Grant List
Represents Grant table in the DB
GET /v1/grants?page%5Bnumber%5D=1384&sort=-abstract
{ "links": { "first": "https://cic-apps.datascience.columbia.edu/v1/grants?page%5Bnumber%5D=1&sort=-abstract", "last": "https://cic-apps.datascience.columbia.edu/v1/grants?page%5Bnumber%5D=1405&sort=-abstract", "next": "https://cic-apps.datascience.columbia.edu/v1/grants?page%5Bnumber%5D=1385&sort=-abstract", "prev": "https://cic-apps.datascience.columbia.edu/v1/grants?page%5Bnumber%5D=1383&sort=-abstract" }, "data": [ { "type": "Grant", "id": "5989", "attributes": { "award_id": "1K23AI159518-01", "title": "Clinical Epidemiology of Pediatric COVID-19 and MIS-C", "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": 20480, "first_name": "Erik J.", "last_name": "Stemmy", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2021-05-01", "end_date": "2025-04-30", "award_amount": 188457, "principal_investigator": { "id": 20481, "first_name": "Carlos Rafael", "last_name": "Oliveira", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 452, "ror": "https://ror.org/03v76x132", "name": "Yale University", "address": "", "city": "", "state": "CT", "zip": "", "country": "United States", "approved": true }, "abstract": "/ ABSTRACT Although the novel Coronavirus (SARS-CoV-2) has accounted for significant health and economic costs throughout the world, relatively little is known about its effect on children. The first pediatric case of SARS- CoV-2 in the United States was reported on March 2, 2020, and within just three months, over 64,000 cases were confirmed. Even though children, as a group, have been relatively spared from the effects of the virus, there has been an increasing body of evidence to suggest that some may become critically ill. Since a number of children with SARS-CoV-2 infections manifest with severe systemic inflammation and multi-organ dysfunction, more research on determinants of disease and long-term outcomes of those affected is critical. Dr. Oliveira is a pediatric infectious disease clinician whose long-term goal is to become an independently funded physician-scientist, who integrates the disciplines of clinical epidemiology, data science, and biomedical informatics to detect and respond to emerging infectious diseases. The work described in this proposal builds on the scientific themes he developed throughout his prior training and aims to mechanistically understand the effects of SARS-CoV-2 in children by integrating three different scientific tools: natural language processing, machine learning, and clinical epidemiology. The first consideration for this K23 award period will be to use novel computational tools to build automated surveillance and data-extraction system that can facilitate the identification and tracking of incident cases of SARS-CoV-2 in children (Aim 1). Using this surveillance system, Dr. Oliveira will create a comprehensive registry and conduct a rigorous, model-based investigation to derive a state-of-the-art prediction model of clinical deterioration in children with SARS-CoV-2 (Aim 2). Last, he will recruit a longitudinal cohort of SARS-Cov-2 and determine the frequency of complications and long-term outcomes after recovery (Aim 3). This mentored research experience will furnish Dr. Oliveira with skills and expertise in various aspects of clinical epidemiology, including the establishment of surveillance systems, conducting longitudinal studies, computer programing, and executing sophisticated analyses of the longitudinal data. Workshops, semester- long courses will complement this practical experience, and one-on-one mentorship by a multidisciplinary team of established, independently funded, internationally respected investigators and pioneers in the fields of epidemiology, infectious diseases, biomedical informatics, and mathematical modeling. After this work, Dr. Oliveira will have produced important science that could improve the care of all the children affected by this pandemic. Furthermore, he will have gained a unique set of skills and built the necessary infrastructure that will allow him to establish a research program integrating the disciplines of clinical epidemiology, data science, and informatics to detect, prevent, and respond to future pandemics.", "keywords": [ "18 year old", "2019-nCoV", "Accident and Emergency department", "Adult", "Affect", "Algorithms", "COVID-19", "COVID-19 patient", "COVID-19 severity", "COVID-19 surveillance", "Caring", "Child", "Child Care", "Childhood", "Clinic", "Clinical", "Clinical Data", "Communicable Diseases", "Complement", "Country", "Critical Illness", "Cross-Sectional Studies", "Data", "Data Analyses", "Data Science", "Data Set", "Detection", "Deterioration", "Diagnosis", "Discipline", "Disease", "Educational workshop", "Electronic Health Record", "Emerging Communicable Diseases", "Emotional", "Enrollment", "Epidemiology", "Failure", "Frequencies", "Fright", "Functional disorder", "Funding", "Future", "Goals", "Health Care Costs", "Health system", "Hospitalized Child", "Hospitals", "Hour", "Infection", "Informatics", "Infrastructure", "International", "Intervention", "Investigation", "Laboratories", "Literature", "Long-Term Effects", "Longitudinal Studies", "Longitudinal cohort", "Longitudinal cohort study", "Lung diseases", "Machine Learning", "Manuals", "Medical center", "Mentored Patient-Oriented Research Career Development Award", "Mentors", "Mentorship", "Modeling", "Multisystem Inflammatory Syndrome in Children", "Names", "Natural Language Processing", "Outcome", "Patient Self-Report", "Patient-Focused Outcomes", "Patients", "Pediatric epidemiology", "Phenotype", "Physicians", "Protocols documentation", "Quality-of-Life Assessment", "Recovery", "Registries", "Reporting", "Research", "Research Personnel", "Risk", "Risk Factors", "SARS-CoV-2 infection", "SARS-CoV-2 positive", "Science", "Scientist", "Severities", "Shock", "Site", "Societies", "Standardization", "State Hospitals", "Structure", "Symptoms", "Syndrome", "System", "Testing", "Therapeutic Intervention", "Training", "United States", "Ventilator", "Virus", "Work", "base", "biomedical informatics", "body system", "clinical care", "clinical epidemiology", "clinical predictors", "clinical risk", "cohort", "computer program", "computerized tools", "data access", "design", "economic cost", "experience", "follow-up", "health related quality of life", "improved", "longitudinal analysis", "mathematical model", "multidisciplinary", "novel", "novel coronavirus", "pandemic disease", "predictive modeling", "prevent", "preventive intervention", "programs", "public health relevance", "recruit", "severe COVID-19", "skills", "structured data", "surveillanc" ], "approved": true } }, { "type": "Grant", "id": "5165", "attributes": { "award_id": "5K23AI159518-02", "title": "Clinical Epidemiology of Pediatric COVID-19 and MIS-C", "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": 18333, "first_name": "Erik J.", "last_name": "Stemmy", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2021-05-01", "end_date": "2025-04-30", "award_amount": 186189, "principal_investigator": { "id": 18334, "first_name": "Carlos Rafael", "last_name": "Oliveira", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 452, "ror": "https://ror.org/03v76x132", "name": "Yale University", "address": "", "city": "", "state": "CT", "zip": "", "country": "United States", "approved": true }, "abstract": "/ ABSTRACT Although the novel Coronavirus (SARS-CoV-2) has accounted for significant health and economic costs throughout the