Goal 2: Reduce Human Disease

The 'other' circulation system - the lymphatic system needs the attention the blood circulation system receives.

Much is still unknown about the lymphatic system. No medical specialist owns it. NHLBI and NCI could work together on understanding lymphatic disease in the direction of understanding how metastasis spreads disease. NHLBI can help by establishing a unit to organize research interest in such an important body system in health and disease.

Submitted by (@jayfk20)

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

Details on the impact of addressing this CQ or CC :

Understanding the lymphatic system and how metastasis facilitates it as a highway to spread disease could save many lives.

Feasibility and challenges of addressing this CQ or CC :

There are several lymphatic diseases such as lymphangiomatosis - which are complex and systemic - through the study of which, we can learn the role the lymphatic system plays in disease - beyond the well-known essential functions of fat absorption, the immune response and in maintaining fluid balance.

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Goal 2: Reduce Human Disease

Adequately powered clinical trials

Pragmatic and adequately powered clinical trials are an ongoing challenge.

­Develop new tools to facilitate identification and recruitment of subjects, remote/wireless data collection, and functional measures.

Submitted by (@societyforvascularsurgery)

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 : Society for Vascular Surgery

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Goal 2: Reduce Human Disease

Reducing Variability in Outcomes from Out of Hospital Cardiac Arrest

Out of hospital cardiac arrest remains a major cause of mortality in the United States and there is a large variability in survival within communities. We need to better understand the reasons for this variability which include patient, event, EMS system and care processes and work as a nation to reduce the variability but adopting best practices and actively addressing the barriers to change which can be social, cultural, ...more »

Submitted by (@dayam0)

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

Details on the impact of addressing this CQ or CC :

If we could reduce variability, we would save more lives and also enhance the chain of survival in our communities

Feasibility and challenges of addressing this CQ or CC :

will require that we connect multiple parts of the community including the population at risk, public health services and the health care system which is not always easy in silo systems or fragmented health care systems

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

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Goal 1: Promote Human Health

THE RELEVANCE OF PREVENTION TRIALS

Prevention trials, implemented to reduce or delay progression to overt disease in a population at risk to the disease, are an important approach to health promotion. Therapies shown to reduce disease severity in patients with a specific disease are obvious, but not the only, candidates for a prevention trial in populations at high risk for prevalent diseases (such as heart failure, diabetes, COPD, asthma in children). ...more »

Submitted by (@media0)

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 impact of implementing such trials is considerable. They will clearly address an important component of NHLBI’s mission with respect to effectiveness of therapies and behavioral interventions, and it has minimal and clearly definable overlap with commercial trials of specific therapeutic products. It will also provide an important public health focus – preventing disease or reducing the impact of disease processes, thus potentially reducing chronic care costs and increasing years of useful life.

Feasibility and challenges of addressing this CQ or CC :

The biggest challenge in designing and implementing prevention trials is identifying the target, “at risk” population most likely to develop the clinical disease from known biomarkers or early signs/symptoms. Increasing availability of large, population-based registries or databases maintained for other purposes provides a very cost-efficient mechanism to electronically screen and identify “at risk” individuals. The same mechanism may also facilitate implementation of pragmatic, electronically managed, cost efficient trials.

Name of idea submitter and other team members who worked on this idea : Sonja McKinlay other Team Members: Susan Assmann and Paul Stark

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Goal 3: Advance Translational Research

Need to Determine the Basis for Difference in Response to Weight Management Approaches

Why does the response to weight loss regimen in terms of weight loss and its sustainability, and improvement in health outcomes vary considerably?

Submitted by (@mturner)

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

Details on the impact of addressing this CQ or CC :

Past research focused on using variations of diet and exercise has revealed important information about the health benefits of weight loss. The limitations of such approaches in producing biologically meaningful and sustained weight loss for the majority have also been recognized. Even within a study population, compliance to weight loss regimen, weight loss and its sustainability, and improvement in health outcomes vary considerably. Research is needed to identify the basis for this variation, which may lead to enhanced outcome and applicability of such approaches.

Feasibility and challenges of addressing this CQ or CC :

Identifying factors that enhance weight management response may lead to translational studies that yield more effective results. A strong support of promising clinical translational research may promote a conducive environment for developing more practical applications.

Name of idea submitter and other team members who worked on this idea : The Obesity Society

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Goal 3: Advance Translational Research

Leverage Information Technology to Improve Patient Safety in Surgery

Progress toward a six-sigma level of safety (already achieved in commercial aviation) has been slow in medicine and surgery. The best cardiac surgery program operates at only 3.5 sigma level. In order to acceletate this process, it is critical to leveage recent advances in information technology, including but not limited to natural language processing (NLP), advanced speech recognition, artificial intelligence.

