Goal 2: Reduce Human Disease

To extend our knowledge of the pathobiology of heart, lung, blood, and sleep disorders and enable clinical investigations that advance the prediction, prevention, preemption, treatment, and cures of human disease.

Goal 2: Reduce Human Disease

Single thing needed to prevent obesity: control the mouth

The cause of obesity is clear and simple: eating > needs, or in > out; that is, energy intake is greater than energy use. For the majority of the public, there is little genetic component to cause obesity or over weight. Rather, personal determination is the single thing that is needed to control body weight. Just control the mouth. Simple and easy, and free. Even for the most favorite food, the amount to eat should be ...more »

Submitted by (@eastcastlegeastcastle007)

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 : eastcastle007

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Goal 2: Reduce Human Disease

Reducing Variability in Outcomes from Out of Hospital Cardiac Arrest

Out of hospital cardiac arrest remains a major cause of mortality in the United States and there is a large variability in survival within communities. We need to better understand the reasons for this variability which include patient, event, EMS system and care processes and work as a nation to reduce the variability but adopting best practices and actively addressing the barriers to change which can be social, cultural, ...more »

Submitted by (@dayam0)

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

Details on the impact of addressing this CQ or CC :

If we could reduce variability, we would save more lives and also enhance the chain of survival in our communities

Feasibility and challenges of addressing this CQ or CC :

will require that we connect multiple parts of the community including the population at risk, public health services and the health care system which is not always easy in silo systems or fragmented health care systems

Name of idea submitter and other team members who worked on this idea : Mohamud Daya

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Goal 2: Reduce Human Disease

Blood Pressure Recommendation

What should be the systolic blood pressure goal for pharmacological treatment, and should it vary by age or by cardiovascular disease (CVD) risk category?

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 :

Despite fifty years of clinical trial research and forty years of national guideline activity, important clinical questions remain under intense scientific debate. The importance of these questions are underline by the scientific consensus that hypertension is most important cardiovascular risk factor globally, in fact, more important than even tobacco use.

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

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Goal 2: Reduce Human Disease

Psychological & Behavioral Phenotyping to Improve Weight Control

What information is needed to improve our understanding of individual characteristics and processes that explain or predict dietary intake patterns, initiation or sustained engagement in physical activity, and sedentary behavior so that we can improve treatment matching and identify novel targets for more efficacious individual- and population-level approaches for weight management?

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 :

Because there is wide variability in response to obesity treatment, strategies that take individual psychological, behavioral, sociocultural, motivational, cognitive and emotional characteristics into account so that treatments can better "match" the individual's needs could greatly improve the efficacy of existing treatments and/or lead to new more effective weight loss strategies.

Feasibility and challenges of addressing this CQ or CC :

By adding measures of key psychological, social, and behavioral processes to ongoing or planned weight control studies, we can learn which characteristics are most predictive of weight loss and maintenance for which participants, leading to better tailoring of weight loss treatments to the individual and potentially improved outcomes.

Despite evidence that use of evidence-based behavioral weight loss strategies can be effective and lead to meaningful improvements in health outcomes, there is wide variability in response to treatment and varying degrees of maintenance of weight loss.

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

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50 up votes
21 down votes
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Goal 2: Reduce Human Disease

Systems Approaches to "Phenosimilar" Diseases

There are diverse diseases that share similar features. For example, many chronic airways diseases (chronic aspiration, ciliary dyskinesia, some COPD) "phenocopy" cystic fibrosis in terms of infectious agents, mucus clearance problems, progressive loss of lung function, etc. Use multiplatform "omics" approaches and Big Data bioinformatics to identify common nodes for therapeutic targeting. Other examples: emphysema and ...more »

Submitted by (@jhagood)

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

Details on the impact of addressing this CQ or CC :

may be able to target multiple diseases with new or repurposed therapies. Might narrow down the broad array of potential "high value" targets to study.

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Goal 2: Reduce Human Disease

Identifying Epistatic Genes in Sickle Cell Disease

What genes are involved in the modulation of phenotype in sickle cell disease?

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 :

The pathophysiology of sickle cell disease results from cellular defects caused directly by the Hb S mutation interacting with the environment and many other gene products—some known, but most yet unidentified–a typical example of epistasis. How normal tissue perfusion is interrupted is complex and why the phenotype of sickle cell disease differs from patient to patient is poorly understood. Answers to this question will provide additional insight into their biological and functional relationships.

Feasibility and challenges of addressing this CQ or CC :

Scientific advances make it feasible to identify additional epistatic genes, which will provide additional insight into their biological and functional relationships.

Name of idea submitter and other team members who worked on this idea : The Sickle Cell Association of New Jersey

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Goal 2: Reduce Human Disease

Development of Optimally Hemostatic, Systemically Safe, Platelet Mimetics or Substitutes

What are the knowledge and technological gaps in production, evaluation and clinical translation of donor-independent platelets for transfusions? Specific questions include: a) How can stem or progenitor cells be expanded to maximize platelet production?; b) What are the hemostatically relevant design and function requirements and evaluation metrics for ideal/optimal “biologic” and “synthetic” platelets? c) What preclinical ...more »

Submitted by (@dtriulzi)

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

Details on the impact of addressing this CQ or CC :

Platelets produced from induced pluripotent stem or progenitor (megakaryocyte) cells (biologic production), as well as, manufactured from engineered biomaterials (synthetic production) could address clinical needs of supply issues and transfusion related function and safety concerns. However, there are key knowledge and technology gaps in both approaches, and in corresponding qualitative and quantitative correlation of the platelet products with hemostatic efficacy and safety. One important step is increasing both stem and progenitor cell expansion in culture. A parallel step is to develop synthetic platelet mimetics using biomaterials engineering. Finally, the hemostatic efficacy and safety of the products need to be established in clinically relevant models and patients.

