Public Health Commons^™

Association Of Common And Rare Variants With Alzheimer’S Disease In More Than 13,000 Diverse Individuals With Whole-Genome Sequencing From The Alzheimer’S Disease Sequencing Project, Wan-Ping Lee, Seung Hoan Choi, Margaret G Shea, Po-Liang Cheng, Beth A Dombroski, Achilleas N Pitsillides, Nancy L Heard-Costa, Hui Wang, Katia Bulekova, Amanda B Kuzma, Yuk Yee Leung, John J Farrell, Honghuang Lin, Brian W Kunkle, Adam Naj, Elizabeth E Blue, Frederick Nusetor, Dongyu Wang, Eric Boerwinkle, William S Bush, Xiaoling Zhang, Philip L De Jager, Josée Dupuis, Lindsay A Farrer, Myriam Fornage, Eden Martin, Margaret Pericak-Vance, Sudha Seshadri, Ellen M Wijsman, Li-San Wang, Alzheimer's Disease Sequencing Project;, Gerard D Schellenberg, Anita L Destefano, Jonathan L Haines, Gina M Peloso

Faculty, Staff and Student Publications

INTRODUCTION: Alzheimer's disease (AD) is a common disorder of the elderly that is both highly heritable and genetically heterogeneous.

METHODS: We investigated the association of AD with both common variants and aggregates of rare coding and non-coding variants in 13,371 individuals of diverse ancestry with whole genome sequencing (WGS) data.

RESULTS: Pooled-population analyses of all individuals identified genetic variants at apolipoprotein E (APOE) and BIN1 associated with AD (p < 5 × 10

DISCUSSION: We observed that complementary pooled-population and subgroup-specific analyses offered unique insights into the genetic architecture of AD.

HIGHLIGHTS: We determine the association of genetic variants with Alzheimer's disease (AD) using …

A Comprehensive Analysis Of In-Hospital Adverse Events After Scopolamine Administration: Insights From A Retrospective Cohort Study Using A Large Nationwide Inpatient Database, George Sun, Marc Torjman, Kevin Min

Department of Anesthesiology Faculty Papers

BACKGROUND: Scopolamine is a widely used antiemetic in anesthetic practice, particularly for postoperative and post-discharge nausea and vomiting. Despite its frequent usage and recognized efficacy, concerns have emerged regarding the potential for increased side effects, particularly in elderly patients. Further research is needed to assess safety and determine age thresholds for adverse events. This study hypothesizes associations between perioperative scopolamine use, worse clinical outcomes, increased pneumonia, delirium, urinary retention, and readmissions.

METHODS: A large, retrospective cohort study was performed using the TriNetX Analytics Network database on patients undergoing major surgical procedures between Jan 1, 2009, and March 21, 2018, to …

Host Dna Depletion On Frozen Human Respiratory Samples Enables Successful Metagenomic Sequencing For Microbiome Studies, Minsik Kim, Raymond C Parrish, Michael J Tisza, Viral S Shah, Thi Tran, Matthew Ross, Juwan Cormier, Aribah Baig, Ching-Ying Huang, Laura Brenner, Isabel Neuringer, Katrine Whiteson, J Kirk Harris, Amy D Willis, Peggy S Lai

Faculty, Staff and Students Publications

Most respiratory microbiome studies use amplicon sequencing due to high host DNA. Metagenomics sequencing offers finer taxonomic resolution, phage assessment, and functional characterization. We evaluated five host DNA depletion methods on frozen nasal swabs from healthy adults, sputum from people with cystic fibrosis (pwCF), and bronchoalveolar lavage (BAL) from critically ill patients. Median sequencing depth was 76.4 million reads per sample. Untreated nasal, sputum, and BAL had 94.1%, 99.2%, and 99.7% host reads, respectively. Host depletion effects varied by sample type, generally increasing microbial reads, species and functional richness; this was mediated by higher effective sequencing depth. Rarefaction curves showed …

Clinical Effects Of Dexamethasone Among Patients With Sickle Cell Disease Hospitalized With Covid-19: Outcomes From A Single Academic Health System, William M. Garneau, Matthew J. Lankiewicz, Catherine R. Lesko, Ashley P. Lauriello, Kelly A. Gebo, Sophie M. Lanzkron

Department of Medicine Faculty Papers

BACKGROUND: Dexamethasone is a steroid used in the treatment of hospitalized patients with severe COVID-19. However, the effect of dexamethasone in patients with SCD remains unclear given that steroids may precipitate vaso-occlusive crisis (VOC) in patients with SCD.

