Goal 2: Reduce Human Disease

Treatment of Major Depression in Patients with Heart Failure

Major depression (MD) is common in patients with heart failure, and it is an independent risk marker for functional decline, hospitalization, and mortality. Two large trials have shown that it can be difficult to treat. SADHART-CHF, a double-blind, placebo-controlled RCT (n=469), found that sertraline was not efficacious for MD in HF. MOOD-HF (n=372) showed that escitalopram was not efficacious. Smaller trials of cognitive-behavioral ...more »

Submitted by (@freedlak)

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

Details on the impact of addressing this CQ or CC :

Major depression causes considerable emotional distress and functional impairment. It follows a chronic or recurrent course in many cases, and untreated episodes can last for months or even years. When superimposed on chronic heart failure, major depression can accelerate functional decline, diminish quality of life, and increase the risks of hospitalization and mortality. Effective treatment of depression can, at minimum, improve quality of life. Treatment may also decrease the risk of adverse medical outcomes, but RCTs will be needed to evaluate the potential medical benefits of treating depression in HF.

Feasibility and challenges of addressing this CQ or CC :

Cognitive behavior therapy is the most promising approach tested so far, but there have been few trials of this intervention, any other psychotherapeutic treatment for depression, or antidepressant medications other than sertraline or escitalopram for major depression in HF. Additional phase II trials may be needed in order to identify the most promising approaches for testing in larger, multicenter RCTs.

Name of idea submitter and other team members who worked on this idea : Kenneth E. Freedland, PhD

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27 up votes
19 down votes
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Goal 2: Reduce Human Disease

HEALTH CARE DISPARITIES IN DIAGNOSIS AND TREATMENT OF COMMON SLEEP AND CIRCADIAN DISORDERS

There is evidence of a higher prevalence of sleep and circadian disorders in different ethnic groups. This is true for both adult and pediatric subjects. There is also evidence that minority populations in lower socioeconomic groups do not seek evaluation for sleep disorders as frequently as other segments of our population. There is also evidence that they are less adherent to treatments such as nasal CPAP for obstructive ...more »

Submitted by (@jnoel0)

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

Details on the impact of addressing this CQ or CC :

Sleep disorders are more common in minority populations. Moreover, these populations have higher rates of the known consequences of these disorders such as stroke, myocardial infarction, hypertension, resistant hypertension. Despite this, current population studies such as the Sleep Heart Health Study have included only a very small percentage of African Americans. The impact of this would be the following:

 

a. Elucidating the basis of barriers to case identification in these group

b. Designing specific intervention to overcome these barriers.

c. Developing methods to improve adherence to therapy in this group.

d. Removing sleep and circadian disorders as a risk factor for consequences such as stroke, cardiovascular disease and resistant hypertension in minority populations

Feasibility and challenges of addressing this CQ or CC :

There is a developing interest in this area in the field of circadian and sleep research. There is a developing knowledge base about health disparities in sleep and circadian disorders. Minority institutions such as Morehouse have developing programs in this area. We also have mobile technology that facilitates study of sleep and circadian disorders in minority populations.

Name of idea submitter and other team members who worked on this idea : Sleep Research Society

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118 net votes
163 up votes
45 down votes
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Goal 3: Advance Translational Research

Treating cardiovascular disease in persons with mental health disorders

How can we most effectively prevent and treat cardiovascular disease among persons with serious mental disorders?

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 :

Clinical anxiety disorders affects 40 million people in the US and the lifetime prevalence of PTSD is 6-8%,. The incidence of PTSD in particular is rapidly expanding in the US; this condition doubles the risk of a cardiac event.

 

The prevalence rates are higher in some populations; 3 out of 10 US military veterans have a diagnosis of PTSD, and many more are undiagnosed. Among patients at a VA, a diagnosis of PTSD increased the probability of circulatory problems (odds ratio 3.7). In another study, every additional PTSD symptom increased the risk of developing cardiovascular disease by 17%. Thus, the impact of developing more effective treatments adapted to the needs of this vulnerable population could be significant.

Feasibility and challenges of addressing this CQ or CC :

As the incidence of many mental health disorders such as PTSD and depression increases, the need for developing and adapting treatments for this population becomes critical.

