Goal 2: Reduce Human Disease

Basic Research for HIV/AIDS and HLB Health and Diseases

What HIV/AIDS-related basic research can NHLBI support in the next 5-10 years to investigate the fundamental mechanisms of HIV-related heart, lung, and/or blood (HLB) diseases alone and in the context of antiretroviral therapy (ART) to improve heart, lung, and blood health outcomes in HIV infections as well as the fundamental mechanisms of hematopoietic stem cell transplantation in potential elimination or eradication ...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 :

Widespread availability of effective antiretroviral therapy (ART) has changed the epidemiology of AIDS. HIV-infected patients on ART can expect to live for many decades, but now chronic diseases are increasingly replacing acute infections as important causes of morbidity and death. A growing body of evidence suggests that HIV may alter and/or accelerate the natural history of fundamental processes underlying atherosclerosis, pulmonary arterial hypertension (PAH), chronic obstructive pulmonary disease (COPD), pulmonary co-infections, anemia, coagulation, thrombotic disorders, and immune senescence.

 

 

 

However, the mechanisms by which HIV and ART may modify these processes have not been fully elucidated, primarily because of the multiple direct and indirect pathways by which HIV and ART induce cellular dysfunction. Advancing knowledge of which cell types are affected by HIV (and serve as reservoirs), as well as increased understanding of the vital interactions between HIV and the host cells as well as interactions between HIV and other elements of the human virome and the broader microbiome is essential to elucidating the pathogenesis of HIV-related HLB diseases.

The use of basic research models will complement and extend the results of clinical studies.

Feasibility and challenges of addressing this CQ or CC :

For HIV infection and heart, lung, and blood health and diseases:

• NHLBI investments in this aspect, including the three RFAs in 2014-2015, two on basic research and one on clinical research, have laid good foundation.

• Collaborations between HIV investigators and HLB investigators that have been facilitated by the NHLBI investments including the three RFAs.

• The Berlin patient has provided the proof of concept that HIV infection can be eradicated, that is, sterilizing cure can be achieved, through HSC transplantation in combination with other therapies.

• New technologies that have been developed recently, such as the deep sequencing techniques and research supported by the NIH Human Microbiome Program and other programs have allowed us to better understand microbiome, especially bacteria in and on humans, and we began to realize the magnitude of the human virome.

 

?

 

For HLB comorbidities of HIV infection, the challenges include:

 

• Closer collaboration between HIV investigators and HLB investigators;

 

• Leverage of resources available both in HIV research and in HLB research.

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

Voting

-22 net votes
14 up votes
36 down votes
Active

Goal 3: Advance Translational Research

What are the most effective strategies for reducing alarm fatigue and optimizing cardiorespiratory monitor alarm management?

Hospital cardiorespiratory monitors have great potential to save lives, but are hampered by high false alarm rates that contribute to alarm fatigue. While the long term solution is developing new medical devices that will do this better, few hospitals will benefit from new device innovations in the next decade. In order to better identify early signs of cardiorespiratory deterioration in the hospital at an early stage ...more »

Submitted by (@chrisbonafide)

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

Details on the impact of addressing this CQ or CC :

Improved strategies for optimally detecting deterioration using existing bedside cardiorespiratory monitoring technologies has the potential to impact the care of hundreds of thousands of hospitalized adults and children each year.

Feasibility and challenges of addressing this CQ or CC :

This is highly feasible with a fairly modest allocation of resources. This work falls under heart and lung disease, hospital medicine, nursing research, and implementation science.

Name of idea submitter and other team members who worked on this idea : Chris Bonafide, MD, MSCE

Voting

-6 net votes
4 up votes
10 down votes
Active

Goal 2: Reduce Human Disease

Mechanism and target identification for cardiovascular disease using database mining and experimental strategies

The big database of -omics and noncoding RNAs provide a valuable search engine to establish the link of various disease conditions with pathways and molecules. During recent year, data mining of available biomedical data and information has merged for target discovery and mechanism identification. However, current database mining research remains limited and largely hypothetical. Comprehensive research using the combinatory ...more »

Submitted by (@hongw0)

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 : Hong Wang, Xiaofeng Yang

Voting

19 net votes
26 up votes
7 down votes
Active

Goal 4: Develop Workforce and Resources

Establishment of an independent study section on Pulmonary Vascular Biology and Translational Research

The research on pulmonary vascular biology including smooth muscle cell biology and endothelial cell biology and related pulmonary vascular diseases such as pulmonary hypertension and related right heart failure, and endothelial dysfunction in lung vascular inflammation and acute lung injury, as well as pulmonary embolism and lung transplantation has been rapidly expanding. The field is attracting an ever increasing ...more »

Submitted by (@yyzhao)

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

Details on the impact of addressing this CQ or CC :

Establishment of a study section on Pulmonary Vascular Biology and Translational Research will provide adequate funding to stimulate innovative research on this rapidly expanding field and promote translational research and thereby promote human health by providing potential novel therapeutic strategies for the devastating diseases such as pulmonary hypertension and acute lung injury.

