Grant List
Represents Grant table in the DB
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{ "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=1392&sort=award_amount", "next": "https://cic-apps.datascience.columbia.edu/v1/grants?page%5Bnumber%5D=2&sort=award_amount", "prev": null }, "data": [ { "type": "Grant", "id": "14594", "attributes": { "award_id": "1I21HX003799-01A1", "title": "Systems Analysis of Healthcare-Associated Infection Prevention during the COVID-19 Pandemic", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [], "program_reference_codes": [], "program_officials": [], "start_date": "2024-05-01", "end_date": "2025-10-31", "award_amount": null, "principal_investigator": { "id": 31260, "first_name": "Julie A", "last_name": "Keating", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 2247, "ror": "", "name": "WM S. MIDDLETON MEMORIAL VETERANS HOSP", "address": "", "city": "", "state": "WI", "zip": "", "country": "United States", "approved": true }, "abstract": "Background: Effective healthcare-associated infection (HAI) prevention requires multiple complex interventions (e.g., hand hygiene, environmental cleaning, personal protective equipment use, and evidence-based patient procedure protocols such as central line maintenance). The COVID-19 pandemic’s effects on healthcare (e.g., staffing shortages, supply chain disruptions, modified protocols to reduce exposure) also impacted HAI prevention. Retrospective analyses have found differential impacts on HAI rates during the pandemic, with some HAIs increasing and others decreasing. However, there has not yet been an assessment of how the COVID-19 pandemic specifically impacted guideline-concordant HAI prevention practices. Significance: This pilot project directly addresses HSR&D’s research priority to enhance the Quality and Safety of Health Care by gathering critical information regarding the implementation of HAI prevention practices during the COVID-19 pandemic. Information gathered here will inform the effective implementation of HAI prevention activities, including resuming guideline-concordant HAI prevention practices, to reduce HAIs across VA and increase the quality and safety of the healthcare received by Veterans. Innovation and Impact: We will conduct a work systems analysis using the Systems Engineering Initiative for Patient Safety (SEIPS) framework, which allows for the assessment of barriers and facilitators within and between each individual work system element (people, tools and technology, task, organization, and environment). This granular analysis allows for identifying and addressing specific barriers to implementation, which can be difficult to identify in complex work systems like those in HAI prevention. By addressing these barriers, we can develop implementation strategies to support the resuming of guideline-concordant HAI prevention practices in work systems that were or are continuing to be affected by COVID-19-related impacts. Specific Aims: In this pilot project, we aim to: 1. Conduct a work systems analysis of HAI prevention during the COVID-19 pandemic among acute inpatient care facilities in VISN12 to identify specific impacts of the pandemic on HAI prevention and HCW-reported needs for improved HAI prevention during the pandemic. 2. Identify barriers and facilitators to resuming IPC best practices in the COVID endemic era. Methodology: We will conduct semi-structured interviews with 1) 1-2 HAI prevention stakeholders and 2) up to 5 frontline nursing personnel at each of the 8 VA medical centers in VISN12. We will use interview guides structured around the CDC’s multidrug-resistant organism prevention strategies and the SEIPS framework to probe pandemic-related changes to HAI prevention practices as well as reasons behind these changes and barriers to resuming practices. We will use a rapid qualitative inquiry approach to analyze interview data, ultimately producing 1) a specific list of HAI prevention practices that were substantially modified during the COVID-19 pandemic and require additional implementation support to resuming practices; 2) work system element barriers and facilitators to conducting these practices during the pandemic; and 3) a logic model guiding the development of a larger research project on priority HAI prevention practices. Next Steps/Implementation: This pilot project will identify specific HAI prevention practices requiring additional implementation support, leading directly to a larger research project to gather VA-wide data on the implementation of these practices. We will also then develop and test implementation strategies to maximize effectiveness of the practice in reducing HAIs while minimizing burden on healthcare workers. This work will thus improve VA’s ability to respond to major disruptions to resources and processes (as COVID-19 was) while maintaining the safety and quality of care for Veterans.", "keywords": [ "Acute", "Address", "Area", "Bathing", "COVID-19", "COVID-19 impact", "COVID-19 pandemic", "COVID-19 pandemic effects", "Catalogs", "Clostridium difficile", "Complex", "Data", "Development", "Devices", "Disease Outbreaks", "Effectiveness", "Elements", "Engineering", "Environment", "Equipment", "Event", "Future", "Goals", "Guidelines", "Hand", "Health Personnel", "Health Priorities", "Health care facility", "Healthcare", "Healthcare Systems", "Hospitals", "Hygiene", "Individual", "Infection", "Infection Control", "Infection prevention", "Inpatients", "Interruption", "Intervention", "Interview", "Logic", "Maintenance", "Measures", "Medical center", "Mental Health", "Methodology", "Modeling", "Nursing Staff", "Oral", "Outcome", "Patient Care", "Patients", "Patterns of Care", "Persons", "Phase", "Pilot Projects", "Prevention strategy", "Procedures", "Process", "Protocols documentation", "Provider", "Quality of Care", "Reporting", "Research Priority", "Research Project Grants", "Resource-limited setting", "Resources", "Risk Reduction", "Route", "Safety", "Sepsis", "Shock", "Structure", "System", "Systems Analysis", "Technology", "Testing", "Training", "United States Department of Veterans Affairs", "Ventilator", "Veterans", "Work", "acute care", "burnout", "evidence base", "healthcare-associated infections", "implementation barriers", "implementation evaluation", "implementation strategy", "implementation study", "improved", "infection rate", "information gathering", "innovation", "inpatient service", "multi-drug resistant pathogen", "pandemic disease", "pandemic impact", "pathogen", "patient safety", "personal protective equipment", "pre-pandemic", "prevent", "prevention practice", "response", "supply chain", "tool", "transmission process", "trend" ], "approved": true } }, { "type": "Grant", "id": "7944", "attributes": { "award_id": "1I01HX003364-01A1", "title": "Dissemination and Implementation of a Videoconference Antimicrobial Stewardship Team (VAST)", "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": 23816, "first_name": "CHARLESNIKA T", "last_name": "EVANS", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [ { "id": 1483, "ror": "https://ror.org/01vrybr67", "name": "Louis Stokes Cleveland VA Medical Center", "address": "", "city": "", "state": "OH", "zip": "", "country": "United States", "approved": true } ] }, "other_investigators": [ { "id": 23817, "first_name": "Robin", "last_name": "Jump", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "awardee_organization": { "id": 1483, "ror": "https://ror.org/01vrybr67", "name": "Louis Stokes Cleveland VA Medical Center", "address": "", "city": "", "state": "OH", "zip": "", "country": "United States", "approved": true }, "abstract": "Background: Antimicrobial stewardship guidelines call for a multidisciplinary