic diseases in the United States, affecting approximately 100,000 people. In the United States, SCD is characterized by a shortened life expectancy of only about 50 years in severe subtypes, significant quality-of-life impairments, and increased healthcare utilization and spending. SCD is characterized by chronic hemolytic anemia, vaso-occlusion, and progressive vascular injury affecting multiple organ systems. The pathophysiology is directly related to polymerization of deoxygenated hemoglobin, leading to a cascade of pathologic events including erythrocyte sickling, vaso-occlusion, tissue ischemia, and reperfusion injury as well as hemolysis, abnormal activation of inflammatory and oxidative pathways, endothelial dysfunction, increased oxidative stress, and activation of coagulation pathways. These multifactorial abnormalities have both acute and chronic clinical consequences across multiple organ systems, including acute pain episodes, chronic pain syndromes, acute chest syndrome, anemia, stroke and silent cerebral infarcts, cognitive dysfunction, pulmonary hypertension, and a wide range of other clinical consequences. Hydroxyurea was the only approved treatment for SCD for nearly 2 decades; in 2017, L-glutamine oral powder was approved for the prevention of the acute complications of SCD. During the last several years there has been a dramatic increase in research into treatments that address distinct elements of SCD pathophysiology and even new curative approaches that provide new hope to patients and physicians for a clinically consequential disease that has long been neglected. Full-text links  Managed Care & Healthcare Communications, LLC 
12. Sickle Cell Disease: A Comprehensive Program of Care From Birth Hematology Am Soc Hematol Educ Program , 2019 (1), 490-495 2019 Dec 6Authors Mariane de Montalembert  1 Léon Tshilolo  2 Slimane Allali  1 Abstract As more children are appropriately being diagnosed, the burden of sickle cell disease is increasing greatly in Africa and in high-resource countries such as the United States and Europe. Early management is mandatory, but newborn screening is not implemented everywhere. Point-of-care testing devices are increasingly being used in low-resource countries, showing good sensitivity and specificity. Because the diagnosis is often traumatic for the families, the announcement should be made by an experienced person. The development of care networks is urgently required to facilitate daily life by defining the respective functions of nearby and highly specialized health care professionals, who should work in close collaboration. Comprehensive programs targeting the prevention of pneumococcal infections, malaria in infested zones, and stroke may substantially improve patient care. Hydroxyurea is increasingly being used, but whether it should be systematically prescribed in all children is debated, and its access is still limited in many African countries. Yearly checkups should be organized early in life in order to screen and then treat any organ impairment. Enhancing parents’ and patients’ knowledge and skills is mandatory. © 2019 by The American Society of Hematology. All rights reserved. Conflict of interest statement Conflict-of-interest disclosure: M.d.M. has received consultancy fees and honoraria from Novartis and Addmedica. L.T. and S.A. declare no competing financial interests.Full-text links  Silverchair Information Systems 
13. A Program of Transition to Adult Care for Sickle Cell Disease Hematology Am Soc Hematol Educ Program , 2019 (1), 496-504 2019 Dec 6Authors Anjelica C Saulsberry  1 Jerlym S Porter  2 Jane S Hankins  1 Abstract Most children with sickle cell disease (SCD) today survive into adulthood. Among emerging adults, there is a marked increase in acute care utilization and a rise in mortality, which can be exacerbated by not establishing or remaining in adult care. Health care transition programs are therefore essential to prepare, transfer, and integrate emerging adults in the adult care setting. The Six Core Elements of Health Care Transition, created by the Center for Health Care Transition Improvement, define the basic components of health care transition support as follows: (1) transition policy, (2) tracking and monitoring progress, (3) assessing transition readiness, (4) planning for adult care, (5) transferring to adult care, and (6) integrating into adult care. Programs that implement the Six Core Elements have experienced significant declines in care abandonment during adolescence and young adulthood and higher early adult care engagement. Most of the core transition activities are not currently reimbursable, however, posing a challenge to sustain transition programs. Ongoing studies are investigating interventions in comparative effectiveness trials to improve health-related quality of life and reduce acute care utilization among emerging adults with SCD. Although these studies will identify best practices for health care transition, it is also important to define how the transition outcomes will be measured, as no consensus definition exists for successful health care transition in SCD. Future research is needed to define best practices for health care transition, systematically assess transition outcomes, and revise payment models to promote sustainability of health care transition programs. © 2019 by The American Society of Hematology. All rights reserved. Conflict of interest statement Conflict-of-interest disclosure: A.C.S., J.S.P., and J.S.H. declare no competing financial interests.Full-text links  Silverchair Information Systems 
