Publications by authors named "Yi-An Ko"

158 Publications

Framing Benefits in Decision Aids: Effects of Varying Contextualizing Statements on Decisions About Sacubitril-Valsartan for Heart Failure.

MDM Policy Pract 2021 Jul-Dec;6(2):23814683211041623. Epub 2021 Oct 18.

Department of Medicine, Division of Cardiology, Emory University School of Medicine, Atlanta, Georgia.

Presenting numeric data alone may result in patients underappreciating clinically significant benefits. Contextualizing statements to counter this may raise concern about absence of neutrality. These issues arose during construction of a decision aid for sacubitril-valsartan, a heart failure medication associated with a ∼3% absolute reduction in 2-year mortality that carries high out-of-pocket cost. A contextualizing statement framing this as a "pretty big benefit" was incorporated. The impact of statements like this within decision aids is unknown. This online Qualtrics survey sought to deepen understanding of benefit framing by testing the impact of varying contextualizing statements within a decision aid for sacubitril-valsartan. Participants were randomly assigned to receive one of six abbreviated versions of a decision aid for sacubitril-valsartan that varied only by contextualizing statement (ranging from strongly neutral to strongly positive and using relative and absolute risk reductions). Participants were asked to answer questions regarding the likelihood of taking the medication at a cost of $50/month and their perception of the drug's benefits. A total of 1873 participants who were demographically similar to the heart failure population completed the survey. Fifty-four percent were willing to take sacubitril-valsartan at $50/month. Each of the five experimental contextualizing statements was compared with the baseline version; no significant differences were observed in reported likelihood of taking sacubitril-valsartan. After controlling for demographics and covariates, group assignment did not predict likelihood of taking the medication. Higher income, better self-reported health status, and younger age were associated with increased likelihood of taking sacubitril-valsartan. This study used a hypothetical scenario and evaluated one method of delivering contextualizing statements. Contextualizing statements as tested within this decision aid did not affect decision making.
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http://dx.doi.org/10.1177/23814683211041623DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8529322PMC
October 2021

Transcutaneous vagal nerve stimulation blocks stress-induced activation of Interleukin-6 and interferon-γ in posttraumatic stress disorder: A double-blind, randomized, sham-controlled trial.

Brain Behav Immun Health 2020 Dec 11;9:100138. Epub 2020 Sep 11.

Departments of Epidemiology, Rollins School of Public Health, Atlanta, GA, USA.

Posttraumatic stress disorder (PTSD) is a highly disabling condition associated with alterations in multiple neurobiological systems, including increases in inflammatory function. Vagus nerve stimulation (VNS) decreases inflammation, however few studies have examined the effects of non-invasive VNS on physiology in human subjects, and no studies in patients with PTSD. The purpose of this study was to assess the effects of transcutaneous cervical VNS (tcVNS) on inflammatory responses to stress. Thirty subjects with a history of exposure to traumatic stress with (N ​= ​10) and without (N ​= ​20) PTSD underwent exposure to stressful tasks immediately followed by active or sham tcVNS and measurement of multiple biomarkers of inflammation (interleukin-(IL)-6, IL-2, IL-1β, Tumor Necrosis Factor alpha (TNFα) and Interferon gamma (IFNγ) over multiple time points. Stressful tasks included exposure to personalized scripts of traumatic events on day 1, and public speech and mental arithmetic (Mental Stress) tasks on days 2 and 3. Traumatic scripts were associated with a pattern of subjective anger measured with Visual Analogue Scales and increased IL-6 and IFNγ in PTSD patients that was blocked by tcVNS (p ​< ​.05). Traumatic stress had minimal effects on these biomarkers in non-PTSD subjects and there was no difference between tcVNS or sham. No significant differences were seen between groups in IL-2, IL-1β, or TNFα. These results demonstrate that tcVNS blocks behavioral and inflammatory responses to stress reminders in PTSD.
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http://dx.doi.org/10.1016/j.bbih.2020.100138DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8474180PMC
December 2020

Associations Between Inflammation, Cardiovascular Regenerative Capacity, and Cardiovascular Events: A Cohort Study.

Arterioscler Thromb Vasc Biol 2021 Sep 23:ATVBAHA121316574. Epub 2021 Sep 23.

Department of Medicine, Division of Cardiology, Emory University School of Medicine, Atlanta, GA. (Z.A., J.H.K., M.G., K.M., B.L., A.M., A.J.S., M.S.H., V.V., A.A.Q.).

Objective: Circulating progenitor cells possess immune modulatory properties and might mitigate inflammation that is characteristic of patients with coronary artery disease. We hypothesized that patients with fewer circulating progenitor cells (CPCs) will have higher inflammatory markers and worse outcomes. Approach and Results: Patients with stable coronary artery disease were enrolled in a prospective study enumerating CPCs as CD (cluster of differentiation)-34-expressing mononuclear cells (CD34+) and inflammation as levels of IL (interleukin)-6 and high-sensitivity CRP (C-reactive protein) levels. Patients were followed for 5 years for the end points of death and myocardial infarction with repeat inflammatory biomarkers measured after a median of 2 years. In the entire cohort of 392 patients, IL-6 and high-sensitivity CRP levels remained unchanged (0.3±2.4 pg/mL and 0.1±1.0 mg/L; =0.45) after 2 years. CPC counts (log-transformed) were inversely correlated with the change in IL-6 levels (r, -0.17; <0.001). Using linear regression, IL-6 and high-sensitivity CRP levels declined by -0.59 (95% CI, -0.90 to -0.20) pg/mL and -0.13 (-0.28 to 0.01) mg/L per 1 log higher CPC counts after adjustment for the demographic and clinical variables, as well as medications. Using Cox models adjusted for these risk factors, a rise in 1 pg/mL of IL-6 was associated with a 11% (95% CI, 9-13) greater risk of death/myocardial infarction. We found that the change in IL6 level partly (by 40%) mediated the higher risk of adverse events among those with low CPC counts.

Conclusions: Reduced cardiovascular regenerative capacity is independently associated with progressive inflammation in patients with coronary artery disease that in turn is associated with poor outcomes.
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http://dx.doi.org/10.1161/ATVBAHA.121.316574DOI Listing
September 2021

Association of physical activity with arterial stiffness among Black adults.

Vasc Med 2021 Sep 22:1358863X211032725. Epub 2021 Sep 22.

Division of Cardiology, Department of Medicine, Emory University School of Medicine, Atlanta, GA, USA.

