Grant List
Represents Grant table in the DB
GET /v1/grants?page%5Bnumber%5D=1384&sort=-approved
{ "links": { "first": "https://cic-apps.datascience.columbia.edu/v1/grants?page%5Bnumber%5D=1&sort=-approved", "last": "https://cic-apps.datascience.columbia.edu/v1/grants?page%5Bnumber%5D=1442&sort=-approved", "next": "https://cic-apps.datascience.columbia.edu/v1/grants?page%5Bnumber%5D=1385&sort=-approved", "prev": "https://cic-apps.datascience.columbia.edu/v1/grants?page%5Bnumber%5D=1383&sort=-approved" }, "data": [ { "type": "Grant", "id": "12085", "attributes": { "award_id": "1K23AI177817-01", "title": "Impact of gestational SARS-CoV-2 and maternal inflammation on child growth and neurodevelopment in a malaria-endemic setting", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [ "National Institute of Allergy and Infectious Diseases (NIAID)" ], "program_reference_codes": [], "program_officials": [ { "id": 6243, "first_name": "BROOKE ALLISON", "last_name": "Bozick", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2023-09-01", "end_date": "2028-08-31", "award_amount": 193320, "principal_investigator": { "id": 27943, "first_name": "Karen Blake", "last_name": "Jacobson", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 769, "ror": "", "name": "KAISER FOUNDATION RESEARCH INSTITUTE", "address": "", "city": "", "state": "CA", "zip": "", "country": "United States", "approved": true }, "abstract": "/ ABSTRACT Since the emergence of SARS-CoV-2 in 2020, millions of pregnancies in malaria-endemic sub-Saharan Africa have been impacted by SARS-CoV-2 infection. High rates of SARS-CoV-2 and malaria co-infections during pregnancy will continue as new SARS-CoV-2 variants emerge and cause re-infections in subsequent waves. SARS-CoV-2 and malaria in pregnancy are both associated with adverse birth and infant outcomes – including preterm birth, low birth weight, and impaired growth and neurodevelopment – possibly mediated through maternal inflammation. Data on long-term developmental effects of gestational SARS-CoV-2 in highly malaria exposed populations are lacking. To address this gap, I will leverage samples and data from mother-infant dyads enrolled in two complementary ongoing NIH-funded antimalarial chemoprevention trials in Busia, Uganda. In the pregnancy trial, pregnant women are randomized to one of three antimalarial chemoprevention regimens and followed through delivery; infants born to these women are being randomized in a separate clinical trial to receive antimalarial chemoprevention or placebo and followed to age 4 years. These trials have coincided with Uganda’s early SARS-CoV-2 surges, and preliminary data indicate high incidence of both SARS-CoV-2 and malaria during pregnancy. Using clinical data and samples collected as part of the ongoing trials, I will test the hypothesis that infants exposed to gestational SARS-CoV-2 will have impaired growth and neurodevelopment in early childhood when compared with unexposed infants, and that this is mediated by maternal inflammation. I further hypothesize that exposure to both SARS-CoV-2 and malaria in pregnancy increases adverse infant outcomes due to the synergistic inflammatory effects of both pathogens. In Aim 1, I will use serologic testing of stored plasma samples to retrospectively identify mothers who experienced SARS-CoV-2 during pregnancy and compare the growth of infants with and without gestational SARS-CoV-2 exposure through age 4 years. In Aim 2, I will compare neurocognitive test scores at ages 24 and 42 months among infants with and without gestational SARS-CoV-2. In Aim 3, I will explore maternal proteomic immune signatures of SARS-CoV-2 in pregnancy and determine if the effect of gestational SARS-CoV-2 on infant growth and neurodevelopment is mediated by specific inflammatory pathways. This cohort is uniquely poised to address the impact of SARS-CoV-2 in pregnancy in a malaria endemic setting, with longitudinal data and samples collected before widespread baseline SARS-CoV- 2 immunity. To accomplish these aims and become an independent translational researcher in tropical perinatal infections, I have assembled an interdisciplinary mentorship team of experts in in infectious diseases, obstetrics, pediatrics, neuropsychology, immunology, and global health. Results from this proposed study have immediate implications for improving care of at-risk infants, and could identify diagnostic or therapeutic targets for future clinical interventions.", "keywords": [ "2 year old", "2019-nCoV", "4 year old", "Address", "Adverse effects", "Africa South of the Sahara", "African", "Age", "Antimalarials", "Birth", "COVID-19 pandemic", "Caring", "Chemoprevention", "Child", "Childhood", "Clinical", "Clinical Data", "Clinical Management", "Clinical Trials", "Cohort Studies", "Collaborations", "Communicable Diseases", "Complex", "Data", "Data Set", "Development", "Diagnostic", "Discipline of obstetrics", "Enrollment", "Epidemiology", "Exclusion", "Exposure to", "Funding", "Future", "Goals", "Growth", "Immune", "Immune response", "Immunity", "Immunology", "Impairment", "Incidence", "Infant", "Infection", "Inflammation", "Inflammation Mediators", "Inflammatory", "Interleukin-1", "Intervention", "Knowledge", "Long-Term Effects", "Low Birth Weight Infant", "Malaria", "Mediating", "Mentorship", "Mothers", "Neurocognitive", "Neurocognitive Deficit", "Neuropsychology", "Outcome", "Pathway interactions", "Pediatrics", "Perinatal Infection", "Placebos", "Plasma", "Population", "Pregnancy", "Pregnant Women", "Premature Birth", "Prevention trial", "Proteomics", "Pyrimethamine", "Randomized", "Regimen", "Research", "Research Personnel", "Resource-limited setting", "Resources", "Risk", "SARS-CoV-2 exposure", "SARS-CoV-2 immunity", "SARS-CoV-2 infection", "SARS-CoV-2 variant", "Sampling", "Serology test", "Signal Pathway", "Sulfadoxine", "Testing", "Toddler", "Training", "Translational Research", "Uganda", "Underweight", "United States National Institutes of Health", "Vaccines", "Woman", "career development", "clinically significant", "co-infection", "cohort", "cytokine", "early childhood", "experience", "fighting", "geographic population", "global health", "improved", "infant outcome", "inflammatory marker", "neurocognitive test", "neurodevelopment", "offspring", "pathogen", "seropositive", "therapeutic target", "translational scientist", "vigilance", "wasting" ], "approved": true } }, { "type": "Grant", "id": "12086", "attributes": { "award_id": "1R21AI178533-01", "title": "Intracellular functions and mechanisms of alphavirus ion channel 6K", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [ "National Institute of Allergy and Infectious Diseases (NIAID)" ], "program_reference_codes": [], "program_officials": [ { "id": 7012, "first_name": "LESLEY CONRAD", "last_name": "Dupuy", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2023-09-01", "end_date": "2025-08-31", "award_amount": 