14. Complications in Pregnant Women With Sickle Cell Disease Hematology Am Soc Hematol Educ Program , 2019 (1), 359-366 2019 Dec 6Author Kim Smith-Whitley  1  Abstract Pregnancy in women with sickle cell disease (SCD) is associated with increased maternal and fetal morbidity and mortality. Outcomes vary widely owing to methodological limitations of clinical studies, but overall, hypertensive disorders of pregnancy, venothromboembolism, poor fetal growth, and maternal and perinatal mortality are increased globally. Few therapeutic interventions have been explored other than prophylactic and selective transfusion therapy. Unfortunately, existing data are limited, and it remains unclear whether prophylactic use of chronic transfusions will improve pregnancy outcomes. Management of pregnant women with SCD is best accomplished with a multidisciplinary team that includes a sickle cell expert and an obstetrician familiar with high-risk pregnancies. Women with SCD should have individualized care plans that outline management of acute pain and guidelines for transfusion therapy. Neonates require close monitoring for neonatal abstinence syndrome and hemolytic disease of the newborn. Ideally all young women with SCD will have a “reproductive life plan” developed as a component of preconception counseling and health promotion. Research leading to improved pregnancy management focused on diminishing adverse maternal and neonatal outcomes is overdue. International collaborations should be considered to improve subject recruitment and foster timely completion of clinical trials. Additional therapeutic interventions outside of transfusion therapy should be explored. © 2019 by The American Society of Hematology. All rights reserved. Conflict of interest statement Conflict-of-interest disclosure: K.S.-W. is on advisory committees for Pfizer, Global Blood Therapeutics (no honoraria), and Celgene (honorarium); has provided nonpaid expert testimony; and is a Sickle Cell Disease Association of America, Inc. Board Member.Full-text links  Silverchair Information Systems 
15. Osteonecrosis in Sickle Cell Disease: An Update on Risk Factors, Diagnosis, and Management Hematology Am Soc Hematol Educ Program , 2019 (1), 351-358 2019 Dec 6Authors Oyebimpe O Adesina  1 Lynne D Neumayr  2 Abstract Osteonecrosis, a form of ischemic bone injury that leads to degenerative joint disease, affects ∼30% of people with sickle cell disease. Although osteonecrosis most commonly affects the femoral head (often bilaterally, with asymmetric clinical and radiographic progression), many people with sickle cell disease also present with multifocal joint involvement. We present the case of a young woman with bilateral osteonecrosis of the femoral head at varying stages of progression; we also highlight other important comorbid complications (eg, chronic pain requiring long-term opioids, debility, and social isolation) and postoperative outcomes. In this review, partly based on recommendations on osteonecrosis management from the 2014 evidence-based report on sickle cell disease from the National Heart, Lung and Blood Institutes, we also discuss early signs or symptoms of osteonecrosis of the femoral head, radiographic diagnosis and staging criteria, hydroxyurea effect on progression to femoral head collapse, and surgical outcomes of total hip arthroplasty in the modern era. In summary, we failed to find an association between hydroxyurea use and femoral head osteonecrosis; we also showed that evidence-based perioperative sickle cell disease management resulted in superior postoperative outcomes after cementless total hip arthroplasty in sickle cell-related osteonecrosis of the femoral head. © 2019 by The American Society of Hematology. All rights reserved. Conflict of interest statement Conflict-of-interest disclosure: O.O.A. and L.D.N. declare no competing financial interests.Full-text links  Silverchair Information Systems 
16. Management of Liver Complications in Sickle Cell Disease Hematology Am Soc Hematol Educ Program , 2019 (1), 345-350 2019 Dec 6Author Abid R Suddle  1 Abstract Liver disease is an important cause of morbidity and mortality in patients with sickle cell disease (SCD). Despite this, the natural history of liver disease is not well characterized and the evidence basis for specific therapeutic intervention is not robust. The spectrum of clinical liver disease encountered includes asymptomatic abnormalities of liver function; acute deteriorations in liver function, sometimes with a dramatic clinical phenotype; and decompensated chronic liver disease. In this paper, the pathophysiology and clinical presentation of patients with acute and chronic liver disease will be outlined. Advice will be given regarding initial assessment and investigation. The evidence for specific medical and surgical interventions will be reviewed, and management recommendations made for each specific clinical presentation. The potential role for liver transplantation will be considered in detail. © 2019 by The American Society of Hematology. All rights reserved. Conflict of interest statement Conflict-of-interest disclosure: A.R.S. declares no competing financial interests.Full-text links  Silverchair Information Systems 
17. Optimal Disease Management and Health Monitoring in Adults With Sickle Cell Disease Hematology Am Soc Hematol Educ Program , 2019 (1), 505-512 2019 Dec 6Authors Jo Howard  1 Swee Lay Thein  2 Abstract In countries with access to organized health care, survival of children with sickle cell disease (SCD) has greatly improved, resulting in a growing population of adults with SCD. Transition from pediatric to adult care presents many challenges for the patient, who now faces the reality of emerging complications in many organs that are cumulative, adding to other age-related nonsickle conditions that interact and add to the disease morbidity. We recommend regular comprehensive annual assessments, monitoring for early signs of organ damage and joint clinics with relevant specialists, if applicable. While maintaining a low threshold for intervention with disease-modifying therapies, we should always keep in mind that there is no single complication that is pathognomonic of SCD, and nonsickle comorbidities should always be excluded and treated if present. We need to reevaluate our approach to managing adults with SCD by putting a greater emphasis on multidisciplinary care while proactively considering curative options (hematopoietic stem cell transplant and gene therapy) and experimental pharmacological agents for adults with SCD of all ages before complications render the patients ineligible for these treatments. © 2019 by The American Society of Hematology. All rights reserved. Conflict of interest statement Conflict-of-interest disclosure: J.H. and S.L.T. declare no competing financial interests.Full-text links  Silverchair Information Systems 
