Grant List
Represents Grant table in the DB
GET /v1/grants?page%5Bnumber%5D=1405&sort=-award_amount
{ "links": { "first": "https://cic-apps.datascience.columbia.edu/v1/grants?page%5Bnumber%5D=1&sort=-award_amount", "last": "https://cic-apps.datascience.columbia.edu/v1/grants?page%5Bnumber%5D=1419&sort=-award_amount", "next": "https://cic-apps.datascience.columbia.edu/v1/grants?page%5Bnumber%5D=1406&sort=-award_amount", "prev": "https://cic-apps.datascience.columbia.edu/v1/grants?page%5Bnumber%5D=1404&sort=-award_amount" }, "data": [ { "type": "Grant", "id": "6696", "attributes": { "award_id": "1I01HX003412-01A1", "title": "Role of Non-pharmacological Pain Treatments in Safe and Effective Opioid Tapering in Chronic Pain", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [], "program_reference_codes": [], "program_officials": [], "start_date": "2022-05-01", "end_date": "2026-04-30", "award_amount": null, "principal_investigator": { "id": 22420, "first_name": "WILLIAM C", "last_name": "BECKER", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [ { "id": 1492, "ror": "https://ror.org/000rgm762", "name": "VA Connecticut Healthcare System", "address": "", "city": "", "state": "CT", "zip": "", "country": "United States", "approved": true } ] }, "other_investigators": [ { "id": 22421, "first_name": "Anne C.", "last_name": "Black", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "awardee_organization": { "id": 1492, "ror": "https://ror.org/000rgm762", "name": "VA Connecticut Healthcare System", "address": "", "city": "", "state": "CT", "zip": "", "country": "United States", "approved": true }, "abstract": "Background: Evidence of risks for serious adverse outcomes and limited benefit of long-term opioid therapy (LTOT) have driven VA recommendations for LTOT tapering or discontinuation when benefits no longer outweigh harms. However, LTOT tapering may also pose risks of harm. Significance: The study addresses a critical need for clear demonstration of LTOT tapering risks and a specific VA call for evaluation of nonpharmacological pain treatments including complementary and integrative health services (NPM/CIH). The goals of this project are to assess the role of NPM/CIH use in effecting safe and clinically meaningful reductions in LTOT regimens for Veterans with chronic pain. Changes in outcomes associated with two major periods -- the implementation of the Whole Health System of care (WHS) and COVID-19 – will be assessed. Innovation and Impact: In ongoing partnership with the Office of Patient-Centered Care and Cultural Transformation (OPCC&CT), the study will broaden the scope of ongoing NPM/CIH evaluation to include outcomes related to substance dependence and addiction. Partnering with Pharmacy Benefits Management Services’ VA Center for Medication Safety (MedSAFE), informed by new pilot data, our team will be one of the first to apply a novel method to optimize determination of LTOT tapering to improve analyses of tapering- related outcomes. The study will inform clinical guidelines addressing multimodal approaches to tapering. Specific Aims are to (1) Characterize NPM/CIH access and utilization among Veterans with LTOT, considering the impact of implementation of the VHA Whole Health System of Care and COVID-19; (2) Compare the effectiveness and safety of opioid tapering for Veterans with LTOT with and without NPM/CIH; (3) Assess the moderating effect of buprenorphine on NPM/CIH effects on outcomes. We hypothesize that use of NPM/CIH will be associated with higher rates of effectiveness and safety, and that use of buprenorphine will be associated with more positive effects of NPM/CIH on these outcomes. Methodology: The project will identify a retrospective cohort between 2016-2020 of approximately 200,000 Veterans receiving LTOT at ≥ 30 mg morphine equivalent daily dose (MEDD) across 54 VA facilities. Leveraging Veterans Health Administration (VHA) electronic health record data, Veterans’ utilization of NPM/CIH within VHA and in the community will be assessed. Applying a novel method developed by VA MedSAFE using VHA electronic pharmacy data within the Corporate Data Warehouse, we will develop models of opioid tapering within the target period. Using quasi-experimental methods, Veterans will be “assigned” to NPM/CIH treatment or no treatment based on their observed service utilization. Propensity score matching will balance baseline differences due to nonrandom assignment. In multilevel models, opioid tapering outcomes will be modeled as a function of NPM/CIH use. The primary tapering effectiveness outcome will be the proportion of Veterans achieving a reduction in prescribed opioid dose of ≥50% of baseline mg MEDD, maintained over six months in the absence of worsened pain intensity. Tapering safety will be measured as the proportion of Veterans experiencing any serious adverse event (SAE), allowing tapering to take all values, including no taper and dose increases. SAE will include hospitalization, emergency department visit, opioid overdose, new mental health disorder, new opioid or other substance use disorder, suicide attempt, and all- cause mortality. Models will assess moderation of NPM/CIH effects by buprenorphine treatment for opioid tapering and for chronic pain. Secondary models will assess the effect of NPM/CIH on LTOT-related side effects and differences in NPM/CIH effect by age, race/ethnicity and gender. Next Steps/Implementation: Operational partners and a Veteran engagement panel will guide interpretation of results and promote dissemination and translation to practice. Results will inform an implementation study to support the scale-up and sustainment of effective practices for pain management and facilitating safe and effective opioid reduction.", "keywords": [ "Address", "Adverse event", "American", "Benefits and Risks", "Buprenorphine", "COVID-19", "Caring", "Centers for Disease Control and Prevention (U.S.)", "Characteristics", "Clinical", "Communities", "Complementary Health", "Data", "Deimplementation", "Dose", "Dropout", "Effectiveness", "Electronic Health Record", "Emergency department visit", "Equilibrium", "Ethnic Origin", "Evaluation", "Evaluation Reports", "Event", "Exercise", "Face", "Feeling suicidal", "Formulation", "Funding", "Gender", "Goals", "Guidelines", "Health", "Health Services", "Health Services Accessibility", "Health Services Research", "Healthcare Systems", "Hospitalization", "Institution", "Integrative Medicine", "Lead", "Measures", "Mental Health", "Mental disorders", "Methodology", "Methods", "Modality", "Modeling", "Opiate Addiction", "Opioid", "Outcome", "Overdose", "Pain", "Pain intensity", "Pain management", "Patient-Centered Care", "Patients", "Pattern", "Perception", "Personal Satisfaction", "Pharmacy facility", "Physiological", "Practice Management", "Prevention Guidelines", "Quasi-experiment", "Race", "Randomized Controlled Trials", "Recommendation", "Recovery", "Regimen", "Research", "Research Design", "Retrospective cohort", "Retrospective cohort study", "Risk", "Role", "Safety", "Sampling", "Serious Adverse Event", "Services", "Site", "Substance Addiction", "Substance Use Disorder", "Suicide attempt", "Testing", "Translations", "United States Department of Veterans Affairs", "Veterans", "Veterans Health Administration", "Withdrawal Symptom", "Work", "Yoga", "addiction", "adverse outcome", "age effect", "base", "buprenorphine treatment", "chiropracty", "chronic pain", "chronic pain patient", "cohort", "comorbidity", "compare effectiveness", "data warehouse", "design", "effective therapy", "effectiveness outcome", "evidence base", "experience", "health service use", "implementation study", "improved", "innovation", "medication safety", "milligram", "morphine equivalent", "mortality", "multidisciplinary", "multilevel analysis", "multimodality", "novel", "opioid mortality", "opioid overdose", "opioid tapering", "opioid therapy", "opioid use", "opioid use disorder", "pharmacy benefit", "physical conditioning", "prescription opioid", "scale up", "secondary analysis", "service uptake", "service utilization", "side effect", "sociodemographics", "substance use", "symposium", "treatment effect", "treat" ], "approved": true } }, { "type": "Grant", "id": "6703", "attributes": { "award_id": "5IK6BX005691-02", "title": "BLRD Research Career Scientist Award Application", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [], "program_reference_codes": [], "program_officials": [], "start_date": "2021-04-01", "end_date": "2026-03-31", "award_amount": null, "principal_investigator": { "id": 22435, "first_name": "Wendy B", "last_name": "Bollag", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [ { "id": 1494, "ror": "https://ror.org/01ng1yh19", "name": "Charlie Norwood VA Medical Center", "address": "", "city": "", "state": "GA", "zip": "", "country": "United States", "approved": true } ] }, "other_investigators": [], "awardee_organization": { "id": 1494, "ror": "https://ror.org/01ng1yh19", "name": "Charlie Norwood VA Medical Center", "address": "", "city": "", "state": "GA", "zip": "", "country": "United States", "approved": true }, "abstract": "This application requests the appointment of Dr. Wendy Bollag, a Research Physiologist at the Charlie Norwood VA Medical Center in Augusta, Georgia and a Professor of Physiology at the affiliate institution (Augusta University), to the position of Research Career Scientist. In the past five years, Dr. Bollag has been productive, publishing 29 peer-reviewed articles and more than 10 invited reviews, book chapters and commentaries, with 52 peer-reviewed articles and 26 invited reviews, book chapters and commentaries in the past 10 years. Dr. Bollag’s research in cell signaling seeks to understand the role of particular signaling molecules in various cell processes; this research has led to interesting findings in her systems of interest, keratinocytes of the skin epidermis and zona glomerulosa cells of the adrenal gland, as well as extension of this knowledge to collaborative projects in other systems, including corneal wound healing. In the case of the skin and the adrenal gland, Dr. Bollag is interested in determining the signaling pathways that underlie keratinocyte proliferation and differentiation to form the epidermis under normal and pathological conditions, as well as those that regulate aldosterone production in the adrenal zona glomerulosa. In the past 10 years the Bollag laboratory has made significant progress in projects examining these two processes, as evidenced by the many publications for which she is the senior author. Dr. Bollag has also received as Principal Investigator (PI) or Co-PI three National Institutes of Health (NIH) R01 awards, one R29 award and one R21 award, five VA Merit Awards (three to support her work in skin, one to fund studies in the adrenal gland and one to support a new study in the cornea), a VA Research Career Scientist Award, two VA Shared Equipment Evaluation Program (ShEEP) awards and multiple state and intramural grant awards. She also recently received, as Contact Co-PI, an NIH T35 training award (with Co-PI, Dr. Carlos Isales) to recruit medical students from three Puerto Rican medical schools to perform summer aging research. She has also served as a Co-Investigator on several awards, including an NIH P01 Program Project Award with her colleague and collaborator of approximately 35 years, Dr. Isales, and as the Lead Mentor on a Department of Defense mentoring partnership award to Albany State University. Last year she received the Augusta University Research Institute Distinguished Investigator Award; she was also invited to give a symposium presentation at the 2019 annual meeting of Experimental Biology. This year she was invited to present in the Blank Forum at the 2020 annual meeting of the Society for Investigative Dermatology (which was unfortunately cancelled due to the pandemic) and to give a named lecture at the Oklahoma Center of Neuroscience (postponed until 2021 because of COVID-19), indicating that she is recognized for her research. Finally, Dr. Bollag is an individual who is engaged with the community and involved in giving back in service at the institutional, local and national levels. Thus, she mentors junior colleagues, including Dr. Debra Irsik, a recent VA Career Development Award recipient, provides educational service to the affiliate institution (for which she has received numerous awards), serves as a reviewer for multiple journals and participates in review panels for several national and international funding agencies, including the VA. Currently, Dr. Bollag is an Editorial Consultant for the Journal of Investigative Dermatology, the highest impact journal in the field of dermatology research, a Senior Editor for the Journal of Endocrinology and the Journal of Molecular Endocrinology and a member of the editorial boards of the Journal of Lipid Research and Molecular Pharmacology. Thus, Dr. Bollag is an established investigator and a recognized mentor, who would adeptly fulfill the responsibilities of the Research Career Scientist designation.", "keywords": [ "Adrenal Glands", "Affect", "Aging", "Aldosterone", "Angiotensin II", "Applications Grants", "Appointment", "Archives", "Award", "Back", "Biology", "Blood Circulation", "Book Chapters", "Book Reviews", "COVID-19", "Calpain", "Cell Maturation", "Cell model", "Cell physiology", "Cells", "Communities", "Cornea", "Corneal Injury", "Department of Defense", "Dermatologic", "Dermatology", "Differentiation and Growth", "Disease", "Endocrinology", "Epidermis", "Equipment", "Exploratory/Developmental Grant for Diagnostic Cancer Imaging", "Fellowship", "Funding", "Funding Agency", "Grant", "Hormones", "Hypertension", "Hypertriglyceridemia", "Individual", "Institution", "International", "Investigational Therapies", "Journals", "K-Series Research Career Programs", "Knowledge", "Laboratories", "Lead", "Legal patent", "Link", "Lipids", "Malignant neoplasm of prostate", "Manuscripts", "Mediating", "Mediation", "Medical Students", "Medical center", "Mentors", "Mesenchymal Stem Cells", "Mitochondria", "Molecular", "Names", "Neurosciences", "Obesity", "Oklahoma", "Oncogenes", "Oncology", "Ophthalmology", "Pathologic", "Patients", "Peer Review", "Pharmaceutical Preparations", "Pharmacology", "Phosphatidylglycerols", "Physiological", "Physiology", "Population", "Positioning Attribute", "Principal Investigator", "Process", "Production", "Program Evaluation", "Program Research Project Grants", "Psoriasis", "Publications", "Published Comment", "Publishing", "Puerto Rican", "Request for Applications", "Research", "Research Institute", "Research Personnel", "Role", "Science", "Scientist", "Services", "Signal Pathway", "Signal Transduction", "Signaling Molecule", "Skin", "Skin Carcinoma", "Societies", "Sodium Chloride", "Soldier", "System", "Training", "United States Food and Drug Administration", "United States National Institutes of Health", "Universities", "Very low density lipoprotein", "Veterans", "Work", "Zona Glomerulosa", "aldosterone hypertension", "anticancer research", "aquaporin 3", "blood pressure regulation", "bone", "career", "cell growth", "colon cancer treatment", "combat", "corneal epithelial wound healing", "corneal epithelium", "cost", "editorial", "high risk", "interest", "keratinocyte", "lectures", "medical schools", "meetings", "member", "novel", "pandemic disease", "phospholipase D2", "posters", "professor", "programs", "protein kinase D", "recruit", "response", "skin disorder", "symposium" ], "approved": true } }, { "type": "Grant", "id": "6710", "attributes": { "award_id": "1I01HX003082-01A2", "title": "The EMBER Trial for Weight Management Engagement", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [], "program_reference_codes": [], "program_officials": [], "start_date": "2022-02-01", "end_date": "2025-08-31", "award_amount": null, "principal_investigator": { "id": 22453, "first_name": "Jessica Yelena", "last_name": "Breland", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [ { "id": 1497, "ror": "", "name": "VETERANS ADMIN PALO ALTO HEALTH CARE SYS", "address": "", "city": "", "state": "CA", "zip": "", "country": "United States", "approved": true } ] }, "other_investigators": [], "awardee_organization": { "id": 1497, "ror": "", "name": "VETERANS ADMIN PALO ALTO HEALTH CARE SYS", "address": "", "city": "", "state": "CA", "zip": "", "country": "United