Goal 2: Reduce Human Disease

Hemostatic treatment with plasma versus 4-factor PCC in the critically ill

For patients in the ICU with coagulopathy and associated World Health Organization (WHO) grade 3 or 4 bleeding, which hemostatic therapy -- plasma versus 4-factor prothrombin complex concentrates -- is preferred?

Submitted by (@darylkor)

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

Details on the impact of addressing this CQ or CC :

Bleeding is frequently encountered in the ICU and is associated with substantial morbidity and associated mortality. When bleeding occurs, coagulopathy is often present and the optimal coagulation factor management regimen remains a matter of debate. Traditionally (and presently in the US), plasma transfusion has been a cornerstone therapy for the replacement of coagulation factor content in this setting. Moreover, recent evidence supporting the use of plasma in the setting of trauma-related hemorrhage seems to have also generated a renewed enthusiasm for plasma transfusion in other critical care settings.

 

In many locations, there is interest in alternatives to plasma transfusion such as four-factor prothrombin complex concentrates (PCC4) for ICU patients with bleeding. In some locations, factor concentrates have entirely replaced plasma transfusion. However, evidence regarding the benefits and risks of PCC4 versus plasma in ICU patients is lacking. Therefore, we would aim to study the comparative efficacy and risks of a hemostatic strategy relying on PCC4 versus plasma for ICU patients with coagulopathy and bleeding.

Feasibility and challenges of addressing this CQ or CC :

Coagulopathy and associated bleeding are common in the intensive care unit environment. Therefore, we believe a multicenter clinical trial evaluating the knowledge gap identified above would be feasible with NHLBI support. Of note, due to the labeled contraindication of disseminated intravascular coagulation for PCC4, such patients would need to be excluded from this trial. Similarly, coagulation abnormalities resulting from congenital coagulation factor deficiencies for which there is a specific coagulation factor product available would also be excluded.

 

Notably, improved management of coagulopathic bleeding has the potential to impact both clinical outcomes and healthcare resource utilization. Therefore, the outcomes of a trial addressing this knowledge gap would include patient-important outcomes (e.g. mortality, length of hospital stay, bleeding, transfusion-related respiratory complications, thromboembolic complications) as well as outcomes related to healthcare utilization (e.g. product cost, total blood products consumed, interventions required to achieve hemostasis such as surgery or embolization).

Name of idea submitter and other team members who worked on this idea : Daryl J. Kor, MD and Walter H. Dzik, MD for the 2015 NHLBI State of the Science in Transfusion Medicine

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28 net votes
43 up votes
15 down votes
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Goal 1: Promote Human Health

Hypertension in children and adolescents - diagnosis and long term outcomes in large populations

Can we improve the thresholds for defining hypertension in children and adolescents based on risks for future adverse cardiovascular sequelae? In addition, can we to better understand how early identification of hypertension impacts long term health outcomes?

Submitted by (@elyse.o.kharbanda)

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 thresholds for diagnosing hypertension in children and adolescents are based on the distribution of BP in general populations but are not linked to clinical outcomes. Most elevated BP in children and adolescents remains unrecognized, and there is little population level data on the benefits of early idnetification and treatment. There is a critical need for longitudinal data on BP with considerations that thresholds for diagnosing hypertension, evaluating for secondary causes and treating in this age group shoudl be linked to risks for long term cardiovasular sequelae. Important to consider is that labeling a child with mildly elevated BP as having hypertension could adversely impact family functioning and childhood health.

Feasibility and challenges of addressing this CQ or CC :

This could be addressed through a population-based, observational cohort study, spanning childhood through young adulthood.

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

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12 net votes
16 up votes
4 down votes
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Goal 3: Advance Translational Research

Translation of scientific information into clinical and public health asthma and allergies practices and programs

More evidence-based, scientifically proven interventions to ensure that scientific information is translated into clinical and public health practices and programs to reduce the burden of asthma and allergies on individuals, families and society

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 : Asthma and Allergy Foundation of America (AAFA)

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

The "Metagenome"

How could we best understand the interplay within the metagenome (the nuclear (nDNA), mitochondrial (mtDNA), and microbiome DNA), and between the metagenome and environment as a cause for individual variability, including susceptibility to disease and therapeutics? Could the genomic “chimerism” possibly be related to reported sex differences in HLBS diseases? • Most factors needed for mitochondria are encoded by nDNA. ...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 :

Would allow understanding the basis for complex individual variations beyond the current focus on the nuclear genome

Feasibility and challenges of addressing this CQ or CC :

Feasible in 10 years.

For example, the issue of “chimerism” between mtDNA and nDNA is intriguing: every cell, male or female, contains mtDNA and mitochondria of female (maternal) origin. Mitochondria are cell’s main energy engine, essential in all cells with high energy expenditure, such as myocytes, but mitochondria are also emerging as a major source of pathogenic reactive oxygen species in connection with a variety of heart, lung, blood, sleep diseases.

