Inhibition of Dihydroorotate Dehydrogenase Overcomes Differentiation Blockade in Acute Myeloid Leukemia.

While acute myeloid leukemia (AML) comprises many disparate genetic subtypes, one shared hallmark is the arrest of leukemic myeloblasts at an immature and self-renewing stage of development. Therapies that overcome differentiation arrest represent a powerful treatment strategy. We leveraged the observation that the majority of AML, despite their genetically heterogeneity, share in the expression of HoxA9, a gene normally downregulated during myeloid differentiation. Using a conditional HoxA9 model system, we performed a high-throughput phenotypic screen and defined compounds that overcame differentiation blockade. Target identification led to the unanticipated discovery that inhibition of the enzyme dihydroorotate dehydrogenase (DHODH) enables myeloid differentiation in human and mouse AML models. In vivo, DHODH inhibitors reduced leukemic cell burden, decreased levels of leukemia-initiating cells, and improved survival. These data demonstrate the role of DHODH as a metabolic regulator of differentiation and point to its inhibition as a strategy for overcoming differentiation blockade in AML.

Racial and ethnic disparities in motor vehicle crash-related outcomes in North Carolina surrounding the COVID-19 pandemic.

Long-term impacts of the COVID-19 pandemic on racial and ethnic disparities in motor vehicle crash (MVC) injuries and death are poorly understood. This study aimed to characterize trends and investigate the heterogeneity of MVC-related disparities in North Carolina across several data sources. Crash reports, emergency department visit records, and death certificates from 2018 to 2021 were used to calculate monthly population-rates of MVC-related public health outcomes. We estimated trendlines using joinpoint regression and compared outcomes across racial and ethnic classifications. MVC and MVC-related injury rates declined in conjunction with NC's stay-at-home order, while rates of severe outcomes remained unimpacted. By December 2021 rates of MVC-related outcomes met or exceeded pre-pandemic levels, with the highest rates observed among non-Hispanic Black individuals. Racial and ethnic disparities in MVC-related outcomes remained prevalent throughout the COVID-19 pandemic. These results highlight the importance of a holistic approach to traffic injury surveillance when assessing the impact of MVCs.

Seasonal Trends in Emergency Department Visits for Mental and Behavioral Health Conditions Among Children and Adolescents Aged 5-17 Years - United States, January 2018-June 2023.

Mental and behavioral health conditions among school-aged children, including substance use disorders and overall emotional well-being, are a public health concern in the United States. Timely data on seasonal patterns in child and adolescent conditions can guide optimal timing of prevention and intervention strategies. CDC examined emergency department (ED) visit data from the National Syndromic Surveillance Program for 25 distinct conditions during January 2018-June 2023 among U.S. children and adolescents aged 5-17 years, stratified by age group. Each year, during 2018-2023, among persons aged 10-14 and 15-17 years, the number and proportion of weekly ED visits for eight conditions increased in the fall school semester and remained elevated throughout the spring semester; ED visits were up to twice as high during school semesters compared with the summer period. Among children aged 5-9 years, the number and proportion of visits increased for five mental and behavioral health conditions. Seasonal increases in ED visits for some conditions among school-aged children warrant enhanced awareness about mental distress symptoms and the challenges and stressors in the school environment. Systemic changes that prioritize protective factors (e.g., physical activity; nutrition; sleep; social, community, or faith-based support; and inclusive school and community environments) and incorporate preparedness for increases in conditions during back-to-school planning might improve child and adolescent mental health.

Feasibility of linking violent death decedents to prior-month emergency department visits in North Carolina, 2019-2020.

OBJECTIVE: Linking data between violent death decedents and other sources can provide valuable insight, highlighting opportunities for prevention of violent injury. This study investigated the feasibility of linking North Carolina Violent Death Reporting System (NC-VDRS) records with North Carolina Disease Event Tracking and Epidemiologic Collection Tool (NC DETECT) emergency department (ED) visit data to identify prior-month ED visits among this population. METHODS: NC-VDRS death records from 2019 through 2020 were linked to NC DETECT ED visit data from December 2018 through 2020 using a probabilistic linkage approach. Linkage variables included date of birth, age, sex, zip code and county of residence, date of event (death/ED visit) and mechanism of injury. Potential linkable ED visits were filtered to those occurring in the month prior to death and manually reviewed for validity. Linked records were compared with the NC-VDRS study population to assess linkage performance and generalisability. RESULTS: Among the 4768 violent deaths identified, we linked 1340 NC-VDRS records to at least one ED visit in the month prior to death. A higher proportion of decedents dying in medical facilities (ED/outpatient, hospital inpatient, hospice or nursing/long-term care facility) linked to a prior-month visit (80%) relative to those dying in other locations (12%). When stratified by place of death, linked decedents demographically resembled the overall NC-VDRS study population. CONCLUSIONS: Though resource intensive, an NC-VDRS-to-NC DETECT linkage was successful in identifying prior-month ED visits among violent death decedents. This linkage should be leveraged to further analyse ED utilisation prior to violent death, expanding the knowledge base surrounding prevention opportunities for violent injuries.

