Goal 3: Advance Translational Research

Preventing Stroke from Atrial Fibrillation

How can health systems develop and implement validated measurement and feedback tools to identify patients with atrial fibrillation, categorize their risk factors for stroke, capture reasons for non-treatment, and develop interventions customized to those reasons to substantially improve the proportion of patients receiving effective oral anticoagulant stroke prevention treatment?

Submitted by (@grang001)

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

Details on the impact of addressing this CQ or CC :

Registries show that only about half of patients with atrial fibrillation and risk for stroke are taking oral anticoagulants. Given 4 million Americans with atrial fibrillation, half of whom (2 million) are not treated, with 5% stroke rate per year, 67% of which can be prevented, there are 67000 strokes occuring in this untreated population per year in the US. Assuming half of these could be treated if programs were develped that were proven effective, this would result in 33,000 strokes prevented per year.

Feasibility and challenges of addressing this CQ or CC :

NIH funds are needed to address the complex set of health system, psychosocial, and health IT issues to answer this question. Atrial fibrillation is a common condition with patients presenting and being treated accross various parts of the health care system. Small programs have shown promise for the use of the electronic health record to systematically identify patients with atrial fibrillation, but health system leadership needs evidence of success and guidance before this will be possible on a broad scale. With evidence of feasibility and impact, performance measures may be developed that would substantially enhance adaptation.

Name of idea submitter and other team members who worked on this idea : Chris Granger

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6 net votes
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Goal 2: Reduce Human Disease

Address bias of doctors treating obese patients

Twice I was allowed to develop severe heart failure symptoms that required hospitalization to treat because my primary care physician assumed that my ONLY problem was that I am fat. Every doctor knows that obesity can lead to the development of diabetes, heart diseases, joint damage and yet too many doctors on the frontlines just say: You're fat go diet. My first experience with this was when I was first diagnosed ...more »

Submitted by (@chriscage)

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

Details on the impact of addressing this CQ or CC :

I'd like to know how many patients die because their primary care doctors don't take their health complains seriously. If you can somehow get primary care doctors to open their eyes and do their jobs, patients like me might not be on the verge of death because their doctors refuse to listen. I had a history of heart failure, I told my primary care doctor that my first doctor completely missed the symptoms in 1996, including swollen ankles and feet, the inability to walk two blocks without stopping and having coughing fits that forced me out of bed into a wing-back chair. I started having those symptoms again in 2011 and ended up spending two and half weeks in a hospital in November 2012 to treat my problems and to drain 96 pounds of fluid from my body. I couldn't bend my legs to get into a car or a truck.

Feasibility and challenges of addressing this CQ or CC :

Of course it is possible to deal with this issue. The question is whether doctors and medical researchers are ready to be honest about the role neglect by primary care physicians plays in the overall health of their patients.

 

Both of the doctors who risked my life had good reputations. I liked them until they stopped listening to me. I had an echocardiogram in October 2011 my ejection fraction was between 20 and 15. I thought I was going to die. My doctor said: numbers don't mean anything??? One year later, I spent two and a half weeks in the hospital.

 

Why do you think I'm hopping mad. How many other patients are dealing with the same types of problems. I literally had to take Xanax because when my symptoms returned I was afraid that my stupid doctors would kill me by ignoring me again. I reported my fears in detail to United Healthcare, I switched to a more competent medical system. I'm losing weight and spent hours walking around Yosemite National Park last month. That's the difference between doctors who listen and doctors who don't. A patient should not be afraid that their doctor is so stupid that she or he will kill them .... accidentally.

Name of idea submitter and other team members who worked on this idea : Mary Crystal Cage

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5 net votes
21 up votes
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Goal 1: Promote Human Health

Epigenetics and Genomics

There is a need to target epigenetic mechanisms as new treatment options for hematologic disorders.

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

Details on the impact of addressing this CQ or CC :

Advances in the field of epigenetics and the understanding of various epigenetic mechanisms has provided a completely new ensemble of therapeutic targets for treating hematologic disorders – both non-malignant and malignant. These mechanisms have enormous implications for understanding the molecular underpinnings of the normal orderly development of hematologic disorders. Although one of the greatest challenges in effectively treating hematologic disorders is the diversity of molecular abnormalities that underlie a disease, there are a number of common threads emerging, including alterations in proteins that function through epigenetic mechanisms. Additional research focusing on epigenetic alterations and emerging targets is needed to identify the role of such proteins in the development of hematologic disorders in order to design potential targeted treatments to counter their effects. This research will further lay the groundwork for precision medicine, and will help to provide more insight on potentially critical determinants of responsiveness to therapeutic regimens.