 

 

High complexity requires researchers working across discipline boundaries, big data science, modeling

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

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-25 net votes
9 up votes
34 down votes
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Goal 1: Promote Human Health

Use of Evolutioinary Biology in Medicine

Given that chronic diseases are 'Evolutionary Biology' in reverse, can we use developmental and phylogenetic principles to diagnose and treat them safely and effectively?

Submitted by (@johntorday)

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

Details on the impact of addressing this CQ or CC :

Biomedical research is currently in crisis. Both basic science and translational science are failing to provide new insights to the causes of disease and their eradication. Instead, we are encouraged as biomedical researchers to devise ways of eliminating the symptoms of disease. This is a very bad practice since it facilitates the retention of maladaptive genes in the gene pool.

 

This practice is the result of continuing to practice biology and medicine descriptively, like Chemistry and Physics were as Alchemy and Astrology. The lack of a fundamental understanding of the First Principles of Biology originating in unicellular organisms fosters continued study of associations and correlations instead of causal mechanisms. If the National Science Foundation were still funding Astrology, we would see the same lack of predictive value that we see in biology and medicine today. Society cannot afford to continue sponsoring such pseudoscience. This problem is already recognized indirectly due to the failure of the Human Genome Project to fulfill its promise of curing common chronic diseases such as heart attack, stroke, diabetes and obesity. But the withholding of funding from the NIH to shake out the dead wood will not solve the problem, because it is due to the use of the wrong paradigm. Understanding how and why vertebrates evolved on the cellular-molecular level offers a way of understanding causation in biology and medicine rendering them predictive.

Feasibility and challenges of addressing this CQ or CC :

This initiative is highly feasible since we already have the methods available to us in the biomedical research community. The problem is in recognizing that applying 'omics' to the problems we face using same old same old Pathophysiology will not solve the problems of medicine. That precept is founded on Health as the absence of disease, which proved useful for a century, but we are now attempting to tackle more difficult fundamental problems that require a more powerful approach. The Evolutionary Biology approach offers the opportunity to define Health objectively rather than relativistically, i.e. health and disease are a continuum generated by the mechanisms of evolution.

Name of idea submitter and other team members who worked on this idea : John Torday, Virender Rehan, Neil Blackstone

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-15 net votes
13 up votes
28 down votes
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Goal 3: Advance Translational Research

Arrhythmia Therapies Based on Understanding Mechanisms

There is a need to translate these new insights of genetic, molecular, cellular, and tissue arrhythmia mechanisms into the development of novel, safe, and new therapeutic interventions for the treatment and prevention of cardiac arrhythmias.

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 :

Reduced socioeconomic burden of cardiac arrhythmias. Development of new technologies and recognition of new arrhythmia mechanisms.

Feasibility and challenges of addressing this CQ or CC :

Several studies have already recognized the unexpected antiarrhythmic effects of some therapies intended for other cardiovascular disease. For example statins, aldosterone blockers, and possibly some essential fatty acids may reduce arrhythmia burden in patients receiving these interventions. Clinical trials should be developed to demonstrate the efficacy of these interventions, and arrhythmia endpoints, including those for atrial fibrillation and sudden cardiac death, should be incorporated into other large clinical trials. Research into novel antiarrhythmic might focus on (a) drug development; (b) cell/gene-based therapy and tissue engineering; and (c) improvements in development and use of devices and ablation to prevent or inhibit arrhythmic electrical activity. Continued research might also focus on targeting of upstream regulatory cascades of ion channel expression and function. Continued antiarrhythmic strategies might include the exploration of novel delivery systems (e.g., utilizing advances in nanotechnology and microelectronics), biological pacemakers, AV node repair/bypass, and treatment and/or reversal of disease-induced myocardial remodeling and tachyarrhythmias. Evaluation of new therapies should include a cost analysis. Studies in both children and adults with congenital heart are needed. New interventions might include new pharmacologic approaches as well as advances in electrophysiologic imaging and improved approaches to ablation.

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

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51 net votes
86 up votes
35 down votes
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Goal 2: Reduce Human Disease

Therapeutic hypothermia and CPR

Is intra-arrest therapeutic hypothermia feasible during CPR, and does it improve outcomes?

Submitted by (@rebecca.lehotzky)

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 : AHA Staff & Volunteers

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

Point of care detection of rare cells in blood

Laboratory analyses at the bedside or in the hinterlands can reduce the cost and increase the capture of disease states in underserved populations. The injection of a blood draw directly into a portable device that requires no further operator interventions is a Critical Challenge. With today’s automated chemistry and a miniaturized flow cytometer this challenge could be met.

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 :

Although portable flow cytometers exist, they are not equipped with chemical automation and rare-cell enrichment capability. An integrated system could be applied to multiple diagnostic goals. A sufficiently versatile design should be able to detect and enumerate specific cell populations at any level (not only rare cells) in the circulation — T-cell subsets in AIDS, for example.

Feasibility and challenges of addressing this CQ or CC :

Automated mixing and labeling, magnetic bioseparations, microfluidics, high-intensity LEDs and sensitive avalanche photodiodes can be combined to address this CC.