team with an infectious disease (ID) physician and ID-trained clinical pharmacist as core members. Unfortunately, there are insufficient ID- trained specialists to staff on-site antimicrobial stewardship programs throughout VA. Significance: This proposal is highly significant for Veterans and the goals of VA. Veterans experience many of the risk factors associated with development of antimicrobial resistant and healthcare-associated infections. The unprecedented effects of the novel Coronavirus disease 2019 (COVID-19) on the health of our Veterans and on our entire healthcare system makes the demand for ID expertise even more apparent, especially in long-term care. Also, this study directly addresses the VA MISSION ACT to improve access to care, timeliness and quality of care, using telehealth services. Finally, this project is aligned with the priorities of our operation partners: VA Antimicrobial Stewardship Taskforce (ASTF), the VA National Infectious Disease Service (NIDS), VA Pharmacy Benefits Management (PBM) Services, and the Office of Rural Health. Innovation and Impact: The design is innovative because we will systematically test and assess implementation barriers to telehealth for antimicrobial stewardship, a novel approach that has not been implemented in VA facilities, other than in our previous pilot study. Further, the Antibiotic Use Reports (AURs) are an innovative adaptation of peer-comparison, an antibiotic stewardship strategy successful in outpatient settings. This project will provide findings for a scalable model that could be deployed nationally to all applicable VAMCs, continuing the role of VHA as a leader in implementing large-scale interventions focused on prevention and management of ID and stewardship. Specific Aims: Our goal is to implement a multidisciplinary videoconference antimicrobial stewardship team (VAST) in VAMCs using SCAN-ECHO. Our central hypothesis is that feedback reports that quantify facility- level antibiotic use will enhance the efficacy of VASTs to support antimicrobial stewardship. We propose a Type 2 hybrid effectiveness-implementation design, comparing clinical effectiveness in sites that implement the VAST alone (VAST-) to sites that implement the VAST augmented by facility-level Antibiotic Use Reports (VAST+). Aims are: 1) Identify and test effective strategies for implementing the VAST; 2) Determine the influence of the VAST overall and VAST+ on the care of Veterans with suspected infections; 3) Determine the influence of the VAST overall and VAST+ on antibiotic use at each VAMC. Methodology: We will randomize rural VAMCs that do not have ID-trained professionals on staff to implement the VAST alone (VAST-) versus VAST + antibiotic use feedback (VAST+). Aim 1: We will assess modification and adaptations at the intervention sites and by the infectious disease experts. Methods will include process maps and semi-structured interviews to gather qualitative data about what key VAST members perceive as facilitators, barriers and burden to VAST implementation. We will also evaluate costs of implementation. Aim 2: We will evaluate the Veteran population served, clinical activities, and user perceptions of the VAST. We will assess the concordance of clinical care with recommendations from evidence-based clinical practice guidelines. VAST members’ perceptions of the quality and timeliness of care will be evaluated. Aim 3: The primary outcome measure will be overall rates of antibiotic use. Secondary outcomes will be changes in the rates of broad-spectrum antibiotic use, antibiotic starts, and length of antibiotic therapy. Next steps/Implementation: Testing effective implementation of the VAST at additional VAMCs is an important step toward augmenting antimicrobial stewardship in both acute- and long-term care settings. In collaboration with VA clinical operation partners, outcomes from this trial will be used to roll-out an implementation playbook to be used by other VAMCs, as well as non-VA settings.", "keywords": [ "Acute", "Address", "Administrator", "Affect", "Antibiotic Therapy", "Antibiotics", "Antimicrobial Resistance", "Area", "COVID-19", "Caring", "Cellulitis", "Cessation of life", "Clinical", "Clinical Nurse Specialists", "Clinical Pharmacists", "Clinical Practice Guideline", "Clinical effectiveness", "Collaborations", "Communicable Diseases", "Community Healthcare", "Complex", "Consultations", "Data", "Development", "Dissemination and Implementation", "Effectiveness", "Evidence based intervention", "Feedback", "Goals", "Guidelines", "Health", "Health Services Accessibility", "Healthcare", "Healthcare Systems", "Improve Access", "Individual", "Infection", "Infection Control", "Intervention", "Interview", "Length", "Long-Term Care", "Maps", "Measures", "Medical center", "Mentors", "Methodology", "Methods", "Modeling", "Modification", "Outcome", "Outcome Measure", "Outpatients", "Participant", "Patient Care", "Perception", "Pharmacists", "Physicians", "Pilot Projects", "Pneumonia", "Policy Maker", "Prevention", "Process", "Provider", "Quality of Care", "Randomized", "Recommendation", "Reporting", "Resources", "Risk Factors", "Role", "Rural", "Rural Health", "Services", "Site", "Specialist", "Structure", "System", "Testing", "Time", "Training", "United States Department of Veterans Affairs", "Urinary tract infection", "Veterans", "Work", "antimicrobial", "base", "care outcomes", "care providers", "clinical care", "combat", "design", "effectiveness implementation design", "effectiveness implementation study", "evidence base", "evidence based guidelines", "experience", "feasibility testing", "geographically distant", "global health", "healthcare-associated infections", "implementation barriers", "implementation cost", "implementation evaluation", "improved", "innovation", "interest", "medical specialties", "member", "military veteran", "multidisciplinary", "novel coronavirus", "novel strategies", "operation", "pathogen", "patient safety", "patient subsets", "peer", "pharmacy benefit", "prevent", "primary outcome", "programs", "secondary outcome", "telehealth" ], "approved": true } }, { "type": "Grant", "id": "7937", "attributes": { "award_id": "1IK6BX005962-01", "title": "BLR&D Research Career Scientist 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": "2022-04-01", "end_date": "2027-03-31", "award_amount": null, "principal_investigator": { "id": 23807, "first_name": "Todd A", "last_name": "Wyatt", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [ { "id": 1645, "ror": "", "name": "OMAHA VA MEDICAL CENTER", "address": "", "city": "", "state": "NE", "zip": "", "country": "United States", "approved": true } ] }, "other_investigators": [], "awardee_organization": { "id": 1645, "ror": "", "name": "OMAHA VA MEDICAL CENTER", "address": "", "city": "", "state": "NE", "zip": "", "country": "United States", "approved": true }, "abstract": "My primary research interests address chronic inflammatory lung disease, and the impact that behavioral and environmental exposures play in the compromise of lung innate defense against pathologic lung infections and injury. Utilizing pre-clinical mouse models and state-of-the-art molecular, biochemical, and cellular approaches, I collaborate closely with pulmonologists who practice at the VA to conduct relevant pre-clinical research that can be used to address current clinical concerns. I translate my findings to Veterans’ health using a well- characterized human lung cell and tissue biobank obtained from our lung transplant program. We have an existing cohort of Veterans with rural/agricultural occupational exposures to conduct relevant studies to our service region. There are 3 major research projects currently underway that impact