Goal 2: Reduce Human Disease

To extend our knowledge of the pathobiology of heart, lung, blood, and sleep disorders and enable clinical investigations that advance the prediction, prevention, preemption, treatment, and cures of human disease.

Goal 2: Reduce Human Disease

The Importance of the Microbiome in Recovery after Hematopoietic Stem Cell Transplantation

Do modifications in the recipient gut or lung microbiome affect development of tolerance and immunologic recovery after allogeneic hematopoietic stem cell transplantation (HCT) and can re-institution of a more normal microbiome lead to improved outcomes?

Submitted by (@marymh)

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

Details on the impact of addressing this CQ or CC :

HCT leads to profound changes in the host microbiome. Some small studies indicate that differential recovery of the gut microbiome is associated with differential outcomes, including graft-versus-host disease and mortality. Less is known about the pulmonary microbiome. Better understanding of the role of the microbiome in facilitating posttransplant recovery could lead to easily administered interventions and provide important insights into the role of different subpopulations of the microbiome on the health of all people.

Feasibility and challenges of addressing this CQ or CC :

Preclinical and clinical studies of this area would be greatly facilitated by a microbiome repository linked to high quality clinical data and would provide opportunity for insight into the role of the microbiome in health and disease.

Name of idea submitter and other team members who worked on this idea : Mary Horowitz

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117 net votes
152 up votes
35 down votes
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Goal 2: Reduce Human Disease

Randomized trial of low carbohydrate high fat dietary pattern

There is a need for a large, simple, hard outcome trial of dietary advice to measure the effects of lowering simple carbohydrates versus lowering unhealthy fats. The main challenge will be to overcome bias favoring the more conventional dietary approach.

Submitted by (@nhlbiforumadministrator)

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

Details on the impact of addressing this CQ or CC :

Substantial numbers are moving towards low carbohydrate/high fat diets to the extent that since 2000 the macronutrient composition of the US diet has changed towards lower carbohydrate and higher fat intakes; however, CV mortality rates continue to decline. The outcome of the trial will help frame future guidelines for healthy diets.

Feasibility and challenges of addressing this CQ or CC :

Yes, since computer or smartphone based intervention materials and passive outcome collections (CMS, NDI, health care organizations) are increasingly being utilized.

Low carbohydrate high fat (LCHF) diets first popularized for weight reduction are increasingly being promoted to prevent diabetes and cardiovascular disease. All trials to date have been small and short term. Compared to more traditional high carbohydrate low fat diets, LCHF diets may be somewhat more beneficial for weight control, glucose homeostasis, and dyslipidemia, but less beneficial for LDL reduction.

Name of idea submitter and other team members who worked on this idea : NHLBI Staff

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-17 net votes
5 up votes
22 down votes
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Goal 2: Reduce Human Disease

What new methods of platelet preparation, processing, and storage are needed for hemostasis in various clinical conditions?

The limitations of 5-day 22˚ C storage significantly impacts platelet availability. It is critical that we develop new methods of collection, processing, storage to extend the storage time of platelets, and evaluate the use of whole blood. The attributes of these products must be understood to optimally alignment product attributes, clinical efficacy and safety with hemostatic needs in a variety of clinical states. Specifically, ...more »

Submitted by (@bldbuddy)

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

Details on the impact of addressing this CQ or CC :

Limitations of current storage methods challenge our ability to meet the increasing demands of cancer chemotherapy and complex surgeries as well as provide platelets to remote areas where trauma frequently occurs. Platelets are transfused to prevent or control bleeding without robust translational or clinical trial evidence of efficacy and safety. In patients with hypoproliferative thrombocytopenia receiving chronic platelet transfusion predominantly for prophylaxis, post-transfusion increments, survival time, and durable hemostatic efficacy are important; however, platelet transfusion alone does not prevent bleeding. The overall state of hemostasis, the endothelium and donor characteristics that affect platelet quality may be important considerations in selecting the best platelet product tailored to individual patients. Better laboratory and clinical measures of platelet function, efficacy and safety are essential for best use of these limited resources. These outcomes should span and link in-vitro testing, animal models, and clinical effects such as thrombotic events, immune, hemostatic, and endothelial effects. Extrinsic, recipient factors (e.g., immune deficiency, platelet or endothelial dysfunction) and intrinsic factors (e.g., donor specific or platelet preparation) should be considered. Systematic analysis of recipients and donors should be broad and include considerations of glycomics, metabolomics, proteomics, genomics, in vivo microscopy, and advanced imaging.

Feasibility and challenges of addressing this CQ or CC :

Radiolabeled platelet recovery and survival methods are well established and feasible to perform at several centers within the US. Currently 4-6 million units of platelets and whole blood are transfused per year. It is very feasible to conduct clinical trials that compare methods of platelet preparation, processing, and storage in children and adults who require platelets for either prophylaxis or active bleeding. Multiple research networks that focus on both pediatric and adult transfusion medicine are motivated to perform the pre-clinical and clinical trials required to establish improved efficacy and safety of platelet-containing blood products.

