Goal 2: Reduce Human Disease

Understanding of chronobiological systems

We know that all life functions are based on circadian and other rhythms; chronobiological systems are interdependent in intricate ways. Disturbances and disorders in one part of a system may affect other vital systems in unexpected but far-reaching ways. Many aspects of circadian rhythms and sleep-wake regulation in normal, healthy humans have been charted. Much of the knowledge thus gained is assumed to be valid also ...more »

Submitted by (@nma120)

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

Details on the impact of addressing this CQ or CC :

As research on the extrinsic Shift Work Disorder shows, disturbances of the normal person’s sleep-wake cycle have consequences. These may include excessive daytime sleepiness, increased risk of traffic and other accidents, dysregulation of metabolic and other systems, obesity, increased risk of cancer, cardiovascular diseases, mood disorders and other diseases. Normal people trying to function on an abnormal schedule may develop conditions that lead to disability or death. Intrinsic CSWD patients suffer many of the same conditions as well as others.

 

These patients desperately need answers: Why am I like this, Do I dare have children, Will it get worse as I age, Can anything be done in addition to light boxes, scototherapy and melatonin, What is really the best timing in use of these treatments, Will I get disability?

 

Research on these patients will likely lead to discoveries that could be the target for future studies, thus impacting the modern fields of sleep and circadian rhythms research.

Feasibility and challenges of addressing this CQ or CC :

The intrinsic CSWDs are:

 

1) Lifelong DSWPD, delayed sleep-wake phase disorder

2) Adolescent DSWPD

3) ASWPD, advanced sleep-wake phase disorder

4) ISWRD, irregular sleep-wake rhythm disorder

5) Blind Non-24, N24SWRD, non-24-hour sleep-wake rhythm disorder in the blind

6) Sighted Non-24, N24SWRD in the non-blind.

 

I have listed 6 disorders; the usual number is 4. The first 2 on my list are usually combined, as are the last 2.

 

Some of the challenges, for different age groups and degrees of severity, are to:

--Find the causes of the disorders that are not yet explained

--Examine genetics and heritability

--Differentiate teens’ DSWPD as adolescent or persistent type

--Discover why adult DSWPD often precedes the development of Non-24 in sighted people

--Validate the use of light therapy, dark therapy and melatonin, including detailed recommendations for the timing and dosage of each of them

--Find other, more reliable, treatments

--Develop simple tests for determining persistent internal circadian desynchronization in an individual.

 

 

Some of the disorders have been explained, in whole or in part. There is great need for work with, at least, the following groups of patients:

-Adult DSWPS

-Pre-puberty children w/ DSWPS

-Adult sighted N24

-Pre-puberty sighted children w/ Non-24

 

Of these, adults with DSWPD are, of course, the most numerous. Research on that disorder may lead to results of interest for N24, these disorders being closely related.

Voting

1 net vote
1 up votes
0 down votes
Active

Goal 4: Develop Workforce and Resources

Which factors are associated with systems performance?

What are the institutional factors, including structure and culture of care, that characterize systems performance? Which of these factors are potentially modifiable and/or scalable?

Submitted by (@rebecca.lehotzky)

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 : AHA Staff & Volunteers

Voting

-3 net votes
2 up votes
5 down votes
Active

Goal 3: Advance Translational Research

Human Heart Systems Biology

In the human failing heart, it is the systems biology that ultimately fails: electrical, mechanical, and chemical perturbations in their function do not manifest in isolation, but critically impact on each other in health and disease. Investigation of human myocardium, unlike inbred rodent models, is challenging since no two humans are identical. There is a need for the collection and assessment of clinical patient data, ...more »

Submitted by (@janssen.10)

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

Details on the impact of addressing this CQ or CC :

Procured/stored tissue from these hearts could be made available NHLBI/NIH-wide, and studied by a large number of investigators on protein levels, RNA/DNA level, and/or histological assessments. This data could then be correlated to any other parameter assessed on these hearts, providing correlative guidance, through systems biology/neural network programming, for future mechanistic studies. For each additional parameter investigated, the number of correlation analysis (with any and all parameters, including clinical and biometric parameters) would mathematically double.

Feasibility and challenges of addressing this CQ or CC :

Supporting the basic collection of these in vivo and in vitro parameters and possibly the logistics for tissue distribution to collect correlative mechanical, proteomics, genomics, and histology data for correlation with the in vivo and in vitro data would allow for an NIH/NHLBI-wide translational approach to human heart failure that could encompass everyone’s “favorite” molecule, protein, pathway, and disease etiology. A logistical challenge is that such a project would likely exceed the funding of a single standard grant, but more importantly would surely exceed the standard 4-5 year duration, requiring long-term vision, planning, and buy in from NIH/NHBLI and investigators.

Name of idea submitter and other team members who worked on this idea : Paul Janssen

Voting

6 net votes
13 up votes
7 down votes
Active

Goal 2: Reduce Human Disease

Linking Clinics and schools to improve asthma control and reduce health disparities

How can we improve communication between schools and clinicians in order to develop support systems for children with severe asthma with health disparities?

 

How can we eliminate inefficiency in medical communication to better serve children with severe asthma?

