Strategic Goal: Goal 2: Reduce Human Disease

Transforming Clinical Practice through Patient-Centered Medical Nutrition and Lifestyle Education

The fact that diet contributes significantly to prevention and treatment of disease is now a foregone conclusion. National and international guidelines offer evidence based recommendations advocating nutrients, foods and eating patterns that are most closely associated with reduced risk. Patients assume that physicians are knowledgeable regarding the role of diet in health and that they are trained to counsel patients ...more »

Submitted by (@lvanhorn)

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

Details on the impact of addressing this CQ or CC :

AHA/ACC guidelines subsequent to the NHLBI ATPIII all provide diet-related recommendations for improving public health that, if followed, could offer tremendous benefits in reduced disability, death and health care costs. However, imperative to the implementation of these life-saving recommendations, is an informed and educated provider base that is skilled in: assessment of patients’ diets and eating behaviors, evaluation of possible risk factor contributors and initiation of diet counseling or referral to a qualified nutritionist.

 

Nowhere is the opportunity greater to assess, evaluate and offer guidance towards improvement of key diet behaviors than in primary care. Patients perceive physicians as credible, respected sources of nutrition counseling. Physician endorsement of diet and lifestyle change favorably influences patient adherence. Research to evaluate patient-centered medical education and training programs is needed to evaluate and compare patient perception, health impact and health outcomes of these translational nutrition efforts. Ultimately, the goal is to further calculate and quantify the economic and personal benefits that accompany these strategies in order to implement transformed medical education aimed at preventive strategies.

Feasibility and challenges of addressing this CQ or CC :

This is a major challenge due to current medical training focused on diagnosis and treatment rather than prevention. Research is needed to demonstrate cost/benefit of transformative education and training that shifts the focus from treatment to prevention. Successful outcomes can provide preliminary evidence needed to promote a paradigm shift across -medical schools and allied health professions with the ultimate goal of - improving medical practice and quality of life. Evidence is needed that documents patient-centered impact resulting from this training and actual practice. Proposed is a comprehensive, team science approach to testing the results of nutrition and lifestyle medicine in primary care and the biomedical, behavioral and economic impact derived from it.

This represents an ambitious task requiring an academic medical center environment that not only has the educational aspect in place but also the capacity to provide the translational effort at the bedside and in outpatient settings to allow measurement of results. It requires leadership in multiple arenas and coordination between education and clinical application that are crucial to successful implementation. It further requires leadership and expertise in big data, economics, biostatistics and the accompanying technology required to

assess, analyze and report all of the aspects and components inherent in a project of this magnitude.

Name of idea submitter and other team members who worked on this idea : Linda Van Horn, PhD, RD

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Strategic Goal: Goal 2: Reduce Human Disease

Consequences of ABO or Rh Type Specific versus Non-Type Specific Platelet Transfusions

What are the consequences, clinically and immunologically, of ABO or Rh type specific vs. non-type specific platelet transfusions? There is widely varying practice as to ABO and Rh matching of platelets for transfusion. Most studies demonstrate that use of ABO unmatched (non-identical) platelets are associated with increased 1) platelet refractoriness (small randomized trials), 2) red cell transfusion needs and hemolysis, ...more »

Submitted by (@cjoseph)

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

Details on the impact of addressing this CQ or CC :

Large randomized trials would answer the ABO and Rh related critical clinical outcomes question for platelet transfusions in all patients who commonly receive multiple platelet transfusions. This would include most patients with acute hematologic diseases, patients undergoing complex cardiac surgery, solid and stem cell transplant recipients and trauma patients. In addition, modeling the effects of ABO and Rh incompatibility/non-identity in animal models and in vitro would provide data on basic platelet immunobiology.

In vitro and animal model studies that might be relevant include effects of ABO immune complexes on endothelial cell and glycan interactions with other cells of the vasculature and blood. Effects on TLR, interleukin receptors and secreted cytokines are additional considerations.

