Grant List
Represents Grant table in the DB
GET /v1/grants?page%5Bnumber%5D=3&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=1392&sort=award_amount", "next": "https://cic-apps.datascience.columbia.edu/v1/grants?page%5Bnumber%5D=4&sort=award_amount", "prev": "https://cic-apps.datascience.columbia.edu/v1/grants?page%5Bnumber%5D=2&sort=award_amount" }, "data": [ { "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": "8228", "attributes": { "award_id": "1I01BX005442-01", "title": "COVID-19: Multi-Omics Approach to Identify Molecular Mechanisms Responsible for Risk and Resilience to Adverse Outcomes", "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": 24057, "first_name": "CHARLES D", "last_name": "SEARLES", "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": "Objective: Emerging data from the COVID-19 pandemic indicate that men and African Americans have higher mortality, and cardiometabolic risk factors, including obesity, diabetes, and hypertension, cluster in patients who develop adverse outcomes to SARS-CoV-2 infection. The Veteran population is particularly vulnerable to COVID-19 because of the very high prevalence of cardiometabolic risk factors. However, not all Veterans with COVID-19 experience severe disease, and there is an urgent need to identify novel molecular pathways underlying risk and resilience to COVID-19. Previous work and preliminary studies from our team have demonstrated that targeted proteomics, metabolomics, and miRNA-omics can identify novel biomarkers and molecular pathways associated with cardiovascular health and disease. In this project, we will use a multi-omics to elucidate novel biomarkers and pathways associated with risk and resilience to severe COVID-19. Research Plan: In Aim 1, we will compare expression of pathway-specific biomarkers in hospitalized patients with severe COVID-19 with expression of these biomarkers in patients who do not develop severe COVID-19. Pathway-specific biomarkers reflecting activation of the renin-angiotensin-aldosterone system, systemic inflammation, oxidative stress, immune activation, thrombogenesis, and myocardial injury and stretch will be assessed. The primary endpoints for severe disease will be pathologic elevation of IL-6 levels or troponin I levels. Secondary endpoints will be requirement for mechanical ventilation, congestive heart failure, change in SOFA score, and death. In Aim 2, we will assess the extracellular miRNA and metabolomic profiles of the same two groups of hospitalized COVID-19 patients and determine miRNAs and metabolites differentially expressed between the two groups. Subsequently, we will examine connectivity between miRNA-metabolome networks and clinical endpoints in COVID-19 patients by performing an integrative analysis of differentially expressed miRNAs and metabolites, which will identify metabolic pathways associated with severe infection. Methods: The proposed studies will analyze de-identified blood samples and clinical data from COVID-19 patients hospitalized at the Atlanta VAMC and Emory University Hospital. The samples will be obtained from a bio repository that is currently banking residual plasma and serum from routine laboratory testing of COVID-19 patients. In Aim 1, we will measure levels of aminothiol (oxidative stress), suPAR (thrombogenesis/immune dysregulation), hsCRP (inflammation), hsTnI (myocardial injury), BNP (myocardial stretch), D-dimers (thrombogenesis), angiotensin II, angiotensin-(1-7) and plasma renin activity. Logistic regression modeling will be performed to identify biomarkers predictive of clinical endpoints. In Aim 2, we will use next generation sequencing, RT-qPCR, and high-throughput metabolomics profiling to assess expression of extracellular miRNAs and metabolites. A metabolome wide association study (MWAS) and ensemble feature selection (EFS) will be used to identify robust biomarkers and develop predictive models for severe COVID-19. Data from EFS analysis will input to the program xMWAS, which will determine connectivity between miRNA-metabolome networks and clinical outcomes. Clinical Relevance: Veterans with cardiovascular conditions are at higher risk for SARS-CoV-2 infection and severe disease progression. Our team has the infrastructure and methods in place to conduct in-depth, multi- omics studies to address predictors of adverse outcomes in Veterans