States", "approved": true }, "abstract": "Background: Almost 40% of Veterans using the Veterans Health Administration (VA) have obesity, putting millions at risk for costly and debilitating conditions, including diabetes, cancer, and severe COVID-19. VA weight management programs effectively reduce weight, morbidity, and mortality. For example, MOVE!, VA’s flagship program for weight management is associated with reductions in cardiovascular disease and diabetes. However, while 94% of eligible Veterans are offered weight management programs, less than 8% use them. Motivational interviewing improves treatment engagement, but clinicians have limited time to apply it. Therefore, we developed EMBER, a self-directed tool with the goal of Enhancing Motivation for Better Engagement and Reach for weight management. It is available in paper and digital formats. EMBER is not a weight management program, instead it engages Veterans in existing programs by informing and guiding choices about weight management. EMBER is the product of an HSR&D Career Development Award (15-257). Significance: If EMBER increases engagement in effective weight management programs, it has the potential to help Veterans lose weight, thereby improving health and quality of life for thousands of patients. As a result, we address many HSR&D priorities, e.g., access to care, virtual care, healthy equity, & primary care. Innovation & Impact: EMBER is the first self-directed, motivational interviewing-based intervention designed to increase Veteran engagement in weight management programs. As opposed to a “one-off” study in a specific population, the proposed work takes a novel, low-touch population health approach that could be translated to other programs (e.g., behavioral pain management). EMBER also includes vignettes relevant to populations at high risk for obesity (e.g., women, people of color). Further, t he Hybrid Type 1 design will ensure results can be scaled and sustained while also advancing implementation science. As such, the proposed work will: 1) advance the science of engagement in behavioral health programs and 2) facilitate future research on the implementation of EMBER and similar interventions. Specific Aims: 1. Assess whether Veterans randomized to EMBER are more likely to have any weight management engagement at 2-month follow-up (per administrative data supplemented with self-report) compared to those randomized to the control arm (information sheet listing available programs). (Primary Outcome) 2. Assess whether Veterans randomized to EMBER have greater weight management program retention, weight management behaviors (e.g., physical activity), weight loss, and quality of life gains at 6-month follow-up compared to those randomized to the control arm. (Secondary Outcomes) 3. Assess factors likely to affect EMBER’s implementation. Preliminary implementation outcomes will be assessed via RE-AIM4 (Reach, Effectiveness, Implementation) and the Proctor et al.5 implementation outcomes framework (Acceptability, Appropriateness, Costs, Fidelity). (Implementation Outcomes) Randomized two site Hybrid Type 1 Effectiveness-Implementation Trial among Veteran primary care patients with obesity in VA (N=470). Participants will be randomized to EMBER or a control condition consisting of a list of available weight management programs. The primary outcome is any weight management engagement 2-months after baseline. Aims 1 and 2 will use self-report and administrative data to assess intervention outcomes. Aim 3 will use patient data and information from research staff. Methodology: Implementation/Next Steps: If effective, we will use implementation strategies suggested by Aim 3 to ensure Veterans receive EMBER. We will test these strategies in a Hybrid Type 2 trial to understand EMBER’s effectiveness in real world contexts and best practices for dissemination and implementation of EMBER and similar interventions.", "keywords": [ "Address", "Affect", "Behavior", "Behavioral", "Belief", "Body Weight decreased", "Cardiovascular Diseases", "Cardiovascular system", "Cessation of life", "Color", "Complications of Diabetes Mellitus", "Data", "Diabetes Mellitus", "Disease", "Dissemination and Implementation", "Effectiveness", "Ensure", "Exercise", "Food Services", "Goals", "Health", "Health Promotion", "Health Services Accessibility", "Health Services Administration", "Heart Diseases", "Hybrids", "Intervention", "Interview", "K-Series Research Career Programs", "Letters", "Malignant Neoplasms", "Methodology", "Methods", "Modeling", "Morbidity - disease rate", "Motivation", "Obesity", "Organization and Administration", "Outcome", "Pain management", "Paper", "Participant", "Patient Self-Report", "Patient-Centered Care", "Patients", "Persons", "Physical activity", "Pilot Projects", "Population", "Primary Health Care", "Quality of life", "Randomized", "Research", "Research Design", "Research Priority", "Risk", "Science", "Self Efficacy", "Self-Direction", "Series", "Services", "Site", "System", "Testing", "Time", "Touch sensation", "Translating", "United States", "United States Health Resources Administration", "Veterans", "Veterans Health Administration", "Weight", "Weight Gain", "Weight maintenance regimen", "Woman", "Work", "arm", "base", "behavioral health", "comorbidity", "cost", "design", "digital", "disorder prevention", "effectiveness implementation trial", "flexibility", "follow-up", "health equity", "health service use", "high risk", "high risk population", "hybrid type 1 design", "hybrid type 1 trial", "hybrid type 2 trial", "implementation outcomes", "implementation science", "implementation strategy", "improved", "innovation", "interest", "mortality", "motivational enhancement therapy", "novel", "nutrition", "obese patients", "obesity risk", "patient oriented", "people of color", "physical conditioning", "population health", "primary outcome", "programs", "secondary outcome", "self help", "severe COVID-19", "smoking cessation", "therapy design", "tool", "virtual healthcare" ], "approved": true } }, { "type": "Grant", "id": "6723", "attributes": { "award_id": "5I01BX005466-02", "title": "Covid-19: Fast-tracking treatment by exploiting the steroid hormone receptor/TMPRSS2 axis", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [], "program_reference_codes": [], "program_officials": [], "start_date": "2021-04-01", "end_date": "2023-03-31", "award_amount": null, "principal_investigator": { "id": 22480, "first_name": "Kerry L.", "last_name": "Burnstein", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [ { "id": 1500, "ror": "", "name": "MIAMI VA HEALTH CARE SYSTEM", "address": "", "city": "", "state": "FL", "zip": "", "country": "United States", "approved": true } ] }, "other_investigators": [], "awardee_organization": { "id": 1500, "ror": "", "name": "MIAMI VA HEALTH CARE SYSTEM", "address": "", "city": "", "state": "FL", "zip": "", "country": "United States", "approved": true }, "abstract": "COVID-19 poses a tremendous health threat, particularly to individuals overrepresented in the US Veteran community. COVID-19 mortality is greater in men than in women; while this disparity is at least partially due to factors such as higher rates of smoking, a hormonal link is likely and can be rapidly tested therapeutically by repurposing existing drugs. The viral etiologic agent of COVID-19, SARS-CoV-2 (CoV-2), attaches to human airway epithelium via the viral spike (S) protein, which binds to angiotensin-converting enzyme 2 (ACE2) on the host cell surface. Viral entry requires S protein cleavage by the serine protease TMPRSS2, which is a known transcriptional target of the androgen receptor (AR). Lung epithelial cells (a target of CoV-2 infection) express transcriptionally active AR. We hypothesize that AR up-regulates TMPRSS2 in lung epithelial cells and thereby promotes viral entry and infectivity. We propose that FDA-approved AR antagonists will decrease CoV-2 entry and spread and can be rapidly repurposed for COVID-19. IL-6 is the major cytokine released in moderate and severe COVID-19 cases and both published and our preliminary data show that IL-6 enhances AR transcriptional activity. We will therefore also examine the contribution of