METHODS AND FINDINGS: We performed a retrospective analysis of patients with SCD who were hospitalized at Johns Hopkins Health System between June 1, 2020 and June 26, 2022. We reviewed individual charts to assess severity of illness and eligibility for dexamethasone treatment. The exposure of interest was treatment with dexamethasone. Outcomes of interest included incident VTE, length of hospital stay, ICU admission, …

Intervention Mapping For Refining A Sport-Based Public Health Intervention In Rural Schools, Mckenna G Major, Janette M Watkins, Janelle M Goss, Derek W Craig, Zack Waggoner, Vanessa M Martinez Kercher, Kyle A Kercher

Faculty, Staff and Student Publications

Sport-based youth development programs, delivered through campus-community partnerships, can create impactful experiences for college students, meet university objectives, and improve the health of children in under-resourced rural communities. This study aimed to pilot test intervention mapping (IM), a systematic approach to intervention development and implementation, to refine the Hoosier Sport intervention, which is a local public health initiative that utilizes the Obesity-Related Behavioral Intervention Trials (ORBITs) model to improve physical activity in middle school children. The IM process, which included a diverse IM planning and advisory group of university representatives and local schools, was guided by self-determination theory (SDT) and …

Mitochondrial Heteroplasmy Improves Risk Prediction For Myeloid Neoplasms, Yun Soo Hong, Sergiu Pasca, Wen Shi, Daniela Puiu, Nicole J Lake, Monkol Lek, Meng Ru, Megan L Grove, Anna Prizment, Corinne E Joshu, Elizabeth A Platz, Eliseo Guallar, Dan E Arking, Lukasz P Gondek

Faculty, Staff and Student Publications

Clonal hematopoiesis of indeterminate potential is the primary pathogenic risk factor for myeloid neoplasms, while heteroplasmy (mutations in a subset of cellular mitochondrial DNA) is another marker of clonal expansion associated with hematological malignancies. We explore how these two markers relate and influence myeloid neoplasms incidence, and their role in risk stratification. We find that heteroplasmy is more common in individuals with clonal hematopoiesis of indeterminate potential, particularly those with higher variant allele fractions, multiple mutations, or spliceosome machinery mutations. Individuals with both markers have a higher risk of myeloid neoplasms than those with either alone. Furthermore, heteroplasmic variants with …

Whole-Genome Analysis Of Plasma Fibrinogen Reveals Population-Differentiated Genetic Regulators With Putative Liver Roles, Jennifer E Huffman, Jayna Nicholas, Julie Hahn, Adam S Heath, Laura M Raffield, Lisa R Yanek, Jennifer A Brody, Florian Thibord, Laura Almasy, Traci M Bartz, Lawrence F Bielak, Russell P Bowler, Germán D Carrasquilla, Daniel I Chasman, Ming-Huei Chen, David B Emmert, Mohsen Ghanbari, Jeffrey Haessler, Jouke-Jan Hottenga, Marcus E Kleber, Ngoc-Quynh Le, Jiwon Lee, Joshua P Lewis, Ruifang Li-Gao, Jian'an Luan, Anni Malmberg, Massimo Mangino, Riccardo E Marioni, Angel Martinez-Perez, Nathan Pankratz, Ozren Polasek, Anne Richmond, Benjamin A T Rodriguez, Jerome I Rotter, Maristella Steri, Pierre Suchon, Stella Trompet, Stefan Weiss, Marjan Zare, Paul Auer, Michael H Cho, Paraskevi Christofidou, Gail Davies, Eco De Geus, Jean-François Deleuze, Graciela E Delgado, Lynette Ekunwe, Nauder Faraday, Martin Gögele, Andreas Greinacher, He Gao, Tom Howard, Peter K Joshi, Tuomas O Kilpeläinen, Jari Lahti, Allan Linneberg, Silvia Naitza, Raymond Noordam, Ferran Paüls-Vergés, Stephen S Rich, Frits R Rosendaal, Igor Rudan, Kathleen A Ryan, Juan Carlos Souto, Frank J A Van Rooij, Heming Wang, Wei Zhao, Lewis C Becker, Andrew Beswick, Michael R Brown, Brian E Cade, Harry Campbell, Kelly Cho, James D Crapo, Joanne E Curran, Moniek P M De Maat, Margaret Doyle, Paul Elliott, James S Floyd, Christian Fuchsberger, Niels Grarup, Xiuqing Guo, Sarah E Harris, Lifang Hou, Ivana Kolcic, Charles Kooperberg, Cristina Menni, Matthias Nauck, Jeffrey R O'Connell, Valeria Orrù, Bruce M Psaty, Katri Räikkönen, Jennifer A Smith, Jose Manuel Soria, David J Stott, Astrid Van Hylckama Vlieg, Hugh Watkins, Gonneke Willemsen, Peter W F Wilson, Yoav Ben-Shlomo, John Blangero, Dorret Boomsma, Simon R Cox, Abbas Dehghan, Johan G Eriksson, Edoardo Fiorillo, Myriam Fornage, Torben Hansen, Caroline Hayward, M Arfan Ikram, J Wouter Jukema, Sharon L R Kardia, Leslie A Lange, Winfried März, Rasika A Mathias, Braxton D Mitchell, Dennis O Mook-Kanamori, Pierre-Emmanuel Morange, Oluf Pedersen, Peter P Pramstaller, Susan Redline, Alexander Reiner, Paul M Ridker, Edwin K Silverman, Tim D Spector, Uwe Völker, Nicholas J Wareham, James F Wilson, Jie Yao, David-Alexandre Trégouët, Andrew D Johnson, Alisa S Wolberg, Paul S De Vries, Maria Sabater-Lleal, Alanna C Morrison, Nicholas L Smith

