Expired blood transfusion and mortality outcomes in combat trauma patients.

BACKGROUND: Expired blood can be transfused if clinically indicated but outcome data do not exist. We hypothesized that modestly outdated blood can effectively support a hemorrhaging patient until surgical control is achieved. This study assessed whether expired blood was associated with mortality in combat trauma patients. STUDY DESIGN AND METHODS: A retrospective analysis of Armed Services Blood Program and Department of Defense Trauma Registry databases evaluated combat casualty records (2001-2023). The intervention of interest was transfusion of at least one unit of whole blood (WB), red blood cells (RBC), or platelets within one week past expiration. The outcome of interest was mortality at discharge. A control cohort that only received in-date blood was matched to the treatment cohort for logistic regression analysis. RESULTS: One hundred patients received expired RBCs (86), WB (11), and platelets (3). Mortality at discharge was 11.6% for expired RBC recipients and 13.4% for the control cohort (p = .97). After adjustment for injury severity, expired RBCs were not associated with mortality (OR = 0.40 [95% CI, 0.14-1.16]; p = .09). Of 10 patients who received the most expired RBCs by volume or storage duration, two were deceased at discharge. All 14 expired WB and platelet recipients were alive at discharge, but sample sizes were underpowered for regression analysis. DISCUSSION: Transfusion of modestly outdated RBCs was not associated with mortality in combat trauma patients. Expired WB and platelet recipients did well, but sample sizes were too small to draw significant conclusions. Expired blood should be further investigated for possible use in extenuating circumstances.

Blood product availability in the Washington state trauma system.

BACKGROUND: Early transfusion can prolong life in injured patients awaiting definitive hemorrhage control. We conducted a community resources assessment of blood product availability at hospitals within the Washington State (WA) Regional Trauma System, with the expectation that a minority of Level IV and V centers would have blood products routinely available for use in resuscitation. METHODS: We designed a questionnaire soliciting information on routinely available unit quantities of red blood cells (RBC), plasma, platelets, cryoprecipitate, and/or whole blood and submitted this questionnaire electronically to the 82 WA designated trauma centers (Levels I-V). Non-responders were contacted directly by telephone. The study was conducted in September and October 2021. US 2020 census data were used to correlate results with local population densities. RESULTS: First-round contact netted responses from 57 (70%) centers; the remaining centers provided information via telephone, for a 100% final response. Packed RBC were available in 79 of the 82 centers (96%; range 6-220 units); plasma, 62 centers (76%, range 1-100 units); platelets, 40 centers (49%, range 1-8 units); cryoprecipitate, 45 centers (55%, range 1-20 units). Whole blood was only available at the Level I center. Three Level V centers, located in 2 of the 8 WA state trauma regions, reported no routine blood availability. The two trauma regions affected represent 12% of the state's population and more than a third of its geographic area. CONCLUSIONS: Within the WA regional trauma system, blood products are wide, if unevenly, available. Large urban/rural disparities in availability exist that should be explored.

Clinical, social, and policy factors in COVID-19 cases and deaths: methodological considerations for feature selection and modeling in county-level analyses.

BACKGROUND: There is a need to evaluate how the choice of time interval contributes to the lack of consistency of SDoH variables that appear as important to COVID-19 disease burden within an analysis for both case counts and death counts. METHODS: This study identified SDoH variables associated with U.S county-level COVID-19 cumulative case and death incidence for six different periods: the first 30, 60, 90, 120, 150, and 180 days since each county had COVID-19 one case per 10,000 residents. The set of SDoH variables were in the following domains: resource deprivation, access to care/health resources, population characteristics, traveling behavior, vulnerable populations, and health status. A generalized variance inflation factor (GVIF) analysis was used to identify variables with high multicollinearity. For each dependent variable, a separate model was built for each of the time periods. We used a mixed-effect generalized linear modeling of counts normalized per 100,000 population using negative binomial regression. We performed a Kolmogorov-Smirnov goodness of fit test, an outlier test, and a dispersion test for each model. Sensitivity analysis included altering the county start date to the day each county reached 10 COVID-19 cases per 10,000. RESULTS: Ninety-seven percent (3059/3140) of the counties were represented in the final analysis. Six features proved important for both the main and sensitivity analysis: adults-with-college-degree, days-sheltering-in-place-at-start, prior-seven-day-median-time-home, percent-black, percent-foreign-born, over-65-years-of-age, black-white-segregation, and days-since-pandemic-start. These variables belonged to the following categories: COVID-19 related, vulnerable populations, and population characteristics. Our diagnostic results show that across our outcomes, the models of the shorter time periods (30 days, 60 days, and 900 days) have a better fit. CONCLUSION: Our findings demonstrate that the set of SDoH features that are significant for COVID-19 outcomes varies based on the time from the start date of the pandemic and when COVID-19 was present in a county. These results could assist researchers with variable selection and inform decision makers when creating public health policy.