interleukin 6 (IL-6) to AR regulation of TMPRRS2. To facilitate these studies in a robust manner, we propose to isolate the SARS-CoV-2 entry mechanism through the use of luciferase-expressing pseudovirions that harbor the SARS-CoV-2 S protein. Such a reporter system has high reproducibility, versatility and dynamic range, allowing for the rapid, accurate and specific assessment of a large range of viral entry regulators into primary human lung epithelial cells and lung adenocarcinoma cell lines under BSL2+ conditions. We will test whether AR inhibition reduces TMPRSS2 and the requisite S protein processing thereby decreasing CoV-2 entry into host lung epithelial cells. Subsequently, we will confirm results on a subset of promising compounds using live SARS-Cov-2 in an approved BSL3 facility. Safe and effective AR antagonists are FDA approved for prostate cancer and this study will provide rationale to repurpose these drugs for use in clinical trials for COVID-19. The glucocorticoid receptor (GR) shares a common DNA response element consensus sequence with AR. Furthermore, GR upregulation of TMPRSS2 has been shown in advanced prostate cancer. Therefore, in parallel, we will examine whether TMPRSS2 is regulated by glucocorticoids (cortisol) and blocked by a GR antagonist in models of human lung epithelia. Patients taking corticosteroids (including the elderly and individuals with diabetes, hypertension and chronic inflammatory disease) are at the highest risk of death from COVID-19. The World Health Organization has provided interim guidance to avoid glucocorticoids in COVID- 19 patients with severe acute respiratory distress syndrome. Therefore, understanding GR regulation of TMPRSS2 is also essential to repurposing the TMPRSS2-inhibitory FDA-approved agents for COVID-19. Our aims are to: (1) Evaluate steroid hormone receptor (AR and GR) regulation of TMPRSS2 in human primary airway and lung epithelial cells and lung adenocarcinoma cell line models and (2) Examine the capacity of FDA-approved AR and GR antagonists to block CoV-2 entry and infectivity in human primary airway and lung epithelial cells. US Veterans represent several demographics acutely afflicted by COVID-19. Older US Veterans are particularly vulnerable because of higher comorbidities including smoking, diabetes, heart disease and hypertension. Burden on the Veteran community is also proportionally higher given the propensity for poor outcome in men as compared to women following COVID-19 infection. Since the anti-androgen therapies to be tested are FDA approved for prostate cancer treatment and have also been used safely in women with breast cancer, our study has potential for immediate impact to all veterans.", "keywords": [ "2019-nCoV", "ACE2", "Acute", "Acute Respiratory Distress Syndrome", "Address", "Adrenal Cortex Hormones", "Affect", "Agonist", "Androgen Antagonists", "Androgen Receptor", "Antiandrogen Therapy", "Binding", "COVID-19", "COVID-19 mortality", "COVID-19 patient", "COVID-19 treatment", "Cell Line", "Cell surface", "Clinical Trials", "Collaborations", "Colorado", "Communities", "Consensus Sequence", "DNA", "Data", "Diabetes Mellitus", "Disease", "Drug usage", "Elderly", "Enrollment", "Epithelial", "Epithelial Cells", "Etiology", "FDA approved", "Genetic Transcription", "Glucocorticoid Receptor", "Glucocorticoids", "Health", "Health Personnel", "Heart Diseases", "Hormonal", "Human", "Hydrocortisone", "Hypertension", "Individual", "Infection", "Interdisciplinary Study", "Interleukin-6", "Ligands", "Link", "Luciferases", "Lung", "Lung Adenocarcinoma", "Malignant neoplasm of prostate", "Measures", "Modeling", "Nuclear Receptors", "Outcome", "Patients", "Pattern", "Pharmaceutical Preparations", "Pharmacological Treatment", "Prostate Cancer therapy", "Proteins", "Proteolysis", "Publishing", "Receptor Inhibition", "Regulation", "Reporter", "Reproducibility", "Research", "Resistance", "Response Elements", "SARS-CoV-2 infection", "SARS-CoV-2 spike protein", "Serine Protease", "Smoking", "Stanolone", "System", "TMPRSS2 gene", "Testing", "Therapeutic", "Universities", "Veterans", "Viral", "Virus", "Woman", "World Health Organization", "advanced prostate cancer", "airway epithelium", "biosafety level 3 facility", "castration resistant prostate cancer", "chronic inflammatory disease", "comorbidity", "cytokine", "demographics", "drug repurposing", "glucocorticoid receptor alpha", "high risk", "human model", "loved ones", "mRNA Expression", "male", "malignant breast neoplasm", "men", "protein expression", "receptor upregulation", "response", "severe COVID-19", "steroid hormone receptor", "therapeutic evaluation", "transcriptome", "viral entry inhibitor" ], "approved": true } }, { "type": "Grant", "id": "6757", "attributes": { "award_id": "5I01BX005432-02", "title": "COVID-19: Elucidating the Role of the NasalEpithelium in SARS-CoV-2 Infection, Transmission, and Prevention", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [], "program_reference_codes": [], "program_officials": [], "start_date": "2021-01-01", "end_date": "2022-12-31", "award_amount": null, "principal_investigator": { "id": 22556, "first_name": "Noam A", "last_name": "Cohen", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [ { "id": 1488, "ror": "https://ror.org/03j05zz84", "name": "Philadelphia VA Medical Center", "address": "", "city": "", "state": "PA", "zip": "", "country": "United States", "approved": true } ] }, "other_investigators": [], "awardee_organization": { "id": 1488, "ror": "https://ror.org/03j05zz84", "name": "Philadelphia VA Medical Center", "address": "", "city": "", "state": "PA", "zip": "", "country": "United States", "approved": true }, "abstract": "Severe acute respiratory syndrome coronavirus SARS-CoV-2, the causative agent of coronavirus disease 2019 (COVID-19) has led to a pandemic with a mortality of approximately 3.5% and a wide range of morbidity outcomes negatively impacted by pre-existing conditions. Given the prevalence of pre-existing comorbid conditions in Veterans, it is imperative to understand the mechanisms of how SARS-CoV-2 invades and replicates within the barrier defense cells of the nose, which is the primary portal for viral entry. Furthermore, current data suggests that the nasal carriage functions as a potential reservoir for viral persistence and transmission (i.e., shedding) at times that are both prior to and during the manifestation of severe respiratory symptoms. This project utilizes a unique biobank of cryopreserved nasal cells collected from over 1000 individuals over 15 years to understand the critical issues surrounding SARS-CoV-2 interaction with the human nasal epithelia. Paradoxically, while SARS-CoV-2 can be detected in nasal swabs prior to its detection in sputum, there is a paucity of rhinologic symptoms (<5% with nasal congestion) associated with COVID-19, with the exception of reversible anosmia in 30-70% of patients. This is particularly problematic because up to 25% of infected individuals remain asymptomatic, but can continue to spread SARS-CoV-2 through airborne droplets. This work seeks to elucidate both the mechanisms controlling which epithelial cell lineages become infected with virus and the type of immune response generated within infected or neighboring epithelia. Through this approach, we will shed light on the issue of why certain individuals never develop symptoms while others progress to severe respiratory failure and death. We will focus on the SARS-CoV-2 receptor Angiotensin Converting Enzyme 2 (ACE2), which is essential and sufficient for the virus to enter cells. Our preliminary data generated from single cell RNA analysis of primary human sinonasal tissue demonstrates that ACE2 is expressed in discrete clusters of nasal epithelia. ACE2- specific immunostaining of human nasal epithelial cells ex vivo and primary ciliated air liquid interface (ALI) cultures corroborates the sc-RNAseq data. Furthermore, our data show that inoculation of primary ALI cultures with SARS-CoV-2 results in approximately 1%-25% of cells becoming infected, suggesting a selective process. These data indicate that we are uniquely poised to test the hypothesis that ACE2 expressing cells constitute a unique