Goal 3: Advance Translational Research

Harnessing the ongoing ‘natural experiments’ of quality improvement

How do we harness the ongoing “natural experiments” of quality improvement (QI) activities in various healthcare systems to facilitate hypothesis-driven research, improve scientific validity to address questions in clinical trials, and implement and disseminate research results? • Current restrictions in human subjects research regulations • Diversity in approaches and methodology rigor to QI initiatives across different ...more »

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 :

• Publication of QI initiatives in peer-review journals

• Wider dissemination and adoption of best practices

• Establishment of methodologically rigorous QI programs with viable career pathways

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

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11 up votes
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Goal 3: Advance Translational Research

Best Implementation Strategies

What are the best implementation strategies to improve adherence to clinical practice guidelines, protocols, and other evidence-based practices that actually lead to the elimination of inequities in preventable disability and death from heart, lung, blood, and sleep diseases?

Submitted by (@nhlbiforumadministrator)

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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12 net votes
20 up votes
8 down votes
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Goal 3: Advance Translational Research

Improving heart, lung, blood, sleep Health Outcomes for Minority and Underserved Men

What are the best strategies to improve implementation of evidence-based practices (EBP) to enhance effective health risk communication strategies among racial and ethnic minority males and underserved men? Examples of several issues that need to be addressed are: • Need for better definition of the role of families/communities in EBP (as co-therapists). • Requires less system fragmentation • Need for improved measurement, ...more »

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 :

Our improved ability to develop, implement and disseminate EBPs tailored specifically for men in health disparity populations may help us move beyond current obstacles in addressing health inequities and improve health outcomes.

Some current challenges:

• High blood pressure affects more than 40 percent of African Americans.

• The odds for stroke, the third leading cause of death in the United States, are especially high for African American men at 70%.

• African Americans are about 50% more likely to experience stroke than Caucasians.

• Sleep apnea is seen more frequent among men than among women, particularly among African-American and Hispanic men.

• Life expectancy for African American men is 4.7 years less than for white men (2010).

• Native American men have an average life expectancy of 71 years old compared to white men who have an average life expectancy of 76.5 year.

Feasibility and challenges of addressing this CQ or CC :

• Shifting demographics of race as well as ageing of the population in this country will have a major impact on the utilization, organization and delivery of health care.

• Country acknowledges significant economic burden of health inequities in the U.S. in the near future.

• Hospitals and health systems are working hard to align quality improvement goals with disparities solutions. Opportunity to leverage these efforts for the development and implementation of targeted health disparities initiatives is timely.

• HL has a number of large population-based studies (such as JHS, Strong Heart, Hispanic Community Health) that could be leveraged to specifically identify EBP for wider implementation and dissemination to underserved areas.

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

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

The importance of cosidering sex and gender in presicion medicine

Precision medicine will be invested in across NIH, as per the President's "Precision Medicine Initiative". It is critical that the population base be reflective of the US population, including 50% women. Gender, especially as it relates to exposures, must be a dominant consideration, as these factors are critical to the development of human disease and therefore will be important to prevention.

Submitted by (@pajohnson)

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

Details on the impact of addressing this CQ or CC :

Precision medicine that can be applied accurately to different groups within o our population, in particular women and racial and ethnic minorities.

Feasibility and challenges of addressing this CQ or CC :

Achieving this goal is feasible and essential.

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

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Goal 3: Advance Translational Research

Translational Bioinformatics Spanning Multiple Scales of Biologic Complexity to Implement Precision Pulmonary Medicine at the Po

What translational bioinformatics tools could be used in pulmonary medicine to allow multidimensional, multi-scale modeling of clinical and biomolecular data to assist clinical decision-making?

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 :

Deployment of bioinformatics tools to construct multi-dimensional, multi-scale models of pulmonary (mal)functioning from large heterogeneous data sets spanning biological molecules, subcellular compartments, signaling pathways, cells, tissues, organs, organ systems and clinical therapeutics trials to predict actionable precision medicine for clinicians at the point of pulmonary care.