with COVID-19 and identify epigenetic and cardiometabolic pathways that determine susceptibility to adverse outcomes. Furthermore, because 50% of the Veteran population at the Atlanta VA Medical Center Veteran is African American, we are in a unique position to address the role of race in susceptibility to severe COVID-19. Discovery of novel biomarkers and pathways associated with severe COVID-19 has broad implications for screening, therapeutics, and implementation of earlier personalized interventional strategies for attenuating adverse outcomes.", "keywords": [ "2019-nCoV", "Address", "African American", "Age", "Angiotensin II", "Arrhythmia", "Attenuated", "Biochemical Pathway", "Biological", "Biological Markers", "Blood", "Blood Banks", "Blood specimen", "Brain natriuretic peptide", "C-reactive protein", "COVID-19", "COVID-19 mortality", "COVID-19 pandemic", "COVID-19 patient", "COVID-19 test", "COVID-19 testing", "Cardiovascular Diseases", "Cardiovascular system", "Centers for Disease Control and Prevention (U.S.)", "Cessation of life", "Characteristics", "China", "Clinical", "Clinical Data", "Congestive Heart Failure", "Coronary Arteriosclerosis", "Data", "Databases", "Development", "Diabetes Mellitus", "Disease", "Disease Outcome", "Disease Progression", "Electronic Health Record", "Enrollment", "Epidemic", "Epigenetic Process", "Ethnic Origin", "Europe", "Fibrin fragment D", "Fibrin split products", "Health", "High Prevalence", "Hypertension", "Immune", "Immune response", "Immunologic Markers", "Infarction", "Infection", "Inflammation", "Infrastructure", "Interleukin-6", "International", "Intervention", "Laboratories", "Lead", "Left", "Logistic Regressions", "Measurement", "Measures", "Mechanical ventilation", "Medical center", "Metabolic", "Metabolic Pathway", "Methods", "MicroRNAs", "Modeling", "Molecular", "Molecular Profiling", "Myocardial", "Myocarditis", "Obesity", "Outcome", "Oxidative Stress", "Participant", "Pathologic", "Pathway interactions", "Patients", "Pilot Projects", "Plasma", "Play", "Positioning Attribute", "Predisposition", "Proteomics", "Protocols documentation", "Race", "Renin", "Renin-Angiotensin-Aldosterone System", "Research", "Residual state", "Risk", "Risk Factors", "Role", "SARS-CoV-2 infection", "Sampling", "Severity of illness", "Stretching", "Structure of respiratory epithelium", "Testing", "Therapeutic", "Therapeutic Intervention", "Troponin I", "University Hospitals", "Urokinase Plasminogen Activator Receptor", "Veterans", "Virus Diseases", "Work", "acute infection", "adverse outcome", "aminothiol", "angiotensin I (1-7)", "biobank", "cardiometabolic risk", "cardiometabolism", "cardiovascular health", "cardiovascular risk factor", "cell injury", "clinical predictors", "clinically relevant", "cohort", "differential expression", "experience", "extracellular", "feature selection", "heart circulation", "hemodynamics", "high risk", "immune activation", "indicated prevention", "inflammat" ], "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": "6934", "attributes": { "award_id": "1IS1BX005516-01", "title": "ShEEP Request for a Replacement Confocal Microscope for the Cell Imaging Core Facility", "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": "2022-09-30", "award_amount": null, "principal_investigator": { "id": 22783, "first_name": "CHRISTINE LINDA", "last_name": "HSIEH", "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": [], "awardee_organization": { "id": 1522, "ror": "", "name": "VETERANS AFFAIRS MED CTR SAN FRANCISCO", "address": "", "city": "", "state": "CA", "zip": "", "country": "United States", "approved": true }, "abstract": "Confocal microscopy is an optical imaging technique that is an essential research tool to determine structure and localization in cells and tissues in two and three-dimensional space. The San Francisco VA Health Care System Cell Imaging Core Facility currently has an aged (>15 years old Zeiss LSM510Meta) confocal fluorescent microscope, which has frequent and recurring malfunctions, is no longer supported by the manufacturer, and no longer provides publication quality resolution for images. To fulfill the imaging needs of current VA-funded research, and to provide an excellent imaging resource for basic and clinical scientists for years to come, we request a state of the art Leica Stellaris 5 fluorescent confocal microscope. The