The relationship of erectile dysfunction and subclinical cardiovascular disease: A systematic review and meta-analysis.

Erectile dysfunction (ED) is associated with cardiovascular disease (CVD) and CVD mortality. However, the relationship between ED and subclinical CVD is less clear. We synthesized the available data on the association of ED and measures of subclinical CVD. We searched multiple databases for published literature on studies examining the association of ED and measures of subclinical CVD across four domains: endothelial dysfunction measured by flow-mediated dilation (FMD), carotid intima-media thickness (cIMT), coronary artery calcification (CAC), and other measures of vascular function such as the ankle-brachial index, toe-brachial index, and pulse wave velocity. We conducted random effects meta-analysis and meta-regression on studies that examined an ED relationship with FMD (15 studies; 2025 participants) and cIMT (12 studies; 1264 participants). ED was associated with a 2.64 percentage-point reduction in FMD compared to those without ED (95% CI: -3.12, -2.15). Persons with ED also had a 0.09-mm (95% CI: 0.06, 0.12) higher cIMT than those without ED. In subgroup meta-analyses, the mean age of the study population, study quality, ED assessment questionnaire (IIEF-5 or IIEF-15), or the publication date did not significantly affect the relationship between ED and cIMT or between ED and FMD. The results for the association of ED and CAC were inconclusive. In conclusion, this study confirms an association between ED and subclinical CVD and may shed additional light on the shared mechanisms between ED and CVD, underscoring the importance of aggressive CVD risk assessment and management in persons with ED.

Association between self-rated health and ideal cardiovascular health: The Baptist Health South Florida Employee Study.

Background: There is increasing evidence of the role psychosocial factors play as determinants of cardiovascular health (CVH). We examined the association between self-rated health (SRH) and ideal CVH among employees of a large healthcare organization. Methods: Data were collected in 2014 from employees of Baptist Health South Florida during an annual voluntary health risk assessment and wellness fair. SRH was measured using a self-administered questionnaire where responses ranged from poor, fair, good, very good to excellent. A CVH score (the proxy for CVH) that ranged from 0 to 14 was calculated, where 0-8 indicate an inadequate score, 9-10, average and 11-14, optimal. A multinomial logistic regression was used to examine the association between SRH and CVH. Results: Of the 9056 participants, 75% were female and mean age (SD) was 43 ± 12 years. The odds of having a higher CVH score increased as SRH improved. With participants who reported their health status as poor-fair serving as reference, adjusted odds ratios for having an optimal CVH score by the categories of SRH were: excellent, 21.04 (15.08-29.36); very good 10.04 (7.25-13.9); and good 3.63 (2.61-5.05). Conclusion: Favorable SRH was consistently associated with better CVH.

Obesity Modifies the Effect of Fitness on Heart Rate Indices during Exercise Stress Testing in Asymptomatic Individuals.

OBJECTIVE: To assess the impact of aerobic fitness on exercise heart rate (HR) indices in an asymptomatic cohort across different body mass index (BMI) categories. METHODS: We performed a cross-sectional analysis of 506 working-class Brazilian subjects, free of known clinical cardiovascular disease(e.g. ischemic heart disease and stroke) who underwent an exercise stress test. RESULTS: There was a significant trend towards decreased HR at peak exercise, HR recovery and chronotropic index (CI) measures as BMI increased, but resting HR increased significantly across BMI categories. In multivariate analysis, the change in CI per unit change in metabolic equivalents of task was greater among the obese subjects than the normal-weight (2.7 vs. ­0.07; p interaction = 0.029)and overweight (2.7 vs. 0.7; p interaction = 0.044) subjects. A similar pattern was seen with peak HR and HR recovery, although the formal tests of interaction did not achieve statistical significance. CONCLUSION: Our findings strongly suggest that fitness is associated with a favorable HR profile and is modified by BMI. Intervention programs should place emphasis on fitness and not only on weight loss.

Beyond BMI: The "Metabolically healthy obese" phenotype & its association with clinical/subclinical cardiovascular disease and all-cause mortality -- a systematic review.

