Goal 3: Advance Translational Research

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

Strategic Goal: 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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3 up votes
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Strategic Goal: 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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-2 net votes
11 up votes
13 down votes
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Strategic Goal: Goal 3: Advance Translational Research

Build a National Surveillance of Chronic CV and Lung Diseases

There is a need to build a robust coordinated surveillance system on the incidence and prevalence of chronic diseases. Surveillance data are needed to: •Describe and monitor the burden, trends, and patterns of these diseases •Set parameters and metrics of research priorities •Identify where to target resources for prevention, treatment, and delivery of care •Track and monitor progress toward public health disease ...more »

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 :

The high prevalence of chronic cardiovascular and lung diseases has created burden in increasing healthcare costs and high mortality rates in the US compared to other developed countries. Even so, they remain among the most preventable health problems. A national surveillance system for chronic cardiovascular and lung diseases would enable data-driven decision-making about public health strategies for prevention, management, and cost containment.

Feasibility and challenges of addressing this CQ or CC :

A 2011 Institute of Medicine (IOM) report concluded that a coordinated surveillance system is needed. It proposed a framework for such a system that would integrate existing information through collective efforts of multiple stakeholders. The time is right to gain from and build upon numerous ongoing broad initiatives in biomedical Big Data, including growing health IT adoption mandated by the HITECH Act, ONCHIT efforts to achieve health IT interoperability, the NIH BD2K initiative, and the multiorganizational network participating in FDA Mini-Sentinel, HCS Collaboratory, and PCORnet, among others. The NHLBI is well-positioned to lead, develop and implement the IOM’s recommended framework and system. (IOM report - http://www.iom.edu/Reports/2011/A-Nationwide-Framework-for-Surveillance-of-Cardiovascular-and-Chronic-Lung-Diseases.aspx)

Existing data sources (i.e., population surveys, registries, cohort studies, administrative data, and vital statistics) do not individually provide nationally representative data, cannot be linked, and are not currently readily accessible to all levels of users. One potential way to build such a system is to integrate and expand existing data sources.

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

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13 up votes
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Strategic Goal: Goal 3: Advance Translational Research

Weight Loss Maintenance

How can we improve and optimize strategies for weight loss maintenance to make them more effective for more individuals?

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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20 net votes
62 up votes
42 down votes
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Strategic Goal: Goal 3: Advance Translational Research

Paradigm shift in cardiac arrest rhythm and resuscitation

What resuscitation strategies targeted toward pulseless electrical activity (PEA)/asystole would be successful in preventing cardiac arrest (CA)? Furthermore, what are animal models of PEA/asystole, what is responsible of this major shift in the underlying rhythm of CA, and what is the phenotype?

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 :

There is a critical need to address continuous shift in the primary rhythm of CA from VT/VF to PEA/asystole with new strategies to improve survival.

Feasibility and challenges of addressing this CQ or CC :

Data from major registries, such as ROC, CARES and other provide the needed population base and platform to analyze existing strategies, explore and develop and test new resuscitation strategies.

With the continuous decline in VT/VF proportion as the primary rhythm leading to cardiac arrest (CA), pulseless electrical activity (PEA) and asystole have become the dominant rhythms in CA. In early 70's VT/VF constituted more than half of the CA, which currently is ~ 28%. Major effort and defibrilation and resuscitation strategies have been successfully targeted toward VT/VF. The survival of PEA/asystole is dismal.

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

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7 up votes
11 down votes
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Strategic Goal: Goal 3: Advance Translational Research

Deriving Cardiac Elements from Pluripotent Human embryonic Stem Cells for Heart Reconstitution

to date, the existing markets lack a clinically-suitable human cardiomyocyte source with adequate myocardium regenerative potential, which has been the major setback in developing safe and effective cell-based therapies for regenerating the damaged human heart in cardiovascular disease.

