Goal 3: Advance Translational Research

To facilitate innovation and accelerate research translation, knowledge dissemination, and implementation science that enhances public health.

Goal 3: Advance Translational Research

Genomics in transfusion medicine

How can RBC genomics be utilized to improve outcomes with transfusion?

Submitted by (@barbarak)

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

Details on the impact of addressing this CQ or CC :

Prevention of alloimmunization with transfusion

Improved understanding of RBC epitope diversity

Feasibility and challenges of addressing this CQ or CC :

Utilize advances in genomics medicine to better understand impact of transfusion and to improve outcomes.

Limited donor pool, particularly in minority populations, presents challenges

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-7 net votes
13 up votes
20 down votes
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Goal 3: Advance Translational Research

Behavioral and Clinical Researcher Interactions

A critical challenge is the need to bring together basic behavioral scientists interested in understanding human behavior at a fundamental level, including how and why people become motivated and capable of undertaking behavioral changes, with clinical researchers interested in developing and testing new strategies for tackling resistant behavioral problems such as obesity and non-adherence.

Submitted by (@nhlbiforumadministrator1)

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

Feasibility and challenges of addressing this CQ or CC :

Obesity and non-adherence are two of the most important yet challenging behavioral problems contributing to cardiovascular morbidity and mortality. One way to address this challenge is to fund a network of “behavior change labs,” each of which bring together teams of basic behavioral scientists who are investigating the bases of behavior and behavior change with clinical researchers interested in designing, optimizing and testing novel ideas for tackling the difficult behavior problems of obesity and non-adherence to cardiac medications.

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

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20 net votes
52 up votes
32 down votes
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Goal 3: Advance Translational Research

Technologies for Ex-Vivo Cardiac Repair

What is needed to develop the technologies that will allow reparative interventions to be performed on excised natural hearts that have been overhauled ex vivo and replanted?

 

This will involve keeping the myocardium alive and sterile for extended periods that are long enough to complete the interventions while being able to also perform the necessary reparative interventions.

Submitted by (@nhlbiforumadministrator1)

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

Details on the impact of addressing this CQ or CC :

The long-term impact would be to alleviate the need for permanent circulatory support devices or transplants by providing a means for hearts to be repaired while patients are temporarily supported using total artificial hearts. The immediate impact of developing the technologies to do this would be that the necessary interventions for ex-vivo cardiac repair could be developed and tested leading to a new therapy.

Feasibility and challenges of addressing this CQ or CC :

A very basic foundation for this already exists. That foundation is an "Organ Care System" currently used in the UK to keep hearts functioning, not simply preserved, until the time of transplant for up to 12 hours. A timeframe of 5-10 years to extend the duration and the function of such a system for the stated purposes would seem feasible.

Repair and recovery of the heart is the currently limited to in vivo therapies. With the availability of artificial hearts and with the proper technologies available, the excised natural hearts from these patients could be overhauled ex vivo and re-implanted. Ideally, the overhaul would allow a way for various reparative interventions to be performed on the excised heart that would help to return it to a healthy functioning state before re-implantation. Such reparative interventions might include, but would not be limited to, surgical repair, adjunctive cell therapy, and stimulated exercise of the myocardium to influence reverse remodeling.

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

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5 up votes
20 down votes
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Goal 3: Advance Translational Research

Animal Models for COPD -- Core Facilities

COPD is a major health problem with more than 140,000 deaths per year and yet there is a relative paucity of treatments that might modify the course of this disease. In part, this is due to the poor efficiency of animal models that require months of exposure to cigarette smoke. Moreover, there are no well validated small animal models of chronic mucus hypersecretion. Funding of core facilities that could both provide ...more »

Submitted by (@rwise0)

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

Details on the impact of addressing this CQ or CC :

Funding of core facilities that could both provide support for researchers wishing to study COPD, and the development of efficient research models as well as models of chronic bronchitis would be a major advance for screening for treatments of COPD.

Feasibility and challenges of addressing this CQ or CC :

Current technology is well established for exposure of small animals to combustible tobacco smoker. However there remains to be developed standardized exposures to e-Cigarettes and Biomass fuels.

Name of idea submitter and other team members who worked on this idea : Robert A. Wise

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20 net votes
24 up votes
4 down votes
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Goal 3: Advance Translational Research

Natural Experiments and Obesity

How can approaches, such as natural experiments, be used to capture the evolution and impact of policies/environmental change that are related to obesity? There needs to be a mechanism that can quickly support the funding of natural experiment research. For instance, NIDDK and NICHD participate in a rapid response PAR that funds natural experiments in a timely manner. It only takes about 4 months from when the application ...more »

Submitted by (@nhlbiforumadministrator1)

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

Details on the impact of addressing this CQ or CC :

Gaining a better understanding of the impact of natural experiments on obesity would help us better understand how best to translate findings into public health action.

