Goal 4: Develop Workforce and Resources

Expanding short term Junior Faculty Training Programs such as the Summer Training Programs for Junior Faculty (PRIDE): Focus

Expanding the base of the program foci (e.g. including NCI in addition to the current HLBS).

Submitted by (@treva0)

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

Details on the impact of addressing this CQ or CC :

Expanding the PRIDE program foci beyond NHLBI’s heart, lung, blood, and sleep foci, may involve a common-fund effort, for example by having multiple institutes involved in the program. It is well accepted that good research today is a collaborative effort that often reaches across institutes. For example, the research interests of several PRIDE/SIPID trainees were at the intersection of cardiology and areas such as cancer, diabetes and aging.

Name of idea submitter and other team members who worked on this idea : Treva Rice for the PRIDE (Programs to increase diversity among individuals engaged in health-related research): Joe GN “Skip” Garcia, Francisco Moreno Girardin Jean-Louis, Gbenga Ogedegbe, DC Rao, Victor Davila-Roman, Mohamed Boutjdir, Betty Pace, Juan Gonzales, Bettina M Beech, Keith Norris, Marino Bruce, Alicia Fernandez, Kirsten Bibbins-Domingo, and Margaret Handley.

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10 net votes
14 up votes
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Goal 2: Reduce Human Disease

Innovations in Red Cell Transfusion in Sickle Cell Disease

Challenges that need to be overcome in blood transfusion, especially in SCD, include: a. Adopting molecular genotyping as the standard in blood transfusion therapy. b. Advancing new generation, anti-oxidant hemoglobin-based oxygen carriers (HBOCs) for use in emergencies such as trauma, stroke, acute hemolysis, and in transfusion in SCD and related disorders. In SCD, HBOCs have the capacity to not only serve as substitutes ...more »

Submitted by (@nhlbiforumadministrator1)

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

Details on the impact of addressing this CQ or CC :

Transfusion of RBC is major adjunct in the management of trauma, acute and chronic illness. Issues in blood transfusion include availability of donors, RBC typing and crossmatching, cold storage of donor cells, and limited viability of stored RBC. Globally, in many situations where blood is critically needed, these systems are not available.

An increasing percentage of people with SCD require regular RBC transfusion to prevent stroke and other major complications. In addition, RBC transfusion is employed repeatedly in the management of serious acute complications of SCD. Transfusion of normal RBC to replace or supplement the patient’s defective RBC is the most effective intervention in the management of SCD.

 

Impacts:

• Molecular genotyping of RBC will reduce alloimmunization.

• Use of new generation HBOCs that do not require blood typing, crossmatching, refrigeration, and that do not transmit infection, would save lives in conditions of severe hemorrhage, stroke, possibly heart attack, especially where there is no immediate access to adequate medical facilities.

• In SCD, HBOCs could prevent pain or reduce its severity and duration, prevent stroke, reduce severity of acute chest syndrome, and other vasoocclusive complications. Finally, HBOCs have the potential to alter the pathogenesis of SCD.

Feasibility and challenges of addressing this CQ or CC :

The problems in managing chronic RBC transfusion in SCD remain the same as they have been for decades: all immunization, iron overload, and infection transmission. It is clear that traditional serological RBC phenotyping is unable to detect several variants of RBC antigens, especially those in the Rh system, in populations of African descent. This leads to erroneous phenotyping and the appearance of “auto antibodies” that are truly alloantibodies resulting from transfusion of mismatched blood. As a result, people with SCD are the most frequent users of the American Rare Donor Program.

Name of idea submitter and other team members who worked on this idea : Kwaku Ohene-Frempong, MD

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47 up votes
18 down votes
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Goal 2: Reduce Human Disease

Does epinephrine improve outcomes in OHCA

Epinephrine is the primary drug that is used in resuscitation but observational studies and a few small RCT suggest that it improves short term but not long term outcomes. Factors such as timing, dose, quality fo CPR and post-resuscitation care all confound the issue. Large RCTs conducted at multiple centers are desperately needed to address this question.

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 :

If short terms outcomes are improved but not long term outcomes, we are only adding costs and not improving population health

Feasibility and challenges of addressing this CQ or CC :

Will require a large prehospital clinical trials network and ideally also a current national registry of OHCA to address secular changes in other confounding variables

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

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1 net vote
3 up votes
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Goal 3: Advance Translational Research

NHLBI Cohort Populations for T4 Implementation Research

How best can NHLBI observational cohorts be utilized to study observational T4 Implementation Research among both general and vulnerable US 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 :

• Would help identify key factor associated with successful implementation that could be studied in interventional T4 implementation research

• Result would refine implementation strategies and health and social policy aimed to reduce heart, lung, blood, sleep diseases and conditions

• Builds on excellent established platform of research with high quality outcomes in well characterized study populations over long term follow-up.