 

Effective treatments may not be optimal for persons with serious mental illnesses and strategies to tailor treatments to the challenges of this vulnerable population are needed.

Individuals with mental illnesses such as major depressive disorder, bipolar disorder, and anxiety disorders are at significantly higher risk for cardiovascular disease than are those without these illnesses. Those with serious mental illnesses die an average of 25 years earlier, frequently from cardiovascular disease. The incidence of PTSD is rapidly expanding in the US; this condition doubles the risk of cardiovascular events.

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

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19 net votes
30 up votes
11 down votes
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Goal 1: Promote Human Health

Promoting health through simultaneous prevention of obesity and eating disorders

How to best promote healthy weight while also not stigmatizing obesity and creating risk for eating disorders (i.e., weight concern and body dissatisfaction) in youth. How to tackle both without contributing in unwitting way to development of either.

Submitted by (@tantillo)

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

Details on the impact of addressing this CQ or CC :

Studies show that diets do not lead to sustained health benefits for the majority of people and several studies indicate that dieting is actually a consistent predictor of future weight gain. Repeated cycles of losing and gaining weight are linked to heart disease, stroke, diabetes and altered immune function. Children and adolescents are especially vulnerable to the impact of dieting. Several long-term research studies show that girls and boys who use unhealthy weight control practices (including dieting) in early teen years are more likely to become overweight five years later, even if they started out at normal weight. These studies also show that early teen boys and girls who use unhealthy weight control practices are at greater risk for binge eating, use of severe weight control practices ( vomiting, diet pills, laxatives and water pills), and eating disorders compared with adolescents not using weight-control behaviors.

 

Since our culture tends to create weight bias and obesity stigmatization, it is not surprising to see our children become increasingly fearful of becoming “fat.” Weight concern can be experienced by underweight, average weight and overweight children and teens. Studies have shown that body dissatisfaction, especially weight concern (for early teen boys and girls), can lead to overweight, binge eating, severe weight control practices, and eating disorders. Weight teasing by family members and peers can also increase the risk for eating disorders.

Feasibility and challenges of addressing this CQ or CC :

Challenges include creating teams of researchers who will collaborate across the two fields. I believe if we could create such teams we could

move both fields ahead with regard to prevention and a focus on health (behaviors that are health promoting), not BMI (a number) or an emphasis on intake.

 

The key to both health problems involves the ecology in which youth are located b/c this ecology influences body image, intake, activity, self regulation and self care.

Name of idea submitter and other team members who worked on this idea : Mary Tantillo PhD PMHCNS-BC FAED

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62 net votes
116 up votes
54 down votes
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Goal 1: Promote Human Health

Do our modern "traditional" sleep schedules defy nature?

Here's an interesting article which shows that the modern tradition of eight hours of unbroken sleep might actually be unnatural, and quite different from what our ancestors typically did: http://www.bbc.com/news/magazine-16964783 So, maybe the majority of our modern societies (even the people without recognized sleep disorders) are unwisely fighting against biology? Perhaps a lot of people's health issues, such as ...more »

Submitted by (@apollia112)

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

Details on the impact of addressing this CQ or CC :

See comments

Feasibility and challenges of addressing this CQ or CC :

See comments

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

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5 net votes
23 up votes
18 down votes
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Goal 3: Advance Translational Research

Novel Mechanism for Clinical Trials of New Pro-Hemostatic Agents in Hemophilia

There are new exciting novel pro-hemostatic therapeutics in early phase clinical trials for hemophilia and hemophilia inhibitor patients. Yet, it is difficult to design randomized trials to compare these agents, or compare them with standard treatment, given the small sample size and competing studies for such patients. It is critical to develop novel approaches to compare new agents in rare populations. For example, ...more »

Submitted by (@ragni01)

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

Details on the impact of addressing this CQ or CC :

Should rare disease-specific strategies for clinical trials be developed, it would revolutionize the approach to study of not only rare disease populations, but all disease groups, no matter their size. If validated, rare disease-specific clinical trial strategies, would potentially reduce the cost, time, patient burden, and research effort to conduct clinical trials. If validated, consideration could be given to drug licensure earlier in the trial process, with a requirement for all such trials to initiate and continue ongoing data collection post-licensure for safety and efficacy.

