Defense Health Agency

The dramatic increase in antimicrobial resistance for pathogenic bacteria constitutes a key threat to human health. The Centers for Disease Control and Prevention has recently stated that the world is on the verge of entering the "post-antibiotic era", one where more people will die from bacterial infections than from cancer. Recently, nanoparticles (NPs) have emerged as new tools that can be used to combat deadly bacterial infections. Nanoparticle-based strategies can overcome the barriers faced by traditional antimicrobials, including antibiotic resistance. In this tutorial review, we have highlighted multiple nanoparticle-based approaches to eliminate bacterial infections, providing crucial insight into the design of elements that play critical roles in creating antimicrobial nanotherapeutics. In particular, we have focused on the pivotal role played by NP-surface functionality in designing nanomaterials as self-therapeutic agents and delivery vehicles for antimicrobial cargo.

Microvascular Changes in the Brain in Covid-19 High-resolution MRI and histopathological study of the brains of patients who had died from Covid-19 showed punctate hyperintensities and punctate or ...

Importance: Myocarditis has been reported with COVID-19 but is not clearly recognized as a possible adverse event following COVID-19 vaccination. Objective: To describe myocarditis presenting after COVID-19 vaccination within the Military Health System. Design, Setting, and Participants: This retrospective case series studied patients within the US Military Health System who experienced myocarditis after COVID-19 vaccination between January and April 2021. Patients who sought care for chest pain following COVID-19 vaccination and were subsequently diagnosed with clinical myocarditis were included. Exposure: Receipt of a messenger RNA (mRNA) COVID-19 vaccine between January 1 and April 30, 2021. Main Outcomes and Measures: Clinical diagnosis of myocarditis after COVID-19 vaccination in the absence of other identified causes. Results: A total of 23 male patients (22 currently serving in the military and 1 retiree; median [range] age, 25 [20-51] years) presented with acute onset of marked chest pain within 4 days after receipt of an mRNA COVID-19 vaccine. All military members were previously healthy with a high level of fitness. Seven received the BNT162b2-mRNA vaccine and 16 received the mRNA-1273 vaccine. A total of 20 patients had symptom onset following the second dose of an appropriately spaced 2-dose series. All patients had significantly elevated cardiac troponin levels. Among 8 patients who underwent cardiac magnetic resonance imaging within the acute phase of illness, all had findings consistent with the clinical diagnosis of myocarditis. Additional testing did not identify other etiologies for myocarditis, including acute COVID-19 and other infections, ischemic injury, or underlying autoimmune conditions. All patients received brief supportive care and were recovered or recovering at the time of this report. The military administered more than 2.8 million doses of mRNA COVID-19 vaccine in this period. While the observed number of myocarditis cases was small, the number was higher than expected among male military members after a second vaccine dose. Conclusions and Relevance: In this case series, myocarditis occurred in previously healthy military patients with similar clinical presentations following receipt of an mRNA COVID-19 vaccine. Further surveillance and evaluation of this adverse event following immunization is warranted. Potential for rare vaccine-related adverse events must be considered in the context of the well-established risk of morbidity, including cardiac injury, following COVID-19 infection.

Importance: Suicide prediction models have the potential to improve the identification of patients at heightened suicide risk by using predictive algorithms on large-scale data sources. Suicide prediction models are being developed for use across enterprise-level health care systems including the US Department of Defense, US Department of Veterans Affairs, and Kaiser Permanente. Objectives: To evaluate the diagnostic accuracy of suicide prediction models in predicting suicide and suicide attempts and to simulate the effects of implementing suicide prediction models using population-level estimates of suicide rates. Evidence Review: A systematic literature search was conducted in MEDLINE, PsycINFO, Embase, and the Cochrane Library to identify research evaluating the predictive accuracy of suicide prediction models in identifying patients at high risk for a suicide attempt or death by suicide. Each database was searched from inception to August 21, 2018. The search strategy included search terms for suicidal behavior, risk prediction, and predictive modeling. Reference lists of included studies were also screened. Two reviewers independently screened and evaluated eligible studies. Findings: From a total of 7306 abstracts reviewed, 17 cohort studies met the inclusion criteria, representing 64 unique prediction models across 5 countries with more than 14 million participants. The research quality of the included studies was generally high. Global classification accuracy was good (≥0.80 in most models), while the predictive validity associated with a positive result for suicide mortality was extremely low (≤0.01 in most models). Simulations of the results suggest very low positive predictive values across a variety of population assessment characteristics. Conclusions and Relevance: To date, suicide prediction models produce accurate overall classification models, but their accuracy of predicting a future event is near 0. Several critical concerns remain unaddressed, precluding their readiness for clinical applications across health systems.