world, relatively little is known about its effect on children. The first pediatric case of SARS- CoV-2 in the United States was reported on March 2, 2020, and within just three months, over 64,000 cases were confirmed. Even though children, as a group, have been relatively spared from the effects of the virus, there has been an increasing body of evidence to suggest that some may become critically ill. Since a number of children with SARS-CoV-2 infections manifest with severe systemic inflammation and multi-organ dysfunction, more research on determinants of disease and long-term outcomes of those affected is critical. Dr. Oliveira is a pediatric infectious disease clinician whose long-term goal is to become an independently funded physician-scientist, who integrates the disciplines of clinical epidemiology, data science, and biomedical informatics to detect and respond to emerging infectious diseases. The work described in this proposal builds on the scientific themes he developed throughout his prior training and aims to mechanistically understand the effects of SARS-CoV-2 in children by integrating three different scientific tools: natural language processing, machine learning, and clinical epidemiology. The first consideration for this K23 award period will be to use novel computational tools to build automated surveillance and data-extraction system that can facilitate the identification and tracking of incident cases of SARS-CoV-2 in children (Aim 1). Using this surveillance system, Dr. Oliveira will create a comprehensive registry and conduct a rigorous, model-based investigation to derive a state-of-the-art prediction model of clinical deterioration in children with SARS-CoV-2 (Aim 2). Last, he will recruit a longitudinal cohort of SARS-Cov-2 and determine the frequency of complications and long-term outcomes after recovery (Aim 3). This mentored research experience will furnish Dr. Oliveira with skills and expertise in various aspects of clinical epidemiology, including the establishment of surveillance systems, conducting longitudinal studies, computer programing, and executing sophisticated analyses of the longitudinal data. Workshops, semester- long courses will complement this practical experience, and one-on-one mentorship by a multidisciplinary team of established, independently funded, internationally respected investigators and pioneers in the fields of epidemiology, infectious diseases, biomedical informatics, and mathematical modeling. After this work, Dr. Oliveira will have produced important science that could improve the care of all the children affected by this pandemic. Furthermore, he will have gained a unique set of skills and built the necessary infrastructure that will allow him to establish a research program integrating the disciplines of clinical epidemiology, data science, and informatics to detect, prevent, and respond to future pandemics.", "keywords": [ "18 year old", "2019-nCoV", "Accident and Emergency department", "Adult", "Affect", "Algorithms", "COVID-19", "COVID-19 patient", "COVID-19 severity", "COVID-19 surveillance", "Caring", "Child", "Child Care", "Childhood", "Clinic", "Clinical", "Clinical Data", "Communicable Diseases", "Complement", "Country", "Critical Illness", "Cross-Sectional Studies", "Data", "Data Analyses", "Data Science", "Data Set", "Detection", "Deterioration", "Diagnosis", "Discipline", "Disease", "Educational workshop", "Electronic Health Record", "Emerging Communicable Diseases", "Emotional", "Enrollment", "Epidemiology", "Failure", "Frequencies", "Fright", "Functional disorder", "Funding", "Future", "Goals", "Health Care Costs", "Health system", "Hospitalized Child", "Hospitals", "Hour", "Infection", "Informatics", "Infrastructure", "International", "Intervention", "Investigation", "Laboratories", "Literature", "Long-Term Effects", "Longitudinal Studies", "Longitudinal cohort", "Longitudinal cohort study", "Machine Learning", "Manuals", "Medical center", "Mentored Patient-Oriented Research Career Development Award", "Mentors", "Mentorship", "Modeling", "Multisystem Inflammatory Syndrome in Children", "Names", "Natural Language Processing", "Outcome", "Patient Self-Report", "Patient-Focused Outcomes", "Patients", "Pediatric epidemiology", "Phenotype", "Physicians", "Protocols documentation", "Quality-of-Life Assessment", "Recovery", "Registries", "Reporting", "Research", "Research Personnel", "Respiratory Disease", "Risk", "Risk Factors", "SARS-CoV-2 infection", "SARS-CoV-2 positive", "Science", "Scientist", "Severities", "Shock", "Site", "Societies", "Standardization", "State Hospitals", "Structure", "Symptoms", "Syndrome", "System", "Testing", "Therapeutic Intervention", "Training", "United States", "Ventilator", "Virus", "Work", "base", "biomedical informatics", "body system", "clinical care", "clinical epidemiology", "clinical predictors", "clinical risk", "cohort", "computer program", "computerized tools", "data access", "design", "economic cost", "experience", "follow-up", "gradient boosting", "health related quality of life", "improved", "longitudinal analysis", "machine learning model", "mathematical model", "multidisciplinary", "novel", "novel coronavirus", "pandemic disease", "predictive modeling", "prevent", "preventive intervention", "programs", "public health relevance", "recruit", "sev" ], "approved": true } }, { "type": "Grant", "id": "7315", "attributes": { "award_id": "3P50HD089922-04S1", "title": "Penn State University's Translational Center for Child Maltreatment Studies TCCMS", "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": 12475, "first_name": "Valerie", "last_name": "Maholmes", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2017-04-20", "end_date": "2022-03-31", "award_amount": 160500, "principal_investigator": { "id": 12995, "first_name": "JENNIE G", "last_name": "NOLL", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [ { "id": 833, "ror": "", "name": "PENNSYLVANIA STATE UNIVERSITY, THE", "address": "", "city": "", "state": "PA", "zip": "", "country": "United States", "approved": true } ] }, "other_investigators": [ { "id": 23105, "first_name": "Hannah Milena Caroline", "last_name": "Schreier", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "awardee_organization": { "id": 833, "ror": "", "name": "PENNSYLVANIA STATE UNIVERSITY, THE", "address": "", "city": "", "state": "PA", "zip": "", "country": "United States", "approved": true }, "abstract": "/ ABSTRACT Although emerging data regarding the current COVID-19 pandemic suggest that children and adolescents have a lower risk of being diagnosed with severe COVID-19 infections, serious adverse effects, including death, have been reported in this age group. Additionally, concerns that children and adolescents with mild COVID-19 infections continue to spread infections remain. Despite being less likely to be diagnosed with cases of COVID-19, youth's lives are profoundly impacted by the COVID-19 pandemic in numerous ways, including due to disrupted daily routines and educational experiences, reduced social contacts with peers and families, and, potentially, increased exposures to unsafe home environments, overwhelmed caregivers, incidents of domestic violence, and, possibly, incidents of child maltreatment. This highlights that youth with a history of child maltreatment may be particularly vulnerable to the direct and indirect effects of the COVID-19 pandemic seeing as they are likely to come from families already experiencing multiple hardships. This impacts a large number of