Faculty, Staff and Student Publications

Genetic studies have identified numerous regions associated with plasma fibrinogen levels in Europeans, yet missing heritability and limited inclusion of non-Europeans necessitates further studies with improved power and sensitivity. Compared with array-based genotyping, whole-genome sequencing (WGS) data provide better coverage of the genome and better representation of non-European variants. To better understand the genetic landscape regulating plasma fibrinogen levels, we meta-analyzed WGS data from the National Heart, Lung, and Blood Institute's Trans-Omics for Precision Medicine (TOPMed) program (n = 32 572), with array-based genotype data from the Cohorts for Heart and Aging Research in Genomic Epidemiology Consortium (n = 131 …

Analyzing Longitudinal Trait Trajectories Using Gwas Identifies Genetic Variants For Kidney Function Decline, Simon Wiegrebe, Mathias Gorski, Janina M Herold, Klaus J Stark, Barbara Thorand, Christian Gieger, Carsten A Böger, Johannes Schödel, Florian Hartig, Han Chen, Thomas W Winkler, Helmut Küchenhoff, Iris M Heid

Faculty, Staff and Student Publications

Understanding the genetics of kidney function decline, or trait change in general, is hampered by scarce longitudinal data for GWAS (longGWAS) and uncertainty about how to analyze such data. We use longitudinal UK Biobank data for creatinine-based estimated glomerular filtration rate from 348,275 individuals to search for genetic variants associated with eGFR-decline. This search was performed both among 595 variants previously associated with eGFR in cross-sectional GWAS and genome-wide. We use seven statistical approaches to analyze the UK Biobank data and simulated data, finding that a linear mixed model is a powerful approach with unbiased effect estimates which is viable …

Association Of Binge Alcohol Use With Functional Outcomes Among Individuals With Covid-19 Infection, Sebastian T. Tong, Michael Gottlieb, Imtiaz Ebna Mannan, Zihan Zheng, Manisha Sinha, Michelle Santangelo, Kristyn Gatling, Efrat Kean, Phillip Watts, Ralph Wang, Juan Carlos Montoy, Ahamed Idris, Samuel Macdonald, Ryan Huebinger, Mandy Hill, Kelli N O'Laughlin, Nicole L. Gentile, Jocelyn Dorney, Caitlin Malicki, Joann G. Elmore, Kate Diaz Roldan, Gary Chan, Zhenqiu Lin, Robert A. Weinstein, Kari A. Stephens

Department of Medicine Faculty Papers

AIMS: Alcohol consumption along with negative sequelae from excess alcohol intake increased during the COVID-19 pandemic. We evaluated the association between binge alcohol use and long-term functional outcomes among COVID-19-positive individuals.

METHODS: Using a prospective, longitudinal, multisite cohort study design, we evaluated the association between binge alcohol use and mental and physical functional outcomes using Patient-Reported Outcomes Measurement Information System (PROMIS)-29 scores three and six months postinfection. Eligible patients were those who presented with COVID-19-like symptoms, tested positive for COVID-19, and completed a three-month survey. Binge drinking was identified at the time of infection using the Tobacco, Alcohol, Prescription medication …

Identifying Barriers To Hepatitis B And Delta Screening, Prevention, And Linkage To Care Among People Who Use Drugs In Philadelphia, Pennsylvania, Usa, Beatrice Zovich, Catherine Freeland, Holly Moore, Kara Sapp, Anousha Qureshi, Amy Jessop, Rachel Holbert, Fiona Borondy-Jenkins, Quinn Plunkett, Chari Cohen

Student Papers, Posters & Projects

BACKGROUND: People who use drugs (PWUD) are at increased risk for blood-borne viruses, including hepatitis B (HBV) and delta (HDV). Despite the public health threats both viruses present, awareness remains low among at-risk communities and providers who serve them. This study assessed barriers to HBV and HDV prevention, diagnosis, and linkage to care, evaluated existing levels of knowledge, and identified educational needs and preferences among both PWUD and service providers.