Feasibility and challenges of addressing this CQ or CC :

A randomized trial in patients undergoing induction therapy for acute leukemia and/or allogeneic stem cell transplant would accrue enough patients rapidly to answer this question in, at most, two-three years, given the repeated transfusions of platelets to such patients. A comparison of current practice, or intentionally employing ABO/Rh major mismatched platelets (no risk of hemolysis) as the control arm, versus only ABO/Rh identical platelets in the experimental arm is feasible and ethical. Outcomes such as bleeding, time to engraftment and survival (100 day and long term) are important and scientifically of interest. Companion scientific mechanism studies of effects on inflammation, immunity (adaptive and innate) and hemostasis and thrombosis would be feasible in vitro, in animal models and in the patients in the clinical trial. A similar trial would be informative in patients undergoing complex adult or pediatric cardiac surgery (e.g., combined valve/CABG, LVAD insertion, single ventricle physiology operations) or adult/pediatric ECMO settings.

4. References

1. Carr R, et al. Br J Haematol 1990;75:408-13.

2. Heal JM, et al. Ann Hematol 1993;66:309.

3. Heal JM, et al. EurJHaematol 1993;50:110-7.

4. Blumberg N, et al. Transfusion 2001;41:790-3.

5. Shanwell A, et al. Vox Sanguinis 2009;96:316-23.

6. Inaba K, et al. Arch Surg 2010;145:899-906. 

Name of idea submitter and other team members who worked on this idea : Cassandra Josephson on behalf of the Platelet Committee from the State of the Science Meeting 2015

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Strategic Goal: Goal 2: Reduce Human Disease

Timing of post-cardiac arrest PCI

The majority of patients who are resuscitated from OHCA have a presumed cardiac etiology. One of the key interventions post cardiac arrest is to study the coronary circulation for underlying thrombosis. Some centers do this routinely but at other centers interventional cardiologists are hesitant to do this since the mortality rates are high and so affect their individual and institutional performance measures related ...more »

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 :

There is variability in practice and no large scale level 1 evidence as to what is the best to do with regards to post ROSC care and PCI as well as timing of the PCI

Feasibility and challenges of addressing this CQ or CC :

Will require funding, broad cooperation between cardiologists and emergency medical services as well as critical care. National groups that conduct performance measures for survival following PCI need to readdress the use of such measures in this group of patients (post-arrest)

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

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Strategic Goal: Goal 4: Develop Workforce and Resources

Translational training programs

The strategic vision to enhance translation and to enhance the workforce both require training that spans the scope of basic science, pre-clinical development, clinical trials. We lack coherent mechanisms for training the next generation of translational researchers, some of whom may be MDs, and some PhDs. A program should provide cross-training of Clinical Fellows and Postdocs to reflect the needed interactions between ...more »

Submitted by (@wjones7)

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 will trainees with more comprehensive exposure and involvement in translation of science from the bench to bedside. MDs will spend more time in labs or involved in pre-clinical work, PhDs will become CITI certified and assist with enrollment of clinical trials and trial design. Journal clubs will span the sciences, the clinical practice and the translational realm including regulatory and industry considerations. Trainees can use this background whether they go on in medicine, science, translation, or industry to fit and contribute to an increasingly translational medical bioscience field.

Feasibility and challenges of addressing this CQ or CC :

Feasibility must include a academic medicine environment active in translational biomedical science such that the mentors can include scientists, physicians and physician/scientists, some of whom are translators. Some of the scientists should be from industry and perhaps projects and funding can involve industry/Pharm as well these will benefit from an educated workforce. Challenges involve individuals at the sites putting the right teams together, but many Universities are doing this with incubators and translational units at present. This will further the clinical involvement to include Fellows in Fellowship programs in Cardiology, Medicine and Surgery.