236286, "principal_investigator": { "id": 27944, "first_name": "Joyce", "last_name": "Jose", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 833, "ror": "", "name": "PENNSYLVANIA STATE UNIVERSITY, THE", "address": "", "city": "", "state": "PA", "zip": "", "country": "United States", "approved": true }, "abstract": "Mosquito-borne alphaviruses such as chikungunya, Mayaro, and Eastern equine encephalitis viruses cause high morbidity and mortality in their mammalian hosts. Alphaviruses are globally distributed arthropod-borne viruses that are enzootic in nature with the potential to disseminate to new geographical regions due to vector adaptations causing new outbreaks. A 2019 outbreak of 38 human cases of Eastern equine encephalitis virus occurred in the United States, raising concerns about its reemergence. In 2005–2006, a chikungunya outbreak started in the Indian Ocean Island of Réunion had spread around the world, infecting millions of people. Chikungunya fever is characterized by debilitating joint pain that can last up to 2–3 years, causing arthritis-like conditions. No effective antiviral strategies or vaccines are available against any of these pathogens. Studying these viruses to gain a molecular understanding of their lifecycle is essential to discovering novel targets for therapeutic intervention. Specifically, the poorly understood intracellular mechanisms that drive alphavirus assembly and budding represent promising antiviral targets. We reported for the first time that the alphavirus- encoded ion channel protein 6K plays an essential part in virus budding by enabling the formation of cytopathic vacuoles-II and envelope spike protein transport to the plasma membrane. The defects due to the deletion of 6K can be restored to varying levels by the expression of a functional HIV-1 Vpu and influenza A virus M2 ion channel. We also demonstrated that ion channel inhibitors could be utilized as antivirals. Building on these observations, in Aim 1, we will characterize chikungunya and Sindbis virus 6K ion channels and their activity by reverse genetics, transport assays in proteoliposomes and fractionated intracellular membrane vesicles, and live-confocal imaging of virus-infected cells with ion-specific fluorescent probes. In Aim 2, by expressing virus- encoded ion channels, including the SARS-CoV-2 E protein in cells and from an alphavirus, we will determine if ion channel-based Golgi remodeling is a standard mechanism used by enveloped RNA viruses for membrane modification and efficient virus budding. With new reverse genetics tools and CRISPR-Cas9 methods, we will investigate the functional involvement of host-encoded ion channels in alphavirus budding. By completing these aims, we will define a novel mechanism by which ion channel proteins modify the secretory pathway for virus budding and how this process can be exploited as an antiviral target. We will also generate new reverse genetics tools that will be useful to the scientific community. The critical knowledge gaps we will address are 1) what are the ions transported by alphavirus 6K? 2) how does 6K participate in virus budding? and 3) an understanding of a general mechanism involving virus and host ion channels utilized by alphaviruses for efficient budding.", "keywords": [ "2019-nCoV", "Acute", "Address", "Affect", "Alphavirus", "Alphavirus Infections", "Americas", "Amiloride", "Antiviral Agents", "Arboviruses", "Arthralgia", "Arthritis", "Biological Assay", "CRISPR library", "CRISPR/Cas technology", "Cell Membrane Permeability", "Cell membrane", "Cell physiology", "Cell surface", "Cells", "Chikungunya fever", "Chikungunya virus", "Chimera organism", "Communities", "Confocal Microscopy", "Defect", "Disease Outbreaks", "Drug Design", "E protein", "Eastern Equine Encephalitis Virus", "Encephalitis", "Family", "Fluorescence-Activated Cell Sorting", "Fluorescent Probes", "Foundations", "Geographic Locations", "Glycoproteins", "Golgi Apparatus", "HIV-1", "Hepatitis C virus", "Homeostasis", "Human", "Immunofluorescence Immunologic", "In Vitro", "Indian Ocean Islands", "Influenza A virus", "Integral Membrane Protein", "Intracellular Membranes", "Ion Channel", "Ion Channel Protein", "Ion Transport", "Ions", "Knock-out", "Knowledge", "Life Cycle Stages", "Mediating", "Membrane", "Methods", "Microscopy", "Mission", "Modification", "Molecular", "Molecular Biology", "Morbidity - disease rate", "Morphogenesis", "Mutation", "National Institute of Allergy and Infectious Disease", "Nature", "Pathway interactions", "Persons", "Pharmaceutical Preparations", "Plaque Assay", "Play", "Polyarthritides", "Process", "Proteins", "Public Health", "Publishing", "Quantitative Reverse Transcriptase PCR", "RNA Viruses", "Reporting", "Reunion Island", "Risk", "Role", "Secretory Vesicles", "Series", "Sindbis Virus", "Structural Protein", "Structure", "Surface", "Testing", "Therapeutic Intervention", "Time", "Togaviridae", "United States", "Vacuole", "Vesicle", "Viral", "Virion", "Virus", "Western Blotting", "Work", "chikungunya", "confocal imaging", "drug repurposing", "env Gene Products", "enzootic", "experimental study", "global health", "inhibitor", "knowledge of results", "member", "mortality", "mosquito-borne", "mutant", "new outbreak", "new therapeutic target", "novel", "pathogen", "premature", "prevent", "protein transport", "proteoliposomes", "reverse genetics", "stable cell line", "tool", "trafficking", "vaccine access", "vector" ], "approved": true } }, { "type": "Grant", "id": "12087", "attributes": { "award_id": "1R21HD110837-01A1", "title": "Reducing Vaccine Hesitancy among Hispanic Parents of COVID-19 Vaccine-Eligible Children", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [ "Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)" ], "program_reference_codes": [], "program_officials": [ { "id": 6227, "first_name": "Tracy", "last_name": "King", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2023-09-01", "end_date": "2025-08-31", "award_amount": 419796, "principal_investigator": { "id": 27945, "first_name": "Sunny Wonsun", "last_name": "Kim", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [ { "id": 27946, "first_name": "Alexis", "last_name": "Koskan", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "awardee_organization": { "id": 912, "ror": "", "name": "ARIZONA STATE UNIVERSITY-TEMPE CAMPUS", "address": "", "city": "", "state": "AZ", "zip": "", "country": "United States", "approved": true }, "abstract": "COVID-19 vaccines, currently available to children over six months old, are a powerful method of preventing new infections and reducing the risk of hospitalization and death due to COVID-19. However, vaccination rates among Hispanic children remain suboptimal. Lower vaccination rates in children are largely due to parental vaccine hesitancy. While national health communication experts have suggested using storytelling