Cancer Hazard Identification Integrating Human Variability: The Case of Coumarin.

Coumarin is a naturally occurring sweet-smelling benzopyrone that may be extracted from plants or synthesized for commercial uses. Its uses include as a flavoring agent, fragrance enhancer, and odor-masking additive. We reviewed and evaluated the scientific evidence on the carcinogenicity of coumarin, integrating information from carcinogenicity studies in animals with mechanistic and other relevant data, including data from toxicogenomic, genotoxicity, and metabolism studies, and studies of human variability of a key enzyme, CYP2A6. Increases in tumors were observed in multiple studies in rats and mice in multiple tissues. Our functional pathway analysis identified several common cancer-related biological processes/pathways affected by coumarin in rat liver following in vivo exposure and in human primary hepatocytes exposed in vitro. When coumarin 7-hydroxylation by CYP2A6 is compromised, this can lead to a shift in metabolism to the 3,4-epoxidation pathway and increased generation of electrophilic metabolites. Mechanistic data align with 3 key characteristics of carcinogens, namely formation of electrophilic metabolites, genotoxicity, and induction of oxidative stress. Considerations of metabolism, human variability in CYP2A6 activity, and coumarin hepatotoxicity in susceptible individuals provide additional support for carcinogenicity concern. Our analysis illustrates the importance of integrating information on human variability in the cancer hazard identification process.

Racial Disparities in Diabetes Care and Outcomes for Patients with Visual Impairment: A Descriptive Analysis of the TriNetX Research Network.

Background: This research delves into the confluence of racial disparities and health inequities among individuals with disabilities, with a focus on those contending with both diabetes and visual impairment. Methods: Utilizing data from the TriNetX Research Network, which includes electronic medical records of roughly 115 million patients from 83 anonymous healthcare organizations, this study employs a directed acyclic graph (DAG) to pinpoint confounders and augment interpretation. We identified patients with visual impairments using ICD-10 codes, deliberately excluding diabetes-related ophthalmology complications. Our approach involved multiple race-stratified analyses, comparing co-morbidities like chronic pulmonary disease in visually impaired patients against their counterparts. We assessed healthcare access disparities by examining the frequency of annual visits, instances of two or more A1c measurements, and glomerular filtration rate (GFR) measurements. Additionally, we evaluated diabetes outcomes by comparing the risk ratio of uncontrolled diabetes (A1c > 9.0) and chronic kidney disease in patients with and without visual impairments. Results: The incidence of diabetes was substantially higher (nearly double) in individuals with visual impairments across White, Asian, and African American populations. Higher rates of chronic kidney disease were observed in visually impaired individuals, with a risk ratio of 1.79 for African American, 2.27 for White, and non-significant for the Asian group. A statistically significant difference in the risk ratio for uncontrolled diabetes was found only in the White cohort (0.843). White individuals without visual impairments were more likely to receive two A1c tests, a trend not significant in other racial groups. African Americans with visual impairments had a higher rate of glomerular filtration rate testing. However, White individuals with visual impairments were less likely to undergo GFR testing, indicating a disparity in kidney health monitoring. This pattern of disparity was not observed in the Asian cohort. Conclusions: This study uncovers pronounced disparities in diabetes incidence and management among individuals with visual impairments, particularly among White, Asian, and African American groups. Our DAG analysis illuminates the intricate interplay between SDoH, healthcare access, and frequency of crucial diabetes monitoring practices, highlighting visual impairment as both a medical and social issue.

Ontology-based modeling, integration, and analysis of heterogeneous clinical, pathological, and molecular kidney data for precision medicine.