Arterial stiffness is a precursor for the development of hypertension and premature cardiovascular disease (CVD). Physical activity has been associated with lower arterial stiffness among largely White populations, but the types of activity required and whether these findings apply to Black adults remain unknown. We examined whether physical activity levels were associated with arterial stiffness among Black adults in two independent cohorts. In the Morehouse-Emory Cardiovascular (MECA) Center for Health Equity, 378 Black adults (age 52.8 ± 10.3, 39.7% male) without known CVD living in Atlanta, GA were recruited. Arterial stiffness was measured as pulse wave velocity (PWV). Total and domain-specific physical activity were assessed by self-report. Multiple linear regression models were used to investigate differences across physical activity levels after adjusting for age, sex, CVD risk factors, and socioeconomic status. Findings were validated in an independent cohort of Black adults ( = 55, age 50.4 ± 9.2, 23.6% male). After adjustment for covariates, lower arterial stiffness was associated with higher self-reported levels of sport/exercise (6.92 ± 1.13 vs 7.75 ± 1.14, < 0.001, highest vs lowest quartile) and home/life activities (7.34 ± 1.24 vs 7.73 ± 1.07, = 0.04, highest vs lowest quartile), but not work, active living, or the overall physical activity scores. These findings were replicated in the independent cohort where higher levels of sport/exercise remained associated with lower arterial stiffness (6.66 ± 0.57 vs 8.21 ± 0.66, < 0.001, highest vs lowest quartile). Higher levels of sport/exercise and home/life-related physical activities (in comparison to occupational physical activity) are associated with lower arterial stiffness in Black adults.
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http://dx.doi.org/10.1177/1358863X211032725DOI Listing
September 2021

Association Between Early Trauma and Ideal Cardiovascular Health Among Black Americans: Results From the Morehouse-Emory Cardiovascular (MECA) Center for Health Equity.

Circ Cardiovasc Qual Outcomes 2021 09 12;14(9):e007904. Epub 2021 Aug 12.

Department of Epidemiology (V.V., T.T.L.), Emory University, Atlanta, GA.

Background: Early trauma (general, emotional, physical, and sexual abuse before age 18 years) has been associated with both cardiovascular disease risk and lifestyle-related risk factors for cardiovascular disease, including smoking, obesity, and physical inactivity. Despite higher prevalence, the association between early trauma and cardiovascular health (CVH) has been understudied in Black Americans, especially those from low-income backgrounds, who may be doubly vulnerable. Therefore, we investigated the association between early trauma and CVH, particularly among low-income Black Americans.

Methods: We recruited 457 Black adults (age 53±10, 38% male) without known cardiovascular disease from the Atlanta, GA, metropolitan area using personalized, community-based recruitment methods. The Early Trauma Inventory was administered to assess overall early traumatic life experiences which include physical, sexual, emotional abuse, and general trauma. Our primary outcome was the American Heart Association Life's Simple 7, which is a set of 7 CVH metrics, including 4 lifestyle-related factors (smoking, body mass index, physical activity, and diet) and three physiologically measured health factors (blood pressure, total blood cholesterol, and blood glucose). We used linear regression models adjusting for age, sex, socioeconomic status, and depression to test the association between early trauma and CVH and tested the early trauma by household income (<$50 000) interaction.

Results: Higher levels of early trauma were associated with lower Life's Simple 7 scores (β, -0.05 [95% CI, -0.09 to -0.01], =0.02, per 1 unit increase in the Early Trauma Inventory score) among lower, but not higher, income Black participants ( value for interaction=0.04). Subtypes of early trauma linked to Life's Simple 7 were general trauma, emotional abuse, and sexual abuse. Exploratory analyses demonstrated that early trauma was only associated with the body mass index and smoking components of Life's Simple 7.

Conclusions: Early trauma, including general trauma, emotional abuse, and sexual abuse, may be associated with worse CVH among low-, but not higher-income Black adults.
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http://dx.doi.org/10.1161/CIRCOUTCOMES.121.007904DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8455434PMC
September 2021

Rapid generation of mouse model for emerging infectious disease with the case of severe COVID-19.

PLoS Pathog 2021 08 11;17(8):e1009758. Epub 2021 Aug 11.

Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan.

Since the pandemic of COVID-19 has intensely struck human society, small animal model for this infectious disease is in urgent need for basic and pharmaceutical research. Although several COVID-19 animal models have been identified, many of them show either minimal or inadequate pathophysiology after SARS-CoV-2 challenge. Here, we describe a new and versatile strategy to rapidly establish a mouse model for emerging infectious diseases in one month by multi-route, multi-serotype transduction with recombinant adeno-associated virus (AAV) vectors expressing viral receptor. In this study, the proposed approach enables profound and enduring systemic expression of SARS-CoV-2-receptor hACE2 in wild-type mice and renders them vulnerable to SARS-CoV-2 infection. Upon virus challenge, generated AAV/hACE2 mice showed pathophysiology closely mimicking the patients with severe COVID-19. The efficacy of a novel therapeutic antibody cocktail RBD-chAbs for COVID-19 was tested and confirmed by using this AAV/hACE2 mouse model, further demonstrating its successful application in drug development.
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http://dx.doi.org/10.1371/journal.ppat.1009758DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8415591PMC
August 2021

A non-neutralizing antibody broadly protects against influenza virus infection by engaging effector cells.

PLoS Pathog 2021 Aug 5;17(8):e1009724. Epub 2021 Aug 5.

Genomics Research Center, Academia Sinica, Taipei, Taiwan.

Hemagglutinin (HA) is the immunodominant protein of the influenza virus. We previously showed that mice injected with a monoglycosylated influenza A HA (HAmg) produced cross-strain-reactive antibodies and were better protected than mice injected with a fully glycosylated HA (HAfg) during lethal dose challenge. We employed a single B-cell screening platform to isolate the cross-protective monoclonal antibody (mAb) 651 from mice immunized with the HAmg of A/Brisbane/59/2007 (H1N1) influenza virus (Bris/07). The mAb 651 recognized the head domain of a broad spectrum of HAs from groups 1 and 2 influenza A viruses and offered prophylactic and therapeutic efficacy against A/California/07/2009 (H1N1) (Cal/09) and Bris/07 infections in mice. The antibody did not possess neutralizing activity; however, antibody-dependent cellular cytotoxicity and antibody-dependent cellular phagocytosis mediated by natural killer cells and alveolar macrophages were important in the protective efficacy of mAb 651. Together, this study highlighted the significance of effector functions for non-neutralizing antibodies to exhibit protection against influenza virus infection.
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http://dx.doi.org/10.1371/journal.ppat.1009724DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8341508PMC
August 2021

Identifying neighbourhood and individual resilience profiles for cardiovascular health: a cross-sectional study of blacks living in the Atlanta metropolitan area.

BMJ Open 2021 07 30;11(7):e041435. Epub 2021 Jul 30.

Department of Epidemiology, Emory University Rollins School of Public Health, Atlanta, Georgia, USA.

Objective: To simultaneously examine multiple individual-level neighbourhood perceptions and psychosocial characteristics and their relationships with cardiovascular health (CVH) among blacks.

Design: Cross-sectional study.

Setting: Subjects were recruited between 2016 and 2018 via convenience sampling.

Participants: 385 Black men and women, age 30-70 living in the Atlanta metropolitan area (Georgia, USA).

Primary Outcome Measure: Individual's CVH was summarised as a composite score using American Heart Association's Life's Simple 7 (LS7) metrics.

Methods: We implemented unsupervised learning (k-means) and supervised learning (Bayesian Dirichlet process clustering) to identify clusters based on 11 self-reported neighbourhood perception and psychosocial characteristics. We also performed principal component analysis to summarise neighbourhood perceptions and psychosocial variables and assess their associations with LS7 scores.