as an effective intervention strategy to promote COVID-19 vaccination, we will take the innovative next steps of creating and evaluating a digital storytelling intervention to reduce Hispanic parental vaccine hesitancy. Working with community health workers, we will engage Hispanic parents and legal guardians who report being previously hesitant to vaccinate their child(ren) against COVID-19 to serve as our digital storytellers. We will ask them to share their stories of conversion in COVID-19 vaccine perspectives to help other parents and legal guardians overcome their unique concerns and mistrust of COVID-19 vaccines. Guided by the Theory of Planned Behavior and storytelling as culture-centric health promotion, we propose to (Aim 1) develop culturally-relevant digital stories (each 2-3 minutes long) with a diverse sample of Hispanic parents and legal guardians who transformed from being COVID-19 vaccine-hesitant to vaccine-accepting. In Aim 2, we will assess the feasibility and acceptability of a web-based pilot digital storytelling intervention vs. information-only control among parents and legal guardians (n=80) of children who are not up-to-update with COVID-19 vaccine doses. We will also explore pre- to post-intervention changes in vaccine perceptions, vaccine hesitancy, intentions to vaccinate children against COVID-19, and children’s vaccine uptake at two- month post-intervention. If our study demonstrates feasibility, acceptability, promising reductions in vaccine hesitancy, and increases in vaccine uptake, we will conduct a full-scale randomized controlled trial to examine the effectiveness of the DST intervention to reduce COVID-19 vaccine hesitancy in our target population. This more extensive study could be used in future DST interventions to increase immunizations (e.g., flu, HPV) among Hispanic children and adolescents. In addition, our innovative research may provide evidence of scalable, disseminatable strategies to reduce vaccine hesitancy and can be used for other rapid vaccination efforts for potential future outbreaks.", "keywords": [ "2 arm randomized control trial", "2019-nCoV", "Address", "Adolescent", "Area", "Attitude", "Behavior", "Belief", "COVID-19", "COVID-19 mortality", "COVID-19 vaccination", "COVID-19 vaccine", "Cessation of life", "Child", "Childhood", "Collaborations", "Communities", "Community Health Aides", "Control Groups", "Disease", "Dose", "Educational workshop", "Elements", "Eligibility Determination", "Emotional", "Family", "Feasibility Studies", "Focus Groups", "Future", "Health", "Health Promotion", "Health behavior", "Hispanic", "Hospitalization", "Human Papillomavirus", "Immunity", "Immunization", "Individual", "Infection", "Inflammatory", "Influentials", "Intervention", "Legal Guardians", "Long COVID", "Methods", "National Institute of Child Health and Human Development", "Not Hispanic or Latino", "Online Systems", "Parents", "Participant", "Pattern", "Perception", "Persuasive Communication", "Planning Theory", "Population", "Public Health", "Randomized Controlled Trials", "Recommendation", "Reporting", "Research", "Risk Reduction", "Sampling", "Social Perception", "Syndrome", "System", "Target Populations", "Testing", "Transportation", "Update", "Vaccinated", "Vaccination", "Vaccines", "Virus", "Work", "acceptability and feasibility", "arm", "community engagement", "cost", "design", "digital", "effective intervention", "effectiveness evaluation", "ethnic minority", "experience", "flu", "future outbreak", "health communication", "improved", "innovation", "insight", "intervention cost", "member", "pandemic disease", "post intervention", "prevent", "racial minority", "recruit", "social norm", "theories", "tool", "vaccine acceptance", "vaccine access", "vaccine hesitancy", "willingness" ], "approved": true } }, { "type": "Grant", "id": "12088", "attributes": { "award_id": "1R33CA281802-01", "title": "Multiplex In-Solution Protein Array (MISPA) for high throughput, quantitative, early profiling of pathogen-induced head and neck", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [ "National Cancer Institute (NCI)" ], "program_reference_codes": [], "program_officials": [ { "id": 27947, "first_name": "Wendy", "last_name": "Wang", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2023-09-01", "end_date": "2026-08-31", "award_amount": 390906, "principal_investigator": { "id": 26311, "first_name": "JOSHUA", "last_name": "LABAER", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 912, "ror": "", "name": "ARIZONA STATE UNIVERSITY-TEMPE CAMPUS", "address": "", "city": "", "state": "AZ", "zip": "", "country": "United States", "approved": true }, "abstract": "Profiling antibody response to disease-associated antigens is important to cancer research. In contrast to the historical approach of testing responses to individual proteins, screening and diagnosis increasingly rely on multiplexed assays to elucidate disease and patient heterogeneity. Protein microarrays allow proteome-scale screening with low sample consumption but are constrained by binding kinetics of surface-bound proteins, non-specific binding, limited dynamic range of fluorescence detection and not readily available in clinics. Peptide-based approaches limit the assay to linear epitopes. With support from IMAT R21, we have developed a next-generation, liquid-phase protein microarray platform, “Multiplex In Solution Protein Array” (MISPA), which exploits the extraordinary dynamic range of next generation sequencing (NGS) with wide applicability in both research and clinical labs. We quantitatively profiled the immune responses of oropharyngeal (OPSCC) patient and control samples using a “barcoded” human papillomavirus (HPV) antigen library for 12 HPV subtypes NGS. The assay successfully detected the positive responses in the OPSCC samples and demonstrated greater signal-to-background ratio, reproducibility, and dynamic range. Subsequently, we have advanced MISPA to assay antibody response against SARS-CoV-2, seasonal coronaviruses, and other respiratory pathogens in more than 1000 samples simultaneously as part of the NCI SeroNet with over 90% overall percent agreement with a clinical COVID-19 diagnosis and commercial EUA serological assays. In the R33 phase, we propose to further develop the MISPA platform to a fully automated research platform that is quantitative, robust, highly reproducible, high-throughput, and inexpensive for early cancer screening. We will establish SOPs for robust protein production, stable protein library storage, and minimal reagent lot-to-lot variations. We will demonstrate the versality of MISPA by increasing the barcoded protein library size to 192 by including antigens from different subtype of HPV, other viruses, bacteria, fungi and tumor antigens. We will improve reproducibility and throughput with end-to end automation for the MISPA platform to support large-scale