Name of idea submitter and other team members who worked on this idea : Terry Gernsheimer, University of Washington, for the 2015 NHLBI State of the Science in Transfusion Medicine

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14 net votes
34 up votes
20 down votes
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Goal 2: Reduce Human Disease

Sleep and obesity

What characteristics of sleep relate to obesity and does improving sleep using medication help with changes linked to obesity and in the end with weight?

Submitted by (@helenahillmanlaroche)

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

Details on the impact of addressing this CQ or CC :

We are getting more information that sleep is linked to obesity. Those of us treating obesity also try to address sleep but often need to try medication in those with chronic insomnia. Whether this will help with weight or perhaps make it worse and whether one medication might be better to choose over another are questions that impact medical practice.

Name of idea submitter and other team members who worked on this idea : Helena Laroche

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27 net votes
36 up votes
9 down votes
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Goal 2: Reduce Human Disease

Optimizing Cardiovasular (CV) Prevention Medicine Use

Heart attacks and strokes cause substantial morbidity and mortality, while implementation of cholesterol and other CV prevention guidelines remain low. Proposed NCQA on-statin in the last year among those with DM was 46% in national field testing, and about 75% in Kaiser Permanente (KP). KP has had some success overcoming barriers to statin, aspirin, and blood pressure medicine adherence. If the nation as a whole is ...more »

Submitted by (@ronald.d.scott)

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

Details on the impact of addressing this CQ or CC :

Improving treatment rates to CV guidleines improves the population health and can be cost saving to the system. Currently statin use among DM and in those with ASCVD Risk >= 7.5% is about 40%. If treatment improved to 60 or 80% many CV avents would be averted and downstream cost savings.

Feasibility and challenges of addressing this CQ or CC :

KP has achieved blood pressure control rates of about 90% demonstrating possibility of high control / treatment rates. Improving treatment rates where there is a treatment gap in cost saving CV prevention should be a priority.

Name of idea submitter and other team members who worked on this idea : Ronald D Scott, MD. Kaiser Permanente Integrated Cardiovascular Health Team

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-11 net votes
3 up votes
14 down votes
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Goal 2: Reduce Human Disease

Basic research

Are we funding enough basic research to support future research?

Submitted by (@nhlbiforumadministrator)

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

Details on the impact of addressing this CQ or CC :

What is the nature of scientific knowledge? Are there enough opportunities for young scientists?

Feasibility and challenges of addressing this CQ or CC :

Funding of young scientists and of generalists is a challenge.

Name of idea submitter and other team members who worked on this idea : Rachel Braun

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82 net votes
107 up votes
25 down votes
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Goal 2: Reduce Human Disease

Rare disease therapeutics high throughput screening

Can we develop model systems for the high throughput screening of new and existing agents as possible therapies for rare diseases?

Submitted by (@nhlbiforumadministrator1)

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

Name of idea submitter and other team members who worked on this idea : NHLBI Staff

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-18 net votes
8 up votes
26 down votes
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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 »

Submitted by (@lakshmanankrishnamurti)

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

Details on the impact of addressing this CQ or CC :

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

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?

Submitted by (@sicklecellwarrior)

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

Details on the impact of addressing this CQ or CC :

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

Funding and Deepening Glycoscience at the NHLBI

See attached document. My comments touch on both 'reducing human disease' and 'developing the workforce'.

Submitted by (@briancobb)

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

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2 net votes
6 up votes
4 down votes
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Goal 2: Reduce Human Disease

Repair and Regenerate the Kidney

Chronic Kidney Disease (CKD) affects millions in the US, and is one of the new diseases on the rise globally. New therapies to slow CKD and to repair and regenerate failing kidneys are drastically needed to reduce health care costs and improve lives.

Submitted by (@ceci00)

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

Details on the impact of addressing this CQ or CC :

New therapies to slow CKD and to repair and regenerate failing kidneys are sorely needed to reduce health care costs and improve lives.

Feasibility and challenges of addressing this CQ or CC :

Our understanding of renal function and risk factors is greater than ever. Our ability to diagnose is technologically advanced. We now need to increase efforts to identify therapeutic targets and develop regenerative approaches to prevent and treat CKD.

Name of idea submitter and other team members who worked on this idea : Ceci Giachelli

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1 net vote
1 up votes
0 down votes
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Goal 2: Reduce Human Disease

Promoting Physical Activity in COPD

The GOLD guidelines recommend regular physical activity in all patients with stable COPD. How we operationalize this is completely unclear. We know pulmonary rehab works but few patients are referred and fewer participate. We also know physical activity, not just exercise, directly measured in the field is associated with COPD-specific outcomes such as acute exacerbations, hospitalizations and death. How do we bring ...more »

Submitted by (@marilynmoy)

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

Name of idea submitter and other team members who worked on this idea : Marilyn Moy,MD

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4 net votes
5 up votes
1 down votes
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