Post-traumatic stress disorder (PTSD) symptoms and alcohol and drug use comorbidity at 25 US level I trauma centers =================================================================================================================== * Jefferson Nguyen * Lauren K Whiteside * Eileen M Bulger * Laura Veach * Kathleen Moloney * Joan Russo * Deepika Nehra * Jin Wang * Douglas F Zatzick ## Abstract **Background** Questions regarding the extent to which post-traumatic stress disorder (PTSD) is comorbid with alcohol and drug use are particularly germane in an era when the American College of Surgeons Committee on Trauma (ACS-COT) is considering policy requiring screening, intervention and/or referral services for patients presenting with psychological sequalae of traumatic injury. Literature review revealed few multisite trauma-center-based investigations that have assessed the association between PTSD symptoms and alcohol and drug use comorbidities in injured patients. **Methods** This investigation was a secondary analysis of baseline data collected prior to randomization in a 25-site trauma center pragmatic clinical trial. All 635 patients included in the investigation had elevated PTSD symptom levels at the time of trauma center admission. Self-report questionnaire screening, laboratory toxicology results, and electronic health record data were combined to assess the frequencies of alcohol, stimulant (i.e., amphetamine and cocaine), opioid and marijuana use comorbidities for injured patients. Logistic regression was used to assess the associations between demographic and injury characteristics and alcohol and drug use comorbidity. **Results** The frequency of patients with one or more alcohol or substance use comorbidity was between 62% and 79%. Over 50% of patients were positive for one or more alcohol or cannabis comorbidity. Approximately 26% of patients were positive for stimulants and 10% for opioid comorbidity. **Discussion** This multisite investigation suggests that between 62% and 79% of hospitalized injury survivors with elevated PTSD symptoms have one or more alcohol or drug use comorbidity. Orchestrated ACS-COT policy and trauma center service delivery development should incorporate the key finding that a substantial majority of patients with high levels of psychological distress (eg, elevated PTSD symptoms) may have alcohol and drug use comorbidities. **Level of evidence** Level II (epidemiological investigation of untreated controls from a multisite randomized clinical trial) **Trial registration number** [NCT02655354](http://tsaco.bmj.com/lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT02655354&atom=%2Ftsaco%2F7%2F1%2Fe000913.atom). * stress disorders, post-traumatic * policy * alcoholism * substance-related disorders #### WHAT IS ALREADY KNOWN ON THIS TOPIC * Few multisite trauma-center-based investigations have assessed the association between post-traumatic stress disorder (PTSD) symptoms and alcohol and drug use comorbidities. #### WHAT THIS STUDY ADDS * Of 635 patients with elevated PTSD symptom levels recruited across 25 US level I trauma center sites, between 21% and 38% demonstrated no alcohol or drug use comorbidity. Over 50% of patients were positive for one or more alcohol or cannabis comorbidity; 26% of patients were positive for stimulants and 10% for opioid comorbidity. #### HOW THIS STUDY MIGHT AFFECT RESEARCH, PRACTICE OR POLICY * Orchestrated policy and trauma center service delivery development should incorporate the key finding that a substantial majority of patients with elevated PTSD symptoms have alcohol and drug use comorbidities. ## Introduction In 2019, approximately 2.8 million Americans were so severely injured that they required inpatient hospital admission.1 Multiple investigations now document a high prevalence of symptoms consistent with post-traumatic stress disorder (PTSD) at rates of 20% or greater among hospitalized US injury survivors.2–6 Elevated early PTSD symptom levels after an injury have been shown to be associated with the later development of a clinical diagnosis of PTSD in the months after an injury hospitalization7 8 After injury, PTSD symptoms are associated with a broad profile of functional impairments and diminished quality of life.9–13 Similarly, extensive literature documents high frequencies of alcohol and drug use, including opioids, amphetamines, other stimulants (eg, cocaine) and marijuana, in trauma center patients. In an initial single-site level I trauma center study, over half of consecutively sampled injured trauma survivors displayed a lifetime alcohol or drug use disorder.14 Subsequent investigations have also documented high frequencies of opioid, stimulant, and cannabis use comorbidity among hospitalized injury survivors.15–17 A recent investigation conducted at three trauma center sites