BACKGROUND: A subgroup has emerged within the obese that do not display the typical metabolic disorders associated with obesity and are hypothesized to have lower risk of complications. The purpose of this review was to analyze the literature which has examined the burden of cardiovascular disease (CVD) and all-cause mortality in the metabolically healthy obese (MHO) population. METHODS: Pubmed, Cochrane Library, and Web of Science were searched from their inception until December 2012. Studies were included which clearly defined the MHO group (using either insulin sensitivity and/or components of metabolic syndrome AND obesity) and its association with either all cause mortality, CVD mortality, incident CVD, and/or subclinical CVD. RESULTS: A total of 20 studies were identified; 15 cohort and 5 cross-sectional. Eight studies used the NCEP Adult Treatment Panel III definition of metabolic syndrome to define "metabolically healthy", while another nine used insulin resistance. Seven studies assessed all-cause mortality, seven assessed CVD mortality, and nine assessed incident CVD. MHO was found to be significantly associated with all-cause mortality in two studies (30%), CVD mortality in one study (14%), and incident CVD in three studies (33%). Of the six studies which examined subclinical disease, four (67%) showed significantly higher mean common carotid artery intima media thickness (CCA-IMT), coronary artery calcium (CAC), or other subclinical CVD markers in the MHO as compared to their MHNW counterparts. CONCLUSIONS: MHO is an important, emerging phenotype with a CVD risk between healthy, normal weight and unhealthy, obese individuals. Successful work towards a universally accepted definition of MHO would improve (and simplify) future studies and aid inter-study comparisons. Usefulness of a definition inclusive of insulin sensitivity and stricter criteria for metabolic syndrome components as well as the potential addition of markers of fatty liver and inflammation should be explored. Clinicians should be hesitant to reassure patients that the metabolically benign phenotype is safe, as increased risk cardiovascular disease and death have been shown.

Association between high risk of obstructive sleep apnea and inflammatory markers in a population sample of young and middle-aged adults in the Miami Heart Study.

STUDY OBJECTIVES: There are limited data depicting the association between high risk of OSA and the levels of inflammatory markers in a population-based sample free from CVD. In a large U.S. cohort enriched with a Hispanic population and free of cardiovascular disease (CVD), we aimed to assess the association between high risk of obstructive sleep apnea (OSA) and inflammatory markers. METHODS: We analyzed data for 2359 clinical CVD-free participants from the Miami Heart Study, aged 40-65 (May 2015 - Sept 2018). High risk of OSA included those with a high risk using the Berlin questionnaire. Poisson regression analyses were utilized to examine the associations between high risk of OSA (reference: low risk of OSA) and hs-CRP, IL-6, and TNF-α levels (continuous) in univariate and multivariate models (adjusting for age, sex, race/ethnicity, and BMI, diabetes, hypertension, high cholesterol, and smoking). RESULTS: 552 (28%) participants were categorized as having a high risk of OSA. Patients with a high risk of OSA had higher median values of hs-CRP (2.3 vs. 1.0), IL-6 (1.9 vs. 1.4), and TNF-α (1.2 vs. 1.1) when compared to those with a low risk of OSA (all p < 0.001). When adjusting for age, sex, and race/ethnicity, the mean difference between patients with high and low risk of OSA in hs-CRP was 2.04 (95% CI 1.85, 2.23), and 0.73 (95% CI 0.57, 0.89) in IL-6. These differences were attenuated when further adjusting for CVD risk factors but remained statistically significant for hs-CRP: (0.38, 95% CI 0.21, 0.55). CONCLUSIONS: After accounting for CVD risk factors, individuals at high risk of OSA had significantly higher levels of hs-CRP, suggesting that OSA screening identified subclinical inflammation in this population sample of individuals free of CVD.

Phenotyping Hepatic Immune-Related Adverse Events in the Setting of Immune Checkpoint Inhibitor Therapy.