veterans’ health: Malondialdehyde-acetaldehyde adducts and lung injury. Alcohol abuse causing increased susceptibility to pneumonia has been known for over 200 years. Because the majority (>90%) individuals misusing alcohol smoke cigarettes, we study the combination lung injury effects of both cigarettes and alcohol. We identified that the lungs represent a unique environment for the formation of stable malondialdehyde-acetaldehyde protein adducts (MAA adducts), but only under conditions of combined cigarette smoke and alcohol exposure. These MAA adducts cause airway epithelial cell cilia slowing and impair the innate pathogen clearance from the lung. Surfactant protein D (SPD) is a major lung protein that gets adducted when lung aldehyde concentrations are elevated during combined smoke and alcohol exposure and SPD-MAA adducts are detected in the lung only in drinkers who also smoke, leading to alterations in innate lung defense. (Funded by BX003635). Veterans- centric COVID-19 research. The pathogenesis of the SARS-CoV-2 virus and clinical outcomes from COVID 19 are far worse in individuals with certain pre-existing conditions and those of advanced age. It is essential to the health of Veterans to fully define which at-risk conditions particularly impact them and their unique needs to empower clinical preventive care during this and future viral pandemics. Old age and alcohol misuse are associated with cilia dysfunction. SPD has been documented to specifically bind to and neutralize the Spike protein of coronavirus. We hypothesize that altered innate lung defense at the level of mucociliary clearance, anti-microbial surfactants, and viral receptor function will negatively impact susceptibility and pathogenesis of SARS-CoV-2, placing Veterans particularly in harm’s way. We are currently identifying differences in SARS- CoV-2 infection responses between normal airway epithelium and lung macrophages and those cells collected from individuals with COPD, with alcohol use disorder, or of old age. Defining the modalities of risk will empower clinicians to make informed clinical preventive care decisions for Veterans (Funded by BX005413). Agricultural organic dust-mediated lung injury. VISN 23 encompasses a region responsible for the largest agricultural output in the nation. In collaboration with Omaha VA physician scientists, we have built a cohort of Veterans with agricultural exposures to explore the impact of organic dusts on chronic lung inflammatory injury. Using established mouse models, we have identified the therapeutic impact of IL-10 on lung repair from dust- mediated injury. We are currently defining the mechanisms of action through an active NIOSH R01 study and the Central States Center for Agricultural safety and Health (Funded by OH010162). With these innovative research programs, I have been able to provide training and mentoring to many undergraduates, graduate students, fellows, junior scientists and physicians at the Omaha VAMC and affiliated University of Nebraska Medical Center (UNMC). Our efforts to investigate the underlying mechanisms and identify targets for pulmonary disease have brought together physician scientists and basic scientists at the Omaha VA medical center and UNMC, which has led to the development of a VA-funded live-animal microCT Core facility, which I supervise and is the only such instrument in Omaha.", "keywords": [ "2019-nCoV", "Acetaldehyde", "Address", "Admission activity", "Age", "Agriculture", "Alcohol abuse", "Alcohol consumption", "Alcohols", "Aldehydes", "Animal Model", "Animals", "Area", "Award", "Bacterial Infections", "Behavioral", "Binding", "Biochemical", "Biological Markers", "COVID-19", "Caring", "Cells", "Chronic", "Chronic Obstructive Pulmonary Disease", "Chronic lung disease", "Cigarette", "Cilia", "Clinical", "Collaborations", "Core Facility", "Coronavirus spike protein", "Cyclic AMP-Dependent Protein Kinases", "Development", "Dust", "Elderly", "Environment", "Environmental Exposure", "Epithelial Cells", "Exposure to", "Extramural Activities", "Functional disorder", "Funding", "Future", "Grant", "Health", "Health Care Costs", "Healthcare", "Healthcare Systems", "Heavy Drinking", "Hospitals", "Human", "Impairment", "Individual", "Inflammation", "Inflammatory", "Injury", "Interleukin-10", "Laboratories", "Life", "Lung", "Lung Transplantation", "Lung diseases", "Lung infections", "Malondialdehyde", "Manuscripts", "Mediating", "Medical center", "Mentors", "Methodology", "Military Personnel", "Modality", "Molecular", "Morbidity - disease rate", "Mucociliary Clearance", "Natural Immunity", "Nebraska", "Occupational Exposure", "Outcome", "Output", "Pathogenesis", "Pathologic", "Peer Review", "Physicians", "Play", "Pneumonia", "Predisposition", "Preventive care", "Proteins", "Pulmonary Surfactant-Associated Protein D", "Recording of previous events", "Regulation", "Research", "Research Project Grants", "Respiratory Syncytial Virus Infections", "Risk", "Role", "Rural", "SARS-CoV-2 infection", "SARS-CoV-2 pathogenesis", "Safety", "Sampling", "Savings", "Science", "Scientist", "Seminal", "Services", "Smoke", "Smoker", "Smoking", "Source", "Substance abuse problem", "Supervision", "System", "TNF-alpha converting enzyme", "Therapeutic", "Time", "Tissues", "Training", "Translating", "Universities", "Veterans", "Viral", "Virus", "Virus Diseases", "Virus Receptors", "Work", "adduct", "agricultural center", "airway epithelium", "airway inflammation", "alcohol exposure", "alcohol misuse", "alcohol response", "alcohol use disorder", "antimicrobial", "biobank", "career", "cell motility", "chronic inflammatory lung disease", "cigarette smoke", "cohort", "cost", "desensitization", "digital", "disorder risk", "experience", "exposure to cigarette smoke", "former smoker", "graduate student", "human old age (65+)", "improved" ], "approved": true } }, { "type": "Grant", "id": "6917", "attributes": { "award_id": "1I21RX003738-01A1", "title": "A Novel Cognitive Remediation Intervention Targeting Poor Decision-Making and Depression in Veterans at High Risk for Suicide: A Safe,Telehealth Approach During the COVID-19 Pandemic", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [], "program_reference_codes": [], "program_officials": [], "start_date": "2022-01-01", "end_date": "2023-12-31", "award_amount": null, "principal_investigator": { "id": 22755, "first_name": "ERIN A.", "last_name": "HAZLETT", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [ { "id": 1533, "ror": "", "name": "JAMES J PETERS VA MEDICAL CENTER", "address": "", "city": "", "state": "NY", "zip": "", "country": "United States", "approved": true } ] }, "other_investigators": [], "awardee_organization": { "id": 1533, "ror": "", "name": "JAMES J PETERS VA MEDICAL CENTER", "address": "", "city": "", "state": "NY", "zip": "", "country": "United States", "approved": true }, "abstract": "Despite large-scale, nationwide efforts to better address suicidal behavior (defined as thoughts and behavior) in high-risk Veterans with major depressive disorder (MDD), the development of interventions that target some of the key risk factors associated with suicide in Veterans with MDD remains limited. That is, while much intervention research continues to investigate treatments like cognitive behavioral therapy (CBT) that target behavioral patterns, emotion processing problems, and cognitive styles associated with suicide risk in MDD, deficits in the neurocognitive substrates that underlie these CBT targets remain under-addressed. Cognitive remediation (CR) and rehabilitation have long been a primary treatment for patients with other psychiatric illnesses, like schizophrenia, for improving cognitive functioning and facilitating transfer of