Goal 3: Advance Translational Research

Addressing Health Inequities through Nontraditional Partnerships

What non-traditional partnerships can be leveraged to address health inequities?

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 :

- Broaden reach to underserved populations

- Increase ability to generate evidence based solutions to address health inequities

- Bring expertise and resources to core partner (NIH)

- Enhance ability to identify unanticipated problems and strengthen efforts across all phases of the implementation research agenda

Feasibility and challenges of addressing this CQ or CC :

Feasibility:

- Increased emphasis on health and health inequities by non-profit and particularly, for-profit organizations

- Affordable Care Act (ACA) includes both general and explicit provisions that could narrow the health disparities gaps through implementation research.

- Can leverage and build upon current research partnerships that exist between government agencies and health care delivery systems to address questions of major public health importance

- Opportune time to employ implementation research addressing health inequities through non-traditional research partnership with sectors such as education, state and local government, transportation (built environment), penal and re-entry systems (health risks and disparities), ministries of health, and for-profits, foundations, and non-profits with health care focus.

 

 

Challenges:

 

 

- Risk of disagreements and friction among partners and management with different priorities

 

- Synchronization of timing for decision making

 

- Achieving partners’ concurrence on decisions that provide the most cost effective solutions

 

- Time needed to establish trust among partners that do not routinely partner to address health inequities

 

- There are limited resources dedicated to fostering Public Private Partnerships

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

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19 up votes
13 down votes
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Goal 2: Reduce Human Disease

RFA on EC-cardiomyocyte interactions in the mechanisms and treatments of cardiovascular diseases

Often under recognized, the cardiac endothelial cells are highly abundant in the heart, and may have important roles in modulating cardiac function, besides simply serving as structural component of blood vessels. Evidences of ours and others have indicated an emerging role of cardiac endothelial cells signaling to cardiomyocytes to mediate important pathophysiological responses. Nonetheless, detailed mechanisms of ...more »

Submitted by (@hcai00)

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

Details on the impact of addressing this CQ or CC :

Successfully addressing this question would no double reveal novel mechanisms and ways of monitoring treatment responses of cardiovascular disease, ultimately leading to novel drug targets, valuable biomarkers and extended new directions of basic research as well.

Feasibility and challenges of addressing this CQ or CC :

Tools of studying these cells are mostly available. Both adult cardiomyocytes and endothelial cells from the heart can be isolated and cultured, although cardiomyotyes need to used within 24 hrs and cannot be passaged. However successful preparation of these cells from WT and transgenic animals would permit co-culture experiments and mechanistic studies. These cells can also be studied using in-situ techniques either detecting molecular changes/events or dynamic interactions. Potential challenges would side in selective targeting of these cells, for example, either ECs or cardiomyocytes, once a potential therapeutic is in the testing. Nonetheless, PECAM-ab conjugated techniques have been employed to specifically deliver proteins to endothelial cells, so I am confident most of the challenges can be worked out, particularly within a RFA awardees group with frequent exchanges of ideas.

Name of idea submitter and other team members who worked on this idea : Hua Linda Cai, University of California Los Angeles

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27 net votes
30 up votes
3 down votes
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Goal 4: Develop Workforce and Resources

Training and mentor support in global health

Why can’t all training grants (T, K, etc) be opened out to all people working in US institutions, regardless of citizenship or green-card?

Why can’t we establish mechanisms for US junior investigators and mentors interested in global NHLBI areas?

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 :

Current policy does not allow non-citizens and green-card holders to apply for most K and T grants. However, given the changing nature of US workforce, this policy needs to change. Current mechanisms do not easily enable US investigators to get support for global work……training and/or research.

Feasibility and challenges of addressing this CQ or CC :

Why not?

Name of idea submitter and other team members who worked on this idea : K.M. Venkat Narayan

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-13 net votes
4 up votes
17 down votes
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Goal 2: Reduce Human Disease

Seeking the secret behind “resilience” to a variety of HLBS diseases

What is the secret behind the “resilience” some people have to heart, lung, blood, and sleep (HLBS) diseases?