reservoir of viral replication and are likely to mount an inflammatory cytokine response that is distinct from non-infected epithelia. Using our established team of experts in nasal epithelial cell biology, viral pathogenesis, inflammatory cytokine biology and genetics we will determine the following: A) which types of epithelia are virally infected, B) what are the local inflammatory cascades in infected vs. non-infected cells, and C) will pharmacologic manipulation of the epithelial innate defense pathways significantly alter SARS-CoV-2 ability to infect, replicate and be released from human nasal epithelia. Successful completion of this work is likely to have a major impact on development of novel strategies to combat COVID19 disease progression within the general population and especially in the U.S. Veteran population.", "keywords": [ "2019-nCoV", "ACE2", "Address", "Affect", "Age", "Air", "Anosmia", "Apical", "Asthma", "Basal Cell", "Biology", "Bronchitis", "COVID-19", "Caring", "Cell Lineage", "Cells", "Cellular biology", "Cessation of life", "Chronic Obstructive Pulmonary Disease", "Collaborations", "Communities", "Congestive", "Cryopreservation", "Data", "Detection", "Development", "Disease Progression", "Double-Stranded RNA", "Epithelial", "Epithelial Cells", "Functional disorder", "Future", "Gender", "General Population", "Genetic", "Genotype", "Goals", "Goblet Cells", "Growth", "Harvest", "Health", "Healthcare Systems", "Human", "Immune", "Immune response", "Immunologic Receptors", "Individual", "Infection", "Inflammatory", "Inflammatory Response Pathway", "Invaded", "Kinetics", "Knowledge", "Lead", "Light", "Liquid substance", "Malignant neoplasm of lung", "Medical", "Morbidity - disease rate", "Mucins", "Mucous Membrane", "Mucous body substance", "Nasal Epithelium", "Natural Immunity", "Nitric Oxide", "Nose", "Nucleocapsid Proteins", "Outcome", "Pathway interactions", "Patients", "Pennsylvania", "Peptide Hydrolases", "Pharmacology", "Predisposition", "Prevalence", "Prevention", "Process", "Production", "Prophylactic treatment", "Protocols documentation", "Pulmonary Emphysema", "RNA analysis", "Race", "Resources", "Respiration Disorders", "Respiratory Disease", "Respiratory Failure", "Respiratory Signs and Symptoms", "Respiratory Tract Infections", "Rhinitis", "Role", "SARS coronavirus", "SARS-CoV-2 infection", "Sampling", "Sinusitis", "Sputum", "Symptoms", "TMPRSS2 gene", "Testing", "Time", "Tissues", "Type 2 Angiotensin II Receptor", "Universities", "Veterans", "Viral", "Viral Genome", "Viral Pathogenesis", "Viral reservoir", "Virus", "Virus Diseases", "Virus Replication", "Virus Shedding", "Vulnerable Populations", "Work", "airway epithelium", "antimicrobial peptide", "asthma exacerbation", "biobank", "biosafety level 3 facility", "burden of illness", "combat", "comorbidity", "cytokine", "demographics", "discrete time", "experimental study", "high risk", "in vitro Model", "innate immune pathways", "insight", "military veteran", "mortality", "nasal swab", "novel strategies", "pandemic disease", "particle", "prophylactic", "racial disparity", "receptor", "screening", "single-cell RNA sequencing", "success", "targeted treatment", "transcriptome sequencing", "transmission process", "ultraviolet irradiation" ], "approved": true } }, { "type": "Grant", "id": "6779", "attributes": { "award_id": "5I01RX003666-02", "title": "Chronic Lung Disease and COVID-19: Understanding Severity, Recovery and Rehabilitation Needs (LAUREL Study)", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [], "program_reference_codes": [], "program_officials": [], "start_date": "2021-01-01", "end_date": "2024-12-31", "award_amount": null, "principal_investigator": { "id": 22583, "first_name": "Kristina Anne", "last_name": "Crothers", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [ { "id": 1512, "ror": "", "name": "VA PUGET SOUND HEALTHCARE SYSTEM", "address": "", "city": "", "state": "WA", "zip": "", "country": "United States", "approved": true } ] }, "other_investigators": [ { "id": 22584, "first_name": "Aaron P.", "last_name": "Turner", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "awardee_organization": { "id": 1512, "ror": "", "name": "VA PUGET SOUND HEALTHCARE SYSTEM", "address": "", "city": "", "state": "WA", "zip": "", "country": "United States", "approved": true }, "abstract": "SARS-CoV-2 (SARS2) infection, which leads to COVID-19, is a global pandemic. Chronic lung disease (CLD), particularly chronic obstructive pulmonary disease (COPD), has emerged as a risk factor for infection and severity of COVID-19. Currently, very little is known of the long-term consequences of COVID-19 and how factors such as CLD, other comorbidities and social determinants of health (SDOH) influence the trajectory of recovery in survivors. While similar complications for COVID-19 survivors and risk factors for poor health recovery may be expected as in other causes of pneumonia and critical illness, long term outcomes of COVID- 19 have not been characterized or quantified. Patients who are hospitalized and critically ill are anticipated to have greater functional deficits, but even those with mild and moderate COVID-19 may have significant impacts on function given systemic involvement of infection; rehabilitation needs may be more likely to be under-recognized and unmet in many of these patients. Overall, functional outcomes may be worse than expected in all COVID-19 patients because of prolonged length of illness and barriers to receiving rehabilitation services, including restricted face-to-face interactions, limited capacity, and limited access for many. Because CLD is associated with increased frailty and impaired function, patients with CLD may be particularly vulnerable not only to infection but also sequalae of COVID-19. Given the current physical distancing environment, we urgently need a new paradigm for rehabilitation of patients recovering from COVID-19 that can inform and apply to other causes of pneumonia as well. In this proposal we will determine patient rehabilitation needs across the spectrum of severity of COVID-19, assessing if needs differ by CLD, comorbidity burden, SDOH or other patient risk factors. We will also assess the feasibility and acceptability of a novel, virtually-delivered, home-based personalized telerehabilitation program for survivors of COVID-19 that contains a COVID Reactivation and Engagement (CORE) intervention with exercise and dyspnea management and additional personalized modules based on patient needs. We will recruit patients treated for COVID-19 as outpatients or discharged directly home for this program. We have a multidisciplinary team with expertise in rehabilitation medicine, psychology, pulmonary, critical care, nursing, complementary and integrative health, quantitative and qualitative observational research and clinical trials, and will accomplish three separate aims: 1) Determine patient factors associated with severity and complications of COVID-19 utilizing VA EHR data; 2) Determine self-reported functional outcomes and trajectory of recovery after COVID- 19 in a prospective study using mixed methods; and 3) Examine the feasibility and acceptability of a virtually- delivered, home-based rehabilitation intervention for survivors of COVID-19, with components based on an individual patient’s needs. Results will characterize the recovery from COVID-19 and identify rehabilitation and care needs across domains of services that can be offered within VA. Our pilot study will inform larger trials to test the efficacy of this newly-developed program to improve functioning, reduce secondary symptoms, and improve quality of life among individuals recovering from COVID-19.", "keywords": [ "Acute", "Admission activity", "Anxiety", "COVID-19", "COVID-19 complications", "COVID-19 patient", "COVID-19 severity", "COVID-19 survivors", "COVID-19 treatment", "Cardiac", "Cardiovascular system", "Caregivers", "Caring", "Cessation of life", "Chronic", "Chronic Obstructive Pulmonary Disease", "Chronic lung disease", "Classification", "Clinical", "Clinical Trials", "Cognition", "Cognitive", "Complementary Health", "Coronavirus", "Critical Illness", "Data", "Dialysis