youth; over one third of U.S. youth are investigated for child maltreatment (CM) before the age of 18. The proposed project will build on the currently ongoing Child Health Study (CHS; HD089922, PI: Noll, Co-I: Schreier), as part of which 775 youth aged 8-13 years who were recently investigated for CM as well as 225 comparison youth without a history of CM are being recruited and followed prospectively. Taking advantage of this unique and exceptionally well-characterized cohort, we will augment the biopsychosocial data already being collected to examine vulnerability and resilience towards COVID-19 infections among these youth, as well as how the additional stress that is currently being experienced by caregivers in the study may spill over to impact youth well-being throughout and following this pandemic. We will examine whether a broad range of physiological, e.g., endocrine, immune, and metabolic, as well as psychosocial, and demographic characteristics of youth are associated with known infections of COVID-19 or with an absence of known infections in the context of having been in close contact with individuals with known infections. Additionally, we will investigate the influence of added caregiver stress on possible exacerbations of existing youth health problems, physiological markers of stress, and new incidents of child maltreatment. Thus, by shedding light on the current and future experiences of some of society's most vulnerable individuals, the resulting data have the potential to provide a powerful jumping-off point for future intervention programs to support these youth who are and will be transitioning into adulthood in the wake of the COVID-19 pandemic. Importantly, this knowledge will also carry forward into informing responses to possible future pandemics which may have similar effects on the everyday lives of individuals.", "keywords": [ "Administrative Supplement", "Adolescent", "Adult", "Adverse effects", "Age", "Behavioral", "COVID-19", "COVID-19 pandemic", "Caregiver Burden", "Caregiver well-being", "Caregivers", "Cessation of life", "Characteristics", "Child", "Child Abuse and Neglect", "Child Health", "Child Welfare", "Childhood", "Data", "Data Set", "Demographic Factors", "Development", "Diagnosis", "Disease Outbreaks", "Domestic Violence", "Endocrine", "Exposure to", "Family", "Financial Hardship", "Funding", "Future", "Health", "Health Care Costs", "Home environment", "Immune", "Individual", "Infection", "Inflammation", "Inflammatory", "Investigation", "Knowledge", "Life", "Light", "Link", "Measures", "Medicaid", "Metabolic", "National Institute of Child Health and Human Development", "Natural experiment", "Outcome", "Parents", "Participant", "Patient Self-Report", "Personal Satisfaction", "Persons", "Pharmaceutical Preparations", "Physiological", "Population", "Predisposition", "Preventive Intervention", "Productivity", "Prospective cohort", "Psychosocial Factor", "Recording of previous events", "Records", "Reporting", "Research Project Grants", "Risk", "Role", "Sampling", "Services", "Sexual abuse", "Societies", "Stress", "Symptoms", "Telephone", "Testing", "Trauma", "Unemployment", "Universities", "Well in self", "Youth", "abuse neglect", "age group", "aged", "anxiety symptoms", "biopsychosocial", "boys", "cardiovascular disorder risk", "case control", "cohort", "cost", "depressive symptoms", "early adolescence", "experience", "girls", "immune function", "individual variation", "interest", "intervention program", "maltreatment", "mortality", "multidimensional data", "pandemic disease", "peer", "physical abuse", "primary caregiver", "prospective", "psychosocial", "recruit", "resilience", "response", "social", "stressor" ], "approved": true } }, { "type": "Grant", "id": "10828", "attributes": { "award_id": "1F30AG077748-01", "title": "Mineral Coated Microparticles for Stabilization and Delivery of Complexed mRNA for Healing of Long Bone Defects", "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": 8478, "first_name": "John", "last_name": "Williams", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2023-01-01", "end_date": "2024-12-31", "award_amount": 37443, "principal_investigator": { "id": 26915, "first_name": "JOSHUA ALAN", "last_name": "CHOE", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 799, "ror": "", "name": "UNIVERSITY OF WISCONSIN-MADISON", "address": "", "city": "", "state": "WI", "zip": "", "country": "United States", "approved": true }, "abstract": "/ ABSTRACT Age related traumatic and pathologic fractures are expected to increase greatly in incidence in the coming decades with aging populations. Older patients are at higher risk for non-healing, ‘critical-size’, bone defects following fracture. This is exacerbated in composite injuries with concomitant soft tissue defects. These require multiple surgical interventions and still a majority of patients remain significantly disabled. Therapies, like bone marrow aspirate concentrate (BMAC), or recombinant bone morphogenetic protein-2 are inconsistent and ineffective or limited by dose related side effects, such as inflammation, respectively. These drawbacks may be overcome by osteogenic stimulation with biomaterial platforms for non-viral gene delivery. The Murphy laboratory has developed nanostructured mineral coated microparticles (MCM) that improve and sustain delivery of therapeutic nucleic acid complexes. These biomimetic mineral coatings were inspired by the structure and characteristics of fossils. Ancient DNA has been recovered from fossils which implicates a role in mineralized surfaces preserving nucleic acids. New stabilization strategies are essential as current mRNA products, like COVID-19 vaccines, require extensive cold-chain infrastructure limiting their application. Biomimetic mineralized materials may provide a platform for the binding, long term stabilization, and delivery of mRNA therapeutics. This fellowship proposal will develop a biomaterials-based method for storage and delivery of mRNA encoding for osteogenic growth factors and train the applicant for a career as a physician scientist. We hypothesize that MCM delivery of mRNA can 1) improve mRNA transfection after lyophilization, 2) promote an osteogenic phenotype in BMAC and 3) mRNA for osteogenic growth factors will reduce inflammation and improve bone defect healing. Aim 1 will optimize and characterize how MCMs stabilize mRNA complexes after lyophilization. Aim 2 will assess the impact of MCM delivery of mRNA for bone morphogenetic protein -2/-7 heterodimers in a rat model of a critical size bone defect. Aim 3 will investigate the efficacy of R- Spondin-2 mRNA on a rat model of composite muscle and bone injury. Outcomes will focus on 1) transfection after simulated accelerated degradation studies, 2/3) gene expression as well as radiographic, biomechanical and histologic bone healing. The goal of this work is to improve storage and application of materials guided mRNA therapeutics for bone regeneration. The proposal will combine the biomaterials and orthopedic expertise of the proposal sponsor, with the vast medical, scientific, graduate training and translational resources available at the University of Wisconsin – Madison. This pre-doctoral fellowship will provide for the development of research, clinical, mentorship, innovation, and communication skills necessary for a career as an independent physician scientist.", "keywords": [ "Adjuvant Therapy", "Affinity", "Aging", "Animals", "Archaeology", "Aspirate substance", "Autologous", "Autologous