projects requiring assaying tens of thousands samples. We will determine the limit of blank, limit of detection, linear dynamic range, precision, and other performance measures for quantitative assays. We will profile the 192 cancer related antibodies in hundreds of patients with OPSCC and cervical cancer and more than 1,000 cancer free controls and benchmark the performance with the current gold standard ELISA platform. Our experience with developing innovative high- throughput immunoproteomics platforms using laboratory automation and the quality of our preliminary data speak for our competency in implementing our proposed development. A quantitatively reproducible assay to measure hundreds of antibodies against full length properly folded proteins in thousands of individuals simultaneously will greatly benefit cancer sero-epidemiology, risk assessment and screening.", "keywords": [ "2019-nCoV", "Agreement", "Antibodies", "Antibody Response", "Antigens", "Autoimmune Diseases", "Automation", "Bacteria", "Bar Codes", "Benchmarking", "Binding", "Binding Proteins", "Biological Assay", "COVID-19 assay", "COVID-19 diagnosis", "COVID-19 pandemic", "COVID-19 patient", "Cancer Biology", "Cancer Burden", "Cancer Diagnostics", "Cancer Patient", "Cervical Squamous Cell Carcinoma", "Characteristics", "Clinic", "Clinical", "Communicable Diseases", "Competence", "Consumption", "DNA", "DNA Sequence", "DNA sequencing", "Data", "Detection", "Development", "Diagnosis", "Diagnostic tests", "Disease", "Disease Progression", "Educational process of instructing", "Enzyme-Linked Immunosorbent Assay", "Epidemiology", "Epitopes", "Etiology", "FDA Emergency Use Authorization", "Fluorescence", "Head and Neck Squamous Cell Carcinoma", "Head and neck structure", "Hepatitis C", "Heterogeneity", "Human", "Human Herpesvirus 4", "Human Papillomavirus", "Immune response", "Immunoassay", "Individual", "Informatics", "Kinetics", "Laboratories", "Legal patent", "Length", "Libraries", "Liquid substance", "Malignant Neoplasms", "Malignant neoplasm of cervix uteri", "Measurement", "Measures", "Methods", "Monitor", "Noise", "Oropharyngeal", "Oropharyngeal Squamous Cell Carcinoma", "Patients", "Peptides", "Performance", "Phase", "Play", "Preparation", "Procedures", "Production", "Protein Array", "Protein Array Analysis", "Protein Microchips", "Proteins", "Proteome", "Protocols documentation", "Quality Control", "Reagent", "Reproducibility", "Research", "Risk Assessment", "Running", "SARS-CoV-2 antibody", "Sampling", "Screening for cancer", "Serology test", "Serum", "Signal Transduction", "Surface", "Technology", "Testing", "Tumor Antigens", "Variant", "Viral Antigens", "Virus", "antibody test", "anticancer research", "carcinogenesis", "co-infection", "comparison control", "cost", "data pipeline", "detection limit", "detection method", "early screening", "experience", "fungus", "improved", "indexing", "innovation", "large scale production", "malignant oropharynx neoplasm", "microbial", "microorganism", "microorganism antigen", "multiplex assay", "next generation", "next generation sequencing", "pathogen", "process optimization", "programs", "protein folding", "respiratory pathogen", "response", "screening", "seasonal coronavirus", "tool" ], "approved": true } }, { "type": "Grant", "id": "12089", "attributes": { "award_id": "1R01NR021234-01", "title": "Differences in Hospital Nursing Resources among Black-Serving Hospitals as a Driver of Patient Outcomes Disparities", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [ "National Institute of Nursing Research (NINR)" ], "program_reference_codes": [], "program_officials": [ { "id": 6234, "first_name": "Dionne", "last_name": "Godette", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2023-09-01", "end_date": "2026-06-30", "award_amount": 406250, "principal_investigator": { "id": 26621, "first_name": "Karen Blanchette", "last_name": "Lasater", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 232, "ror": "https://ror.org/00b30xv10", "name": "University of Pennsylvania", "address": "", "city": "", "state": "PA", "zip": "", "country": "United States", "approved": true }, "abstract": "Black Americans are more likely to receive care in lower quality hospitals that confer worse health outcomes to patients. The intractable hospital outcomes disparities have been described for decades and most recently came to the forefront of public attention with COVID-19 mortality disproportionally affecting Black communities. Despite multiple studies which attribute a large share of outcome disparities to quality differences in hospitals where significant proportions of Black patients are treated (i.e., Black-serving hospitals), little is known about what modifiable factors underlie the poorer quality care. This proposal takes a multilevel perspective to identify the contributions of individual, social, and hospital determinants to identify modifiable factors that can be targeted through `upstream' interventions to achieve health equity for Black individuals. We hypothesize that disparities in hospital outcomes are due, in large part, to inequities in the modifiable nurse resources of hospitals—with fewer nurse resources in Black-serving hospitals. This uneven distribution of nurse resources is a vestige of racism that continues to pervade hospital care more than 50 years after the legal desegregation of hospitals. We focus on nurse resources, since having enough nursing staff to deliver timely and effective care, a favorable work environment in which nurses have clinical autonomy in their practice and strong interdisciplinary teamwork, a skill mix rich in registered nurses, and high proportions of bachelors-prepared nurses and advanced practice nurses, have all been associated with better patient outcomes, particularly for minority patients. In this study, we evaluate the impact of hospital-level differences in nurse resources on patient outcomes, including in-hospital and 30-day mortality, readmission, and hospital length of stay. This observational study of over 900,000 older adult patients in nearly 250 hospitals investigates (1) whether differences in nurse resources between Black-serving and other hospitals explain outcomes disparities; (2) whether the outcomes-advantages of having superior hospital nurse resources are enhanced in the presence of other hospital characteristics, including for example, physician staffing, greater numbers of APRNs, or teaching hospitals; and (3) estimates the improvements in patient outcomes, such as lives saved, that could be expected if nurse resources in Black-serving hospitals were similar to other hospitals. Nurse resources are measured using survey data from over 16,000 nurses in nearly 250 hospitals to describe multiple aspects of the clinical nurse resources. Using a unique hospital identifier, nurse responses will be linked with Medicare patient records, demographic