A primary focus on principles of psychology may result in significantly improved control of the obesity epidemic. Effective interventions could reduce the risk of diabetes, sleep apnea, and hypertension. This research could also affect clinical practice guidelines for weight loss and obesity treatment.

Psychological science has been successful in developing effective treatments for a number of conditions, including sleep disorders, depressive symptoms, anxiety and phobias. Many of the behavioral principles employed in such interventions (e.g., cognitive restructuring, motivational methods) could be translated for the prevention and treatment of obesity within a reasonable time frame. Additional attention should be directed to the needs of population subgroups in which obesity is most prevalent.
In their Viewpoint article on weight loss intervention research, Pagoto and Appelhans (JAMA, 2013, see attachment) question whether a continued focus on dietary factors in research on weight loss and obesity is warranted. Their commentary raises the importance of attention to the individual psychological characteristics that influence adherence to weight loss interventions rather than dietary composition.

Approximately 20% of the population are characterized by elevated circulating levels of lipoprotein(a), regardless of age, gender or blood cholesterol levels. Estimates suggest that up to 90% of the variation in plasma lipoprotein(a) levels could be due to genetic factors, which makes lipoprotein(a) the most prevalent inherited risk factor for cardiovascular diseases (CVD). Large-scale genetic studies have shown that Lipoprotein(a) was the strongest genetic determinant of CVD such as atherosclerosis and aortic stenosis. Lipoprotein(a) is one of the strongest predictors of residual CVD risk and has been shown to improve CVD risk prediction in several population-based studies. Lipoprotein(a) is also one of the strongest known risk factors for spontaneous ischemic stroke in childhood.
A comprehensive research strategy aiming at identifying, evaluating interaction with other risk factors, treating and educating patients with elevated lipoprotein(a) levels would result in substantial reductions of health care costs in the US and around the globe by reducing the burden of CVD while simultaneously improving the quality of life of these patients.

The list of pharmaceutical agents that reduce lipoprotein(a) levels is steadily increasing. There are approximately half a dozen strategies that have been shown to significantly and safely lower lipoprotein(a) levels. One of the challenges of this research strategy will be to determine which of these strategies represent the most efficient, safe, cost-effective and widely applicable approach to lower lipoprotein(a) levels and CVD outcomes.
Increasing awareness on lipoprotein(a) and CVD will also be of utmost importance for this effort as relatively few physicians perform lipoprotein(a) testing and even fewer patients are aware of their lipoprotein(a) level. The first sign of high lipoprotein(a) is often a heart attack or stroke. Our challenge will be to identify patients with high lipoprotein(a) that could be enrolled in trials of risk characterization and lipoprotein(a)-lowering.

Venous thrombotic events (VTE) are now occurring in 1/200 children admitted to a tertiary pediatric facility. In around 70-90% of cases, VTE occurs in children with an underlying condition, amongst which cancer represents up to 1/3 of patients. Within this group of patients, the thrombotic complications are associated with a higher morbidity (e.g. higher recurrence rates, high rate of CNS events in acute leukemia) and mortality. Nevertheless, the clinical challenges highlighted in the itemized Critical Challenge Section illustrate the lack of basic science, translational and clinical research available, as well as the paucity of evidence-based medicine recommendations necessary to acoount for the increasing number of patients with this complication.
On the other hand, pediatric oncology is one of the areas of pediatric care where the medical progresses of the last decades have drastically changed the natural history of cancer in children. In light of much higher survival rates for almost all types of pediatric cancer, the focus has now shifted towards decreasing treatment-related, as well as disease-related morbidities, increasing the quality of life of the many survivors. Because VTE is now recognized as one of the significant remaining complications within this patient population, addressing the list summarized herein would contribute to further improve the care of children with cancer.

The infrastructure that is already in place under the Children's Oncology Group (COG), where almost any new clinical and/or translational idea related to the care of children with cancer becomes part of a clinical trial, could be rolled over to explore many of the items listed under the CC Section.
As a principle, VTE in children with cancer develop due to: a) host-related factors; b) chemotherapy/treatment-related factors; and c) disease-related issues. Therefore, protocol- and disease-specific studies could address, under the auspices of COG, the prevalence of VTE according to cancer type in a prospective manner. Similarly, high risk groups for VTE could be submitted to standardized imaging and/or biomarker investigation prospectivelly, in addition to collection of outcome data related to VTE and to anticoagulation protocols. Furthermore, tumor specimens/genetic markers could be evaluated and correlated to the study outcomes. The challenges of reaching consensus during protocol development would allow identification of equipoise for certain clinical scenarios, obviating the need of trials, or the use of consensus techniques, before diagnostic/therapeutic protocols could be adopted.
In conclusion, the develoment of a multidisciplinary task force (i.e. pediatric radiologists, oncologists, hematologists, molecular biology experts), which, for the most part, is already in place (i.e. COG), would be instrumental to foster research on this extremely clinically relevant area.

