Goal 2: Reduce Human Disease

To extend our knowledge of the pathobiology of heart, lung, blood, and sleep disorders and enable clinical investigations that advance the prediction, prevention, preemption, treatment, and cures of human disease.

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

Voting

3 net votes
4 up votes
1 down votes
Active

Goal 2: Reduce Human Disease

Funding Limitations Block Intervention Research

The cap on R01 research grants at $500,000 per year has not changed in over 20 years. In the current fiscal crisis for research it has become an immovable block to submitting intervention studies (randomized clinical trials on treatment). Routine advice from NIH staff is to not even try for a larger study. The cap applies to every year, so one can design a trial that costs less than $2.5 million but exceeds $500,000 in ...more »

Submitted by (@stephen.fortmann)

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

Details on the impact of addressing this CQ or CC :

While it is difficult to argue for increasing funding for anything these days, the $500,000 cap on R01 funding is exerting a perverse bias on research. Very few intervention trials can be accomplished without exceeding this limit in at least one year. This means that trials are limited to those of interest to the NIH staff and to the pharmaceutical industry. Investigators interested in solving therapeutic problems are being force to abandon trials and rely on natural experiments and observational studies, which cannot address all important questions. The natural creativity of the scientific community is being artificially suppressed, distorting the field. The notion that pragmatic trials can substitute for explanatory trials is misplaced. Many unsettled questions cannot be pursued in pragmatic trials, which generally reduce informed consent to a degree to call into question their ethics. It is also unclear that many pragmatic trials can be done under the cap, since they often require extensive work with providers and the healthcare delivery system hierarchy.

Feasibility and challenges of addressing this CQ or CC :

Even a modest change in the cap would be very helpful. Perhaps allowing 1-2 years to be as high as $600,000 without triggering the permission process. Alternatively, the review process for studies exceeding $500,000 could be streamlined if the total does not exceed $2.5 million. Other ways to introduce flexibility are possible. This would allow more ideas to go to review and the staff, who are increasingly deciding which grants get funded, will have more to choose from.

Name of idea submitter and other team members who worked on this idea : Stephen P. Fortmann

Voting

3 net votes
6 up votes
3 down votes
Active

Goal 2: Reduce Human Disease

Mitigating risks due to the RBC storage lesion and vulnerable patients

What are the underlying dependencies (genomic, metabolic, disease) in individual donors that either accelerate or delay the changes to red blood cells during refrigerated storage? What methods of preparation might protect patients from the risks posed by the accelerated degradation of RBCs provided by "poor storers"? What characteristics of individual patients make them particularly vulnerable to transfusion of red ...more »

Submitted by (@andrew.dunham)

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 changes in red blood cells during refrigerated storage have been well documented and associated with negative clinical sequelae in the peer reviewed literature. While the impact of this so-called storage lesion does not impact every patient during every transfusion it is reasonable to expect that when a unit of blood is transfused to a particularly vulnerable patient from a donor that has red blood cells pre-disposed to degradation, stored in a manner that has allowed significant change to occur, the risk of a negative clinical sequelae is increased. In this case it will be important to understand what underlies the likelihood of a donors blood to store poorly, the changes that occur during storage that could impact vulnerable patients and design approaches to mitigate the degradation that could result.

Feasibility and challenges of addressing this CQ or CC :

We believe mitigating the impact of the storage lesion is feasible by reducing and controlling the oxygen concentration in the RBC unit prior to refrigerated storage. We are continuing our development of a device to do this and to generate the data demonstrating the effect of deoxygenation and anaerobic storage.

Name of idea submitter and other team members who worked on this idea : Andrew Dunham

Voting

3 net votes
3 up votes
0 down votes
Active

Goal 2: Reduce Human Disease

Use of health communication principles in management of obesity

What approaches can utilize current knowledge on health literacy/health communications as a research development tool and/or strategy to enhance obesity prevention and treatment efforts?

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 :

Allow the use of non-activity and non-dietary based approaches for managing overweight and obesity

Feasibility and challenges of addressing this CQ or CC :

Health communication and health literacy are of interest in the US Healthy People 2020 goals. The methodology and principles of health communications and the relationship between health literacy and health outcomes are emerging especially for obesity. There is a sufficient pool of scientists trained to conduct this type of work.

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

Voting

22 net votes
49 up votes
27 down votes
Active

Goal 2: Reduce Human Disease

Interstitial Lung Disease

Is FVC a valid surrogate for mortality in patients with idiopathic pulmonary disease?

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 :

This question is central to all future clinical research in the field and MUST be answered in the context of an interventional clinical trial. Longitudinal cohort studies correlating FVC change with survival are insufficient. The intervention that would make the most sense to test currently is pirfenidone. It is approved for use in many countries and many experts (including the submitter of this compelling question) believe it is likely effective. A mortality-driven clinical trial of pirfenidone vs. placebo would address this question directly, as well as determine the true impact of pirfenidone on clinically meaningful endpoints.

Name of idea submitter and other team members who worked on this idea : ATS Member

Voting

1 net vote
1 up votes
0 down votes
Active

Goal 2: Reduce Human Disease

Systems biology and pathobiology

What are systems-based approaches to better define disease endotypes and develop more effective therapies, especially in multiple chronic conditions?