Submitted by (@marcozenati)

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

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Goal 2: Reduce Human Disease

Evidence based approaches to Red Blood Cell transfusion

What are the optimal RBC transfusion thresholds for adult and pediatric cancer patients undergoing chemotherapy regimens that may improve functional status and quality of life?

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 :

Cancer patients undergo intensive medical and surgical therapies to treat their underlying disease. Treatment commonly results in anemia requiring RBC and platelet transfusions to support the patient through the hypoproliferative phase of chemotherapy. This is particularly true for those patients requiring hematopoetic stem cell transplantation (HSCT). Following therapy, cancer outpatients commonly receive RBC transfusions for weeks to months to maintain their functional status.

 

Common causes of death in patients with hematological malignancies and other cancers are infections and bleeding. A meta-analysis of clinical trials suggested that liberal transfusion is associated with greater risk of infection. Conversely, restrictive transfusion could adversely affect quality of life and functional status in oncology populations. In addition, pre-clinical and clinical studies support that concomitant anemia and thrombocytopenia significantly compound bleeding risk, and that hemostasis can be optimized in thrombocytopenia by maintaining a higher hematocrit. Although bleeding risks in relation to platelet transfusion thresholds are well studied in patients with hematological malignancy, optimal hemoglobin levels in thrombocytopenic patients are not known. Despite the significant allocation of blood components to cancer patients as a whole, RBC transfusion practices are not well studied within this group.

Feasibility and challenges of addressing this CQ or CC :

Randomized controlled clinical trials and other studies investigating optimal transfusion thresholds and other measures of practice are required to provide health care providers with evidence to guide one of the most common therapies administered in the setting of malignancy. The clinically important end points of well-designed studies could include: 1) quality of life and functional status for both inpatients and outpatients; 2) neurocognitive development in pediatric populations; 3) bleeding events / bleeding scores; 4) impact on immunity including immunomodulation and infection; 5) reconstitution of hematopoiesis; and 6) survival and/or recurrence of disease.. Besides a generalizable study population, certain target populations of interest are those with high risk disease, HSCT patients, patients undergoing radiation therapy, and pediatric patients.

 

There are >1.6 million new cases of cancer annually in the USA, including >50,000 with leukemia and >6,000 with HSCT. Cancer therapies are rapidly advancing in the era of genomics and immunotherapy. Capitalizing on the tradition of research in cancer, single and multicenter studies of RBC transfusion are feasible using randomized controlled designs in conjunction with clinical trials of chemotherapeutic regimens. The results of these studies will impact a large patient population’s quality of life, and may ultimately impact healthcare cost and blood demand.

Name of idea submitter and other team members who worked on this idea : Nareg Roubinian, MD and Naomi Luban, MD for the 2015 NHLBI State of the Science in Transfusion Medicine

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Goal 1: Promote Human Health

Promoting health through simultaneous prevention of obesity and eating disorders

How to best promote healthy weight while also not stigmatizing obesity and creating risk for eating disorders (i.e., weight concern and body dissatisfaction) in youth. How to tackle both without contributing in unwitting way to development of either.

Submitted by (@tantillo)

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

Details on the impact of addressing this CQ or CC :

Studies show that diets do not lead to sustained health benefits for the majority of people and several studies indicate that dieting is actually a consistent predictor of future weight gain. Repeated cycles of losing and gaining weight are linked to heart disease, stroke, diabetes and altered immune function. Children and adolescents are especially vulnerable to the impact of dieting. Several long-term research studies show that girls and boys who use unhealthy weight control practices (including dieting) in early teen years are more likely to become overweight five years later, even if they started out at normal weight. These studies also show that early teen boys and girls who use unhealthy weight control practices are at greater risk for binge eating, use of severe weight control practices ( vomiting, diet pills, laxatives and water pills), and eating disorders compared with adolescents not using weight-control behaviors.

 

Since our culture tends to create weight bias and obesity stigmatization, it is not surprising to see our children become increasingly fearful of becoming “fat.” Weight concern can be experienced by underweight, average weight and overweight children and teens. Studies have shown that body dissatisfaction, especially weight concern (for early teen boys and girls), can lead to overweight, binge eating, severe weight control practices, and eating disorders. Weight teasing by family members and peers can also increase the risk for eating disorders.

Feasibility and challenges of addressing this CQ or CC :

Challenges include creating teams of researchers who will collaborate across the two fields. I believe if we could create such teams we could

move both fields ahead with regard to prevention and a focus on health (behaviors that are health promoting), not BMI (a number) or an emphasis on intake.