and social determinant of health indices. Our analytic approach uses multi-level nested (hierarchically-related) linear and logistic regression models (with interaction terms) to accomplish our aims. If our hypotheses are confirmed, the findings will add evidence to inform high-impact actionable `upstream' solutions to dismantle structural remnants of racism that pervade our healthcare system, by leveraging the most abundant patient care resource already existing in every hospital—nurses.", "keywords": [ "Academy", "Accounting", "Address", "Admission activity", "Advanced Practice Nurse", "Advocate", "Affect", "Age", "Attention", "Beds", "Black American", "Black Populations", "Black race", "COVID-19 mortality", "COVID-19 pandemic", "Caring", "Characteristics", "Clinical", "Clinical Nursing", "Communities", "Comprehensive Health Care", "Data", "Decision Making", "Desegregation", "Diagnosis", "Discipline of Nursing", "Disparity", "Educational process of instructing", "Elderly", "Family", "Floor", "Fostering", "Goals", "Healthcare", "Healthcare Systems", "Hospital Nursing", "Hospitalists", "Hospitalization", "Hospitals", "Individual", "Inequity", "Infrastructure", "Intervention", "Investments", "Legal", "Length of Stay", "Linear Regressions", "Link", "Logistic Regressions", "Measures", "Medical", "Medicare", "Medicine", "Modeling", "New York City", "Nurse&apos", "s Role", "Nurses", "Nursing Staff", "Observational Study", "Operative Surgical Procedures", "Outcome", "Patient Care", "Patient-Focused Outcomes", "Patients", "Physicians", "Policies", "Quality of Care", "Racial Segregation", "Records", "Registered nurse", "Reporting", "Research", "Resources", "Severity of illness", "Surveys", "Teaching Hospitals", "Technology", "Translational Research", "Urban Hospitals", "black patient", "care outcomes", "comorbidity", "coronavirus disease", "disparity reduction", "fortification", "health determinants", "health equity", "hospital care", "hospital readmission", "improved", "improved outcome", "indexing", "minority patient", "mortality", "novel strategies", "outcome disparities", "poor health outcome", "professional atmosphere", "racial disparity", "racial health disparity", "racial minority", "racism", "recruit", "response", "sex", "skills", "social", "social health determinants" ], "approved": true } }, { "type": "Grant", "id": "12090", "attributes": { "award_id": "1I01HX003635-01A1", "title": "Leveraging COVID-19 to modernize depression care for VA primary care populations", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [], "program_reference_codes": [], "program_officials": [], "start_date": "2023-09-01", "end_date": "2025-08-31", "award_amount": null, "principal_investigator": { "id": 27447, "first_name": "Lucinda B", "last_name": "Leung", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 1708, "ror": "https://ror.org/05xcarb80", "name": "VA Greater Los Angeles Healthcare System", "address": "", "city": "", "state": "CA", "zip": "", "country": "United States", "approved": true }, "abstract": "Background: As part of comprehensive suicide prevention, VA integrated mental and physical health services to better detect and treat depression. Primary care nurses conduct screening annually. Clinicians, including Primary Care Mental Health Integration (PC-MHI) specialists, follow up as-needed for treatment. Depression detection and management processes are complex, involve multilevel stakeholders, and subject to significant disruption from COVID-19 and from resulting expansion of telehealth aiming to preserve care access. Fewer VA visits during the pandemic may signify lowered depression care quality and worsened patient outcomes. Significance: Depression affects 1 in 5 Veterans and is a leading cause of suicidality and disability. It contributes substantially to the current pandemic-related mental health crisis. Depression symptoms, including suicidal thoughts/behaviors, and related functional impairment have increased since COVID onset. Partnering with Primary Care, Mental Health, and Connected Care leaders, we propose to study pandemic-related service disruptions for depression, which may help to mitigate acute care use and mortality in the Veteran population. We apply established depression quality indicators from our prior research to a broad national scale at a critical time. We will also obtain feedback to improve current hybrid (virtual/in-person) care models from VA providers and Veterans who screened positive, including those who were not detected to have depression. Specific Aims: To improve virtual and in-person services for the VA primary care population during recovery, this proposal will examine how the pandemic disrupted depression care delivery mechanisms, including expanded telehealth, and patient outcomes. Our Specific Aims are: 1) To examine engagement in guideline- concordant care for depression (virtual or in-person) following screening, before and during the pandemic; 2) To compare psychiatric emergency/hospital visits and mortality from suicide between Veterans who screened positive and were detected versus not detected to have depression by clinicians; 3) To understand VA patients’ and providers’ current perspectives on addressing new depressive episodes using virtual and in-person modalities during the pandemic and eventual recovery. Methodology: Given hypothesized care disruption (lowered care quality) during COVID-19, Aim 1 proposes to extend our preliminary VISN methods nationally to assess the VA population’s trajectory from a new positive depression (and suicide-risk) screen to appropriate treatment (i.e., medication, therapy) in FY19-22/23. We will also examine the changing mix of virtual and in-person depression care delivered. Aim 2 will use interrupted time series analyses to explore the extent to which acute care use may be mitigated by clinician detection of depression nationally. We will also compare mortality rates between patients detected and not detected to have depression. Sub-analyses will reveal where (e.g., clinics with low PC-MHI access) and for whom (e.g., minorities) detection does not systematically occur, and downstream negative sequelae, to guide future intervention. Finally, Aim 3 will interview (1) 40 Veterans who were detected and not detected to have depression per Aims 1 & 2 about care-seeking behavior change, digital divide, etc. and (2) 40 VA primary care and PC-MHI providers about staffing shortage, telehealth adoption, etc. across three VAs (GLA, Syracuse, and Durham). In addition to contextualizing disrupted care findings, qualitative data will help isolate best practices on patient-to-provider and provider-to-provider (e.g., handoffs) interactions in hybrid depression care models. Next Steps/Implementation: The COVID-19 pandemic provides the VA with an opportunity to improve upon a system-wide proactive response to depression and suicide, one