METHODS: For this mixed-methods study, data were collected through an anonymous online provider-focused survey, and interviews with PWUD, non-medical staff, and healthcare providers at a harm reduction organization in Philadelphia, …

Lung Tissue Multilayer Network Analysis Uncovers The Molecular Heterogeneity Of Chronic Obstructive Pulmonary Disease, Nuria Olvera, Jon Sánchez-Valle, Iker Núñez-Carpintero, Joselyn Rojas-Quintero, Guillaume Noell, Sandra Casas-Recasens, Alen Faiz, Philip Hansbro, Angela Guirao, Rosalba Lepore, Davide Cirillo, Alvar Agustí, Francesca Polverino, Alfonso Valencia, Rosa Faner

Faculty, Staff and Students Publications

Rationale: Chronic obstructive pulmonary disease (COPD) is a heterogeneous condition. Objectives: We hypothesized that the unbiased integration of different COPD lung omics using a novel multilayer approach might unravel mechanisms associated with clinical characteristics.

Methods: We profiled mRNA, microRNA and methylome in lung tissue samples from 135 former smokers with COPD. For each omic (layer), we built a patient network on the basis of molecular similarity. The three networks were used to build a multilayer network, and optimization of multiplex modularity was used to identify patient communities across the three distinct layers. Uncovered communities were related to clinical features.

Measurements …

Racial And Ethnic Disparities In Perceived Health Status Among Patients With Cardiovascular Disease, Marjan Zakeri, Lincy S Lal, Susan M Abughosh, Shubhada Sansgiry, E James Essien, Sujit S Sansgiry

Faculty, Staff and Students Publications

Introduction: Understanding health outcomes among people with cardiovascular disease (CVD) is crucial for improving treatment strategies and patient quality of life. This study investigated racial and ethnic disparities in perceived health status among non-Hispanic Black, Hispanic, and non-Hispanic White adults with CVD.

Methods: The study had a retrospective cross-sectional design and used data from the Medical Expenditure Panel Survey spanning 8 calendar years (2014-2021). The study population consisted of adults diagnosed with various CVDs. We used ordinal logistic regression models adjusted for demographic and socioeconomic characteristics, CVD severity, comorbidities, and health care expenditures to assess racial and ethnic differences in …

Underutilization Of Influenza Antiviral Treatment Among Children And Adolescents At Higher Risk For Influenza-Associated Complications - United States, 2023-2024., Aaron M. Frutos, Haris M. Ahmad, Dawud Ujamaa, Alissa C. O'Halloran, Janet A. Englund, Eileen J. Klein, Danielle M. Zerr, Melanie Crossland, Holly Staten, Julie A. Boom, Leila C. Sahni, Natasha B. Halasa, Laura S. Stewart, Olla Hamdan, Tess Stopczynski, William Schaffner, H Keipp Talbot, Marian G. Michaels, John V. Williams, Melissa Sutton, M Andraya Hendrick, Mary A. Staat, Elizabeth P. Schlaudecker, Brenda L. Tesini, Christina B. Felsen, Geoffrey A. Weinberg, Peter G. Szilagyi, Bridget J. Anderson, Jemma V. Rowlands, Murtada Khalifa, Marc Martinez, Rangaraj Selvarangan, Jennifer E. Schuster, Ruth Lynfield, Melissa Mcmahon, Sue Kim, Val Tellez Nunez, Patricia A. Ryan, Maya L. Monroe, Yun F. Wang, Kyle P. Openo, James Meek, Kimberly Yousey-Hindes, Nisha B. Alden, Isaac Armistead, Suchitra Rao, Shua J. Chai, Pam Daily Kirley, Ariana P. Toepfer, Fatimah S. Dawood, Heidi L. Moline, Timothy M. Uyeki, Sascha Ellington, Shikha Garg, Catherine H. Bozio, Samantha M. Olson

Manuscripts, Articles, Book Chapters and Other Papers

Annually, tens of thousands of U.S. children and adolescents are hospitalized with seasonal influenza virus infection. Both influenza vaccination and early initiation of antiviral treatment can reduce complications of influenza. Using data from two U.S. influenza surveillance networks for children and adolescents agedattended, laboratory-confirmed influenza for whom antiviral treatment is recommended, the percentage who received treatment was calculated. Trends in antiviral treatment of children and adolescents hospitalized with influenza from the 2017-18 to the 2023-2024 influenza seasons were also examined. Since 2017-18, when 70%-86% of hospitalized children and adolescents with influenza received antiviral treatment, the proportion receiving treatment notably declined. …

Effectiveness Of Mailed Outreach And Patient Navigation To Promote Hcc Screening Process Completion: A Multicentre Pragmatic Randomised Clinical Trial, Amit G Singal, Manasa Narasimman, Darine Daher, Sruthi Yekkaluri, Yan Liu, Minjae Lee, Vanessa Cerda, Aisha Khan, Karim Seif El Dahan, Jennifer Kramer, Purva Gopal, Caitlin Murphy, Ruben Hernaez

Faculty, Staff and Students Publications

Background: Hepatocellular carcinoma (HCC) is plagued by failures across the cancer care continuum, leading to frequent late-stage diagnoses and high mortality. We evaluated the effectiveness of mailed outreach invitations plus patient navigation to promote HCC screening process completion in patients with cirrhosis.