Results: K-means and Bayesian clustering resulted in 4 and 5 clusters, respectively. Based on the posterior distributions, higher LS7 scores were associated with better neighbourhood perceptions and psychosocial characteristics, including neighbourhood safety, social cohesion, activities with neighbours, environmental mastery, purpose in life, resilient coping and no depression. Taken together, the first principal components of neighbourhood perceptions and psychosocial characteristics were associated with an increase of 0.07 (95% CI -0.17 to 0.31) and 0.31 (95% CI 0.06 to 0.55) in LS7 score, respectively, after accounting for age, sex, household income and education level.

Conclusion: Both neighbourhood perception and psychosocial domains were related to CVH, but individual psychosocial characteristics appeared to contribute to CVH most. Approaches that acknowledge the importance of factors in both domains may prove most beneficial for enhancing resilience and promoting CVH among black communities.
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http://dx.doi.org/10.1136/bmjopen-2020-041435DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8327812PMC
July 2021

Temporal trends in the association of social vulnerability and race/ethnicity with county-level COVID-19 incidence and outcomes in the USA: an ecological analysis.

BMJ Open 2021 07 22;11(7):e048086. Epub 2021 Jul 22.

Department of Medicine, Division of Cardiology, Emory University School of Medicine, Atlanta, Georgia, USA

Background: The COVID-19 pandemic adversely affected the socially vulnerable and minority communities in the USA initially, but the temporal trends during the year-long pandemic remain unknown.

Objective: We examined the temporal association of county-level Social Vulnerability Index (SVI), a percentile-based measure of social vulnerability to disasters, its subcomponents and race/ethnic composition with COVID-19 incidence and mortality in the USA in the year starting in March 2020.

Methods: Counties (n=3091) with ≥50 COVID-19 cases by 6 March 2021 were included in the study. Associations between SVI (and its subcomponents) and county-level racial composition with incidence and death per capita were assessed by fitting a negative-binomial mixed-effects model. This model was also used to examine potential time-varying associations between weekly number of cases/deaths and SVI or racial composition. Data were adjusted for percentage of population aged ≥65 years, state-level testing rate, comorbidities using the average Hierarchical Condition Category score, and environmental factors including average fine particulate matter of diameter ≥2.5 μm, temperature and precipitation.

Results: Higher SVI, indicative of greater social vulnerability, was independently associated with higher COVID-19 incidence (adjusted incidence rate ratio per 10 percentile increase: 1.02, 95% CI 1.02 to 1.03, p<0.001) and death per capita (1.04, 95% CI 1.04 to 1.05, p<0.001). SVI became an independent predictor of incidence starting from March 2020, but this association became weak or insignificant by the winter, a period that coincided with a sharp increase in infection rates and mortality, and when counties with higher proportion of white residents were disproportionately represented ('third wave'). By spring of 2021, SVI was again a predictor of COVID-19 outcomes. Counties with greater proportion of black residents also observed similar temporal trends in COVID-19-related adverse outcomes. Counties with greater proportion of Hispanic residents had worse outcomes throughout the duration of the analysis.

Conclusion: Except for the winter 'third wave', when majority of the white communities had the highest incidence of cases, counties with greater social vulnerability and proportionately higher minority populations experienced worse COVID-19 outcomes.
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http://dx.doi.org/10.1136/bmjopen-2020-048086DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8300549PMC
July 2021

Non-Invasive Cervical Vagal Nerve Stimulation Alters Brain Activity During Traumatic Stress in Individuals with Posttraumatic Stress Disorder.

Psychosom Med 2021 Jul 21. Epub 2021 Jul 21.

Department of Psychiatry & Behavioral Sciences, Emory University School of Medicine, Atlanta, GA School of Electrical and Computer Engineering, Georgia Institute of Technology, Atlanta GA Department of Radiology and Imaging Sciences, Emory University School of Medicine, Atlanta, GA Department of Epidemiology, Rollins School of Public Health, Emory University, Atlanta GA Department of Medicine (Cardiology), Emory University School of Medicine, Atlanta, GA Atlanta VA Medical Center, Decatur, GA Department of Biostatistics and Bioinformatics, Rollins School of Public Health, Emory University, Atlanta GA Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology, Atlanta, GA.

Objective: Posttraumatic stress disorder (PTSD) is a disabling condition affecting a large segment of the population, however current treatment options have limitations. New interventions that target the neurobiological alterations underlying symptoms of PTSD could be highly beneficial. Transcutaneous cervical (neck) vagal nerve stimulation (tcVNS) has the potential to represent such an intervention. The goal of this study is to determine the effects of tcVNS on neural responses to reminders of traumatic stress in PTSD.

Methods: Twenty-two participants were randomized to receive either sham (n = 11) or active (n = 11) tcVNS stimulation in conjunction with exposure to neutral and personalized traumatic stress scripts with High-Resolution Positron Emission Tomography scanning with radiolabeled water for brain blood flow measurements.

Results: Compared to sham, tcVNS increased brain activations during trauma scripts (p < 0.005) within the bilateral frontal and temporal lobes, left hippocampus, posterior cingulate, and anterior cingulate (dorsal and pregenual), and right postcentral gyrus. Greater deactivations (p < 0.005) with tcVNS were observed within the bilateral frontal and parietal lobes and left thalamus. Compared to tcVNS, sham elicited greater activations (p < 0.005) in the bilateral frontal lobe, left precentral gyrus, precuneus, and thalamus, and right temporal and parietal lobes, hippocampus, insula, and posterior cingulate. Greater (p < 0.005) deactivations were observed with sham in the right temporal lobe, posterior cingulate, hippocampus, left anterior cingulate, and bilateral cerebellum.

Conclusion: tcVNS increased anterior cingulate and hippocampus activation during trauma scripts, potentially indicating a reversal of neurobiological changes with PTSD consistent with improved autonomic control.Trial Registration#NCT02992899.
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http://dx.doi.org/10.1097/PSY.0000000000000987DOI Listing
July 2021

A genome-first approach to mortality and metabolic phenotypes in p.Ala165Thr (rs2642438) heterozygotes and homozygotes.

Med (N Y) 2021 Jul;2(7):851-863.e3

Division of Translational Medicine and Human Genetics, The Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.

Background: A coding variant in (rs2642438; p.Ala165Thr) was recently associated with protection from cirrhosis in European individuals. However, its impact on overall and cause-specific mortality remained elusive.

Methods: Using a genome-first approach, we explored a range of metabolic phenotypes and outcomes associated with p.Ala165Thr in the UKBiobank and the Penn-Medicine BioBank.

Findings: p.Ala165Thr was significantly associated with higher triglycerides, lower total cholesterol, lower LDL-C, lower ApoB, lower HDL-C, lower ApoA-I and higher IGF-1. Per each minor allele, the risk of NAFLD was reduced by ~15%. The ALT-lowering and NAFLD-protective effect of p.Ala165Thr was amplified by obesity, diabetes mellitus and presence of rs738409:G. In African-American and Black-British individuals, the allele frequency of p.Ala165Thr was lower, but carriers showed the same distinctive lipid phenotype. Importantly, p.Ala165Thr carriers did not show higher cardiovascular disease burden as evidenced by cardiac MRI and carotid ultrasound. In prospective analyses, the homozygous minor allele was associated with up to 39% lower rates of liver-related mortality, while no risk of increased overall or cardiovascular death could be observed. Strikingly, liver-related mortality was more than 50% reduced in diabetic participants or carriers of rs738409:G.