Name of idea submitter and other team members who worked on this idea : Keith Jones

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Strategic Goal: 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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Strategic Goal: Goal 2: Reduce Human Disease

RFA on EC-cardiomyocyte interactions in the mechanisms and treatments of cardiovascular diseases

Often under recognized, the cardiac endothelial cells are highly abundant in the heart, and may have important roles in modulating cardiac function, besides simply serving as structural component of blood vessels. Evidences of ours and others have indicated an emerging role of cardiac endothelial cells signaling to cardiomyocytes to mediate important pathophysiological responses. Nonetheless, detailed mechanisms of ...more »

Submitted by (@hcai00)

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

Details on the impact of addressing this CQ or CC :

Successfully addressing this question would no double reveal novel mechanisms and ways of monitoring treatment responses of cardiovascular disease, ultimately leading to novel drug targets, valuable biomarkers and extended new directions of basic research as well.

Feasibility and challenges of addressing this CQ or CC :

Tools of studying these cells are mostly available. Both adult cardiomyocytes and endothelial cells from the heart can be isolated and cultured, although cardiomyotyes need to used within 24 hrs and cannot be passaged. However successful preparation of these cells from WT and transgenic animals would permit co-culture experiments and mechanistic studies. These cells can also be studied using in-situ techniques either detecting molecular changes/events or dynamic interactions. Potential challenges would side in selective targeting of these cells, for example, either ECs or cardiomyocytes, once a potential therapeutic is in the testing. Nonetheless, PECAM-ab conjugated techniques have been employed to specifically deliver proteins to endothelial cells, so I am confident most of the challenges can be worked out, particularly within a RFA awardees group with frequent exchanges of ideas.

Name of idea submitter and other team members who worked on this idea : Hua Linda Cai, University of California Los Angeles

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Strategic Goal: Goal 1: Promote Human Health

Human normal variation and resilience across lifespan

What is the measureable normal human variation at the -omic, cellular, organ, and system levels within the population and across the lifespan? • What are the range of normal human cellular functions that create resilience at all levels—cells, organs, organ systems? • What inter-organ, tissue, and cellular communications maintain individual health and the health of populations? • How do we understand why individuals with ...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 :

• Will provide a better definition of what is normal in order to better interpret and exploit the big data available through increased personalized monitoring and use of EMRs.

• Insights into the underlying mechanisms of resilient phenotypes will provide new paradigms for disease prevention and treatment.

Feasibility and challenges of addressing this CQ or CC :

Feasibility will depend on the level of investment (large) and accessibility to commons data.

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

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Strategic Goal: 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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Strategic Goal: Goal 2: Reduce Human Disease

Defining critical elements for irreversible myocardial injury

What are the critical mechanisms that account for progression from reversible to irreversible ischemia and reperfusion injury?

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 :

Understanding the mechanism of how myocardium becomes irreversibly injured will provide clarity for therapeutic intervention.

Feasibility and challenges of addressing this CQ or CC :

Advances in proteomics and databases of post-translational modifications may support the feasibility of discoveries in this area.

This information is key for designing novel therapeutic strategies for acute myocardial ischemic injury. This understanding will define the critical timing, location, and distribution of modulators, and amplitude required for activation of components involved in protective pathways.

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Strategic Goal: Goal 2: Reduce Human Disease

Sleep Disorders and Brain Maturation

What is the effect of sleep disorders on child development? Specifically, how sleep apnea with intermittent hypoxia and or sleep deprivation alters the normal trajectory of maturation of brain regions controlling cognition, behavior and the cardiovascular system?

Submitted by (@raouf.amin)

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 significance of the behavioral and cardiovascular findings in children as they relate to health during adulthood is unknown. It remains to be defined whether the behavioral and cardiovascular abnormalities observed in children with sleep apnea are a reflection of structural and functional brain abnormalities, which might persist into adulthood and predispose to health problems at an older age.

A fundamental question that deserve investigation whether brain maturation in children with sleep apnea and sleep deprivation deviate from normal trajectory and whether brain plasticity can restore normal structure and function.