that is conceptualized to care for the entire Veteran population. This proposed research will provide the basis for testable hypotheses (e.g., acceptable virtual depression treatments in primary care), and clinical recommendations (e.g., satisfactory virtual provider- to-provider handoffs for new patient referrals), to improve virtual and in-person VA depression services.", "keywords": [ "Address", "Adoption", "Affect", "Behavior", "COVID-19", "COVID-19 pandemic", "Caring", "Clinic", "Clinical", "Complex", "Consultations", "Data", "Detection", "Drops", "Feedback", "Feeling suicidal", "Future", "Guidelines", "Health", "Health Services Accessibility", "Hospitalization", "Hospitals", "Hybrids", "Interruption", "Intervention", "Interview", "Los Angeles", "Mental Depression", "Mental Health", "Mental Health Services", "Methodology", "Methods", "Minority", "Modality", "Modeling", "Modernization", "Morbidity - disease rate", "Outcome", "Patient-Focused Outcomes", "Patients", "Persons", "Pharmaceutical Preparations", "Population", "Primary Care", "Primary Nursing Care", "Process", "Provider", "Quality Indicator", "Quality of Care", "Recommendation", "Recovery", "Research", "Services", "Solid", "Specialist", "Suicide", "Suicide prevention", "System", "Testing", "Time", "Time Series Analysis", "Veterans", "Visit", "Work", "acute care", "adverse outcome", "behavior change", "care delivery", "care seeking", "collaborative care", "connected care", "coronavirus disease", "cost", "current pandemic", "depression prevention", "depressive symptoms", "digital", "disability", "effective therapy", "experience", "follow-up", "functional disability", "improved", "innovation", "military veteran", "mortality", "multidisciplinary", "pandemic disease", "physical conditioning", "physical health service", "population based", "population health", "preservation", "provider to provider", "psychiatric emergency", "response", "routine screening", "screening", "suicidal", "suicidal behavior", "suicidal risk", "suicide mortality", "telehealth", "tool", "virtual", "virtual healthcare" ], "approved": true } }, { "type": "Grant", "id": "12091", "attributes": { "award_id": "1RF1AG082992-01", "title": "Family care to nursing home residents and state essential caregiver programs during the COVID-19 pandemic: impact on dementia care, outcomes, and disparities", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [ "National Institute on Aging (NIA)" ], "program_reference_codes": [], "program_officials": [ { "id": 7229, "first_name": "Elena", "last_name": "Fazio", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2023-09-01", "end_date": "2027-08-31", "award_amount": 1092079, "principal_investigator": { "id": 27948, "first_name": "YUE", "last_name": "LI", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 464, "ror": "https://ror.org/022kthw22", "name": "University of Rochester", "address": "", "city": "", "state": "NY", "zip": "", "country": "United States", "approved": true }, "abstract": "Approximately 6.5 million older adults in the United States currently live with Alzheimer's Disease or Related Dementia (ADRD) and this number is projected to increase to 12.7 million by 2050. Most persons with ADRD require nursing home (NH) care during the course of their illness, and about 70% of them die in NHs. Among NH residents, almost 50% have a diagnosis of ADRD. The risk of dementia is higher for racial/ethnic minorities than non-Hispanic whites, and racial/ethnic minorities with ADRD experience higher levels of cognitive impairment and higher prevalence of behavioral and psychiatric symptoms of dementia. Together, these increase the risk of NH placement for racial/ethnic minority older adults, and the level of NH care they need after placement. However, strong evidence suggests that racial/ethnic minority NH residents with ADRD receive less adequate care (e.g. more feeding tube use) and have worse health outcomes (e.g. higher hospitalization rate) than non-Hispanic white ADRD residents. Informal care, or unpaid care provided by family members or friends, is common for NH residents with and without ADRD. However, family care to NH residents was seriously disrupted during the COVID-19 pandemic due to extended NH lockdown. To mitigate the disrupted family care,18 states established essential caregiver (EC) programs during 2020-21 which allowed NH residents to have in-person access to family or other caregivers under national public health emergency. This study proposes to determine (1) the impacts of informal family care on the health outcomes of NH residents with and without ADRD, their family caregivers, and racial/ethnic residents with ADRD; and (2) the associations of state EC programs with informal caregiving during the COVID-19 pandemic, and with resident and family caregiver health outcomes. This project will employ the 2008-22 Health and Retirement Study (HRS) survey data and other existing data files to address study aims. Findings of the study will provide critical insights into the role of family caregiving to the health of NH residents with ADRD and their families, and into the potential impact of state policies designed to foster family caregiving in NHs during future public health emergencies.", "keywords": [ "Accounting", "Address", "Alzheimer&apos", "s disease diagnosis", "Alzheimer&apos", "s disease related dementia", "Behavioral Symptoms", "COVID-19 pandemic", "Caregivers", "Caring", "Characteristics", "Data", "Data Files", "Databases", "Dementia", "Disparity", "Elderly", "Enteral Feeding", "Ethnic Origin", "Family", "Family Caregiver", "Family member", "Fostering", "Friends", "Future", "Geography", "Health", "Health and Retirement Study", "High Prevalence", "Home Nursing Care", "Hour", "Impaired cognition", "Knowledge", "Link", "Medicare claim", "Not Hispanic or Latino", "Nursing Homes", "Outcome", "Personal Satisfaction", "Persons", "Policies", "Race", "Risk", "Role", "Sampling", "Surveys", "Testing", "United States", "Visiting Nurse", "behavioral impairment", "dementia care", "dementia risk", "design", "ethnic disparity", "ethnic health disparity", "ethnic minority", "expectation", "experience", "family caregiving", "hospitalization rates", "improved", "individual variation", "informal care", "informal caregiving", "insight", "poor health outcome", "programs", "psychiatric symptom", "public health emergency", "racial disparity", "racial minority" ], "approved": true } }, { "type": "Grant", "id": "12092", "attributes": { "award_id": "1U18FD008001-01", "title": "Acquisition of Quant Studio 5 as replacement of aging thermocycler for diagnostic testing", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [], "program_reference_codes": [], "program_officials": [ { "id": 24456, "first_name": "Olgica", "last_name": "Ceric", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2023-09-01", "end_date": "2024-08-31", "award_amount": 