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 :

Results of such research should reveal physiological mechanisms of resilience that could be used to develop interventions that would prevent or cure a variety of heart, lung, blood, and sleep diseases.

Feasibility and challenges of addressing this CQ or CC :

Advances in omics, clinical testing

, accumulation of large sets of clinical data and samples

, big data tools

, and increased interest from public (normal volunteers) and patients to participate in large scientific experiments make it feasible.

For instance, these may be healthy people carrying genetic mutations strongly associated with HLBS diseases (or causing rare/familial genetic diseases – these might easier to focus on first), but also people who are not hypertensive, hypercholesterolemic, or diabetic in spite of consistently making bad dietary choices, people who did not develop lung conditions in spite of high pollutant exposure, or are otherwise “protected” from other heart, lung, blood and sleep diseases. This reasoning is not very different from that used to identify ApoA Milano, or even PCSK9 or the “longevity genes”. Such information should reveal physiological mechanisms that could be leveraged to develop interventions to prevent or cure HLBS diseases.

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

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19 net votes
26 up votes
7 down votes
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Goal 1: Promote Human Health

Environmental Exposures and Atopic Disease

As the current chair of the Research and Training Division, I would like to convey that the AAAAI membership would like the NHLBI to consider the following in the development of its strategic plan:

 

What are the molecular and cellular responses in the lung that occur after environmental stimuli (including allergens) that predict homeostatic resilience or transition to atopic diseases?

Submitted by (@wheeze)

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 : Mitchell Grayson on behalf of the American Academy of Allergy, Asthma, and Immunology

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-7 net votes
8 up votes
15 down votes
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Goal 2: Reduce Human Disease

What about the impact of regulation of genes in response to external stimulation on human health

We are focusing a lot on the genes that may be protective or harmful to our lives. But what about the regulation of genes in response to external stimulations, such as psychosocial and/or environmental, that are probably more accountable for whether we live healthier or not.

Submitted by (@jiang001)

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

Details on the impact of addressing this CQ or CC :

Rationale: Years of research in the mind-heart field have set examples that looking at changes during dynamic stimulations (chronic, acute, and acute superimposed on chronic) are more meaningful for us to better understand how the body truly works. Therefore, research design in mimicking real dynamic process is necessary to truly capture the healthy or harmful phenotypes driven by genotypes. I suggest the NHLBI to establish a platform gathering resources to promote more sophisticated research from basic to clinical to better understand the underlying mechanisms of psychosocial impact on cardiovascular diseases that has come to a sizable problem for the human being in US and world wide.

Feasibility and challenges of addressing this CQ or CC :

We have performed researches that allow us to identify phenotypes that are only appearing under emotional stress testing. Currently we are examining whether certain intervention may modify these kinds of changes. Even our studies fail to demonstrate changes with intervention, the findings support future studies focusing on testing dynamic changes under stress that reflects daily living. Resting data obtained in laboratory does not truly represent what human beings experiences.

Name of idea submitter and other team members who worked on this idea : Wei Jiang from Duke University

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-4 net votes
5 up votes
9 down votes
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Goal 3: Advance Translational Research

Genetics and Genomics of Heart Disease

Identification of new genetic/genomic variants and risk genes often opens a new window to explore the fundamental molecular mechanisms underlying a disease and to develop new methods and strategies for diagnosis and treatment. Existing genomic variants and/or mutations explain only 10% to 20% heritability of common heart diseases. Much remains to be done in this important area. However, most genetic projects are discovery-driven ...more »

Submitted by (@wangq2)

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

Details on the impact of addressing this CQ or CC :

Identification of new genetic/genomic variants and risk genes often opens a new window to explore the fundamental molecular mechanisms underlying a disease and to develop new methods and strategies for diagnosis and treatment. Existing genomic variants and/or mutations explain only 10% to 20% heritability of common heart diseases. Much remains to be done in this important area. However, most genetic projects are discovery-driven and not hypothesis-driven, so that finding in this area has been extremely low. We recommend that genetics and genomics should be placed as a strong priority for NIH funding for the coming years.