INTRODUCTION: Discussions about sexual health are uncommon in clinical encounters, despite the sexual dysfunction associated with many common health conditions. Understanding of the importance of sexual health and sexual satisfaction in U.S. adults is limited. AIM: To provide epidemiologic data on the importance of sexual health for quality of life and people's satisfaction with their sex lives and to examine how each is associated with demographic and health factors. METHODS: Data are from a cross-sectional self-report questionnaire from a sample of 3,515 English-speaking U.S. adults recruited from an online panel that uses address-based probability sampling. MAIN OUTCOME MEASURES: We report ratings of importance of sexual health to quality of life (single item with five-point response) and the Patient-Reported Outcomes Measurement Information System Satisfaction With Sex Life score (five items, each with five-point responses, scores centered on the U.S. mean). RESULTS: High importance of sexual health to quality of life was reported by 62.2% of men (95% CI = 59.4-65.0) and 42.8% of women (95% CI = 39.6-46.1, P < .001). Importance of sexual health varied by sex, age, sexual activity status, and general self-rated health. For the 55% of men and 45% of women who reported sexual activity in the previous 30 days, satisfaction with sex life differed by sex, age, race-ethnicity (among men only), and health. Men and women in excellent health had significantly higher satisfaction than participants in fair or poor health. Women with hypertension reported significantly lower satisfaction (especially younger women), as did men with depression or anxiety (especially younger men). CONCLUSION: In this large study of U.S. adults' ratings of the importance of sexual health and satisfaction with sex life, sexual health was a highly important aspect of quality of life for many participants, including participants in poor health. Moreover, participants in poorer health reported lower sexual satisfaction. Accordingly, sexual health should be a routine part of clinicians' assessments of their patients. Health care systems that state a commitment to improving patients' overall health must have resources in place to address sexual concerns. These resources should be available for all patients across the lifespan.

Importance: Although the Afghanistan and Iraq conflicts have the lowest US case-fatality rates in history, no comprehensive assessment of combat casualty care statistics, major interventions, or risk factors has been reported to date after 16 years of conflict. Objectives: To analyze trends in overall combat casualty statistics, to assess aggregate measures of injury and interventions, and to simulate how mortality rates would have changed had the interventions not occurred. Design, Setting, and Participants: Retrospective analysis of all available aggregate and weighted individual administrative data compiled from Department of Defense databases on all 56 763 US military casualties injured in battle in Afghanistan and Iraq from October 1, 2001, through December 31, 2017. Casualty outcomes were compared with period-specific ratios of the use of tourniquets, blood transfusions, and transport to a surgical facility within 60 minutes. Main Outcomes and Measures: Main outcomes were casualty status (alive, killed in action [KIA], or died of wounds [DOW]) and the case-fatality rate (CFR). Regression, simulation, and decomposition analyses were used to assess associations between covariates, interventions, and individual casualty status; estimate casualty transitions (KIA to DOW, KIA to alive, and DOW to alive); and estimate the contribution of interventions to changes in CFR. Results: In aggregate data for 56 763 casualties, CFR decreased in Afghanistan (20.0% to 8.6%) and Iraq (20.4% to 10.1%) from early stages to later stages of the conflicts. Survival for critically injured casualties (Injury Severity Score, 25-75 [critical]) increased from 2.2% to 39.9% in Afghanistan and from 8.9% to 32.9% in Iraq. Simulations using data from 23 699 individual casualties showed that without interventions assessed, CFR would likely have been higher in Afghanistan (15.6% estimated vs 8.6% observed) and Iraq (16.3% estimated vs 10.1% observed), equating to 3672 additional deaths (95% CI, 3209-4244 deaths), of which 1623 (44.2%) were associated with the interventions studied: 474 deaths (12.9%) (95% CI, 439-510) associated with the use of tourniquets, 873 (23.8%) (95% CI, 840-910) with blood transfusion, and 275 (7.5%) (95% CI, 259-292) with prehospital transport times. Conclusions and Relevance: Our analysis suggests that increased use of tourniquets, blood transfusions, and more rapid prehospital transport were associated with 44.2% of total mortality reduction. More critically injured casualties reached surgical care, with increased survival, implying improvements in prehospital and hospital care.