Feasibility and challenges of addressing this CQ or CC :

• Big data is developing methods to link large data sets from national, state, and community level surveys – surveys that can define exposures to various policies and interventions in place, time, and population.

• A family of high quality cohorts are available for ancillary observation studies

• Collection of community level and more broad policy level exposures is feasible through data already collected and through potentially new data collection.

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

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11 up votes
15 down votes
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Goal 3: Advance Translational Research

The Designation of Human Cardiac Stem Cell therapy Products for Human Trials or First-in-Human Studies

For successful pharmaceutical development of cardiac stem cell therapy, the human cardiac stem cell therapy product must meet certain commercial criteria in plasticity, specificity, and stability before entry into clinical trials.

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 :

For successful pharmaceutical development of cardiac stem cell therapy, the human cardiac stem cell therapy product must meet certain commercial criteria in plasticity, specificity, and stability before entry into clinical trials. Moving stem cell research from current studies in animals into human trials must address such practical issues for commercial and therapeutic uses: 1) such human stem cells or their cardiac derivatives must be able to be manufactured in a commercial scale; 2) such human stem cells and their cardiac derivatives must be able to retain their normality or stability for a long term; and 3) such human stem cells must be able to differentiate or generate a sufficient number of functional or contractile cardiomyocytes for repair. Those practical issues are essential for designating any human cardiac stem cells as a human cardiac stem cell therapy product for investigational new drug (IND)-filing and entry into clinical trials. So far, the therapeutic effects, if any, of human cardiac stem cells in the existing market, including those derived from patients’ heart tissues, were mediated by protective or tropic mechanism to rescue dying host cardiomyocytes, but not related to myocardium regeneration.

Feasibility and challenges of addressing this CQ or CC :

Opportunity: Recent breakthrough stem cell technologies have demonstrated the direct pharmacologic utility and capacity of pluripotent human embryonic stem cell (hESC) therapy derivatives for human CNS and myocardium regeneration and, thus, have presented the hESC cell therapy derivatives as a powerful pharmacologic agent of cellular entity for a wide range of CNS and heart diseases. The hESC cardiomyocyte cell therapy derivatives by novel small molecule induction provide a large scale of high quality human cardiomyocyte source for myocardium regeneration and, thus, meet the designation of human stem cell therapy products in plasticity, specificity, and stability for commercial development and human trials or first-in-human studies in cardiovascular diseases.

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

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12 up votes
26 down votes
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Goal 2: Reduce Human Disease

How to organize artificial pulsatile propelling of blood maintaining the balanced circulation?

Venous pressure, being very low, distends (deforms) the ventricle - but due to elastic or viscous law of deformation? Elastic deformation depends on stress (pressure) only and the viscous one - on stress and time. When pressures are low you can't get large distention due to stress only (time-independent) unlike the case when you apply low stress and long time interval. If we want to use venous pressure as one of regulators ...more »

Submitted by (@yuri.astrakhan)

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 impact (in case of constructive solution of the problem) can be expected as a breakthrough in the field of engineering of extracorporal circulatory devices and artificial heart. More exactly: the impact will concern the dosage of blood while filling of the ventricle - without intrusion into the essential levels of venous pressure (the levels play the role of regulators together with levels of diastolic arterial pressure).

Feasibility and challenges of addressing this CQ or CC :

The feasibility of implementation (engineering of a device) of the above idea depends on preliminary supercomputer modeling of blood circulation based on simulation of viscous relaxation of ventricle combined with the controlling of circulation according to the deduced equation (see the reference).

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

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-9 net votes
2 up votes
11 down votes
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Goal 2: Reduce Human Disease

Reducing Disparities

NHLBI should continue to support prospective cohort studies, projects, and investigators that evaluate longitudinal outcomes in minority populations where longitudinal data are scarce and difficult to obtain. The resources generated remain invaluable and can be used to conduct crosscutting translational research (i.e. the Jackson Heart Study, Strong Heart Study, and others).

Submitted by (@golan0)

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

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

The potency and safety of transfusable red blood cells

Can we identify approaches to improve potency and/or safety of transfusable RBCs? 42 day pre-transfusion storage of RBCs maximizes utilization, while minimizing waste. However, RBCs undergo changes during collection, manipulation and storage that may reduce their potency or safety. Progress in understanding markers that predict transfusion success at the time of collection and with storage remains slow. New technologies ...more »

Submitted by (@nareg.roubinian)

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

Details on the impact of addressing this CQ or CC :

While novel RBC storage methods have been described, the mechanisms underlying their efficacy has not been defined, a step that will be important for further improvements in this area. Some of these methods appear to improve efficacy of the RBC bioenergetic pathways; however, to date there have not been notable advances in reducing cytoskeletal defects common in stored RBCs. The development of new RBC preservation methods that minimize the impact of the storage lesion on specific areas of concern (e.g., diminished oxidation/peroxidation, decreased membrane fragility) is needed.