Leica STELLARIS 5 Spectral Inverted Tandem Scanner Confocal with LIGHTENING Super Resolution and Tau Sense Lifetime is equipped with many innovative and unique features to provide high-quality and fast imaging for a broad spectrum of fluorescent probes. This microscope was just released in May 2020 and offers exciting new and key features including 1) a white light tunable supercontinuum laser to excite fluors over a broad range of wavelengths, 2) high class glycerol-based immersion confocal grade objective lenses with motorized correction to visualize imaging in thicker tissues, 3) Power HyD S super sensitive detectors that improve image contrast and quantitation, 4) fast and high confocal resolution over large areas, and 5) a navigator tool that enables continuous back and forth viewing between an overview image and a targeted area of interest. A functional and innovative confocal microscope with these exciting new features will attract users to the core facility. We expect that usage fees from all users will be sufficient for maintenance. Research projects advancing studies of diseases highly relevant to the Veterans’ community that will be supported by this equipment include studies focusing on brain diseases, such as traumatic brain injury (TBI), stroke, and frontotemporal dementia (FTD). Confocal microscopy is required to simultaneously image multiple brain cells in affected tissues to determine cellular localization and gene expression. Lung transplant studies will be served by this equipment to image fluorescent telomere-specific peptide nucleic acid probes and natural killer (NK) cells in lung transplant tissues. Infectious disease research projects related to Neisseria gonorrhoeae, HIV, and SARS-CoV-2 will be able to utilize this equipment to better understand the pathogenic mechanisms of infection and persistence. Studies of prostate cancer will also utilize this equipment to characterize prognostic biomarkers. We are excited to request the Leica Stellaris 5, a state of the art confocal microscope that will provide innovative and outstanding images for research studies to advance Veterans’ health. This replacement is much needed; the current microscope has been not supported by the manufacturer for a few years now and is frequently non-functional. We anticipate the Leica Stellaris 5 to provide services essential towards accomplishing VA’s research goals to understand and treat diseases of high importance to the Veteran population.", "keywords": [ "15 year old", "2019-nCoV", "3-Dimensional", "Address", "Affect", "Area", "Back", "Biological", "Brain Diseases", "COVID-19", "Cells", "Clinical", "Communicable Diseases", "Communities", "Community Services", "Confocal Microscopy", "Core Facility", "Data", "Dementia", "Diagnostic", "Disease", "Equipment", "Fees", "Fluorescent Probes", "Frontotemporal Dementia", "Funding", "Future", "Gene Expression", "Glycerol", "Goals", "HIV", "Health", "Health Services Research", "Healthcare Systems", "Image", "Imaging Techniques", "Immersion", "Infection", "Infectious Diseases Research", "Laboratories", "Lasers", "Light", "Lung Transplantation", "Maintenance", "Malignant neoplasm of prostate", "Manufacturer Name", "Microscope", "Microscopy", "Mind", "Natural Killer Cells", "Neisseria gonorrhoeae", "Nucleic Acid Probes", "Oils", "Pathogenicity", "Peptide Nucleic Acids", "Process", "Prognostic Marker", "Publications", "Refractive Indices", "Research", "Research Project Grants", "Resolution", "Resources", "Sampling", "San Francisco", "Scanning", "Scientist", "Services", "Sheep", "Stroke", "Structure", "System", "Thick", "Tissue Transplantation", "Tissues", "Traumatic Brain Injury", "United States Department of Veterans Affairs", "Veterans", "aged", "base", "brain cell", "cellular imaging", "contrast imaging", "cost effective", "design", "detector", "fluorescence imaging", "fluorescence microscope", "high resolution imaging", "imaging facilities", "improved", "innovation", "interest", "lens", "military veteran", "optical imaging", "prognostic", "research study", "tau Proteins", "telomere", "tool", "two-dimensional" ], "approved": true } }, { "type": "Grant", "id": "10787", "attributes": { "award_id": "1I01HX003576-01A1", "title": "Impact of COVID-19 on Continuity of Care for Veterans on Antipsychotic