The underlying mechanisms by which severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) leads to acute and long-term neurological manifestations remains obscure. We aimed to characterize the neuropathological changes in patients with coronavirus disease 2019 and determine the underlying pathophysiological mechanisms. In this autopsy study of the brain, we characterized the vascular pathology, the neuroinflammatory changes and cellular and humoral immune responses by immunohistochemistry. All patients died during the first wave of the pandemic from March to July 2020. All patients were adults who died after a short duration of the infection, some had died suddenly with minimal respiratory involvement. Infection with SARS-CoV-2 was confirmed on ante-mortem or post-mortem testing. Descriptive analysis of the pathological changes and quantitative analyses of the infiltrates and vascular changes were performed. All patients had multifocal vascular damage as determined by leakage of serum proteins into the brain parenchyma. This was accompanied by widespread endothelial cell activation. Platelet aggregates and microthrombi were found adherent to the endothelial cells along vascular lumina. Immune complexes with activation of the classical complement pathway were found on the endothelial cells and platelets. Perivascular infiltrates consisted of predominantly macrophages and some CD8+ T cells. Only rare CD4+ T cells and CD20+ B cells were present. Astrogliosis was also prominent in the perivascular regions. Microglial nodules were predominant in the hindbrain, which were associated with focal neuronal loss and neuronophagia. Antibody-mediated cytotoxicity directed against the endothelial cells is the most likely initiating event that leads to vascular leakage, platelet aggregation, neuroinflammation and neuronal injury. Therapeutic modalities directed against immune complexes should be considered.

INTRODUCTION: Noncombat injuries ("injuries") greatly impact soldier health and United States (U.S.) Army readiness; they are the leading cause of outpatient medical encounters (more than two million annually) among active component (AC) soldiers. Noncombat musculoskeletal injuries ("MSKIs") may account for nearly 60% of soldiers' limited duty days and 65% of soldiers who cannot deploy for medical reasons. Injuries primarily affect readiness through increased limited duty days, decreased deployability rates, and increased medical separation rates. MSKIs are also responsible for exorbitant medical costs to the U.S. government, including service-connected disability compensation. A significant subset of soldiers develops chronic pain or long-term disability after injury; this may increase their risk for chronic disease or secondary health deficits potentially associated with MSKIs. The authors will review trends in U.S. Army MSKI rates, summarize MSKI readiness-related impacts, and highlight the importance of standardizing surveillance approaches, including injury definitions used in injury surveillance. MATERIALS/METHODS: This review summarizes current reports and U.S. Department of Defense internal policy documents. MSKIs are defined as musculoskeletal disorders resulting from mechanical energy transfer, including traumatic and overuse injuries, which may cause pain and/or limit function. This review focuses on various U.S. Army populations, based on setting, sex, and age; the review excludes combat or battle injuries. RESULTS: More than half of all AC soldiers sustained at least one injury (MSKI or non-MSKI) in 2017. Overuse injuries comprise at least 70% of all injuries among AC soldiers. Female soldiers are at greater risk for MSKI than men. Female soldiers' aerobic and muscular fitness performances are typically lower than men's performances, which could account for their higher injury rates. Older soldiers are at greater injury risk than younger soldiers. Soldiers in noncombat arms units tend to have higher incidences of reported MSKIs, more limited duty days, and higher rates of limited duty days for chronic MSKIs than soldiers in combat arms units. MSKIs account for 65% of medically nondeployable AC soldiers. At any time, 4% of AC soldiers cannot deploy because of MSKIs. Once deployed, nonbattle injuries accounted for approximately 30% of all medical evacuations, and were the largest category of soldier evacuations from both recent major combat theaters (Iraq and Afghanistan). More than 85% of service members medically evacuated for MSKIs failed to return to the theater. MSKIs factored into (1) nearly 70% of medical disability discharges across the Army from 2011 through 2016 and (2) more than 90% of disability discharges within enlisted soldiers' first year of service from 2010 to 2015. MSKI-related, service-connected (SC) disabilities account for 44% of all SC disabilities (more than any other body system) among compensated U.S. Global War on Terrorism veterans. CONCLUSIONS: MSKIs significantly impact soldier health and U.S. Army readiness. MSKIs also figure prominently in medical disability discharges and long-term, service-connected disability costs. MSKI patterns and trends vary between trainees and soldiers in operational units and among military occupations and types of operational units. Coordinated injury surveillance efforts are needed to provide standardized metrics and accurately measure temporal changes in injury rates.