Conclusions: Together these data highlight as an important liver disease modifier that influences plasma lipids in an allele-dose-dependent manner without increasing cardiovascular outcomes. Our results point toward potential mechanisms and reveal a remarkable association with liver-related mortality calling for future studies exploring its therapeutic potential.

Funding: This study was funded by the German Research Foundation (DFG).
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http://dx.doi.org/10.1016/j.medj.2021.04.011DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8274545PMC
July 2021

Evaluation of two population screening programmes for founder mutations in the Australian Jewish community: a protocol paper.

BMJ Open 2021 06 25;11(6):e041186. Epub 2021 Jun 25.

Hereditary Cancer Centre, Prince of Wales Hospital Cancer Services, Randwick, New South Wales, Australia.

Introduction: People of Ashkenazi Jewish (AJ) ancestry are more likely than unselected populations to have a pathogenic variant, which cause a significantly increased risk of breast, ovarian and prostate cancer. Three specific pathogenic variants, referred to as -Jewish founder mutations (B-JFM), account for >90% of pathogenic variants in people of AJ ancestry. Current practice of identifying eligible individuals for testing based on personal and/or family history has been shown to miss at least 50% of people who have one of these variants. Here we describe the protocol of the JeneScreen study-a study established to develop and evaluate two different population-based B-JFM screening programmes, offered to people of Jewish ancestry in Sydney and Melbourne, Australia.

Methods And Analysis: To rmeasure the acceptability of population-based B-JFM screening in Australia, two screening programmes using different methodologies have been developed. The Sydney JeneScreen programme provides information and obtains informed consent by way of an online tool. The Melbourne JeneScreen programme does this by way of community sessions attended in person. Participants complete questionnaires to measure clinical and psychosocial outcomes at baseline, and for those who have testing, 2 weeks postresult. Participants who decline testing are sent a questionnaire regarding reasons for declining. Participants with a B-JFM are sent questionnaires 12-month and 24-month post-testing. The questionnaires incorporate validated scales, which measure anxiety, decisional conflict and regret, and test-related distress and positive experiences, and other items specifically developed or adapted for the study. These measures will be assessed for each programme and the two population-based B-JFM screening methods will be compared.

Ethics And Dissemination: Institutional Human Research Ethics Committee approval was obtained from the South Eastern Area Health Service Human Research Ethics Committee: HREC Ref 16/125.Following the analysis of the study results, the findings will be disseminated widely through conferences and publications, and directly to participants in writing.
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http://dx.doi.org/10.1136/bmjopen-2020-041186DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8237737PMC
June 2021

Ecological Analysis of the Temporal Trends in the Association of Social Vulnerability and Race/Ethnicity with County-Level COVID-19 Incidence and Outcomes in the United States.

medRxiv 2021 Jun 7. Epub 2021 Jun 7.

Department of Medicine, Division of Cardiology, Emory University School of Medicine, Atlanta, GA.

Background: The COVID-19 pandemic adversely affected the socially vulnerable and minority communities in the U.S. initially, but the temporal trends during the year-long pandemic remain unknown.

Objective: We examined the temporal association between the county-level Social Vulnerability Index (SVI), a percentile-based measure of social vulnerability to disasters, its subcomponents and race/ethnic composition with COVID-19 incidence and mortality in the U.S. in the year starting in March 2020.

Methods: Counties (n=3091) with ≥ 50 COVID-19 cases by March 6 , 2021 were included in the study. Associations between SVI (and its subcomponents) and county level racial composition with the incidence and death per capita were assessed by fitting a negative-binomial mixed-effects model. This model was also used to examine potential time varying associations between weekly number of cases/deaths and SVI or racial composition. Data was adjusted for percentage of population aged ≥65 years, state level testing rate, comorbidities using the average Hierarchical Condition Category (HCC) score, and environmental factors including average fine particulate matter (PM ), temperature and precipitation.

Results: Higher SVI, indicative of greater social vulnerability, was independently associated with higher COVID-19 incidence (adjusted incidence rate ratio [IRR] per-10 percentile increase:1.02, (95% CI 1.02, 1.03, p<0.001), and death per capita (1.04, (95% CI 1.04, 1.05, p<0.001). SVI became an independent predictor of incidence starting from March 2020, but this association became weak or insignificant by the winter, a period that coincided with a sharp increase in infection rates and mortality, and when counties with higher proportion of White residents were disproportionately represented ("third wave"). By Spring of 2021, SVI was again a predictor of COVID-19 outcomes. Counties with greater proportion of Black residents also observed similar temporal trends COVID-19-related adverse outcomes. Counties with greater proportion of Hispanic residents had worse outcomes throughout the duration of the analysis.

Conclusion: Except for the winter "third wave" when majority White communities had the highest incidence of cases, counties with greater social vulnerability and proportionately higher minority populations, experienced worse COVID-19 outcomes.

Article Summary/strengths & Limitations: Examined full 12 months of county-level data in the US delineating the temporal trends in the association between social vulnerability index and COVID-19 outcomesInvestigated COVID-19 outcomes in predominantly Black and Hispanic communities in comparison to White communities in the USAnalysis is ecological, descriptive, and on the county-level rather than on an individual levelAnalysis adjusted for confounders including county level age ≥ 65, comorbidities, and environmental factorsAnalysis limited to the US.
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http://dx.doi.org/10.1101/2021.06.04.21258355DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8202439PMC
June 2021

Association of Depressive Symptoms with Sleep Disturbance: A Co-twin Control Study.

Ann Behav Med 2021 May 15. Epub 2021 May 15.

Department of Epidemiology, Rollins School of Public Health, Emory University, Atlanta, GA, USA.

Background: Few studies have comprehensively evaluated the association of depression with sleep disturbance using a controlled twin study design.

Purpose: To cross-sectionally evaluate the association of depression with both objective and subjective sleep disturbance.

Methods: We studied 246 members of the Vietnam Era Twin Registry. We measured depressive symptoms using the Beck Depression Inventory-II (BDI) and assessed major depression using structured clinical interviews. Twins underwent one-night polysomnography and 7-day actigraphy to derive measures of objective sleep and completed the Pittsburgh Sleep Quality Index for subjective sleep. Multivariable mixed-effects models were used to examine the association.

Results: Twins were all male, mostly white (97%), with a mean (SD) age of 68 (2). The mean (SD) BDI was 5.9 (6.3), and 49 (20%) met the criteria for major depression. For polysomnography, each 5-unit higher BDI, within-pair, was significantly associated with 19.7 min longer rapid eye movement (REM) sleep latency, and 1.1% shorter REM sleep after multivariable adjustment. BDI was not associated with sleep architecture or sleep-disordered breathing. For actigraphy, a higher BDI, within-pair, was significantly associated with lower sleep efficiency, more fragmentation and higher variability in sleep duration. BDI was associated with almost all dimensions of self-reported sleep disturbance. Results did not differ by zygosity, and remained consistent using major depression instead of BDI and were independent of the presence of comorbid posttraumatic stress disorder and antidepressant use.

