Showing 33 ideas for tag "sickle"

Goal 2: Reduce Human Disease

What is the place of curative therapies in the management of Sickle Cell Disease

Advances in the care of pediatric patients with sickle cell disease ( SCD) have resulted in improved survival to adulthood.However, adulthood is marked by rapid disease progression, impaired quality of life and premature mortality. Hematopoietic cell transplantation(HCT) from matched sibling donor has curative potential, but has been offered mainly to children. Refinements in the conditioning regimen, supportive care,... more »

Is this idea a Compelling Question (CQ) or Critical Challenge (CC)? Compelling Question (CQ)

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To overcome this obstacle to progress in the field, we propose the creation of the funding mechanisms for a multicenter clinical trial consortium which would bring together investigators in field and facilitate study the outcomes of CT for patients with different types of donors and stem cell sources and compare them to outcomes in phenotypically matched controls receiving best available standard of care.Answering the compelling question about the role of CT in the management of SCD has the potential to have a catalytic effect in progress in this field. Patients are are then more likely to receive CT or standard of care at the appropriate time and in the manner in which they are most likely to have a positive outcome. This has the potential to reduce morbidity and premature mortality and in the long run, to decrease the burden of the disease on the healthcare system. The advent of clinical trials of gene therapies for SCD offers the prospect of even greater applicability of curative therapies. Thus, a consortium developed to answer this CQ would serve as a crucial vehicle for providing access to a greater proportion of patient to these personalized curative therapies . Such studies would also be powered to answer the question about who should receive the curative therapy, when they should receive it, and how it would impact their SCD related complications, late effects, survival and quality of life and help families make informed choice appropriate for their situation.

Feasibility and challenges of addressing this CQ or CC

The increasing applicability and acceptability of HCT for SCD is evidenced by the doubling in the number of such procedures reported to CIBMTR in the decade starting 2001. Refinements in conditioning regimen and supportive care continue to improve outcomes in children and now in adults with SCD undergoing HCT from HLA matched related donors. Recently, HCT from unrelated donors and from haplo-identical donors have further increased the applicability of HCT. Opening of gene therapy trials has further raised the prospect of cure for a greater proportion of patients. These developments are evidence of the feasibility of recruitment to large multi-center comparative trials of SCD and standard of care. Recently, there has been increasing collaboration among investigators in the field with informal consortia being developed by investigators coming together to study HCT for children, adults or HCT from haplo-identical donors. These groups are also increasingly working with SCD hematologists, families and other stakeholders. There is also increasing cross-cutting collaborations with other medical specialists and behavioral and translational scientists Thus, the convergence of several factors described above suggests that the time is fortuitous for a major initiative from the NHLBI to bring investigators together and create the infrastructure that will enable these investigators to seek definitive answers to the challenging question “What is the place of curative therapy in SCD?”.

Name of idea submitter and other team members who worked on this idea Lakshmanan Krishnamurti, MD, Allistair Abraham MD, John Horan MD and members of the Sickle cell Transplantation and Research Alliance

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112 net votes
141 up votes
29 down votes
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Goal 2: Reduce Human Disease

Predictors of Sickle Cell Disease Severity

Can better predictors of disease severity such as specific biomarkers and/or genetic polymorphisms be identified so as to help understand the course and progression of sickle cell disease in various patients?

Is this idea a Compelling Question (CQ) or Critical Challenge (CC)? Compelling Question (CQ)

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The high clinical variability in sickle cell disease (SCD) and the lack of sufficient data to help understand and or predict the course of an individual’s disease warrants the identification of better predictors of disease severity. The identification of predictors of disease severity, such as biomarkers, will be vital in the management and treatment of SCD, especially since more recently several plasma biomarkers and certain genetic polymorphisms have been proposed to influence specific clinical outcomes, including stroke, sickle cell nephropathy, and survival. Furthermore, studies of biomarkers or genetic markers in the context of clinical drug trials may be helpful in predicting response rates, thus allowing for more personalized therapeutic decisions.

Name of idea submitter and other team members who worked on this idea Alice Kuaban on behalf of the American Society of Hematology (ASH)

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58 net votes
76 up votes
18 down votes
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Goal 2: Reduce Human Disease

Optimization of Existing Therapies for Sickle Cell Disease

How can the safety, dosing and benefits of existing therapies for sickle cell disease such as hydroxyurea, be optimized in order to increase its efficacy and improve patient adherence?