The effect of increased emergency department demand on throughput times and disposition status for pediatric psychiatric patients.

OBJECTIVES: Emergency department (ED) crowding has been shown to increase throughput measures of length of stay (LOS), wait time, and boarding time. Psychiatric utilization of the ED has increased, particularly among younger patients. This investigation quantifies the effect of ED demand on throughput times and discharge disposition for pediatric psychiatric patients in the ED. METHODS: Using electronic medical record data from 1,151,396 ED visits in eight North Carolina EDs from January 1, 2018, through December 31, 2020, we identified 14,092 pediatric psychiatric visits. Measures of ED daily demand rates included overall occupancy as well as daily proportion of non-psychiatric pediatric patients, adult psychiatric patients, and pediatric psychiatric patients. Controlling for patient-level factors such as age, sex, race, insurance, and triage acuity, we used linear regression to predict throughput times and logistic regression to predict disposition status. We estimated effects of ED demand by academic versus community hospital status due to ED and inpatient resource differences. RESULTS: Most ED demand measures had insignificant or only very small associations with throughput measures for pediatric psychiatric patients. Notable exceptions were that a one percentage point increase in the proportion of non-psychiatric pediatric ED visits increased boarding times at community sites by 1.06 hours (95% CI: 0.20-1.92), while a one percentage point increase in the proportion of pediatric psychiatric ED visits increased LOS by 3.64 hours (95% CI: 2.04-5.23) at the academic site. We found that ED demand had a minimal effect on disposition status, with small increases in demand rates favoring <1 percentage point increases in the likelihood of discharge. Instead, patient-level factors played a much stronger role in predicting discharge disposition. CONCLUSIONS: ED demand has a meaningful effect on throughput times, but a minimal effect on disposition status. Further research is needed to validate these findings across other state and healthcare systems.

TCRD and Pharos 2021: mining the human proteome for disease biology.

In 2014, the National Institutes of Health (NIH) initiated the Illuminating the Druggable Genome (IDG) program to identify and improve our understanding of poorly characterized proteins that can potentially be modulated using small molecules or biologics. Two resources produced from these efforts are: The Target Central Resource Database (TCRD) (http://juniper.health.unm.edu/tcrd/) and Pharos (https://pharos.nih.gov/), a web interface to browse the TCRD. The ultimate goal of these resources is to highlight and facilitate research into currently understudied proteins, by aggregating a multitude of data sources, and ranking targets based on the amount of data available, and presenting data in machine learning ready format. Since the 2017 release, both TCRD and Pharos have produced two major releases, which have incorporated or expanded an additional 25 data sources. Recently incorporated data types include human and viral-human protein-protein interactions, protein-disease and protein-phenotype associations, and drug-induced gene signatures, among others. These aggregated data have enabled us to generate new visualizations and content sections in Pharos, in order to empower users to find new areas of study in the druggable genome.

Evaluation of an Emergency Department Visit Data Mental Health Dashboard.

CONTEXT: Local health departments (LHDs) need timely county-level and subcounty-level data to monitor health-related trends, identify health disparities, and inform areas of highest need for interventions as part of their ongoing assessment responsibilities; yet, many health departments rely on secondary data that are not timely and cannot provide subcounty insights. OBJECTIVE: We developed and evaluated a mental health dashboard in Tableau for an LHD audience featuring statewide syndromic surveillance emergency department (ED) data in North Carolina from the North Carolina Disease Event Tracking and Epidemiologic Collection Tool (NC DETECT). DESIGN: We developed a dashboard that provides counts, crude rates, and ED visit percentages at statewide and county levels, as well as breakdowns by zip code, sex, age group, race, ethnicity, and insurance coverage for 5 mental health conditions. We evaluated the dashboards through semistructured interviews and a Web-based survey that included the standardized usability questions from the System Usability Scale. PARTICIPANTS: Convenience sample of LHD public health epidemiologists, health educators, evaluators, and public health informaticians. RESULTS: Six semistructured interview participants successfully navigated the dashboard but identified usability issues when asked to compare county-level trends displayed in different outputs (eg, tables vs graphs). Thirty respondents answered all questions on the System Usability Scale for the dashboard, which received an above average score of 86. CONCLUSIONS: The dashboards scored well on the System Usability Scale, but more research is needed to identify best practices in disseminating multiyear syndromic surveillance ED visit data on mental health conditions to LHDs.