Many data resources generate, process, store, or provide kidney related molecular, pathological, and clinical data. Reference ontologies offer an opportunity to support knowledge and data integration. The Kidney Precision Medicine Project (KPMP) team contributed to the representation and addition of 329 kidney phenotype terms to the Human Phenotype Ontology (HPO), and identified many subcategories of acute kidney injury (AKI) or chronic kidney disease (CKD). The Kidney Tissue Atlas Ontology (KTAO) imports and integrates kidney-related terms from existing ontologies (e.g., HPO, CL, and Uberon) and represents 259 kidney-related biomarkers. We also developed a precision medicine metadata ontology (PMMO) to integrate 50 variables from KPMP and CZ CellxGene data resources and applied PMMO for integrative kidney data analysis. The gene expression profiles of kidney gene biomarkers were specifically analyzed under healthy control or AKI/CKD disease statuses. This work demonstrates how ontology-based approaches support multi-domain data and knowledge integration in precision medicine.

Development of a social and environmental determinants of health informatics maturity model.

Introduction: Integrating social and environmental determinants of health (SEDoH) into enterprise-wide clinical workflows and decision-making is one of the most important and challenging aspects of improving health equity. We engaged domain experts to develop a SEDoH informatics maturity model (SIMM) to help guide organizations to address technical, operational, and policy gaps. Methods: We established a core expert group consisting of developers, informaticists, and subject matter experts to identify different SIMM domains and define maturity levels. The candidate model (v0.9) was evaluated by 15 informaticists at a Center for Data to Health community meeting. After incorporating feedback, a second evaluation round for v1.0 collected feedback and self-assessments from 35 respondents from the National COVID Cohort Collaborative, the Center for Leading Innovation and Collaboration's Informatics Enterprise Committee, and a publicly available online self-assessment tool. Results: We developed a SIMM comprising seven maturity levels across five domains: data collection policies, data collection methods and technologies, technology platforms for analysis and visualization, analytics capacity, and operational and strategic impact. The evaluation demonstrated relatively high maturity in analytics and technological capacity, but more moderate maturity in operational and strategic impact among academic medical centers. Changes made to the tool in between rounds improved its ability to discriminate between intermediate maturity levels. Conclusion: The SIMM can help organizations identify current gaps and next steps in improving SEDoH informatics. Improving the collection and use of SEDoH data is one important component of addressing health inequities.

Telehealth and digital health innovations: A mixed landscape of access.

In the wake of emergent natural and anthropogenic disasters, telehealth presents opportunities to improve access to healthcare when physical access is not possible. Yet, since the beginning of the COVID pandemic, lessons learned reveal that various populations in the United States do not or cannot adopt telehealth due to inequitable access. We explored the Digital Determinants of Health (DDoHs) for telehealth, characterizing the role of accessibility, broadband connectivity and electrical grids, and patient intersectionality. In addition to its role as an existing Social Determinant of Health, Policies and Laws directly and indirectly affect these DDoHs, making access more complex for marginalized populations. Digital systems lack the flexibility, accessibility, and usability to inclusively provide the essential services patients need in telehealth. We propose the following recommendations: (1) design technology and systems using accessibility and value sensitive design principles; (2) support a range of technologies and settings; (3) support multiple and diverse users; and (4) support clear paths for repair when technical systems fail to meet users' needs. Addressing these requires change not only from providers but also from the institutions providing these systems.

Developing a National Trauma Research Action Plan: Results from the trauma systems and informatics panel Delphi survey.