procedure", "Disease", "Dyspnea", "Dyspnea Management", "Electronic Health Record", "Environment", "Event", "Exercise", "Future", "Health", "Healthcare Systems", "Home", "Hospitalization", "Hospitals", "Impairment", "Individual", "Infection", "Influenza", "Inpatients", "Integrative Medicine", "Intensive Care Units", "International", "Intervention", "Interview", "Location", "Lung", "Mental Depression", "Mental Health", "Methods", "Nurses", "Observational Study", "Outcome", "Outpatients", "Oxygen", "Pain", "Patient Recruitments", "Patient Self-Report", "Patient risk", "Patient-Focused Outcomes", "Patients", "Personal Satisfaction", "Physical Function", "Physical Medicine", "Pilot Projects", "Pneumonia", "Predisposition", "Prospective Studies", "Psychology", "Quality of life", "Recovery", "Rehabilitation therapy", "Reporting", "Risk", "Risk Factors", "SARS-CoV-2 infection", "Services", "Severities", "Stroke", "Surveys", "Survivors", "Symptoms", "Syndrome", "Time", "Veterans", "Veterans Health Administration", "acceptability and feasibility", "base", "community acquired pneumonia", "comorbidity", "coronavirus disease", "critical care nursing", "design", "disability", "efficacy testing", "feasibility testing", "follow-up", "frailty", "functional outcomes", "health administration", "health related quality of life", "hospital readmission", "illness length", "improved", "improved functioning", "individual patient", "infection risk", "long term consequences of COVID-19", "mortality", "multidisciplinary", "novel", "pandemic disease", "pilot test", "programs", "prospective", "rehabilitation paradigm", "rehabilitation service", "rehabilitative care", "satisfaction", "social health determinants", "telerehabilitation", "uptake", "virtual delivery" ], "approved": true } }, { "type": "Grant", "id": "6801", "attributes": { "award_id": "5I01BX005447-02", "title": "Immune mediated lung injury in COVID-19", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [], "program_reference_codes": [], "program_officials": [], "start_date": "2021-04-01", "end_date": "2023-03-31", "award_amount": null, "principal_investigator": { "id": 21877, "first_name": "Jane C", "last_name": "Deng", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [ { "id": 770, "ror": "", "name": "UNIVERSITY OF MICHIGAN AT ANN ARBOR", "address": "", "city": "", "state": "MI", "zip": "", "country": "United States", "approved": true } ] }, "other_investigators": [], "awardee_organization": { "id": 1477, "ror": "https://ror.org/05eq41471", "name": "Veterans Health Administration", "address": "", "city": "", "state": "MI", "zip": "", "country": "United States", "approved": true }, "abstract": "SARS-CoV-2 and the disease it causes (COVID-19) has emerged as a major global public health threat in the span of a few months. In particular, SARS-CoV-2 adds to the present number of acute respiratory infections, including influenza and bacterial pneumonia, which are endangering the health of our veterans and aging population. In particular, severe COVID-19 disease is characterized by severe lung injury, which results in severely impaired oxygen delivery and ultimately multiple organ failure and death. Our ongoing research has focused on a population of white blood cells called neutrophils, which are the most abundant white blood cell in our body and which have been shown to be a pivotal immune cell that contributes greatly to lung injury. However, our current medical knowledge is inadequate for understanding what neutrophils do in the context of viral infection. Although neutrophils are critical for eliminating many types of infections, they are believed to be a major contributor to the development of lung injury, and how to balance their beneficial activities with their harmful functions is poorly understood. Therefore, a better understanding of how neutrophils behavior and phenotype are altered during severe SARS-CoV-2 and other viral infections would aid in developing novel therapies to improve their antimicrobial functions, while limiting their injurious effects. The research we propose in this grant will examine how well neutrophils eliminate SARS-CoV-2 viruses, or if they are an excessively activated population of immune cells recruited to the lung whose harmful activities outweighs their benefits. We also will test an exciting new treatment approach developed by our collaborator at UCLA to see if this can block the damaging effects of neutrophils on lung cells, while blocking viral replication. The results of this 2-year project will provide insights into the beneficial versus harmful contributions of neutrophils in the development of severe COVID-19 disease, and potentially identify new therapies to benefit veterans and other vulnerable patients.", "keywords": [ "2019-nCoV", "Acute", "Acute Lung Injury", "Acute Respiratory Distress Syndrome", "Acute respiratory infection", "Age", "Animal Model", "Antiviral Agents", "Apoptosis", "Bacterial Pneumonia", "COVID-19", "COVID-19 pandemic", "Cardiopulmonary", "Cell Death", "Cells", "Cessation of life", "Chronic", "Coculture Techniques", "Collaborations", "Coronavirus", "Coronavirus Infections", "Data", "Development", "Disease", "Elderly", "Epithelial Cells", "Equilibrium", "Exposure to", "Failure", "Funding", "Grant", "Health", "Histones", "Host Defense", "Human", "Immune", "Immune response", "Immunology", "Immunotherapy", "Impairment", "In Vitro", "Infection", "Inflammation", "Inflammation Mediators", "Inflammatory Response", "International", "Knowledge", "Lead", "Leukocytes", "Literature", "Lung", "Lung infections", "Mechanical ventilation", "Mediating", "Mediator of activation protein", "Medical", "Modeling", "Morbidity - disease rate", "Mouse Strains", "Multiple Organ Failure", "Murine hepatitis virus", "Mus", "Natural Killer Cells", "Oxygen", "Pathogenesis", "Pathogenicity", "Pathology", "Patients", "Peptides", "Play", "Population", "Positioning Attribute", "Public Health", "Pulmonary Pathology", "Reporting", "Research", "Research Proposals", "Resolution", "Risk", "Risk Factors", "Role", "SARS-CoV-2 immunity", "SARS-CoV-2 infection", "Severe Acute Respiratory Syndrome", "Testing", "Veterans", "Viral", "Virus", "Virus Diseases", "Virus Replication", "Virus Shedding", "aging population", "antimicrobial", "antiviral immunity", "base", "behavioral phenotyping", "comorbidity", "cytotoxicity", "design", "extracellular", "fighting", "global health", "improved", "in vivo", "influenza pneumonia", "insight", "lung development", "lung injury", "male", "military veteran", "mortality", "neutrophil", "novel", "novel therapeutics", "pathogen", "patient population", "preservation", "prevent", "recruit", "repaired", "response", "severe COVID-19" ], "approved": true } }, { "type": "Grant", "id": "6810", "attributes": { "award_id": "5I01BX005434-02", "title": "COVID19: Optimized Endosome-Targeting Compounds for SARS-CoV-2 and Emerging Coronaviruses", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [], "program_reference_codes": [], "program_officials": [], "start_date": "2021-04-01", "end_date": "2023-03-31", "award_amount": null, "principal_investigator": { "id": 22628, "first_name": "Joseph Stone", "last_name": "Doggett", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [ { "id": 1518, "ror": "https://ror.org/02v3txv81", "name": "Portland VA Medical Center", "address": "", "city": "", "state": "OR", "zip": "", "country": "United States", "approved": true } ] }, "other_investigators": [], "awardee_organization": { "id": 1518, "ror": "https://ror.org/02v3txv81", "name": "Portland VA Medical Center", "address": "", "city": "", "state": "OR", "zip": "", "country": "United States", "approved": true }, "abstract": "COVID-19 is a global health crisis that must be countered with the full capacity of government agencies, the private sector and the scientific community. New drugs that are broadly effective against coronaviruses are a crucial tool for ending this pandemic and preventing future coronavirus pandemics. Veterans are particularly at risk for severe COVID-19 due to older age and higher rates of cardiovascular disease. Initial efforts to repurpose drugs for COVID-19 have revived interest in the antiviral activity of the 4- aminoquinolines: chloroquine and hydroxychloroquine. Chloroquine has shown promise as an antiviral against many pathogenic viruses in past preclinical studies, but these results have not translated into clinical benefit. Initial clinical observations in China suggested that hydroxychloroquine may improve clinical outcomes, but as of yet, this evidence remains inconclusive. Overall, chloroquine’s broad antiviral activity indicates a promising antiviral mechanism that should be optimized by evaluating mechanistically similar compounds that target intracellular endosomes that are essential for viral pathogenesis. This research proposal will test a focused chemical library of 4-aminoquinolines and aminoacridones that are mechanistically similar to hydroxychloroquine against SARS-CoV-2 and related human coronaviruses. These compounds were designed to have less cardiac toxicity than chloroquine and enhanced accumulation in the Plasmodium digestive vacuole; properties that will likely lead to greater antiviral efficacy by creating higher drug concentrations in the intracellular endosomes that viruses require for host cell entry. Initial antiviral testing will both identify hits for preclinical evaluation and prioritization, and provide an extensive structure-activity- relationship to guide synthesis of new compounds with greater antiviral potency. The most potent compounds that are not toxic to human cells will be tested for target specificity, cardiac toxicity, and pharmacokinetic feasibility. The early lead compounds from these studies will be rapidly advanced to testing in animal models of SARS-CoV-2, other pathogenic coronaviruses and further preclinical testing via a separate funding mechanism. For the structure-activity-relationship, computational pharmacophore modeling will use the results of the initial antiviral testing, human cytotoxicity studies and target identification to identify structural features that enhance antiviral activity. Based on these models, new antiviral 4-aminoquinolines will be created and evaluated in the same manner as the hit compounds from the antiviral screen. This research will build on the repurposed compound, hydroxychloroquine, to quickly identify endosome targeting antivirals with greater clinical efficacy and safety for coronaviruses.", "keywords": [ "2019-nCoV", "4-aminoquinoline", "Age", "Animal Model", "Animals", "Antiviral Agents", "Biological Assay", "COVID-19", "COVID-19 pandemic", "COVID-19 treatment", "Cardiotoxicity", "Cardiovascular Diseases", "Cells", "China", "Chiroptera", "Chloroquine", "Clinical", "Clinical Trials", "Communities", "Coronavirus", "Dose", "Drug Kinetics", "Drug Screening", "Economics", "Endosomes", "Evaluation", "Funding Mechanisms", "Future", "Government Agencies", "Health", "Health protection", "Healthcare Systems", "Human", "Human Cell Line", "Hydroxychloroquine", "Image", "In Vitro", "Industry", "Infection", "Investigation", "Knowledge", "Lead", "Life", "Measures", "Metabolic", "Middle East Respiratory Syndrome", "Modeling", "Mus", "Oral", "Outcome", "Pathogenicity", "Pathway interactions", "Pharmaceutical Preparations", "Plasmodium", "Populations at Risk", "Preclinical Testing", "Prevalence", "Private Sector", "Property", "Prophylactic treatment", "Public Health", "Pulmonary Hypertension", "Reporting", "Research", "Research Proposals", "Risk", "SARS coronavirus", "SARS-CoV-2 inhibitor", "SARS-CoV-2 transmission", "Safety", "Science", "Severe Acute Respiratory Syndrome", "Specificity", "Structure-Activity Relationship", "Survival Analysis", "Symptoms", "Testing", "Toxic effect", "United States", "Vaccines", "Vacuole", "Vero Cells", "Veterans", "Viral Pathogenesis", "Virus", "Virus Replication", "Vulnerable Populations", "amphiphilicity", "anti-viral efficacy", "base", "clinical efficacy", "compound 30", "cytotoxicity", "design", "drug repurposing", "effective therapy", "global health", "human coronavirus", "human old age (65+)", "improved", "in vitro activity", "interest", "mortality", "novel coronavirus", "novel therapeutics", "pandemic disease", "pathogenic virus", "pharmacophore", "preclinical evaluation", "preclinical study", "prevent", "response", "severe COVID-19", "small molecule libraries", "tertiary amine", "tool", "transmission process", "warfighter", "zoonotic coronavirus" ], "approved": true } }, { "type": "Grant", "id": "6840", "attributes": { "award_id": "1IK2CX002192-01A2", "title": "Predictor Profiles of Opioid Use Disorders and Overdose Among Post-9/11 Veterans", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [], "program_reference_codes": [], "program_officials": [], "start_date": "2022-04-01", "end_date": "2027-03-31", "award_amount": null, "principal_investigator": { "id": 22670, "first_name": "Jennifer R", "last_name": "Fonda", "orcid": "https://orcid.org/0000-0001-9482-2918", "emails": "[email protected]", "private_emails": null, "keywords": "[]", "approved": true, "websites": "[]", "desired_collaboration": "", "comments": "", "affiliations": [ { "id": 1521, "ror": "", "name": "VA BOSTON HEALTH CARE SYSTEM", "address": "", "city": "", "state": "MA", "zip": "", "country": "United States", "approved": true } ] }, "other_investigators": [], "awardee_organization": { "id": 1521, "ror": "", "name": "VA BOSTON HEALTH CARE SYSTEM", "address": "", "city": "", "state": "MA", "zip": "", "country": "United States", "approved": true }, "abstract": "The overall aim of this proposed study is to use machine learning prediction models to evaluate the multifaceted, additive and multiplicative interactions of known and novel risk factors for opioid use disorder (OUD) and overdose in Post-9/11 Veterans. The proposed study will also investigate the short- and long-term impact of the coronavirus disease 2019 (COVID-19) pandemic on the risk of OUD and overdose. TRAINING PLAN: The CDA-2 training plan will facilitate the applicant’s primary career goal of becoming a fully funded, independent epidemiologic researcher at the Department of Veterans Affairs (VA), with a focus on addiction and suicidal behavior. The CDA-2 will provide additional training necessary to lead an independent program of research investigating the multifaceted sociodemographic, physical, psychological, and behavioral factors mediating and moderating the risk of addiction and suicidal behavior. The first step of achieving this goal is to complete the following training aims: 1) gaining expertise in the biological and behavioral basis of addiction; 2) gaining expertise in the assessment of the problems of TBI and blast exposure, psychiatric disorders, and suicidal behavior, which is pervasive in this generation of Veterans; 3) gaining expertise in advanced analytic techniques employed in health data science, including machine learning algorithms; and 4) professional development to achieve career independence as a VA funded epidemiologic researcher. RESEARCH DESIGN & METHODS: The proposed study will use Veterans Health Administration (VHA) electronic medical records to develop models predicting OUD and overdose risk. The sample will include Post- 9/11 Veterans who are aged 18-65, receive care in the VHA, and will have completed the VA primary TBI screen between October 2007 and February 2020 (n~1,267,000). We will assess the risk of incident and recurrent OUD and overdose events, as separate outcomes, using machine learning algorithmic models. We will examine whether overdose was 1) fatal and non-fatal and 2) intentional and unintentional. For Aims 1 and 2, we will examine the risk of OUD and overdose events between October 1, 2007 and February 29, 2020. For Exploratory Aim 3, we will examine the risk of OUD and overdose events between March 1, 2020 and September 30, 2025. We will use several machine learning classification-tree modeling approaches, including classification and regression trees, random forest, and gradient boosting, to develop predictor profiles of OUD and overdose incorporating important risk factors and interactions. The validity (sensitivity and specificity) and prediction accuracy (area under the curve) will be assessed for all prediction profile models. OBJECTIVES: Aim 1: Develop and evaluate the performance of predictor profiles incorporating known and