Submitted by (@xuejunparsons)

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

Details on the impact of addressing this CQ or CC :

Given the limited capacity of the heart for self-repair or renewal, cell-based therapy represents a promising therapeutic approach closest to provide a cure to restore normal heart tissue and function for CVD. There is no evidence that adult stem/precursor/progenitor cells derived from mature tissues, such as bone marrow, cord blood, umbilical cord, mesenchymal stem cells, patients’ heart tissue, placenta, or fat tissue, are able to give rise to the contractile heart muscle cells following transplantation into the heart. Despite numerous reports about cell populations expressing stem/precursor/progenitor cell markers identified in the adult hearts, the minuscule quantities and growing evidences indicating that they are not genuine heart cells and that they give rise predominantly to non-functional smooth muscle cells rather than functional contractile cardiomyocytes have caused skepticism if they can potentially be harnessed for cardiac repair. In recent years, reprogrammed or trans-differentiated adult cells, as a result of being backed by excess sum of government and private funding, have been rekindled as the adult alternates. However, major drawbacks such as abnormal gene expression, accelerated aging, immune rejection, not graftable, and extremely low efficiencies, have severely impaired the utility of reprogrammed or trans-differentiated somatic cells as viable therapeutic approaches.

Feasibility and challenges of addressing this CQ or CC :

Opportunity: Derivation of pluripotent human embryonic stem cells (hESCs) from the IVF leftover embryos has brought a new era of cellular medicine for the heart. The intrinsic ability of a hESC for both unlimited self-renewal and differentiation into clinically-relevant lineages makes it a practically inexhaustible source of replacement cells for human tissue and function restoration. Therefore, it has been regarded as an ideal source to provide a large supply of functional human cells to heal the damaged or lost tissues that have naturally limited capacity for renewal, such as the human heart and the human brain. Although a vast sum of NHLBI funding has been spent on looking for adult alternates, such as reprogramming and trans-differentiation of fibroblasts or mature tissues, so far, only human cardiac stem/precursor/progenitor cells derived from embryo-originated hESCs have shown such cellular pharmacologic utility and capacity adequate for myocardium regeneration in pharmaceutical development of stem cell therapy for the damaged human heart.

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

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10 up votes
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Strategic Goal: Goal 3: Advance Translational Research

The impact of a COPD patient education program

What is the impact of an organized, comprehensive, COPD patient education program, on medication delivery effectiveness, care plan adherence, appropriate use of LTOT and Pulmonary Rehabilitation? Metrics could include incidence and severity of exacerbations, and health care resource consumption.

Submitted by (@dprieto)

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

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11 net votes
15 up votes
4 down votes
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Strategic Goal: Goal 3: Advance Translational Research

Development of Novel Apheresis Adsorption Technologies to More Effectively and Safely Treat Hematologic Diseases

Current FDA approved apheresis technology currently uses elutriation/centrifugation separation techniques to remove pathologic cellular and/or plasma elements. These techniques are non-specific, limited by inefficient removal kinetics and often require considerable blood product exposure. Despite tremendous improvement in our understanding of the pathophysiology of a variety of disease, our ability to treat many of ...more »

Submitted by (@ewong0)

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

Details on the impact of addressing this CQ or CC :

More efficient and novel means of selectively removing pathologic cellular and/or plasma elements are needed when a disease specific pathologic cellular element or plasma element is identified (i.e. anti-RBC autoantibodies in patient with severe autoimmune hemolytic anemia, anti-platelet antibody in patients with autoimmune thrombocytopenic purpura, anti-platelet factor four antibodies associated with heparin associated thrombocytopenia, complement fixing, donor specific antibodies in antibody mediated cardiac rejection, antibodies implicated in catastrophic antiphospholipid syndrome, mediators of the inflammatory response in sepsis, etc. ).

 

These are especially needed in patients who are critically ill and in need of rapid removal of these pathologic blood elements. Selectively and rapidly removing disease associated cellular and/or plasma elements while returning the remainder of the patient’s cells and/or plasma can minimize additional blood product exposure with its attendant risks, reduce duration of treatment significantly, and offer new forms of treatment either not available in the U.S. or not previously considered.

Feasibility and challenges of addressing this CQ or CC :

Selective removal of pathologic plasma elements has been demonstrated by the development of selective adsorption columns which bind inflammatory mediators and immunoglobulins, but are not currently being used in the U.S. Current technology exists to remove specific pathologic plasma elements. For example, immunoadsorption technology, which incorporates polyclonal sheep anti-human IgG antibodies bound covalently to sepharose columns can remove >98% of all IgG subclasses after multiple treatment sessions. Similar effect can be obtained by Protein A sepharose column (Prosorba) technology which had been approved for use by the FDA for rheumatoid arthritis; however, in 2006 the manufacturer stopped producing the column due to financial reasons. Clearly, research into the use of these columns in the context of well designed, randomized clinical trials would be readily feasible with the appropriate IND and require industry support.

