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

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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 :

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Feasibility and challenges of addressing this CQ or CC :

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

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Goal 2: Reduce Human Disease

What is the place of curative therapies in the management of Sickle Cell Disease

Advances in the care of pediatric patients with sickle cell disease ( SCD) have resulted in improved survival to adulthood.However, adulthood is marked by rapid disease progression, impaired quality of life and premature mortality. Hematopoietic cell transplantation(HCT) from matched sibling donor has curative potential, but has been offered mainly to children. Refinements in the conditioning regimen, supportive care, ...more »

Submitted by (@lakshmanankrishnamurti)

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

Details on the impact of addressing this CQ or CC :

To overcome this obstacle to progress in the field, we propose the creation of the funding mechanisms for a multicenter clinical trial consortium which would bring together investigators in field and facilitate study the outcomes of CT for patients with different types of donors and stem cell sources and compare them to outcomes in phenotypically matched controls receiving best available standard of care.Answering the compelling question about the role of CT in the management of SCD has the potential to have a catalytic effect in progress in this field. Patients are are then more likely to receive CT or standard of care at the appropriate time and in the manner in which they are most likely to have a positive outcome. This has the potential to reduce morbidity and premature mortality and in the long run, to decrease the burden of the disease on the healthcare system. The advent of clinical trials of gene therapies for SCD offers the prospect of even greater applicability of curative therapies. Thus, a consortium developed to answer this CQ would serve as a crucial vehicle for providing access to a greater proportion of patient to these personalized curative therapies . Such studies would also be powered to answer the question about who should receive the curative therapy, when they should receive it, and how it would impact their SCD related complications, late effects, survival and quality of life and help families make informed choice appropriate for their situation.

Feasibility and challenges of addressing this CQ or CC :

The increasing applicability and acceptability of HCT for SCD is evidenced by the doubling in the number of such procedures reported to CIBMTR in the decade starting 2001. Refinements in conditioning regimen and supportive care continue to improve outcomes in children and now in adults with SCD undergoing HCT from HLA matched related donors. Recently, HCT from unrelated donors and from haplo-identical donors have further increased the applicability of HCT. Opening of gene therapy trials has further raised the prospect of cure for a greater proportion of patients. These developments are evidence of the feasibility of recruitment to large multi-center comparative trials of SCD and standard of care. Recently, there has been increasing collaboration among investigators in the field with informal consortia being developed by investigators coming together to study HCT for children, adults or HCT from haplo-identical donors. These groups are also increasingly working with SCD hematologists, families and other stakeholders. There is also increasing cross-cutting collaborations with other medical specialists and behavioral and translational scientists Thus, the convergence of several factors described above suggests that the time is fortuitous for a major initiative from the NHLBI to bring investigators together and create the infrastructure that will enable these investigators to seek definitive answers to the challenging question “What is the place of curative therapy in SCD?”.

Name of idea submitter and other team members who worked on this idea : Lakshmanan Krishnamurti, MD, Allistair Abraham MD, John Horan MD and members of the Sickle cell Transplantation and Research Alliance

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Goal 2: Reduce Human Disease

National network to study the pathobiology of sepsis

Sepsis is the leading cause of death in hospitalized patients, the 3rd leading cause of death in all people in the US, the most common condition leading to widespread vascular collapse, among the most common causes of respiratory failure, and a frequent cause of acute cardiac dysfunction.

Submitted by (@greg.martin)

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

Details on the impact of addressing this CQ or CC :

Developing a national network to address important aspects of sepsis (causes and consequences of cardiac dysfunction, molecular determinants of respiratory failure) and serve as a trials group for testing novel interventions for new discoveries.

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

Mast cell changes in COPD

What are there specific alterations of mast cell populations in COPD, and what role do they have in determining specific histopathological phenotypes of the disease?

Submitted by (@nhlbiforumadministrator1)

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 : NHLBI Staff

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Goal 2: Reduce Human Disease

Identify Pathways of Risk Linking Psychosocial Stress to Ischemic Heart Disease in Women

Women differ from men in their manifestations of ischemic heart disease (IHD). They also differ from men with respect to prevalence of psychosocial factors and vulnerability to specific mental disorders. Young women, in particular, appear to be highly susceptible to the adverse cardiovascular effects of psychosocial stress. Those who already have clinical manifestations of IHD display high psychosocial burden which could ...more »

Submitted by (@viola.vaccarino)

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 study of young women from the community, and women with early-onset IHD, could be critical in uncovering women-specific pathways of IHD risk related to psychosocial stress. Investigations of the association between psychosocial factors and IHD should include sufficient numbers of young and middle-aged adults, and rather than only adjusting for sex, should conduct analyses stratified by sex. If psychosocial stress is a major risk factor for early-onset IHD in women, then psychosocial interventions specifically tailored to address women’s stressors and applied early in women’s lives should be especially helpful in improving or reverting IHD risk in this group. Most psychosocial or drug treatment interventions for depression have not been effective for improving IHD outcomes particularly among women, suggesting that more attention should be given to psychosocial pathways specific for women and to the identification of vulnerable subsets.