found that 30% of trauma patients screened positive for one or more psychoactive drugs, including methamphetamine, opioids, phencyclidine, methylenedioxymethamphetamine (ecstasy), cannabinoids, tricyclic antidepressants, benzodiazepines and barbiturates.15 This investigation also documented an association between psychoactive drug use at admission and worsened physical and mental health outcomes after admission.15 Studies have linked specific trauma center patient clinical and demographic characteristics with higher risk of alcohol and drug use comorbidity. One investigation found that trauma survivors with psychoactive drug use were more likely to be younger, have a lower income and education level, and have a history of tobacco and substance use.15 Other single-site investigations have found that trauma survivors of younger age, Caucasian race and male sex were more likely to be suffering from alcohol and drug use comorbidity.16 17 Additionally, an investigation of the Canadian Hospitals Injury Reporting and Prevention Program found that alcohol and drug use were more frequently associated with intentional injuries compared with unintentional injuries; the investigation also found that trauma survivors presenting with alcohol and drug use were more likely to be younger and male.18 Literature review revealed few trauma center-based investigations that have assessed the association between PTSD and alcohol and drug use comorbidities in injured patients. One prior investigation at a single level I trauma center found that among 878 randomly sampled hospitalized injury survivors, approximately 80% presented with either elevated PTSD symptom levels and/or alcohol, opioid, stimulant, and marijuana comorbidities.19 Other investigations have documented that alcohol and drug use comorbidity at the time of trauma center admission do not predict the development of PTSD symptoms during the course of 6 months after injury.20 21 Literature review revealed no previous multisite investigations that have assessed the extent to which surgical inpatients with elevated early postinjury PTSD symptom levels have comorbid alcohol and drug use comorbidity. Questions regarding the extent to which PTSD is comorbid with alcohol and drug use become particularly germane in an era when the American College of Surgeons Committee on Trauma (ACS-COT) is considering policy requirements for the screening and treatment of patients presenting with psychological sequalae of traumatic injury. A more comprehensive multisite examination of the comorbidity between PTSD and substance use could inform screening, intervention, and referral service delivery development at US trauma centers. The current study sought to corroborate and extend previous investigations examining the inter-relationships between PTSD and alcohol and drug use comorbidities in injured trauma survivors. The investigation harnessed data previously collected in a 25-site trauma center study to describe the frequencies of alcohol, opioids, stimulant and cannabis use comorbidity among inpatients with elevated PTSD symptoms.22 The investigation hypothesized that patients presenting with elevated levels of PTSD symptoms would also present with high rates of alcohol and drug use comorbidities. The demographic and clinical characteristics associated with specific patient alcohol and drug comorbidities were also described. ## Patients and Methods ### Study design This investigation was a secondary analysis of baseline data collected prior to randomization in a 25-trauma center site pragmatic clinical trial.22 The 25 sites constituted a representative subsample of US level I trauma centers.23 All study procedures were approved by the Western Institutional Review Board before the initiation of the investigation.24 The complete study procedures have been described in previous publications22 23 25 26 and are briefly summarized as follows. ### Study setting and participants Between January 2016 and November 2018, 635 hospitalized traumatic injury survivors were recruited across the 25 sites. English-speaking survivors of intentional and unintentional injuries were screened. Patients were excluded if they displayed acute psychiatric symptoms that required immediate intervention (eg, suicidal ideation) or were currently incarcerated. The study team had previously developed a 10-domain electronic health record (EHR) screen to detect patients with a high likelihood of demonstrating PTSD symptomatic distress as hospitalized inpatients; patients with a score of ≥3 on the EHR screen were eligible to participate in the clinical portion of the study.22 The 10-domain PTSD risk factor items pulled from the EHR are (1) Blood Alcohol Concentration (BAC) or drug toxicology positive or any substance disorder International Classification of Diseases (ICD) from