Feasibility and challenges of addressing this CQ or CC :

It is feasible to address the impact of natural experiments and obesity because there are currently naturally experiments taking place and we should capitalize on it.

There are a growing number of policies (e.g., caloric labeling) and environmental changes (e.g., bicycle lanes), being implemented to address obesity. These policy and environmental changes can be seen as natural experiments and should be evaluated. While there are challenges to revaluating real-world implementation of polices/environmental changes, there is the opportunity to increase external validity.

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

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32 net votes
62 up votes
30 down votes
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Goal 3: Advance Translational Research

Community Trials for Cardiovascular Health Enhancement

There is a need to initiate innovative community trials that are: theory-based; are integrated multi-component, multi-setting, and multi-level (i.e., they target individual, family, community, and built environment); engage community stakeholders; and use community-participatory research principles to enhance cardiovascular health (CVH) in vulnerable and diverse populations.

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 :

Global impact on cardiovascular health.

Feasibility and challenges of addressing this CQ or CC :

There are smaller scale community interventions but none in the literature that focuses on larger-scale multi-level trials as proposed here. This CQ would target vulnerable and diverse populations to reduce health disparities.

NHLBI supported the stroke belt initiative, and the exemplars in community CV health research: (e.g., the Stanford 5 City Project, The Minnesota Heart Health Program, The Pawtucket Heart Health). The next generation of community CVH research should harness the lessons from these studies, findings for the 8 Americas (Chris Murray), and numerous results from NHLBI cohort studies to implement large-scale community trials for cardiovascular health enhancement.

Resources for a large scale study could be a challenge. Ability to motivate a whole community, to prevent contamination, and to sustain interventions would be a challenge.

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

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-1 net votes
9 up votes
10 down votes
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Goal 3: Advance Translational Research

Allogeneic transplantation as a safe and universally available therapeutic strategy for treating non-malignant blood diseases

Can new advances in allogeneic blood or marrow transplantation (BMT) make the procedure a safe and universally available therapeutic strategy for treating non-malignant blood and immune disorders such as sickle cell anemia, thalassemia, aplastic anemia, and severe combined immune deficiency?

Submitted by (@rjjones)

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

Details on the impact of addressing this CQ or CC :

The ability of allogeneic blood or marrow transplantation (BMT) to cure diverse non-malignant diseases is well-documented. However, widespread use in diseases such as sickle cell anemia that cause substantial morbidity and shorten life but are not immediately life-threatening, has been limited by transplant-related toxicity and mortality especially in the majority of these patients who lack HLA-matched donors. Several new therapeutic approaches now exist that are promising strategies, separately or in combination, for addressing issues of donor availability, graft rejection, organ toxicity and acute and chronic graft-versus-host disease more effectively. Evaluation and refinement of these therapeutic strategies in both preclinical and Phase I-III clinical trials now offers a real possibility that allogeneic BMT could be applied early in the course of these diseases, allowing normal growth, development, quality of life and lifespan. If successful, allogeneic BMT offers a major advantage over gene therapy approaches even if such approaches become possible in the future; i.e., allogeneic BMT can be done with low-dose, non-toxic conditioning while gene therapy requires high-dose myeloablative therapy which not only can be toxic/fatal to these patients who often have end-organ dysfunction but also universally induces infertility, a major concern of patient groups who usually survive beyond child-bearing years.

Feasibility and challenges of addressing this CQ or CC :

There are now single institution and registry (CIBMTR) data showing that related haploidentical allogeneic BMT using post-transplantation cyclophosphamide (PTCy) produces results similar to those seen with HLA-matched sibling donors. Accordingly, every patient in need of allogeneic BMT now can safely undergo the procedure, including those ethnic groups (such as African-Americans and Hispanics) who are unlikely to find a donor in unrelated registries. Combining PTCy with other approaches for preventing graft-versus-host disease (GVHD) can even eliminate GVHD and transplant-related mortality. Although recurrence of malignant diseases remains an issue, especially as GVHD is eliminated, relapse is not a concern for non-malignant diseases after successful allogeneic engraftment. Moreover, the average cost of allogeneic BMT, about $150K, is a cost-savings over the long-term management of many of these diseases. The NHLBI-funded BMT Clinical Trials Network (CTN) has developed the infrastructure to rapidly and efficiently carry out large multi-institutional BMT trials. Over the last 15 year, thousands of patients have been entered on BMT CTN trials. Of note, African-Americans and Hispanics remarkably represent 30% of the accruals on one such trial, CTN1101, studying unrelated umbilical cord and related haploidentical allogeneic BMT. However, funding for the infrastructure for continuing this work remains problematic, since BMT trials generally lack corporate funding.