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

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-6 net votes
4 up votes
10 down votes
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Goal 4: Develop Workforce and Resources

Using virtual learning technologies for workforce development

How can we harness virtual learning technologies to address the competency development needs of the modern and future biomedical workforce? Virtual learning tools, e.g. immersive learning simulations and serious games, offer tremendous possibilities for creating engaging and compelling learning experiences for biomedical scientists and providing them with opportunities to practice research skills within the context of ...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 :

Virtual learning technologies have been successfully used to promote workforce competency development in a variety of fields including defense, business, and surgery, particularly in areas that require higher-order cognitive skills, such as critical thinking, problem solving, decision making by simulating the real-life situations and conditions under which these skills are developed. We believe that significant improvements can be achieved in the overall preparedness of the biomedical workforce through the use of flexible virtual training and education tools that can help address the critical competency areas that have the most impact on research success. For instance, considering the team-based nature of most biomedical research efforts requiring effective communication and collaboration of experts from different fields, new workforce development approaches must be grounded in team science. Virtual learning environments provide an excellent opportunity to practice effective teamwork skills within the context of realistic scenarios, virtual and live character interactions, and structured reflection/debriefing exercises. Similarly, harnessing the power of virtual learning tools to train up-and-coming biomedical scientists to think through scientific and organizational challenges in a disciplined yet creative way, leveraging evidence from decades of research on decision making, would help accelerate the expertise development process of a new generation of biomedical researchers

Feasibility and challenges of addressing this CQ or CC :

Virtual learning tools represent a powerful mechanism for activating the principles of problem-based learning and experiential learning through anchored instruction, meaningful contextualization, active participation, intrinsic motivation, and continuous assessment. While there is a growing interest in bringing virtual learning tools to the biomedical science domain, this area remains relatively untapped and calls to advance an understanding of how particular types of instructional strategies and virtual learning tools/resources compare in terms of promoting target competencies, behaviors, and research outcomes in real life, i.e. the learning transfer. This remains a challenge considering the lack of funding opportunities available to explore not only the feasibility of bringing these tools to the biomedical sciences domain but also examining the sustaining effects of the novel training and education interventions going forward. We feel that NHLBI is better positioned than ma ny other NIH entities to address this challenge and spearhead the learning innovation efforts for the biomedical research workforce, as it reaches across a very diverse community of biomedical scientists who need to work together effectively and efficiently to solve the most pressing biomedical and healthcare challenges we face today.

Name of idea submitter and other team members who worked on this idea : Anya Andrews, Ph.D., PMP, Director of Research Initiatives, Associate Professor of Medicine, University of Central Florida College of Medicine

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2 net votes
5 up votes
3 down votes
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Goal 2: Reduce Human Disease

Genetic engineering in lung progenitor cells

Can genome engineering be used to correct or alter lung stem/progenitor cells to ameliorate lung disease and promote regeneration?

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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-15 net votes
3 up votes
18 down votes
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Goal 2: Reduce Human Disease

Image Repository

There is a need to digitize, remove identifiers, and archive, and catalog physical images, and to promote their use in clinical investigations.

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 :

Enable leveraging existing resources and possible re-purposing of existing resources to address a wide variety of research questions.

 

This is a cross-study, cross-NHLBI, and even cross-NIH or beyond, need.

Feasibility and challenges of addressing this CQ or CC :

Digitized imaging data files are enormous. Advances in data storage, with corresponding decreases in cost, have enabled storage of these files. For some types of images, data format standards have also arisen.

Many studies have collected data using a wide variety of imaging technologies. While the extracted data have been utilized in analyses and incorporated into shared data resources, additional research could be done on the original images.

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

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4 net votes
12 up votes
8 down votes
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Goal 2: Reduce Human Disease

Conduct a clinical trial whether maximizing melatonin using orange eyeglasses in the evning reduces breast cancer.

Epidemiological studies have shown totally blind women have about half the incidence of breast cancer as blind women who retain light control of melatonin suppression or of women with normal vision. Studies show shift worker that reduces melatonin and disrupts the circadian rhythm increases the risk of breast cancer. Studies show human breast cancer grafts grown on rats but supplied with human blood grow rapidly if the ...more »

Submitted by (@rhansler)

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

Details on the impact of addressing this CQ or CC :

About 250,000 new cases of breast cancer are diagnosed each year in just the U.S. The evidence suggests this number could be cut in half by simply changing to low-blue light bulbs or by wearing blue blocking glasses for a few hours before bedtime. A similar situation exists for prostate cancer. Without clinical trials the medical community will not believe it is true, despite all the evidence.Since there are no expensive drugs involved, no drug company will fund this type of trial so the federal government or foundations are the only likely funders. Reducing breast cancer incidence to half is worth billions of dollars to say nothing about the reduction in human suffering.

Feasibility and challenges of addressing this CQ or CC :

By using women at high risk for cancer the time to carry out a trial of modest size will be reduced. Since there is essentially no risk and improved sleep is a side effect, compliance should be high.

Name of idea submitter and other team members who worked on this idea : Richardd L. Hansler PhD Edward Carome PhD Vilnis Kubulins MS

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-3 net votes
7 up votes
10 down votes
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