Goal 2: Reduce Human Disease

Antibiotic prophylaxis of infective endocarditis

What is the optimal use of antibiotics for prophylaxis of infective endocarditis?

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 :

Answering this question would provide an evidence base for the use of antibiotics for prophylaxis of infective endocarditis (IE). Clinicians in the US remain skeptical of the 2007 AHA guidelines reducing the use of antibiotics, and the guidelines, themselves, cited the need for additional prospective studies. In addition, a recent study by Dayer et al reports an increase in the incidence of IE in the UK following adoption of similar guidelines.

Feasibility and challenges of addressing this CQ or CC :

The question is actually overdue to be addressed following adoption of the 2007 guidelines.

Challenge: Considering the severe consequences of infective endocarditis, it may be difficult to design a definitive placebo-controlled clinical trial.

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

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-6 net votes
3 up votes
9 down votes
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Goal 2: Reduce Human Disease

The Use of Therapeutic Apheresis to Reduce Circulating Levels of Galectin-3 and other Cancer and Inflammation Promoting Factors

Inflammation plays roles in cancer initiation, promotion, and progression. Elevated circulating galectin-3 (Gal-3) protein and other cancer and inflammation promoting factors (CIPFs) such as C-reactive protein and VEGF are associated with tumorigenesis and may play causative roles. Plasma Gal-3 is a biomarker, prognosticator, and pathogenic mediator of diverse cancers and is emerging as a therapeutic target. Preliminary ...more »

Submitted by (@elaine)

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

Details on the impact of addressing this CQ or CC :

Apheresis therapy in a clinical setting, both alone and in combination with conventional protocols, shows great potential to enhance treatment regimens, reduce dosage and side effects, improve drug deliver to target tissues, reduce long term treatment related morbidity and improve outcomes with significant benefits for patients with a broad range of cancer types and stages.

Feasibility and challenges of addressing this CQ or CC :

The need for well designed, randomized clinical trials would be readily feasible with the appropriate IND. Grant support will be needed for further development of this concept, as well as to develop columns with more optimized and specific capabilities, in addition to clinical trials demonstrating efficacy.

 

Apheresis is highly underutilized and underfunded in the US, while Apheresis research and development is much more advanced and widely utilized in Europe and Asia.

Name of idea submitter and other team members who worked on this idea : Isaac Eliaz, MD

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33 net votes
40 up votes
7 down votes
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Goal 2: Reduce Human Disease

Funding for Cardiothoracic Surgery Research

The continued development of new technologies requires cardiothoracic surgeons to maintain a strong level of research to ensure the highest quality of patient care and surgical outcomes are received across the world. The level of support for CT surgery within the NIH has continued to drop over the last decade. This is a substantial problem for the specialty as the limited funding available creates difficulty in the continued ...more »

Submitted by (@meaton)

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

Details on the impact of addressing this CQ or CC :

CT Surgeons are performing procedures on some of the sickest patients while effecting some of the most dramatic favorable outcomes and the continue support for research in this specialty is essential to ensuring improvements in quality patient care. CT surgeons are provided the opportunity to participate in both the research lab and operating room which provides an important opportunity for a role in both the scientific discovery and implementation of new outcomes.

Feasibility and challenges of addressing this CQ or CC :

Cardiothoracic diseases are one of the top health issues facing the global population and the research being conducted is integral in helping cure the issues facing the current generation. With expanded support for research, new areas of the heart, lung, and esophagus can be studied with the hopes of identifying new technologies and procedures to help ensure the next generation is given the highest quality of care possible.

Name of idea submitter and other team members who worked on this idea : Matt E.

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105 net votes
155 up votes
50 down votes
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Goal 3: Advance Translational Research

Direct Upregulation of Antioxidant Defenses as a Therapeutic Strategy

Clinical trials involving administration of antioxidants such as vitamin C or vitamin E as therapeutic strategies for cardiovascular diseases associated with oxidant stress have proven to be surprisingly disappointing. A particularly attractive alternative approach is direct upregulation of endogenous antioxidant defenses such as NRF2 via dietary approaches. NRF2 is a master antioxidant and cell protective transcription ...more »

Submitted by (@jlombard)

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

Details on the impact of addressing this CQ or CC :

Direct upregulation of endogenous antioxidant defenses such as NRF2 via dietary approaches will avoid the well known caveats of drug-based approaches such as off target effects and detrimental side effects. Dietary supplements such as Protandim are already available; and beneficial effects of other NRF2 up-regulators such as resveratrol and sulforaphane are beginning to be recognized. The dietary approach is minimally invasive and has high preventative value.

Feasibility and challenges of addressing this CQ or CC :

Addressing this CQ is clearly feasible, as dietary supplements are currently available for humans, and the beneficial effects of foods containing compounds that upregulate the NRF2 system, e.g., broccoli, cauliflower, red wine, and grape juice are currently recognized. One challenge in addressing this question in animal models to date is that the only genetic model lacking NRF2 is a knockout mouse model, which have substantial limitations for in vivo physiological studies due to their small size. However, a recent R21 grant (#1R21OD018309-J. H. Lombard, P.I.) has allowed the development of a NRF2 knockout rat model which is better suited for physiological studies than the mouse model. In addition, the techniques used to develop the NRF2 knockout rat can be applied to multiple disease-sensitized strains, e.g., the Dahl salt-sensitive rat. Fawn Hooded Hypertensive rat, Obese Zucker rat, etc. Similar disease sensitized rodent genetic strains are not available in mice.

Name of idea submitter and other team members who worked on this idea : Julian H. Lombard

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-5 net votes
2 up votes
7 down votes
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Goal 2: Reduce Human Disease

Pulmonary Vascular Diseases

Does pulmonary rehabilitation or regular exercise improve outcomes in patients with PVD?

