Goal 2: Reduce Human Disease

Evidence based approaches to Red Blood Cell transfusion

What are the optimal RBC transfusion thresholds for adult and pediatric cancer patients undergoing chemotherapy regimens that may improve functional status and quality of life?

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

Details on the impact of addressing this CQ or CC

Cancer patients undergo intensive medical and surgical therapies to treat their underlying disease. Treatment commonly results in anemia requiring RBC and platelet transfusions to support the patient through the hypoproliferative phase of chemotherapy. This is particularly true for those patients requiring hematopoetic stem cell transplantation (HSCT). Following therapy, cancer outpatients commonly receive RBC transfusions for weeks to months to maintain their functional status.

Common causes of death in patients with hematological malignancies and other cancers are infections and bleeding. A meta-analysis of clinical trials suggested that liberal transfusion is associated with greater risk of infection. Conversely, restrictive transfusion could adversely affect quality of life and functional status in oncology populations. In addition, pre-clinical and clinical studies support that concomitant anemia and thrombocytopenia significantly compound bleeding risk, and that hemostasis can be optimized in thrombocytopenia by maintaining a higher hematocrit. Although bleeding risks in relation to platelet transfusion thresholds are well studied in patients with hematological malignancy, optimal hemoglobin levels in thrombocytopenic patients are not known. Despite the significant allocation of blood components to cancer patients as a whole, RBC transfusion practices are not well studied within this group.

Feasibility and challenges of addressing this CQ or CC

Randomized controlled clinical trials and other studies investigating optimal transfusion thresholds and other measures of practice are required to provide health care providers with evidence to guide one of the most common therapies administered in the setting of malignancy. The clinically important end points of well-designed studies could include: 1) quality of life and functional status for both inpatients and outpatients; 2) neurocognitive development in pediatric populations; 3) bleeding events / bleeding scores; 4) impact on immunity including immunomodulation and infection; 5) reconstitution of hematopoiesis; and 6) survival and/or recurrence of disease.. Besides a generalizable study population, certain target populations of interest are those with high risk disease, HSCT patients, patients undergoing radiation therapy, and pediatric patients.

There are >1.6 million new cases of cancer annually in the USA, including >50,000 with leukemia and >6,000 with HSCT. Cancer therapies are rapidly advancing in the era of genomics and immunotherapy. Capitalizing on the tradition of research in cancer, single and multicenter studies of RBC transfusion are feasible using randomized controlled designs in conjunction with clinical trials of chemotherapeutic regimens. The results of these studies will impact a large patient population’s quality of life, and may ultimately impact healthcare cost and blood demand.

Name of idea submitter and other team members who worked on this idea Nareg Roubinian, MD and Naomi Luban, MD for the 2015 NHLBI State of the Science in Transfusion Medicine

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18 down votes
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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 »

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

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19 net votes
26 up votes
7 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 »

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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Goal 2: Reduce Human Disease

Stem Cell Immunology

We now can create critical cell types like cardiomyocytes etc. from stem cells. Additionally, we are learning the rules of using these cells to rebuild tissues. A major gap in our knowledge relates to the immunobiology of these cells. Lessons from transplantation medicine are only partially applicable, because solid organs are more complex and likely more immunogenic than defined cell populations.

How does the immune... more »

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

Details on the impact of addressing this CQ or CC

We now can generate large quantities of critical cell types whose deficiencies underlie many chronic diseases like heart failure. This breakthrough brings us to the next-level impediment: the immune system. While induced pluripotent stem cells have the potential to obviate rejection, in practical terms this is cost-prohibitive: It will cost huge amounts of money to produce and qualify a single patient's cell dose. Moreover, human cardiomyocytes are potent when given to infarcted hearts in the acute or sub-acute phase of infarction, but they have no benefit with chronic heart failure. The 6 months required to produce iPSC-cardiomyocytes precludes their autologous use for myocardial infarction.

We need an off the shelf cell therapy product for myocardial infarction that can be mass produced and qualified for large numbers of patients. This means an allogeneic product is necessary. Identifying the immune response to cardiomyocytes or other cell products will teach us how to precisely immunosuppress the patient, thereby minimizing complications, or alternatively, how to engineer the cells so as to avoid immunogenicity in the first place.

Lessons from the study of cardiomyocyte transplantation could extend to dopamine neurons, pancreatic beta-cells, retinal cells, myelinating cells and many other areas that cause common chronic disease.

Feasibility and challenges of addressing this CQ or CC

We know a great deal of transplant immunology from hematopoietic stem cell transplantation (graft versus host) and from solid organ transplantation (host versus graft). There are good mouse and large animal (including non-human primate) models of stem cell differentiation and organ transplantation. This offers low hanging fruit where, in perhaps 5 years, we could discern the critical similarities and differences between transplanting stem cell derivatives and organ or marrow transplantation. These studies will inform clinical trials of allogeneic human stem cell derivatives that will be underway by then.