novel risk factors and interactions for OUD and overdose over proximal (30, 60, and 90 days) and distal (180, 365, 730, 1095 and >1460 days) prediction intervals using machine learning classification algorithms. Hypothesis 1a: The machine learning algorithms will have high validity and prediction accuracy (e.g., sensitivity and specificity and area under the curve) >0.8. Hypothesis 1b: Accuracy and predictive ability will be higher in the proximal vs. distal prediction intervals. Aim 2: Examine gender, race/ethnicity, deployment-related trauma (e.g., TBI and prevalent psychiatric and substance disorders), and close-blast exposure as moderators of the risk of OUD and overdose. Hypothesis 2: There will be novel risk factors and differential variable importance impacting the risk of OUD and overdose within the subgroup-specific predictor profiles. Exploratory Aim 3: Investigate the short- and long-term impact of the COVID-19 pandemic on the risk of OUD and overdose using machine learning classification algorithms to develop predictor profiles of known and novel risk factors and interactions. Hypothesis 3: The COVID-19 pandemic will have both a direct effect on the risk for OUD and overdose and an indirect effect through the onset or exacerbation of mental health symptoms and psychiatric conditions.", "keywords": [ "Adverse event", "Afghanistan", "Amalgam", "Anxiety", "Area Under Curve", "Behavioral", "Biological", "COVID-19 pandemic", "Caring", "Complex", "Computerized Medical Record", "Conflict (Psychology)", "Data", "Data Science", "Databases", "Development", "Disease", "Distal", "Domestic Violence", "Early Intervention", "Epidemiology", "Ethnic Origin", "Event", "Funding", "Gender", "General Population", "Generations", "Goals", "Health Services Accessibility", "High Prevalence", "Individual", "Intervention", "Iraq", "Lead", "Machine Learning", "Measures", "Mediating", "Mental Depression", "Mental Health", "Mental disorders", "Modeling", "Opioid", "Outcome", "Overdose", "Performance", "Population", "Post-Traumatic Stress Disorders", "Public Health", "Race", "Recording of previous events", "Recurrence", "Research", "Research Design", "Research Methodology", "Research Personnel", "Risk", "Risk Factors", "Sampling", "Sensitivity and Specificity", "Social Distance", "Subgroup", "Substance Use Disorder", "Symptoms", "Techniques", "Testing", "Training", "Trauma", "Traumatic Brain Injury", "United States", "United States Department of Veterans Affairs", "Veterans", "Veterans Health Administration", "Work", "addiction", "advanced analytics", "aged", "blast exposure", "career", "chronic pain", "classification algorithm", "classification trees", "cohort", "comorbidity", "disorder risk", "epidemiology study", "gradient boosting", "health data", "high risk", "improved", "machine learning algorithm", "machine learning classification", "machine learning method", "machine learning prediction", "military veteran", "novel", "opioid epidemic", "opioid misuse", "opioid use disorder", "overdose risk", "pandemic disease", "post 9/11", "precision medicine", "predictive modeling", "programs", "psychologic", "random forest", "regression trees", "sociodemographics", "study population", "suicidal behavior", "targeted treatment", "trauma exposure" ], "approved": true } }, { "type": "Grant", "id": "6841", "attributes": { "award_id": "1I01CX002322-01A1", "title": "Neural and cognitive consequences of COVID-19 survival.", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [], "program_reference_codes": [], "program_officials": [], "start_date": "2021-10-01", "end_date": "2025-09-30", "award_amount": null, "principal_investigator": { "id": 22671, "first_name": "Judith M", "last_name": "Ford", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [ { "id": 1522, "ror": "", "name": "VETERANS AFFAIRS MED CTR SAN FRANCISCO", "address": "", "city": "", "state": "CA", "zip": "", "country": "United States", "approved": true } ] }, "other_investigators": [ { "id": 22672, "first_name": "Lynn", "last_name": "PULLIAM", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "awardee_organization": { "id": 1522, "ror": "", "name": "VETERANS AFFAIRS MED CTR SAN FRANCISCO", "address": "", "city": "", "state": "CA", "zip": "", "country": "United States", "approved": true }, "abstract": "The SARS-CoV-2 pandemic has been going on for over a year worldwide, with 115,000,000 confirmed cases and over 2,500,000 deaths (as of Mar 3, 2021). We are seeing people recover from the initial COVID19 infection with complaints of ongoing problems. An increasing number of people are complaining of cognitive deficits and depression/anxiety. Veterans are at a higher risk of COVID19 infection as well as suffering complications due to a number of co-morbidities. Veterans with neurocognitive complications may experience premature aging and neurodegeneration that could manifest as a huge burden for health care. We have brought together two laboratories studying neurocognitive impairment using an EEG, MRI, and behavioral approach as well as laboratory-based data. The Ford lab proposes to query neuropsychological function in Veterans using a computerized internet-based neuropsychological battery, EEG-based measures, functional MRI (connectivity) and structural MRI (gray and white matter volumes, myelin, micro-bleeds). The Pulliam lab has preliminary data to show a continued increase in plasma cytokines in COVID19 survivors. Plasma isolated neuronal enriched extracellular vesicles (nEVs) showed an increase in amyloid beta, neurofilament light and pT181- Tau, all proteins associated with neurodegeneration. The Overall Aim is to determine the extent of the cognitive, clinical, and neurological damage in people recovered from COVID19. The Specific Aims are to: 1) characterize neuropsychological function in COVID19 survivors, 2) assess EEG and MRI data in COVID19 survivors, 3) determine whether peripheral inflammation and markers of neuroinflammation, aging, and neurodegeneration persist in nEVs, and 4) explore relationships between neurodegenerative and inflammatory blood markers and EEG/MRI/NP measures while considering pre-existing co-morbidities and complications of COVID19.", "keywords": [ "Age", "Aging", "Amyloid beta-Protein", "Anxiety", "Attention", "Auditory", "Behavioral", "Biological", "Biological Assay", "Biological Markers", "Blood", "Blood Vessels", "Brain", "Brain imaging", "COVID-19", "COVID-19 complications", "COVID-19 pandemic", "COVID-19 survivors", "Cells", "Cessation of life", "Clinic", "Clinical", "Cognition", "Cognitive", "Cognitive deficits", "Collaborations", "Data", "Diabetes Mellitus", "Electroencephalography", "Event", "Event-Related Potentials", "Functional Magnetic Resonance Imaging", "Functional disorder", "HIV", "Healthcare", "Impaired cognition", "Infection", "Inflammatory", "Internet", "Laboratories", "Laboratory Study", "Light", "Lung", "Magnetic Resonance Imaging", "Measures", "Memory", "Mental Depression", "Methods", "Myelin", "Nerve Degeneration", "Nervous System Trauma", "Neural Cell Adhesion Molecule L1", "Neurocognitive", "Neurocognitive Deficit", "Neurologic", "Neuronal Dysfunction", "Neurons", "Neurophysiology - biologic function", "Neuropsychology", "Obesity", "P300 Event-Related Potentials", "Parents", "Pathologic", "Patient Recruitments", "Peripheral", "Persons", "Pilot Projects", "Plasma", "Precipitation", "Premature aging syndrome", "Proteins", "Psychological Tests", "Reporting", "Rest", "SARS-CoV-2 infection", "SARS-CoV-2 positive", "San Francisco", "Signal Transduction", "Smoking", "Techniques", "Time", "Translating", "Veterans", "Work", "base", "body system", "cell injury", "cognitive function", "comorbidity", "computerized", "coronavirus disease", "cytokine", "experience", "experimental study", "extracellular vesicles", "gray matter", "high risk", "inflammatory marker", "long-term sequelae", "magnetic resonance imaging/electroencephalography", "neurofilament", "neuroimaging", "neuroinflammation", "neurophysiology", "novel coronavirus", "post-COVID-19", "relating to nervous system", "response", "tau Proteins", "white matter" ], "approved": true } } ], "meta": { "pagination": { "page": 1405, "pages": 1419, "count": 14184 } } }