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 is a view of problems in the field.

Pulmonary Hypertension Clinical Research: Current Problems and Possibilities

Current studies limited to the short term, with soft outcomes.

No mechanistic studies embedded in trials.

Control of phenotype is weak.

Small n: lumping of cohorts.

No factorial of advanced design.

No biological samples obtained for study.

Failure to study basic management issues.

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
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Goal 1: Promote Human Health

ESTABLISH NORMATIVE AGE- AND GENDER-SPECIFIC DATA FOR SLEEP DISRUPTION, SLEEP QUALITY AND CIRCADIAN TIMING

There is growing evidence that sleep durations are progressively declining in the United States. Moreover, sleep durations are different at different ages and in different ethnic groups. Currently definitions of normal are based on consensus since there is a lack of key data. Defining normal as with FEV1 is a critical step.

Submitted by (@jnoel0)

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 developing evidence from both basic research and clinical research on the role of insufficient sleep in different co-morbidities. These include cardiovascular disease, hypertension and metabolic disorders. The Centers for Disease Control (CDC) has appreciated the importance of this that adequate sleep is one of the pillars of health. As part of the CDC-supported program on sleep health, a consensus statement has been issued on normal sleep duration. The group doing this on behalf of the American Academic of Sleep Medicine and Sleep Research Society realized that our evidence base is inadequate at this time. Thus, there is a need to focus on this critical challenge. Sleep duration varies across the lifespan and there is some evidence that it is different in different ethnic groups. Thus, there is a need for comprehensive efforts to address this question and to obtain normative data for sleep duration that is age-, gender-specific and with respect to different ethnic groups.

Feasibility and challenges of addressing this CQ or CC :

There are now recent cohorts at NIH assessing sleep duration using not only self-report but also actigraphy. These could be used as an initial approach to address this question. This will require some degree of coordination between NIH Institutes. In the future a cohort that is specific to addressing questions about sleep duration and other sleep problems would be optimal. There are major prevalent public health issues. This would be facilitated by development of new mobile approaches to assessing these behaviors in an objective way.

Name of idea submitter and other team members who worked on this idea : Sleep Research Society

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157 net votes
214 up votes
57 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

Childhood Interstitial Lung Disease

What is the relationship of ChILD disorders to more common childhood respiratory diseases?

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 :

For example, what is the role of surfactant-related sequence variants in chronic lung disease of prematurity? Cystic fibrosis? Severe bronchiolitis? Refractory asthma?

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

Pulmonary Vascular Diseases

Does treatment with spironolactone improve outcomes in patients with pulmonary arterial hypertension (and/or pulmonary hypertension associated with diffuse parenchymal lung disease or COPD)? Spironolactone has been shown beneficial in CHF and many of the same mechanisms are at plan in RV failure from pulmonary hypertension. Again, no clear evidence whether this is a useful treatment or not, and no evidence to guide ...more »

Submitted by (@nhlbiforumadministrator)

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

Feasibility and challenges of addressing this CQ or CC :

This is a view of problems in the field.

Pulmonary Hypertension Clinical Research: Current Problems and Possibilities

Current studies limited to the short term, with soft outcomes.

No mechanistic studies embedded in trials.

Control of phenotype is weak.

Small n: lumping of cohorts.

No factorial of advanced design.

No biological samples obtained for study.

Failure to study basic management issues.

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

Voting

2 net votes
2 up votes
0 down votes
Active

Goal 2: Reduce Human Disease

How can we more safely deliver stem cells to Sickle Cell patients

Newer therapies using gene correction, rather than gene addition, are needed for sickle cell disease. Even with this potential advantage, there needs to be a way to safely deliver gene corrected HSC to the sickle cell patient. Chemotherapy is poorly tolerated, and often is the reason patients do not choose the BMT option. What is the status of other less toxic non myeloablative approaches, and how can they best be ...more »

Submitted by (@freddigoldman)

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

Details on the impact of addressing this CQ or CC :

would open up opportunities for more patients to get cured of their sickle cell disease without co morbidity of the BMT process

Feasibility and challenges of addressing this CQ or CC :

Need to develop animal models and also newer marrow niche clearing agents.

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51 net votes
67 up votes
16 down votes
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Goal 3: Advance Translational Research

Developing Curative Approaches to Cardiovascular Disease rather than Chronic Magement

Most Pharmacological interventions in cardiovascular diseases tend to address to be used in palliative manner and chronically. There is urgent need for treatments that are curative. This goes to identifying molecular drivers of the diseases and targeting them to correct the underlying pathophysiology rather than symptom suppression.

Submitted by (@john.buolamwini)

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

Details on the impact of addressing this CQ or CC :

True conquer of cardiovascular diseases, and reversing the chronic nature of these diseases.

Feasibility and challenges of addressing this CQ or CC :

Possible but challenging requiring a highly multidisciplinary approach and collaboration.

Name of idea submitter and other team members who worked on this idea : John. K. Buolamwini

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1 net vote
2 up votes
1 down votes
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Goal 3: Advance Translational Research

Implementation science research to reduce adverse effects of SCD

From various publications and reports, we have characterized the risks associated with sickle cell disease (SCD) and understand many of the barriers for treatment of SCD in LMICs. How can implementation science research be used to reduce the negative outcomes of SCD in low/middle income countries?

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 :

• Reduction of deaths and negative outcomes associated with SCD and in LMICs

• Provide the evidence base that supports culturally relevant implementation strategies that reduce deaths associated with SCD in LIMCs

Feasibility and challenges of addressing this CQ or CC :

• Yes

, this is feasible

• Common goals and deliverables between NHLBI and partners will need to be identified

• Partnerships can be with international organizations, Ministries of Health and other partners

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

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18 net votes
31 up votes
13 down votes
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