 

The key to both health problems involves the ecology in which youth are located b/c this ecology influences body image, intake, activity, self regulation and self care.

Name of idea submitter and other team members who worked on this idea : Mary Tantillo PhD PMHCNS-BC FAED

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Goal 1: Promote Human Health

The coupling of mechanical stress to biochemistry, molecular biology and electrophysiology

Cells aren’t beakers holding soluble reactants waiting to be mixed. Cells are structured objects where life forms as a flow of free energy between three pools: chemical, electrical and mechanical. Most papers in the literature ignore structure (except of Xray or EM of specific proteins) and almost all ignore the coupling of mechanics to the other pools. Cells cannot be studied with in vitro experiments. We can study single ...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 :

If we learn how a third of all cellular energy is used we have a better chance of understanding the other 2/3.

Feasibility and challenges of addressing this CQ or CC :

See more at: http://grants.nih.gov/grants/guide/notice-files/NOT-HL-15-252.html#sthash.7xHiSbcd.dpuf

Name of idea submitter and other team members who worked on this idea : Dr. Frederick Sachs

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Goal 3: Advance Translational Research

Scientific priorities for HIV-related cardiovascular research

Millions of virally suppressed patients with HIV/AIDS survive to older ages and will become increasingly vulnerable to inflammation-associated cardiovascular disease. The critical challenge is to determine whether age-driven cardiovascular declines that occur HIV-infected people are exacerbated by the persistent systemic inflammatory drive that occurs in virally suppressed patients. Studies that document cardiovascular ...more »

Submitted by (@bgelman)

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 impact of this critical challenge would be to heighten the translational impact of HIV-related cardiovascular research. Key facets of this challenge are: 1) To give high priority to studies that use human tissue specimens that have been carefully annotated and biobanked, 2) To be certain that proposed studies employ tissue from age-appropriate comparison patients who were not HIV infected, and 3) To avoid giving undue credence to acute infection or in vitro infection models (as with tat and gp120 toxicology) that do not reflect immunologic and virologic mechanisms in virally suppressed patients. Millions of virally suppressed patients with HIV/AIDS survive to older ages, and become increasingly vulnerable to cardiovascular disease. Ischemia-related disease causes dysfunction especially in organs that depend on abundant blood flow such heart, brain and kidneys. All these organs are affected to some extent by persistent inflammation in virally suppressed HIV-infected patents. The compelling question/critical challenge is to determine whether age-associated cardiovascular changes are exacerbated by persistent mild systemic inflammatory drive that are found in blood vessels of virally suppressed patients. Studies that document the presence of cardiovascular changes in older infected people without controls, or in vitro models of acute infection, both do not address issues of high translational relevancy. Using human tissue specimens from age-appropriate controls does.

Feasibility and challenges of addressing this CQ or CC :

Feasibility:

1) Obtaining well-annotated organ specimens from HIV infected and noninfected people is feasible. The National NeuroAIDS Tissue Consortium (NNTC) collection goes well beyond the CNS and includes heart, lung, kidney, gut, liver, spleen and other organs. Many of the organs specimens in the collection have been annotated with virological and immunological markers already.

2) Over 900 autopsies on HIV infected patients are banked by the NNTC and over 100 of these decedents were over the age of 50. Over 200 controls are effectively banked. These specimens and related clinical data are in the public domain at this time.

3) Age appropriate autopsies were done by the NNTC, and a large number of NIA sponsored tissue repositories have accumulated tissue from elderly patients.

Challenges:

1) The limitations of using autopsy material and the limits of a cross sectional view need to be better understood and appreciated. These studies should not be written off scientifically as "observational" or "not hypothesis driven."

2) The lessons of not using age-appropriate controls have NOT yet been learned in the HIV/AIDS research community. A prime example is an overabundance of brain aging surveys in HIV infected populations that did not contain age-appropriate controls. A controversial and inconclusive brain aging pathology literature was produced because of that.

Name of idea submitter and other team members who worked on this idea : Benjamin Gelman

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Goal 4: Develop Workforce and Resources

Exposing students of all ages to Discovery science

What kinds of incentives, reforms, and exposures would work best with students from diverse and disadvantaged backgrounds to pursue careers in science?

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 :

• It would produce an excited scientific workforce that will enhance healthcare and sustain discovery in the fields served by NHLBI.

Feasibility and challenges of addressing this CQ or CC :

• It is entirely feasible to develop programs for teachers and incentives for students.

• Pilot programs may be needed to establish feasibility of clinical training for PhDs and research training for MDs.

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

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