The incidence of traumatic brain injury (TBI) in the United States was 3.5 million cases in 2009, according to the Centers for Disease Control and Prevention. It is a contributing factor in 30.5% of injury-related deaths among civilians. Additionally, since 2000, more than 260,000 service members were diagnosed with TBI, with the vast majority classified as mild or concussive (76%). The objective assessment of TBI via imaging is a critical research gap, both in the military and civilian communities. In 2011, the Department of Defense (DoD) prepared a congressional report summarizing the effectiveness of seven neuroimaging modalities (computed tomography [CT], magnetic resonance imaging [MRI], transcranial Doppler [TCD], positron emission tomography, single photon emission computed tomography, electrophysiologic techniques [magnetoencephalography and electroencephalography], and functional near-infrared spectroscopy) to assess the spectrum of TBI from concussion to coma. For this report, neuroimaging experts identified the most relevant peer-reviewed publications and assessed the quality of the literature for each of these imaging technique in the clinical and research settings. Although CT, MRI, and TCD were determined to be the most useful modalities in the clinical setting, no single imaging modality proved sufficient for all patients due to the heterogeneity of TBI. All imaging modalities reviewed demonstrated the potential to emerge as part of future clinical care. This paper describes and updates the results of the DoD report and also expands on the use of angiography in patients with TBI.

STUDY OBJECTIVES: Short sleep duration (SSD) is common among deployed soldiers. The prevalence of SSD during redeployment, however, is unknown. DESIGN: Cross-sectional study of a brigade combat team (n = 3152 US Army soldiers) surveyed 90-180 days after completing a 6-15 month deployment to Iraq as part of Operation Iraqi Freedom (OIF). Survey items targeted sleep habits and comorbid medical conditions. Multivariate logistic regression analyses were performed to calculate adjusted odds ratios of medical comorbidities associated with SSD. SETTING: US Army Infantry Post. SUBJECTS: All soldiers from a redeploying brigade combat team participated in a health assessment between 90 and 180 days upon return to Ft. Lewis from Iraq. INTERVENTIONS: None. MEASUREMENTS AND RESULTS: A total of 2738 (86.9%) soldiers answered questions regarding self-perceived sleep and were included in the analysis. Mean sleep duration was 5.8 ± 1.2 hours. Nineteen hundred fifty-nine (72%) slept ≤ 6 h, but only 16% reported a daytime nap or felt their job performance was affected due to lack of sleep. Short sleep was more common among soldiers who reported combat exposure. After controlling for combat exposure, short sleep duration (SSD) was associated with symptoms of depression, posttraumatic stress disorder, panic syndrome, and with high-risk health behaviors such as abuse of tobacco and alcohol products, and suicide attempts. CONCLUSIONS: SSD is common among redeployed soldiers. Soldiers who experienced combat are at increased risk for persistent SSD and comorbidities associated with SSD. Efforts to reestablish good sleep habits and aggressive evaluation of soldiers with persistent SSD following deployment may aid in the prevention and management of associated medical conditions.

This article reports on the outcome of a presidential initiative of 2012 American Psychological Association President Suzanne Bennett Johnson to delineate competencies for primary care (PC) psychology in six broad domains: science, systems, professionalism, relationships, application, and education. Essential knowledge, skills, and attitudes are described for each PC psychology competency. Two behavioral examples are provided to illustrate each competency. Clinical vignettes demonstrate the competencies in action. Delineation of these competencies is intended to inform education, practice, and research in PC psychology and efforts to further develop team-based competencies in PC.