Is this idea a Compelling Question (CQ) or Critical Challenge (CC)? Compelling Question (CQ)

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Hydroxyurea is a widely available disease-modifying therapy for sickle cell disease (SCD), but its effectiveness is currently limited by inadequate utilization, and less than optimal response. Research is needed to improve adherence to this evidence-based therapy and emphasis needs to be placed on determining whether therapy with hydroxyurea can prevent or even reverse organ dysfunction. In addition, research identifying new adjunct therapies to blood transfusion and hydroxyurea, as well as disease-specific therapies for co-morbidities such as kidney disease, hypertension, obstructive lung disease, and pulmonary hypertension will be valuable in the management and treatment of SCD.

Name of idea submitter and other team members who worked on this idea Alice Kuaban on behalf of the American Society of Hematology (ASH)

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54 net votes
74 up votes
20 down votes
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Goal 2: Reduce Human Disease

Sickle Cell anemia and Aplastic anemia survivors: Late effects and quality of life issues in Stem Cell Transplant Survivors

Most of the patients suffering from non-malignant hematologic conditions are cured of the original disease with Hematopoitec Stem Cell Transplant (HSCT) but still their survival is less compared to age matched general population, and additionally they suffer from unique complications of HSCT culminating into a variety of late physical, psychologic, financial, and social complications (“late effects”). Considerable improvements... more »

Is this idea a Compelling Question (CQ) or Critical Challenge (CC)? Compelling Question (CQ)

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One million HSCT mile stone was recently reached and the utilization of HSCTs continues to increase. For many non-malignant hematologic conditions particularly sickle cell anemia and bone marrow failure syndromes, HSCT is the only potentially curative option. Most HSCT survivors are living beyond a year, but can suffer from devastating complications of HSCT which include graft-versus-host-disease, second cancers, diabetes, infertility, congestive heart failure, blindness, and bronchiolitis obliterans, besides many others which lead to increased overall HSCT related disease burden. A lot of efforts are currently being put in cancer survivorship by the ACS, NCI, ASCO and other societies, but very little emphasis is being laid on sickle cell or aplastic anemia survivors. This area of HSCT survivorship becomes more important from health disparities perspective too, since majority of the hemoglobinopathy HSCTs performed in the US are in racial minorities. Comparative effectiveness research (CER) in HSCT survivorship is essential to delineate the overall disease burden this population and understand the risks and outcomes of HSCT late effects. To compare the effectiveness of survivorship programs and research, especially for those survivors who are at risk of health disparities is a top priority of the Institute of Medicine CER 2009 initiative.

Feasibility and challenges of addressing this CQ or CC

Majority of the HSCT survivors of benign hematologic conditions are now living beyond 2 years post-HSCT. Blood and Marrow Transplant (BMT) Clinical Trials Network (CTN) was established in 2001 to conduct large Multi-Institutional clinical trials and is funded by the NHLBI. Since the infrastructure is in place to conduct studies related to all aspects of HSCT, this would be an area to explore first from feasibility perspective since thousands of patients have already been successfully enrolled through the BMT-CTN studies. From NHLBI strategic perspective, this would place CTN (and Emmes Corporation) in an excellent unique position of addressing CER for survivorship issues and health disparities within one study, since the population understudy would mainly be consistent of racial minorities – with the overall goal of improving the long term health, preventing late effects, improving quality of life, and reduce the overall health burden (DALYs and societal costs) of thousands of HSCT survivors in the US and globally.

Name of idea submitter and other team members who worked on this idea Shahrukh Hashmi

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71 net votes
89 up votes
18 down votes
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Goal 2: Reduce Human Disease

Apheresis Medicine in the Management of Sickle Cell Disease

Despite advances in care, patients with sickle cell disease have significant morbidity and mortality. One challenge is the optimal use of simple vs exchange transfusion vs no transfusion when managing these patients. Simple transfusions lead to iron overload while exchange transfusions may expose patients to increase numbers of red blood cell units. The mechanism of benefit from transfusion (oxygen delivery vs marrow... more »

Is this idea a Compelling Question (CQ) or Critical Challenge (CC)? Critical Challenge (CC)

