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

Interaction with Office of Rare Diseases

NHLBI should engage more interactively with the Office of Rare Diseases (ORD).

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 :

There is a synergy that comes with collaboration with rare disease clinical science from other institutes. Some of this synergy is scientific, much of it falls into the support engendered to the patient support groups that are partners in filling the funding gap that many NHLBI initiatives have.

Feasibility and challenges of addressing this CQ or CC :

To go it alone in rare disease dissociates the lung disease clinicians from the huge movements in registry science that will impact the field for years to come.

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

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

Rare disease therapeutics high throughput screening

Can we develop model systems for the high throughput screening of new and existing agents as possible therapies for rare diseases?

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

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-18 net votes
8 up votes
26 down votes
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Goal 2: Reduce Human Disease

Mechanics of aortic dissection

The mechanical events in the wall leading to aortic dissection are not well described because merely stating that cellular or biopolymer connections have weakened does not predict the path of the rupture through the media or the risk of rupture. Elucidate the mechanical role of substructures such as collagen fibers, elastin sheets, smooth muscle cells and interstitial fluid in the progression of dissection. Study in animal ...more »

Submitted by (@haslach)

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

Details on the impact of addressing this CQ or CC :

While in recent years the lives of patients with aortic dissection have increasingly been saved, an understanding of the mechanisms involved might suggest new techniques to increase the percentage who survive aortic dissection.

Feasibility and challenges of addressing this CQ or CC :

Knowing the mechanisms involved in dissection is more important than attempting to determine and measure some critical rupture stress because of the large differences between specimen aortas within a given species.

Name of idea submitter and other team members who worked on this idea : Henry W. Haslach, Jr.

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7 net votes
17 up votes
10 down votes
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Goal 2: Reduce Human Disease

How should platelet (PLT) transfusions be used to treat active bleeding?

Multiple randomized controlled trials have been performed to evaluate the use of prophylactic PLT transfusions in non-bleeding, thrombocytopenic hematology-oncology patients. However no high-quality data exist to guide PLT transfusions in actively bleeding patients inclduing pediatric and adult medical and surgical patients. After hematology-oncology patients, cardiac surgery patients are the next largest group of PLT ...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 :

PLT count is almost always the only laboratory result considered in deciding to transfuse PLTs. But PLT counts provide no information about PLT hemostatic function and its contribution to bleeding. A variety of in vitro coagulation tests have been developed: viscoelastography, whole blood PLT aggregometry, etc. But while testing-based transfusion algorithms may reduce blood product utilization, it has not been established that any in vitro test can either predict or help reduce bleeding. There is a gold standard method to assess clinical efficacy of transfused PLTs: incidence of grade 2 or higher bleeding in clinical trials of thrombocytopenic hematology-oncology patients receiving prophylactic PLT transfusions. No analogous gold standard of PLT hemostatic efficacy exists for therapeutic PLT transfusions to treat active bleeding. There is a pressing need to develop such a standard. Establishing reliable methods for evaluating the effects of PLT transfusion in actively bleeding patients will improve our understanding of how different factors (storage conditions, pathogen reduction etc.) affect the functional performance of PLTs.

Feasibility and challenges of addressing this CQ or CC :

PLT transfusions are administered routinely to support bleeding pediatric and adult medical and surgical patients. Opportunities to conduct clinical trials in various settings (cardiac surgery, neurosurgery, orthopedic surgery, trauma, etc.) are widely available. PLT transfusion is commonly used to support bleeding patients receiving perioperative supportive therapies such as extracorporeal membrane oxygenation (ECMO). These clinical situations represent critical opportunities to improve the care of bleeding patients. This approach will simultaneously facilitate comprehensive evaluation and validation of both current and novel in vitro tests of hemostasis. If a given in vitro test were reproducibly shown to correlate strongly with bleeding reduction caused by PLT transfusion, then by definition that would be a clinically meaningful test. Finally, this line of inquiry will allow assessment of the adverse effects of PLT transfusion in bleeding patients.

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

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30 net votes
44 up votes
14 down votes
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Goal 2: Reduce Human Disease

Optimizing Utilization of Composite and Repeat Endpoints in RCT

The use of win-ratio and other new statistical methods to analyze endpoints in new and existing clinical trials.

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 :

It could enable trials to be powered with smaller sample sizes. It can also be used to combine diverse information in a way to better guide clinical decisions.

Feasibility and challenges of addressing this CQ or CC :

The methodology exists and the need is growing as we try to sort out smaller treatment effects and our focus shifts from MI (which is fairly easy to define) to heart failure (which is more nebulous).

Traditional time-to-first endpoint analyses of clinical trials fail to capture the full impact of treatment in diseases with recurring endpoints (like heart failure hospitalization) or to capture the net benefit/risk of treatments with significant opposing effects (like the anti-thrombotic pro-bleeding effects of drugs like warfarin and dabigatran in atrial fibrillation or dual anti-platelet therapy after cardiovascular stenting), New statistical methods like the (win-ratio) when used together with patient- and clinician-based rankings of the importance of possible outcomes might provide a quantitative way to optimize the relevance of trials with multiple diverse endpoints to practical clinical decision making. I propose to encourage the use of these and other similar methodologies to analyze endpoints in new and existing trials. It would require a paradigm shift in how trialists look at endpoint data and in how regulators interpret trials.

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

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-3 net votes
10 up votes
13 down votes
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Goal 2: Reduce Human Disease

Lipid apheresis as adjunct therapy in peripheral vascular disease

What is the roll of inflammation and how does lipid apheresis alter inflammation in peripheral vascular disease when added to standard therapy and/or when used alone? Does lipid apheresis result in long-term improvement with reduced morbidity, mortality, and expense compared to standard therapy?