Submitted by (@stanley.szefler)

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

Details on the impact of addressing this CQ or CC :

Children with asthma, especially severe asthma, are compromised by school absence and sleep disturbance. School scan play a significant role in identifying these children, assisting in monitoring their adherence to therapy and supporting the clinician's management plan. However, steps must be taken to improve communication systems that link clinics to schools and allow schools to communicate effectively with clinicians. While systems are in place for some schools that have active asthma management programs, there are many schools that do not have these resources or infrastructure. Model systems can be developed to assist these schools and improve the overall care of asthma in the United States.

Feasibility and challenges of addressing this CQ or CC :

Challenges that must be overcome is standardization of communication forms and harmonization of approach to asthma care, as well resolving barriers that exist due to confidentiality barriers in sharing medical information.

Name of idea submitter and other team members who worked on this idea : Stanley Szefler, MD

Voting

6 net votes
12 up votes
6 down votes
Active

Goal 2: Reduce Human Disease

How to organize artificial pulsatile propelling of blood maintaining the balanced circulation?

Venous pressure, being very low, distends (deforms) the ventricle - but due to elastic or viscous law of deformation? Elastic deformation depends on stress (pressure) only and the viscous one - on stress and time. When pressures are low you can't get large distention due to stress only (time-independent) unlike the case when you apply low stress and long time interval. If we want to use venous pressure as one of regulators ...more »

Submitted by (@yuri.astrakhan)

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 impact (in case of constructive solution of the problem) can be expected as a breakthrough in the field of engineering of extracorporal circulatory devices and artificial heart. More exactly: the impact will concern the dosage of blood while filling of the ventricle - without intrusion into the essential levels of venous pressure (the levels play the role of regulators together with levels of diastolic arterial pressure).

Feasibility and challenges of addressing this CQ or CC :

The feasibility of implementation (engineering of a device) of the above idea depends on preliminary supercomputer modeling of blood circulation based on simulation of viscous relaxation of ventricle combined with the controlling of circulation according to the deduced equation (see the reference).

Name of idea submitter and other team members who worked on this idea : Kamnev Yuri

Voting

-9 net votes
2 up votes
11 down votes
Active

Goal 1: Promote Human Health

Cardiac Engineering – Deciphering the Cardiome

To maintain cardiac health and prevent disease, there is a need to decipher the cardiome of cells and genes and use this knowledge (1) to better understand cardiac structure and function and (2) to engineer systems on the level of organs, organ systems, and the entire individual.

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 :

Improved CV health

Feasibility and challenges of addressing this CQ or CC :

new advances in study of the cardiome

Advances in in the sub-micro-world over the past several years have led to greater opportunities to better understand cells and genes. These new developments have and will continue to provide greater insight into understanding cardiac structure and function, which has and will likely to result in improved therapies for heart disease. The advances being made in science and technology have expanded the frontiers of cardiology as a result of important advances in micro-imagining and molecular diagnostic methods. These advances have transformed classical study of the macro-world of living human beings and the cardiac disease that afflict them.

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

Voting

-16 net votes
10 up votes
26 down votes
Active

Goal 1: Promote Human Health

Phenotypically accurate models of human heart, lung, blood, and sleep systems

There is a need to develop phenotypically accurate models of human heart, lung, blood, and sleep systems.

Submitted by (@nhlbiforumadministrator1)

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 : NHLBI Staff

Voting

28 net votes
42 up votes
14 down votes
Active

Goal 3: Advance Translational Research

Leveraging Networks of Federally Qualified Healthcare Centers

How best do we leverage the existing Federally Qualified Healthcare Center’s (FQHC) infrastructure to study T4 Implementation Research for heart, lung, blood, sleep diseases and conditions among high risk and vulnerable populations?

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 :

• Develop strategies to reduced Health Inequities

• Potentially be scaled up across an entire health system with huge population impact

• Studies would be done in the environment and context where the findings with be implemented leading to better uptake and sustainability.

Feasibility and challenges of addressing this CQ or CC :

• Formative FQHC groups are already being organized but do not have strong leadership and support

• FQHCs have ready access to the high risk and vulnerable populations that would benefit most from the research

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

Goal 3: Advance Translational Research

Embedding Clinical Trials in Learning Health Systems

What are the best methods for using genotype information and other EMR data to randomize heart, lung, blood, sleep patients to different treatment strategies? One big challenge is how to consent patients for this sort of trial. Must patients be consented separately for every such trial or could there be blanket consent for participating in the learning health care model? This would also require a paradigm shift in how ...more »

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 :

If successful this approach should enable the conduct of cheap pragmatic trials that are fueled by data from clinical care. The integration into clinical care helps assure efficiency and generalizability of results.

Feasibility and challenges of addressing this CQ or CC :

The advent of electronic medical records and the explosion of big data technology has made it possible to gain access to and analyze data in a manner that would have been unthinkable 10 years ago. This is already going on in other fields.

Health care systems are increasingly using "big data" approaches to track outcomes in the patients treated with different strategies and drugs, and apply the knowledge gained from outcomes in previous patients to inform decision making in subsequent patients ("learning"). This approach could be used to personalize treatment. A recent example from cancer is to genotype lung tumors, and tailor the treatment of a new patients to drugs producing good results in patients with similar tumor genotypes. When two or more treatments produce similar results, one could randomize. Cardiovascular disease presents a challenge in using genotyping information to personalize treatment, because the manifestations are the results of complex genetic and environmental risk factors.

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

Voting

4 net votes
15 up votes
11 down votes
Active