49623, "principal_investigator": { "id": 24612, "first_name": "Ailam Lee", "last_name": "Lim", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [ { "id": 799, "ror": "", "name": "UNIVERSITY OF WISCONSIN-MADISON", "address": "", "city": "", "state": "WI", "zip": "", "country": "United States", "approved": true } ] }, "other_investigators": [], "awardee_organization": { "id": 799, "ror": "", "name": "UNIVERSITY OF WISCONSIN-MADISON", "address": "", "city": "", "state": "WI", "zip": "", "country": "United States", "approved": true }, "abstract": "The Wisconsin Veterinary Diagnostic Laboratory (WVDL) has participated in sample analysis for the FDA Vet-LIRN, either for surveillance, during an animal food/drug emergency outbreak or during a large-scale animal food/drug emergency event for surge capacity. During the past years, we have implemented culture for Salmonella from dog feed and feces, culture of Listeria from animal feed, culture and direct Campylobacter jejuni PCR from dog feces. We had also investigated in E. coli carbapenem-resistant gene PCR assay. Additionally, we have participated in several investigations with Vet-LIRN or our human health partners including necropsy of a cat infected with SARS-CoV-2 and C. jejuni isolation from a dog consuming a raw meat diet. We have been very active in supporting SARS-CoV-2 PCR testing of exposed animals from positive households with real-time PCR as an integral part of these testing efforts. The WVDL continue to develop and validate new PCR assays to meet testing need for both large and small animals. For companion animals testing, we worked very closely with the UW shelter medicine program in responding to various disease outbreak in shelters across the country. The specific request for this proposal is to replace an aging ABI 7500 Fast thermocycler with a newer model of Quant Studio 5 to aid WVDL in maintaining our capacity in molecular testing and critical response to animal food/drug emergency or disease outbreak. As a Vet-LIRN laboratory, we are always stand ready to response to these emergency testing needs.", "keywords": [], "approved": true } }, { "type": "Grant", "id": "12093", "attributes": { "award_id": "1R35GM151169-01", "title": "The role of conformational dynamics of enveloped virus spike proteins in cell entry", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [ "National Institute of General Medical Sciences (NIGMS)" ], "program_reference_codes": [], "program_officials": [ { "id": 22244, "first_name": "MICHAEL", "last_name": "SAKALIAN", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2023-09-01", "end_date": "2028-08-31", "award_amount": 372500, "principal_investigator": { "id": 27949, "first_name": "Maolin", "last_name": "Lu", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 846, "ror": "", "name": "UNIVERSITY OF TEXAS HLTH CTR AT TYLER", "address": "", "city": "", "state": "TX", "zip": "", "country": "United States", "approved": true }, "abstract": "Research Abstract: The spike/fusion glycoproteins residing on the surface of human enveloped viruses are targets of immune response and are the focus of researchers developing vaccines and antiviral treatments. The conformational dynamics of spike proteins drive the entry of enveloped viruses into cells via viral membrane fusion and facilitate antibody recognition. However, the lack of deep insights into dynamics has prevented a complete elucidation of the molecular mechanism by which spike proteins promote virus entry. Many viruses, such as coronavirus SARS-CoV-2, respiratory syncytial virus (RSV), and HIV-1, share a similar viral fusion mechanism (type-I) mediated by their respective spike proteins. These spikes undergo dramatic structural changes, and the energy released from conformational transitions overcomes the fusion kinetic barriers. However, our understanding of the multi-step fusion process mainly relies on individual structural snapshots of spike proteins at fusion endpoints. How these endpoints are correlated in a time-resolved manner and the order and frequency of conformational events underlying virus entry remain largely elusive. The proposed research extends our efforts to explore viral membrane fusion and is supported by our experience probing the conformational dynamics of the SARS-CoV-2 spike (S) and HIV-1 envelope (Env) glycoproteins. The overarching goal of this project is to integrate our knowledge into a generic working model that will describe a time-resolved stepwise framework of the type-I fusion mechanism, in which the conformational trajectories of fusion proteins are explicitly defined in space and time. We pioneered the use of the single-molecule Förster resonance energy transfer (smFRET) to study S and revealed multiple S conformations on the virus. We delineated sequential transitions of S from closed to open conformations upon activation by cellular receptors. We provided the first experimental evidence of decelerated transition dynamics from open states, suggesting increased stability of the fusion-reactive open state to be part of the SARS-CoV-2 adaption strategies. Here, we will use an integrated platform of smFRET and virus-to-cell fusion in combination with computational and structural tools to reveal the conformational plasticity S adapts during virus evolution and to visualize the conformational trajectory S undergoes during fusion. We will perform comparative studies on another respiratory virus - RSV fusion (F) protein, with interest in other type-I spike proteins of newly emerging viruses. We will elucidate conformational events and transition dynamics of F-mediated viral membrane fusion and evaluate whether conformation- presentation of F-based vaccine candidates represents the predominant state exposed to the host. The studies are expected to allow us to identify the common and divergent traits of the S- and F-mediated fusion processes that will advance our knowledge and help us define the common theme of the type-I fusion mechanism. We envision that this program of research using different advanced technologies will reveal unrecognized insights into virus entry that lay the foundation for advances in anti-viral interventions, in line with the mission of NIGMS.", "keywords": [ "2019-nCoV", "Antibodies", "Cell fusion", "Cells", "Chimeric Proteins", "Comparative Study", "Deceleration", "Event", "Evolution", "Exposure to", "Fluorescence Resonance Energy Transfer", "Foundations", "Frequencies", "Future", "Glycoproteins", "Goals", "HIV-1", "Human", "Immune Targeting", "Immune response", "Individual", "Infection", "Intervention", "Kinetics", "Knowledge", "Lung", "Mediating", "Membrane Fusion", "Mission", "Modeling", "Molecular", "Molecular Conformation", "National Institute of General Medical Sciences", "Process", "Proteins", "Public Health", "Research", "Research Personnel", "Respiratory syncytial