Transplantation", "BMP2 gene", "Binding", "Biocompatible Materials", "Biomechanics", "Biomimetics", "Bone Injury", "Bone Marrow", "Bone Regeneration", "COVID-19", "COVID-19 vaccine", "Characteristics", "Clinical", "Cold Chains", "Communication", "Complex", "Cryopreservation", "Cues", "DNA", "Defect", "Developmental Biology", "Disabled Persons", "Dose", "Economics", "Elderly", "Evaluation", "Fellowship", "Fossils", "Fracture", "Freeze Drying", "Freezing", "Gene Expression", "Goals", "Gold", "Growth Factor", "Harvest", "Healthcare Systems", "Histologic", "Human", "In Vitro", "Incidence", "Inflammation", "Inflammatory", "Infrastructure", "Injury", "Laboratories", "Measures", "Mediating", "Medical", "Mentorship", "Messenger RNA", "Methods", "Minerals", "Modeling", "Muscle", "Musculoskeletal", "Myoblasts", "Nanostructures", "Natural regeneration", "Nucleic Acids", "Operative Surgical Procedures", "Orthopedics", "Osteogenesis", "Outcome", "Pathological fracture", "Patients", "Phenotype", "Physicians", "Play", "Population", "Post-Translational Protein Processing", "Procedures", "Production", "Protein Isoforms", "Proteins", "Rattus", "Recombinants", "Recovery", "Regenerative Medicine", "Resources", "Role", "Scientist", "Source", "Structure", "Surface", "Temperature", "Testing", "Therapeutic", "Tissues", "Training", "Transfection", "Universities", "WNT Signaling Pathway", "Wisconsin", "Work", "age related", "base", "bone", "bone healing", "calcium phosphate", "career", "cell growth", "cytotoxicity", "effective therapy", "gene therapy", "healing", "high risk", "improved", "ineffective therapies", "innovation", "interest", "long bone", "mRNA Stability", "mRNA delivery", "mesenchymal stromal cell", "minimally invasive", "myogenesis", "neuromuscular", "non-viral gene delivery", "novel therapeutics", "nucleic acid-based therapeutics", "older patient", "osteogenic", "patient variability", "pre-doctoral", "preservation", "protective effect", "protein folding", "radiological imaging", "recombinant human bone morphogenetic protein-2", "regenerative approach", "regenerative biology", "repaired", "research and development", "response", "side effect", "skills", "soft tissue" ], "approved": true } }, { "type": "Grant", "id": "8374", "attributes": { "award_id": "5K23AI153390-02", "title": "Protection of at-risk low birth weight infants against influenza via maternal antibody", "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": "2021-06-01", "end_date": "2026-05-31", "award_amount": 188460, "principal_investigator": { "id": 11103, "first_name": "Alisa", "last_name": "Kachikis", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [ { "id": 159, "ror": "https://ror.org/00cvxb145", "name": "University of Washington", "address": "", "city": "", "state": "WA", "zip": "", "country": "United States", "approved": true } ] }, "other_investigators": [], "awardee_organization": { "id": 159, "ror": "https://ror.org/00cvxb145", "name": "University of Washington", "address": "", "city": "", "state": "WA", "zip": "", "country": "United States", "approved": true }, "abstract": "/ ABSTRACT Acute respiratory infections are the leading cause of mortality among neonates globally, particularly among low birthweight infants from pregnancies complicated by prematurity or placental insufficiency. Maternal immuniza- tion, the vaccination of pregnant women to enhance antibody transported across the placenta to the fetus, is utilized increasingly as an infection prevention strategy to protect neonates from pathogens such as influenza, and may be critical as new vaccines against SARS-CoV-2 are developed. This proposal aims to better eluci- date transplacental antibody transfer in low- and high-risk pregnancies, specifically those with prematurity or placental insufficiency, which is not known. It also describes a research training program that will allow me to become an independent physician-scientist with a translational research program focusing on infectious diseases and vaccines in pregnancy. This proposal builds upon my training in high-risk obstetrics and global health, and provides a detailed plan to improve my knowledge of virology, immunology, vaccinology, cohort studies and statistical analysis. It incorporates the expertise of an outstanding mentorship team, including experts in infectious diseases, immunology, pathology, statistics, and computational biology who are dedicated to the success of this project and the development of my career as an independent clinical researcher. The first aim of this proposal involves establishing normal and high-risk pregnancy cohorts and quantifying transplacental antibody transfer in the context of pregnancies resulting in both normal and low birth weight infants, including those complicated by placental insufficiency leading to small for gestational age infants or prematurity. I will compare quantity of transplacental antibody transfer of total IgG, influenza- and SARS-CoV- 2- specific antibodies, and expression of neonatal Fc receptor in placentas. I will also compare neonatal immunity against influenza among women who did and did not receive influenza vaccine during pregnancy, allowing the opportunity to develop multivariable models and adjust for multiple clinical covariates. For my second aim, I will characterize antibody profiles and transplacental transfer in the same cohorts using a systems serology approach to determine biophysical and effector functions of maternal and fetal immunology. Through accomplishing the aims in this proposal, I will contribute significantly to our knowledge of maternal immunizations, maternal and neonatal immune interactions and neonatal immunity against influenza and SARS-CoV-2. Improved understanding and characterization of transplacental antibody transfer in the context of maternal immunizations may provide insight in the optimization and individualization of vaccine delivery and timing in high-risk pregnancies and, ultimately, has the potential to improve neonatal survival globally. This proposal will allow me to develop a unique set of cross-disciplinary skills and expertise in order to transition to independence as a physician scientist with a larger research program specializing in respiratory infectious diseases and vaccines within the context of low- and high-risk pregnancies.", "keywords": [ "2019-nCoV", "Acute respiratory infection", "Affect", "Antibodies", "Antibody titer measurement", "Antigens", "Biological Assay", "Biophysics", "COVID-19 vaccine", "Chorionic villi", "Clinical", "Clinical Trials", "Cohort Studies", "Communicable Diseases", "Computational Biology", "Computer Analysis", "Development", "Discipline of obstetrics", "Effector Cell", "Enzyme-Linked Immunosorbent Assay", "Fc Receptor", "Fetus", "Gestational Age", "Goals", "Gold", "High-Risk Pregnancy", "Immune", "Immunity", "Immunization Programs", "Immunoglobulin G", "Immunohistochemistry", "Immunology", "Impairment", "Incidence", "Infant", "Infection", "Infection prevention", "Inflammatory", "Influenza", "Knowledge", "Low Birth Weight Infant", "Lytic", "Maternal antibody", "Mentorship", "Methods", "Modeling", "Mothers", "Nature", "Neonatal", "Neonatal Mortality", "Pathology", "Perinatal mortality demographics", "Physicians", "Placenta", "Placental Insufficiency", "Plasma", "Population", "Pregnancy", "Pregnant Women", "Prevention strategy", "Process", "Research", "Research Personnel", "Research Training", "Resource-limited setting", "Respiratory Disease", "Respiratory Tract Infections", "Risk", "Sampling", "Scientist", "Serology", "Shapes", "Small