PURPOSE: We present and validate a rule-based algorithm for the detection of moderate to severe liver-related immune-related adverse events (irAEs) in a real-world patient cohort. The algorithm can be applied to studies of irAEs in large data sets. METHODS: We developed a set of criteria to define hepatic irAEs. The criteria include: the temporality of elevated laboratory measurements in the first 2-14 weeks of immune checkpoint inhibitor (ICI) treatment, steroid intervention within 2 weeks of the onset of elevated laboratory measurements, and intervention with a duration of at least 2 weeks. These criteria are based on the kinetics of patients who experienced moderate to severe hepatotoxicity (Common Terminology Criteria for Adverse Events grades 2-4). We applied these criteria to a retrospective cohort of 682 patients diagnosed with hepatocellular carcinoma and treated with ICI. All patients were required to have baseline laboratory measurements before and after the initiation of ICI. RESULTS: A set of 63 equally sampled patients were reviewed by two blinded, clinical adjudicators. Disagreements were reviewed and consensus was taken to be the ground truth. Of these, 25 patients with irAEs were identified, 16 were determined to be hepatic irAEs, 36 patients were nonadverse events, and two patients were of indeterminant status. Reviewers agreed in 44 of 63 patients, including 19 patients with irAEs (0.70 concordance, Fleiss' kappa: 0.43). By comparison, the algorithm achieved a sensitivity and specificity of identifying hepatic irAEs of 0.63 and 0.81, respectively, with a test efficiency (percent correctly classified) of 0.78 and outcome-weighted F1 score of 0.74. CONCLUSION: The algorithm achieves greater concordance with the ground truth than either individual clinical adjudicator for the detection of irAEs.

Lipoprotein(a) and Coronary Plaque in Asymptomatic Individuals: The Miami Heart Study at Baptist Health South Florida.

BACKGROUND: Elevated levels of lipoprotein(a) (Lp(a)) are independently associated with an increased risk of atherosclerotic cardiovascular disease events. However, the mechanisms driving this association are poorly understood. We aimed to evaluate the association between Lp(a) and coronary plaque characteristics in a contemporary US cohort without clinical atherosclerotic cardiovascular disease, undergoing coronary computed tomography angiography, the noninvasive gold standard for the assessment of coronary atherosclerosis. METHODS: We used baseline data from the Miami Heart Study-a community-based, prospective cohort study-which included asymptomatic adults aged 40 to 65 years evaluated using coronary computed tomography angiography. Those taking any lipid-lowering therapies were excluded. Elevated Lp(a) was defined as ≥125 nmol/L. Outcomes included any plaque, coronary artery calcium score >0, maximal stenosis ≥50%, presence of any high-risk plaque feature (positive remodeling, spotty calcification, low-attenuation plaque, napkin ring), and the presence of ≥2 high-risk plaque features. RESULTS: Among 1795 participants (median age, 52 years; 54.3% women; 49.6% Hispanic), 291 (16.2%) had Lp(a) ≥125 nmol/L. In unadjusted analyses, individuals with Lp(a) ≥125 nmol/L had a higher prevalence of all outcomes compared with Lp(a) <125 nmol/L, although differences were only statistically significant for the presence of any coronary plaque and ≥2 high-risk features. In multivariable models, elevated Lp(a) was independently associated with the presence of any coronary plaque (odds ratio, 1.40, [95% CI, 1.05-1.86]) and with ≥2 high-risk features (odds ratio, 3.94, [95% CI, 1.82-8.52]), although only 35 participants had this finding. Among participants with a coronary artery calcium score of 0 (n=1200), those with Lp(a) ≥125 nmol/L had a significantly higher percentage of any plaque compared with those with Lp(a) <125 nmol/L (24.2% versus 14.2%; P<0.001). CONCLUSIONS: In this contemporary analysis, elevated Lp(a) was independently associated with the presence of coronary plaque. Larger studies are needed to confirm the strong association observed with the presence of multiple high-risk coronary plaque features.

Matching Patients to Accelerate Clinical Trials (MPACT): Enabling Technology for Oncology Clinical Trial Workflow.