Success in this area will require bringing together researchers interested in stem cell biology and transplant immunology. A properly resourced RFA from NIH could be just the thing needed to promote this interaction.

Name of idea submitter and other team members who worked on this idea Charles Murry, MD, PhD

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23 net votes
45 up votes
22 down votes
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Goal 2: Reduce Human Disease

Clinical Trials in Pediatric Sleep Disorders

Long-term risk of recurrence of obstructive sleep apnea in children successfully treated with surgery during childhood.

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

Details on the impact of addressing this CQ or CC

Very small, incomplete, retrospective studies, and some new emerging data from Hong Kong, suggest that a significant number of children with obstructive sleep apnea syndrome will develop progressive symptoms later in life, or will develop recurrence of OSAS after adenotonsillectomy. Further studies are needed to determine the long-term risk of recurrence. Results of this trial will influence clinical management in regards to ongoing surveillance and secondary prevention techniques.

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

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1 net vote
1 up votes
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Goal 2: Reduce Human Disease

The effects of environmental factors on heart, lung, blood, sleep disease development across the lifespan

How do growth, development, exposure, and behavior affect heart, lung, blood, sleep disease development and outcome throughout the lifespan?

 

How do you improve organ function/capacity during childhood?

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

Details on the impact of addressing this CQ or CC

Defining earliest elements of disease and strategies for prevention

Feasibility and challenges of addressing this CQ or CC

If we don’t start now, it will never get done
. Challenges:
• Determine if elements of cell aging, including stem cell aging and senescence, affect disease progression and the effectiveness of therapeutic interventions
• Can we develop iPS based or other cell based bioengineered tools to more precisely define cellular and molecular responses to particular exposures?
• How do we identify, prioritize and measure relevant environmental exposures?

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

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12 net votes
32 up votes
20 down votes
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Goal 2: Reduce Human Disease

Non-Adherence of Patients with Chronic Respiratory Diseases

There are various reasons responsible for patients’ non-adherence. One of them is insufficient or lack of education about medications and equipment required for their treatment.

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 critical need to develop uniform guidelines and handouts addressing the confusion over the proper use of medications (particularly inhalers) and equipment (i.e. oxygen). Improper use leads to diminished or no benefit, frustration, and, ultimately, even to a patient's decision to stop the treatment.

Feasibility and challenges of addressing this CQ or CC

This is an issue that has been universally acknowledged for a number of years. With the help of patient focus groups, convened at the NHLBI, national pulmonological conferences, or at local venues around the country, appropriate materials can be created to benefit patients and reduce a huge burden on nation's economy due to decreased productivity and increase in hospital admissions.

Name of idea submitter and other team members who worked on this idea COPD-ALERT

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20 up votes
20 down votes
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Goal 2: Reduce Human Disease

Preventing or reversing myocardial fibrosis

Conduct proof-of-concept studies and explore whether strategies to reverse or prevent fibrosis are feasible.

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

Details on the impact of addressing this CQ or CC

This challenge will lead to early studies of potential therapeutics for arrhythmias and heart failure. If successful, this would have huge impact.

Feasibility and challenges of addressing this CQ or CC

Recent studies have identified some compelling signaling pathways that activate fibrosis so it is feasible to test them through creative experimentation.
Fibrosis and fibrogenesis in the myocardium are clear indications that heart function is either declining or progressing towards decline. Although much of the current research continues to focus on unraveling mechanisms that lead to fibrosis and activation of fibrogenesis, there is as yet less focus on potential mechanisms to prevent or reverse fibrosis. This was in part due to insufficient understanding of major causes of fibrosis and mechanisms that activate fibrogenesis. However, findings from recent studies show that there are several compelling therapeutic targets that are ready to be tested to see whether fibrosis can be reversed or prevented.
May need strategies on how to best to succeed in implementing the research - e.g., what research mechanisms, what kind of teams, what kind of expertise, etc. To fine tune this, a focused workshop for advice may be helpful.

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

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19 net votes
33 up votes
14 down votes
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Goal 2: Reduce Human Disease

Optimizing weight loss

For patients with obesity and medical comorbidities, what is the optimal approach utilizing multiple therapies (low calorie structured diet, intensive lifestyle, weight loss medications) in combination to optimize weight loss?

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

Details on the impact of addressing this CQ or CC

Weight loss has health benefits in diabetes reduction, risk factor improvement, improvement in symptoms of sleep apnea, improvement in NAFLD, improvement in feeling and function (knee pain, urinary stress incontinence, sexual function). In all these circumstances, greater weight loss yields more benefit. Our best lifestyle interventions, delivered by the most skilled behaviorists yield weight loss of, on average 8% and one third of persons undergoing the intervention do not lose even 5%. How can we use multiple approaches together to improve the amount and durability of weight loss achieved in our counseling programs.