for Gestational Age Infant", "Statistical Data Interpretation", "Syncytiotrophoblast", "System", "Testing", "Training", "Training Programs", "Umbilical Cord Blood", "Vaccinated", "Vaccination", "Vaccines", "Woman", "antibody transfer", "biophysical properties", "burden of illness", "career", "cohort", "fetal", "global health", "high risk", "high risk population", "immune function", "improved", "influenza virus vaccine", "innovation", "insight", "maternal vaccination", "mortality", "neonatal Fc receptor", "neonatal immune system", "neonatal immunity", "neonatal infection", "neonate", "novel", "novel strategies", "novel vaccines", "pathogen", "placental morphology", "premature", "programs", "prospective", "receptor expression", "respiratory", "respiratory pathogen", "respiratory virus", "skills", "statistics", "success", "translational research program", "vaccination strategy", "vaccine delivery", "vaccinology", "virology" ], "approved": true } }, { "type": "Grant", "id": "5793", "attributes": { "award_id": "1K23AI153390-01A1", "title": "Protection of at-risk low birth weight infants against influenza via maternal antibody", "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": 19913, "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": "2021-06-01", "end_date": "2026-05-31", "award_amount": 188460, "principal_investigator": { "id": 19914, "first_name": "Alisa", "last_name": "Kachikis", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 159, "ror": "https://ror.org/00cvxb145", "name": "University of Washington", "address": "", "city": "", "state": "WA", "zip": "", "country": "United States", "approved": true }, "abstract": "/ ABSTRACT Acute respiratory infections are the leading cause of mortality among neonates globally, particularly among low birthweight infants from pregnancies complicated by prematurity or placental insufficiency. Maternal immuniza- tion, the vaccination of pregnant women to enhance antibody transported across the placenta to the fetus, is utilized increasingly as an infection prevention strategy to protect neonates from pathogens such as influenza, and may be critical as new vaccines against SARS-CoV-2 are developed. This proposal aims to better eluci- date transplacental antibody transfer in low- and high-risk pregnancies, specifically those with prematurity or placental insufficiency, which is not known. It also describes a research training program that will allow me to become an independent physician-scientist with a translational research program focusing on infectious diseases and vaccines in pregnancy. This proposal builds upon my training in high-risk obstetrics and global health, and provides a detailed plan to improve my knowledge of virology, immunology, vaccinology, cohort studies and statistical analysis. It incorporates the expertise of an outstanding mentorship team, including experts in infectious diseases, immunology, pathology, statistics, and computational biology who are dedicated to the success of this project and the development of my career as an independent clinical researcher. The first aim of this proposal involves establishing normal and high-risk pregnancy cohorts and quantifying transplacental antibody transfer in the context of pregnancies resulting in both normal and low birth weight infants, including those complicated by placental insufficiency leading to small for gestational age infants or prematurity. I will compare quantity of transplacental antibody transfer of total IgG, influenza- and SARS-CoV- 2- specific antibodies, and expression of neonatal Fc receptor in placentas. I will also compare neonatal immunity against influenza among women who did and did not receive influenza vaccine during pregnancy, allowing the opportunity to develop multivariable models and adjust for multiple clinical covariates. For my second aim, I will characterize antibody profiles and transplacental transfer in the same cohorts using a systems serology approach to determine biophysical and effector functions of maternal and fetal immunology. Through accomplishing the aims in this proposal, I will contribute significantly to our knowledge of maternal immunizations, maternal and neonatal immune interactions and neonatal immunity against influenza and SARS-CoV-2. Improved understanding and characterization of transplacental antibody transfer in the context of maternal immunizations may provide insight in the optimization and individualization of vaccine delivery and timing in high-risk pregnancies and, ultimately, has the potential to improve neonatal survival globally. This proposal will allow me to develop a unique set of cross-disciplinary skills and expertise in order to transition to independence as a physician scientist with a larger research program specializing in respiratory infectious diseases and vaccines within the context of low- and high-risk pregnancies.", "keywords": [ "2019-nCoV", "Acute respiratory infection", "Affect", "Antibodies", "Antibody titer measurement", "Antigens", "Biological Assay", "Biophysics", "COVID-19 vaccine", "Chorionic villi", "Clinical", "Clinical Trials", "Cohort Studies", "Communicable Diseases", "Computational Biology", "Computer Analysis", "Development", "Discipline of obstetrics", "Effector Cell", "Enzyme-Linked Immunosorbent Assay", "Fc Receptor", "Fetus", "Gestational Age", "Goals", "Gold", "High-Risk Pregnancy", "Immune", "Immunity", "Immunization Programs", "Immunoglobulin G", "Immunohistochemistry", "Immunology", "Impairment", "Incidence", "Infant", "Infection", "Infection prevention", "Inflammatory", "Influenza", "Knowledge", "Low Birth Weight Infant", "Lung diseases", "Maternal antibody", "Mentorship", "Methods", "Modeling", "Mothers", "Nature", "Neonatal", "Neonatal Mortality", "Pathology", "Perinatal mortality demographics", "Physicians", "Placenta", "Placental Insufficiency", "Plasma", "Population", "Pregnancy", "Pregnant Women", "Prevention strategy", "Process", "Research", "Research Personnel", "Research Training", "Resources", "Respiratory Tract Infections", "Risk", "Sampling", "Scientist", "Serology", "Shapes", "Small for Gestational Age Infant", "Statistical Data Interpretation", "Syncytiotrophoblast", "System", "Testing", "Training", "Training Programs", "Umbilical Cord Blood", "Vaccinated", "Vaccination", "Vaccines", "Woman", "antibody transfer", "biophysical properties", "burden of illness", "career", "cohort", "fetal", "global health", "high risk", "high risk population", "immune function", "improved", "influenza virus vaccine", "innovation", "insight", "maternal vaccination", "mortality", "neonatal Fc receptor", "neonatal immune system", "neonatal immunity", "neonatal infection", "neonate", "novel", "novel strategies", "novel vaccines", "pathogen", "placental morphology", "premature", "programs", "prospective", "receptor expression", "respiratory", "respiratory pathogen", "respiratory virus", "skills", "statistics", "success", "translational research program", "vaccine delivery", "vaccinology", "virology" ], "approved": true } }, { "type": "Grant", "id": "12061", "attributes": { "award_id": "1U24HL166784-01A1", "title": "2/2: PREcision VENTilation to attenuate Ventilation-Induced Lung Injury (PREVENT VILI)", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [ "National Heart Lung and Blood Institute (NHLBI)" ], "program_reference_codes": [], "program_officials": [ { "id": 22589, "first_name": "CHRISTIAN RENE", "last_name": "Gomez", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2023-09-01", "end_date": "2030-08-31", "award_amount": 