Goal 2: Reduce Human Disease

Personalized therapy of HCT complications

Can biomarkers make all the use of new predictive biomarkers enable earlier and more effective treatment of acute GVHD? Can biomarkers accurately guide reduction in therapy for patients who will respond to standard steroid treatment? Can biomarkers enable earlier and thus more effective therapy for high risk GVHD? Can new biomarkers (proteomic, genomic or a combination) also predict patients who are risk of relapse?

Submitted by (@james.ferrara)

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

Details on the impact of addressing this CQ or CC :

Despite enormous advances in immunology over the past several decades, there are no validated new therapies for acute GVHD, the major complication of allogeneic HCT. Several biomarkers have now been identified at the onset of GVHD that can predict response to treatment and provide a personalized profile of patients. But these biomarkers have not yet been used to guide therapy, and definitive clinical trials are needed to answer this question

Feasibility and challenges of addressing this CQ or CC :

Need for consistent and accurate biomarker determination available for a large number of centers

Name of idea submitter and other team members who worked on this idea : John Levine and James Ferrara

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74 net votes
99 up votes
25 down votes
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Goal 2: Reduce Human Disease

Is there a Biomarker for the Pulmonary Fibrosis of HPS?

Hermansky-Pudlak Syndrome is characterized by a bleeding disorder as well as pulmonary fibrosis. Invasive procedures such as a lung biopsy are contraindicated due to bleeding and bronchoscopy is not without risk. Finding a biomarker would reduce the necessity for more invasive data collection while improving outcomes.

Submitted by (@dappell)

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

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

Addition of albumin to fluid conservative management of AL

Does the addition of albumin to fluid conservative management of ALI (ARDSnet FACTT trial protocol, Wiedemann et al) further shorten ventilator time and/or improve survival?

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

Liberal versus restrictive plasma prior to invasive procedures

At what INR threshold does prophylactic plasma transfusion, in non-bleeding critically ill patients who are planned to undergo an invasive procedure, prevent bleeding complications and improve patient outcomes?

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 :

Millions of plasma units continue to be transfused to non-bleeding critically ill patients. This practice persists despite the lack of high quality evidence indicating improved patient outcomes with prophylactic plasma transfusion triggered by the INR. Studies testing restrictive versus liberal transfusion triggers are now well-established in academic medicine for Red Blood Cell products. More recently, multicenter clinical trials of prophylactic platelet transfusion vs no-prophylaxis have been conducted as well. However, there remains substantial equipoise on the topic of prophylactic plasma transfusion. A large definitive clinical trial that aims to identify the INR threshold at which prophylactic plasma transfusion prevents bleeding complications in non-bleeding critically ill patients would impact clinical practice in a very meaningful way.

Feasibility and challenges of addressing this CQ or CC :

Abnormal coagulation tests are common in the ICU and plasma is frequently administered in this specific clinical setting. Indeed, more plasma is administered in the ICU environment than in any other clinical area. Therefore, a multi-center clinical trial addressing the knowledge gap identified above would be feasible with NHLBI support.

 

Importantly, healthcare providers become increasingly uncomfortable with the avoidance of coagulation factor replacement as coagulation screening test results drift further from the normal range. To address this concern, an adaptive clinical trial may be desirable. In this design, a targeted cohort with modest elevations in the INR measurement would be screened for enrollment (e.g. INR results ranging from 1.5 - 2.0). If the avoidance of plasma transfusion is noted to be safe, the study would advance to the next stage of recruitment, targeting a higher range of INR values (e.g. 2.0 - 2.5).

 

Finally, the value of the INR in predicting bleeding complications is increasingly scrutinized. Therefore, it can be argued that the INR is not the ideal "trigger" for plasma transfusion. Despite this, it must be acknowledged that the INR remains the primary driver of decisions related to plasma transfusion. Therefore, a large definitive trial specifically detailing the the efficacy of the current practice versus a more conservative approach to prophylactic plasma transfusion would be practice changing and potentially very transformative.

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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19 net votes
39 up votes
20 down votes
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Goal 2: Reduce Human Disease

Additional research needed to identify various contributors of obesity

What are the specific contributors of obesity that lead to chronic positive energy balance and surplus energy storage?

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 :

Obesity is a health crisis of epic proportions. About 34% of adults in the US have obesity, up from 31 % in 1999 and about 15% in the years 1960 to 1980. The chronic diseases that result from obesity annually cost over $150 billion in weight-related medical bills. Reduction of obesity improves cardiovascular and other health outcomes, yet what is currently known about obesity is inadequate to combat the global obesity epidemic. A comprehensive understanding about the mechanics of obesity may help in developing more effective preventive and treatment strategies, which in turn will substantially improve cardiovascular and other health measures.