Feasibility and challenges of addressing this CQ or CC :

Feasible

Name of idea submitter and other team members who worked on this idea : Qing Kenneth Wang

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

Implementation of Evidence-based Guidelines in LMICs

How can implementation strategies be tested in low and middle income countries for contextually and culturally adapted evidence-based clinical care guidelines with a focus on prevalent non-communicable diseases with large burdens such as sickle cell disease, hypertension, heart disease, stroke, asthma, and COPD?

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 :

Evidence-based guidelines for heart, lung, and blood diseases, developed within high income countries are challenging to implement within low and middle income countries because delivery capacity and health care infrastructure is often limited. Contextually, culturally and language adapted guidelines implementable within low and middle income countries can impart substantial benefit while distributing more evenly global knowledge of proven effective interventions while improving health equity. Proven effective interventions would get delivered in an effective manner across low and middle income countries which will improve heart, lung, and blood health outcomes.

Feasibility and challenges of addressing this CQ or CC :

The NHLBI Global Health Think Tank recommended research on implementation of contextually, culturally and language-adapted clinical care guidelines in low and middle income countries and encouraged addressing this issue in the near future.

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

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-10 net votes
8 up votes
18 down votes
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Goal 4: Develop Workforce and Resources

Suipport new research using the R21 mechanism

The decision by NHLBI to not support the R21 mechanism may be stifling new and innovative research, partcularly by young investigators who do not have a track record of R01 funding. The critical challenge is to keep funding new ideas from younger investigators to keep their careers viable while they obtain the data and publications necessary for further R01-level funding.

Submitted by (@georgeporter)

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

Details on the impact of addressing this CQ or CC :

The state of NHLBI funding rates for R01s are so low that we are undoubtedly loosing many young researchers as the fail to obtain adequate support for their research. Funding R21 grants will allow new, innovative, and perhps risky projects to proceed, while keeping less established researchers in the field. Re-establishing R21 funding may prevent the impression that NHLBI is more interested in supporting established labs and not advocating for and supporting new investigators.

Feasibility and challenges of addressing this CQ or CC :

Given the limited budget of R21s, they will not have as large an impact on the overall budget of NHLBI as the equivalent number of funded R01 grants. Therefore, this change is feasible from a financial standpoint. Obviously, funding R21s will decrease funding for other mechanisms. Finally, it is possible that many of these grants will not lead to advances in the field, but it is my understanding that studies show the same thing about R01s.

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

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87 net votes
101 up votes
14 down votes
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Goal 3: Advance Translational Research

Advanced Models for Translational Cardiovascular Research and Drug Development

Although the study of the cardiovascular (CV) system has benefited significantly from the use of gene-targeted and transgenic mouse models, small rodents do not always accurately reflect human cardiovascular physiology. Many discoveries using mouse CVD models failed to translate into human applications.

Submitted by (@echenum)

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

Details on the impact of addressing this CQ or CC :

Outcomes from large animal studies are likely to translate into more favorable results in human studies. Historically, some of the most significant advances in modern CV medicine are indebted to large animals.

Feasibility and challenges of addressing this CQ or CC :

Recent advances in mammalian genome projects and gene targeting technologies enable the production of large animal models. Genome information is now available for many animal species including pigs, rabbits, dogs, cats, horses and cows. Customizable nucleases, such as Zinc Finger Nuclease (ZFN), Transcription Activator-Like Effector Nuclease (TALEN), CRISPRs (clustered regularly interspaced short palindromic repeats) associated protein-9 nuclease (Cas9) has enabled the production of gene targeted animals in many of these species lacking germline transmitting embryonic stem (ES) cells, with satisfactory results. Integration of these novel knowledge and technologies in non-primate large animals will lead to production of an array of novel models of human CVD. Research in these models will help identify and establish suitable animal models that faithfully predict the outcomes in human clinical trials of new medicines and treatments. This is believed to have a major impact in the medical research field in general and significantly move cardiovascular research and drug development forward.