Name of idea submitter and other team members who worked on this idea : Rick Jones

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164 net votes
214 up votes
50 down votes
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Goal 3: Advance Translational Research

Translating cardiac development/genetics knowledge into therapy

What is needed to translate our knowledge of cardiac development and congenital heart disease genetics into novel diagnostic and/or therapeutic strategies for congenital or acquired heart disease?

Submitted by (@nhlbiforumadministrator)

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

Details on the impact of addressing this CQ or CC :

Develop new therapies for congenital or acquired heart disease.

Feasibility and challenges of addressing this CQ or CC :

We are poised to take advantage of the incredible advances in our understanding of cardiac development and genetics which have resulted from the development of high throughput technologies.

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

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10 net votes
21 up votes
11 down votes
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Goal 3: Advance Translational Research

Microvascular Dementia

The catchword Alzheimer's Disease (AD) is used to describe almost all types of dementia these days, and a lot of work has gone into developing preventive and/or therapeutic interventions for AD, but studies show that 40% of "AD" patients may in fact have something else. Microvascular Dementia (MD) presents with a similar phenotype. Delineating these two entities and then developing treatment strategies for MD is my ...more »

Submitted by (@wmars0)

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

Details on the impact of addressing this CQ or CC :

Developing therapeutics for AD that target amyloid and/or tau are not going to work on 40% of the population that have incorrectly been diagnosed with AD when they may instead have MD. The compelling question is how to easily delineate the two followed by the challenge of how to treat the population that has MD.

Feasibility and challenges of addressing this CQ or CC :

Accurate diagnostic imaging for true AD (with plaques) is now possible. Therefore, in the presence of cognitive decline, delineating AD versus other entities is now a reasonable, albeit expensive and time consuming, goal. Step one would be to bring costs and time to diagnosis down by developing a less expensive means of testing for true AD versus MD while verifying with the more expensive technologies. The next step would be to determine what contributes to the pathology of MD. For example, is it another type of plaque that is forming (little clots)? Or is the AD plaque injuring the vasculature? Is there genetic predisposition? As far as I know this area is not being explored in depth (other than possibly, the relationship to stroke). Finally, the one could seek to target therapeutics for this particular form of dementia.

Name of idea submitter and other team members who worked on this idea : Wendy Mars

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8 net votes
16 up votes
8 down votes
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Goal 3: Advance Translational Research

Effectiveness of pulmonary rehabilitation

1. Does pulmonary rehabilitation (PR) reduce mortality risk? 2. Does PR in the post-hospitalization period reduce subsequent health care utilization? 3. Can the principles of PR be applied more broadly across the disease spectrum to reduce morbidity, mortality, and health care expenditures in patients with COPD? 4. Does early PR following hospitalization for acute exacerbation reduce mortality and readmission rates ...more »

Submitted by (@nhlbiforumadministrator)

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

Feasibility and challenges of addressing this CQ or CC :

Does improved sleep following pulmonary rehabilitation contribute to improvement in symptoms and quality of life in these patients?

Name of idea submitter and other team members who worked on this idea : American Thoracic Society member

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2 net votes
2 up votes
0 down votes
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Goal 3: Advance Translational Research

Translation of novel computed tomography technologies

Computed tomography and related x-ray imaging techniques are mainstays of cardiovascular imaging and treatment. Novel technologies are emerging for CT that promise further improvements for cardiovascular disease, such as spectral CT, phase contrast CT or nanoparticle contrast agents. However, many challenges remain for their translation to patients.

Submitted by (@davidcormode)

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

Details on the impact of addressing this CQ or CC :

Spectral and phase contrast CT promise enhanced diagnoses of cardiovascular disease due to their improved soft tissue contrast and increased sensitivity towards contrast agents. Novel contrast agents are starting to allow molecular imaging with CT. These technologies could allow sophisticated characterization of atherosclerotic plaque and other diseases. This would provide enhanced diagnoses, tailored treatments and monitoring of response to therapies.

Feasibility and challenges of addressing this CQ or CC :

Improvements and innovations need to be made in beam filtration, detector systems, electronics and image reconstruction algorithms to allow clinical versions of spectral and phase contrast CT systems to be developed that have similar performance in terms of speed and radiation dose of current clinical systems. Investments need to be made in the development of novel, targeted nanoparticle contrast agent materials and studying their safety prior to clinical trials. While these are very significant challenges, with innovative approaches it should be possible to overcome these problems.

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

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-7 net votes
4 up votes
11 down votes
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Goal 3: Advance Translational Research

The impact of team consultation on COPD outcomes

Does use of periodic and automatic multidisciplinary team consultation improve care and health outcomes of patients with COPD?

Submitted by (@freeborn1956)

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 : John Linnell, COPD Foundation Minnesota State Captain

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16 net votes
18 up votes
2 down votes
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