Medications", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [], "program_reference_codes": [], "program_officials": [], "start_date": "2022-11-01", "end_date": "2024-10-31", "award_amount": null, "principal_investigator": { "id": 26863, "first_name": "ANOUK L", "last_name": "GRUBAUGH", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 1782, "ror": "", "name": "RALPH H JOHNSON VA MEDICAL CENTER", "address": "", "city": "", "state": "SC", "zip": "", "country": "United States", "approved": true }, "abstract": "Background: Severe mental illnesses are consistently ranked as some of the most debilitating health conditions worldwide due to their early age of onset, chronicity, and impact on functioning. Fortunately, a number of antipsychotic medications have been found to be effective for managing the symptoms of severe mental illness (SMI) and for preventing relapse and rehospitalization. Despite their efficacy, treatment non-compliance for individuals on these medications is high due to a number of factors including poor insight into illness, negative attitudes about medication, and medication related side effects. Further complicating care and outcomes for this clinical population, providers must maintain close oversight of patients on antipsychotics due to the impact of these medications on metabolic and cardiac functioning which confer an increased risk of obesity, diabetes, heart problems, and other chronic illnesses. This oversight includes regular monitoring of weight, blood pressure, fasting blood glucose, and lipid levels. Additionally, clozapine, indicated for treatment-resistant schizophrenia, requires weekly-to-monthly monitoring of absolute neutrophil counts to prevent potentially fatal clozapine- induced agranulocytosis. Significance: The proposed project has significant and immediate relevance to Veterans and the VHA in that it seeks to better understand if and to what extent COVID-19 related care disruptions impacted care and outcomes for Veterans with SMI prescribed antipsychotic medications. Given pre- existing challenges in the treatment of this Veteran population, this is an important area of inquiry as well as one for which little is known. Added strengths of the proposed study include the use of a mixed methods approach that includes national level data from multiple sources. Aside from addressing a critical knowledge gap, the proposed study targets what is unarguably one of the most vulnerable patient populations within the VA and other healthcare systems—patients with SMI prescribed antipsychotic medications. Specific Aims: Aim 1: To assess the impact of COVID-19 related care disruptions on healthcare use and outcomes for Veterans on antipsychotic medications using robust statistical methods and national level data; Aim 2: To assess whether the impact of COVID-19 related care disruptions differ by race/ethnicity, gender, age, and rural/urban status using national level data; Aim 3: To conduct thematic interviews with provider and patient stakeholder groups at the national level to better understand COVID-19 related care disruptions. Provider stakeholders (e.g., psychiatrists, advanced nurse practitioners) will be interviewed to better understand COVID-19 related changes in practice behaviors, the perceived impact of these changes on care continuity and outcomes, and to solicit suggestions to mitigate the impact of interrupted care in the future; Veterans prescribed antipsychotic medication prescriptions in the pre COVID-19 window will be interviewed to better understand the impact of COVID-19 related care disruptions on treatment seeking behaviors, obstacles encountered with regard to access, and to explore other factors potentially impacting outcomes in this patient group. Methodology: The proposed study will employ a mixed-methods (quantitative/qualitative) approach. For Aims 1 & 2 we will employ retrospective, observational analyses using a national cohort of Veterans (N>250,000) with an ICD-CM-10 diagnostic code for schizophrenia or bipolar disorder prescribed a first-generation or second-generation antipsychotic [1/19-12/21]. Veterans of all ages, genders, racial groups, military eras will be included in the cohort. Aim 3 will involve individual thematic interviews with provider (n=35-45) and patient stakeholders (n=50-60). Next Steps/Implementation: Findings from this 2-year project will be of immediate relevance and impact for