Name of idea submitter and other team members who worked on this idea : Youyang Zhao, Kurt Denmark, Asrar B. Malik, Mark Gladwin, Jahar Bhattacharya, Michael Matthay, Sharon Rounds, Jason Yuan

Voting

23 net votes
50 up votes
27 down votes
Active

Goal 3: Advance Translational Research

Improve patient compliance through community health workers

What are effective strategies for community-based participatory dissemination and implementation research initiatives in rural settings? • Limited number of studies that adapt evidence- or practice-based interventions to rural settings • Needs innovative approaches to engaging the rural community • New intervention approaches needs testing in rural communities • Building a team would have to involve of local community ...more »

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 :

• Nearly 60 million Americans living in rural communities face additional barriers to receiving effective prevention and treatment services.

• Rural residents often enter care later in the course of their illness than their urban peers, enter care with more serious symptoms, and require more intensive and expensive treatment.

• The rural communities in the US are closely connected and can be leveraged to disseminate heart, lung, blood, and sleep relevant preventive and/or treatment options within those communities.

• Enhance understanding of community resilience factors, cultural, and individual factors that may enhance the provision and utilization of prevention and treatment services in these communities.

• Generate knowledge to improve the organization, efficiency, effectiveness, quality, and services for rural and frontier populations.

• Support movement of evidence-based effective health care and prevention and the public health knowledge base in rural communities in the US.

• Stimulate implementation science in rural and frontier communities

• High return on investment.

Feasibility and challenges of addressing this CQ or CC :

• NHLBI investigators could initiate controlled trials that would maximize the opportunities available in rural communities.

• Documented sustainable interventions and scientific research could serve to reduce morbidity and mortality in high-risk rural populations.

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

Voting

7 net votes
15 up votes
8 down votes
Active

Goal 3: Advance Translational Research

Infrastructure for human translational research

With the reduction in NCAT support for human translational research, infrastructure support will need to come from the NHLBI. This will increase the cost of most human, mechanistic based RO1 studies by 20-30%. This will exceed the current cap of $500K in many circumstances. The cap will need to be raised or NHLBI and other institutes need to determine how NIH can continue to provide this critical infrastructure.

Submitted by (@gwilliams)

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

Details on the impact of addressing this CQ or CC :

With the pending loss of infrastructure support by NCAT for human translational, mechanistic studies, a contiued decline in resources to support this critical resources for N of 1 studies. With appropriate support there will be increased capacity to determine which pre-clinical data is applicable to humans and to design more percise, mechanism based clinical trials to increase the likelihood of precision, personalized medicine for many of NHLBI's targeted diseases, e.g, hypertension, stroke, cardiovascular disease with diabetes and hypertension, asthma, and sleep apnea.

Feasibility and challenges of addressing this CQ or CC :

The template for addressing this challenge is already available. The specific funding mechanism(s) will need to be addressed.

Name of idea submitter and other team members who worked on this idea : Gordon Williams, Gail Adler, Charles Czeisler, Ellen Seely, Lindsey Baden

Voting

3 net votes
6 up votes
3 down votes
Active

Goal 2: Reduce Human Disease

Improving patient-centered outcome assessments in HLBS studies

What types of newer patient-centered quality of life assessment tools can be employed in heart, lung, blood and sleep studies so that they can be validated and refined to improve our measurement of quality of life outcomes in populations of interest to NHLBI?

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 :

Improving our ability to precisely measure heart, lung, blood, and sleep patients' quality of life can enable evaluation of a treatment's impact on patient-centered outcomes such as overall quality of life and its components -- pain, symptoms, and a patients' social, psychological, and physical functioning.

Feasibility and challenges of addressing this CQ or CC :

New tools have been developed, notably through the PROMIS common fund project, that allow potentially more precise, reliable, valid and sensitive measurement of Q of L outcomes, with less patient burden. These tools are available but require validation in HLBS populations to allow widespread adoption and routine use in NHLBI-supported clinical trials and population studies.