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34 net votes
84 up votes
50 down votes
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Goal 2: Reduce Human Disease

How gene mutations contribute to defects in vascular development

How do gene mutations in endoglin and alk 1 create arteriovenous malformations leading to disease. Alk 1 and endoglin are receptors in TGFB/BMP family signaling. TGFB/BMP have roles in vascular development, remodeling and maintenance in vascular integrity. Understanding the downstream effect will lead to advancements in reducing genetic diseases such as HHT as well as vascular malformations in general

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 Marianne Clancy MPA, Chris Hughes PhD

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

Relevance of cardiovascular disease associated with autoimmunity research

NIH estimates up to 23.5 million Americans suffer from autoimmune disease (AD) and up to 24 million from heart diseases. As a result, NIH and AHA estimates the annual direct health care costs for AD to be in the range of $100 billion and $200 billion for heart and stroke diseases. Yet this area of research has been neglected and underfunded. The proposition is for NHLBI to partner with other NIH institutes dealing with... more »

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

Details on the impact of addressing this CQ or CC

Reduce the impact of autoimmune diseases on the heart and vascular system.

Feasibility and challenges of addressing this CQ or CC

Generate RFAs dedicated to the field of autoimmune associated cardiovascular diseases.

Name of idea submitter and other team members who worked on this idea M. Boutjdir

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11 net votes
15 up votes
4 down votes
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Goal 2: Reduce Human Disease

Pulseless Electrical Activity (PEA) - replacing VF/VT

As VF/VT rates continue to decrease in cardiac arrest to levels below 25%, the importance of understanding the pathways and epidemiology of PEA gains public health importance. Additionally, there is a need to determine the co-morbidities and/or pharmacologic agents that contribute to the causation of this rhythm.

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

Details on the impact of addressing this CQ or CC

Greater understanding of PEA would lead to better treatment (good CPR only treatment currently) and higher survival rate in CA

Feasibility and challenges of addressing this CQ or CC

How will be treat the majority of cardiac arrest when it becomes PEA?

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

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-9 net votes
7 up votes
16 down votes
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Goal 2: Reduce Human Disease

Harnessing the Tsunami of Patient-Generated Health Data

How can the NHLBI foster the development of effective tools and methodologies to harness the tsunami of patient-generated health data into a valuable resource for conducting patient-centered research? Some challenges to overcome might include a) how to enable the collaboration of the more traditional clinical scientists with scientists from other disciplines such as informatics or computational and data-enabled science... more »

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

Details on the impact of addressing this CQ or CC

Methodological research results in this area could be translated into clinical settings – specifically, they could help physicians interpret such data without being overwhelmed by their sheer volume, and even further use them as helpful adjunct tools to more traditional ways of diagnosing and/or treating diseases.

Feasibility and challenges of addressing this CQ or CC

The increasing number of smartphones, mobile apps, and remote monitoring devices are producing a vast amount of patient-generated health-related data. However, there are no widely established tools, methodologies, or strategies to ensure optimal use and management of these data. The time is right to move forward quickly in furthering research in this field over the next 5 to 10 years.

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

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-1 net votes
10 up votes
11 down votes
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Goal 2: Reduce Human Disease

Biomarkers and Response Predictors in Asthma

As the current chair of the Research and Training Division, I would like to convey that the AAAAI membership would like the NHLBI to consider the following in the development of its strategic plan: Given the development of specific biologic therapy for asthma, what are the biomarkers and predictors of response that will allow clinicians to choose the best therapeutic combination of medications (biologic and otherwise)... more »

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 Mitchell Grayson on behalf of the American Academy of Allergy, Asthma, and Immunology

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7 net votes
18 up votes
11 down votes
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Goal 2: Reduce Human Disease

Novel technologies to save minutes and lives

There is a need to develop hand-held portable imaging or other technologies that can help paramedics to collect and transmit data when patients are undergoing cardiovascular events.

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

Details on the impact of addressing this CQ or CC

Save time and lives for patients destined to Emergency

Feasibility and challenges of addressing this CQ or CC

The component technologies are developed enough to integrate them in the next 5-10 years
Time spent waiting for an ambulance, driving to a hospital and enduring diagnostic tests before medical intervention can quickly add up, especially with patients undergoing cardiovascular events. In the era of internet, smartphones, and portable imaging and handheld technologies, saving valuable time during which paramedics can be assisting the emergency physicians in diagnosing heart attacks and help to identify and start the needed intervention at once when the patient arrive at the hospital.

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

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6 net votes
13 up votes
7 down votes
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