Recent efforts to evaluate biomarkers for VTE occurrence and recurrence have led to the identification of multiple potential candidates, including P-selectin, E-selectin, D-dimer, various microparticles, and various inflammatory cytokines. However, no specific biomarker has yet emerged for routine clinical use for individual VTE risk stratification and personal targeted therapeutics. The development of improved animal models will advance the study of VTE pathophysiology, allowing for more accurate evaluation of emerging biomarkers and initial assessments of potential advanced therapeutic interventions. Also, the identification and prioritization of novel VTE biomarkers will be needed to help improve our understanding of the molecular mechanisms underlying VTE, so as to shepherd the development of novel mechanisms of therapy beyond anticoagulation.

AFib increases stroke risk by five-fold and doubles the risk that a stroke will result in permanent disability. While oral anticoagulation (OAC) is highly effective at reducing stroke risk, elderly patients are often under-anticoagulated. This is in part due to an under-appreciation of the stroke risk associated with AFib and the tendency of some health care professionals to prioritize perceived bleeding risk over stroke prophylaxis. Because current bleeding risk assessment tools are imperfect and largely unable to predict patients who are likely to have bleeding complications, they are often not utilized—or if used, do not truly predict which patients are at risk of a bleed. An improved bleeding risk tool is critical to improved risk assessment in the elderly. That bleeding risk tool should then be combined with the stroke risk tool for single risk stratification to streamline anticoagulation decision-making.

Developing effective integrated risk assessment tools is feasible only if there is consensus on the validity of the clinical information being provided. The approach to this critical challenge is two-fold. First, needed research that improves the reliability of bleeding risk assessment in the elderly should be pursued. Second, stroke and bleeding risk tools should be combined into a single risk stratification tool. This will require significant investment and focus, but the resulting bleeding risk assessment combined with the accepted CHA2DS2-VASc score, would significantly impact the 40 - 60% of patients who are currently not on an anticoagulant and are at increased risk of stroke and death.

Several risk factors have been identified that identify individuals at risk for developing COPD including low birth weight, poor maximally attained lung function and the presence of asthma. Strategies to prevent COPD development in these individuals are needed.

The Lung Health Study demonstrated that smoking cessation prevents COPD progression. Studies of similar size and duration should be organized to address other risk factors.

Identify strategies to prevent or reduce recurrence of atrial fibrillation using available lifestyle and medical therapies.

There is a large population of patients with atrial fibrillation available to test this hypothesis along with strategies for treatment of modifiable risk factors. A challenge is to identify the good strategies to ensure adherence.

By improving our understanding of cardiovascular risk in patients with congenital heart disease we may be able to improve our surveillance for disease and intervene earlier to address this risk factors. The adult population with congenital heart disease is undergoing rapid growth.

The adult population with congenital heart disease is undergoing rapid growth. Novel uses of electronic health records (EHRs) and registries may enable us to answer these questions in a cost-efficient manner.

Effective and safe VTE prophylaxis regimens are widely available but near universal prophylaxis of hospitalized patients has failed to reduce the occurrence of VTE. Moreover, about half of all VTE events in the community are unrelated to hospitalization. Known major VTE risk factors account for about 85% of all VTE disease in the community but have a poor predictive value for the individual. Identifying the high VTE-risk individual by incorporating genetic variation and biomarkers into clinical risk prediction scores will reduce VTE occurrence by allowing providers to stratify VTE risk and target risk factor modification and/or intensive VTE prophylaxis to the high VTE-risk individual.