Methods: Between April 2018 and September 2021, we conducted a multicentre pragmatic randomised clinical trial comparing mailed outreach plus patient navigation for HCC screening (n=1436) versus usual care with visit-based screening (n=1436) among patients with cirrhosis at three US health systems. Our primary outcome was screening process completion over a 36-month period, and our secondary outcome was the …

Evaluation Of A Trauma-Informed Care (Tic) Training Program Across Community Health Centers In Texas: A Qualitative Study, Jihye Choi, Efrat K Gabay, Aimee Rachel, Aniela Brown, Roxana Cruz, Qiheng Yan, Paula M Cuccaro

Faculty, Staff and Student Publications

BACKGROUND: In April 2019, Texas Association of Community Health Centers launched the Trauma-Informed Care (TIC) program in community health centers across Texas. This initiative aimed to transform organizational culture for consistent delivery of TIC by providing training and coaching opportunities for Trainers and Champions in each health center. This study is an interim qualitative evaluation to gain participants' insights into their experiences of and perceptions about TIC training as part of the TIC initiative.

METHODS: We conducted semi-structured key informant interviews via Zoom with Trainers across four cohorts of participating health centers between February 2020 and April 2023. We used …

Validation Of An Artificial Intelligence-Based Prognostic Biomarker In Patients With Oligometastatic Castration-Sensitive Prostate Cancer, Jarey H. Wang, Matthew P. Deek, Adrianna A. Mendes, Yang Song, Amol Shetty, Soha Bazyar, Kim Van Der Eecken, Emmalyn Chen, Timothy N. Showalter, Trevor J. Royce, Tamara Todorovic, Huei-Chung Huang, Scott A. Houck, Rikiya Yamashita, Ana P. Kiess, Daniel Y. Song, Tamara Lotan, Theodore Deweese, Luigi Marchionni, Lei Ren, Amit Sawant, Nicole L. Simone, Alejandro Berlin, Cem Onal, Andre Esteva, Felix Y. Feng, Phuoc T. Tran, Philip Sutera, Piet Ost

Department of Radiation Oncology Faculty Papers

BACKGROUND: There is a need for clinically actionable prognostic and predictive tools to guide the management of oligometastatic castration-sensitive prostate cancer (omCSPC).

METHODS: This is a multicenter retrospective study to assess the prognostic and predictive performance of a multimodal artificial intelligence biomarker (MMAI; the ArteraAI Prostate Test) in men with omCSPC (n = 222). The cohort also included 51 patients from the STOMP and ORIOLE phase 2 clinical trials which randomized patients to observation versus metastasis-directed therapy (MDT). MMAI scores were computed from digitized histopathology slides and clinical variables. Overall survival (OS) and time to castration-resistant prostate cancer (TTCRPC) were …

Evaluation Of Sirtuin 1 As A Predictor Of Cardiovascular Outcomes In Diabetic Patients With Limb-Threatening Ischemia, Federico Biscetti, Maria Margherita Rando, Maria Anna Nicolazzi, Enrica Rossini, Michele Santoro, Flavia Angelini, Roberto Iezzi, Luis H. Eraso, Paul J. Dimuzio, Dario Pitocco, Massimo Massetti, Antonio Gasbarrini, Andrea Flex

Department of Surgery Faculty Papers

Chronic limb-threatening ischemia (CLTI) significantly increases the risk of major adverse limb events (MALE) and major adverse cardiac events (MACE) after lower extremity revascularization (LER). This study aims to identify novel biomarkers that help to further reduce the risk of postoperative cardiovascular complications. In this prospective, nonrandomized, observational study, baseline serum levels of sirtuin 1 (SIRT1) were assessed in 147 diabetic patients scheduled for LER due to CLTI, and participants were followed for the occurrence of MALE and MACE over 12 months. Fifty-three patients experienced MALE, and 33 experienced MACE within the follow-up period. Lower baseline SIRT1 levels were significantly …

Understanding The Impact Of Covid-19 On Yoga Instruction: Examining Teaching Methodology, Class Components, And Injury Patterns In The Northeastern Us, Sojung Kim, June Solow, Donald H Lein, Harshvardhan Singh

Rowan-Virtua School of Osteopathic Medicine Departmental Research

OBJECTIVES: This study aimed to examine the impact of COVID-19 on the perspectives of yoga instructors (YIs) regarding teaching methodology, class components, and yoga-related injuries among their clients DESIGN: A cross-sectional design in this study.