Name of idea submitter and other team members who worked on this idea : Alice Kuaban on behalf of the American Society of Hematology (ASH)

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13 up votes
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Goal 2: Reduce Human Disease

Consequences of drug interactions leading to QTc prolongation

Better understand the consequences of drug interactions leading to QTc prolongation. About 1/3 of cardiac ICU patients develop QT prolongation and about 45% receive drugs that are possibly contributing to this problem. The full spectrum of contributors and causes, as well as the patient-centered and health-system-centered clinical outcomes, are not known.

Submitted by (@greg.martin)

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 in adverse drug events and preventable deaths

Feasibility and challenges of addressing this CQ or CC :

Combining the power of predictive analytics of high dimensional data streaming continuously from critically ill patients, combined with precision medicine genomics and metabolomics, makes this imminently feasible.

Name of idea submitter and other team members who worked on this idea : Society of Critical Care Medicine Executive Council

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Goal 4: Develop Workforce and Resources

Moderating Positive Feedback between Research Funding and PhD/postdoc Numbers

A critical challenge will be to limit future destabilizing expansion of the number of PhD students and postdoc trainees. Because 75-80% of biomedical PhD students and postdocs now supported by NIH are funded by RO1 and other research funding, if/when research grant budget increase the number of PhD and postdoc “slots” would automatically expand--even if there is no expectation of comparable increases in demand for ...more »

Submitted by (@teitelbaum)

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

Details on the impact of addressing this CQ or CC :

Many including National Academies committees suggest that the 75-80% figure should be gradually reduced to around 50%, without increasing overall numbers, i.e. both limiting numbers supported under research grants and increasing numbers supported under training programs. Moderating the currently strong linkages of PhD/postdoc numbers to research funding should make future biomedical research careers more attractive than they have been in recent years.

Name of idea submitter and other team members who worked on this idea : Michael S. Teitelbaum

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5 net votes
15 up votes
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Goal 2: Reduce Human Disease

Phase III efficacy trials of tuberculosis drugs

1) Phase III efficacy trials of new tuberculosis drugs (e.g., bedaquiline, delamanid, PA-824) that have shown promise in early phase studies for multidrug-resistant tuberculosis. 2) Phase III efficacy trials of new and existing tuberculosis drugs to development very short course regimens (3-4 months). 3) Phase III efficacy trials of new and existing drugs for treatment of latent tuberculosis infection in contacts of ...more »

Submitted by (@nhlbiforumadministrator)

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 : American Thoracic Society member

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Goal 2: Reduce Human Disease

Biomarkers and phenotypic characteristics of asthma patients

Are there biomarkers or phenotypic characteristics that will allow us to identify the patients with asthma who will experience a more rapid decline in lung function?

Submitted by (@nhlbiforumadministrator)

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 : American Thoracic Society

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Goal 2: Reduce Human Disease

How do comorbidity of SDB, ED,(and others?) in sleep indicate or predict CAD?

CQ

Submitted by (@davinc)

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

Details on the impact of addressing this CQ or CC :

Can be early warnings

Feasibility and challenges of addressing this CQ or CC :

Easy to measure and assess

Name of idea submitter and other team members who worked on this idea : D. Davis

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Goal 2: Reduce Human Disease

Reducing Disparities

Given the dearth of information on cardiovascular, lung, and hematologic outcomes in minorities, NHLBI should develop strategic aims that promote evaluation of these outcomes and potential interactions with kidney disease that disproportionately affect minorities.

Submitted by (@golan0)

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

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Goal 2: Reduce Human Disease

mechansisms of post thrombotic syndrome

No good medical therapy exists to prevent and treat post thrombotic syndrome, the most common sequlae from a deep vein thrombosis. Recent trial data suggests that compression stockings do not prevent PTS, and thrombolysis is expensive and risky. The basic mechanisms related to fibrosis of the vein wall are not well understood.

Submitted by (@henke0)

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

Details on the impact of addressing this CQ or CC :

Further research into this area, both at the human and animal model level would allow potential translation of novel agents without the risks of anticoagulatnts, as well as shine light on basic fibrotic vascular disease processes.