cognitive skills to every-day functioning. However, scant work has examined CR that addresses the neurocognitive deficits underlying suicidal behavior in individuals with MDD. Empirical work has identified key executive functioning (EF) deficits that may be specific to MDD patients with suicidal behavior, and meta-analytic work indicates that CR has moderate effect sizes on cognitive functioning, depression, and daily functioning in MDD. Thus, the field is in dire need of work that examines CR as a recovery-oriented treatment approach for MDD patients at risk for suicide. The proposed study aims to collect pilot data to test the feasibility and acceptability of adjunctive neuroplasticity-based CR on key treatment targets delivered via telehealth during this time of COVID-19 in a sample of 36 Veterans with MDD and a history of suicide attempt(s). Specifically, it will test the effects of an adjunctive evidence-based cognitive remediation (CR) therapy (adjunctive to treatment as usual) augmented with manualized “Bridging” sessions on transfer and practice of cognitive control and decision-making/problem- solving strategies for real-world situations and problems, including those that trigger suicidal thoughts. We propose to administer the Neuropsychological Educational Approach to Cognitive Remediation (NEAR, termed CR plus “Bridging” session, CR+Bridging) to a total of 36 Veterans with MDD and a history of suicide attempt(s). The intervention will be delivered in 20 90-minute sessions (2x/week for 10 weeks). Pre-treatment assessments of neurocognitive, clinical, social, and real-world functioning will be conducted, including measures that examine the impact of COVID-19 and its accompanying “social-distancing” restrictions. Post- treatment assessments of the same targets will be conducted to determine clinical response to and feasibility of this therapeutic intervention immediately following conclusion of the intervention (Week 10) and at a follow- up assessment (Week 20). This application is novel in that it constitutes the first implementation of this intervention in Veterans with MDD and suicidal behavior. Consistent with RR&D’s SPiRE mechanism, this study is high risk, but it has high potential impact and promise to help improve quality of life for Veterans at high risk for suicide.", "keywords": [ "Address", "Aftercare", "Behavior", "Behavioral", "COVID-19", "COVID-19 pandemic", "Client satisfaction", "Clinical", "Cognitive", "Cognitive Therapy", "Cognitive remediation", "Data", "Decision Making", "Elderly", "Emotions", "Evaluation", "Executive Dysfunction", "Feeling suicidal", "Gambling", "Goals", "Impairment", "Individual", "Intervention", "Intervention Studies", "Iowa", "Language", "Major Depressive Disorder", "Measures", "Mental Depression", "Mental disorders", "Names", "Neurocognitive", "Neurocognitive Deficit", "Neuronal Plasticity", "Neuropsychology", "Participant", "Patients", "Pattern", "Performance", "Pilot Projects", "Problem Solving", "Public Health", "Quality of life", "Questionnaires", "Recording of previous events", "Recovery", "Rehabilitation therapy", "Reporting", "Risk Factors", "Sampling", "Schizophrenia", "Semantics", "Services", "Severities", "Social Adjustment", "Social Distance", "Suicide", "Suicide attempt", "Testing", "Therapeutic Intervention", "Thinking", "Time", "Veterans", "Work", "acceptability and feasibility", "base", "cognitive control", "cognitive function", "cognitive rehabilitation", "cognitive skill", "cognitive testing", "daily functioning", "depressive symptoms", "evidence base", "executive function", "feasibility testing", "follow up assessment", "follow-up", "high risk", "implementation intervention", "improved", "innovation", "military veteran", "novel", "recruit", "response", "skills", "social", "stressor", "suicidal behavior", "suicidal risk", "symptomatology", "targeted treatment", "telehealth", "therapy development", "tool", "treatment as usual", "virtual" ], "approved": true } }, { "type": "Grant", "id": "14853", "attributes": { "award_id": "1I01CX002739-01", "title": "Characteristics and Determinants of Post-COVID Neurocognitive Dysfunction", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [], "program_reference_codes": [], "program_officials": [], "start_date": "2024-07-01", "end_date": "2028-06-30", "award_amount": null, "principal_investigator": { "id": 31536, "first_name": "Roger", "last_name": "Bedimo", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [ { "id": 31537, "first_name": "Amy Yomiko", "last_name": "Vittor", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "awardee_organization": { "id": 2503, "ror": "https://ror.org/01nzxq896", "name": "VA North Texas Health Care System", "address": "", "city": "", "state": "TX", "zip": "", "country": "United States", "approved": true }, "abstract": "Neurologic symptoms are among the most common post-acute sequelae of COVID-19 (PASC). Recent studies show that there is a very high rate of neurocognitive changes among Veterans surviving acute COVID- 19 infection. The long-term neurocognitive changes of this infection could be even worse and remains incompletely characterized. Moreover, neurological sequelae have been considered the most disabling of the long-term complications. Possible mechanisms of neuronal damage from SARS CoV-2 infection include direct viral CNS invasion through the cribriform plate or hematogenous route, or retrograde neuronal dissemination, or indirect injury mediated by systemic inflammation, and secondary degenerative mechanisms. Whether neurocognitive changes can be predicted by biomarkers – or imaging evidence of – inflammation, neuronal damage or disruption of blood brain barrier has never been evaluated in a well-characterized cohort. Furthermore, no treatment strategies exist at present, but preliminary data suggests that antivirals may prevent the occurrence of cognitive impairment in PASC. VHA has established a nationwide COVID-19 cohort early in the pandemic. This objective of this cohort – called Epidemiology, Immunology and Clinical Characteristics of COVID-19 (EPIC3) – is to characterize the natural history, clinical outcomes, and the development of immunity while also gathering biospecimens for future study as questions emerge about this new pathogen. We will leverage the data and samples from this study to compare participants who received antivirals during their acute COVID-19 illness with those who did not, by 1) conducting longitudinal cognitive assessments of participants of EPIC3 and characterize trajectories of cognitive changes, using a novel tablet-based tool; 2) carrying out detailed longitudinal analyses of biomarkers of neuronal damage, neurodegeneration and blood-brain barrier disruption or participants with and without COVID-19, and 3) performing advanced structural and functional imaging of a subset of these participants. We will then correlate biomarkers and imaging findings to the presence, degree and trajectories of neurocognitive changes in COVID-19 patients who did and did not receive antivirals. We have assembled a multidisciplinary team with expertise critical to answering the challenging questions posed by neurocognitive changes of PASC. Expected findings of our study will have immediate clinical impact: 1) they will establish whether PASC is an additional goal for antiviral therapy, 2) they will establish a benchmark for standardized, validated assessment of possible neurocognitive changes in patients with COVID-19; this will provide a basis for future interventions and management guidelines; 2) determine whether these cognitive changes could be predicted or monitored using well validated biomarkers of neuronal damage and/or blood-brain barrier disruption; 