Conclusions: Depression is associated with REM sleep disruption in lab and sleep fragmentation and sleep variability at home, but not with sleep architecture or sleep-disordered breathing.
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http://dx.doi.org/10.1093/abm/kaab040DOI Listing
May 2021

Impact of Technology-Based Intervention for Improving Self-Management Behaviors in Black Adults with Poor Cardiovascular Health: A Randomized Control Trial.

Int J Environ Res Public Health 2021 04 1;18(7). Epub 2021 Apr 1.

Department of Medicine, Morehouse School of Medicine, Atlanta, GA 30310, USA.

Cardiovascular disease (CVD) is the number one killer of adults in the U.S., with marked ethnic/racial disparities in prevalence, risk factors, associated health behaviors, and death rates. In this study, we recruited and randomized Blacks with poor cardiovascular health in the Atlanta Metro area to receive an intervention comparing two approaches to engagement with a behavioral intervention technology for CVD. Generalized Linear Mixed Models results from a 6-month intervention indicate that 53% of all participants experienced a statistical improvement in Life's Simple 7 (LS7), 54% in BMI, 61% in blood glucose, and 53% in systolic blood pressure. Females demonstrated a statistically significant improvement in BMI and diastolic blood pressure and a reduction in self-reported physical activity. We found no significant differences in changes in LS7 or their constituent parts but found strong evidence that health coaches can help improve overall LS7 in participants living in at-risk neighborhoods. In terms of clinical significance, our result indicates that improvements in LS7 correspond to a 7% lifetime reduction of incident CVD. Our findings suggest that technology-enabled self-management can be effective for managing selected CVD risk factors among Blacks.
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http://dx.doi.org/10.3390/ijerph18073660DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8036364PMC
April 2021

Vascular Regenerative Capacity and the Obesity Paradox in Coronary Artery Disease.

Arterioscler Thromb Vasc Biol 2021 06 15;41(6):2097-2108. Epub 2021 Apr 15.

Division of Cardiology, Department of Medicine, Emory Clinical Cardiovascular Research Institute (A. Mehta, S.J.I., D.S.D., Z.A., A.N., A.A.A., A.H., A.V., S.F.A., A. Mokhtari, I.H., L.S.S., Y.-A.K., A.A.Q.), Emory University School of Medicine, Atlanta, GA.

[Figure: see text].
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http://dx.doi.org/10.1161/ATVBAHA.120.315703DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8147702PMC
June 2021

Age, rehabilitation and surgery characteristics are re-injury risk factors for adolescents following anterior cruciate ligament reconstruction.

Phys Ther Sport 2021 May 8;49:196-203. Epub 2021 Mar 8.

Department of Physical Therapy, Georgia State University, Atlanta, GA, USA. Electronic address:

Objectives: To examine the effect of age on post-ACLR rehabilitative outcomes and identify surgical/rehabilitative characteristics as ACL re-injury risk factors in adolescents.

Design: Cohort study.

Setting: Children's hospital.

Participants: 273 adolescents with first-time ACLR.

Main Outcome Measures: Demographics, injury history, surgery, and outcomes documented during post-ACLR physical therapy (PT) sessions were extracted from medical records. Effects of age on outcomes were examined using multivariate regression. ACL re-injury risk factors were identified using survival analysis with Cox regression.

Results: Re-injury was recorded in 47 patients (17.2%) with a median follow-up time of 3.1 years and median re-injury time of 13.4 months post-surgery. Younger age (Hazard-Ratio, HR = 1.264 per year decrease; P = 0.005), receiving surgery within 1 month post-injury (HR = 3.378 vs. >3 months; P = 0.012), starting PT within 3 days post-surgery (HR = 3.068; P = 0.022), and decreased number of PT sessions (HR = 1.118 per 3-session decrease; P = 0.010) increased re-injury risk. Although age was associated with re-injury risk, age was not associated with any outcome (P > 0.059).

Conclusion: Adolescents who are younger, receive surgery and post-surgery PT sooner, or attend fewer PT sessions may be at an increased re-injury risk. Younger patients achieved similar outcomes despite elevated re-injury risk. Current discharge criteria are inadequate in identifying high re-injury risk patients.
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http://dx.doi.org/10.1016/j.ptsp.2021.03.003DOI Listing
May 2021

Creation and Validation of a Novel Sex-Specific Mortality Risk Score in LVAD Recipients.

J Am Heart Assoc 2021 04 25;10(7):e020019. Epub 2021 Mar 25.

Division of Cardiology Department of Medicine Emory Clinical Cardiovascular Research InstituteEmory University School of Medicine Atlanta GA.

Background Prior studies have shown that women have worse 3-month survival after receiving a left ventricular assist device compared with men. Currently used prognostic scores, including the Heartmate II Risk Score, do not account for the increased residual risk in women. We used the IMACS (International Society for Heart and Lung Transplantation Mechanically Assisted Circulatory Support) registry to create and validate a sex-specific risk score for early mortality in left ventricular assist device recipients. Methods and Results Adult patients with a continuous-flow LVAD from the IMACS registry were randomly divided into a derivation cohort (DC; n=9113; 21% female) and a validation cohort (VC; n=6074; 21% female). The IMACS Risk Score was developed in the DC to predict 3-month mortality, from preoperative candidate predictors selected using the Akaike information criterion, or significant sex × variable interaction. In the DC, age, cardiogenic shock at implantation, body mass index, blood urea nitrogen, bilirubin, hemoglobin, albumin, platelet count, left ventricular end-diastolic diameter, tricuspid regurgitation, dialysis, and major infection before implantation were retained as significant predictors of 3-month mortality. There was significant ischemic heart failure × sex and platelet count × sex interaction. For each quartile increase in IMACS risk score, men (odds ratio [OR], 1.86; 95% CI, 1.74-2.00; <0.0001), and women (OR, 1.93; 95% CI, 1.47-2.59; <0.0001) had higher odds of 3-month mortality. The IMACS risk score represented a significant improvement over Heartmate II Risk Score (IMACS risk score area under the receiver operating characteristic curve: men: DC, 0.71; 95% CI, 0.69-0.73; VC, 0.69; 95% CI, 0.66-0.72; women: DC, 0.73; 95% CI, 0.70-0.77; VC, 0.71 [95% CI, 0.66-0.76; <0.01 for improvement in receiver operating characteristic) and provided excellent risk calibration in both sexes. Removal of sex-specific interaction terms resulted in significant loss of model fit. Conclusions A sex-specific risk score provides excellent risk prediction in LVAD recipients.
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http://dx.doi.org/10.1161/JAHA.120.020019DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8174331PMC
April 2021

Genetically determined NLRP3 inflammasome activation associates with systemic inflammation and cardiovascular mortality.

Eur Heart J 2021 05;42(18):1742-1756

Emory Clinical Cardiovascular Research Institute, Division of Cardiology, Emory University School of Medicine, 1462 Clifton Road NE, Atlanta, GA 30322, USA.