SETTING: A total of 407 YIs from Northeastern United States completed a customized, web-based survey.

MAIN OUTCOME MEASURES: Chi-square tests were carried out to determine changes in yoga teaching format before and during the pandemic, as well as the counts of yoga related injuries between face-to-face (FtoF) and online teaching format. Independent t tests were used to compare the characteristics of yoga teaching elements.

RESULTS: …

Post-Artesunate Delayed Hemolysis In Pediatric Malaria Patients In The United States, Sesh A Sundararaman, Karen L Hanze Villavicencio, Brianne Roper, Ziyi Wang, Amy K F Davis, Jonathan A Mayhew, Michelle L Wang, Nina L Tang, Vijaya L Soma, Gail F Shust, Margaret E Feeney, Indi Trehan, Jill E Weatherhead, Chandy C John, Jeffrey S Gerber, Audrey R Odom John

Faculty, Staff and Students Publications

Post-artesunate delayed hemolysis (PADH) occurred in 6 of 24 children treated with artesunate for severe malaria in the United States; however, severe hemolysis requiring hospitalization or transfusion was rare. In children in the United States treated with artesunate, counseling, and symptom monitoring may be preferred to weekly laboratory surveillance for PADH.

Federally Qualified Health Centers And Performance Of Medicare Accountable Care Organizations, Kun Li, Yucheng Hou, Frank Mcstay, Jonathan Gonzalez-Smith, Robert S Saunders

Faculty, Staff and Student Publications

IMPORTANCE: Federally qualified health centers (FQHCs) have increasingly participated in the Medicare Shared Savings Program (MSSP) accountable care organizations (ACOs), one of the most widespread value-based programs. Although FQHCs may strengthen ACOs' ability to provide affordable care to diverse Medicare beneficiaries, evidence on ACOs' performance by FQHC participation is limited.

OBJECTIVES: To compare beneficiary characteristics, utilization, expenditure, and quality between ACOs with and without FQHC participation and assess changes in ACO performance after including first FQHCs.

DESIGN, SETTING, AND PARTICIPANTS: Using MSSP public use files, this cross-sectional study compared performance of ACOs that always had FQHC participation with ACOs that …

Genetic Risk Factors Underlying White Matter Hyperintensities And Cortical Atrophy, Yash Patel, Jean Shin, Eeva Sliz, Ariana Tang, Aniket Mishra, Rui Xia, Edith Hofer, Hema Sekhar Reddy Rajula, Ruiqi Wang, Frauke Beyer, Katrin Horn, Max Riedl, Jing Yu, Henry Völzke, Robin Bülow, Uwe Völker, Stefan Frenzel, Katharina Wittfeld, Sandra Van Der Auwera, Thomas H Mosley, Vincent Bouteloup, Jean-Charles Lambert, Geneviève Chêne, Carole Dufouil, Christophe Tzourio, Jean-François Mangin, Rebecca F Gottesman, Myriam Fornage, Reinhold Schmidt, Qiong Yang, Veronica Witte, Markus Scholz, Markus Loeffler, Gennady V Roshchupkin, M Arfan Ikram, Hans J Grabe, Sudha Seshadri, Stephanie Debette, Tomas Paus, Zdenka Pausova

Faculty, Staff and Student Publications

White matter hyperintensities index structural abnormalities in the cerebral white matter, including axonal damage. The latter may promote atrophy of the cerebral cortex, a key feature of dementia. Here, we report a study of 51,065 individuals from 10 cohorts demonstrating that higher white matter hyperintensity volume associates with lower cortical thickness. The meta-GWAS of white matter hyperintensities-associated cortical 'atrophy' identifies 20 genome-wide significant loci, and enrichment in genes specific to vascular cell types, astrocytes, and oligodendrocytes. White matter hyperintensities-associated cortical 'atrophy' showed positive genetic correlations with vascular-risk traits and plasma biomarkers of neurodegeneration, and negative genetic correlations with cognitive functioning. …

Protein Consumption And Risk Of Cvd Among Us Adults: The Multi-Ethnic Study Of Atherosclerosis (Mesa), Ji Yun Tark, Ruosha Li, Bing Yu, Alexis C Wood, Nikhil S Padhye, Marcia C De Oliveira Otto

Faculty, Staff and Students Publications

BACKGROUND: Although some randomized trials have reported beneficial effects of protein intake on cardiometabolic risk factors, evidence from prospective studies have not supported a strong link between protein intake and cardiovascular disease (CVD) risk. It is also unclear whether diversity in protein intake plays a role in CVD risk.

OBJECTIVE: We investigated prospective associations of (1) protein intake, overall and by food source and (2) diversity of protein sources with risk of CVD, coronary heart disease (CHD), and stroke.