Clinical trial enrollment is impeded by the significant time burden placed on research coordinators screening eligible patients. With 50,000 new cancer cases every year, the Veterans Health Administration (VHA) has made increased access for Veterans to high-quality clinical trials a priority. To aid in this effort, we worked with research coordinators to build the MPACT (Matching Patients to Accelerate Clinical Trials) platform with a goal of improving efficiency in the screening process. MPACT supports both a trial prescreening workflow and a screening workflow, employing Natural Language Processing and Data Science methods to produce reliable phenotypes of trial eligibility criteria. MPACT also has a functionality to track a patient's eligibility status over time. Qualitative feedback has been promising with users reporting a reduction in time spent on identifying eligible patients.

Atherosclerotic plaque in individuals without known cardiovascular disease but with established obstructive sleep apnea and at high risk of obstructive sleep apnea.

Objectives: In a large U.S. cohort free of CVD evaluated by coronary computed CT angiography, we aimed to assess the association between established / high risk of Obstructive Sleep Apnea (OSA) and coronary plaque. Background: There are limited data available depicting the association between established / high risk of OSA and the presence of coronary plaque in a population-based sample free from CVD. Methods: Cross-sectional data from 2359 participants enrolled in the Miami Heart Study (MiHeart) who underwent coronary CT angiography was used for this study. The Berlin questionnaire was used to stratify patients as having high or low risk of OSA. Multiple multivariable logistic regression analyses were conducted to investigate the association between the risk of developing OSA with the presence, volume, and composition of plaque. Results: According to the Berlin questionnaire, 1559 participants were (66.1%) at low risk of OSA and 800 patients (33.9%) with established / high risk of OSA. Plaque characterization on CCTA revealed a greater incidence of any possible plaque composition in the established / high risk of OSA category (59.6% vs. 43.5%) compared to the low risk of OSA cohort. In logistic regression models, after adjusting for demographics and cardiovascular risk factors, a significant association could still be noted between established / high risk of OSA and any coronary plaque on CCTA (OR=1.31, CI 1.05, 1.63, p = 0.016). Subgroup analysis in the Hispanic population also portrayed a significant association between established / high risk of OSA and the presence of coronary plaque on CCTA (OR = 1.55 CI 1.13, 2.12, p = 0.007). Conclusion: After accounting for CVD risk factors, individuals at established / high risk of OSA have a higher likelihood of the presence of coronary plaque. Future studies should focus on OSA presence or risk, OSA severity, and the longitudinal consequences of coronary atherosclerosis.

The association of sex-specific hormones with coronary artery plaque characteristics from Miami Heart (MiHeart) study.

Objective: The association of sex-specific hormones with coronary computed tomography angiography(CCTA)-based plaque characteristics in women without cardiovascular disease is not well understood. We investigated the association of sex-specific hormones with coronary artery plaque characteristics in a contemporary multiracial cohort with no clinical coronary artery disease (CAD). Methods: In this cross-sectional analysis, we utilized data from 2,325 individuals with no clinical CAD from the Miami Heart (MiHeart) study. Multivariable logistic regression models were used to investigate the association of sex hormones: sex hormone binding globulin (SHBG), dehydroepiandrosterone (DHEA), free and total testosterone, estradiol, with plaque characteristics among women and men. Results: Of the 1,155 women, 34.2% had any plaque and 3.4% had any high-risk plaque features (HRP) while among men (n = 1170), 63.1% had any plaque and 10.4% had HRP. Among women, estradiol and SHBG were associated with lower odds of any plaque after adjusting for age and race-ethnicity (estradiol OR per SD increase: 0.87, 95%CI: 0.76-0.98; SHBG OR per SD increase: 0.82, 95%CI: 0.72-0.93) but the significance did not persist after adjustment of cardiovascular risk factors. High free testosterone was associated with higher odds of HRP (aOR:3.48, 95%CI:1.07-11.26) but null associations for the other sex hormones with HRP, in the context of limited sample size. Among men, there were no significant associations between sex-specific hormones and plaque or HRP. Conclusion: Among young to middle-aged women with no clinical CAD, increasing estradiol and SHBG were associated with lower odds of any plaque and higher free testosterone was associated with HRP. Larger cohorts may be needed to validate this.