3) determine whether structural and function brain imaging could assist in further studies of mechanisms of neuronal damage and/or neurocognitive dysfunction from COVID-19 infection. Here we propose addressing current gaps in our understanding of cognitive function in PASC by following the trajectories of cognitive function over three years using validated, tablet-based neuropsychological tests, analyzing the relationship between co-morbidities prevalent amongst veterans such as PTSD and depressive disorders and cognitive impairment following COVID-19. This study will link key neurological and immunological markers, clinical outcomes, and imaging of cerebral blood flow and demyelination, thereby contributing a cohesive understanding of the mechanisms of neurological injury.", "keywords": [], "approved": true } }, { "type": "Grant", "id": "6913", "attributes": { "award_id": "2I01BX004270-04A1", "title": "Development of Novel Second Generation Anti-inflammatory Substrate-selective p38 MAP Kinase Inhibitors as Therapy for Acute Respiratory Distress Syndrome", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [], "program_reference_codes": [], "program_officials": [], "start_date": "2018-07-01", "end_date": "2025-12-31", "award_amount": null, "principal_investigator": { "id": 22751, "first_name": "JEFFREY D", "last_name": "HASDAY", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [ { "id": 1532, "ror": "https://ror.org/036a0e562", "name": "Baltimore VA Medical Center", "address": "", "city": "", "state": "MD", "zip": "", "country": "United States", "approved": true } ] }, "other_investigators": [], "awardee_organization": { "id": 1532, "ror": "https://ror.org/036a0e562", "name": "Baltimore VA Medical Center", "address": "", "city": "", "state": "MD", "zip": "", "country": "United States", "approved": true }, "abstract": "Acute Respiratory Distress Syndrome (ARDS) affects ~190,000 patients and causes ~75,000 deaths per year in the U.S.A. ARDS has a mortality rate of ~40% and causes significant morbidity in survivors. Respiratory viruses, including influenza and now Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2), are important causes of ARDS with limited therapeutic options. The VA patient population has many of the risk factors for having poor outcomes with ARDS, including older age, obesity, hypertension, diabetes, and chronic lung and heart disease. There are no currently available pharmacologic therapies proven to be effective in ARDS. To address this need, we developed a novel class of substrate- and function-selective p38 mitogen- activated protein kinases (MAPK) inhibitors with anti-inflammatory and endothelial-barrier stabilizing activity. Compared with conventional p38 catalytic inhibitors that block all downstream signaling including anti- inflammatory pathways, our novel compounds target one of the substrate docking sites and therefore only block certain p38-dependent processes. Together with my co-investigators, Drs. Shapiro, MacKerell, and Fletcher, we used computer-aided drug design (CADD) to identify a lead compound, UM101, that binds a pocket near the ED substrate docking site on p38a and exhibits a unique profile of biological activities. We developed a second-generation analog, SF7044, with greater solubility and improved endothelial barrier- stabilizing, anti-inflammatory, and lung-protective activities. We are currently collaborating with Gen1e Life Sciences, LLC, which licensed the patents for these compounds, completed preclinical testing and began clinical testing of SF7044. During our current Merit Award, we identified and screened 200 additional compounds targeted to the same substrate docking site as UM101 using a refined CADD strategy. We identified four new lead compounds with superior endothelial barrier stabilizing activity and p38a-binding compared with UM101 and SF7044 and distinct anti-inflammatory effect profiles, but poor solubility. In vivo testing in a mouse model will require reformulation or chemical modification of these new lead compounds to improve solubility (like UM101). The overall objective of this renewal is to use the same strategy as used for development of SF7044 to design, synthesize, and characterize second-generation analogs of the four new lead compounds with improved activity and drug-like properties. Since the new lead compounds have greater endothelial-stabilizing activity and p38a-binding than either UM101 or SF7044 we expect to develop second- generation analogs with substantially improved lung-protective activity. We will utilize CADD and medicinal chemistry principles, protein binding assays and human cell and mouse models of ALI: 1. Design and synthesize at least 20 analogs of each the 4 newly discovered lead compounds to improve p38a-binding and drug-like properties. 2. Analyze the second-generation analogs for target binding and biological activities. 3. Analyze toxicity and effectiveness of the most active second-generation analogs in mouse models of the exudative (LPS/hyperthermia) and fibroproliferative (bleomycin) phases of ARDS. 4. Evaluate new compounds for off-target effects At the conclusion of this work, we will have developed second generation analogs of novel non-catalytic p38α inhibitors with improved efficacy and safety profiles in mouse lung injury models to provide a pipeline of new compounds that are ready for advanced preclinical testing prior to clinical testing in ARDS.", "keywords": [ "2019-nCoV", "Acute Lung Injury", "Acute Respiratory Distress Syndrome", "Address", "Affect", "Affinity", "Age", "Anti-Inflammatory Agents", "Antiinflammatory Effect", "Aspartate", "Award", "Binding", "Binding Proteins", "Biological", "Biological Assay", "Biological Sciences", "Bleomycin", "Blood Vessels", "COVID-19", "COVID-19/ARDS", "Catalytic Domain", "Cell model", "Cells", "Cessation of life", "Chemicals", "Chronic lung disease", "Clinic", "Clinical Trials", "Complication", "Computer Assisted", "Computers", "Databases", "Death Rate", "Development", "Diabetes Mellitus", "Docking", "Dose", "Drug Design", "Drug Kinetics", "Effectiveness", "Endothelium", "Exhibits", "Fever", "Funding", "Future", "Generations", "Glutamates", "Goals", "Heart Diseases", "Human", "Hypertension", "Hyperthermia", "In Vitro", "Infection", "Inflammation", "Influenza", "Injury", "Lead", "Legal patent", "Lung", "Maps", "Maryland", "Mitogen-Activated Protein Kinase Inhibitor", "Mitogen-Activated Protein Kinases", "Mitogens", "Modeling", "Modification", "Molecular", "Monkeys", "Morbidity - disease rate", "Mus", "Obesity", "Outcome", "Pathogenicity", "Pathway interactions", "Patients", "Permeability", "Pharmaceutical Chemistry", "Pharmaceutical Preparations", "Pharmacodynamics", "Pharmacology", "Pharmacy Schools", "Phase", "Phosphotransferases", "Plasma", "Preclinical Testing", "Preparation", "Process", "Program Development", "Property", "Protective Agents", "Protein Kinase", "Protein phosphatase", "RPS6KA5 gene", "Rattus", "Research Personnel", "Risk Factors", "Safety", "Services", "Signal Transduction", "Site", "Solubility", "Specificity", "Surface Plasmon Resonance", "Survivors", "Testing", "Therapeutic", "Thrombin", "Toxic effect", "Universities", "Veterans", "Virus", "Work", "analog", "aqueous", "cytokine", "design", "disability", "drug candidate", "drug development", "efficacy testing", "epithelial injury", "improved", "in vivo", "in vivo evaluation", "inhibitor/antagonist", "kinase inhibitor", "lung injury", "mortality", "mouse model", "multimodality", "novel", "novel therapeutics", "p38 Mitogen Activated Protein Kinase", "patient population", "protective effect", "pulmonary artery endothelial cell", "receptor", "receptor binding", "research clinical testing", "respiratory