Advances in biomedical science mean we are living longer with chronic diseases, and the goal of treatment increasingly focuses on disease management, maximizing function, and improving quality of life, not just lengthening life. In addition, patient-centered approaches to health care encourage a view of patients as “whole persons” with emphasis on function and capturing the "patient's voice," not just mortality/morbidity outcomes. Functional and quality of life outcomes, e.g., assessment of pain, symptoms, emotional distress, physical & social functioning, are critically important outcomes to many HLBS patients, but their measurement requires self-reports of patient experiences and thus pose challenges to precise, valid and reliable assessment.

 

Assessment tools using computerized adaptive testing (CAT), such as those developed in the Patient-Reported Outcomes Measurement Information System (PROMIS) project, have been shown to be precise, valid, sensitive to change and easier to administer than traditional Q of L measures in a limited number of studies, but they require validation in HLBS patient populations before they can be used more widely in NHLBI-funded studies.

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

Voting

11 net votes
20 up votes
9 down votes
Active

Goal 3: Advance Translational Research

Addressing Health Care Disparities Requires Pragmatic Research

Jumpstarting progress in eliminating health care disparities requires comparative effectiveness and implementation research (T3 and T4) regarding optimal strategies for ensuring health care equity in the real world. Ensuring minority and other socially disadvantaged groups receive and benefit from evidence-based interventions at the same rate as others requires pragmatic research that identifies and addresses barriers ...more »

Submitted by (@kevinfiscella)

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

Details on the impact of addressing this CQ or CC :

Meeting this challenge offers promise for elimination of disparities in morbidity and mortality among minority and other socially disadvantaged groups. Many major health care organizations are hungry for science-based interventions and implementation strategies for ensuring equitable care relevant to heart, lung, blood and sleep conditions. Pragmatic scientific evidence in these areas is urgently needed.

Feasibility and challenges of addressing this CQ or CC :

There are several feasibility challenges. The first is the broader challenge surrounding pragmatic, comparative effectiveness and implementation research including its integration within health care systems. Too little of this type research is conducted by funded institutions within their own health care systems. This failure reduces the likelihood that research findings, including best strategies for improving equity in health care delivery, will be adopted by health care systems. Ultimately, those responsible for implementation along with those receiving care must be active research partners in conducting pragmatic research in order to ensure that the research addresses real world priorities and feasibility issues.This represents a major shift in research paradigms but is critical to the success of health care disparities research.

 

The second challenge is that research funding streams narrow along the translational continuum. This poses a challenge to pragmatic research that focuses on equity in care. There is no doubt that research along the entire research continuum is needed to address health and health care disparities. However, research focusing on ensuring provision of evidenced-based interventions for groups least likely to receive them will have the most immediate impact.

Name of idea submitter and other team members who worked on this idea : Kevin Fiscella, MD, MPH

Voting

6 net votes
9 up votes
3 down votes
Active

Goal 2: Reduce Human Disease

A Program of Research in the Prevention of Chronic Heart Failure

There is a need to improve identification and surveillance of persons at risk for heart failure and pathological ventricular remodeling prior to development of clinically overt heart failure.

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 :

Substantially reduce the age-adjusted incidence and population burden of chronic heart failure.

Feasibility and challenges of addressing this CQ or CC :

The big data and omics revolutions have made it feasible to collect and analyze a variety of data in large numbers of persons within a relatively short time. A very large sample size provides excellent statistical power. Also, the public health and economic magnitude of the problem create the urgency needed to address the critical challenge expeditiously.

Chronic heart failure (HF) is easily the most common and growing cardiovascular cause of hospitalization and impaired functional status and quality of life in the U.S. and much of the world. This is the case despite improved pharmacologic and lifestyle treatment of HF, as well as improved control of blood pressure in the general population. While some HF in the very elderly may reflect the aging process, the epidemiology suggests that most incident cases could be prevented or postponed for years. Also, there are major ethnic and socioeconomic disparities in the incidence of HF.