18. Treatment for Avascular Necrosis of Bone in People With Sickle Cell Disease Cochrane Database Syst Rev , 12 (12), CD004344 2019 Dec 5Authors Arturo J Martí-Carvajal  1 Ivan Solà  2 Luis H Agreda-Pérez  3  Abstract Background: Avascular necrosis of bone is a frequent and severe complication of sickle cell disease and its treatment is not standardised. This is an update of a previously published Cochrane Review. 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 both ongoing trial registries and the reference lists of papers identified by the search strategy. Date of the most recent search of the Group’s Haemoglobinopathies Trials Register: 17 September 2019. Selection criteria: Randomized clinical trials comparing specific therapies for avascular necrosis of bone in people with sickle cell disease. Data collection and analysis: Each author independently extracted data and assessed trial quality. The quality of the evidence was assessed using GRADE. Given only one trial was identified, meta-analyses were not possible. Main results: One trial (46 participants) was eligible for inclusion. After randomization eight participants were withdrawn, mainly because they declined to participate in the trial. Data were analysed for 38 participants at the end of the trial. After a mean follow-up of three years, hip core decompression and physical therapy did not show clinical improvement when compared with physical therapy alone using the score from the original trial (an improvement of 18.1 points for those treated with intervention therapy versus an improvement of 15.7 points with control therapy). We are very uncertain whether there is any difference between groups regarding major complications (hip pain, risk ratio 0.95 (95% confidence interval 0.56 to 1.60; vaso-occlusive crises, risk ratio 1.14 (95% confidence interval 0.72 to 1.80; very low quality of evidence); and acute chest syndrome, risk ratio 1.06 (95% confidence interval 0.44 to 2.56; very low quality of evidence)). This trial did not report results on mortality or quality of life. Authors’ conclusions: We found no evidence that adding hip core decompression to physical therapy achieves clinical improvement in people with sickle cell disease with avascular necrosis of bone compared to physical therapy alone. However, we highlight that our conclusion is based on one trial with high attrition rates. Further randomized controlled trials are necessary to evaluate the role of hip-core depression for this clinical condition. Endpoints should focus on participants’ subjective experience (e.g. quality of life and pain) as well as more objective ‘time-to-event’ measures (e.g. mortality, survival, hip longevity). The availability of participants to allow adequate trial power will be a key consideration for endpoint choice. Copyright © 2019 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd. Conflict of interest statement All authors: none known.Update of Cochrane Database Syst Rev. doi: 10.1002/14651858.CD004344.pub651 references Publication types Review Full-text links  Wiley 
19. 2019 Sickle Cell Disease Guidelines by the American Society of Hematology: Methodology, Challenges, and Innovations Blood Adv , 3 (23), 3945-3950 2019 Dec 10Authors M Hassan Murad  1 Robert I Liem  2 Eddy S Lang  3 Elie A Akl  4 Joerg J Meerpohl  5 Michael R DeBaun  6 John F Tisdale  7 Amanda M Brandow  8 Sophie M Lanzkron  9 Stella T Chou  10 Starr Webb  11 Reem A Mustafa  12 Abstract The American Society of Hematology (ASH) convened 5 guideline panels to develop clinical practice recommendations addressing 5 management areas of highest importance to individuals living with sickle cell disease: pain, cerebrovascular complications, pulmonary and kidney complications, transfusion, and hematopoietic stem cell transplant. Panels were multidisciplinary and consisted of patient representatives, content experts, and methodologists. The Mayo Clinic Evidence-Based Practice Center conducted systematic reviews based on a priori selected questions. In this exposition, we describe the process used by ASH, including the GRADE approach (Grades of Recommendations, Assessment, Development and Evaluation) for rating certainty of the evidence and the GRADE Evidence to Decision Framework. We also describe several unique challenges faced by the guideline panels and the specific innovations and solutions used to address them, including a curriculum to train patients to engage in guideline development, dealing with the opioid crisis, and working with indirect and noncomparative evidence. Full-text links  Silverchair Information Systems 
20. Chronic Transfusion Therapy Effectiveness as Primary Stroke Prophylaxis in Sickle Cell Disease Patients Hematol Transfus Cell Ther 2019 Oct 31[Online ahead of print]Authors Juliana Moreira Franco  1 Carla Caroline Lopes Borges  2 Marília Alves Ansaloni  2 Renata Dudnick de Lima Mauro  2 Ylle Carolinne da Cruz Souza  2 Josefina Aparecida Pellegrini Braga  2 Abstract Introduction: About 10% of sickle cell anemia patients will have ischemic stroke. Adams showed stroke incidence reduction in children receiving monthly erythrocyte transfusions by reducing transcranial Doppler (TCD) velocities. Since then, chronic transfusion is recommended as primary stroke prophylaxis. This study aims to assess the effectiveness of chronic transfusions as stroke prophylaxis. Method: Retrospective study, reviewing medical records from 15 sickle cell anemia patients undergoing chronic transfusion. Data collected were age, sex, adverse reactions, stroke, hemoglobin, reticulocytes, ferritin, HbS and TCD values (baseline, after 12 and 24months of treatment). Results: The mean age was 118.67±41.40 months; six patients experienced allergic reactions. No stroke was recorded. One patient had alloimmunization. There was a decrease in the HbS rate and an increase in hemoglobin values in the first 12months. Values were maintained after 24months, but with no improvement of data. Before treatment, the mean HbS rate was 75.18%±11.69; after 12months, 41.63±14.99 and after 24months, 43.78±10.6. Thirteen patients initiated chelation after 12months from the beginning of chronic transfusions and ferritin decline after 24months. Pre-transfusional TCD velocities were 204.28±9.41cm/s (right) and 198.85±33.37cm/s (left). After a 12-month treatment, these values were 158.5±28.89cm/s and 157.62±34.43cm/s, respectively, and this reduction was statistically significant (p=0.002 right and p=0.02 left). After 24months, these values were 149.63±26.95cm/s (right) and 143.7±32.27cm/s (left). Conclusion: Significant reduction of TCD velocity occurred after treatment with chronic transfusion in sickle cell anemia patients, leading to a normal or conditional test and reducing stroke risk in all but one patient. Keywords: Sickle cell anemia; Stroke; Transcranial doppler erythrocyte transfusion children. Copyright © 2019 Associação Brasileira de Hematologia, Hemoterapia e Terapia Celular. Published by Elsevier Editora Ltda. All rights reserved. Full-text links  Elsevier Science 

