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The COVID-19 pandemic has been mitigated primarily using social and behavioral intervention strategies, and these strategies have social and economic impacts, as well as potential downstream health impacts that require further study. Digital and community-based interventions are being increasingly relied upon to address these health impacts and bridge the gap in health care access despite insufficient research of these interventions as a replacement for, not an adjunct to, in-person clinical care. As SARS-CoV-2 testing expands, research on encouraging uptake and appropriate interpretation of these test results is needed. All of these issues are disproportionately impacting underserved, vulnerable, and health disparities populations. This commentary describes the various initiatives of the National Institutes of Health to address these social, behavioral, economic, and health disparities impacts of the pandemic, the findings from which can improve our response to the current pandemic and prepare us better for future infectious disease outbreaks.

To inform the retirement of NIH-owned chimpanzees, we analyzed the outcomes of 764 NIH-owned chimpanzees that were located at various points in time in at least one of 4 specific locations. All chimpanzees considered were alive and at least 10 years of age on January 1, 2005; transfers to a federal sanctuary began a few months later. During a median follow-up of just over 7 years, there were 314 deaths. In a Cox proportional hazards model that accounted for age, sex, and location (which was treated as a time-dependent covariate), age and sex were strong predictors of mortality, but location was only marginally predictive. Among 273 chimpanzees who were transferred to the federal sanctuary, we found no material increased risk in mortality in the first 30 days after arrival. During a median follow-up at the sanctuary of 3.5 years, age was strongly predictive of mortality, but other variables – sex, season of arrival, and ambient temperature on the day of arrival – were not predictive. We confirmed our regression findings using random survival forests. In summary, in a large cohort of captive chimpanzees, we find no evidence of materially important associations of location of residence or recent transfer with premature mortality.

There are conflicting data about the ability of peer review percentile rankings to predict grant productivity, as measured through publications and citations. To understand the nature of these apparent conflicting findings, we analyzed bibliometric outcomes of 6873 de novo cardiovascular R01 grants funded by the National Heart, Lung, and Blood Institute (NHLBI) between 1980 and 2011. Our outcomes focus on top-10% articles, meaning articles that were cited more often than 90% of other articles on the same topic, of the same type (eg, article, editorial), and published in the same year. The 6873 grants yielded 62 468 articles, of which 13 507 (or 22%) were top-10% articles. There was a modest association between better grant percentile ranking and number of top-10% articles. However, discrimination was poor (area under receiver operating characteristic curve [ROC], 0.52; 95% confidence interval, 0.51–0.53). Furthermore, better percentile ranking was also associated with higher annual and total inflation-adjusted grant budgets. There was no association between grant percentile ranking and grant outcome as assessed by number of top-10% articles per $million spent. Hence, the seemingly conflicting findings on peer review percentile ranking of grants and subsequent productivity largely reflect differing questions and outcomes. Taken together, these findings raise questions about how best National Institutes of Health (NIH) should use peer review assessments to make complex funding decisions.

The interest in Comparative Effectiveness Research (CER) in the international community is growing. A panel titled “What Can Comparative Effectiveness Research Contribute to Integrative Health in International Perspective?” took place at the 3rd International Research Congress on Integrative Medicine and Health in Portland, Oregon, in 2012. The presentations at this panel highlighted different perspectives on CER, including the funders' and the stakeholders' perspectives from the United States, as well as experiences with economic evaluations from Australia and pragmatic trials in Europe. The funders' perspective emphasized the need for innovation and controlling costs in large-scale studies. The stakeholder's perspective stressed the need to gather the input of stakeholders in shaping the framework for more informative, more decision-maker-driven research. Several examples of cost-effectiveness analyses were offered from Australia. The importance of balancing rigor and pragmatism was also discussed in a presentation of the efficacy–effectiveness continuum. A wide-ranging discussion explored additional questions concerning the translation of evidence into practice; the effect of pragmatic trials on funding or policy; evidentiary distinctions between and among pragmatic trials and traditional randomized clinical trials; and the multiple roles of stakeholders, particularly in generating new information and knowledge. The presentations and discussions showed that more development of methods is needed. This includes developments on study design and statistical approaches, as well as methods for stakeholder involvement and mechanisms to bring these results into practice.