Feasibility and challenges of addressing this CQ or CC :

A variety of existing powerful informatics methods for integrating a vast wealth of clinical and high-dimensional data across DNA to organism compartments to develop multi-scale modeling approaches to improve point-of-care precision medicine. Consistent with a continuous learning healthcare system, precision medicine modeling is recursive, tentative pending better understanding and therefore continuously learning.

Fundamental to implementation of precision medicine is the ability to extract heterogeneous data from basic and clinical research to be integrated systematically into clinical practice in a cohesive and large-scale manner. Deployment of precision medicine models to predict (mal)functioning progression and response the treatment in daily practice relies strongly on the availability of an efficient bioinformatics platform that assists in the translation of basic and clinical science knowledge.

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

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-2 net votes
10 up votes
12 down votes
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Goal 2: Reduce Human Disease

Stem Cell Immunology

We now can create critical cell types like cardiomyocytes etc. from stem cells. Additionally, we are learning the rules of using these cells to rebuild tissues. A major gap in our knowledge relates to the immunobiology of these cells. Lessons from transplantation medicine are only partially applicable, because solid organs are more complex and likely more immunogenic than defined cell populations. How does the immune ...more »

Submitted by (@murry0)

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 now can generate large quantities of critical cell types whose deficiencies underlie many chronic diseases like heart failure. This breakthrough brings us to the next-level impediment: the immune system. While induced pluripotent stem cells have the potential to obviate rejection, in practical terms this is cost-prohibitive: It will cost huge amounts of money to produce and qualify a single patient's cell dose. Moreover, human cardiomyocytes are potent when given to infarcted hearts in the acute or sub-acute phase of infarction, but they have no benefit with chronic heart failure. The 6 months required to produce iPSC-cardiomyocytes precludes their autologous use for myocardial infarction.

 

We need an off the shelf cell therapy product for myocardial infarction that can be mass produced and qualified for large numbers of patients. This means an allogeneic product is necessary. Identifying the immune response to cardiomyocytes or other cell products will teach us how to precisely immunosuppress the patient, thereby minimizing complications, or alternatively, how to engineer the cells so as to avoid immunogenicity in the first place.

 

Lessons from the study of cardiomyocyte transplantation could extend to dopamine neurons, pancreatic beta-cells, retinal cells, myelinating cells and many other areas that cause common chronic disease.

Feasibility and challenges of addressing this CQ or CC :

We know a great deal of transplant immunology from hematopoietic stem cell transplantation (graft versus host) and from solid organ transplantation (host versus graft). There are good mouse and large animal (including non-human primate) models of stem cell differentiation and organ transplantation. This offers low hanging fruit where, in perhaps 5 years, we could discern the critical similarities and differences between transplanting stem cell derivatives and organ or marrow transplantation. These studies will inform clinical trials of allogeneic human stem cell derivatives that will be underway by then.

 

Success in this area will require bringing together researchers interested in stem cell biology and transplant immunology. A properly resourced RFA from NIH could be just the thing needed to promote this interaction.

Name of idea submitter and other team members who worked on this idea : Charles Murry, MD, PhD

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23 net votes
45 up votes
22 down votes
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Goal 1: Promote Human Health

Predictive analytics to engage healthy behaviors and maintain health while reducing cost

Predictive Health employs the principle that using modern health testing and predictive analytics will better define true health (not just absence of disease) and, in combination with large-scale data analytics, will facilitate predicting deviations from the healthy trajectory earlier than traditional disease diagnosis, thus allowing more effective and less costly interventions to maintain health. Predictive Health educates ...more »

Submitted by (@greg.martin)

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

Details on the impact of addressing this CQ or CC :

By addressing this CC the health of the nation will be improved: better national and individual understanding of health, greater longevity of sustained health and productivity, reduced costs of healthcare by focusing on health than on disease diagnosis and management.