local, regional, and national level administrators and mental health providers as well as the VA Office of Mental Health and Suicide Prevention and VA Pharmacy Benefits Management Services. Collectively, data from this project will serve to identify potential strategies to further mitigate the impact of COVID-19 on the care and outcomes of Veterans with SMI as well as prepare for future public health and/or other national emergencies.", "keywords": [ "Address", "Adherence", "Administrator", "Admission activity", "Age", "Age of Onset", "Agranulocytosis", "Antipsychotic Agents", "Area", "Attitude", "Behavior", "Bipolar Disorder", "Blood Glucose", "Blood Pressure", "COVID-19", "COVID-19 impact", "Caring", "Chronic", "Chronic Disease", "Clinical", "Clozapine", "Code", "Continuity of Patient Care", "Data", "Data Sources", "Diabetes Mellitus", "Diagnostic", "Disease", "Drug Prescriptions", "Emergency Care", "Emergency Situation", "Ethnic Origin", "Event", "Fasting", "Future", "Gender", "Generations", "Guidelines", "Health", "Health Personnel", "Healthcare", "Healthcare Systems", "Heart", "Heart Diseases", "Individual", "Inpatients", "Interruption", "Interview", "Knowledge", "Lipids", "Malignant Neoplasms", "Mental Health", "Mental disorders", "Metabolic", "Methodology", "Methods", "Military Personnel", "Minority Women", "Monitor", "Nurse Practitioners", "Outcome", "Outpatients", "Patients", "Pharmaceutical Preparations", "Pharmacists", "Population", "Provider", "Psychiatrist", "Public Health", "Race", "Relapse", "Research Design", "Resistance", "Rural", "Safety", "Schizophrenia", "Services", "Statistical Methods", "Suggestion", "Suicide", "Suicide prevention", "System", "Testing", "Time", "Veterans", "Visit", "Weight", "behavioral outcome", "care outcomes", "cohort", "cost", "economic impact", "experience", "health care availability", "health care delivery", "health care service utilization", "heart function", "hospital readmission", "insight", "military veteran", "mortality", "multiple data sources", "neutrophil", "non-compliance", "obesity risk", "patient population", "pharmacy benefit", "post-COVID-19", "prevent", "racial and ethnic", "rural area", "severe mental illness", "side effect", "symptom management", "urban dwelling" ], "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": "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": "7971", "attributes": { "award_id": "1I01HX003277-01A1", "title": "Hospital In Home: Evaluating Need and Readiness for Implementation (HENRI)", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [], "program_reference_codes": [], "program_officials": [], "start_date": "2022-06-01", "end_date": "2026-05-31", "award_amount": null, "principal_investigator": { "id": 23857, "first_name": "William W.,MPH, MD", "last_name": "Hung", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [ { "id": 1653, "ror": "", "name": "VETERANS AFFAIRS, UNITED STATES DEPARTMENT OF", "address": "", "city": "", "state": "NY", "zip": "", "country": "United States", "approved": true } ] }, "other_investigators": [ { "id": 23858, "first_name": "ORNA K.", "last_name": "INTRATOR", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, { "id": 23859, "first_name": "Jennifer L", "last_name": "Sullivan", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "awardee_organization": { "id": 1653, "ror": "", "name": "VETERANS AFFAIRS, UNITED STATES DEPARTMENT OF", "address": "", "city": "", "state": "NY", "zip": "", "country": "United States", "approved": true }, "abstract": "Background: The Department of Veterans Affairs (VA's) Hospital In Home (HIH) program, designed from experiences of the Hospital At Home community program, is a model of care that delivers patient-centered, acute-level hospital care at home which has demonstrated safety, effectiveness and patient satisfaction beyond those observed in hospitals. Since 2010, the VHA Office of Geriatrics & Extended Care (GEC), through its transformational programs and mentored partnerships has spurred the development of [12] HIH program sites nationally, which have all been sustained by their parent station. Significance/Impact: [Hospital In Home is a mix of interventions and levels of implementations; understanding how to weave these successfully is the overarching aim of this project.] Continued spread of HIH across the VA requires evidence be established regarding