 

Furthermore, the technology that is used to couple sheep anti-human IgG antibodies to sepharose, can used to create antigen specific adsorption columns for removal of specific pathologic antibodies, for example, anti-PF4 antibodies that are involved in heparin associated thrombocytopenia, or Clq dependent (C1q) donor specific HLA antibodies that are involved in antibody mediated cardiac rejection. Industry support/small business grant support will be needed for development of these columns in addition to clinical trials demonstrating efficacy

Name of idea submitter and other team members who worked on this idea : Edward Wong on behalf of ASFA

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93 net votes
112 up votes
19 down votes
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Strategic Goal: Goal 3: Advance Translational Research

Interventions to Eliminate Health Inequities

There is a need to identify effective interventions for heart, lung, blood, and sleep diseases that could have a transformative population level impact on health inequities if expanded at the national level.

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 :

• Provide new knowledge for implementing strategies that will tackle inequities

• Provides opportunity to create multidiscipline research communities focused on health inequities

• Will gain momentum from federal and national implementation institutions to promote effective interventions to address health inequities

Feasibility and challenges of addressing this CQ or CC :

• Capitalizing on new methods, metrics and tapping big data could provide a promising platform to use systems science to better understand the barriers to eliminating health inequities in a short timeframe

• Identifying barriers will allow investigators to devise innovative implementation strategies that can reduce health inequities

• NHLBI could encourage communities of researchers to use team science to both identify barriers and link with other teams to implement strategies to reduce and eliminate barriers

• Established NHLBI health inequities Think Tank and space for developing innovative strategies to address health inequities.

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

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32 net votes
47 up votes
15 down votes
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Strategic Goal: Goal 3: Advance Translational Research

Understanding Chronic Lung Disease Subtypes

What are the subtypes of chronic obstructive lung disease that share a common pathogenesis and can be a basis for precision medicine?

Submitted by (@jdc000)

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

Details on the impact of addressing this CQ or CC :

Chronic Obstructive Pulmonary Disease (COPD) is a complex heterogeneous syndrome. The current approach of regarding this disease as a single entity has limited the ability to develop effective therapies and prevention. Understanding the major subtypes of COPD could lead to more biologically relevant disease classifications, improved prognostic information, and precision medicine treatment.

Feasibility and challenges of addressing this CQ or CC :

The optimal analytical approaches and data types to define complex disease subtypes have not been determined.

Name of idea submitter and other team members who worked on this idea : Ed Silverman, James Crapo and COPDGene Executive Committee

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32 net votes
50 up votes
18 down votes
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Strategic Goal: Goal 3: Advance Translational Research

High cost, high risk and unclear benefits of current COPD care

Challenge the unspoken of high cost, high risk and unclear benefits of current COPD care a. PRCT of lung transplantation vs. optimized medical care b. Noninvasive ventilation for treatment of chronic severe respiratory failure c. Chronic combined vs. de-escalation of chronic bronchodilator therapy to as needed for GOLD stages III-IV d. Self management programs in COPD e. Telemedicine in outpatient management of severe ...more »

Submitted by (@nhlbiforumadministrator)

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 : American Thoracic Society member

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2 up votes
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Strategic Goal: Goal 3: Advance Translational Research

Leveraging Networks of Federally Qualified Healthcare Centers

How best do we leverage the existing Federally Qualified Healthcare Center’s (FQHC) infrastructure to study T4 Implementation Research for heart, lung, blood, sleep diseases and conditions among high risk and vulnerable populations?

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 strategies to reduced Health Inequities

• Potentially be scaled up across an entire health system with huge population impact

• Studies would be done in the environment and context where the findings with be implemented leading to better uptake and sustainability.

Feasibility and challenges of addressing this CQ or CC :

• Formative FQHC groups are already being organized but do not have strong leadership and support

• FQHCs have ready access to the high risk and vulnerable populations that would benefit most from the research

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

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-14 net votes
7 up votes
21 down votes
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