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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.

At this year’s State of the Union address, the President announced a new $215 million Precision Medicine Initiative in the 2016 budget that will pioneer a new model of patient-empowered research that promises to accelerate biomedical discoveries and provide clinicians with new tools, knowledge, and therapies to select which treatments will work best for which patients [1, 2]. Concurrently, Directors of the National Institutes of Health and the National Cancer Institute, Drs. Francis Collins and Harold Varmus, respectively, published an article in the New England Journal of Medicine that describes two main components of this initiative, a near-term focus on cancer therapy and a longer-term effort to generate knowledge applicable to a wide range of health and disease [3]. This longer-term initiative seeks to generate a cohort of one million or more Americans to “enable better assessment of disease risk, understanding of disease mechanisms, and the prediction of optimal therapy for many more diseases, with the goal of expanding the benefits of precision medicine into myriad aspects of health and healthcare” [3]. Matching treatment to the unique biological, behavioral, or environmental characteristics of the individual is nothing new. Matching blood type for transfusions has been common practice for nearly a century [4]. The guidelines for the management of cholesterol have been based on individual patient factors for over a decade [5]. Tailored behavioral interventions have been evaluated for over two decades. Although early treatment matching studies were disappointing [6], tailored behavioral interventions, especially computerized tailored interventions, have generally been found more efficacious than untailored interventions [7, 8]. The concept of precision medicine is not new, but recent advances in genome sequencing, cohort study designs, health informatics, and mobile/wireless technologies make now an opportune time for a large precision medicine cohort initiative.

AIM: To examine the association of left ventricular hypertrophy (LVH) on admission electrocardiography with adverse outcomes in acute coronary syndrome (ACS) patients. METHODS AND RESULTS: A total of 7443 non-ST-elevation ACS patients in Global Utilization of STrategies to Open occluded arteries (GUSTO) IV ACS trial had admission electrocardiograms analysed at a core laboratory. LVH [>or=20 mm Cornell voltage (LV voltage) (women) or >or=28 mm (men) plus strain patterns] was observed in 586 (7.9%) patients, and women accounted for 74%. LVH patients were also older and had more co-morbidities, ST-depression >or= 0.5 mm, elevated C-reactive protein and N-terminal pro-brain naturetic peptide (NT-proBNP), and lower troponin T. Invasive procedures occurred less often in LVH patients (cardiac catheterization: 31 vs. 38%, P = 0.001; percutaneous coronary intervention: 12 vs. 20%, P < 0.001). Mortality was significantly higher in patients with LVH (30 day: 5 vs. 3%, P = 0.046; 1 year: 14 vs. 7%, P < 0.001), whereas 30 day myocardial infarction (MI) and death/MI did not differ. After baseline adjustment including NT-proBNP, LVH remained associated with increased hazard of 1 year mortality in women, but not in men [P-interaction = 0.033; women: adjusted hazard ratio (LVH vs. no LVH): 1.42 (1.04-1.94), P = 0.029]. CONCLUSION: Electrocardiographic-LVH identifies an important subset of ACS patients with a higher risk of long-term mortality, particularly among women. These novel findings highlight opportunities to improve treatment and outcome among similar ACS patients. Udgivelsesdato: 2007-Sep

An entity of patients with mixed physiology of constriction and restriction has been reported, however, the characteristics of these patients have not been well documented. We evaluated the clinical features and the outcome of these patients.Study subjects consisted of 38 patients (57+/-14 years, 8 females, 30 males) who were diagnosed as having mixed physiology based on transthoracic and/or transesophageal echocardiography, MRI (or CT), cardiac catheterization, endomyocardial biopsy and/or surgical findings. Prior radiation therapy was the most frequent (50%) cause of mixed physiology followed by coronary artery bypass graft without prior radiation (24%) and heart transplantation (8%). The respiratory variation of peak early diastolic transmitral flow velocity by pulsed Doppler transesophageal echocardiography was 10.7% in patients with sinus rhythm and 18.1% in patients with atrial arrhythmia. Pericardial thickening was noted adjacent to the right-sided chambers in 19 patients, left-sided chambers in 10 patients, or both in 9 patients. All-cause 5-year mortality was 40% and unrelated to age, etiology, left ventricular systolic function and therapeutic course. There was a statistically significant difference (p0.01) between the survival rates in patients with mixed physiology and in patients with pure constriction (n=125).Due to the high mortality in this disease, discrimination of the entity from the patients with pure constriction is mandatory. Transthoracic and transesophageal echocardiography are helpful noninvasive techniques in the diagnosis and the understanding of the physiology of patients with mixed constriction and restriction.