virus", "safety study", "scaffold", "screening", "stress activated protein kinase", "therapeutic candidate", "therapeutic target" ], "approved": true } }, { "type": "Grant", "id": "8960", "attributes": { "award_id": "1I01HX003269-01A2", "title": "Social and Behavioral Determinants of Health in High-Risk 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": "2021-10-01", "end_date": "2025-09-30", "award_amount": null, "principal_investigator": { "id": 24796, "first_name": "MATTHEW L", "last_name": "MACIEJEWSKI", "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": [ { "id": 24797, "first_name": "Donna Michelle", "last_name": "Zulman", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "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. Social factors exert a substantially more potent impact on health than does health care, especially among disadvantaged populations such as VA users. Adverse social determinants of health (SDH)—factors such as housing instability, food insecurity, social isolation, and transportation barriers—are linked to problems with access, poorer clinical outcomes, and increased health care costs. Despite the clinical and business case for integrating SDHs into health care, these factors are not systematically assessed or addressed in clinical settings. Significance/Impact. This study will leverage a previous survey of Veterans at high-risk for hospitalization, and a new survey to be fielded to a nationally-representative sample of Veterans, to determine how SDHs influence clinical, health care utilization, and experience outcomes. Review of findings by key stakeholders will generate recommended SDH measures for universal screening within VA. These steps, coupled with qualitative interviews about implementation challenges, will inform the future integration of high-value patient-reported SDH measures into VA’s health record. Innovation. The proposed work is innovative in its evaluation of a broad array of SDHs in high-need Veterans to identify candidate measures for electronic health record (EHR) integration. The study will leverage a theoretically-driven survey of SDH measures with a data-driven approach to identifying the associations between these SDHs and a range of health, utilization, and patient experience outcomes. Results from these analyses will inform a facilitated deliberative process to prioritize high-value, validated, and actionable measures that are predictive of outcomes that are important to Veterans and the VA. Specific Aims. In Aim 1, we will use data from an Office of Primary Care-funded survey of Veterans at high-risk for hospitalization to examine relationships between patient-reported SDH measures and utilization, cost, and days in the community outcomes. In Aim 2, we will field a survey to a nationally-representative sample of VA patients to determine the association between SDH measures and key outcomes, and to examine the prevalence of SDHs in subpopulations of Veterans who are disproportionately affected by disparities (e.g., women, racial/ethnic minorities, and rural Veterans). Aims 1 and 2 will inform partner and stakeholder discussions in Aim 3 to identify measures that are associated with key outcomes and that are perceived by operations partners as actionable (i.e., addressable through VA or community services) and thereby good candidates for EHR integration. Methodology. In Aim 1, we will leverage data from an operations-funded survey that our team administered in 2018. Using survey data for 4,685 Veterans at high-risk for hospitalization, we will examine the association between patient-reported SDHs and utilization (i.e., VA and Medicare emergency department visits and hospitalizations), VA and Medicare costs, and days in the community. In Aim 2, we will field a similar survey to a nationally-representative sample of Veterans, evaluate the association between SDHs, patient experiences (e.g., perceived access and coordination), and 12-month VA emergency department visits, hospitalizations, and costs, and describe the prevalence of SDHs in the general VA population and Veterans who are at risk for health disparities. In Aim 3, we will use a facilitated deliberative process with key stakeholders to prioritize actionable SDH measures for EHR integration, and then conduct qualitative interviews with health system leaders, clinicians, staff, and patients to examine implementation barriers and facilitators to assessing select SDH measures at point of care. Implementation/Next Steps. This study addresses health equity, particularly relevant in light of COVID-19, and will be conducted with partners from VA’s Offices of Primary Care, Health Equity, Rural Health, and Women’s Health. The study is especially timely with VA’s transition to the new Cerner EHR as the proposed aims will identify SDH measures for potential EHR integration that are concise, actionable, and predictive of important outcomes.", "keywords": [ "Academy", "Accident and Emergency department", "Address", "Affect", "Area", "Bed Occupancy", "Behavioral", "Businesses", "COVID-19", "COVID-19 pandemic", "Caregivers", "Caring", "Clinical", "Communities", "Community Services", "Coupled", "Data", "Disadvantaged", "Economics", "Electronic Health Record", "Emergency department visit", "Environmental Risk Factor", "Evaluation", "Financial Hardship", "Funding", "Future", "Goals", "Health", "Health Care Costs", "Health system", "Healthcare", "Hospital Costs", "Hospital Departments", "Hospitalization", "Hospitals", "Individual", "Integrated Health Care Systems", "Intervention", "Interview", "Lead", "Leadership", "Life", "Light", "Link", "Measurement", "Measures", "Medicare", "Medicine", "Methodology", "Minority", "Modeling", "Outcome", "Patients", "Population", "Positioning Attribute", "Predictive Value", "Prevalence", "Prevention", "Primary Health Care", "Procedures", "Process", "Recommendation", "Reporting", "Research", "Research Personnel", "Respondent", "Rest", "Risk", "Risk Adjustment", "Rural", "Rural Health", "Sampling", "Screening procedure", "Shapes", "Social isolation", "Surveys", "System", "Time", "Transportation", "Trust", "United States Department of Veterans Affairs", "Variant", "Veterans", "Veterans Health Administration", "Woman", "Women&apos", "s Health", "Work", "base", "clinical care", "cost", "disadvantaged population", "economic outcome", "ethnic minority population", "experience", "food insecurity", "health care service utilization", "health care settings", "health disparity", "health equity", "health record", "high risk", "housing instability", "implementation barriers", "implementation facilitators", "improved", "innovation", "interoperability", "operation", "outcome prediction", "patient population", "point of care", "racial and ethnic", "screening", "social", "social factors", "social health determinants", "social vulnerability" ], "approved": true } }, { "type": "Grant", "id": "6912", "attributes": { "award_id": "1IK2RX003546-01A2", "title": "Enhanced Home-Based Exercise Therapy for Peripheral Arterial Disease through Mobile Health and Remote Monitoring", "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": "2026-09-30", "award_amount": null, "principal_investigator": { "id": 22750, "first_name": "Arash", "last_name": "Harzand", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [ { "id": 1477, "ror": "https://ror.org/05eq41471", "name": "Veterans Health Administration", "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": "An estimated 8.5 million Americans (or 7% of US adults) and nearly 10% of veterans are estimated to have peripheral arterial disease (PAD). Significantly debilitating and negatively impacting quality of life, the primary symptom of PAD is claudication (reproducible leg pain with ambulation) that leads to impaired mobility, loss of functional independence, and a heightened risk for amputation. Veterans are at an increased risk of developing symptomatic PAD due to their disproportionately high rates of PAD risk factors such as diabetes, smoking, and hypertension, the most prominent PAD risk factors. Supervised exercise therapy is proven to decrease claudication and enhance mobility in PAD; however, fewer than 25% of eligible patients enroll. Participation in this facility-based program requires travel to a rehabilitation center 3 times per week for 12-weeks, which can be burdensome and costly for Veterans, many of whom live in rural areas and on fixed incomes. There is, therefore, a need to develop a convenient and effective alternative exercise rehabilitation program for Veterans with PAD, particularly in light of safety considerations now associated with this population’s travel to group facilities in the current COVID pandemic. A promising approach to increase access to exercise rehabilitation for PAD is remote, home-based exercise therapy (HBET). Our group has successfully delivered a smartphone-enabled HBET program to Veterans with coronary artery disease with a 3-fold increase in participation and high satisfaction (80%). To this end, we are committed to utilizing technology innovations to implement HBET for Veterans with PAD successfully. HBET programs combine self-led walking exercises with health coaching and exercise tracking with a wearable activity monitor. Adapting HBET to PAD is difficult, however, due to the added complexity of an exercise prescription that requires the patient to walk until they experience near-maximal leg pain. Even with active coaching, successfully implementing HBET for PAD with long-term adherence has been difficult in the past. Our goal, therefore, is to leverage newer mobile health (mHealth) tools to adapt HBET for PAD. We propose to test our technology-enhanced approach for HBET by partnering with a successful VA lifestyle program, MOVE!, which has demonstrated success in achieving sustained weight loss and reduced diabetes onset through lifestyle modification. As increased physical activity is a core element of MOVE!, participation may help increase adherence with HBET for PAD. Our newly proposed program, Smart MOVE!, will be a multi-component program featuring a tailored version of MOVE! and a novel mHealth device called the LifeQ to improve convenience, access, and adherence to HBET for PAD. Aim 1 (Years 1-2): Identify barriers and facilitators to MOVE! participation among Veterans with PAD. Aim 2 (Years 1-2): Evaluate the feasibility of the LifeQ device to monitor exercise during HBET Aim 3 (Years 2-5): Determine the feasibility of proceeding with Smart MOVE! through a pilot randomized trial. As a VA physician actively treating Veterans with PAD, I have seen first-hand the challenges they face in accessing guideline-directed treatments such as supervised exercise. This study will lay the groundwork and provide evidence to proceed with Smart MOVE!, a much-needed patient-centered exercise rehabilitation program for PAD. Additionally, the proposed training plan will support my progress towards becoming an independent VA rehabilitation clinician-scientist focused on improving care quality and treatment outcomes for Veterans with PAD.", "keywords": [ "Accelerometer", "Activities of Daily Living", "Adherence", "Adult", "Affect", "American", "Amputation", "Behavioral", "Body Weight decreased", "COVID-19 pandemic", "Cardiac rehabilitation", "Cellular Phone", "Clinical", "Complex", "Coronary Arteriosclerosis", "Data", "Devices", "Diabetes Mellitus", "Elements", "Enhancement Technology", "Enrollment", "Exercise", "Exercise Therapy", "Face", "Goals", "Gold", "Guidelines", "Health", "Health Technology", "Home", "Hospitals", "Hypertension", "Impairment", "Income", "Indirect Calorimetry", "Intervention", "Interview", "Leadership", "Leg", "Life Style", "Life Style Modification", "Light", "Measurement", "Monitor", "Myocardial Infarction", "Oxygen Consumption", "Pain in lower limb", "Patient Education", "Patients", "Peripheral arterial disease", "Physical activity", "Physicians", "Population", "Provider", "Quality of Care", "Quality of life", "Rehabilitation Centers", "Rehabilitation therapy", "Reproducibility", "Resolution", "Risk", "Risk Factors", "Safety", "Scientist", "Smoking", "Stroke", "Structure", "Supervision", "Symptoms", "Technology", "Testing", "Time", "Training", "Travel", "Treatment outcome", "Vertebral column", "Veterans", "Walking", "aged", "base", "behavior change", "claudication", "cost", "design", "evidence base", "exercise prescription", "exercise program", "exercise regimen", "exercise rehabilitation", "experience", "functional independence", "functional loss", "functional outcomes", "high risk", "improved", "improved mobility", "informant", "innovation", "mHealth", "mortality risk", "multi-component intervention", "novel", "patient oriented", "primary outcome", "programs", "randomized trial", "remote monitoring", "rural area", "satisfaction", "success", "symptomatic improvement", "tool" ], "approved": true } }, { "type": "Grant", "id": "8200", "attributes": { "award_id": "5I01BX005490-02", "title": "COVID-19: SARS-CoV-2 Neutralizing Agents", "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": 24037, "first_name": "SUBHRA", "last_name": "MOHAPATRA", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [ { "id": 1638, "ror": "", "name": "JAMES A. HALEY VA MEDICAL CENTER", "address": "", "city": "", "state": "FL", "zip": "", "country": "United States", "approved": true } ] }, "other_investigators": [ { "id": 23775, "first_name": "Shyam S", "last_name": "Mohapatra", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [ { "id": 1638, "ror": "", "name": "JAMES A. HALEY VA MEDICAL CENTER", "address": "", "city": "", "state": "FL", "zip": "", "country": "United States", "approved": true } ] } ], "awardee_organization": { "id": 1638, "ror": "", "name": "JAMES A. HALEY VA MEDICAL CENTER", "address": "", "city": "", "state": "FL", "zip": "", "country": "United States", "approved": true }, "abstract": "COVID-19 super pandemic is still suffering from the lack of a vaccine or infection control measures and the lack of any treatments against this new virus. One of the unique features of SARS-CoV-2 is that it has an R0=2.2 (the ability of an infected patient to spread the disease) vs R0=1 for SARS-CoV and R0=0.3 for Influenza. Due to this, individuals infected with SARS-CoV-2 remain asymptomatic and yet pass on the virus to family, friends and colleagues at work, thus expanding the COVID-19 cases. Given the impending second wave of the pandemic and the potential of SARS-CoV-2 being a seasonal virus, there is a dire urgent need to develop prophylactic vaccines and/or therapy (PV/T), which can treat the viral infection during the virus expansion in the lung and during oxygen therapy. This proposal addresses the COVID-19 pandemic by developing a PV/T, which will be a unique approach that has not been tested before. This project is inspired by discovery of a special agent, i.e., a nanoscale 10 kDa chitosan, derived using proprietary methods from chitosan used as a common diet supplement [‘generally regarded as safe’ (GRAS) by FDA] , referred to as nanoscale chitosan derivative (NCD). NCD1 and other chemical derivatives were synthesized and tested for their anti-viral activity by neutralizing RNA of viruses, such as HIV, respiratory syncytial virus (RSV) and Coxsackie virus. Thus, in preliminary studies, 5 out of 9 examined showed significant anti-viral (80-90%) effects. Further, molecular docking studies showed that NCD1 can dock to the