Genetic variation and plasma biomarkers associated with VTE have been identified among individuals of European ancestry and are readily available for incorporation into clinical VTE risk prediction tools. Limited work has identified genetic variation associated with VTE among individuals of African ancestry but more work is needed in this area. Active cancer accounts for about 20% of all incident VTE and genetic variation associated with VTE compounds VTE risk in cancer patients. More work is needed to identify plasma biomarkers and cancer tissue expression characteristics that are associated with VTE in cancer patients. Acute trauma/fracture accounts for about 12% of all VTE in the community and these patients are at high risk for both VTE and anticoagulant-associated bleeding. More work is needed to incorporate genetic variation and plasma biomarkers into risk prediction scores for the individual acute trauma/fracture patient. Finally, large candidate gene and GWA studies have identified relatively common, low VTE-risk genetic variation that together account for about 5% of VTE. Clearly, additional as yet, unidentified high VTE-risk genes exist. Additional studies are needed to identify these high VTE-risk genes, both in populations of European and African origin.

Management of hypertension and other cardiovascular risk factors among young adults (18 to <40 years old) in the U.S.

The size of the US and global population qualifying for treatment with a statin or aspirin for primary prevention of ASCVD is immense. Given the performance of risk estimation, even if risk estimation were universally implemented, patients would be misclassified with the consequence of being under or over treated. If treatment based on presence of subclinical disease is more cost-effective, the benefits of preventive therapies can be enjoyed by larger proportions of our population and more ASCVD can be averted. Given the ionizing radiation, albeit low intensity, associated with CT scanning, it is incumbent on the biomedical research community to document the advantages, if any, of a subclinical disease guided approach to provision of clinical primary prevention services for ASCVD.

Many people will be concordant for the two methods of guiding provision of therapy, about 65% of middle aged and older adults. That is, many people will be high risk and have subclinical disease and many people will below risk and not have subclinical disease. It is only the discordant people, i.e., high risk people without subclinical disease and low risk people with subclinical disease, who will be informative study participants. Hence, many people will need to be screened to identify the roughly 35% who are discordant, and would be treated differently by the two approaches.

People may be unwilling to accept randomization once they know the information about their estimated risk and presence or absence of subclinical disease. If a low participation rate among eligible persons is observed, an even larger population of screenees would be needed.

A vanguard phase could provide information about these potential challenges.

Decisions on whether or not to place a patient with atrial fibrillation on chronic anticoagulation or on statin therapy are often based on guidelines and cardiovascular risk calculators.

Patients with a higher risk of stroke are more likely to receive anticoagulation and patients with a higher risk of a myocardial infarction are more likely to receive statin therapy.

However, these cardiovascular risk calculators do not really take into account the potential side effects and impact on the lifestyle of the patients.

Physicians will stop anticoagulation in a patient with atrial fibrillation if the patient has suffered a life-threatening bleed but there are no specific evidence-based guidelines as to how one should proceed if the bleeding is minor.

it is easy to compute the cardiovascular risk and overall mortality benefit of placing a patient on statins but how does one factor in the impact that statins have on the quality of life of an individual?

Developing novel evidence-based approaches to individualize therapies that factor in cardiovascular benefits as well as potential side effects and diminished quality of life could have a major impact on appropriately using treatments and reduce the arbitrariness of some medical decisions.

Chemotherapy for breast cancer stages I-III is known to be associated with or induce cardiotoxicity. Over 35% of these women develop progressive fatigue and exercise intolerance, and heart failure limiting their daily activities and frequently interfering with their ability to return to work. CV disease are the leading cause of morbidity and mortality for those surviving beyond 5 to 8 years from their breast cancer diagnosis. The excess of CV morbidity and mortality in these patients threatens to offset reductions in cancer-related survival. Identifying breast cancer survivors at high risk for CV morbidity and mortality could allow targeting of cardiovascular disease reducing therapeutic interventions.

creating a multisite registry of women with Stage 1-3 breast cancer scheduled to receive chemotherapy and a control population women of similar demographic and CV risk profile without neoplasia, would allow to collect data at baseline and during/after cancer treatment related modern therapy, pre/post treatment functional status, including fatigue, behavioral and psychosocial risk factors and quality of life, and serum biomarkers indicative of myocardial injury, fibrosis, and heart failure.

More accurate risk estimates would provide clinicians with clearer guidance in selecting how and when to intervene in valvular heart disease.

The advent and rapid advance of transcatheter therapy for valvular heart disease makes this an opportune time to develop metrics to determine whether transcatheter or surgical intervention is most appropriate and when.
The decision to intervene, as well as the type of intervention, is based on individual risk scores such as the STS risk estimate or the Euroscore. However, these scores are derived only from surgical patients and do not take into account procedure-specific impediments, major organ system compromise, comorbidities, or the frailty of the patient.