Aims: Inflammation plays an important role in cardiovascular disease (CVD) development. The NOD-like receptor protein-3 (NLRP3) inflammasome contributes to the development of atherosclerosis in animal models. Components of the NLRP3 inflammasome pathway such as interleukin-1β can therapeutically be targeted. Associations of genetically determined inflammasome-mediated systemic inflammation with CVD and mortality in humans are unknown.

Methods And Results: We explored the association of genetic NLRP3 variants with prevalent CVD and cardiovascular mortality in 538 167 subjects on the individual participant level in an explorative gene-centric approach without performing multiple testing. Functional relevance of single-nucleotide polymorphisms on NLRP3 inflammasome activation has been evaluated in monocyte-enriched peripheral blood mononuclear cells (PBMCs). Genetic analyses identified the highly prevalent (minor allele frequency 39.9%) intronic NLRP3 variant rs10754555 to affect NLRP3 gene expression. rs10754555 carriers showed significantly higher C-reactive protein and serum amyloid A plasma levels. Carriers of the G allele showed higher NLRP3 inflammasome activation in isolated human PBMCs. In carriers of the rs10754555 variant, the prevalence of coronary artery disease was significantly higher as compared to non-carriers with a significant interaction between rs10754555 and age. Importantly, rs10754555 carriers had significantly higher risk for cardiovascular mortality during follow-up. Inflammasome inducers (e.g. urate, triglycerides, apolipoprotein C3) modulated the association between rs10754555 and mortality.

Conclusion: The NLRP3 intronic variant rs10754555 is associated with increased systemic inflammation, inflammasome activation, prevalent coronary artery disease, and mortality. This study provides evidence for a substantial role of genetically driven systemic inflammation in CVD and highlights the NLRP3 inflammasome as a therapeutic target.
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http://dx.doi.org/10.1093/eurheartj/ehab107DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8244638PMC
May 2021

Genome-first approach to rare EYA4 variants and cardio-auditory phenotypes in adults.

Hum Genet 2021 Jun 21;140(6):957-967. Epub 2021 Mar 21.

Department of Genetics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.

While newborns and children with hearing loss are routinely offered genetic testing, adults are rarely clinically tested for a genetic etiology. One clinically actionable result from genetic testing in children is the discovery of variants in syndromic hearing loss genes. EYA4 is a known hearing loss gene which is also involved in important pathways in cardiac tissue. The pleiotropic effects of rare EYA4 variants are poorly understood and their prevalence in a large cohort has not been previously reported. We investigated cardio-auditory phenotypes in 11,451 individuals in a large biobank using a rare variant, genome-first approach to EYA4. We filtered 256 EYA4 variants carried by 6737 participants to 26 rare and predicted deleterious variants carried by 42 heterozygotes. We aggregated predicted deleterious EYA4 gene variants into a combined variable (i.e. "gene burden") and performed association studies across phenotypes compared to wildtype controls. We validated findings with replication in three independent cohorts and human tissue expression data. EYA4 gene burden was significantly associated with audiometric-proven HL (p = [Formula: see text], Mobitz Type II AV block (p = [Formula: see text]) and the syndromic presentation of HL and primary cardiomyopathy (p = 0.0194). Analyses on audiogram, echocardiogram, and electrocardiogram data validated these associations. Prior reports have focused on identifying variants in families with severe or syndromic phenotypes. In contrast, we found, using a genotype-first approach, that gene burden in EYA4 is associated with more subtle cardio-auditory phenotypes in an adult medical biobank population, including cardiac conduction disorders which have not been previously reported. We show the value of using a focused approach to uncover human disease related to pleiotropic gene variants and suggest a role for genetic testing in adults presenting with hearing loss.
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http://dx.doi.org/10.1007/s00439-021-02263-6DOI Listing
June 2021

Impaired Peripheral Microvascular Function and Risk of Major Adverse Cardiovascular Events in Patients With Coronary Artery Disease.

Arterioscler Thromb Vasc Biol 2021 05 18;41(5):1801-1809. Epub 2021 Mar 18.

Department of Epidemiology (A.Y., MG., S.M.S., C.L., K.M., A.J.S., B.P., I.U., V.V.), Rollins School of Public Health, Emory University, Atlanta, GA.

[Figure: see text].
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http://dx.doi.org/10.1161/ATVBAHA.121.316083DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8062308PMC
May 2021

Reframing Recruitment: Evaluating Framing in Authorization for Research Contact Programs.

AJOB Empir Bioeth 2021 Jul-Sep;12(3):206-213. Epub 2021 Mar 15.

Emory University, School of Medicine, Atlanta, Georgia, USA.

Background: The changing clinical research recruitment landscape involves practical challenges but introduces opportunities. Researchers can now identify large numbers of eligible patients through electronic health record review and can directly contact those who have authorized contact. Applying behavioral science-driven strategies to design and frame communication could affect patients' willingness to authorize contact and their understanding of these programs. The ethical and practical implications of various strategies warrant empirical evaluation.

Methods: We conducted an online survey ( = 1070) using a nationally-representative sample. Participants were asked to imagine being asked for authorization for research contact in clinic. They were randomly assigned to view one of three flyers: #1-neutral text flyer; #2-a positive text flyer; or #3-positive graphics-based flyer. Primary outcomes included likelihood of enrollment and comprehension of the program. Chi-Square tests and regression analyses were used to examine whether those who saw the positive flyers were more likely to enroll and had increased comprehension.

Results: Compared to the neutral flyer, individuals who received the positive text flyer were numerically more likely to enroll, but this was not statistically significant (24.2% v. 19.0%,  = 0.11). Individuals who received the positive graphics flyer were more likely to enroll (28.7% v. 19.0%,  = 0.002). After adjustment, individuals assigned to both novel flyers had increased odds of being likely to enroll (OR = 1.55 95%CI [1.04, 2.31] and OR = 1.95 95%CI [1.31, 2.91]). Flyer type did not affect overall comprehension ( = 0.21), and greater likelihood of enrollment was observed only in individuals with better comprehension.

Conclusions: This study demonstrated that employing behavioral science-driven communication strategies for authorization for research contact had an effect on likelihood of hypothetical enrollment but did not significantly affect comprehension. Strategies using simple, positive language and visual tools may be effective and ethically appropriate. Further studies should explore how these and other approaches can help to optimize research recruitment.
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http://dx.doi.org/10.1080/23294515.2021.1887962DOI Listing
October 2021

Quantification of abdominal fat from computed tomography using deep learning and its association with electronic health records in an academic biobank.

J Am Med Inform Assoc 2021 06;28(6):1178-1187

Department of Radiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.

Objective: The objective was to develop a fully automated algorithm for abdominal fat segmentation and to deploy this method at scale in an academic biobank.

Materials And Methods: We built a fully automated image curation and labeling technique using deep learning and distributive computing to identify subcutaneous and visceral abdominal fat compartments from 52,844 computed tomography scans in 13,502 patients in the Penn Medicine Biobank (PMBB). A classification network identified the inferior and superior borders of the abdomen, and a segmentation network differentiated visceral and subcutaneous fat. Following technical evaluation of our method, we conducted studies to validate known relationships with visceral and subcutaneous fat.