Aims To determine whether the presence and severity of aortic atheroma predict long-term all-cause mortality among patients undergoing cardiac surgery. Methods and results We followed 8581 patients who underwent cardiac surgery and had routine intraoperative transoesophageal echocardiography for 2.8 years (range 0.06–6.0 years). Data regarding multiple potential confounders were prospectively collected and electronically recorded. There were 2878 (34%) patients with no atheroma; 4129 (48%) patients with mild atheroma; 1215 (14%) with moderate atheroma; and 359 (4%) with severe atheroma. There were 1000 deaths. Death rates were increased in patients with moderate [relative risk (RR) 3.29, 95% CI 2.50–4.32, P < 0.0001) and severe atheroma (RR 5.21, 95% CI 3.65–7.41, P < 0.0001). After adjusting for multiple other confounders, severe atheroma remained modestly predictive of risk (adjusted RR 1.46, 95% CI 1.07–2.00, P = 0.02); but moderate atheroma and mild atheroma were not predictive of increased risk. In a propensity analysis that matched patients with comparable range of variables, severe atheroma was no longer predictive of risk (adjusted RR 1.39, 95% CI 0.87–2.23, P = 0.17). Conclusion Our study shows that severe atheroma is associated with increased long-term mortality in patients undergoing cardiac surgery; however, the relationship is weak using propensity analysis, suggesting no causal association.

Many modern physician specialists like to think of their work as grounded in strong science. Yet 5 years ago, a group of cardiologists published their findings on the science underlying over 2700 practice recommendations issued by their specialty societies.1 Only 314 (or 11%) were based on ‘level A’ evidence, that is, evidence based on multiple well-done randomized trials. Nearly half of the recommendations were based solely on ‘expert opinion.’ Even more disconcerting is the fact that despite the activities of many researchers, the vast majority of ongoing clinical trials are too small to provide evidence relevant to patients and clinicians.2 Robust trials that can support recommendations grounded in solid science are few and far between, in part because they have become too expensive and complicated to run. Our biomedical enterprise is conducting many clinical trials, yet we may not be getting all that much for what we spend.3 No wonder that too often, patients and caregivers seeking information on how best to improve their health or the health of their loved ones find that biomedicine does not have answers for questions they ask. Too often, clinicians cannot tell patients which therapies are likely to work best for individuals like them. Too often risks, benefits, and impact on quality of life are uncertain. Providing accurate answers based on the highest levels of scientific evidence for the majority of unresolved clinical questions is a revolutionary dream shared by patients, providers, payers, health plans, researchers, and policy makers alike. PCORnet, the National Patient-Centered Clinical Research … Correspondence to Dr Kathy L Hudson, National Institutes of Health, 9000 Rockville Pike, Bethesda, MD 20892, USA; kathy.hudson{at}nih.gov