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

Voting

14 net votes
28 up votes
14 down votes
Active

Goal 2: Reduce Human Disease

The potency and safety of transfusable red blood cells

Can we identify approaches to improve potency and/or safety of transfusable RBCs? 42 day pre-transfusion storage of RBCs maximizes utilization, while minimizing waste. However, RBCs undergo changes during collection, manipulation and storage that may reduce their potency or safety. Progress in understanding markers that predict transfusion success at the time of collection and with storage remains slow. New technologies ...more »

Submitted by (@nareg.roubinian)

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 novel RBC storage methods have been described, the mechanisms underlying their efficacy has not been defined, a step that will be important for further improvements in this area. Some of these methods appear to improve efficacy of the RBC bioenergetic pathways; however, to date there have not been notable advances in reducing cytoskeletal defects common in stored RBCs. The development of new RBC preservation methods that minimize the impact of the storage lesion on specific areas of concern (e.g., diminished oxidation/peroxidation, decreased membrane fragility) is needed.

 

Use of ex vivo generated RBCs is an alternative to conventional donor-derived RBCs which can potentially improve product consistency, reduce the storage lesion, and improve safety. However, advances are needed before this approach is feasible on a large scale. While the development of blood substitutes including blood pharming will likely require more than 3-10 years before it can be ready for the clinic, Blood Pharming from hematopoietic stem/progenitor cells is now technically feasible and the recent development of genome editing methods suggests the exciting possibility of generating GMP compliant “immortal” stem cell sources to produce transfusable RBCs.

Feasibility and challenges of addressing this CQ or CC :

Research should include both pre-clinical and clinical studies to define optimal combinations of known factors preserving red cells (e.g. hypo-osmolarity, energy sources, antioxidants), and the development of methods for RBC pathogen reduction that do not increase the storage lesion.

 

Procedures for generating blood cells from cultured stem/progenitor cells is not currently cost-effective, limiting near term applications to special patient populations such as specific RBC phenotyping of rare donors for chronically transfused patients. Areas of research needed to advance the development of blood substitutes and blood pharming include: (a) new approaches to blood substitutes including artificial oxygen carriers generated from red cell lysates/components or engineered from combinatorial chemico-biological approaches (e.g., derivatization of hemoglobin, encapsidation of modulated oxygen carriers); (b) a better understanding of the biological properties of cultured RBCs with the goal of reducing blood pharming costs; (c) optimizing methods to expand stem cell populations while allowing differentiation to selected clinically relevant blood cell populations at clinically relevant levels; and (d) optimizing methodologies that faithfully replicate embryonic development to develop the cells of interest.

Name of idea submitter and other team members who worked on this idea : Nareg Roubinian, MD and Naomi Luban, MD for the NHLBI State of the Science in Transfusion Medicine

Voting

14 net votes
31 up votes
17 down votes
Active

Goal 3: Advance Translational Research

Accelerating Translational Research

NHLBI should define a strategy to promote collaborative research between clinician-scientists who perform patient-oriented research, and basic scientists who focus on the preclinical realm. There is not enough cross-talk between these two groups, and yet much to be gained from increasing interactions between the two (e.g. accelerating the translation of bench science findings into the clinic). In particular, funding strategies ...more »

Submitted by (@golan0)

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

Voting

2 net votes
2 up votes
0 down votes
Active

Goal 2: Reduce Human Disease

Understanding the Genetic & Epigenetic Basis of Congenital Heart Disease?

Over the last thirty years, our fundamental understanding of the genetics and pathogenesis of congenital heart disease has lagged the tremendous advances in the surgical and clinical care of infants with this group of disorders. We need to close this gap with investigation into the genetic basis of congenital heart malformations to develop new models of disease. The goall is translate an improved molecular genetic and ...more »

Submitted by (@jamesr.priestmd)

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

Details on the impact of addressing this CQ or CC :

Congenital heart disease (CHD) is the most common congenital malformation and the most common cause of mortality during the first year of life. Approximately 70% of cases occur sporadically without a strong family history or identifiable genetic syndrome, and the primary heritable basis of most non-syndromic CHD has yet to be identified. Studies of affected kindreds, syndromic disease, and more recently genome wide association studies (GWAS) have shed light on a handful of causal loci, while exome sequencing and studies of structural variation uncovering rare de novo variants in trios have yielded only an 8-10% rate of diagnosis in cohorts with CHD. Despite the application of contemporary techniques and study design to genetic discovery in CHD, the majority of the genetic risk for human cardiac malformations remains unexplained.

Feasibility and challenges of addressing this CQ or CC :

One key challenge is that many of the stakeholders including those affected with congenital heart disease (children), along with the physicians make a diagnosis and referral (obstetricians, neonatologists, general pediatricians), are generally funded by other agencies (NICHD). Trans-agency collaboration and cooperation is necessary to improve the translational research structures necessary to improve disease.

Voting

22 net votes
37 up votes
15 down votes
Active