Feasibility and challenges of addressing this CQ or CC :

Years of obesity research have revealed the complex nature of this disease and its multi-factorial etiology. While research has firmly established the role of energy balance in weight gain and weight loss, it is important to discover upstream factors that predispose only certain individuals to energy imbalance. This may be addressed by further focusing on newly identified putative contributors of obesity, including but not limited to the impact of sleep deprivation, ambient temperature, age at first pregnancy, intrauterine and intergenerational factors, neuro-endocrine factors, epigenetics, environmental chemicals and endocrine disruptors, gut microbes, infections and the immune system, and social and behavioral factors associated with obesogenic behaviors. These studies may provide mechanistic insight that may also lead to the development of new pharmacological approaches. It is possible that cause-specific prevention or treatment approaches may yield more effective results than generic approaches that do not necessarily consider upstream modulators of energy imbalance, or inter-individual differences.

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

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8 net votes
18 up votes
10 down votes
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Goal 4: Develop Workforce and Resources

Training the new generation: not all about “big data” & "omics"

How do we attract more students/trainees into fields that are not popularized by “catchy” names?

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 :

Training the next generation of scientists

Feasibility and challenges of addressing this CQ or CC :

While the need to train the next generation of scientists in emerging fields (e.g. “omics” and “big data”), we should not overlook the need for nurturing “old fashioned” scientists (e.g. physiologists, integrative biologists) which are on the decline.

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

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23 net votes
35 up votes
12 down votes
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Goal 4: Develop Workforce and Resources

Funding & Review Mechanisms

Funding and review mechanisms are essential resources that can facilitate or hinder innovative research to meet the NHLBI goals. These resources must be refocused to result in identification and funding of the type of innovative research being sought by NHLBI. The opportunities for leveraging available NHLBI funds with other sources should be considered formally as a component of overall budget planning, not just on ...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 should be more equitable access to funds, as perceived by potential recipients; provision of funds for high-priority topics; and revitalized, refocused review groups that are willing and able to consider recommending high risk, innovative approaches.

Feasibility and challenges of addressing this CQ or CC :

This is a very specific challenge that may require incremental implementation with some experimentation/pretesting and solicitation of ideas from a range of stakeholders identified during this goal-setting exercise. While the Institute may be able to make changes in how funding mechanisms are employed, making changes to review group membership may be more challenging, especially in the current context of recruiting members. Incentives for this service may also need to be reviewed, innovatively, under current budget constraints.

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

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4 net votes
8 up votes
4 down votes
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Goal 1: Promote Human Health

What is the potential effect of the burden of COPD on the US workforce?

COPD currently affects approximately 25 million individuals in the US alone, many of whom are of working age, according to the most recent BFRSS data. Many of those people are encouraged by their doctors or families to apply for disability and receive it, even though there are still jobs they could do. This is going to have an impact on business and industry as these people who are at the peak of their careers leave. ...more »

Submitted by (@jmrommes)

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

Details on the impact of addressing this CQ or CC :

I think if this question were answered and that industry understood the impact of COPD on the potential workforce going forward, there would be significant interest from business and industry to do several things:

prevent COPD; develop accommodations that would allow people with COPD to continue to work; reduce the burden to both industry and individuals with COPD by allowing them to continue to work and produce until planned retirement.

Feasibility and challenges of addressing this CQ or CC :

This would not be a difficult question to answer. More difficult would be the education of both individuals and business and industry in how to accommodate people with COPD so they can continue to work until their planned retirement. Techniques and strategies could be developed, however, benefiting both business and the individual.

Name of idea submitter and other team members who worked on this idea : Jean M. Rommes

Voting

8 net votes
15 up votes
7 down votes
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Goal 2: Reduce Human Disease

What are the molecular mechanisms of lung injury, and how do they differ in children?

Both adults and children have significant morbidity and mortality due to lung injury, but have different etiologies and outcomes. It is possible that the underlying pathobiology in the two groups is different. There are no targeted therapies for lung injury, indicating that the cause is still not understood.

Submitted by (@rft2106)

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

Details on the impact of addressing this CQ or CC :

Mortality rates for acute lung injury in pediatrics vary from about 10-30%. Immunosuppressed patients and those with cancer have higher rates. Morbidity following long ICU stays have social impacts on family and education, and can put patients at risk of future lung complications.

 

Though ECMO shows promise of improving outcomes, large clinical studies are lacking. ECMO is also fraught with signifiant risks and high costs. A molecular understanding of the pathobiology of lung injury could lead to specific therapies to improve survival and decrease morbidity.

Feasibility and challenges of addressing this CQ or CC :

(1) The heterogeneity of both adults and children with lung injury hinders the applicability of clinical and translational studies. (2) Reliable animal models of pediatric lung injury are lacking.

Name of idea submitter and other team members who worked on this idea : Rebecca Turcotte

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4 net votes
4 up votes
0 down votes
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Goal 2: Reduce Human Disease

Pathobiology of COPD

Define the pathobiology of the disorder (COPD)

a. Mechanisms of lung injury

b. Mechanisms of lung repair

c. Balance of lung and systemic pathobiologic manifestations and mechanisms

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

Life-Course Approach to Science

We encourage the NHLBI to include research focused on children as a priority in their strategic vision. We encourage them to consider the implications of a life-course approach, where childhood presents a unique opportunity to set the trajectory for health risk as an adult. This also implies that interventions targeting children may have the greatest impact on the population as a whole in the long term.

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 Society of Pediatric Nephrology (ASPN)

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2 net votes
2 up votes
0 down votes
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