Results: When compared with 100 manually annotated cases, the classification network was on average within one 5-mm slice for both the superior (0.4 ± 1.1 slice) and inferior (0.4 ± 0.6 slice) borders. The segmentation network also demonstrated excellent performance with intraclass correlation coefficients of 1.00 (P < 2 × 10-16) for subcutaneous and 1.00 (P < 2 × 10-16) for visceral fat on 100 testing cases. We performed integrative analyses of abdominal fat with the phenome extracted from the electronic health record and found highly significant associations with diabetes mellitus, hypertension, and renal failure, among other phenotypes.

Conclusions: This work presents a fully automated and highly accurate method for the quantification of abdominal fat that can be applied to routine clinical imaging studies to fuel translational scientific discovery.
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http://dx.doi.org/10.1093/jamia/ocaa342DOI Listing
June 2021

Kidney disease genetic risk variants alter lysosomal beta-mannosidase () expression and disease severity.

Sci Transl Med 2021 01;13(576)

Department of Medicine Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.

More than 800 million people in the world suffer from chronic kidney disease (CKD). Genome-wide association studies (GWAS) have identified hundreds of loci where genetic variants are associated with kidney function; however, causal genes and pathways for CKD remain unknown. Here, we performed integration of kidney function GWAS and human kidney-specific expression quantitative trait analysis and identified that the expression of beta-mannosidase () was lower in kidneys of subjects with CKD risk genotype. We also show an increased incidence of renal failure in subjects with rare heterozygous loss-of-function coding variants in using phenome-wide association analysis of 40,963 subjects with exome sequencing data. is a lysosomal gene highly expressed in kidney tubule cells. Deep phenotyping revealed structural and functional lysosomal alterations in human kidneys from subjects with CKD risk alleles and mice with genetic deletion of heterozygous and knockout mice developed more severe kidney fibrosis when subjected to toxic injury induced by cisplatin or folic acid. loss altered multiple pathways, including endocytosis and autophagy. In the absence of toxic acute tubule injury induced inflammasome activation and fibrosis. Together, these results illustrate the convergence of common noncoding and rare coding variants in in kidney disease development and demonstrate the role of the endolysosomal system in kidney disease development.
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http://dx.doi.org/10.1126/scitranslmed.aaz1458DOI Listing
January 2021

Transcutaneous cervical vagal nerve stimulation reduces sympathetic responses to stress in posttraumatic stress disorder: A double-blind, randomized, sham controlled trial.

Neurobiol Stress 2020 Nov 20;13:100264. Epub 2020 Oct 20.

Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, GA, USA.

Objective: Exacerbated autonomic responses to acute stress are prevalent in posttraumatic stress disorder (PTSD). The purpose of this study was to assess the effects of transcutaneous cervical VNS (tcVNS) on autonomic responses to acute stress in patients with PTSD. The authors hypothesized tcVNS would reduce the sympathetic response to stress compared to a sham device.

Methods: Using a randomized double-blind approach, we studied the effects of tcVNS on physiological responses to stress in patients with PTSD (n = 25) using noninvasive sensing modalities. Participants received either sham (n = 12) or active tcVNS (n = 13) after exposure to acute personalized traumatic script stress and mental stress (public speech, mental arithmetic) over a three-day protocol. Physiological parameters related to sympathetic responses to stress were investigated.

Results: Relative to sham, tcVNS paired to traumatic script stress decreased sympathetic function as measured by: decreased heart rate (adjusted β = -5.7%; 95% CI: ±3.6%, effect size d = 0.43, p < 0.01), increased photoplethysmogram amplitude (peripheral vasodilation) (30.8%; ±28%, 0.29, p < 0.05), and increased pulse arrival time (vascular function) (6.3%; ±1.9%, 0.57, p < 0.0001). Similar (p < 0.05) autonomic, cardiovascular, and vascular effects were observed when tcVNS was applied after mental stress or without acute stress.

Conclusion: tcVNS attenuates sympathetic arousal associated with stress related to traumatic memories as well as mental stress in patients with PTSD, with effects persisting throughout multiple traumatic stress and stimulation testing days. These findings show that tcVNS has beneficial effects on the underlying neurophysiology of PTSD. Such autonomic metrics may also be evaluated in daily life settings in tandem with tcVNS therapy to provide closed-loop delivery and measure efficacy.ClinicalTrials.gov Registration # NCT02992899.
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http://dx.doi.org/10.1016/j.ynstr.2020.100264DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7739181PMC
November 2020

Neighborhood characteristics and ideal cardiovascular health among Black adults: results from the Morehouse-Emory Cardiovascular (MECA) Center for Health Equity.

Ann Epidemiol 2020 Dec 5. Epub 2020 Dec 5.

Department of Epidemiology, Rollins School of Public Health, Emory University, Atlanta, GA. Electronic address:

Purpose: Neighborhood environment is increasingly recognized as an important determinant of cardiovascular health (CVH) among Black adults. Most research to date has focused on negative aspects of the neighborhood environment, with little attention being paid to the specific positive features, in particular the social environment, that promote cardiovascular resilience among Black adults.We examined whether better neighborhood physical and social characteristics are associated with ideal CVH among Black adults, as measured by Life's Simple 7 (LS7) scores.

Methods: We recruited 392 Black adults (age 53 ± 10 years, 39% men) without known CV disease living in Atlanta, GA. Seven neighborhood domains were assessed via questionnaire: asthetic quality, walking environment, safety, food access, social cohesion, activity with neighbors, and violence. CVH was determined by LS7 scores calculated from measured blood pressure; glucose; cholesterol; body mass index (BMI); and self-reported exercise, diet, and smoking, and categorized into poor (0-8), intermediate (9-10), and ideal (11-14). Multinomial logistic regression was used to examine the association between neighborhood characteristics and the odds of intermediate/ideal CVH categories compared with poor CVH after adjustment for age, gender, household income, education, marital status, and employment status.

Results: Better scores in the neighborhood domains of social cohesion and activity with neighbors were significantly associated with higher adjusted odds of ideal LS7 scores (OR 2.02, 95% CI [1.36-3.01] and 1.71 [1.20-2.45] per 1 standard deviation [SD] increase in respective scores). These associations were stronger for both social cohesion (OR 2.61, 95% CI [1.48-4.61] vs. 1.40 [0.82-2.40]) and activity with neighbors (OR 1.82, 95% CI [1.15-2.86] vs. 1.53 [0.84-2.78]) in Black women than men. Specifically, better scores in social cohesion were associated with higher odds of ideal CVH in exercise (OR 1.73 [1.16-2.59]), diet (OR 1.90 [1.11-3.26]), and BMI (OR 1.52 [1.09-2.09]); better scores in activity with neighbors were also similarly associated with higher odds of ideal CVH in exercise (OR 1.48 [1.00-2.19]), diet (OR 2.15 [1.23-3.77]), and BMI (OR 1.45 [1.07-1.98]; per 1 SD in respective scores).

Conclusions: More desirable neighborhood characteristics, particularly social cohesion and activity with neighbors, were associated with better CVH among Black adults.
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http://dx.doi.org/10.1016/j.annepidem.2020.11.009DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8178422PMC
December 2020

Public attitudes toward an authorization for contact program for clinical research.