Sickle Cell Conferences and Events

1st regional conference(Gujarat-Maharashtra-Madhya Pradesh) SICKLE CELL UPDATE 2020 is on 19th January 2020 in Bardoli – INDIA. 

Web address www.sicklecellupdate2020.in 

E Mail sicklegujarat@gmail.com

The Hemoglobinopathy Counselor Training Course will be held in Cincinnati on April 15-16, 2020.  The two-day course, presented by the Cincinnati Comprehensive Sickle Cell Center, will be held at Cincinnati Children’s Hospital Medical Center.  The course registration fee is $250.  The deadline to register is April 1, 2020 and registration space is limited.  For more information, please email: SCDEvents@cchmc.org.  Registration is available online at www.cincinnatichildrens.org/HemoglobinopathyCTC.

4th Global Congress on SCD
On April 7-9, 2020, the 4th Global Congress on Sickle Cell Disease will take place at the United Nations Educational, Scientific and Cultural Organization Headquarters in Paris, France. Stay tuned for more information. 

14TH ANNUAL SICKLE CELL DISEASE RESEARCH & EDUCATIONAL SYMPOSIUM & 43rd NATIONAL SICKLE CELL DISEASE SCIENTIFIC MEETING

June 12 – 14, 2020 – FORT LAUDERDALE MARRIOTT HARBOR BEACH RESORT & SPA

3030 Holiday Drive, Fort Lauderdale, FL 33316 https://fscdr.org/the-symposium/