Submitted by (@winters.jeffrey)

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 prevalence of peripheral vascular disease (PVD) in the United States is estimated to be 5.9%, affecting up to 20% of adults over the age of 65. Therapy for PVD is vascular surgical intervention for limb ischemia; combined with medical therapy and anti-platelet agents but morbidity and mortality remains high. Low density lipoprotein cholesterol (LDL-c) is associated with increased risk for development and progression of PVD. Preliminary studies of the use of lipid apheresis have demonstrated improvement in symptoms and a variety of laboratory measures with decreased morbidity when added to standard therapy. The mechanism of this treatment may go beyond reducing LDL-c as the columns also affect levels of inflammatory cytokines, alter blood rheology, and affect other lipids.

Feasibility and challenges of addressing this CQ or CC :

Currently two lipid apheresis devices have been cleared by the Food and Drug Administration and are in use in the United States. The presence of cleared devices, the large number of affected patients, and availability of testing for lipoproteins, fibrinogen, CRP, PAI-1, IL-6, IL-17, IL-1, IL-10, INF-γ, VEGF, PGI2, IGF-I and rheology factors make the enrollment and evaluation of patients into a clinical trial examining the use of this treatment of PVD feasible. Challenges for the performance of a clinical trial would include the limited number of centers offering lipid apheresis, the chronic nature and length of time needed to perform lipid apheresis, and the expense of the lipid apheresis devices and disposables.

Name of idea submitter and other team members who worked on this idea : Bruce Sachais on behalf of ASFA

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96 net votes
116 up votes
20 down votes
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Goal 2: Reduce Human Disease

Developing approaches to the dissemination of behavioral weight loss programs

The Challenge is to make behavioral weight loss programs readily available to he many overweight and obese patients who need them. Behaivoral weight loss programs are effective in producing weight losses of 7-10% of initial body weight, which has been shown to have major beneficial effects on a number of diseases relevant to NHLBI--including hypertension and sleep apnea. However, at present, these programs are not widely ...more »

Submitted by (@rwing0)

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

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3 net votes
17 up votes
14 down votes
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Goal 2: Reduce Human Disease

Translational and basic research on high triglycerides as an additional risk for cardiovascular disease.

Compelling Question (CQ)

Submitted by (@hwu000)

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

Details on the impact of addressing this CQ or CC :

Previous studies have focused on high cholesterol as a risk factor for cardiovascular disease (CVD). Recent epidemiologic and genetic studies with apoCIII mutation, for example, have identified significant contribution of high triglycerides (TGs) to the development of atherosclerotic CVD. In particular, the epidemics of obesity, even from young age, in the US and worldwide have caused significant increases in the prevalence of hypertriglyceridemia, which has become a serious health problem. However, how hypertriglyceridemia increases risk for atherosclerotic CVD remains largely unknown. Further translational and basic studies would be needed to examine how TG-rich lipoproteins and cholesterol-rich lipoproteins cooperate to increase the risk for CVD. Basic research would need to be conducted at integrative, cellular and molecular levels including examining how TGs are metabolized and how TG-rich lipoproteins, along with cholesterol-rich lipoproteins, cause atherosclerosis. These studies would guide clinical approach on TG- versus cholesterol-lowering therapy for prevention and treatment of atherosclerotic CVD.

Feasibility and challenges of addressing this CQ or CC :

The challenges include combining large clinical studies and basic research. Clinical studies includes confirming high TGs as an independent risk for atherosclerotic CVD, developing novel TG-lowering therapy and examining whether these novel TG-lowering therapy, with apoCIII as a target for example, would be beneficial in prevention and treatment of CVD. It is also important to examine effects of novel TG-lowering therapy on adiposity, adipose tissue function and risk of diabetes. Basic science needs to elucidate how TGs are metabolized in vivo, causing hypertriglyceridemia, and how hypertriglyceridemia increases risk for atherosclerotic CVD, and identify novel pathways for these pathophysiological processes, which would provide novel strategies for development of new therapy for CVD. Collaborative approach with great financial support will make all these feasible.

Name of idea submitter and other team members who worked on this idea : Huaizhu Wu, MD

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

Maternal sleep apnea treatment effects

Does assessment and treatment of sleep apnea in pregnancy reduce the risk of maternal heart, lung and blood disease and complications associated with delivery and risk factors in offspring (e.g., obesity)?

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

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-4 net votes
19 up votes
23 down votes
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Goal 2: Reduce Human Disease

Benefits of intraosseous access on outcomes from OHCA

Vascular access is a challenge in the setting of out-of-hospital cardiac arrest (OHCA). The failure of medications to impact outcomes may be in part related to the delay in drug delivery from the IV route. EMS systems have adopted intraosseous (IO) access but it is not clear if these are affecting outcome and there has been no large RCT. The current IO access devices are expensive and use different routes (sternal, tibia, ...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 :

At over a 100 dollars per device, the costs of using an IO line for estimated 300K arrests in the United States is 30 million dollars. We need to know if this route works and the optimal location for placement.

Feasibility and challenges of addressing this CQ or CC :

Funding, willingness to study this in a well designed clinical trial

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

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

Basic Research & Precision Medicine

How can NHLBI best encourage basic research areas that are critical to the development of precision medicine approaches for lung disease?

Submitted by (@skrenrich)

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 : Cystic Fibrosis Foundation

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-2 net votes
3 up votes
5 down votes
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