Coronary Atherosclerosis Across the Glycemic Spectrum Among Asymptomatic Adults: The Miami Heart Study at Baptist Health South Florida.

BACKGROUND: The contemporary burden and characteristics of coronary atherosclerosis, assessed using coronary computed tomography angiography (CCTA), is unknown among asymptomatic adults with diabetes and prediabetes in the United States. The pooled cohort equations and coronary artery calcium (CAC) score stratify atherosclerotic cardiovascular disease risk, but their association with CCTA findings across glycemic categories is not well established. METHODS: Asymptomatic adults without atherosclerotic cardiovascular disease enrolled in the Miami Heart Study were included. Participants underwent CAC and CCTA testing and were classified into glycemic categories. Prevalence of coronary atherosclerosis (any plaque, noncalcified plaque, plaque with ≥1 high-risk feature, maximal stenosis ≥50%) assessed by CCTA was described across glycemic categories and further stratified by pooled cohort equations-estimated atherosclerotic cardiovascular disease risk and CAC score. Adjusted logistic regression was used to evaluate the associations between glycemic categories and coronary outcomes. RESULTS: Among 2352 participants (49.5% women), the prevalence of euglycemia, prediabetes, and diabetes was 63%, 30%, and 7%, respectively. Coronary plaque was more commonly present across worsening glycemic categories (euglycemia, 43%; prediabetes, 58%; diabetes, 69%), and similar pattern was observed for other coronary outcomes. In adjusted analyses, compared with euglycemia, prediabetes and diabetes were each associated with higher odds of any coronary plaque (OR, 1.30 [95% CI, 1.05-1.60] and 1.75 [1.17-2.61], respectively), noncalcified plaque (OR, 1.47 [1.19-1.81] and 1.99 [1.38-2.87], respectively), and plaque with ≥1 high-risk feature (OR, 1.65 [1.14-2.39] and 2.53 [1.48-4.33], respectively). Diabetes was associated with stenosis ≥50% (OR, 3.01 [1.79-5.08]; reference=euglycemia). Among participants with diabetes and estimated atherosclerotic cardiovascular disease risk <5%, 46% had coronary plaque and 10% had stenosis ≥50%. Among participants with diabetes and CAC=0, 30% had coronary plaque and 3% had stenosis ≥50%. CONCLUSIONS: Among asymptomatic adults, worse glycemic status is associated with higher prevalence and extent of coronary atherosclerosis, high-risk plaque, and stenosis. In diabetes, CAC was more closely associated with CCTA findings and informative in a larger population than the pooled cohort equations.

Coronary Atherosclerosis in an Asymptomatic U.S. Population: Miami Heart Study at Baptist Health South Florida.

BACKGROUND: The burden of total coronary plaque, plaque subtypes, and high-risk plaque features was unknown in asymptomatic individuals from the general U.S. primary prevention population. OBJECTIVES: In a large, asymptomatic U.S. cohort evaluated using coronary computed tomography angiography (CCTA), we aimed to assess the burden of total coronary plaque, plaque subtypes, and high-risk plaque features; the interplay between CCTA findings and coronary artery calcium (CAC) scores; and identify independent predictors of coronary plaque. METHODS: Cross-sectional analysis in the MiHeart (Miami Heart Study), a cohort of 2,359 asymptomatic individuals from the Greater Miami Area (mean age 53 years, 50% women, 47% Hispanic/Latino, 43% non-Hispanic White). We estimated the burden of CAC (=0, >0 to <100, ≥100), CCTA-based plaque features (any plaque, stenosis ≥50%, ≥70%, high-risk features), and their interplay. RESULTS: Overall, 58% participants had CAC = 0, 28% CAC >0 to <100, and 13% CAC ≥100. A total of 49% participants had plaque on the CCTA, including 16% among those with CAC = 0. Overall, 6% participants had coronary stenosis ≥50% (12% among those with coronary plaque), 1.8% had stenosis ≥70% (3.7% among those with plaque), and 7% had at least 1 coronary plaque with ≥1 high-risk feature (13.8% among those with plaque). Only 0.8% participants with CAC = 0 had stenosis ≥50%, 0.1% stenosis ≥70%, and 2.3% plaque with high-risk features. In logistic regression models, independent predictors of coronary plaque and high-risk plaque were older age, male sex, tobacco use, diabetes, overweight, and obesity. Male sex, overweight, and obesity were independent predictors of plaque if CAC = 0. CONCLUSIONS: The Miami Heart Study confirms substantial prevalence of coronary plaque in asymptomatic individuals. Overall, 49% of participants had coronary plaque, 6% had stenosis ≥50%, and 7% had plaques with at least 1 high-risk feature. These proportions were 16%, 0.8%, and 2.3%, respectively, among those with CAC = 0. Longitudinal follow-up will shed further light on the prognostic implications of these findings in asymptomatic individuals.