BACKGROUND: The National Academies of Sciences, Engineering, and Medicine 2016 report on the trauma care system recommended establishing a National Trauma Research Action Plan to strengthen and guide future trauma research. To address this recommendation, the Department of Defense funded a study to generate a comprehensive research agenda spanning the trauma and burn care continuum. Panels were created to conduct a gap analysis and identify high-priority research questions. The National Trauma Research Action Plan panel reported here addressed trauma systems and informatics. METHODS: Experts were recruited to identify current gaps in trauma systems research, generate research questions, and establish the priorities using an iterative Delphi survey approach from November 2019 through August 2020. Panelists were identified to ensure heterogeneity and generalizability, including military and civilian representation. Panelists were encouraged to use a PICO format to generate research questions: patient/population, intervention, compare/control, and outcome. In subsequent surveys, panelists prioritized each research question on a 9-point Likert scale, categorized as low-, medium-, and high-priority items. Consensus was defined as ≥60% agreement. RESULTS: Twenty-seven subject matter experts generated 570 research questions, of which 427 (75%) achieved the consensus threshold. Of the consensus reaching questions, 209 (49%) were rated high priority, 213 (50%) medium priority, and 5 (1%) low priority. Gaps in understanding the broad array of interventions were identified, including those related to health care infrastructure, technology products, education/training, resuscitation, and operative intervention. The prehospital phase of care was highlighted as an area needing focused research. CONCLUSION: This Delphi gap analysis of trauma systems and informatics research identified high-priority research questions that will help guide investigators and funding agencies in setting research priorities to continue to work toward Zero Preventable Deaths after trauma. LEVEL OF EVIDENCE: Therapeutic/Care Management; Level IV.

Advancing Interoperability of Patient-level Social Determinants of Health Data to Support COVID-19 Research.

Including social determinants of health (SDoH) data in health outcomes research is essential for studying the sources of healthcare disparities and developing strategies to mitigate stressors. In this report, we describe a pragmatic design and approach to explore the encoding needs for transmitting SDoH screening tool responses from a large safety-net hospital into the National Covid Cohort Collaborative (N3C) OMOP dataset. We provide a stepwise account of designing data mapping and ingestion for patient-level SDoH and summarize the results of screening. Our approach demonstrates that sharing of these important data - typically stored as non-standard, EHR vendor specific codes - is feasible. As SDoH screening gains broader use nationally, the approach described in this paper could be used for other screening instruments and improve the interoperability of these important data.

Developing a national trauma research action plan: Results from the Burn Research Gap Delphi Survey.

BACKGROUND: The 2016 National Academies of Science, Engineering and Medicine call for a national integrated, military-civilian trauma action plan to achieve zero preventable deaths and disability after injury included a proposal to establish a National Trauma Research Action Plan to "strengthen trauma research and ensure that the resources available for this research are commensurate with the importance of injury and the potential for improvement in patient outcomes." The Department of Defense funded the Coalition for National Trauma Research to generate a comprehensive research agenda spanning the continuum of trauma/burn care from prehospital to rehabilitation. The Burn/Reconstructive Surgery group represents one focus area for this research agenda development. METHODS: Experts in burn and reconstructive surgery research identified gaps in knowledge, generated research questions and prioritized questions using a consensus driven Delphi survey approach. Participants were identified using established Delphi recruitment guidelines to ensure heterogeneity and generalizability with military and civilian representatives. Literature reviews informed the panel. Panelists were encouraged to use a PICO format to generate research questions: Patient/Population; Intervention; Compare/Control; Outcome. Participants ranked the priority of each question on a nine-point Likert scale, which was categorized to represent low, medium, and high priority items. Consensus was defined based on ≥60% panelist agreement. RESULTS: Subject matter experts generated 949 research questions in 29 Burn & 26 Reconstruction topics. Five hundred ninety-seven questions reached consensus. Of these, 338 (57%) were high-priority, 180 (30%), medium-priority, and 78 (13%) low-priority questions. CONCLUSION: Many high-priority questions translate to complex wound management and outcomes. Panel recognition that significant gaps in knowledge exist in understanding functional outcomes after injury underscores the importance of long-term recovery metrics even when studying acute injury or interventions such as resuscitation or inhalation injury. Funding agencies and burn/reconstructive surgery researchers should consider these gaps when they prioritize future research. LEVEL OF EVIDENCE: Expert consensus, Level IV.

Social Determinants of Health Factors for Gene-Environment COVID-19 Research: Challenges and Opportunities.

The characteristics of a person's health status are often guided by how they live, grow, learn, their genetics, as well as their access to health care. Yet, all too often, studies examining the relationship between social determinants of health (behavioral, sociocultural, and physical environmental factors), the role of demographics, and health outcomes poorly represent these relationships, leading to misinterpretations, limited study reproducibility, and datasets with limited representativeness and secondary research use capacity. This is a profound hurdle in what questions can or cannot be rigorously studied about COVID-19. In practice, gene-environment interactions studies have paved the way for including these factors into research. Similarly, our understanding of social determinants of health continues to expand with diverse data collection modalities as health systems, patients, and community health engagement aim to fill the knowledge gaps toward promoting health and wellness. Here, a conceptual framework is proposed, adapted from the population health framework, socioecological model, and causal modeling in gene-environment interaction studies to integrate the core constructs from each domain with practical considerations needed for multidisciplinary science.