EHR; (2) female sex; (3) non-white race/Hispanic ethnicity; (4) public insurance, Veterans’ insurance, or uninsured; (5) treated in the intensive care unit (ICU) during the injury admission; (6) any psychiatric disorder ICD from EHR; (7) PTSD ICD from EHR; (8) tobacco use; (9) injury inflicted by another (ie, intentional injury); and (10) at least one prior emergency department or hospital inpatient visit. Research study staff identified potential patient subjects who met the criteria of having ≥3 PTSD EHR risk factor domains positive as potential candidates for approach for informed consent. During the course of the study, 171 303 trauma patients were admitted to the 25 US level I trauma center sites; 163 849 patients were not screened for the investigation. An additional 3256 patients were unable to undergo the study assessment (eg, cognitive impairment, non-English speaking). Seventeen hundred and six patients did not meet the EHR ≥3 domains positive screening criteria for the study and/or were excluded before consent was attempted. Eight hundred and eleven patients were discharged before consent was attempted; 617 patients declined to participate; 380 patients screened out of the study with a score of <35 on the PTSD Checklist; 46 patients were unable to complete the baseline interview and 3 patients withdrew, leaving 635 patients who completed the baseline surgical ward interview with scores of ≥35 on the PTSD Checklist. After obtaining patient written informed consent, research staff administered a baseline interview that began with the PTSD Checklist–Civilian (PCL-C) Version, *Diagnostic and Statistical Manual of Mental Disorders*, Fourth Edition (DSM-IV) assessment. Patients with elevated levels of PTSD symptom as indicated by a score of ≥35 or higher on the PCL-C completed the baseline interview.7 27 After completing all baseline measures, patients were entered into the longitudinal portion of the study and randomized. The current secondary analysis includes the baseline prerandomization data for 635 trauma surgical patients from the 25 sites with elevated PTSD symptom levels as indicated by a score of ≥35. ### Measures #### PTSD symptoms The study’s baseline interview used the 17-item PCL-C Version for the DSM-IV to assess initial PTSD symptom levels.7 27 28 The PTSD Checklist asks patients about the intrusive, avoidant, and arousal symptoms that constitute a DSM-IV diagnosis of PTSD. For the purposes of the current investigation, the PTSD Checklist items were anchored to the injury event. For example, patients were asked, ‘Since you were injured, how bothered have you been by repeated, disturbing memories, thoughts, or images of the event…?’ The 17 items are asked on a 1 to 5 scale, with ‘1’ being not at all and ‘5’ being extremely bothered; the 17-item scale score ranges from 17 to 85. Prior study team investigations have established the reliability and validity of this measure when used with hospitalized traumatic injury survivors; these prior investigations have also established a cut-off score of ≥35 as optimally predictive of later development of a PTSD diagnosis.7 28 #### Alcohol use comorbidity The baseline interview also included the Alcohol Use Disorder Identification Test Three-item Version (AUDIT-C) to assess alcohol use comorbidity in the 12 months before the injury hospitalization.29 30 As recommended, a cut-off on the AUDIT-C of 4 or more for men and 3 or more for women was used to identify an alcohol use problem.29 30 To develop a comprehensive indicator of alcohol use comorbidity at the time of trauma surgery inpatient admission,19 the investigation supplemented the AUDIT-C self-report data with documented positive alcohol laboratory toxicology results and alcohol use disorder diagnoses derived from the EHR. #### Drug use comorbidity The baseline interview included a single-item drug screen to assess the preinjury use of opioids, amphetamines, cocaine, and marijuana; amphetamine and cocaine use were collapsed into a single stimulant use comorbidity category.22 31 As part of the baseline interview, injury survivors were asked, ‘In the past 12 months prior to your injury, how often have you used each drug?’ Response options included, ‘never’, ‘monthly or less’, ‘two to four times a month’, ‘two to three times a week’, or ‘four or more times a week’. For the purposes of data analyses, responses were dichotomized as drug use (monthly or less or more frequent use) versus no use (never). With the exception of opioids, which are often administered in the prehospital or acute care setting by medical providers, to develop comprehensive indicators of drug use comorbidity, the study team augmented this self-report information with documentation of positive laboratory toxicology results. An additional, more conservative threshold for substance use comorbidity was also estimated that incorporated patients who endorsed use of any substance four or more times each week. #### Other assessments Patient demographic characteristics such as age, sex, race, ethnicity, education, employment, and marital status were obtained from the baseline interview. Other demographic injury and clinical characteristics such as ICU stay, prior hospitalizations, insurance status and injury severity and medical comorbidity scores were obtained from the EHR and from site trauma registry data. ### Data analysis The investigation first described the frequencies of self-report, EHR and/or toxicology documented alcohol, opioid, stimulant, and marijuana use for the 635 patients with elevated PTSD symptom levels. Next, the study team estimated two thresholds for substance use comorbidity, a comprehensive threshold that incorporated AUDIT-C, BAC/toxicology positive, and monthly or less self-report use of any drug (ie, opioid, stimulant, or marijuana) and a conservative threshold that included only AUDIT-C alcohol use problem criteria cutoffs combined with any self-report drug use four or more times each week. The extent to which alcohol, opioid, stimulant, and marijuana use occurred as comorbid conditions was assessed using the more comprehensive threshold. Finally, the associations between demographic and clinical characteristics and individual alcohol, opioid, stimulant and marijuana use comorbidity were assessed. Baseline demographic, injury and clinical characteristics including age, sex, race, ethnicity, insurance status, employment status, educational status, marital status, injury type, injury severity, prior hospitalizations, ICU stays, current tobacco use, psychiatric diagnosis, and medical comorbidities were entered into a logistic regression model using a stepwise backwards elimination procedure.32 Variables with significant independent associations at the p<0.05 level were retained in the final models that accounted for the clustering of characteristics across sites. ## Results At baseline, 54.2% of patients were positive for one or more alcohol indicator, and 50.2% were positive for one or more cannabis indicator (table 1). Approximately 26% of patients were positive for one or stimulant indicator and 9.8% endorsed self-reported opioid use. Of note, 11.8% of patients were missing trauma registry-derived urine toxicology values. View this table: [Table 1](http://tsaco.bmj.com/content/7/1/e000913/T1) Table 1 Alcohol, stimulant,* opioid and cannabis comorbidities in trauma center patients with Post-traumatic Stress Disorder Checklist scores ≥35 (N=635) Approximately 21% of patients demonstrated no alcohol or drug use comorbidity (figure 1). Twenty percent of patients only used alcohol; 16.5% used alcohol and cannabis; 12.0% used alcohol, cannabis, opioids, and stimulants; and 5.4% used alcohol, opioids, and stimulants. Twelve percent of patients reported using cannabis only and 3.1% of patients reported using stimulants and opioids only. Incorporation of the more conservative thresholds for substance use comorbidity identified 62% of the sample as having an alcohol or substance use comorbidity. ![Figure 1](http://tsaco.bmj.com/http://tsaco.smart01.highwire.org/content/tsaco/7/1/e000913/F1.medium.gif) [Figure 1](http://tsaco.bmj.com/content/7/1/e000913/F1) Figure 1 Breakdown of alcohol, stimulant, opioid and cannabis comorbidity for all patients (N=635). The final study cohort consisted of 308 women (48.5%) and 327 men (51.5%) (table 2). The mean age of the cohort was 39.0 years (SD=14.2) (table 2). Over 50% of participants were non-white and 16% were Hispanic. Fifty six percent of participants endorsed using tobacco. Further demographic and clinical details are provided in table 2. View this table: [Table 2](http://tsaco.bmj.com/content/7/1/e000913/T2) Table 2 Demographic and clinical characteristics of Patients with alcohol and drug use comorbidities The frequency of the 10-domain EHR risk factors among the n=635 patients is detailed in table 3. Of particular note, 397 (63) of patients had a positive blood alcohol/urine toxicology or alcohol or drug use diagnosis during the hospitalization (table 3). View this table: [Table 3](http://tsaco.bmj.com/content/7/1/e000913/T3) Table 3 Frequency of 10-domain electronic health record risk factors among N=635 patients The mean PTSD Checklist score for the entire cohort was 52.1 (SD=12.2). Patients with one or more positive indicators for opioids (mean=54.5, SD=13.1; mean=54.6, SD=12.2) and stimulants had on average higher PTSD Checklist scores when compared with patients with one or more positive indicators for alcohol (mean=52.0, SD=12.2) and cannabis (mean=52.8, SD=11.9). Tobacco use was associated with a significantly increased odds of alcohol use comorbidity, whereas preinjury unemployment was