Details on the impact of addressing this CQ or CC

SCD is the most common genetic disease in the United States affecting 100,000 individuals or 1 in 400 African American births. Pain, stroke, acute chest syndrome and priapism are common morbidities affecting patients with sickle cell disease, which often result in emergency room visits and/or hospitalizations. Despite advances in treatment, sickle cell disease is associated with significant mortality and shortened life expectancy. Defining the optimal role of red blood cell exchange and plasma exchange (which may be used to remove plasma molecules such as inflammatory factors and free hemoglobin) in the management and prevention of the complications of sickle cell disease and may not only prolong the life of these patients but is expected to improve the quality of their lives. In addition, clearly defining the indications for simple verses exchange transfusion therapy has the potential to minimize both alloimmunization to red blood cells (reported to occur in up to 75% of patients with sickle cell disease) and iron overload associated with transfusion.

Transfusion therapy may be efficacious to sickle cell patients by providing increased oxygen delivery to tissues and/or decreasing the amount of sickle hemoglobin present by suppression of erythropoiesis. Understanding the relative contributions of these mechanisms will assist with optimal use of transfusion therapy as well as inform the development of novel alternative therapies

Feasibility and challenges of addressing this CQ or CC

Multi-center trials should be feasible, given the number of patients with sickle cell disease in the US. Participation by larger academic centers which care for sickle cell patients should facilitate trials. Methods for automated red cell exchange and plasma exchange are available and in common use at many centers. Great interest exists among physicians caring for sickle cell patients (as exemplified by the recent NIH consensus document and ASFA sickle cell consensus conference) which is a strength of this proposal. Challenges include agreement on standard treatment protocols across centers and long term follow up of patients. Maintaining vascular access in sickle cell patients is another challenge when performing apheresis procedures on sickle cell patients

Name of idea submitter and other team members who worked on this idea Bruce Sachais on behalf of ASFA

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130 net votes
152 up votes
22 down votes
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Goal 2: Reduce Human Disease

Enhanced Pain Research in Sickle Cell Disease

There is a need for more enhanced pain research in order to help improve sickle cell disease patient outcomes and quality of life.

Is this idea a Compelling Question (CQ) or Critical Challenge (CC)? Critical Challenge (CC)

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Pain is the most common clinical manifestation of sickle cell disease (SCD) and accounts for a large proportion of emergency department visits and hospitalizations. Due to its impact on the patients’ quality of life, there is a need for more basic and clinical research studies focused on understanding the mechanisms of different pain syndromes as well as the role of neurotransmitters and inflammation in acute and chronic SCD pain. Also, comparative effectiveness studies in the management of chronic pain will be crucial in helping to improve the patients’ overall quality of life.

Name of idea submitter and other team members who worked on this idea Alice Kuaban on behalf of the American Society of Hematology (ASH)

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39 net votes
58 up votes
19 down votes
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Goal 2: Reduce Human Disease

Innovations in Red Cell Transfusion in Sickle Cell Disease

Challenges that need to be overcome in blood transfusion, especially in SCD, include:
a. Adopting molecular genotyping as the standard in blood transfusion therapy.
b. Advancing new generation, anti-oxidant hemoglobin-based oxygen carriers (HBOCs) for use in emergencies such as trauma, stroke, acute hemolysis, and in transfusion in SCD and related disorders. In SCD, HBOCs have the capacity to not only serve as substitutes... more »

Is this idea a Compelling Question (CQ) or Critical Challenge (CC)? Critical Challenge (CC)

Details on the impact of addressing this CQ or CC

Transfusion of RBC is major adjunct in the management of trauma, acute and chronic illness. Issues in blood transfusion include availability of donors, RBC typing and crossmatching, cold storage of donor cells, and limited viability of stored RBC. Globally, in many situations where blood is critically needed, these systems are not available.
An increasing percentage of people with SCD require regular RBC transfusion to prevent stroke and other major complications. In addition, RBC transfusion is employed repeatedly in the management of serious acute complications of SCD. Transfusion of normal RBC to replace or supplement the patient’s defective RBC is the most effective intervention in the management of SCD.