Developing a National Trauma Research Action Plan: Results from the injury prevention research gap Delphi survey.

BACKGROUND: In its 2016 report on trauma care, the National Academies of Sciences, Engineering, and Medicine called for the establishment of a National Trauma Research Action Plan to strengthen and guide future trauma research. To address this recommendation, the Department of Defense funded the Coalition for National Trauma Research to generate a comprehensive research agenda spanning the continuum of trauma and burn care. We describe the gap analysis and high priority research questions generated from the National Trauma Research Action Plan panel on injury prevention. METHODS: Experts in injury prevention research were recruited to identify current gaps in injury prevention research, generate research questions and establish the priority of these questions using a consensus-driven Delphi survey approach from December 2019 through September 2020. Participants were identified using established Delphi recruitment guidelines to ensure heterogeneity and generalizability with both military and civilian representatives. Participants were encouraged, but not required, to use a Patient/Population, Intervention, Comparison, and Outcome format to generate research questions: Patient/Population; Intervention; Compare/Control; Outcome model. On subsequent surveys, participants were asked to rank the priority of each research question on a nine-point Likert scale, categorized to represent low-, medium-, and high-priority items. Consensus was defined as 60% or greater of panelists agreeing on the priority category. RESULTS: Twenty-eight subject matter experts generated 394 questions in 12 topic areas. By round 3 of the Delphi, 367 (93.1%) questions reached consensus, of which 169 (46.1%) were determined to be high priority, 196 (53.4%) medium priority, and 2 (0.5%) low priority. Among the 169 high priority questions, suicide (29.6%), firearm violence (20.1%), and violence prevention (18.3%) were the most prevalent topic areas. CONCLUSION: This Delphi gap analysis of injury prevention research identified 169 high priority research questions that will help guide investigators in future injury prevention research. Funding agencies and researchers should consider these gaps when they prioritize future research. LEVEL OF EVIDENCE: Therepeutic/Care Management; Level IV.

Developing a National Trauma Research Action Plan: Results from the Pediatric Research Gap Delphi Survey.

BACKGROUND: In 2016, the National Academies of Sciences, Engineering, and Medicine trauma report recommended a National Trauma Research Action Plan to "strengthen trauma research and ensure that the resources available for this research are commensurate with the importance of injury and the potential for improvement in patient outcomes." With a contract from the Department of Defense, the Coalition for National Trauma Research created 11 expert panels to address this recommendation, with the goal of developing a comprehensive research agenda, spanning the continuum of trauma and burn care. This report outlines the work of the group focused on pediatric trauma. METHODS: Experts in pediatric trauma clinical care and research were recruited to identify gaps in current clinical pediatric trauma research, generate research questions, and establish the priority of these questions using a consensus-driven Delphi survey approach. Using successive surveys, participants were asked to rank the priority of each research question on a 9-point Likert scale categorized to represent priority. Consensus was defined as >60% agreement within the priority category. Priority questions were coded based on a dictionary of 118 National Trauma Research Action Plan taxonomy concepts in 9 categories to support comparative analysis across all panels. RESULTS: Thirty-seven subject matter experts generated 625 questions. A total of 493 questions (79%) reached consensus on priority level. Of those reaching consensus, 159 (32%) were high, 325 (66%) were medium, and 9 (2%) were low priority. The highest priority research questions related to surgical interventions for traumatic brain injury (intracranial pressure monitoring and craniotomy); the second highest priority was hemorrhagic shock. The prehospital setting was the highest priority phase of care. CONCLUSION: This diverse panel of experts determined that most significant pediatric trauma research gaps were in traumatic brain injury, hemorrhagic shock, and the prehospital phase of care. These research domains should be top priorities for funding agencies. LEVEL OF EVIDENCE: Therapeutic / Care Management; Level IV.

Developing a National Trauma Research Action Plan: Results from the geriatric research gap Delphi survey.