Firearm-Related Injury and Death in North Carolina: Trends During the COVID-19 Pandemic.

The COVID-19 pandemic has had far-reaching impacts on the health and well-being of North Carolinians, including injury and violence. Firearm purchases surged and, as the pandemic evolved, North Carolinians experienced increases in firearm-related deaths and injuries. This paper describes firearm injuries and deaths in the state from 2017 to 2021.

A Randomized Trial of E-Cigarettes versus Nicotine-Replacement Therapy.

BACKGROUND: E-cigarettes are commonly used in attempts to stop smoking, but evidence is limited regarding their effectiveness as compared with that of nicotine products approved as smoking-cessation treatments. METHODS: We randomly assigned adults attending U.K. National Health Service stop-smoking services to either nicotine-replacement products of their choice, including product combinations, provided for up to 3 months, or an e-cigarette starter pack (a second-generation refillable e-cigarette with one bottle of nicotine e-liquid [18 mg per milliliter]), with a recommendation to purchase further e-liquids of the flavor and strength of their choice. Treatment included weekly behavioral support for at least 4 weeks. The primary outcome was sustained abstinence for 1 year, which was validated biochemically at the final visit. Participants who were lost to follow-up or did not provide biochemical validation were considered to not be abstinent. Secondary outcomes included participant-reported treatment usage and respiratory symptoms. RESULTS: A total of 886 participants underwent randomization. The 1-year abstinence rate was 18.0% in the e-cigarette group, as compared with 9.9% in the nicotine-replacement group (relative risk, 1.83; 95% confidence interval [CI], 1.30 to 2.58; P<0.001). Among participants with 1-year abstinence, those in the e-cigarette group were more likely than those in the nicotine-replacement group to use their assigned product at 52 weeks (80% [63 of 79 participants] vs. 9% [4 of 44 participants]). Overall, throat or mouth irritation was reported more frequently in the e-cigarette group (65.3%, vs. 51.2% in the nicotine-replacement group) and nausea more frequently in the nicotine-replacement group (37.9%, vs. 31.3% in the e-cigarette group). The e-cigarette group reported greater declines in the incidence of cough and phlegm production from baseline to 52 weeks than did the nicotine-replacement group (relative risk for cough, 0.8; 95% CI, 0.6 to 0.9; relative risk for phlegm, 0.7; 95% CI, 0.6 to 0.9). There were no significant between-group differences in the incidence of wheezing or shortness of breath. CONCLUSIONS: E-cigarettes were more effective for smoking cessation than nicotine-replacement therapy, when both products were accompanied by behavioral support. (Funded by the National Institute for Health Research and Cancer Research UK; Current Controlled Trials number, ISRCTN60477608 .).

TIGA: target illumination GWAS analytics.

MOTIVATION: Genome-wide association studies can reveal important genotype-phenotype associations; however, data quality and interpretability issues must be addressed. For drug discovery scientists seeking to prioritize targets based on the available evidence, these issues go beyond the single study. RESULTS: Here, we describe rational ranking, filtering and interpretation of inferred gene-trait associations and data aggregation across studies by leveraging existing curation and harmonization efforts. Each gene-trait association is evaluated for confidence, with scores derived solely from aggregated statistics, linking a protein-coding gene and phenotype. We propose a method for assessing confidence in gene-trait associations from evidence aggregated across studies, including a bibliometric assessment of scientific consensus based on the iCite relative citation ratio, and meanRank scores, to aggregate multivariate evidence.This method, intended for drug target hypothesis generation, scoring and ranking, has been implemented as an analytical pipeline, available as open source, with public datasets of results, and a web application designed for usability by drug discovery scientists. AVAILABILITY AND IMPLEMENTATION: Web application, datasets and source code via https://unmtid-shinyapps.net/tiga/. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Nicotine Delivery and User Ratings of IQOS Heated Tobacco System Compared With Cigarettes, Juul, and Refillable E-Cigarettes.