the need for HIH and about the implementation of existing HIH programs. Understanding barriers and facilitators and processes of implementation of HIH programs will allow more facile adoption of HIH programs allowing for substantial cost savings of about $3,000 per inpatient event. Especially in the era of the Mission Act, having HIH available may incentivize Veterans to choose VA. [With the recent Covid-19 pandemic, HIH has been identified as a potential contributor to addressing the disease and sequelae.] Innovation: This project will generate generalizable knowledge regarding implementation of HIH models and will advance implementation science from its application of implementation science frameworks, Re-Aim- PRISM and novel methods such as Implementation Mapping. The project will curate knowledge garnered from the existing programs and develop tools to disseminate it. It will develop and conduct readiness for implementation surveys. Finally, it will “dry-run” implementations in sites with greater readiness for implementation. The results of the “dry runs” will provide feedback to the implementation planning thus increasing their probability of successful adoption of HIH and its sustainment and growth. Specific Aims: 1. Establish evidence regarding the implementation of the existing HIH sites using a mixed methods approach. Deliverables: An evaluation framework and report summarizing the experiences of the existing sites. 2. Develop operational implementation tools and a readiness for implementation survey to be conducted. Deliverables: A survey of readiness for implementation and prioritization of sites ready to implement; implementation tools. 3. Select ten new sites with the greatest evidence of readiness for implementation to conduct “dry-runs” and create blueprints for implementation; identify causal loop diagram(s); catalog the evidence. Deliverables: Report summarizing common and site specific implementation themes; Site-specific Implementation logic models; Searchable catalog of HIH implementation strategies. Methodology: This mixed-methods project will conduct quantitative analyses, interviews, focus groups and “dry runs” applying implementation science frameworks and methods (RE-AIM-PRISM, implementation mapping) and system science to understand the existing HIH programs and to create implementation tools, evaluation framework, readiness survey, causal loop diagrams and a searchable catalog of HIH implementation evidence. Implementation/Next Steps: Future work will develop simulation studies and conduct evaluations of newly implemented sites as well as a hybrid II implementation trial of the effectiveness and safety of the HIH model.", "keywords": [ "Accident and Emergency department", "Acute", "Address", "Admission activity", "Adoption", "Beds", "Benchmarking", "COVID-19 pandemic", "Caring", "Catalogs", "Client satisfaction", "Communities", "Complex", "Contracts", "Cost Savings", "Development", "Disease", "Effectiveness", "Evaluation", "Evaluation Reports", "Event", "Feedback", "Focus Groups", "Future", "Geriatrics", "Growth", "Health Services Accessibility", "Home", "Hospital safety", "Hospitals", "Hybrids", "Implementation readiness", "Incentives", "Inpatients", "Intervention", "Interview", "Knowledge", "Learning", "Logic", "Long-Term Care", "Mentors", "Methodology", "Methods", "Mission", "Modeling", "Parents", "Patient-Focused Outcomes", "Probability", "Process", "Quality of Care", "Quantitative Evaluations", "Reach Effectiveness Adoption Implementation and Maintenance", "Readiness", "Reporting", "Resources", "Running", "Safety", "Science", "Series", "Site", "Standardization", "Surveys", "System", "Techniques", "United States Department of Veterans Affairs", "Variant", "Veterans", "Work", "base", "design", "effectiveness implementation trial", "experience", "experimental study", "guidebooks", "implementation barriers", "implementation evaluation", "implementation framework", "implementation science", "implementation strategy", "implementation tool", "informant", "innovation", "interest", "novel", "patient oriented", "preference", "programs", "simulation", "stem", "tool" ], "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": "8201", "attributes": { "award_id": "1I01BX005490-01", "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. 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