Impacts:
• Molecular genotyping of RBC will reduce alloimmunization.
• Use of new generation HBOCs that do not require blood typing, crossmatching, refrigeration, and that do not transmit infection, would save lives in conditions of severe hemorrhage, stroke, possibly heart attack, especially where there is no immediate access to adequate medical facilities.
• In SCD, HBOCs could prevent pain or reduce its severity and duration, prevent stroke, reduce severity of acute chest syndrome, and other vasoocclusive complications. Finally, HBOCs have the potential to alter the pathogenesis of SCD.

Feasibility and challenges of addressing this CQ or CC

The problems in managing chronic RBC transfusion in SCD remain the same as they have been for decades: all immunization, iron overload, and infection transmission. It is clear that traditional serological RBC phenotyping is unable to detect several variants of RBC antigens, especially those in the Rh system, in populations of African descent. This leads to erroneous phenotyping and the appearance of “auto antibodies” that are truly alloantibodies resulting from transfusion of mismatched blood. As a result, people with SCD are the most frequent users of the American Rare Donor Program.

Name of idea submitter and other team members who worked on this idea Kwaku Ohene-Frempong, MD

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29 net votes
47 up votes
18 down votes
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Goal 2: Reduce Human Disease

How can we more safely deliver stem cells to Sickle Cell patients

Newer therapies using gene correction, rather than gene addition, are needed for sickle cell disease. Even with this potential advantage, there needs to be a way to safely deliver gene corrected HSC to the sickle cell patient. Chemotherapy is poorly tolerated, and often is the reason patients do not choose the BMT option. What is the status of other less toxic non myeloablative approaches, and how can they best be... more »

Is this idea a Compelling Question (CQ) or Critical Challenge (CC)? Critical Challenge (CC)

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would open up opportunities for more patients to get cured of their sickle cell disease without co morbidity of the BMT process

Feasibility and challenges of addressing this CQ or CC

Need to develop animal models and also newer marrow niche clearing agents.

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51 net votes
67 up votes
16 down votes
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Goal 2: Reduce Human Disease

Alternative treatments in sickle cell disease

There is a growing desire for the development of alternative treatments and natural therapies for the treatment of sickle cell disease.

Is this idea a Compelling Question (CQ) or Critical Challenge (CC)? Critical Challenge (CC)

Details on the impact of addressing this CQ or CC

Studies have indicated higher levels of fetal hemoglobin, even moderate levels, as being capable of reducing pain episodes. Development of therapies other than hydroxyurea, may be beneficial to individuals with SCD, specifically natural compounds as opposed to chemical based drugs. Additionally, it may be beneficial to the SCD survivors and the medical community to come up with biomedical alternatives to opiates and heavy narcotics used to induce relief and quiet the discomfort of the patient, even at the risk of addiction, resulting from prolonged usage (a life time).

Name of idea submitter and other team members who worked on this idea Sickle Cell Warriors, Inc. community members

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27 net votes
42 up votes
15 down votes
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Goal 2: Reduce Human Disease

Neurocognitive development and delays in sickle cell disease

Are neurocognitive developmental delays significantly present in children and adolescents living with sickle cell disease? What effect do these delays have on the overall morbidity associated with sickle cell disease?

Is this idea a Compelling Question (CQ) or Critical Challenge (CC)? Compelling Question (CQ)

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Conversations among the sickle cell population are increasingly focusing on mental health, neuropsycology as it relates to mental health, and the need to develop community life skills and personal development.

Name of idea submitter and other team members who worked on this idea Sickle Cell Warriors, Inc. community members

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30 net votes
41 up votes
11 down votes
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Goal 2: Reduce Human Disease

Hypoxia, acute chest syndrome and sickle cell disease

What markers in sickle cell disease can predict hypoxia after acute chest syndrome or pneumonia?

Is this idea a Compelling Question (CQ) or Critical Challenge (CC)? Compelling Question (CQ)

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Understanding that sickle cell disease has a character of depriving oxygen, is there any predicators that can tell if a child will have hypoxia after experiencing acute chest syndrome or pneumonia.

Name of idea submitter and other team members who worked on this idea Sickle Cell Warriors, Inc. community members

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32 net votes
41 up votes
9 down votes
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Goal 2: Reduce Human Disease

The treatment of asthma in patients with SCD prevents the development of ACS and VOS.

Does the aggressive treatment of asthma prevent the developement of acute chest syndrome (ACS) and vaso-occlusive syndrome (VOS) in patients with sickle cell disease (SCD)?