In 2012, the National Cancer Institute (NCI) engaged the scientific community to provide a vision for cancer epidemiology in the 21st century. Eight overarching thematic recommendations, with proposed corresponding actions for consideration by funding agencies, professional societies, and the research community emerged from the collective intellectual discourse. The themes are (i) extending the reach of epidemiology beyond discovery and etiologic research to include multilevel analysis, intervention evaluation, implementation, and outcomes research; (ii) transforming the practice of epidemiology by moving toward more access and sharing of protocols, data, metadata, and specimens to foster collaboration, to ensure reproducibility and replication, and accelerate translation; (iii) expanding cohort studies to collect exposure, clinical, and other information across the life course and examining multiple health-related endpoints; (iv) developing and validating reliable methods and technologies to quantify exposures and outcomes on a massive scale, and to assess concomitantly the role of multiple factors in complex diseases; (v) integrating “big data” science into the practice of epidemiology; (vi) expanding knowledge integration to drive research, policy, and practice; (vii) transforming training of 21st century epidemiologists to address interdisciplinary and translational research; and (viii) optimizing the use of resources and infrastructure for epidemiologic studies. These recommendations can transform cancer epidemiology and the field of epidemiology, in general, by enhancing transparency, interdisciplinary collaboration, and strategic applications of new technologies. They should lay a strong scientific foundation for accelerated translation of scientific discoveries into individual and population health benefits. Cancer Epidemiol Biomarkers Prev; 22(4); 508–16. ©2013 AACR.

Over the past 60 years, revolutionary discoveries made by epidemiologists have contributed to marked declines in cardiovascular disease morbidity and mortality. Now, in an era of increasingly constrained resources, researchers in cardiovascular epidemiology face a number of challenges that call for novel, paradigm-shifting approaches. In this paper, the authors pose to the community 4 critical questions: 1) How can we avoid wasting resources on studies that provide little incremental knowledge? 2) How can we assure that we direct our resources as economically as possible towards innovative science? 3) How can we be nimble, responding quickly to new opportunities? 4) How can we identify prospectively the most meritorious research questions? Senior program staff at the National Heart, Lung, and Blood Institute invite the epidemiology community to join them in an ongoing Web-based blog conversation so that together we might develop novel approaches that will facilitate the next generation of high-impact discoveries.

Background— We sought to determine whether treadmill exercise time may be of value as an initial prognostic screening tool in ambulatory patients with impaired systolic function who are referred for cardiopulmonary exercise testing. Methods and Results— We studied 2231 adult systolic heart failure patients (27% of whom were women) who underwent cardiopulmonary stress testing using a modified Naughton protocol. We assessed the value of treadmill exercise time for prediction of all-cause death and a composite of death or United Network for Organ Sharing status 1 heart transplantation. During a mean follow-up of 5 years, 742 patients (33%) died. There were 249 United Network for Organ Sharing status 1 heart transplants (11%). Treadmill exercise time was predictive of death and the composite outcome in both women and men, even after accounting for peak oxygen consumption and other clinical covariates (adjusted hazard ratio of lowest versus high sex-specific quartile for prediction of death 1.70, 95% confidence interval 1.05 to 2.75, P =0.03; for prediction of the composite outcome, 1.75, 95% confidence interval 1.15 to 2.66, P =0.009). For a 1-minute change in exercise time, there was a 7% increased hazard of death (eg, comparing 480 to 540 seconds, hazard ratio =1.07, 95% confidence interval 1.02 to 1.12, P =0.004). Conclusions— Because cardiopulmonary stress testing is not available in every hospital, treadmill exercise time with a modified Naughton protocol may be of value as an initial prognostic screening tool.