associated with a significantly decreased odds of alcohol use comorbidity (table 4). Preinjury unemployment was associated with a significantly increased odds of opioid use, whereas non-white race, being female, and increasing age were associated with a significantly decreased odds of opioid use. Tobacco use, intentional injury, not being married, and preinjury unemployment were associated with a significantly increased odds of stimulant comorbidity, whereas older age was associated with a significantly decreased odds of stimulant comorbidity. Finally, tobacco use and intentional injury were associated with a significantly increased odds of cannabis comorbidity, whereas attending college, less severe injury, and increasing age were associated with a significantly decreased odds of cannabis comorbidity. View this table: [Table 4](http://tsaco.bmj.com/content/7/1/e000913/T4) Table 4 Significant associations between demographic and clinical characteristics and alcohol and drug use comorbidities ## Discussion This investigation combined self-report screening, laboratory toxicology results, and EHR data to assess the frequencies of alcohol, stimulant, opioid and marijuana use comorbidity among 635 trauma surgery inpatients with elevated PTSD symptom levels recruited from 25 US level I trauma center sites. The investigation found that 79% of the hospitalized trauma survivors with elevated PTSD symptom levels had one or more positive alcohol, opioid, stimulant or cannabis comorbidity. Sensitivity analyses that used a more conservative threshold for comorbidity inclusion identified that 62% of patients had one or more comorbidity. The investigation documented particularly high frequencies of alcohol and cannabis comorbidities, with over 50% of patients having one or more positive indicators. Approximately one-quarter of patients had one or more positive indicators for stimulant use, and approximately 10% of patients had a positive indicator for opioid use. The current study findings corroborate and extend reports from prior investigations of PTSD symptom and alcohol and drug use comorbidities among injured trauma survivors. In a prior single-site study of 878 randomly sampled trauma center inpatients, approximately 80% of inpatients presented with one or more alcohol or drug comorbidity and/or elevated PTSD symptom-level comorbidities.19 The current investigation extends these previous findings by documenting that in a sample of 635 trauma inpatients with elevated baseline PTSD symptom levels derived from 25 US level I trauma center sites, between 62% and 79% of patients had one or more positive indicators for an alcohol, stimulant, opioid or cannabis use comorbidity. Prior investigations beyond the trauma center setting also document high rates of substance use comorbidity in patients with PTSD.33 34 These observations have important implications for the development screening, intervention, and referral procedures for patients with elevated levels of PTSD symptoms at US trauma centers. A recent national survey documented that approximately 30% of US trauma center sites were routinely screening for PTSD symptoms after injury admission.35 Over half of sites that were conducting PTSD screening were building PTSD services on existing alcohol screening and intervention services. The results of the current investigation suggest that building PTSD screening and intervention services on existing trauma center alcohol service delivery is an optimal approach, given the very high rates of PTSD and alcohol comorbidity. Also, of note, a recent national survey documents that social workers appear to conduct the majority of trauma center alcohol and drug use screening. With regard to screening, optimal procedures may need to incorporate EHR efficiencies to be able to simultaneously screen for PTSD risk and also incorporating multiple alcohol and drug comorbidities.7 The current study findings also have important implications for research on optimal PTSD intervention strategies for US trauma centers. Collaborative care interventions that combine elements of substance use treatments36 37 (eg, motivational interviewing for alcohol) and PTSD focused treatments (eg, PTSD pharmacotherapy, cognitive behavioral therapy elements embedded within care management) have demonstrated effectiveness in simultaneously addressing comorbid PTSD symptoms and alcohol use.8 22 38 39 In contrast, acute care psychotherapeutic interventions with an isolated focus on PTSD symptoms, such as session-based cognitive behavioral therapies, have demonstrated mixed results with some40 41 but not all42–44 randomized trials reporting treatment effectiveness in injury survivors. Meta-analysis has identified collaborative care interventions as the optimal treatment approach for injured trauma survivors with PTSD and comorbidities