Feasibility and challenges of addressing this CQ or CC :

The Emory/Georgia Tech Predictive Health Institute (http://predictivehealth.emory.edu) was founded ~10 years ago by launching educational (http://predictivehealth.emory.edu/education/index.html) and scientific (http://predictivehealth.emory.edu/chd/index.html) programs to achieve the Predictive Health goals. The scientific approach created a prospective longitudinal cohort of individuals who have been richly phenotyped according to traditional medical testing (clinical laboratory, stress testing, etc) and research testing (genomics, metabolomics, regenerative cell potential, oxidative stress) to create the deepest understanding of current and future health. The success of the Predictive Health Institute demonstrates the feasibility and potential success of such a critical challenge to both human health and healthcare expenditures.

Name of idea submitter and other team members who worked on this idea : Greg Martin, for the Emory/Georgia Tech Predictive Health Institute

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5 net votes
9 up votes
4 down votes
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Goal 1: Promote Human Health

Qigong and Tai Chi for Chronic Disease Prevention

Non-pharmacological interventions for pain and stress have gained tremendous momentum. Mind-Body Practice -- Qigong and Tai Chi -- are group based and inexpensive to implement. The evidence base suggests that these practices are safe and effective for a multitude of preventable chronic disorders.. THE QUESTION: Given safety and efficacy, should there be vigorous research on implementation of Qigong and Tai Chi and ...more »

Submitted by (@rogerjahnke)

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

Details on the impact of addressing this CQ or CC :

What can we do to assure that safe, effective, inexpensive non-parmacological approaches like Qigong and Tai Chi become widely diffused into communities, agencies, organizations, schools, health systems and businesses.

Feasibility and challenges of addressing this CQ or CC :

We have participated in a number of studies that have contributed to the evidence base for Mind-Body Practice as a safe and effective non-pharmacological programming.

 

The key -- group based. For the financing, group based is inexpensive. For the efficacy group based supports compliance.

Name of idea submitter and other team members who worked on this idea : Dr Roger Jahnke, http://IIQTC.org

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2 net votes
33 up votes
31 down votes
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Goal 3: Advance Translational Research

Stem Cell Biology

There is a need to develop “designer platelets” and “designer red cells,” as well as facilitate large-scale production of these products for therapeutic and diagnostic use.

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 reprogramming of adult stem cells has resulted in the generation of induced pluripotent stem cells (iPSCs) that can develop into any tissue of the body. These iPSCs ultimately may be used as a transplantable source of stem cells for a variety of hematologic diseases. Although this technology has enabled the generation of patient-specific or disease-specific stem cells that are also amenable to genetic manipulation, the major scientific hurdle has been the ability to create clinically meaningful functional blood products, including transplantable HSCs from differentiating iPSCs. The production of clinically functional blood products -- i.e. red blood cells derived from autologous iPSCs --could replace allogeneic products in highly immunized patients and the generation of megakaryocytes for patient-specific platelet production from iPSCs could drive significant progress in this area. Furthermore, disease-specific iPSCs could serve as targets for both drug development and drug screening in patients with rare hematologic disorders. In addition, support for scale-up and GMP processes, which are difficult to fund via the R01 mechanism will require specific grant opportunities tailored to infrastructure and process development.

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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25 net votes
53 up votes
28 down votes
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Goal 2: Reduce Human Disease

DEVELOPMENT OF A PERSONALIZED APPROACH TO SLEEP AND CIRCADIAN DISORDERS

There is developing evidence of major individual differences in pathways to different common sleep disorders such as obstructive sleep apnea. Moreover, there is evidence of different clinical presentations of disease and different outcomes. For example, some subjects with obstructive sleep apnea who get excessive sleepiness while others do not. The latter are still at risk for other consequences of the disorder such ...more »

Submitted by (@jnoel0)

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

Details on the impact of addressing this CQ or CC :

There is a strong rationale for application of a personalized approach to sleep disorders. This requires approaching this question using multiple domains as in other areas of medicine—clinical features, physiological factors, application of the –omic approaches, genetics. The impact of this will be several:

 

a. A new way to classify sleep disorders.

b. Identification of subgroups of patients with apparently the same disorder who will have different outcomes of therapy.

c. Identification of subgroups of patients who will have different approaches to diagnosis.

d. Identification of subgroups of patients with apparently the same disorder who will have different therapeutic approaches.