INTRODUCTION: Reduced-risk nicotine products are more likely to replace smoking if they match cigarettes in nicotine delivery and user satisfaction. AIMS AND METHODS: We examined the nicotine delivery profile and user ratings of IQOS heated tobacco system and compared it with own brand cigarettes (OBC), Juul, and refillable e-cigarettes (EC).Participants (N = 22) who were daily vapers smoking <1 cigarette per day on average, attended after overnight abstinence from smoking and vaping, to test at separate sessions OBC, IQOS, and Juul. Eight participants also tested two refillable EC using e-liquid with 20 mg/mL nicotine. At each session, a baseline blood sample was taken before participants used the product ad libitum for 5 minutes. Further samples were taken at 2, 4, 6, 8, 10, and 30 minutes. Maximum nicotine concentration (Cmax), time to Cmax (Tmax), and nicotine delivered over 30 minutes (AUC0->30) were calculated. Participants rated their urge to smoke and product characteristics. RESULTS: IQOS delivered less nicotine than OBC (AUC0->30: z = -2.73, p = .006), and than Juul (AUC0->30: z = -3.08, p = .002; Cmax: z = -2.65, p = .008), and received less favorable ratings than Juul (effect on urges to smoke: z = -3.23, p = .001; speed of urge relief: z = -2.75, p = .006; recommendation to friends: z = -2.45, p = .014). Compared with refillable EC, IQOS delivered nicotine faster (Tmax: z = -2.37, p = .018), but received less favorable overall ratings (recommended to friends: z = -2.32, p = .021). CONCLUSIONS: IQOS' pharmacokinetic profile suggests that it may be less effective than Juul for smoking cessation, but at least as effective as refillable EC; although participants, who were experienced vapers rather than IQOS users, preferred refillable EC. IMPLICATIONS: Because IQOS provided less efficient nicotine delivery than cigarettes and Juul in this sample, and also had a weaker effect on urges to smoke than Juul, it could be less helpful than Juul in assisting such dual users, and possibly smokers generally, to switch to an alternative product. IQOS, however, provided nicotine faster than refillable EC products, although participants preferred EC.

The impact of the COVID-19 pandemic on the utilization of emergency department services for the treatment of injuries.

CONTEXT: The global COVID-19 pandemic has had a major impact on the utilization of healthcare services; however, the impact on population-level emergency department (ED) utilization patterns for the treatment of acute injuries has not been fully characterized. OBJECTIVE: This study examined the frequency of North Carolina (NC) EDs visits for selected injury mechanisms during the first eleven months of the COVID-19 pandemic. METHODS: Data were obtained from the NC Disease Event Tracking and Epidemiologic Collection Tool (NC DETECT), NC's legislatively mandated statewide syndromic surveillance system for the years 2019 and 2020. Frequencies of January - November 2020 NC ED visits were compared to frequencies of 2019 visits for selected injury mechanisms, classified according to International Classification of Diseases, 10th Revision, Clinical Modification (ICD-10-CM) injury diagnosis and mechanism codes. RESULTS: In 2020, the total number of injury-related visits declined by 19.5% (N = 651,158) as compared to 2019 (N = 809,095). Visits related to motor vehicle traffic crashes declined by a greater percentage (29%) and falls (19%) declined by a comparable percentage to total injury-related visits. Visits related to assault (15%) and self-harm (10%) declined by smaller percentages. Medication/drug overdose visits increased (10%), the only injury mechanism studied to increase during this period. CONCLUSION: Both ED avoidance and decreased exposures may have contributed to these declines, creating implications for injury morbidity and mortality. Injury outcomes exacerbated by the pandemic should be addressed by timely public health responses.

An Appraisal of School Nurse Health Services and Programs in North Carolina Public Schools, 2006-2016.

School nurses are instrumental in delivering health services to children in schools. This study addresses the gap in school nurse health services data, examining patterns in health services and programs provided by school nurses between 2006 and 2016 for students in North Carolina public schools. This study focused on services and programs related to asthma and diabetes, two health conditions that affect millions of children in the United States. Over 1.46 million children attend North Carolina public schools. In 2006, the average school nurse-to-student ratio was 1:1,340. By 2016, the average school nurse-to-student ratio decreased to 1:1,086, a 19% improvement. Over the 10-year study time period, there were statistically significant increases in the rate of occurrence of all health conditions that students received health services for (p < .001), asthma (p < .001), type I diabetes (p = .0003), orders for all health-care procedures (p = .01), all school nurse-led health counseling (p = .004), and diabetes health counseling (p < .01).