Spike protein of SARS-CoV-2 virus. Finally, we have developed lung targeted nanomedicine methods to combine NCD1 with remdesivir for improving treatment efficacy and expanding its use for prevention. Based on data at hand, it is hypothesized that NCDs by themselves or in combination with remdesivir will provide an excellent PV/T against COVID-19. To test this hypothesis, it is planned to examine in both prophylactic and therapeutic settings: the antiviral effectiveness of NCDs in vitro lung epithelial cell cultures (aim #1), the effectiveness of select top two NCDs with or without remdesivir in EpiAlveolar 3D co-culture model (MatTek) of the air-blood barrier (aim #2), and efficacy of select NCD with or without remdesivir in in vivo mouse models (aim #3). The results will provide us in identifying one or two NCDs as a single agent or in combination with remdesivir as COVID-19 PV/T regimen(s), which will inhibit SARS-CoV-2 infection. The results of these studies will uniquely contribute to the repertoire of COVID-19 prophylactics and therapeutics and allow us to move towards regulatory approval and future clinical trials. The team is uniquely poised to conduct these studies and has appropriate expertise. The successful completion of the proposed research is expected to lead to obtaining regulatory approval for a clinical trial.", "keywords": [ "2019-nCoV", "3-Dimensional", "ACE2", "Acute Respiratory Distress Syndrome", "Address", "Affect", "Antiviral Agents", "Biological", "Biological Assay", "Blood-Air Barrier", "COVID-19", "COVID-19 pandemic", "COVID-19 patient", "COVID-19 treatment", "Cell Culture Techniques", "Cell model", "Cells", "Cessation of life", "Chemicals", "Chitosan", "Clinical Trials", "Coculture Techniques", "Combined Modality Therapy", "Country", "Coxsackie Viruses", "Data", "Diagnosis", "Disease", "Docking", "Effectiveness", "Endothelial Cells", "Enzyme-Linked Immunosorbent Assay", "Epithelial Cells", "Evolution", "FDA approved", "Family", "Fibroblasts", "Friends", "Future", "HIV", "Hand", "Human", "In Vitro", "Individual", "Infection", "Infection Control", "Influenza", "Lead", "Lung", "Measures", "Methods", "Modeling", "Molecular", "Oxygen", "Oxygen Therapy Care", "Patients", "Pharmaceutical Preparations", "Prevention", "Preventive vaccine", "Prophylactic treatment", "RNA Viruses", "Regimen", "Research", "Respiratory syncytial virus", "SARS coronavirus", "SARS-CoV-2 infection", "SARS-CoV-2 inhibitor", "SARS-CoV-2 spike protein", "Testing", "Therapeutic", "Toxic effect", "Treatment Efficacy", "Vaccines", "Viral", "Viral Load result", "Viral Physiology", "Virus", "Virus Diseases", "Work", "alveolar epithelium", "base", "crosslink", "dietary supplements", "efficacy evaluation", "efficacy testing", "immunocytochemistry", "improved", "in vivo", "innovation", "mouse model", "nanomedicine", "nanoscale", "novel coronavirus", "novel virus", "overexpression", "pandemic disease", "particle", "prophylactic", "remdesivir", "response", "tripolyphosphate" ], "approved": true } }, { "type": "Grant", "id": "11779", "attributes": { "award_id": "1I01BX006010-01A1", "title": "Vaccinating at Mucosal Surfaces with Nanoparticle-conjugated Antigen and Adjuvant", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [], "program_reference_codes": [], "program_officials": [], "start_date": "2023-04-01", "end_date": "2027-03-31", "award_amount": null, "principal_investigator": { "id": 27656, "first_name": "SEBASTIAN", "last_name": "JOYCE", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "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": "The incidence of tuberculosis (TB) has increased among Veterans in recent years because global TB burden has escalated with the emergence of multidrug-resistant and extremely drug resistant Mycobacterium tuberculosis (Mtb) strains. Further, current vaccines do not elicit long-lasting protective immunity against TB, especially in adults. Hence, this application addresses a critical unmet need for an effective vaccine against TB and thereby, significantly improve the quality of life of our Veterans. Herein, we propose pre-clinical studies that will identify protective CD8+ T cell epitopes and develop intranasal vaccine delivery platforms for the design of next generation TB vaccines. The global burden of TB caused by Mycobacterium tuberculosis (Mtb) infection is enormous. A third of the world’s population is currently infected with Mtb, an airborne pathogen that causes ~1.5 million deaths annually. The escalating emergence of multidrug-resistant and extremely drug resistant Mtb strains for which treatment options are costly and limited, further exacerbates global burden. This problem persists because current vaccines do not elicit long-lasting protective immunity against TB, especially in adults. The challenge is multifaceted because Mtb enters the host through the respiratory tract and, therefore, optimal protection will require installation of lung-resident CD4+ and CD8+ memory T cells positioned at the frontline to respond immediately to an infection. Traditional vaccines and approved adjuvants typically elicit weak, short- lived T cell responses, and parenteral vaccination is ineffective at installing protective immunity within the mucosae. Moreover, most virus-vectored and subunit TB vaccines employ a small subset of Mtb antigens, resulting in insufficient epitope diversity for optimal protection, partly because the epitopes that are presented during Mtb infection and confer protective immunity are not fully defined. Hence, our overall objective is to discover immunogenic, protective Mtb epitopes and to incorporate them in an innovative nanoparticle (NP)- based intranasal vaccine designed to promote a balanced CD4+ and CD8+ T cell responses in the lungs that are protective against TB. As a means to accomplish this goal, we discovered >10,000 peptides that bind to HLA- A*02:01, B*07:02, B*35:01, & B*35:03 in a high-throughput binding assay using ultrahigh-density peptide arrays. Now the challenge is to identify epitopes recognised by Mtb-reactive CD8+ T cells that can protect against infection in a preclinical, humanised HLA-Itg mouse models. Moreover, using different infection models, we have developed multiple nanoparticle platforms for simultaneous delivery of antigens and adjuvants that efficiently generate protective, tissue resident CD8+ T cells (Trm). Guided by these exciting published and preliminary results, we will test this central hypothesis: Intranasal immunization with subunit vaccines consisting of novel Mtb antigens and adjuvant will generate CD8+ Trm responses in the lungs. Installation of Mtb-reactive CD8+ Trm at the port of pathogen entry will protect against a lethal, aerosol challenge of three novel humanised mouse models with [there] clinical isolate of virulent Mtb, [including] HN878. Our strategy to test this hypothesis is to, (a) define immunodominant CD8+ T cell epitopes presented by HLA-B*07:02 that protect B7.2tg mice from Mtb infections; and (b) define common immunodominant CD8+ T cell epitopes presented by multiple B*07:02-related alleles [called B7 supertype] that protect HLA-I transgenic mouse models from Mtb infections. Our multidisciplinary team —consisting of biochemists, immunologists, microbiologists, and bioengineer, is ideally situated to pursue the stated Specific Aims. We anticipate that successful completion of the proposed research will inform next generation vaccine design against Mtb infections and TB disease. Our innovative “discover and deliver” approach to vaccine design will impact clinical practice paradigms against TB and other pulmonary infectious diseases such as SARS-COVID19 and Flu. 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