when compared with cognitive behavioral therapy, as the collaborative care combination of effective evidence-based medication and psychotherapeutic treatments with care management results in expanded intervention reach and greater overall population impact for patients presenting to trauma center settings.45 46 Collaborative care interventions have the additional potential advantage of being able to flexibly incorporate new developments in the acute care treatment of drug use comorbidity (eg, medications for opioid use disorder).47 48 With regard to trauma center-to-primary care and community referral for patients with PTSD, these linkages may need to incorporate treatment planning for alcohol and drug use comorbidities.8 22 38 39 The investigation also assessed the associations between demographic and clinical characteristics of patients with elevated PTSD symptoms and alcohol, opioid, stimulant and cannabis comorbidity table 4. Tobacco use was associated with an increased odds of alcohol, stimulant, and cannabis use comorbidity. Older age was associated with decreased odds of opioid, stimulant, and cannabis comorbidity. Preinjury unemployment was associated with an increased risk of amphetamine and opioid use comorbidity, and a decreased risk of alcohol comorbidity. These findings suggest that, along with specific demographic characteristics, the social determinants of health that impact patients with mental health and substance use disorders nationally also affect injured patients presenting to US trauma centers. ### Limitations This investigation has limitations. The study indicators for substance use include the association of a positive urine drug screen toxicology screen with trauma center inpatient admission. The study team is aware that, in some cases (eg, cannabis use), toxicology positive screens may span weeks and may not be directly associated with injury events that constitute drug use problems by precipitating trauma center inpatient admissions. This could result in an overestimate of drug use comorbidity, particularly for cannabis; to mitigate this concern the study team has included a sensitivity analysis that conservatively estimates drug use comorbidity through endorsement of use four or more times each week. Similarly, unlike prior epidemiologically focused studies of PTSD and substance use comorbidity,19 the current investigation did not employ a random sampling frame, and the 10-domain EHR screen that prioritized patients for assessment included an alcohol and drug use domain; thus, the observation of 62%–79% substance use comorbidity among patients with elevated PTSD symptom levels does not represent a prevalence estimate. Moreover, with regard to comorbidity, it is acknowledged that prescribed use of marijuana may constitute some of the marijuana consumption described in the article, and thus, estimates of marijuana use comorbidity may be inflated. An additional limitation was that approximately 12% of patients were missing urine toxicology data derived from the trauma registry. Finally, as a cross-sectional investigation of trauma surgery inpatients, the investigation did not assess alcohol and drug use as predictors of the development of PTSD symptoms20 21 or the temporal sequencing of the development of PTSD symptoms and substance use comorbidity.49 ## Conclusion Beyond these considerations, the investigation has important implications for ACS-COT policy regarding mental health and substance use disorders. The ACS-COT has previously required alcohol screening and intervention at US level I and II trauma centers.50 Recent investigation has established widespread adherence among trauma centers nationally to the ACS-COT alcohol requirement.35 Orchestrated ACS-COT policy and trauma center service delivery development should incorporate the key finding that a substantial majority of patients with high levels of psychological distress (eg, elevated PTSD symptoms) may have alcohol and drug use comorbidities. ## Data availability statement Data are available upon reasonable request. The study data will be shared; details of data sharing are currently being worked out by the investigative team. ## Ethics statements ### Patient consent for publication Not applicable. ### Ethics approval This study involves human participants and was approved by Western Institutional Review Board (study number 1155305). Participants gave informed consent to participate in the study before taking part. ## Acknowledgments The authors acknowledge Khadija Abu for assisting with the formatting of the article for publication submission. ## Footnotes * Contributors JN contributed to the literature review, study design, and writing and critical revision of the article; LKW contributed to the literature search, data interpretation, and writing and critical revision of the