J Am Med Inform Assoc 2021 02;28(2):354-359

Georgia Clinical and Translational Science Alliance, Emory University School of Medicine, Atlanta, Georgia, USA.

We conducted an online experimental survey to evaluate attitudes toward an authorization for contact (AFC) program allowing researchers to contact patients about studies based on electronic record review. A total of 1070 participants were randomly assigned to 1 of 3 flyers varying in design and framing. Participants were asked to select concerns about and reasons for signing up for AFC. Logistic regression and latent class analysis were conducted. The most commonly selected concerns included needing more information (43%), privacy (40%), and needing more time to think (28%). A minority were not interested in participating in research (16%) and did not want to be bothered (15%). Latent class analysis identified clusters with specific concerns about privacy, lack of interest in research, and not wanting to be bothered. A novel flyer with simple and positive framing was associated with lower odds of both not wanting to be bothered (P = .01) and not being interested in research (P = .01). Many concerns about AFC programs appear nonspecific. Addressing privacy, lack of interest in research, and not wanting to be bothered warrant further study as ways to enhance recruitment.
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http://dx.doi.org/10.1093/jamia/ocaa214DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7883977PMC
February 2021

Relation of Neighborhood Disadvantage to Heart Failure Symptoms and Hospitalizations.

Am J Cardiol 2021 02 2;140:83-90. Epub 2020 Nov 2.

Department of Medicine, Emory University School of Medicine, Atlanta, Georgia; Division of Cardiology, Emory University School of Medicine, Atlanta, Georgia. Electronic address:

Residence in socioeconomically deprived neighborhoods may influence patient's health-related behaviors and overall health. We evaluated the association of neighborhood disadvantage on heart failure (HF) symptom burden and hospitalization rates. We characterized neighborhood deprivation in 359 HF subjects (age 56 ± 13 years, 52% black) in metropolitan Atlanta using the Area Deprivation Index (ADI). ANOVA was used to compare HF symptoms measured using the Kansas City Cardiomyopathy Questionnaire, and HF Self-Care Index across ADI tertiles. Zero-inflated Poisson regression was used to compare rates of recurrent HF hospitalization (HFH) across ADI tertiles. Subjects living in more deprived neighborhoods were more likely to be black, have Medicare or Medicaid insurance, and have a lower ejection fraction than those living in less deprived neighborhoods (all p ≤ 0.005). Subjects in more deprived neighborhoods had more severe HF symptoms (p < 0.001), but there was no difference in HF Self-Care Index scores across ADI tertiles. Subjects living in more deprived neighborhoods had a higher odds of being hospitalized for HF than subjects in less deprived neighborhoods. Once subjects had experienced a HFH, however, the association between ADI and the risk of recurrent HFH varied by racial group. In whites, increasing ADI was associated with a marginally decreased risk of recurrent HFH, while there was no association between ADI and recurrent HFH in blacks. In conclusion, patients with HF living in more deprived neighborhoods have greater symptom burden and are more likely to experience a HFH than those living in less deprived neighborhoods.
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http://dx.doi.org/10.1016/j.amjcard.2020.10.057DOI Listing
February 2021

Gender Differences in Mortality After Left Ventricular Assist Device Implant: A Causal Mediation Analysis Approach.

ASAIO J 2021 06;67(6):614-621

From the Division of Cardiology, Department of Medicine, Emory Clinical Cardiovascular Research Institute, Emory University School of Medicine, Atlanta, Georgia.

We used the International Society for Heart and Lung Transplantation (ISHLT) Registry for Mechanically Assisted Circulatory Support (IMACS) database to examine 1) gender differences in post-left ventricular assist device (LVAD) mortality in the contemporary era and 2) preimplant clinical factors that might mediate any observed differences. Adults who received continuous-flow (CF)-LVAD from January 2013 to September 2017 (n = 9,565, age: 56.2 ± 13.2 years, 21.6% female, 31.1% centrifugal pumps) were analyzed. An inverse probability weighted Cox proportional hazards model was used to estimate association of female gender with all-cause mortality, adjusting for known covariates. Causal mediation analysis was performed to test plausible preimplant mediators mechanistically underlying any association between female gender and mortality. Females had higher mortality after LVAD (adjusted hazard ratio [HR]: 1.36; p < 0.0001), with significant gender × time interaction (p = 0.02). An early period of increased risk was identified, with females experiencing a higher risk of mortality during the first 4 months after implant (adjusted HR: 1.74; p < 0.0001), but not after (adjusted HR: 1.18; p = 0.16). More severe tricuspid regurgitation and smaller left ventricular end-diastolic diameter at baseline mediated ≈21.9% of the increased early hazard of death in females; however, most of the underlying mechanisms remain unexplained. Therefore, females have increased mortality only in the first 4 months after LVAD implantation, partially driven by worsening right ventricular dysfunction and LV-LVAD size mismatch.
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http://dx.doi.org/10.1097/MAT.0000000000001288DOI Listing
June 2021

Coronary Vascular Function and Cardiomyocyte Injury: A Report From the WISE-CVD.

Arterioscler Thromb Vasc Biol 2020 12 8;40(12):3015-3021. Epub 2020 Oct 8.

Barbra Streisand Women's Heart Center, Cedars-Sinai Smidt Heart Institute, Los Angeles, CA (J.W., O.Q., B.A., B.S., T.D.H., J.V.E., C.N.B.M.).

Objective: Women with symptoms or signs of myocardial ischemia but no obstructive coronary artery disease (INOCA) often have coronary vascular dysfunction and elevated risk for adverse cardiovascular events. We hypothesized that u-hscTnI (ultra-high-sensitivity cardiac troponin I), a sensitive indicator of ischemic cardiomyocyte injury, is associated with coronary vascular dysfunction in women with INOCA. Approach and Results: Women (N=263) with INOCA enrolled in the WISE-CVD study (Women's Ischemic Syndrome Evaluation-Coronary Vascular Dysfunction) underwent invasive coronary vascular function testing and u-hscTnI measurements (Simoa HD-1 Analyzer; Quanterix Corporation, Lexington, MA). Logistic regression models, adjusted for traditional cardiovascular risk factors were used to evaluate associations between u-hscTnI and coronary vascular function. Women with coronary vascular dysfunction (microvascular constriction and limited coronary epicardial dilation) had higher plasma u-hscTnI levels (both =0.001). u-hscTnI levels were associated with microvascular constriction (odds ratio, 1.38 per doubling of u-hscTnI [95% CI, 1.03-1.84]; =0.033) and limited coronary epicardial dilation (odds ratio, 1.37 per doubling of u-hscTnI [95% CI, 1.04-1.81]; =0.026). u-hscTnI levels were not associated with microvascular dilation or coronary epicardial constriction.

Conclusions: Our findings indicate that higher u-hscTnI is associated with coronary vascular dysfunction in women with INOCA. This suggests that ischemic cardiomyocyte injury in the setting of coronary vascular dysfunction has the potential to contribute to adverse cardiovascular outcomes observed in these women. Additional studies are needed to confirm and investigate mechanisms underlying these findings in INOCA. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT00832702.
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http://dx.doi.org/10.1161/ATVBAHA.120.314260DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8079158PMC
December 2020
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