1175434, "principal_investigator": { "id": 27913, "first_name": "Elias", "last_name": "Baedorf Kassis", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [ { "id": 27914, "first_name": "TIMOTHY T", "last_name": "HOULE", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "awardee_organization": { "id": 771, "ror": "https://ror.org/04drvxt59", "name": "Beth Israel Deaconess Medical Center", "address": "", "city": "", "state": "MA", "zip": "", "country": "United States", "approved": true }, "abstract": "/ ABSTRACT Acute respiratory distress syndrome (ARDS) occurs in up to one-quarter of all critically ill adults receiving mechanical ventilation and is associated with high risk of morbidity and mortality, which is compounded by ventilation-induced lung injury (VILI). Current ventilation strategies and standard care attempt to lessen the effects of VILI, but have not been uniformly successful. The need for improved ventilation strategies have become more compelling and urgent in the context of the COVID-19 pandemic. Precise ventilator titration of tidal volumes to maintain driving pressure ≤ 12 cm H2O may improve overdistension injury and application of positive end expiratory pressure (PEEP) with titration to transpulmonary pressure of 0±2cmH2O may prevent injury from lung collapse. This U24 grant application will establish a Data Coordinating Center (DCC) that supports the PREcision VENTilation to attenuate VILI Clinical Coordinating Center (CCC) in conducting a multicenter, prospective phase III randomized trial to test the hypothesis that this precision ventilation strategy will improve 60-day mortality compared to guided usual care in patients with moderate or severe ARDS. The DCC will provide the infrastructure, support, oversight and quality control necessary to conduct this trial guided by the following aims: Aim 1 - To collaborate in the protocol development. The DCC will assist the CCC in defining the overarching plan of the trial, and ensure the inclusion of essential sections within the protocol document. Aim 2 - To design and execute an appropriate, pre-determined, innovative statistical plan including analysis of study data, assessment of safety, investigation of mechanism of benefit, and facilitation of manuscript preparation. Aim 3 – To facilitate a patient centered study, with community engagement, by providing video-assisted consent materials, real-time reporting of accrual rates, with emphasis on ensuring a diverse participant population and ensuring patient safety by providing clear instructions on identification and timing of adverse event reporting and creation of the Data and Safety Monitoring Board. Aim 4 - To support an advanced physiological core laboratory to integrate physiological expertise into trial conduct and data management and to ensure rigor and reproducibility of respiratory waveform interpretation used for protocol-directed ventilator management in the intervention arm. The DCC will review all physiological waveforms submitted by sites and provide feedback regarding quality and interpretation. Aim 5 - To provide data administration and monitor trial activities. The DCC will build the eCRFs on a state-of-the-art electronic data capture system. During enrollment, the DCC will ensure high-quality data collection and measure and improve protocol compliance. To foster site communication and identity, the DCC will develop a trial website and quarterly newsletter, and assist the CCC in organizing meetings and conference calls. Aim 6 - To ensure completeness of the study and post-trial activities. This includes meeting milestones and end-of-trial support for participating sites and providing the funding agency with a finalized, deidentified, and locked data set for public use.", "keywords": [ "Acute Respiratory Distress Syndrome", "Address", "Admission activity", "Adult", "Adverse event", "Applications Grants", "Attenuated", "Automobile Driving", "Biological Markers", "Body Weight", "Breathing", "COVID-19 mortality", "COVID-19 pandemic", "Case Report Form", "Cause of Death", "Clinical", "Clinical Trials Data Monitoring Committees", "Collaborations", "Communication", "Consent", "Critical Illness", "Data", "Data Collection", "Data Coordinating Center", "Data Set", "Electronics", "Enrollment", "Ensure", "Feedback", "Fostering", "Funding Agency", "Goals", "Grant", "Healthcare Systems", "Infrastructure", "Injury", "Instruction", "Intervention", "Investigation", "Laboratories", "Lung", "Maintenance", "Manuscripts", "Measurement", "Measures", "Mechanical ventilation", "Methodology", "Monitor", "Morbidity - disease rate", "Newsletter", "Outcome", "Participant", "Patients", "Phase", "Physiological", "Population", "Positive-Pressure Respiration", "Preparation", "Prevention strategy", "Protocol Compliance", "Protocols documentation", "Quality Control", "Randomized Controlled Trials", "Recording of previous events", "Recovery", "Reporting", "Reproducibility", "Research", "Research Personnel", "Respiratory Mechanics", "Risk", "Shock", "Site", "Stress", "Techniques", "Teleconferences", "Testing", "Tidal Volume", "Time", "Titrations", "Ventilator", "Ventilator-induced lung injury", "arm", "atelectrauma", "community engagement", "cost", "data management", "design", "efficacy testing", "electronic data capture system", "evidence base", "expiration", "hemodynamics", "high risk", "high standard", "improved", "innovation", "lung injury", "lung pressure", "meetings", "mortality", "novel", "patient oriented", "patient safety", "personalized approach", "personalized strategies", "pre-pandemic", "pressure", "prevent", "primary outcome", "prospective", "protocol development", "randomized trial", "respiratory", "safety assessment", "standard care", "standard of care", "statistical center", "support tools", "symposium", "treatment arm", "treatment as usual", "trial planning", "usual care arm", "ventilation", "web site" ], "approved": true } }, { "type": "Grant", "id": "15437", "attributes": { "award_id": "5U24HL166784-02", "title": "2/2: PREcision VENTilation to attenuate Ventilation-Induced Lung Injury (PREVENT VILI)", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [ "National Heart Lung and Blood Institute (NHLBI)" ], "program_reference_codes": [], "program_officials": [ { "id": 22589, "first_name": "CHRISTIAN RENE", "last_name": "Gomez", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2023-09-01", "end_date": "2030-08-31", "award_amount": 661149, "principal_investigator": { "id": 27913, "first_name": "Elias", "last_name": "Baedorf Kassis", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [ { "id": 27914, "first_name": "TIMOTHY T", "last_name": "HOULE", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "awardee_organization": { "id": 771, "ror": "https://ror.org/04drvxt59", "name": "Beth Israel Deaconess Medical Center", "address": "", "city": "", "state": "MA", "zip": "", "country": "United States", "approved": true }, "abstract": "/ ABSTRACT Acute respiratory distress syndrome (ARDS) occurs in up to one-quarter of all critically ill adults receiving mechanical ventilation and is associated with high risk of morbidity and mortality, which is compounded by ventilation-induced lung injury (VILI). Current ventilation strategies and standard care attempt to lessen the effects of VILI, but have not been uniformly successful. The need for improved ventilation strategies have become more compelling and urgent in the context of the COVID-19 pandemic. Precise ventilator titration of tidal