BACKGROUND: Treating older trauma patients requires a focus on the confluence of age-related physiological changes and the impact of the injury itself. Therefore, the primary way to improve the care of geriatric trauma patients is through the development of universal, systematic multidisciplinary research. To achieve this, the Coalition for National Trauma Research has developed the National Trauma Research Action Plan that has generated a comprehensive research agenda spanning the continuum of geriatric trauma care from prehospital to rehabilitation. METHODS: Experts in geriatric trauma care and research were recruited to identify current gaps in clinical geriatric research, generate research questions, and establish the priority of these questions using a consensus-driven Delphi survey approach. Participants were identified using established Delphi recruitment guidelines ensuring heterogeneity and generalizability. On subsequent surveys, participants were asked to rank the priority of each research question on a nine-point Likert scale, categorized to represent low-, medium-, and high-priority items. The consensus was defined as more than 60% of panelists agreeing on the priority category. RESULTS: A total of 24 subject matter experts generated questions in 109 key topic areas. After editing for duplication, 514 questions were included in the priority ranking. By round 3, 362 questions (70%) reached 60% consensus. Of these, 161 (44%) were high, 198 (55%) medium, and 3 (1%) low priority. CONCLUSION: Among the questions prioritized as high priority, questions related to three types of injuries (i.e., rib fracture, traumatic brain injury, and lower extremity injury) occurred with the greatest frequency. Among the 25 highest priority questions, the key topics with the highest frequency were pain management, frailty, and anticoagulation-related interventions. The most common types of research proposed were interventional clinical trials and comparative effectiveness studies, outcome research, and health care systems research.

Toward informatics-enabled preparedness for natural hazards to minimize health impacts of climate change.

Natural hazards (NHs) associated with climate change have been increasing in frequency and intensity. These acute events impact humans both directly and through their effects on social and environmental determinants of health. Rather than relying on a fully reactive incident response disposition, it is crucial to ramp up preparedness initiatives for worsening case scenarios. In this perspective, we review the landscape of NH effects for human health and explore the potential of health informatics to address associated challenges, specifically from a preparedness angle. We outline important components in a health informatics agenda for hazard preparedness involving hazard-disease associations, social determinants of health, and hazard forecasting models, and call for novel methods to integrate them toward projecting healthcare needs in the wake of a hazard. We describe potential gaps and barriers in implementing these components and propose some high-level ideas to address them.

Developing a National Trauma Research Action Plan: Results from the prehospital and mass casualty research Delphi survey.

BACKGROUND: The National Academies of Sciences, Engineering, and Medicine 2016 trauma system report recommended a National Trauma Research Action Plan to strengthen and guide future trauma research. To address this recommendation, 11 expert panels completed a Delphi survey process to create a comprehensive research agenda, spanning the continuum of trauma care. We describe the gap analysis and high-priority research questions generated from the National Trauma Research Action Plan panel on prehospital and mass casualty trauma care. METHODS: We recruited interdisciplinary national experts to identify gaps in the prehospital and mass casualty trauma evidence base and generate prioritized research questions using a consensus-driven Delphi survey approach. We included military and civilian representatives. Panelists were encouraged to use the Patient/Population, Intervention, Compare/Control, and Outcome format to generate research questions. We conducted four Delphi rounds in which participants generated key research questions and then prioritized the questions on a 9-point Likert scale to low-, medium-, and high-priority items. We defined consensus as ≥60% agreement on the priority category and coded research questions using a taxonomy of 118 research concepts in 9 categories. RESULTS: Thirty-one interdisciplinary subject matter experts generated 490 research questions, of which 433 (88%) reached consensus on priority. The rankings of the 433 questions were as follows: 81 (19%) high priority, 339 (78%) medium priority, and 13 (3%) low priority. Among the 81 high-priority questions, there were 46 taxonomy concepts, including health systems of care (36 questions), interventional clinical trials and comparative effectiveness (32 questions), mortality as an outcome (30 questions), prehospital time/transport mode/level of responder (24 questions), system benchmarks (17 questions), and fluid/blood product resuscitation (17 questions). CONCLUSION: This Delphi gap analysis of prehospital and mass casualty care identified 81 high-priority research questions to guide investigators and funding agencies for future trauma research.