 

Use of ex vivo generated RBCs is an alternative to conventional donor-derived RBCs which can potentially improve product consistency, reduce the storage lesion, and improve safety. However, advances are needed before this approach is feasible on a large scale. While the development of blood substitutes including blood pharming will likely require more than 3-10 years before it can be ready for the clinic, Blood Pharming from hematopoietic stem/progenitor cells is now technically feasible and the recent development of genome editing methods suggests the exciting possibility of generating GMP compliant “immortal” stem cell sources to produce transfusable RBCs.

Feasibility and challenges of addressing this CQ or CC :

Research should include both pre-clinical and clinical studies to define optimal combinations of known factors preserving red cells (e.g. hypo-osmolarity, energy sources, antioxidants), and the development of methods for RBC pathogen reduction that do not increase the storage lesion.

 

Procedures for generating blood cells from cultured stem/progenitor cells is not currently cost-effective, limiting near term applications to special patient populations such as specific RBC phenotyping of rare donors for chronically transfused patients. Areas of research needed to advance the development of blood substitutes and blood pharming include: (a) new approaches to blood substitutes including artificial oxygen carriers generated from red cell lysates/components or engineered from combinatorial chemico-biological approaches (e.g., derivatization of hemoglobin, encapsidation of modulated oxygen carriers); (b) a better understanding of the biological properties of cultured RBCs with the goal of reducing blood pharming costs; (c) optimizing methods to expand stem cell populations while allowing differentiation to selected clinically relevant blood cell populations at clinically relevant levels; and (d) optimizing methodologies that faithfully replicate embryonic development to develop the cells of interest.

Name of idea submitter and other team members who worked on this idea : Nareg Roubinian, MD and Naomi Luban, MD for the NHLBI State of the Science in Transfusion Medicine

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14 net votes
31 up votes
17 down votes
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Goal 2: Reduce Human Disease

Long-term pulmonary function in survivors of critical illness

Pulmonary function is known to suffer during the early recovery phases from critical illness, but the long-term patterns of recovery and associated consequences are uncertain. In addition, the clinical and molecular determinants of progressive deterioration or recovery of pulmonary function remain unknown.

Submitted by (@greg.martin)

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 : Society of Critical Care Medicine Executive Committee/Council

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4 net votes
7 up votes
3 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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2 net votes
2 up votes
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Goal 4: Develop Workforce and Resources

Enhance funding for population and public health research

Many challenges posted here focus on increasing translation and development of interdisciplinary teams. Diverse backgrounds and epidemiological training makes population and public health scientists ideal candidates to connect teams in different areas of research around translation to human health. While funding exists specifically for career development of physician and pre-clinical scientists, none exists for epidemiologists. ...more »

Submitted by (@mmongrawchaffin)

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

Details on the impact of addressing this CQ or CC :

NHLBI is currently investing heavily in training epidemiologists at the PhD and postdoctoral level, but may be losing those researchers during the transition to independence and mid-career stages. Compared to those with clinical backgrounds or basic science skills, PhD epidemiologists rarely have alternative resources to fall back on when NIH funding is reduced and may have less interest in joining industry if their primary research interest is improving public health at the population level. This may make epidemiologists particularly vulnerable to leaving the field of health research. Dedicated funding that prioritizes human studies and population level research would help retain well-trained epidemiologists whose primary dedication is to improving chronic disease outcomes.

Feasibility and challenges of addressing this CQ or CC :

While the current level of funding is a challenge to everyone working in science right now, adding funding mechanisms specifically for epidemiology like those that already exist for clinician scientists and pre-clinical research could play an essential role in maintaining the pace of innovation and implementation of research.

Name of idea submitter and other team members who worked on this idea : Morgana Mongraw-Chaffin

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16 net votes
29 up votes
13 down votes
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Goal 3: Advance Translational Research

Screening the work force for genetic arrhythmias

Is anyone in your family at risk for a potentially lethal genetic arrhythmia? 4000 young people die each year because they bear a genetic mutation that makes them susceptible to a sudden fatal arrhythmia. The symptoms are easy to identify and awareness of these symptoms would help unsuspecting families.

 

It is estimated that one of these syndromes (LQTS) is 3 times more common in the US than childhood leukemia.

Submitted by (@andygolden)

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 are 3 simple warning signs for families bearing dominant mutations that could lead to arrhythmia and sudden death. These are unexplained fainting or seizure during exercise or startle, an unexplained sudden death of a young family member, chest pain and/or shortness of breath during exercise. A simple questionnaire of all families with children entering school or any athlete signing up for a sport, or any adult entering the work force would help identify potential family members at risk for these genetic arrythmias.

Feasibility and challenges of addressing this CQ or CC :

A simple questionnaire of all families with children entering school or any athlete signing up for a sport, or any adult entering the work force would help identify potential family members at risk for these genetic arrythmias. Such potential patients could then be further screening by a EKG and a consult with a cardiologist.

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

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12 down votes
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