Examining the Effect of Pedestrian Crashes on Vulnerable Populations in North Carolina.

BACKGROUND: Over the last several years, pedestrian fatalities have increased in North Carolina; however, fatalities represent a small proportion of the total number of nonfatally injured pedestrians. Therefore, we linked statewide motor vehicle crash (MVC) and emergency department (ED) visit data to better understand the circumstances and characteristics of pedestrians treated in North Carolina emergency departments (EDs) for injuries related to crashes. METHODS: We linked information for pedestrians and bicyclists from 2017 North Carolina police-reported MVCs to population-based ED visit data using hierarchical deterministic methods. RESULTS: We linked 45% of pedestrian crash records to ED visit records (N = 1383 incident ED visits). The rate of pedestrians treated in North Carolina EDs for their injuries was 13.6 ED visits per 100,000 person years. For pedestrian injuries treated in North Carolina EDs, rates (per 100,000 person years in parentheses) were higher among men (15.5) and Black pedestrians (22.7) than women (10.6) and White pedestrians (8.2). Sociodemographic characteristics associated with serious injuries included age, sex, race/ethnicity, and expected source of payment for the ED visit. Crash characteristics associated with serious injuries included posted speed limit, ambient light, number of lanes, and striking vehicle type. LIMITATIONS: The study involved the use of secondary data, not collected specifically for pedestrian injury surveillance. CONCLUSIONS: Pedestrian injuries and fatalities place a considerable burden on the population of North Carolina, especially among persons of color and older adults. Injury prevention programs are actively addressing this problem, but more needs to be done.

Begin risk assessment for falls in women at 45, not 65.

The clinical and epidemiological literature provides guidelines for fall prevention starting at age 65; however, the focus on age ≥65 is not evidence based. Therefore, this study examined state-wide North Carolina emergency department visit data to examine the characteristics of falls across the age spectrum, identify the age at which the incidence of fall-related emergency department visits started to increase and determine whether these trends were similar for men and women. We determined that incidence rates of fall-related emergency department visits began to increase in early middle age, particularly for women. Since fall risk assessment and prevention activities should be initiated prior to an injurious fall, we recommend beginning these activities before age 65.

Pharos: Collating protein information to shed light on the druggable genome.

The 'druggable genome' encompasses several protein families, but only a subset of targets within them have attracted significant research attention and thus have information about them publicly available. The Illuminating the Druggable Genome (IDG) program was initiated in 2014, has the goal of developing experimental techniques and a Knowledge Management Center (KMC) that would collect and organize information about protein targets from four families, representing the most common druggable targets with an emphasis on understudied proteins. Here, we describe two resources developed by the KMC: the Target Central Resource Database (TCRD) which collates many heterogeneous gene/protein datasets and Pharos (https://pharos.nih.gov), a multimodal web interface that presents the data from TCRD. We briefly describe the types and sources of data considered by the KMC and then highlight features of the Pharos interface designed to enable intuitive access to the IDG knowledgebase. The aim of Pharos is to encourage 'serendipitous browsing', whereby related, relevant information is made easily discoverable. We conclude by describing two use cases that highlight the utility of Pharos and TCRD.

TIN-X: target importance and novelty explorer.

MOTIVATION: The increasing amount of peer-reviewed manuscripts requires the development of specific mining tools to facilitate the visual exploration of evidence linking diseases and proteins. RESULTS: We developed TIN-X, the Target Importance and Novelty eXplorer, to visualize the association between proteins and diseases, based on text mining data processed from scientific literature. In the current implementation, TIN-X supports exploration of data for G-protein coupled receptors, kinases, ion channels, and nuclear receptors. TIN-X supports browsing and navigating across proteins and diseases based on ontology classes, and displays a scatter plot with two proposed new bibliometric statistics: Importance and Novelty. AVAILABILITY AND IMPLEMENTATION: http://www.newdrugtargets.org. CONTACT: cbologa@salud.unm.edu.

Acute Pancreatitis: Updates for Emergency Clinicians.