article; EMB contributed to the data interpretation and writing and critical revision of the article; LV contributed to the data collection, data interpretation, and writing and critical revision of the article; KM contributed to the data analysis, data interpretation, and writing and critical revision of the article; JR contributed to the study design, data collection, data analysis, data interpretation, and writing and critical revision of the article; DN contributed to the data interpretation and writing and critical revision of the article; JW contributed to the study design, data collection, data analysis, data interpretation, and the writing and critical revision of the article; DFZ contributed to the study design, literature search, data collection, data interpretation, and writing and critical revision of the article. DFZ accepts full responsibility for the work and/or the conduct of the study, had access to the data, and controlled the decision to publish. All authors approved the final version of the article. * Funding This research was supported within the National Institutes of Health (NIH) Health Care Systems Research Collaboratory by cooperative agreementUH2MH106338-01/UH3MH106338-02 from the NIH Common Fund and by UH3MH 106338-05S1 from the National Institute for Mental Health (NIMH). Support was also provided by the NIH Common Fund through cooperative agreement U24AT009676 from the Office of Strategic Coordination within the Office of the NIH director. This investigation was also supported in part by the Patient-Centered Outcomes Research Institute (PCORI) Award (IHS-2017C1-6151).The content is solely the responsibility of the authors and does not necessarily represent the official views of NIH or PCORI or its Board of Governors or Methodology Committee. * Competing interests DFZ has provided forensic expert consultation/testimony related to post-traumatic stress disorder for the Washington State Attorney General, the City of Seattle, and other agencies/firms. * Provenance and peer review Not commissioned; externally peer reviewed. [http://creativecommons.org/licenses/by-nc/4.0/](http://creativecommons.org/licenses/by-nc/4.0/) This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See: [http://creativecommons.org/licenses/by-nc/4.0/](http://creativecommons.org/licenses/by-nc/4.0/). ## References 1. Centers for Disease Control and Prevention. Web-based Injury Statistics Query and Reporting System (WISQARS) [Internet], 2021. 2. Michaels AJ, Michaels CE, Moon CH, Smith JS, Zimmerman MA, Taheri PA, Peterson C. Posttraumatic stress disorder after injury: impact on general health outcome and early risk assessment. J Trauma 1999;47:460–7.[doi:10.1097/00005373-199909000-00005](http://dx.doi.org/10.1097/00005373-199909000-00005)pmid:http://www.ncbi.nlm.nih.gov/pubmed/10498298 [PubMed](http://tsaco.bmj.com/lookup/external-ref?access_num=10498298&link_type=MED&atom=%2Ftsaco%2F7%2F1%2Fe000913.atom) [Web of Science](http://tsaco.bmj.com/lookup/external-ref?access_num=000082607700005&link_type=ISI) 3. Zatzick DF, Rivara FP, Nathens AB, Jurkovich GJ, Wang J, Fan M-Y, Russo J, Salkever DS, Mackenzie EJ. A nationwide US study of post-traumatic stress after hospitalization for physical injury. Psychol Med 2007;37:1469–80.[doi:10.1017/S0033291707000943](http://dx.doi.org/10.1017/S0033291707000943)pmid:http://www.ncbi.nlm.nih.gov/pubmed/17559704 [PubMed](http://tsaco.bmj.com/lookup/external-ref?access_num=17559704&link_type=MED&atom=%2Ftsaco%2F7%2F1%2Fe000913.atom) [Web of Science](http://tsaco.bmj.com/lookup/external-ref?access_num=000250429800009&link_type=ISI) 4. Shih RA, Schell TL, Hambarsoomian K, Belzberg H, Marshall GN. Prevalence of posttraumatic stress disorder and major depression after trauma center hospitalization. J Trauma 2010;69:1560–6.[doi:10.1097/TA.0b013e3181e59c05](http://dx.doi.org/10.1097/TA.0b013e3181e59c05)pmid:http://www.ncbi.nlm.nih.gov/pubmed/20693915 [PubMed](http://tsaco.bmj.com/lookup/external-ref?access_num=20693915&link_type=MED&atom=%2Ftsaco%2F7%2F1%2Fe000913.atom) 5. Shalev A, Liberzon I, Marmar C. Post-Traumatic stress disorder. N Engl J Med 2017;376:2459–69.[doi:10.1056/NEJMra1612499](http://dx.doi.org/10.1056/NEJMra1612499)pmid:http://www.ncbi.nlm.nih.gov/pubmed/28636846 [CrossRef](http://tsaco.bmj.com/lookup/external-ref?access_num=10.1056/NEJMra1612499&link_type=DOI) [PubMed](http://tsaco.bmj.com/lookup/external-ref?access_num=28636846&link_type=MED&atom=%2Ftsaco%2F7%2F1%2Fe000913.atom) 6. deRoon-Cassini TA, Hunt JC, Geier TJ, Warren AM, Ruggiero KJ, Scott K, George J, Halling M, Jurkovich G, Fakhry SM, et al. Screening and treating hospitalized trauma survivors for posttraumatic stress disorder and depression. J Trauma Acute Care Surg 2019;87:440–50.