Feasibility and challenges of addressing this CQ or CC :

Calls for proposals for mechanistic studies and intervention trials targeted to young women and men at risk for IHD or sampled according to different exposure levels should be a feasible starting point to investigate this area and begin identifying vulnerable subgroups and sex differences.

Name of idea submitter and other team members who worked on this idea : Viola Vaccarino

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Goal 2: Reduce Human Disease

Asymptomatic carotid artery disease

What is the most effective approach to asymptomatic carotid artery disease to reduce the burden of stroke?

Submitted by (@societyforvascularsurgery)

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 improved understanding of factors associated with carotid plaque progression and the reliable identification of higher risk asymptomatic lesions. This will lead to improved selection of asymptomatic patients for carotid intervention, a critical area of controversy and a highly prevalent condition.

Name of idea submitter and other team members who worked on this idea : Society for Vascular Surgery

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Goal 2: Reduce Human Disease

Cardiovascular dysfunction in geriatric trauma patients

There is too little research funding addressing cardiovascular dysfunction in geriatric trauma patients. There have been little interest in funding this work. Yet, the geriatric population is growing. Geriatric trauma patients are predominantly women. Historically, the trauma societies provide guidance for diagnosis and treatment of severe trauma. However, "trauma guidance" historically was the same for children, ...more »

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 :

Document and understand the role of cardiac dysfunction in contributing to morbidity and mortality of geriatric trauma patients.

 

Reduce mortality rates in geriatric trauma patients.

Feasibility and challenges of addressing this CQ or CC :

Little research has been conducted to understand the role of cardiac dysfunction in elderly trauma patients. These patients may be intubated and treated with pain meds, so the normal symptoms of cardiac ischemia are silenced. Because 12 lead ECGs or cardiac enzymes are not routinely collected in these patients after admission, the question is what types of cardiac dysfunction occur and can they be prevented?

 

While evidence is scant, we conducted a structured chart review of WMD Shock Trauma patients' medical records in fiscal year 1999 data. Mean age was 76 and mean ISS of 24. In reviewing charts we found 71% of patients had one or more risk factors for ischemic heart disease (beyond age) and 30% had a history of ischemic heart disease. On admission 29% had ECG changes consistent with acute cardiac ischemia, but ischemic changes were noted equally between patients with and without a history of IHD. Cardiac enzymes were ordered for 45% of patients and 19% were positive. We found that patients with acute cardiac ischemia on admission (ECG or enzymes) had more adverse in-hospital cardiac events than those without ischemia on admission. Patients experiencing adverse events were significantly more likely to die.

 

We believe these findings suggest a substantial role of cardiac dysfunction in this population, but we were unable to generate interest in the topic.

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

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Goal 2: Reduce Human Disease

Exercise effects on cellular level

What cellular and/or intracellular signaling events are activated in response to acute or chronic physical activity that lead to or explain improvements in health outcomes, prevention, or treatment of lung diseases?

Which metabolic signatures induced by exercise/physical activity would be predictive/ associated with poor lung disease prognosis?

Submitted by (@nhlbiforumadministrator1)

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 : NHLBI Staff

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Goal 2: Reduce Human Disease

How can we control environmental risks (smoking, obesity, activity levels)?

How can we control environmental risks (smoking, obesity, activity levels)?

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 topic of primary prevention has received considerable discussion by President Obama and others. We certainly support research into vaccinations, tobacco cessation, clean air and other measures to prevent lung disease. In addition, we would like to broaden the discussion to secondary prevention. For example, chronic obstructive pulmonary disease (COPD) affects roughly 10% of people over age 40 years with its victims commonly succumbing to cardiovascular disease and cancer. Although clearly cardiovascular disease and cancer are important topics, we advocate for further research into the underlying lung disease. Similarly, people with sleep apnea are at risk of cardiometabolic complications, but currently more effort is placed on managing the complications than the underlying cause.

Name of idea submitter and other team members who worked on this idea : Research Advocacy Committee, American Thoracic Society

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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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Goal 2: Reduce Human Disease

COPD health maintenance experiment

There needs to be a rehab type maintenance study for COPD patients to determine if such a program would slow progression, improve health and reduce exacerbations/hospitalizations going forward. Thus, reducing costs to patient/hospital/public aid programs.

Submitted by (@patgaramella)

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

Details on the impact of addressing this CQ or CC :

improving health, cost reduction, reduce re-admissions

Feasibility and challenges of addressing this CQ or CC :

unsure

Name of idea submitter and other team members who worked on this idea : Pat Garamella & Anthony Bowman

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