Submitted by (@nhlbiforumadministrator1)

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

Voting

11 net votes
19 up votes
8 down votes
Active

Goal 2: Reduce Human Disease

e-cigarette and mental health

What is nicotine addiction in the absence of other materials? What cues are associated with smoking? We would like to see brain reward studies in special populations. We are also interested in understanding possible reduced harm in people who use e-cigarettes in cessation attempts, and understanding whether e-cigs are a gateway to other risky behaviors for young people who are experimenting.

Submitted by (@anna.adachimejia)

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 : Anna Adachi-Mejia for colleagues at Dartmouth

Voting

1 net vote
1 up votes
0 down votes
Active

Goal 2: Reduce Human Disease

What new methods of platelet preparation, processing, and storage are needed for hemostasis in various clinical conditions?

The limitations of 5-day 22˚ C storage significantly impacts platelet availability. It is critical that we develop new methods of collection, processing, storage to extend the storage time of platelets, and evaluate the use of whole blood. The attributes of these products must be understood to optimally alignment product attributes, clinical efficacy and safety with hemostatic needs in a variety of clinical states. Specifically, ...more »

Submitted by (@bldbuddy)

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

Details on the impact of addressing this CQ or CC :

Limitations of current storage methods challenge our ability to meet the increasing demands of cancer chemotherapy and complex surgeries as well as provide platelets to remote areas where trauma frequently occurs. Platelets are transfused to prevent or control bleeding without robust translational or clinical trial evidence of efficacy and safety. In patients with hypoproliferative thrombocytopenia receiving chronic platelet transfusion predominantly for prophylaxis, post-transfusion increments, survival time, and durable hemostatic efficacy are important; however, platelet transfusion alone does not prevent bleeding. The overall state of hemostasis, the endothelium and donor characteristics that affect platelet quality may be important considerations in selecting the best platelet product tailored to individual patients. Better laboratory and clinical measures of platelet function, efficacy and safety are essential for best use of these limited resources. These outcomes should span and link in-vitro testing, animal models, and clinical effects such as thrombotic events, immune, hemostatic, and endothelial effects. Extrinsic, recipient factors (e.g., immune deficiency, platelet or endothelial dysfunction) and intrinsic factors (e.g., donor specific or platelet preparation) should be considered. Systematic analysis of recipients and donors should be broad and include considerations of glycomics, metabolomics, proteomics, genomics, in vivo microscopy, and advanced imaging.

Feasibility and challenges of addressing this CQ or CC :

Radiolabeled platelet recovery and survival methods are well established and feasible to perform at several centers within the US. Currently 4-6 million units of platelets and whole blood are transfused per year. It is very feasible to conduct clinical trials that compare methods of platelet preparation, processing, and storage in children and adults who require platelets for either prophylaxis or active bleeding. Multiple research networks that focus on both pediatric and adult transfusion medicine are motivated to perform the pre-clinical and clinical trials required to establish improved efficacy and safety of platelet-containing blood products.

Name of idea submitter and other team members who worked on this idea : Terry Gernsheimer, University of Washington, for the 2015 NHLBI State of the Science in Transfusion Medicine

Voting

14 net votes
34 up votes
20 down votes
Active

Goal 2: Reduce Human Disease

Sleep Apnea

Does treating sleep apnea benefit patients with obstructive lung disease?

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 : ATS Member

Voting

1 net vote
1 up votes
0 down votes
Active

Goal 2: Reduce Human Disease

How do we address health disparities especially in our most vulnerable populations?

How do we address health disparities especially in our most vulnerable populations, including children?

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 : Research Advocacy Committee, American Thoracic Society

Voting

0 net votes
1 up votes
1 down votes
Active

Goal 2: Reduce Human Disease

Improve vascular healing and extend long term benefit of interventions

How can we develop new approaches to improve vascular healing and extend the long term benefits of vascular interventions for more patients?

Submitted by (@societyforvascularsurgery)

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 response to vascular injury, whether it be catheter interventions, bypass surgery, or chronic implants, is a reactive process characterized by inflammation, cell proliferation, and fibrosis leading to failure. Better understanding of the mechanisms of vessel remodeling, and restoring homeostasis, is needed to improve prediction, develop and translate new treatments. This remains the leading scientific problem in vascular medicine and surgery. New approaches such as proteomics, lipidomics, molecular imaging offer new opportunities in this realm.

Name of idea submitter and other team members who worked on this idea : Society for Vascular Surgery

Voting

0 net votes
1 up votes
1 down votes
Active

Goal 2: Reduce Human Disease

Coconut oil and the Effect on Lipids

What is the effect of coconut oil (high in saturated fat) on blood lipids and cardiovascular disease (CVD) risk?

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 :

Coconut oil is a highly saturated fat yet it is being promoted heavily in the popular media as a healthy fat. It is touted as a cure all for several chronic conditions including CVD risk factors. It is important to determine how coconut oil impacts blood lipids for public health.

Feasibility and challenges of addressing this CQ or CC :

A feeding trial would provide clear results on the effect of coconut oil on the effect of lipids.

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

Voting

-14 net votes
7 up votes
21 down votes
Active