Machine-learning-based predictions of direct-acting antiviral therapy duration for patients with hepatitis C.

INTRODUCTION: Hepatitis C, which affects 71 million persons worldwide, is the most common blood-borne pathogen in the United States. Chronic infections can be treated effectively thanks to the availability of modern direct-acting antiviral (DAA) therapies. Real-world data on the duration of DAA therapy, which can be used to optimize and guide the course of therapy, may also be useful in determining quality of life enhancements based upon total required supply of medication and long-term improvements to quality of life. We developed a machine learning model to identify patient characteristics associated with prolonged DAA treatment duration. METHODS: A nationwide U.S. commercial managed care plan with claims data that covers about 60 million beneficiaries from 2009 to 2019 were used in the retrospective study. We examined differences in age, gender, and multiple comorbidities among patients treated with different durations of DAA treatment. We also examined the performance of machine learning models for predicting a prolonged course of DAA based on the area under the receiver operating characteristic curve (AUC). RESULTS: We identified 3943 cases with hepatitis C who received sofosbuvir/ledipasvir as the first course of DAA and were eligible for the study. Patients receiving prolonged treatment (n = 240, 6.1%) were more likely to have compensated cirrhosis, decompensated cirrhosis, and other comorbidities (P < 0.001). For distinguishing patients who received prolonged DAA treatment for hepatitis C from patients received standard treatment, the optimal predictive model, constructed with XGBoost, had an AUC of 0.745 ± 0.031 (P < 0.001). CONCLUSIONS: The risk of antiviral resistance and the cost of DAA are strong motivators to ensure that first-round DAA therapy is effective. For the dominant DAA treatment during the course of this analysis, we present a model that identifies factors already captured in established guidelines and adds to those age, comorbidity burden, and type 2 diabetes status; patient characteristics that are predictive of extended treatment.

The Miami Heart Study (MiHeart) at Baptist Health South Florida, A prospective study of subclinical cardiovascular disease and emerging cardiovascular risk factors in asymptomatic young and middle-aged adults: The Miami Heart Study: Rationale and Design.