As many as 70 per cent of primary care visits in the United States are related to behavioral health needs. And many common medical problems seen in primary care involve poor health habits that may have initiated or exacerbated the symptoms, yet medical providers often lack the training or time to help patients manage these behaviors. The authors of this book draw on years of experience to provide practical information for behavioral care practitioners who wish to work effectively in this fast-paced setting.Interwoven through each chapter are practical tips for success and traps to avoid. The book includes a rich array of reproducible assessment questions, patient handouts, and sample scripts. All of these help the clinician condense the traditional 50-minute session into the 30-minute consultations typical of managed care. Each chapter addresses a single clinical topic or content area following the 5A's model of assessment and intervention: Assess, Advise, Agree, Assist and Arrange. Detailed guidance is provided for these common health problems: generalized anxiety disorder, panic disorder, posttraumatic stress disorder, depression, tobacco use, weight issues, sleep problems, diabetes, asthma, irritable bowel syndrome, cardiovascular disorders, pain disorders, sexual problems, and health anxiety. Special chapters cover cultural competency, special concerns for older adults, women's health, and 'health anxiety'.This comprehensive book belongs on the bookshelf of a range of clinicians including psychologists and social workers, as well as family physicians, physician assistants, nurses, and health care educators.

The American Joint Committee on Cancer (AJCC) tumor, node, metastasis (TNM) staging for all cancer sites has been periodically updated as a published manual for many years. The last update, the eighth edition AJCC Cancer Staging Manual went into use on January 1, 2018. The AJCC has since restructured and updated its processes, and all AJCC staging-related data are now housed on its new application programming interface. Consequently, the next AJCC TNM staging update, AJCC version 9 TNM staging, will be published electronically and will be released chapter by chapter. The first chapter of version 9 AJCC TNM staging is the updated cervical cancer staging, which is now published. This article highlights the changes to the AJCC TNM cervical cancer staging; these changes align with the International Federation of Gynecology and Obstetrics staging. The most important of the changes are: 1) the incorporation of imaging and surgical findings, 2) the elimination of lateral spread from T1a, 3) the addition of a subcategory to T1b (T1b3), and 4) histopathology is updated to reflect human papillomavirus-associated and human papillomavirus-independent carcinomas.

BACKGROUND: Although myocarditis/pericarditis (MP) has been identified as an adverse event following smallpox vaccine (SPX), the prospective incidence of this reaction and new onset cardiac symptoms, including possible subclinical injury, has not been prospectively defined. PURPOSE: The study's primary objective was to determine the prospective incidence of new onset cardiac symptoms, clinical and possible subclinical MP in temporal association with immunization. METHODS: New onset cardiac symptoms, clinical MP and cardiac specific troponin T (cTnT) elevations following SPX (above individual baseline values) were measured in a multi-center prospective, active surveillance cohort study of healthy subjects receiving either smallpox vaccine or trivalent influenza vaccine (TIV). RESULTS: New onset chest pain, dyspnea, and/or palpitations occurred in 10.6% of SPX-vaccinees and 2.6% of TIV-vaccinees within 30 days of immunization (relative risk (RR) 4.0, 95% CI: 1.7-9.3). Among the 1081 SPX-vaccinees with complete follow-up, 4 Caucasian males were diagnosed with probable myocarditis and 1 female with suspected pericarditis. This indicates a post-SPX incidence rate more than 200-times higher than the pre-SPX background population surveillance rate of myocarditis/pericarditis (RR 214, 95% CI 65-558). Additionally, 31 SPX-vaccinees without specific cardiac symptoms were found to have over 2-fold increases in cTnT (>99th percentile) from baseline (pre-SPX) during the window of risk for clinical myocarditis/pericarditis and meeting a proposed case definition for possible subclinical myocarditis. This rate is 60-times higher than the incidence rate of overt clinical cases. No clinical or possible subclinical myocarditis cases were identified in the TIV-vaccinated group. CONCLUSIONS: Passive surveillance significantly underestimates the true incidence of myocarditis/pericarditis after smallpox immunization. Evidence of subclinical transient cardiac muscle injury post-vaccinia immunization is a finding that requires further study to include long-term outcomes surveillance. Active safety surveillance is needed to identify adverse events that are not well understood or previously recognized.

The relationship between muscle length, integrated electromyographic activity, and torque of the biceps femoris muscle was investigated while the line of action of the muscle at the knee was held constant. Muscle length was changed by varying the hip joint angle. Sixteen subjects produced 1) maximal isometric contractions, 2) contractions with constant submaximal torque, and 3) contractions with constant submaximal muscle activity at four different hip positions (0, 45, 90, and 135 degrees of flexion). Simultaneous readings of hip angle, muscle torque, and raw and integrated electromyographic activity revealed that changes in muscle length influence production of integrated muscle activity and development of torque differently. During maximal isometric contraction, an increase in integrated electromyographic activity and a decrease in torque occurred as the muscle was shortened; the opposite occurred when the muscle was at lengthened positions. A greater difference in this relationship was noted when the respective electromyographic activity and torque were held constant. Some clinical questions were raised.