METHODS: In a multi-ethnic cohort of 5879 U.S. adults (45-84 years), who were free of CVD at baseline, protein intake was …

Act With Cf: A Randomized Trial Of Acceptance And Commitment Therapy Vs Supportive Psychotherapy For Adults With Cystic Fibrosis, C. Virginia O'Hayer, Patrick J. Smith, Christopher F. Drescher, Heather Bruschwein, Chelsi N. Nurse, Hallie M. Kushner, Krista Ingle, Michael J. Stephen, Jeffrey B. Hoag

Department of Psychiatry and Human Behavior Faculty Papers

PURPOSE: Psychological distress, including anxiety and depression, is common among adults with CF, associating with poor quality of life, lung function, and healthcare utilization. This 3-year, multi-site, telehealth-delivered randomized trial sought to determine whether Acceptance and Commitment Therapy (ACT with CF) is superior to supportive psychotherapy (SP), in improving psychological functioning for adults with CF.

METHODS: One hundred twenty-four adults with CF and elevated anxiety and/or depressive symptoms were recruited coincident with the first COVID lockdown, from Thomas Jefferson University Hospitals, University of Virginia, Augusta University, Duke University Medical Center, and social media. Participants were randomized to 6 weeks of …

Polygenic Risk Scores And Extreme Coronary Artery Calcium Phenotypes (Cac=0 And Cac≥1000) In Adults ≥75 Years Old: The Aric Study, Omar Dzaye, Alexander C Razavi, Zeina A Dardari, Frances M Wang, Yasuyuki Honda, Khurram Nasir, Josef Coresh, Candace M Howard-Claudio, Jin Jin, Bing Yu, Paul S De Vries, Lynne Wagenknecht, Aaron R Folsom, Ron Blankstein, Tanika N Kelly, Seamus P Whelton, Martin Bødtker Mortensen, Ziqiao Wang, Nilanjan Chatterjee, Kunihiro Matsushita, Michael J Blaha

Faculty, Staff and Student Publications

Background: Coronary artery calcium (CAC) is heterogeneous in older age and is incompletely explained by traditional atherosclerotic cardiovascular disease risk factors. The extremes of subclinical atherosclerosis burden are strongly associated with either a low or high 10-year risk of incident atherosclerotic cardiovascular disease, respectively. However, the genetic underpinnings of differences in arterial aging remain unclear. We sought to determine the independent association of 2 polygenic scores for coronary heart disease (CHD) with CAC in adults ≥75 years of age.

Methods: There were 1865 ARIC (Atherosclerosis Risk in Communities) participants who underwent genetic testing at visit 1 (1987-1989) and CAC scans …

Effectiveness Of Original Monovalent And Bivalent Covid-19 Vaccines Against Covid-19-Associated Hospitalization And Severe In-Hospital Outcomes Among Adults In The United States, September 2022-August 2023, Jennifer Decuir, Diya Surie, Yuwei Zhu, Adam S Lauring, Manjusha Gaglani, Tresa Mcneal, Shekhar Ghamande, Ithan D Peltan, Samuel M Brown, Adit A Ginde, Aimee Steinwand, Nicholas M Mohr, Kevin W Gibbs, David N Hager, Harith Ali, Anne Frosch, Michelle N Gong, Amira Mohamed, Nicholas J Johnson, Vasisht Srinivasan, Jay S Steingrub, Akram Khan, Laurence W Busse, Abhijit Duggal, Jennifer G Wilson, Nida Qadir, Steven Y Chang, Christopher Mallow, Jennie H Kwon, Matthew C Exline, Nathan I Shapiro, Cristie Columbus, Ivana A Vaughn, Mayur Ramesh, Basmah Safdar, Jarrod M Mosier, Jonathan D Casey, H Keipp Talbot, Todd W Rice, Natasha Halasa, James D Chappell, Carlos G Grijalva, Adrienne Baughman, Kelsey N Womack, Jillian P Rhoads, Sydney A Swan, Cassandra Johnson, Nathaniel Lewis, Sascha Ellington, Fatimah S Dawood, Meredith Mcmorrow, Wesley H Self, Investigating Respiratory Viruses In The Acutely Ill (Ivy) Network

Faculty, Staff and Students Publications

BACKGROUND: Assessments of COVID-19 vaccine effectiveness are needed to monitor the protection provided by updated vaccines against severe COVID-19. We evaluated the effectiveness of original monovalent and bivalent (ancestral strain and Omicron BA.4/5) COVID-19 vaccination against COVID-19-associated hospitalization and severe in-hospital outcomes.

METHODS: During September 8, 2022 to August 31, 2023, adults aged ≥ 18 years hospitalized with COVID-19-like illness were enrolled at 26 hospitals in 20 US states. Using a test-negative case-control design, we estimated vaccine effectiveness (VE) with multivariable logistic regression adjusted for age, sex, race/ethnicity, admission date, and geographic region.