Is this idea a Compelling Question (CQ) or Critical Challenge (CC)? Critical Challenge (CC)

Details on the impact of addressing this CQ or CC

Improvement of health for persons with SCD.
Decreased hospitalizations and use of health resources.
Better understanding of the role of bronchospastic/inflammatory airway disease and hypoxemia as causes of acute chest syndrome and VOC.

Feasibility and challenges of addressing this CQ or CC

Feasible but stumbling block could be enrollment of patients since many patients with SCD are not seen by asthma specialists. Study could be a multicenter study with two hospitals in one major city and in one center, patients with SCD receive usual care and at another center they receive aggressive treatment and monitoring of their lung disease.

Name of idea submitter and other team members who worked on this idea Scott Schroeder

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13 net votes
27 up votes
14 down votes
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Goal 2: Reduce Human Disease

Assess the true impact of sickle cell trait on cardiovascular health across then age spectrum

Sickle cell disease is now understood as a disease of inflammation in addition to abnormal red blood cells. It is likely persons with sickle cell trait are also negatively affected by the damage caused by inflammation. There is a significant racial disparity in hypertension, stroke, and chronic kidney disease. It remains unclear the degree to which sickle cell trait contributes to this disparity. It also remains unclear... more »

Is this idea a Compelling Question (CQ) or Critical Challenge (CC)? Compelling Question (CQ)

Details on the impact of addressing this CQ or CC

Recent evidence in the United States emphasizes the possible health risks for individuals with HbAS including increased incidence
of renal failure and malignancy, thromboembolic disorders, splenic infarction as a high altitude complication, and exercise-related sudden death. Additional concerns include the increase risk of hypertension from endothelial scaring and additional vascular abnormalities. Early preventative therapies for persons with HbAS (sickle cell trait) could reduce the progression of cardiovascular disease in manny individuals if found to be of concern.

Feasibility and challenges of addressing this CQ or CC
  1. Several identified impediments to research of sickle cell trait have included under-representation of the African– American community in preclinical and translational research projects and limited study in health disparities research (Am J Hematol . 2012 March ; 87(3): 340–346).
  2. Ethical considerations in screening athletes and other individuals seeking labor intensive occupations for sickle cell trait
  3. The diagnosis of the carrier state for a genetic disease may be associated with serious health problems that can lead to widespread bioethical and social stigmatization and additional concerns including the increased need for testing and counseling

Name of idea submitter and other team members who worked on this idea Julie Kanter

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17 net votes
31 up votes
14 down votes
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Goal 2: Reduce Human Disease

Single nucleotide polymorphisms, microarray and sickle cell disease

Do SNPs account for any of the variability seen in the phenotypic expression of sickle cell disease? Can microarray analysis be used to map these SNPs, promoting refined care plans for those living with sickle cell disease?

Is this idea a Compelling Question (CQ) or Critical Challenge (CC)? Compelling Question (CQ)

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Multiple Single Nucleotide Polymorphisms (SNPs) have previously been identified in the mu opioid receptor and it is estimated that millions might exist throughout the genome. Drastic phenotypic variability exists among patients in the sickle cell community. Do SNPs account for any of this variability and can this information be used to more effectively treat sickle cell disease.

Name of idea submitter and other team members who worked on this idea Sickle Cell Warriors, Inc. community members

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18 net votes
32 up votes
14 down votes
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Goal 2: Reduce Human Disease

Mental health and wellness in sickle cell disease

A growing concern among the sickle cell community surrounds the lack of mental health and wellness services. Many in the community deal with anxiety and depression. It is well known how intricately connected mental and physical health are. So if we know that stress can trigger a psychological crisis which in turn triggers a physical pain crisis, why do we not automatically include mental health services within patient... more »

Is this idea a Compelling Question (CQ) or Critical Challenge (CC)? Critical Challenge (CC)

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Many in the SCD community feel like providers do not take a proactive approach to mental health. A comprehensive approach to developing mental health and wellness services and programs provides an opportunity to address factors contributing to morbidity, and perhaps mortality, in the SCD community, outside of the hospital walls.

Name of idea submitter and other team members who worked on this idea Sickle Cell Warriors, Inc. community members

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25 net votes
38 up votes
13 down votes
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