OBJECTIVE: The Miami Heart Study (MiHeart) at Baptist Health South Florida is an ongoing, community-based, prospective cohort study aimed at characterizing the prevalence, characteristics, and prognostic value of diverse markers of early subclinical coronary atherosclerosis and of various potential demographic, psychosocial, and metabolic risk factors. We present the study objectives, detailed research methods, and preliminary baseline results of MiHeart. METHODS: MiHeart enrolled 2,459 middle-aged male and female participants from the general population of the Greater Miami Area. Enrollment occurred between May 2015 and September 2018 and was restricted to participants aged 40-65 years free of clinical cardiovascular disease (CVD). The baseline examination included assessment of demographics, lifestyles, medical history, and a detailed evaluation of psychosocial characteristics; a comprehensive physical exam; measurement of multiple blood biomarkers including measures of inflammation, advanced lipid testing, and genomics; assessment of subclinical coronary atherosclerotic plaque and vascular function using coronary computed tomography angiography, the coronary artery calcium score, carotid intima-media thickness, pulse wave velocity, and peripheral arterial tonometry; and other tests including 12-lead electrocardiography and assessment of pulmonary function. Blood samples were biobanked to facilitate future ancillary research. RESULTS: MiHeart enrolled 1,261 men (51.3%) and 1,198 women (48.7%). Mean age was 53 years, 85.6% participants were White and 47.4% were of Hispanic/Latino ethnicity. The study included 7% individuals with diabetes, 33% with hypertension, and 15% used statin therapy at baseline. Overweight or obese participants comprised 72% of the population and 3% were smokers. Median 10-year estimated atherosclerotic CVD risk using the Pooled Cohort Equations was 4%. CONCLUSION: MiHeart will provide important, novel insights into the pathophysiology of early subclinical atherosclerosis and further our understanding of its role in the genesis of clinical CVD. The study findings will have important implications, further refining current cardiovascular prevention paradigms and risk assessment and management approaches moving forward.

Stretching DNA to twice the normal length with single-molecule hydrodynamic trapping.

Single-molecule force spectroscopy has brought many new insights into nanoscale biology, from the functioning of molecular motors to the mechanical response of soft materials within the cell. To expand the single-molecule toolbox, we have developed a surface-free force spectroscopy assay based on a high-speed hydrodynamic trap capable of applying extremely high tensions for long periods of time. High-speed single-molecule trapping is enabled by a rigid and gas-impermeable microfluidic chip, rapidly and inexpensively fabricated out of glass, double-sided tape and UV-curable adhesive. Our approach does not require difficult covalent attachment chemistries, and enables simultaneous force application and single-molecule fluorescence. Using this approach, we have induced a highly extended state with twice the contour length of B-DNA in regions of partially intercalated double-stranded (dsDNA) by applying forces up to 250 pN. This highly extended state resembles the hyperstretched state of dsDNA, which was initially discovered as a structure fully intercalated by dyes under high tension. It has been hypothesized that hyperstretched DNA could also be induced without the aid of intercalators if high-enough forces were applied, which matches our observation. Combining force application with single-molecule fluorescence imaging is critical for distinguishing hyperstretched DNA from single-stranded DNA that can result from peeling. High-speed hydrodynamic trapping is a powerful yet accessible force spectroscopy method that enables the mechanics of biomolecules to be probed in previously difficult to access regimes.

An application to support COVID-19 occupational health and patient tracking at a Veterans Affairs medical center.

OBJECTIVE: Reducing risk of coronavirus disease 2019 (COVID-19) infection among healthcare personnel requires a robust occupational health response involving multiple disciplines. We describe a flexible informatics solution to enable such coordination, and we make it available as open-source software. MATERIALS AND METHODS: We developed a stand-alone application that integrates data from several sources, including electronic health record data and data captured outside the electronic health record. RESULTS: The application facilitates workflows from different hospital departments, including Occupational Health and Infection Control, and has been used extensively. As of June 2020, 4629 employees and 7768 patients and have been added for tracking by the application, and the application has been accessed over 46 000 times. DISCUSSION: Data captured by the application provides both a historical and real-time view into the operational impact of COVID-19 within the hospital, enabling aggregate and patient-level reporting to support identification of new cases, contact tracing, outbreak investigations, and employee workforce management. CONCLUSIONS: We have developed an open-source application that facilitates communication and workflow across multiple disciplines to manage hospital employees impacted by the COVID-19 pandemic.

Impact of high-dose atorvastatin in coronary heart disease patients age 65 to 78 years.