RESULTS: Among 7028 patients, 2924 (41.6%) were …

Covid-19 Breakthrough Infection After Vaccination And Substance Use Disorders: A Longitudinal Cohort Of People With And Without Hiv Receiving Care In The United States Veterans Health Administration, Elena M Soyer, Kathleen A Mcginnis, Amy C Justice, Evelyn Hsieh, Maria C Rodriguez-Barradas, Emily C Williams, Lesley S Park

Faculty, Staff and Students Publications

Research regarding HIV, substance use disorders (SUD), and SARS-CoV-2 infections after COVID-19 vaccination is limited. In the Veterans Aging Cohort Study (VACS)-HIV cohort, we followed vaccinated persons with HIV (PWH) and without HIV (PWoH) from 12/2020 to 3/2022 and linked SARS-CoV-2 test results for laboratory-confirmed breakthrough infection through 9/2022. We examined associations of substance use (alcohol use disorder [AUD], other SUD, smoking status) and HIV status and severity with breakthrough infections, using Cox proportional hazards regression hazard ratios (HR). To test for potential interactions between substance use and HIV, we fit survival models with a multiplicative interaction term. Among 24,253 …

Transcriptomic And Epigenomic Signatures Distinguish High- And Low-Risk Endotypes For Liver Tumor Development, Sandra L Grimm, Tia Talley, Rahul K Jangid, Amrit Koirala, Micah B Castillo, Preethi H Gunaratne, Cristian Coarfa, Cheryl L Walker

Faculty, Staff and Students Publications

The epigenome is a target for environmental exposures and a potential determinant of inter-individual differences in response. In genetically identical C57Bl/6 mice exposed from gestation to weaning to the endocrine-disrupting chemical (EDC) tributyltin (TBT), hepatic tumor development later in life varied across multiple cohorts over time and depending on sex and diet. In one cohort where approximately half of TBT-exposed male mice developed liver tumors at 10 months (Katz et al. Hepatic tumor formation in adult mice developmentally exposed to organotin, Environmental Health Perspectives, 128 (1), 17010, 2020), transcriptomic (RNA-seq) and epigenomic (ChIP-seq) profiling was performed on blood and liver …

Prognostic Stratification In Dlbcl Patients With Aberrant Myc Gene, Jian-Rong Li, Vikram R Shaw, Abi Parthasarathy, Yong Li, Christopher I Amos, Chao Cheng

Faculty, Staff and Students Publications

Diffuse large B-cell lymphoma (DLBCL) is a heterogeneous disease characterized by a subset of patients who exhibit treatment resistance and poor prognoses. Genomic assays have been widely employed to identify high-risk individuals characterized by rearrangements in the MYC, BCL2 and BCL6 genes. These patients typically undergo more aggressive therapeutic treatments; however, there remains a significant variation in their treatment outcomes. This study introduces an MYC signature score (MYCSS) derived from gene expression profiles, specifically designed to evaluate MYC overactivation in DLBCL patients. MYCSS was validated across several independent cohorts to assess its ability to stratify patients based on MYC-related genetic …

Identifying High-Risk Multiple Myeloma Patients: A Novel Approach Using A Clonal Gene Signature, Jian-Rong Li, Christiana Wang, Chao Cheng

Faculty, Staff and Students Publications

Multiple myeloma (MM) is a heterogeneous disease with a small subset of high-risk patients having poor prognoses. Identifying these patients is crucial for treatment management and strategic decisions. In this study, we developed a novel computational framework to define prognostic gene signatures by selecting genes with expression driven by clonal copy number alterations. We applied this framework to MM and developed a clonal gene signature (CGS) consisting of 22 genes and evaluated in five independent datasets. The CGS provided significant prognostic values after adjusting for well-established factors including cytogenetic abnormalities, International Staging System (ISS), and Revised ISS (R-ISS). Importantly, CGS …

Residential Proximity To Oil And Gas Developments And Childhood Cancer Survival, Thanh T Hoang, Rutu A Rathod, Omar Rosales, Maria I Castellanos, Jeremy M Schraw, Elyse Burgess, Erin C Peckham-Gregory, Abiodun O Oluyomi, Michael E Scheurer, Amy E Hughes, Philip J Lupo

Faculty, Staff and Students Publications

Background: Environmental toxicants may impact survival in children with cancer, but the literature investigating these associations remains limited. Because oil and gas developments emit several hazardous air pollutants, the authors evaluated the relationship between residential proximity to oil or gas development and survival across 21 different pediatric cancers.

Methods: The Texas Cancer Registry had 29,730 children (≤19 years old) diagnosed with a primary cancer between 1995 to 2017. Geocoded data were available for 285,266 active oil or gas wells and 109,965 horizontal wells. The authors calculated whether each case lived within 1000 m (yes/no) from each type of oil or …