BACKGROUND: Acute pancreatitis is a frequent reason for patient presentation to the emergency department (ED) and the most common gastrointestinal disease resulting in admission. Emergency clinicians are often responsible for the diagnosis and initial management of acute pancreatitis. OBJECTIVE: This review article provides emergency clinicians with a focused overview of the diagnosis and management of pancreatitis. DISCUSSION: Pancreatitis is an inflammatory process within the pancreas. While the disease is often mild, severe forms can have a mortality rate of up to 30%. The diagnosis of pancreatitis requires two of the following three criteria: epigastric abdominal pain, an elevated lipase, and imaging findings of pancreatic inflammation. The most common etiologies include gallbladder disease and alcohol use. After the diagnosis has been made, it is important to identify underlying etiologies requiring specific intervention, as well as obtain a right upper quadrant ultrasound. The initial management of choice is fluid resuscitation and pain control. Recent data have suggested that more cautious fluid resuscitation in the first 24 h might be more appropriate for some patients. Intravenous opiates are generally safe if used judiciously. Appropriate disposition is a multifactorial decision, which can be facilitated by using Ranson criteria or the Bedside Index of Severity in Acute Pancreatitis score. Complications, though rare, can be severe. CONCLUSIONS: Pancreatitis is a potentially deadly disease that commonly presents to most emergency departments. It is important for clinicians to be aware of the current evidence regarding the diagnosis, treatment, and disposition of these patients.

Snakebites Treated in North Carolina Emergency Departments, October 2013-September 2015.

INTRODUCTION: North Carolina (NC) is home to more than 30 species of indigenous venomous and nonvenomous snakes. Snakebites can cause debilitating and potentially fatal injuries. However, there is a lack of current information available describing the incidence of snakebites in NC. Therefore, we performed this study of snakebites treated in NC emergency departments (EDs) using the statewide syndromic surveillance system, the North Carolina Disease Event Tracking and Epidemiologic Collection Tool (NC DETECT). METHODS: This was a descriptive epidemiologic study characterizing NC ED visits collected by NC DETECT between October 1, 2013 and September 30, 2015 with an assigned International Classification of Diseases, 9th Revision, Clinical Modification code or keyword indicating a snakebite. RESULTS: Over the 2-year period, the absolute count of snakebite-related ED visits was 2080 visits with an incidence rate of 10.4 visits per 100 000 person-years (95% confidence interval: 10.0-10.9). The frequency of snakebite was highest during the summer months and evening hours. Men had higher incidence rates of snakebite-related ED visits than women, and residents of the Coastal Plain geographic region of NC had higher incidence rates than persons in other regions. CONCLUSIONS: The current study indicated that snakebites are common injuries treated at NC EDs, with a strong seasonal and geographic component. Additional research is needed to further characterize the circumstances associated with snakebites for the development of preventive measures and public health education.

Motor Vehicle Crash Case Definitions and How They Impact Injury Surveillance.

BACKGROUND Motor vehicle crashes are a leading cause of injury in North Carolina. Motor vehicle crash injury surveillance that relies on hospital diagnostic codes alone may underestimate injury. Our objective was to describe how motor vehicle crash injury case definitions can impact results when using hospital data.METHODS We received motor vehicle crash-related emergency department visits from 1 large metropolitan county in North Carolina for the year 2013. Emergency department visits were categorized based on 3 mutually exclusive case definitions: motor vehicle crash injuries identified using external cause-of-injury codes, text searches for motor vehicle crash-related key words in triage notes or chief complaint fields, and motor vehicle crash injuries identified using both text searches and external cause-of-injury codes. Descriptive statistics were used to examine differences in patient characteristics according to case definition.RESULTS Most emergency department visits contained both motor vehicle crash text and motor vehicle crash external cause-of-injury codes (N = 13,422, 76%). Patients identified using external cause-of-injury codes only were more likely to be male, arrive by ambulance, and be admitted to the hospital compared to patients identified by text searches or both text and external cause-of-injury codes. Twenty-eight percent of the patients (N = 5,021) received non-injury related diagnoses in the emergency department. Among these patients, the most frequently used first diagnoses were for vague or chronic pain conditions.LIMITATIONS We relied on secondary data and were unable to perform medical chart reviews; hospital data have limited information surrounding the crash event.CONCLUSION The choice of case definition used for motor vehicle crash surveillance impacts the picture of motor vehicle crash injury severity. It is important for researchers to be aware of the impact case definition has on their results.