Description: In September 2019, the U.S. Department of Veterans Affairs (VA) and the U.S. Department of Defense (DoD) approved a new joint clinical practice guideline for assessing and managing patients with chronic insomnia disorder and obstructive sleep apnea (OSA). This guideline is intended to give health care teams a framework by which to screen, evaluate, treat, and manage the individual needs and preferences of VA and DoD patients with either of these conditions. Methods: In October 2017, the VA/DoD Evidence-Based Practice Work Group initiated a joint VA/DoD guideline development effort that included clinical stakeholders and conformed to the Institute of Medicine's tenets for trustworthy clinical practice guidelines. The guideline panel developed key questions, systematically searched and evaluated the literature, created three 1-page algorithms, and advanced 41 recommendations using the GRADE (Grading of Recommendations Assessment, Development and Evaluation) system. Recommendations: This synopsis summarizes the key recommendations of the guideline in 3 areas: diagnosis and assessment of OSA and chronic insomnia disorder, treatment and management of OSA, and treatment and management of chronic insomnia disorder. Three clinical practice algorithms are also included.

Chaplains play important roles in caring for Veterans and Service members with mental health problems. As part of the Department of Veterans Affairs (VA) and Department of Defense (DoD) Integrated Mental Health Strategy, we used a sequential approach to examining intersections between chaplaincy and mental health by gathering and building upon: 1) input from key subject matter experts; 2) quantitative data from the VA / DoD Chaplain Survey (N = 2,163; response rate of 75% in VA and 60% in DoD); and 3) qualitative data from site visits to 33 VA and DoD facilities. Findings indicate that chaplains are extensively involved in caring for individuals with mental health problems, yet integration between mental health and chaplaincy is frequently limited due to difficulties between the disciplines in establishing familiarity and trust. We present recommendations for improving integration of services, and we suggest key domains for future research.

OBJECTIVE: To address the clinical and regulatory challenges of optimal primary endpoints for bleeding patients by developing consensus-based recommendations for primary clinical outcomes for pivotal trials in patients within 6 categories of significant bleeding, (1) traumatic injury, (2) intracranial hemorrhage, (3) cardiac surgery, (4) gastrointestinal hemorrhage, (5) inherited bleeding disorders, and (6) hypoproliferative thrombocytopenia. BACKGROUND: A standardized primary outcome in clinical trials evaluating hemostatic products and strategies for the treatment of clinically significant bleeding will facilitate the conduct, interpretation, and translation into clinical practice of hemostasis research and support alignment among funders, investigators, clinicians, and regulators. METHODS: An international panel of experts was convened by the National Heart Lung and Blood Institute and the United States Department of Defense on September 23 and 24, 2019. For patients suffering hemorrhagic shock, the 26 trauma working-group members met for almost a year, utilizing biweekly phone conferences and then an in-person meeting, evaluating the strengths and weaknesses of previous high quality studies. The selection of the recommended primary outcome was guided by goals of patient-centeredness, expected or demonstrated sensitivity to beneficial treatment effects, biologic plausibility, clinical and logistical feasibility, and broad applicability. CONCLUSIONS: For patients suffering hemorrhagic shock, and especially from truncal hemorrhage, the recommended primary outcome was 3 to 6-hour all-cause mortality, chosen to coincide with the physiology of hemorrhagic death and to avoid bias from competing risks. Particular attention was recommended to injury and treatment time, as well as robust assessments of multiple safety related outcomes.

Analysis and review of combat casualty care challenges in future large-scale and medical multi-domain operations from the perspective of past, present, and potential future conflicts.

A recent large civilian randomized controlled trial on the use of tranexamic acid (TXA) for trauma reported important survival benefits. Subsequently, successful use of TXA for combat casualties in Afghanistan was also reported. As a result of these promising studies, there has been growing interest in the use of TXA for trauma. Potential adverse effects of TXA have also been reported. A US Department of Defense committee conducted a review and assessment of knowledge gaps and research requirements regarding the use of TXA for the treatment of casualties that have experienced traumatic hemorrhage. We present identified knowledge gaps and associated research priorities. We believe that important knowledge gaps exist and that a targeted, prioritized research effort will contribute to the refinement of practice guidelines over time.