Name of idea submitter and other team members who worked on this idea : Eugene Chen from University of Michigan

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11 net votes
16 up votes
5 down votes
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Goal 2: Reduce Human Disease

COPD and co-morbidities

Society is ageing and chronic degenerative diseases including COPD are increasingly occurring together. The critical question is whether certain diseases occur together by chance or are they occurring together because they share pathobiological commonalities and mechanisms? This leads to a series of practical consequences and questions 1. Which diseases are occurring concurrent with COPD more than chance alone would ...more »

Submitted by (@bcelli)

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

Details on the impact of addressing this CQ or CC :

It is entirely possible and actually likely that several diseases manifesting in different organ systems may have shared pathobiological mechanisms. This could be the case of systemic inflammation or abnormal repair, precipitated by interaction with external agents such as pollution or smoking. This would manifest as different diseases affecting different organ systems (as could be the case of COPD and Lung Cancer) using today's taxonomy.

As it stands (taking the COPD Lung Cancer example) each is treated differently and actually strategically and clinically, they are handled as separate entitites. In all reality, if we can identify the diseases that share common pathogenetic mechanism, it is likely that we can develop common biomarker profiles that will detect disease predisposition so that early intervention can be planned.

In addition and equally important, once common co-morbidities can be grouped by pathobiology, plans can be developed by the medical establishment including health authorities to develop common approaches rather than the disjointed separate specialties that today handle each of the different organ systems.

Finally, the potential of aggregation of diseases into common pathobiological fields can reduce health care cost by integrating fields and voiding dispersion of resources.

Feasibility and challenges of addressing this CQ or CC :

It is entirely possible to use large throughput data analysis such as system network analysis to determine in a hypothesis free environment, what is the relationship amongst diseases. This analysis, that can be facilitated by the availability of electronic medical records can provide a first glance evidence of commonality amongst certain diseases.

This can be validated in other cohorts and a plan for profiling a representative sample of those cohorts in order to determine their proteomic and metabolomics profile. This will provide insight into the mechanisms responsible for the expression of the diseases and can lead to translational research aimed at identifying the mechanisms for the generation of the syndrome and potential therapeutic targets.

Once proven correct, it will be possible to identify and treat several diseases simultaneously with targeted therapy once appropriate trials have been completed.

The project here presented is already feasible and likely to offer new roads leading to a better taxonomy, identification and treatment of what now represents a puzzle of different pieces poorly interlocked.

Given the magnitude of the population that is and will be even more affected by multiple chronic diseases, this is a field that is ready for prime research efforts.

Name of idea submitter and other team members who worked on this idea : COPD and co-morbidities: Chance or Fate?

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20 net votes
22 up votes
2 down votes
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Goal 2: Reduce Human Disease

Timing of post-cardiac arrest PCI

The majority of patients who are resuscitated from OHCA have a presumed cardiac etiology. One of the key interventions post cardiac arrest is to study the coronary circulation for underlying thrombosis. Some centers do this routinely but at other centers interventional cardiologists are hesitant to do this since the mortality rates are high and so affect their individual and institutional performance measures related ...more »

Submitted by (@dayam0)

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

Details on the impact of addressing this CQ or CC :

There is variability in practice and no large scale level 1 evidence as to what is the best to do with regards to post ROSC care and PCI as well as timing of the PCI

Feasibility and challenges of addressing this CQ or CC :

Will require funding, broad cooperation between cardiologists and emergency medical services as well as critical care. National groups that conduct performance measures for survival following PCI need to readdress the use of such measures in this group of patients (post-arrest)

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

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2 up votes
3 down votes
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