We introduce random survival forests, a random forests method for the analysis of right-censored survival data. New survival splitting rules for growing survival trees are introduced, as is a new missing data algorithm for imputing missing data. A conservation-of-events principle for survival forests is introduced and used to define ensemble mortality, a simple interpretable measure of mortality that can be used as a predicted outcome. Several illustrative examples are given, including a case study of the prognostic implications of body mass for individuals with coronary artery disease. Computations for all examples were implemented using the freely available R-software package, randomSurvivalForest., Published in at http://dx.doi.org/10.1214/08-AOAS169 the Annals of Applied Statistics (http://www.imstat.org/aoas/) by the Institute of Mathematical Statistics (http://www.imstat.org)

Chronic kidney disease (CKD) increases cardiovascular risk and mortality. However, traditional cardiovascular risk factors do not adequately account for the substantial increase in mortality observed in CKD. The aim of this study was to examine the relative contributions of novel cardiovascular risk factors to the risk between CKD and mortality. The study population included 4,680 consecutive new patients from a tertiary care preventive cardiology program from 1996 to 2005. Estimated glomerular filtration rate was calculated using the Modification of Diet in Renal Disease (MDRD) method. Baseline levels of traditional (low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, hypertension, triglycerides, total cholesterol, and fasting glucose) and emerging (apolipoproteins A-I and B, lipoprotein[a], fibrinogen, homocysteine, and high-sensitivity C-reactive protein) risk factors were examined. All-cause mortality was obtained from the Social Security Death Index. There were 278 deaths over a median follow-up period of 22 months. CKD (estimated glomerular filtration rateor=60 ml/min/1.73 m(2)) was strongly associated with mortality after adjusting for traditional cardiovascular risk factors (hazard ratio 2.31, 95% confidence interval 1.77 to 3.11, p0.001) and with the addition of propensity score (hazard ratio 2.33, 95% confidence interval 1.75 to 3.10, p0.001). Of all the traditional and emerging risk factors monitored, only the addition of homocysteine and fibrinogen significantly attenuated the association between CKD and mortality (adjusted hazard ratio 1.73, 95% confidence interval 1.23 to 2.34, p0.001), explaining 38% of the attributable mortality risk from CKD. A significant interaction (p=0.004) between homocysteine and estimated glomerular filtration rate was observed whereby the annual mortality rate in subjects with CKD with homocysteine10 micromol/L (the bottom tertile) was similar to those with normal renal function (1% per year), whereas homocysteine levelsor=12.5 micromol/L (the top tertile) were associated with a sevenfold greater mortality risk. In conclusion, homocysteine and fibrinogen levels explain nearly 40% of the attributable mortality risk from CKD.

ObjectivesWe identified predictors of mortality in patients with preserved ejection fraction (EF) and clinical heart failure (HF).BackgroundAlthough diastolic HF is common, the factors that predict mortality have not been clearly defined.MethodsWe studied 988 patients with HF and preserved EF enrolled in the Digitalis Investigation Group (DIG) trial. Survival analyses were employed to identify variables associated with mortality.ResultsDuring 3.1 years of follow-up, 231 (23%) patients died. Among 18 variables considered, the strongest independent predictors of death were glomerular filtration rate (adjusted hazard ratio for one standard deviation decrease 1.50, 95% confidence interval [CI] 1.35 to 1.67, p < 0.0001), New York Heart Association functional class III or IV (adjusted hazard ratio 1.64, 95% CI 1.20 to 2.18, p = 0.0011), male gender (adjusted hazard ratio 1.71, 95% CI 1.26 to 2.32, p = 0.0005), and older age (adjusted hazard ratio for one standard deviation increase of age21.28, 95% CI 1.08 to 1.50, p = 0.0019). A risk score was developed to estimate long-term mortality.ConclusionsDiastolic HF is associated with a high death rate. Important predictors of death include impaired renal function, worse functional class, male gender, and older age.