Feasibility and challenges of addressing this CQ or CC :

The above questions can be addressed by establishing high throughput screens for compounds that expand CD34 or CD41 cells or trigger platelet release and ploidy, developing culture methods using 3D scaffolds to mimic bone marrow perivascular niche, using proteomics or RNA-sequencing to reveal molecules critical for terminal megakaryocyte maturation and platelet formation. Large-scale bioreactors can be adapted to test molecules, triggers and conditions for amplifying platelet production. For synthetic platelet mimics, the benefits of integrating natural platelet’s physico-mechanical properties with its hemostatic biochemical properties on synthetic biomaterial platforms, can be studied in vitro. Scaled-up particle fabrication technologies with control over particle geometries and surface chemistries, can be adapted for manufacturing synthetic platelets. Large-scale production of platelets through biologic and synthetic routes would enable studies in animal models with clinically relevant bleeding disorders, to correlate design and dosage with hemostatic function and safety. Subsequently, clinical studies can be carried out in Phase 1 for safety analysis in dose escalation and in vivo kinetics (recovery and survival for biologic, degradation and clearance for synthetic). Phase II studies can evaluate bleeding incidence, transfusion requirements and thrombotic events in a controlled population of thrombocytopenic patients under-doing chemotherapy or stem cell transplantation.

Name of idea submitter and other team members who worked on this idea : NHLBI 2015 State of the Science in Transfusion Medicine

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Goal 2: Reduce Human Disease

Novel methods to diagnose and treat microvascular ischemia

Microvascular ischemia is common, particularly in the setting of critical illness. We need better ways to evaluate, diagnose and treat these conditions, whether they relate to microvascular myocardial ischemia, as a primary diagnosis of complication of other acute illness, or non-myocardial ischemia during the course of surgery, injury, infection or acute illness.

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 :

Development of effective diagnostics would lead to improved treatments for myocardial and non-myocardial microvascular ischemia, and also advance understanding to extend the advance beyond this setting.

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

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Goal 2: Reduce Human Disease

Improve Repair of injured lung

Why can’t we improve outcomes following acute lung injury. A half century of ICU interventions have resulted in only incremental improvements in survival and morbidity following acute lung injury. While we have pursued innumerable strategies for decreasing ventilator associated exacerbation of lung injury, we have failed to identify treatable common or selective pathways from the initial injury that can be targeted post ...more »

Submitted by (@dcenter)

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

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Goal 2: Reduce Human Disease

Improve ineffective treatments for circadian rhythm disorders

I have extreme delayed sleep phase disorder (DSPD), a circadian rhythm disorder (CRD). I fall asleep at dawn and wake up early afternoon. My dim light melatonin onset (DLMO) is at 5:30 am. A normal person’s DLMO may be at 9 pm, for example. CRD treatment—prolonged bright light after temperature nadir, dark restriction/melatonin starting several hours before natural bedtime, darkness till temperature nadir—does not work ...more »

Submitted by (@susanpl)

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

Details on the impact of addressing this CQ or CC :

Circadian rhythm disorders (delayed sleep phase disorder, non-24-hour sleep-wake disorder, irregular sleep-wake disorder) have been ignored by many sleep researchers. They should not be. First, they reduce lives to rubble: education, employment, partnering, and parenting suffer or are not possible. Second, nocturnals who force themselves to live a diurnal life are at higher risk of disease (as are diurnals who work 3rd shift) and accidents. Third, evidence is mounting that circadian rhythms play a significant role in immunity, cancer, heart disease, diabetes, obesity, metabolic (dys)regulation, mental health, medication administration, and public health (think of the spike in accidents after spring and fall time changes).

Feasibility and challenges of addressing this CQ or CC :

To date, most circadian research has been conducted on "normals" who don't have CRDs. But their responses to light and dark cues differ from those of CRD patients. Please conduct circadian research on CRD patients--just as you would conduct diabetes research on diabetics.

 

Also needed: convenient ways to test for dim light melatonin onset, temperature nadir, and other circadian biomarkers. Right now, such tests are limited to study settings.

Name of idea submitter and other team members who worked on this idea : Maya Kochav

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103 up votes
28 down votes
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Goal 2: Reduce Human Disease

Management of COPD in the presence of comorbidity

Management of COPD in the presence of comorbidity • Does a protocol-based screening for commonly occurring comorbid conditions in patients with COPD (eg. CAD, CHF, depression, sleep apnea) improve management and outcomes for patients with COPD? • How should providers coordinate management strategies and treatment goals in patients with COPD and other co-existing chronic diseases? • What is the comparative effectiveness ...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

Incorporate important co-morbidities of COPD into treatment guidelines

Incorporate important co-morbidities of COPD into treatment guidelines. This becomes crucially important with cardiovascular disease (CVD) which shares risk factors and pathogenesis

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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