Feasibility and challenges of addressing this CQ or CC :

Novel statistical methodologies are greatly needed to help with rare disease research. NHLBI might consider a grant mechanism RFA to encourage development of novel clinical trial strategies utilizing smaller sample size. The proof would be to develop the methodology as part of a feasibility study, and then, if feasible, adapt the novel approach to development and conduct of a clinical trial in a rare disease clinical tria,l to test the concept.

Name of idea submitter and other team members who worked on this idea : Margaret V. Ragni, MD, MPH (aspects discussed with Don Brambilla PhD.

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6 net votes
15 up votes
9 down votes
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Goal 2: Reduce Human Disease

DEVELOPMENT OF A PERSONALIZED APPROACH TO SLEEP AND CIRCADIAN DISORDERS

There is developing evidence of major individual differences in pathways to different common sleep disorders such as obstructive sleep apnea. Moreover, there is evidence of different clinical presentations of disease and different outcomes. For example, some subjects with obstructive sleep apnea who get excessive sleepiness while others do not. The latter are still at risk for other consequences of the disorder such ...more »

Submitted by (@jnoel0)

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 strong rationale for application of a personalized approach to sleep disorders. This requires approaching this question using multiple domains as in other areas of medicine—clinical features, physiological factors, application of the –omic approaches, genetics. The impact of this will be several:

 

a. A new way to classify sleep disorders.

b. Identification of subgroups of patients with apparently the same disorder who will have different outcomes of therapy.

c. Identification of subgroups of patients who will have different approaches to diagnosis.

d. Identification of subgroups of patients with apparently the same disorder who will have different therapeutic approaches.

Feasibility and challenges of addressing this CQ or CC :

These sleep and circadian disorders are extremely common. There is a risk infrastructure for this type of research based on the large number of accredited sleep centers in the United States that could be used for subject recruitment and who can adopt similar techniques. There is also a rich set of data obtained from sleep studies that could be used to identify new patterns that reflect different subgroups of subjects. These studies need to be based on clinical populations of patients who present with the different disorders rather than on population-based cohorts.

Name of idea submitter and other team members who worked on this idea : Sleep Research Society

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220 up votes
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Goal 3: Advance Translational Research

Screening for SDB and Sleep Disorders in School-Aged Chidren by School Nurses

Can school nurses effectively screen for SDB and Sleep Disorders in school aged children? Who else in the school setting could provide such screening? Should such screening be limited to "at risk" children who display identified markers, or be open to all children? What is the role of teachers to "identify" children in need of such screening? What role will such screening serve to mitigate learning, behavioral, developmental ...more »

Submitted by (@nancyh.rothstein)

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 impact of screening at risk children for sleep disorders and sleep disordered breathing, including subsequent referrals and professional treatment, may serve to mitigate future health, learning, developmental and behavioral risks/issues for children by addressing these issues in early childhood. Research based protocols will be accessed and used for screening.

Feasibility and challenges of addressing this CQ or CC :

Additional considerations:

Does the nurse refer an at risk child to the Pediatrician? Dentist? ENT?

What questionnaires or other identifiers would be used for screening? Is there a bio test to assess risk for a SD or SDB?

What should the target age level be for children undergoing proposed screening?

 

How can sleep education and training be integrated with this screening process to promote good sleeping habits/hygiene at home, for all children, parents and caretakers, as well as teachers. Who creates and provides the educational material? Who does the teaching?

 

Parental involvement- KEY!

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

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6 up votes
1 down votes
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Goal 2: Reduce Human Disease

Cause of disparity in prevalence and progression of various vascular disorders

What are the causative factors underlying the disparity in prevalence and progression of various vascular disorders (PAD, CVD, aneurysm) across populations?

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 :

­Genetic, epigenetic, biochemical, nutritional, environmental, and psychosocial factors should be characterized.