Such knowledge on brain maturation and plasticity in children with sleep disorders could lead to the identification of brain biomarkers that might signal risk for future mood and behavioral disorders and or cardiovascular diseases. The new knowledge will also identify sensitive period(s) during child development for interventions.

Feasibility and challenges of addressing this CQ or CC :

In the last decade, the application of new technologies of fMRI and diffusion MRI have permitted the study of the evolving brain connectome across all stages of development and created new potentials to inform our etiologic understanding of many pediatric and adult diseases.

We now can for the first time examine the brain developmental trajectories in children with chronic medical conditions including sleep disorders and compare the findings to normative data.

Name of idea submitter and other team members who worked on this idea : Raouf Amin, Mark DiFrancesco, Scott Holland

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Strategic Goal: Goal 3: Advance Translational Research

Clinical Tools for Pediatric CVD Risk Reduction and Asthma Treat

What are effective strategies and clinical decision support tools that can maximize pediatric care providers’ adoption of evidence-based recommendations for assessment and treatment of cardiovascular risk factors and/or asthma? • Clinical recommendations and associated implementation tools are often incorporated into electronic medical records (EMRs). Currently there is no standard EMR format and therefore it is difficult ...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 :

• Cardiovascular disease (CVD) remains the leading cause of death and disability in North America. There is extensive evidence documenting the initiation of the atherosclerotic process, the pathologic basis for clinical heart disease, in childhood. Additionally, asthma a chronic condition that affects more than 7 million children in the U.S. and leading to numerous emergency visits.

• Among the major factors that are associated with increased clinical recommendation use are ease of access and feasibility. A common obstacle that providers face is the availability of proper information at the point of care.

• The Community Preventive Services Task Force recommends clinical decision-support systems for prevention of cardiovascular disease based on sufficient evidence of effectiveness in improving screening for CVD risk factors and practices for CVD-related preventive care services, clinical tests, and treatments. Mobile solutions may help to further facilitate this process.

• Successful implementation of clinical recommendations for prevention and treatment of CVD pediatric risk factors and asthma could greatly reduce the number of youth moving into adulthood at increased risk for CVD and could improve health outcomes for children with asthma.

Feasibility and challenges of addressing this CQ or CC :

• Most care providers have mobile devices or computers for use in the clinical setting. There is good evidence that clinical decision support tools (and other implementation tools) can help facilitate adoption of clinical recommendation.

• It is important to test strategies in a large scale intervention that will measure clinical CVD outcomes.

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

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Strategic Goal: Goal 3: Advance Translational Research

Advanced Models for Translational Cardiovascular Research and Drug Development

Although the study of the cardiovascular (CV) system has benefited significantly from the use of gene-targeted and transgenic mouse models, small rodents do not always accurately reflect human cardiovascular physiology. Many discoveries using mouse CVD models failed to translate into human applications.

Submitted by (@echenum)

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

Details on the impact of addressing this CQ or CC :

Outcomes from large animal studies are likely to translate into more favorable results in human studies. Historically, some of the most significant advances in modern CV medicine are indebted to large animals.

Feasibility and challenges of addressing this CQ or CC :

Recent advances in mammalian genome projects and gene targeting technologies enable the production of large animal models. Genome information is now available for many animal species including pigs, rabbits, dogs, cats, horses and cows. Customizable nucleases, such as Zinc Finger Nuclease (ZFN), Transcription Activator-Like Effector Nuclease (TALEN), CRISPRs (clustered regularly interspaced short palindromic repeats) associated protein-9 nuclease (Cas9) has enabled the production of gene targeted animals in many of these species lacking germline transmitting embryonic stem (ES) cells, with satisfactory results. Integration of these novel knowledge and technologies in non-primate large animals will lead to production of an array of novel models of human CVD. Research in these models will help identify and establish suitable animal models that faithfully predict the outcomes in human clinical trials of new medicines and treatments. This is believed to have a major impact in the medical research field in general and significantly move cardiovascular research and drug development forward.

Name of idea submitter and other team members who worked on this idea : Eugene Chen from University of Michigan

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