volumes to maintain driving pressure ≤ 12 cm H2O may improve overdistension injury and application of positive end expiratory pressure (PEEP) with titration to transpulmonary pressure of 0±2cmH2O may prevent injury from lung collapse. This U24 grant application will establish a Data Coordinating Center (DCC) that supports the PREcision VENTilation to attenuate VILI Clinical Coordinating Center (CCC) in conducting a multicenter, prospective phase III randomized trial to test the hypothesis that this precision ventilation strategy will improve 60-day mortality compared to guided usual care in patients with moderate or severe ARDS. The DCC will provide the infrastructure, support, oversight and quality control necessary to conduct this trial guided by the following aims: Aim 1 - To collaborate in the protocol development. The DCC will assist the CCC in defining the overarching plan of the trial, and ensure the inclusion of essential sections within the protocol document. Aim 2 - To design and execute an appropriate, pre-determined, innovative statistical plan including analysis of study data, assessment of safety, investigation of mechanism of benefit, and facilitation of manuscript preparation. Aim 3 – To facilitate a patient centered study, with community engagement, by providing video-assisted consent materials, real-time reporting of accrual rates, with emphasis on ensuring a diverse participant population and ensuring patient safety by providing clear instructions on identification and timing of adverse event reporting and creation of the Data and Safety Monitoring Board. Aim 4 - To support an advanced physiological core laboratory to integrate physiological expertise into trial conduct and data management and to ensure rigor and reproducibility of respiratory waveform interpretation used for protocol-directed ventilator management in the intervention arm. The DCC will review all physiological waveforms submitted by sites and provide feedback regarding quality and interpretation. Aim 5 - To provide data administration and monitor trial activities. The DCC will build the eCRFs on a state-of-the-art electronic data capture system. During enrollment, the DCC will ensure high-quality data collection and measure and improve protocol compliance. To foster site communication and identity, the DCC will develop a trial website and quarterly newsletter, and assist the CCC in organizing meetings and conference calls. Aim 6 - To ensure completeness of the study and post-trial activities. This includes meeting milestones and end-of-trial support for participating sites and providing the funding agency with a finalized, deidentified, and locked data set for public use.", "keywords": [], "approved": true } }, { "type": "Grant", "id": "12107", "attributes": { "award_id": "1UG3HL166785-01A1", "title": "1/2: PREcision VENTilation to attenuate Ventilation-Induced Lung Injury (PREVENT VILI)", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [ "National Heart Lung and Blood Institute (NHLBI)" ], "program_reference_codes": [], "program_officials": [ { "id": 22589, "first_name": "CHRISTIAN RENE", "last_name": "Gomez", "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": 1445727, "principal_investigator": { "id": 27970, "first_name": "Jeremy R.", "last_name": "Beitler", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [ { "id": 27971, "first_name": "Daniel Stuart", "last_name": "Talmor", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "awardee_organization": { "id": 771, "ror": "https://ror.org/04drvxt59", "name": "Beth Israel Deaconess Medical Center", "address": "", "city": "", "state": "MA", "zip": "", "country": "United States", "approved": true }, "abstract": "/ ABSTRACT Acute respiratory distress syndrome (ARDS) is a severe form of lung injury requiring hospitalization in intensive care and often invasive mechanical ventilation in effort to sustain life. ARDS can result from a variety of insults (e.g. pneumonia, sepsis, trauma, and pancreatitis), posing broad risk to the public health. With the COVID-19 pandemic, ARDS has become a leading cause of death in the US and globally. Yet, even pre-pandemic, ARDS occurred in 10% of US ICU admissions and had an associated mortality of 30-45%. Regardless of ARDS etiology, many survivors experience cognitive, psychological, and physical impairments persisting years after the acute illness resolves. Thus, there remains an urgent need to identify effective ARDS therapies. Invasive mechanical ventilation is potentially life-saving, but can worsen lung injury and patient outcomes if not precisely titrated to attenuate lung stress, which varies by patient with overdistension and atelectrauma (repetitive opening/closure of potentially recruitable lung). Alveolar edema and atelectasis reduce the functional aerated lung volume, such that tidal volume scaled to estimated healthy lung size (i.e. 6 mL/kg predicted body weight) may not always prevent overdistension. Similarly, positive end-expiratory pressure (PEEP) is routinely increased to recruit lung in patients with more severe hypoxemia, an approach that may exacerbate overdistension injury in patients most susceptible. An integrated strategy that mitigates the competing risks of atelectrauma and overdistension is needed. The range of lung stress observed in patients with ARDS receiving standard-of-care ventilation is often larger than that observed in healthy adults due to perturbed lung and chest wall mechanics, increasing risk of both atelectrauma and overdistension. In preclinical models and human cohort studies, lung injury and mortality are less when the ventilator is set to maintain lung stress in the healthy normal range. PREcision VENTilation to attenuate Ventilation-Induced Lung Injury (PREVENT VILI) is a phase III multicenter randomized trial for adults with moderate-severe ARDS that tests whether precise ventilator titration to maintain lung stress within 0-12 cm H2O, the healthy normal range during relaxed breathing, will improve patient outcomes compared to guided usual care. In the precision ventilation arm, PEEP will be individualized to achieve lung stress of 0 cm H2O at end-expiration, and tidal volume individualized to achieve driving pressure of 12 cm H2O or the lowest possible. In the guided usual care arm, PEEP will be adjusted per usual care within limits set to avoid practice extremes; tidal volume of 6-8 mL/kg predicted body weight will be targeted unless plateau pressure exceeds 30 cm H2O, in which case tidal volume will be lowered. We will evaluate the effect of ventilator strategy on 60-day mortality (Aim 1), lung injury (Aim 2), and hemodynamic instability (Aim 3). Findings will help determine the role for individualizing ventilator support to reduce lung stress in ARDS and have potential to improve survival from this leading cause of death worldwide.", "keywords": [ "Acute", "Acute Respiratory Distress Syndrome", "Adipose tissue", "Admission activity", "Adult", "Alveolar", "Anatomy", "Atelectasis", "Attenuated", "Automobile Driving", "Blinded", "Body Weight", "Breathing", "COVID-19", "COVID-19 mortality", "COVID-19 pandemic", "Cause of Death", "Chest wall structure", "Clinical", "Clinical Management", "Cognitive", "Cohort Studies", "Edema", "Esophagus", "Etiology", "Fibrosis", "Grant", "Healthcare Systems", "Heterogeneity", "Histologic", "Hospitalization", "Human", "Hypoxemia", "Impairment", "Injury", "Insufflation", "Intensive Care", "Intra-abdominal", "Life", "Lung", "Manometry", "Measures", "Mechanical Stress", "Mechanical