BACKGROUND: High-dose statin therapy may be underutilized in aged patients due to doubts about efficacy and safety. HYPOTHESIS: To investigate outcomes and safety in patients aged 65-78 years compared with patients aged < 65 years in the ALLIANCE study. METHODS: A total of 2,442 stable coronary heart disease (CHD) patients with dyslipidemia were randomized to either aggressive treatment (low-density lipoprotein cholesterol titration goal of < 80 mg/dL or maximum 80 mg/d of atorvastatin) or usual care (continuation of baseline lipid-lowering therapy, with changes and laboratory analyses directed by treating physicians). RESULTS: A total of 1,001 patients aged 65-78 years were followed for a median period of 53.9 mo. Older, aggressively treated atorvastatin patients experienced a 27% relative risk reduction for the primary composite endpoint of adverse cardiovascular outcomes (hazard ratio [HR]: 0.73; 95% confidence intervals [CI]: 0.57-0.94; p = 0.016). In addition, significant risk reductions were observed for nonfatal myocardial infarction (MI; HR: 0.43; 95% CI: 0.23-0.79; p = 0.006), cardiac revascularization (HR: 0.67; 95% CI: 0.48-0.93; p = 0.017), and the combined endpoint of cardiac death and nonfatal MI (HR: 0.48; 95% CI: 0.32-0.72; p = 0.001). The rate of significant liver transaminase elevations in atorvastatin patients was low and not age related. There were no cases of rhabdomyolysis. The rate of study discontinuations due to serious adverse events was higher in patients aged 65-78 years than in those younger than 65 years, but was similar between the treatment groups. CONCLUSIONS: Our data support the efficacy and safety of aggressive lipid management with atorvastatin in older CHD patients.

The Veterans Precision Oncology Data Commons: Transforming VA data into a national resource for research in precision oncology.

The Department of Veterans Affairs (VA) has a strong track record providing high-quality, evidence-based care to cancer patients. In order to accelerate discoveries that will further improve care for Veterans with cancer, the VA has partnered with the Center for Translational Data Science at the University of Chicago and the Open Commons Consortium to establish a data sharing platform, the Veterans Precision Oncology Data Commons (VPODC). The VPODC makes clinical, genomic, and imaging data from the VA available to the research community at large. In this paper, we detail our motivation for data sharing, describe the VPODC, and outline our collaboration model. By transforming VA data into a national resource for research in precision oncology, the VPODC seeks to foster innovation through collaboration and resource sharing that will ultimately lead to improved care for Veterans with cancer.

Lipoprotein Sub-Fractions by Ion-Mobility Analysis and Its Association with Subclinical Coronary Atherosclerosis in High-Risk Individuals.

AIMS: There is limited knowledge about the association of lipoprotein particles and markers of coronary atherosclerosis such as coronary artery calcification (CAC) in relatively young high-risk persons. This study examines the association of lipoprotein subfractions and CAC in high cardiometabolic risk individuals. METHODS: The study presents analysis from baseline data of a randomized trial targeted at high-risk workers. Employees of Baptist Health South Florida with metabolic syndrome or diabetes were recruited. At baseline, all 182 participants had lipoprotein subfraction analysis using the ion mobility technique and participants above 35 years (N=170) had CAC test done. Principal components (PC) were computed for the combination of lipoprotein subclasses. Multiple bootstrapped regression analyses (BSA) were conducted to assess the relationship between lipoprotein subfractions and CAC. RESULTS: The study population (N=170) was largely female (84%) with a mean age of 58 years. Three PCs accounted for 88% variation in the sample. PC2, with main contributions from VLDL particles in the positive direction and large LDL particles in the negative direction was associated with a 22% increase in CAC odds (P value ＜0.05 in 100% of BSA). PC3, with main contributions from HDL lipoprotein particles in the positive direction and small/medium LDL and large IDL particles in the negative direction, was associated with a 9% reduction in CAC odds (P＜0.05 in 88% of BSA). PC1, which had approximately even contributions from HDL, LDL, IDL and VLDL lipoprotein subfractions in the positive direction, was not associated with CAC. CONCLUSION: In a relatively young but high-risk population, a lipoprotein profile predominated by triglyceride-rich lipoproteins was associated with increased risk of CAC, while one predominated by HDL lipoproteins offered modest protection. Lipoprotein sub-fraction analysis may help to further discriminate patients who require more intensive cardiovascular work-up and treatment.