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

SLEEP DISORDERS AS A MODIFIABLE RISK FACTOR FOR CHRONIC DISEASE

There is developing evidence that sleep disorders, in particular obstructive sleep apnea and inadequate sleep, can influence the course of other chronic diseases. Observational studies show that CPAP treatment of patients with pre-diabetes who have OSA reduces the incidence of future diabetes. Moreover, animal and human data indicate that insufficient sleep and sleep apnea can affect the rate of progression of neurodegenerative ...more »

Submitted by (@jnoel0)

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

Details on the impact of addressing this CQ or CC :

This question will have considerable impact. Sleep apnea is an independent risk factor for insulin resistance. Moreover, observational studies show that treatment of OSA reduces the rate of future diabetes compared to that which occurs in untreated OSA. Therefore, identifying OSA and treating this could have a profound impact on reducing the rate of diabetes, i.e., a preventative strategy.

 

Both sleep loss and obstructive sleep apnea have also been shown to be risk factors for subsequent development of Alzheimer’s disease. This has been shown in mouse models and in epidemiological studies to address whether insufficient sleep and sleep apnea are independent risk factors for development of Alzheimer’s disease, in particular accelerating their onset. Determining whether this is so and whether interventions to treat these sleep disorders delay onset of diabetes and Alzheimer’s disease would have profound public health significance.

Feasibility and challenges of addressing this CQ or CC :

These disorders are extremely common so that recruitment of subjects is not challenging. Moreover, new technology reduces protocol burden to assess individuals. All studies can be done in the patients’ home. There are existing cohort studies focused on diabetes and the Alzheimer’s Center program that could be used for these studies. Thus, the studies are extremely feasible in the near term.

Name of idea submitter and other team members who worked on this idea : Sleep Research Society

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156 net votes
211 up votes
55 down votes
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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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112 net votes
141 up votes
29 down votes
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Goal 4: Develop Workforce and Resources

NOVEL APPROACHES TO TRAINING IN SLEEP AND CIRCADIAN RESEARCH

Sleep and circadian disorders are relatively new areas of medicine. Most universities currently lack a critical mass of investigators to develop institutional T32 grants. Thus, there are, unfortunately, few such programs nationally. The Sleep Research Society has recognized this and is taking active steps to facilitate development of other T32 institutional training grants. This will not, however, help the majority ...more »

Submitted by (@jnoel0)

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

Details on the impact of addressing this CQ or CC :

The current status of research training in sleep and circadian disorders suggest that new approaches are needed. The field has developed one multi-center training grant to bring training to different institutions. This is focused on genetic/genomic approaches. It is run by the University of Pennsylvania which has a well developed program in this area. The fellows in training are, however, at other institutions, i.e., Johns Hopkins, University of Michigan and Stanford. Web-based approaches are used for work-in-progress seminars, grant development workshops and group mentorship, and didactic lectures. This strategy could be used more broadly to develop research training in other areas of sleep and circadian research. Stimulating this would have a major impact on research training in this new field of medicine.

 

Another relevant strategy would be to encourage adding slots in a competitive way for sleep/circadian research to other existing institutional T32 grants.

 

There are multiple mechanisms in place to communicate opportunities to the sleep/circadian academic community, i.e., Sleep-L, administered by the National Center for Sleep Disorders Research; Sleep Research Society biweekly blog; the Sleep Research Network. Specific encouragement of this approach would broaden the base for research training and would be of high impact.

Feasibility and challenges of addressing this CQ or CC :

The field of sleep and circadian research has had a long commitment to facilitating research training. The Sleep Research Society has hosted Trainee Day at our annual meeting for 20 years. The Sleep Research Society is funding early-stage investigators through its Foundation. The American Academy of Sleep Medicine runs, in collaboration with the NHLBI, an event at NIH for early-stage investigators in clinical research. The American Academy of Sleep Medicine Foundation has a “Bridge to K Award” program that provides funds to early-stage investigators who just missed funding on their first application for a K award. The Sleep Research Society has provided travel funds for early-stage investigators to attend recent workshops held by different NIH Institutes including National Heart, Lung and Blood Institute. Thus, there is no doubt of the commitment of the field and its professional organizations.

 

The impact of these new initiatives would be to broaden the base for research training beyond a few institutions. The number of institutions with a critical mass of investigators to mount successful T32 institutional training grants is not sufficient to provide the necessary future biomedical research workforce in this area. Novel approaches, based on modern communication IT technology, are needed.

Name of idea submitter and other team members who worked on this idea : Sleep Research Society

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209 up votes
67 down votes
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