virus", "Role", "Surface", "Technology", "Time", "Vaccines", "Viral", "Virus", "Visualization", "biochemical tools", "biophysical tools", "conformational conversion", "design", "experience", "insight", "interest", "pathogenic virus", "prevent", "programs", "receptor", "respiratory", "respiratory virus", "single molecule", "therapeutic target", "tool", "trait", "vaccine candidate", "vaccine development" ], "approved": true } }, { "type": "Grant", "id": "12094", "attributes": { "award_id": "1R43AI179391-01", "title": "Oral Dissolvable Strips (ODS) as new pediatric and adult delivery mode of therapy for latent tuberculosis", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [ "National Institute of Allergy and Infectious Diseases (NIAID)" ], "program_reference_codes": [], "program_officials": [ { "id": 27950, "first_name": "Barbara E.", "last_name": "Laughon", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2023-09-01", "end_date": "2024-02-29", "award_amount": 273458, "principal_investigator": { "id": 27951, "first_name": "EDWARD G", "last_name": "MALISKI", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 2063, "ror": "", "name": "OAK THERAPEUTICS, INC.", "address": "", "city": "", "state": "KS", "zip": "", "country": "United States", "approved": true }, "abstract": "Tuberculosis (TB) remains one of the major sources of mortality from infectious diseases worldwide. In 2021 an estimated 6.4 million were newly diagnosed with TB globally, approximately 10.6 million fell ill from it, and 1.4 million died from the disease. Of those who died from the disease, 54% were men, 32% women, and 14% were children aged <15 years. TB is also a leading cause of death for people infected with HIV, with 187,000 deaths due to tuberculosis among HIV-positive people in 2021 (WHO, 2022). People living with HIV are on average 19 times more likely to develop active TB disease than people without HIV, and approximately 1 in 3 HIV deaths are due to TB. Furthermore, there is a recent increase in TB cases attributable to resources being diverted for COVID 19. One model, developed by researchers at the London School of Hygiene and Tropical Medicine, projects that there will be around 200,000 additional deaths from TB across China, India, and South Africa between 2020 and 2024. While TB is a treatable and curable disease, the treatment of patients with antimicrobial drugs remains challenging. The extraordinarily long duration of the regimen (min. 6 months), combined with the phenomenon of dysphagia – especially in pediatric and geriatric patients – is one of the root causes for the lack of patient adherence. As a result, there is further spreading of the disease and an even more serious problem, drug resistance. Globally, an estimated 484,000 people developed rifampin resistant or multidrug-resistant TB (RR/MDR-TB) in 2018. Costs for treating the most drug resistant form of TB are around $513,000, significantly higher than the average cost of $18,000 for treating nonresistant TB. Oak Therapeutics is developing a technology that allows life-saving TB drugs to be delivered via Oral Dispersing Strips (ODS). The ODS approach solves many of the problems associated with current delivery by tablets, capsules, or liquids, especially when used by infants and small children. In this proposal, Oak Therapeutics’ proprietary technology will be used to create two distinct fixed doses (1 pediatric and 1 adult) of Isoniazid- Rifapentine (INH-RPT) multi-drug ODS, with the goal of simplifying therapy administration, improving patient/caregiver privacy and ultimately successfully treating latent TB. In Aim 1 Oak Therapeutics plans to develop Rifapentine RPT-ODS. Despite being efficacious, RPT is not stable in the presence of long-term exposure to moisture, heat or direct light. As such, RPT and INH will be encapsulated to minimize the negative effects of these environmental conditions on the stability of RPT-ODS as well as to make it palatable. In Aim 2, using experimental design strategy, Oak Therapeutics will determine appropriate conditions for multidrug formulation and the resulting INH-RPT ODS will be tested against bioequivalent tablets formulation in an in vivo pharmacokinetic study to be performed in Aim 3. The successful completion of Phase I will lay the foundation of a Phase II that will focus on the packaging design for the ODS, strategy for provider and caregiver training and instructional materials and measures for pediatric adherence. Then, a submission packet (505 (b)(2)) will be prepared for WHO and US FDA review and approval.", "keywords": [ "Address", "Adherence", "Adolescent", "Adolescent and Young Adult", "Adult", "Affect", "Africa", "Antibiotics", "Biotechnology", "COVID-19", "Caregivers", "Cause of Death", "Cessation of life", "Child", "Childhood", "China", "Choking", "Clinical", "Communicable Diseases", "Deglutition Disorders", "Development", "Disease", "Doctor of Philosophy", "Dose", "Drug Formulations", "Drug Kinetics", "Drug resistance", "Drug resistance in tuberculosis", "Elderly", "Encapsulated", "Experimental Designs", "Exposure to", "Extreme drug resistant tuberculosis", "Film", "Formulation", "Foundations", "Future", "Goals", "HIV", "HIV Seropositivity", "Health", "Human", "Hygiene", "In Vitro", "India", "Infant", "Legal patent", "Life", "Light", "Liquid substance", "London", "Low income", "Masks", "Measures", "Medical", "Modeling", "Multidrug-Resistant Tuberculosis", "Newly Diagnosed", "Oral", "Oral cavity", "Patients", "Persons", "Pharmaceutical Chemistry", "Pharmaceutical Preparations", "Pharmacologic Substance", "Phase", "Polymers", "Population", "Preparation", "Preventive treatment", "Privacy", "Property", "Provider", "Rattus", "Recommendation", "Reference Standards", "Refrigeration", "Regimen", "Research Personnel", "Resource-limited setting", "Resources", "Rifampicin resistance", "Rifampin", "Sampling", "Schools", "Small Business Innovation Research Grant", "Source", "South Africa", "Tablets", "Taste Perception", "Technology", "Test Result", "Testing", "Therapeutic", "Therapeutic Equivalency", "Treatment Protocols", "Tropical Medicine", "Tuberculosis", "United States National Institutes of Health", "Water", "Woman", "aged", "antimicrobial drug", "barrier to care", "capsule", "caregiver education", "comorbidity", "comparative", "compliance behavior", "cost", "design", "falls", "global health", "human study", "improved", "in vivo", "in vivo evaluation", "innovative technologies", "isoniazid", "lead candidate", "learning materials", "men", "mortality", "nanoparticle", "nervous system disorder", "novel", "pediatric patients", "physical property", "prevention service", "rifapentine", "social stigma", "socioeconomics", "standard care", "tablet formulation", "treatment adherence", "treatment services", "tuberculosis drugs", "tuberculosis treatment" ], "approved": true } } ], "meta": { "pagination": { "page": 1384, "pages": 1442, "count": 14420 } } }