For 40 days and 40 nights, Noah, his wife, his three sons and their wives, and myriads of animal pairs remained safe in their Ark while massive flooding destroyed the rest of the world. After several more weeks, the Ark settled on dry land, and Noah and his family emerged. What was among Noah’s first acts upon leaving the Ark? He “drank of the wine and became drunk,” and his sons had to protect him from embarrassment ( 1 ). Thus, the book of Genesis reports one of the first episodes demonstrating the dangers of alcohol. Alcoholic beverages have been with us throughout the human history. During the last century, ill-advised efforts were made to eliminate its dangers by passing a constitutional amendment prohibiting its manufacture, sale, and distribution. As is well known, this created a social disaster and was later repealed. Beyond its social dangers, many of alcohol’s medical dangers are well known and have been known for a long time, including acute intoxication; chronic destructive addiction; cirrhosis of the liver; dilated cardiomyopathy; fetal alcohol syndrome; and increased risks for hypertension, stroke, cardiac arrhythmias, and fatal motor vehicle accidents. Over the past 20 – 30 years, the medical position on alcohol has become somewhat more nuanced. Investigations of large-scale observational cohorts have suggested that light to moderate drinking may be associated with decreased mortality rates and with decreased risk of cardiovascular disease ( 2 ). Some studies ( 3 ), but not all ( 4 , 5 ), have suggested that wine may provide additional benefi ts over and above the effects of alcohol, perhaps because of antioxidant or other types of effects of non-alcohol grape chemicals like resveratrol ( 6 ). Some investigators have been so intrigued by the possible benefi ts of low-dose alcohol that they have gone so far as to consider mechanisms by which alcohol can have salutary cardiovascular effects ( 4 ). These include increased levels of high- density lipoprotein cholesterol and a decreased tendency to thrombosis. Combining these reported biological benefi ts with epidemiological fi ndings, some medical organizations have stated that low levels of alcohol consumption maybe considered safe ( 7 ) or may be a legitimate “item of discussion between physician and patient” ( 8 ). In this issue of the Journal, Allen et al. ( 9 ) present fascinating fi ndings that should give us pause. Allen et al. have systematically surveyed more than 1 million women who between 1996 and 2001 attended breast cancer screening clinics in the United Kingdom. They found that after 7 years of follow-up, even light to moderate levels of alcohol consumption were predictive of an increased risk of several common cancers, including those of the breast, rectum, liver, esophagus, and oropharynx. Taking into account the prevalence of alcohol consumption and its observed relative risks, the authors estimated that about 13% of cancers of the breast, aerodigestive tract, liver, and rectum could be attributed to alcohol. Because of an enormous sample size, systematic survey methodology, and an ability to capture nearly all incident diagnoses of cancer, the authors could make a number of important, heretofore unappreciated, discoveries. Previous investigations have focused on the association between alcohol and mortality ( 5 ), including mortality due to cancer, but have not been able to so carefully assess the association of alcohol intake with the subsequent diagnosis of cancer. Allen et al. could estimate the association of different levels of alcohol intake with many different kinds of cancer. Perhaps more importantly, they could evaluate key interactions for specifi c cancer types; for example, they demonstrated that alcohol use was strongly predictive of cancer of the upper aerodigestive tract but only in current smokers. From a standpoint of cancer risk, the message of this report could not be clearer. There is no level of alcohol consumption that can be considered safe. How are we to interpret the fi ndings of Allen et al. given previous investigations suggesting that alcohol may be safe or even benefi cial when taken in relatively low doses ( 2 , 4 )? Despite their study’s many strengths, there are some important limitations that must be considered. The study was limited to women who were seen in breast cancer screening clinics; there is evidence that these women may be different in some respects from those of the general population ( 10 ). Nearly all the baseline clinical data were based on answers to a questionnaire, not direct measurement; this might be considered an acceptable sacrifi ce given the study’s enormous sample size. This is also a limitation inherent to essentially all epidemiological investigations of alcohol use; it is doubtful that a systematic bias exists whereby women who are destined to develop cancer will misclassify their alcohol intake. Finally, the authors provide no information on all-cause mortality or incident cardiovascular disease events, despite the ability of their data to provide this information. We must hope that the authors plan to report on these outcomes in future publications. Despite these limitations, the message from this report takes on a greater sense of urgency when considering the limitations of the many investigations suggesting benefi cial cardiovascular effects of alcohol. Some have suggested that there is no real cardioprotective