Feasibility and challenges of addressing this CQ or CC :

Doable with both well defined human patients, and animal models of the disease that are similar to humans

Name of idea submitter and other team members who worked on this idea : peter henke

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Goal 2: Reduce Human Disease

Bringing Personalized Biochemistry and Biophysics to Bear on Problems of Personalized Heart, Lung and Blood Medicine

Precision medicine will provide unprecedented opportunities to tailor health care based on knowledge of personal patterns of genetic variations. These variations usually impact protein or RNA sequences, resulting in altered properties. These alterations can result in increased susceptibility to a particular disease or intolerance to common therapeutics. To take full advantage of knowing a patient’s set of gene variations, ...more »

Submitted by (@chuck.sanders)

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 detailed in the attached review (Kroncke et al. Biochemistry 2015, 54, 2551−2559) the successful practice of personalized medicine will in many cases require a molecular-level understanding of the nature of the defects that are caused by disease-predisposing genetic variations. As widespread personal genome sequencing becomes routine, numerous genetic variations (many millions) of uncertain significance will be discovered. Using both experimental and computational tools associated with the fields of biochemistry, biophysics, and structural biology it is in many cases possible to ascertain whether a newly-discovered gene variation adversely impacts a critical protein or RNA function and, if so, how. Among various clinical applications this information can be used (i) to project whether a patient not currently showing symptoms for a particular disease is likely to present with that disease in the future (sometimes enabling prophylactic therapy), (ii) to help establish the molecular etiology of a disease currently afflicting the patient, and (iii) to guide the therapeutic strategy pursued for that patient.

Feasibility and challenges of addressing this CQ or CC :

My lab is already participating in a project (RO1 HL122010) with two other labs (those of Drs. Jens Meiler--Vanderbilt and Alfred George--Northwestern) to develop personalized biochemical and biophysical approaches for application to genetic variations impacting the KCNQ1 gene, potentially predisposing patients to long QT syndrome, a cardiac arrhythmia. However, our project deals with one gene and one disorder only. There clearly is a need for improved and expanded communication and collaboration between those practicing personalized/precision medicine and those who are well-equipped to provide medically actionable molecular insight using the approaches of personalized biochemistry, biophysics, and structural biology.

Name of idea submitter and other team members who worked on this idea : Charles R. Sanders, Prof. of Biochemistry, Vanderbilt University (With Drs. Alfred George--Northwestern University and Jens Meiler--Vanderbilt University)

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Goal 3: Advance Translational Research

Promoting Research on Translation of Evidence into Practice within Academic Medical Health Care Systems

Academic Medical Centers (AMCs) must become translational research leaders by conducting implementation research (IR) within their own health care systems. Doing so will require new paradigms, breaking down silos between research and operations, new incentives, and new funding streams. Steps include CTSA renewal requirements for significant IR and building on the QUERI (Quality Enhancement Research Initiatives) from ...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 :

AMCs are the engines of scientific research in the US. They possess the brain power, resources and reputation necessary to alter the trajectory of the translational continuum of research. Currently 62 AMCs are funded through CTSA in 31 states. Through their own health systems and their affiliates, AMCs provide health care to a sizable portion of the US population. Most AMCs now use the same EHR (EPIC). Nearly all are embarking on system change including establishing accountable care organizations, bundled payments, and medical centered homes. These assets provide fertile ground for research on how to best implement scientific evidence into health care to achieve the triple aim: improved care to patients, improved health to populations, and reduced costs. If AMCs take IR to heart, this could be a game changer. Success could establish a virtuous cycle whereby improved health and reduced costs convinces a skeptical Congress to authorize greater funding for NIH tagged to IR. This change requires moving AMC rhetoric into action and becoming leaders in IR in their own back yards.

Feasibility and challenges of addressing this CQ or CC :

The major challenges are new paradigms, incentives, infrastructure, and funding. Most AMCs regard health care systems operations and research as separate. Despite the mantra to become "learning health care systems" few AMCs conduct IR within their own health systems. Changing this paradigm will require incentive to change, new infrastructure including new types of teams, and funding streams. The CTSA renewal mechanism represents a starting place but this will need to be coupled with program announcements and center awards that establish a QUERI like infrastructure including teams of IR researchers, health care administrators and PBRNs. The challenge is great but a new paradigm is critical if scientific research is to guide the seismic changes that are occurring in within US health care.

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

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19 up votes
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