The National Heart, Lung, and Blood Institute (NHLBI) Strategic Plan describes an ambitious agenda in cardiovascular disease research, with most of it implemented via grants and contracts to extramural scientists. There are over 85 NHLBI program scientists, who work to initiate, catalyze, evaluate, and oversee cardiovascular research efforts. These scientists are divided into 8 branches within an overarching Division of Cardiovascular Sciences (DCVS). The DCVS represents the union of 2 previously existing divisions, the Division of Cardiovascular Disease and the Division of Prevention and Population Sciences; both divisions recently prepared detailed strategic plans (1,2). DCVS provides leadership and supports basic, clinical, population, and health services research on the causes, prevention, and treatment of cardiovascular diseases. The Division fosters research in disease areas, such as atherothrombosis, heart attack and heart failure, high blood pressure, stroke, atrial and ventricular arrhythmias, sudden cardiac death, adult and pediatric congenital heart disease, cardiovascular complications of diabetes and obesity, and other cardiovascular disorders. Research also includes a number of well-known epidemiological cohort studies that describe disease and risk factor patterns in populations; clinical trials of interventions to prevent disease and to prevent or modulate risk factors; studies of genetic, behavioral, sociocultural, health systems, and environmental influences on disease risk and outcomes; and studies of the application of prevention and treatment strategies to determine how to improve clinical care and public health. The Division supports training and career development for these areas of research. DCVS is organized operationally into 8 scientific branches, a career development office, and an Office of Biostatistics Research.

Objectives.This study sought to establish the prognostic implications of ischemic and viable myocardium identified by dobutamine echocardiography in patients with left ventricular dysfunction.Background.Recent studies have suggested that in patients with viable myocardium identified by positron emission tomography, medical treatment is associated with recurrent cardiac events. Dobutamine echocardiography has been used to identify viable myocardium in patients with left ventricular dysfunction, but the prognostic significance of this test is undefined.Methods.One hundred thirty-six consecutive patients (mean [±SD] age 67 ± 7.9 years; 104 men) with moderate or severe left ventricular dysfunction (left ventricular ejection fraction 30 ± 5%) undergoing dobutamine echocardiography were included in the study. Dobutamine was administered using a standard incremental protocol (5 to 40 μg/kg body weight per min intravenously in 3-min stages) with additional atropine (1 mg intravenously) as required. Standard body weight echocardiographic views were digitized on-line and compared using a side-by-side display. Viable myocardium was identified by enhancement of regional function at low dose (

More than 50 years have passed since the Framingham Heart Study investigators published their first major report on “risk factors” for coronary heart disease [(1)][1]. Kannel et al. [(1)][1] discovered 3 risk factors, namely elevated blood pressure, elevated cholesterol levels, and

Policy and science often interact. Typically, we think of policymakers looking to scientists for advice on issues informed by science. We may appreciate less the opposite look: where people outside science inform policies that affect the conduct of science. In clinical medicine, we are forced to make decisions about practices for which there is insufficient, inadequate evidence to know whether they improve clinical outcomes, yet the health care system may not be structured to rapidly generate needed evidence. For example, when the Centers for Medicare and Medicaid Services noted insufficient evidence to support routine use of computed tomography angiography and they called for a national commitment to completion of randomized trials, their call ran into substantial opposition. I use the computed tomography angiography story to illustrate how we might consider a “policy for science” in which stakeholders would band together to identify evidence gaps and to use their influence to promote the efficient design, implementation, and completion of high-quality randomized trials. Such a policy for science could create a culture that incentivizes and invigorates the rapid generation of evidence, ultimately engaging all clinicians, all patients, and indeed all stakeholders into the scientific enterprise.

In the current issue of Population Health Metrics, two reports paint a bleak picture of American public health. Both physical inactivity and obesity remain highly prevalent; yet, it is not clear that increased physical activity will reduce the burden of obesity. There continue to be widespread disparities in life expectancy across United States counties. These reports appear against a backdrop of debate regarding how we should allocate our scarce resources for improving health: should we focus more on improving access to high-quality medical care, or should we instead focus on more and better public health interventions? While optimal solutions remain obscure, a look at prior successes suggests that ultimately they will come from the conduct and implementation of rigorous science, and in particular event-driven trials.