Feasibility and challenges of addressing this CQ or CC :

These sleep and circadian disorders are extremely common. There is a risk infrastructure for this type of research based on the large number of accredited sleep centers in the United States that could be used for subject recruitment and who can adopt similar techniques. There is also a rich set of data obtained from sleep studies that could be used to identify new patterns that reflect different subgroups of subjects. These studies need to be based on clinical populations of patients who present with the different disorders rather than on population-based cohorts.

Name of idea submitter and other team members who worked on this idea : Sleep Research Society

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167 net votes
220 up votes
53 down votes
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Goal 2: Reduce Human Disease

Consequences of drug interactions leading to QTc prolongation

Better understand the consequences of drug interactions leading to QTc prolongation. About 1/3 of cardiac ICU patients develop QT prolongation and about 45% receive drugs that are possibly contributing to this problem. The full spectrum of contributors and causes, as well as the patient-centered and health-system-centered clinical outcomes, are not known.

Submitted by (@greg.martin)

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

Details on the impact of addressing this CQ or CC :

Reduction in adverse drug events and preventable deaths

Feasibility and challenges of addressing this CQ or CC :

Combining the power of predictive analytics of high dimensional data streaming continuously from critically ill patients, combined with precision medicine genomics and metabolomics, makes this imminently feasible.

Name of idea submitter and other team members who worked on this idea : Society of Critical Care Medicine Executive Council

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Goal 3: Advance Translational Research

Use isogenic iPS cells to advance Precision Medicine

The goals of Precision Medicine can be achieved if we determine the biological basis of disease-associated variants for NHLBI diseases. Advances in genetic research have yielded hundreds of disease-associated DNA polymorphisms, yet we lack robust methods to experimentally test their functional relevance in human cells. Determining the molecular and cellular basis of human phenotypic variation is one of the great challenges ...more »

Submitted by (@bconklin)

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

Details on the impact of addressing this CQ or CC :

Identifying how disease mutations result in cellular phenotypes will provide an experimental basis for Precision Medicine. Advances in genome engineering and iPS cell technology now offer a unique opportunity for NHLBI researchers to make a focused effort to produce isogenic disease models, to determining the function of putative disease loci. Just a few years ago, the barriers to this type of project seemed insurmountable, as iPS cells were made with damaging DNA insertions, designer nucleases were difficult to make, complex material-transfer agreements (MTAs) inhibited the open sharing of reagents, and cell-engineering methods were cumbersome. Remarkably, all of these barriers have fallen substantially in recent years, to reveal strategic new opportunities. The phenotypes are determined in isogenic human iPS-models, these observations can be applied to animal models, and human clinical studies.

Feasibility and challenges of addressing this CQ or CC :

Progress towards this goal is being made, but slow pace does not meet opportunity that the NHLBI community has. The NHLBI has a much larger opportunity than other institutes because so many genetic variants have already been determined via excellent genetic studies using robust physiological phenotypes. The genetic variants provide hypotheses that are ripe for direct experimental testing in isogenic iPS cell models. Fortunately, many diseases of interest to NHLBI can be modeled in iPS-derived tissues. Other part of NIH (e.g. NIMH, NIDA, NIAAA ) lack abundance of high probability genetic "hits" that NHLBI now has. NHLBI should take advantage of this opportunity.

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

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8 up votes
27 down votes
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