ventilation", "Mechanics", "Modeling", "Morbidity - disease rate", "Multi-Institutional Clinical Trial", "National Heart Lung and Blood Institute", "Normal Range", "Outcome", "Pancreatitis", "Patient-Focused Outcomes", "Patients", "Periodicity", "Phase", "Pleural", "Pleural effusion disorder", "Pneumonia", "Positioning Attribute", "Positive-Pressure Respiration", "Pre-Clinical Model", "Predisposition", "Public Health", "Pulmonary Edema", "Randomized Controlled Trials", "Recovery", "Relaxation", "Research", "Risk", "Role", "Safety", "Sepsis", "Shapes", "Shock", "Stress", "Structure of parenchyma of lung", "Survivors", "Testing", "Tidal Volume", "Time", "Titrations", "Trauma", "Ventilator", "Ventilator-induced lung injury", "abdominal pressure", "arm", "atelectrauma", "circulating biomarkers", "cost", "experience", "expiration", "hemodynamics", "improved", "lung injury", "lung volume", "mortality", "novel", "personalized approach", "personalized strategies", "pre-clinical", "pre-pandemic", "pressure", "prevent", "psychologic", "randomized trial", "receptor for advanced glycation endproducts", "recruit", "soft tissue", "standard care", "standard of care", "stress reduction", "surfactant", "systemic inflammatory response", "treatment as usual", "usual care arm", "ventilation", "volunteer" ], "approved": true } }, { "type": "Grant", "id": "7471", "attributes": { "award_id": "3UH3DK114920-04S2", "title": "Nicotinamide Riboside for AKI in COVID-19 positive inpatients", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [ "National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)" ], "program_reference_codes": [], "program_officials": [ { "id": 20726, "first_name": "Cindy", "last_name": "Roy", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2017-09-15", "end_date": "2022-06-30", "award_amount": 502216, "principal_investigator": { "id": 20727, "first_name": "Kumar", "last_name": "Sharma", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [ { "id": 748, "ror": "", "name": "UNIVERSITY OF TEXAS HLTH SCIENCE CENTER", "address": "", "city": "", "state": "TX", "zip": "", "country": "United States", "approved": true } ] }, "other_investigators": [], "awardee_organization": { "id": 748, "ror": "", "name": "UNIVERSITY OF TEXAS HLTH SCIENCE CENTER", "address": "", "city": "", "state": "TX", "zip": "", "country": "United States", "approved": true }, "abstract": "/ Abstract Acute kidney injury (AKI) has been as high as 68% in COVID-19 patients admitted to intensive care unit (ICU) and 90% in patients on mechanical ventilation in New York City, NY. Moreover, up to 86% of deaths were associated with AKI using standard Kidney Disease: Improving Global Outcomes (KDIGO) definition. Kidney contain abundance of mitochondria and impaired mitochondrial function is now well recognized as a major susceptibility feature for AKI. It is generally believed based on histopathological evidence that the underlying origin of AKI is inflammation or “cytokine storm” which suppresses PPAR-gamma-coactivator-1alpha (PGC1α) – the primary regulator of mitochondrial biogenesis and a regulator of nicotinamide adenine dinucleotide (NAD+). Lower availability of NAD+ limits existing mitochondrial function by reducing electron donors to the mitochondria. Stimulation of pathways that lead to enhancement of NAD+ appears to be beneficial in mitigating AKI occurrence and severity in both animal models and humans. Recent studies using oral Nicotinamide (NAM) and Nicotinamide Riboside (NR) as NAD+ donors have been found to be safe, well-tolerated, and upregulate NAD+ pathways in a dose-dependent manner. In addition, NAM use during perioperative period in patients undergoing cardiothoracic surgery showed reduced incidence of AKI in a small number of patients without any adverse events. It has been demonstrated that NR is more orally bioavailable than NAM and has no major adverse events in Phase I studies. At the present time no standard medical treatment for AKI is available and supportive care remains the mainstay of therapy. Therefore, the application of agents to safely restore mitochondrial function may provide a major benefit for reduced incidence and severity of AKI and potentially lower multi-organ failure and mortality. We specifically hypothesize that at admission supplementation with NR will improve markers of AKI including indices of mitochondrial function in SARS-CoV-2 patients without significant adverse events. We will test this hypothesis in a pilot clinical study named: NIRVANA: NIcotinamide Riboside in SARS-CoV-2 pAtients for reNAl protection. The primary aim of this pilot study is to determine the effects of NR to reduce severity of AKI in newly admitted patients with SARS-CoV-2 using a randomized, double-blinded placebo- controlled clinical trial of 10-day consecutive treatment with oral nicotinamide riboside (NR) 500 mg twice daily (versus placebo). The primary outcome will be incidence of AKI defined by the KDIGO guidelines. A total of 100 SARS-CoV-2 patients ≥18 years of age admitted to hospitals affiliated with 3 major medical academic institutions (University of Texas Health San Antonio (UTHSA), Icahn School of Medicine at Mount Sinai, New York, NY, and University of Washington at Seattle (UW) will be enrolled into this pilot study. To evaluate secondary and exploratory outcomes, we will determine severity of AKI, the effects of NR on biomarkers of AKI and mitochondrial function by analyzing putative markers related to renal involvement, inflammation, and metabolomics in timed biosamples collected from the study participants.", "keywords": [ "18 year old", "2019-nCoV", "Acute Renal Failure with Renal Papillary Necrosis", "Admission activity", "Adverse event", "Animal Model", "Bioavailable", "Biogenesis", "Biological Markers", "Blood", "COVID-19", "Cardiac Output", "Cessation of life", "Clinical Research", "Clinical Trials", "Controlled Clinical Trials", "Dose", "Double-Blind Method", "Effectiveness", "Enrollment", "Exhibits", "Failure", "Functional disorder", "Guidelines", "Health", "Hematuria", "Hospitals", "Human", "Impairment", "Incidence", "Infection", "Inflammation", "Injury to Kidney", "Inpatients", "Institution", "Intensive Care Units", "Intervention", "Kidney", "Kidney Diseases", "Lead", "Life", "Liquid substance", "Measures", "Mechanical ventilation", "Medical", "Mitochondria", "Modeling", "Names", "New York", "New York City", "Niacinamide", "Nicotinamide adenine dinucleotide", "Obesity", "Operative Surgical Procedures", "Oral", "Organ Model", "Organ failure", "Outcome", "PPAR gamma", "Participant", "Pathway interactions", "Patients", "Perioperative", "Pharmaceutical Preparations", "Pilot Projects", "Placebos", "Pneumonia", "Pre-Clinical Model", "Predisposition", "Process", "Production", "Proteinuria", "Randomized", "Reperfusion Injury", "Reporting", "Research", "Role", "Septic Shock", "Severities", "Supplementation", "Supportive care", "Testing", "Texas", "Therapeutic", "Time", "Titrations", "Universities", "Urine", "Washington", "base", "blood pressure regulation", "cytokine release syndrome", "dietary supplements", "electron donor", "high risk", "human morbidity", "human mortality", "improved", "indexing", "medical schools", "metabolomics", "mortality", "nicotinamide-beta-riboside", "novel coronavirus", "pandemic disease", "phase 1 study", "prevent", "primary endpoint", "primary outcome", "pulmonary function", "targeted treatment" ], "approved": true } } ], "meta": { "pagination": { "page": 1384, "pages": 1405, "count": 14046 } } }