[doi:10.1097/TA.0000000000002370](http://dx.doi.org/10.1097/TA.0000000000002370)pmid:http://www.ncbi.nlm.nih.gov/pubmed/31348404 [PubMed](http://tsaco.bmj.com/lookup/external-ref?access_num=http://www.n&link_type=MED&atom=%2Ftsaco%2F7%2F1%2Fe000913.atom) 7. Russo J, Katon W, Zatzick D. The development of a population-based automated screening procedure for PTSD in acutely injured hospitalized trauma survivors. Gen Hosp Psychiatry 2013;35:485–91.[doi:10.1016/j.genhosppsych.2013.04.016](http://dx.doi.org/10.1016/j.genhosppsych.2013.04.016)pmid:http://www.ncbi.nlm.nih.gov/pubmed/23806535 [CrossRef](http://tsaco.bmj.com/lookup/external-ref?access_num=10.1016/j.genhosppsych.2013.04.016&link_type=DOI) [PubMed](http://tsaco.bmj.com/lookup/external-ref?access_num=23806535&link_type=MED&atom=%2Ftsaco%2F7%2F1%2Fe000913.atom) [Web of Science](http://tsaco.bmj.com/lookup/external-ref?access_num=000324473900008&link_type=ISI) 8. Zatzick D, Jurkovich G, Rivara FP, Russo J, Wagner A, Wang J, Dunn C, Lord SP, Petrie M, Oʼconnor SS, et al. A randomized stepped care intervention trial targeting posttraumatic stress disorder for surgically hospitalized injury survivors. Ann Surg 2013;257:390–9.[doi:10.1097/SLA.0b013e31826bc313](http://dx.doi.org/10.1097/SLA.0b013e31826bc313)pmid:http://www.ncbi.nlm.nih.gov/pubmed/23222034 [CrossRef](http://tsaco.bmj.com/lookup/external-ref?access_num=10.1097/SLA.0b013e31826bc313&link_type=DOI) [PubMed](http://tsaco.bmj.com/lookup/external-ref?access_num=23222034&link_type=MED&atom=%2Ftsaco%2F7%2F1%2Fe000913.atom) 9. Holbrook TL, Anderson JP, Sieber WJ, Browner D, Hoyt DB. Outcome after major trauma: 12-month and 18-month follow-up results from the trauma recovery project. J Trauma 1999;46:765–73.[doi:10.1097/00005373-199905000-00003](http://dx.doi.org/10.1097/00005373-199905000-00003)pmid:http://www.ncbi.nlm.nih.gov/pubmed/10338392 [CrossRef](http://tsaco.bmj.com/lookup/external-ref?access_num=10.1097/00005373-199905000-00003&link_type=DOI) [PubMed](http://tsaco.bmj.com/lookup/external-ref?access_num=10338392&link_type=MED&atom=%2Ftsaco%2F7%2F1%2Fe000913.atom) [Web of Science](http://tsaco.bmj.com/lookup/external-ref?access_num=000080295000005&link_type=ISI) 10. Gabbe BJ, Simpson PM, Harrison JE, Lyons RA, Ameratunga S, Ponsford J, Fitzgerald M, Judson R, Collie A, Cameron PA. Return to work and functional outcomes after major trauma: who recovers, when, and how well? Ann Surg 2016;263:623–32.[doi:10.1097/SLA.0000000000001564](http://dx.doi.org/10.1097/SLA.0000000000001564)pmid:http://www.ncbi.nlm.nih.gov/pubmed/26779977 [PubMed](http://tsaco.bmj.com/lookup/external-ref?access_num=http://www.n&link_type=MED&atom=%2Ftsaco%2F7%2F1%2Fe000913.atom) 11. Greenberg PE, Stiglin LE, Finkelstein SN, Berndt ER. The economic burden of depression in 1990. J Clin Psychiatry 1993;54:405–18.pmid:http://www.ncbi.nlm.nih.gov/pubmed/8270583 [PubMed](http://tsaco.bmj.com/lookup/external-ref?access_num=8270583&link_type=MED&atom=%2Ftsaco%2F7%2F1%2Fe000913.atom) [Web of Science](http://tsaco.bmj.com/lookup/external-ref?access_num=A1993MR34500001&link_type=ISI) 12. Zatzick D, Jurkovich GJ, Rivara FP, Wang J, Fan M-Y, Joesch J, Mackenzie E. A national US study of posttraumatic stress disorder, depression, and work and functional outcomes after hospitalization for traumatic injury. Ann Surg 2008;248:429–37.[doi:10.1097/SLA.0b013e318185a6b8](http://dx.doi.org/10.1097/SLA.0b013e318185a6b8)pmid:http://www.ncbi.nlm.nih.gov/pubmed/18791363 [PubMed](http://tsaco.bmj.com/lookup/external-ref?access_num=18791363&link_type=MED&atom=%2Ftsaco%2F7%2F1%2Fe000913.atom) [Web of Science](http://tsaco.bmj.com/lookup/external-ref?access_num=000259475200016&link_type=ISI) 13. O'Donnell ML, Holmes AC, Creamer MC, Ellen S, Judson R, McFarlane AC, Silove DM, Bryant RA. The role of post-traumatic stress disorder and depression in predicting disability after injury. Med J Aust 2009;190:S71–4.[doi:10.5694/j.1326-5377.2009.tb02474.x](http://dx.doi.org/10.5694/j.1326-5377.2009.tb02474.x)pmid:http://www.ncbi.nlm.nih.gov/pubmed/19351297 [PubMed](http://tsaco.bmj.com/lookup/external-ref?access_num=19351297&link_type=MED&atom=%2Ftsaco%2F7%2F1%2Fe000913.atom) [Web of Science](http://tsaco.bmj.com/lookup/external-ref?access_num=000266222500005&link_type=ISI) 14. Soderstrom CA, Smith GS, Dischinger PC, McDuff DR, Hebel JR, Gorelick DA, Kerns TJ, Ho SM, Read KM. Psychoactive substance use disorders among seriously injured trauma center patients. JAMA 1997;277:1769.[doi:10.1001/jama.1997.03540460033029](http://dx.doi.org/10.1001/jama.1997.03540460033029)pmid:http://www.ncbi.nlm.nih.gov/pubmed/9178789 [CrossRef](http://tsaco.bmj.com/lookup/external-ref?access_num=10.1001/jama.1997.03540460033029&link_type=DOI) [PubMed](http://tsaco.bmj.com/lookup/external-ref?access_num=9178789&link_type=MED&atom=%2Ftsaco%2F7%2F1%2Fe000913.atom) [Web of Science](http://tsaco.bmj.com/lookup/external-ref?access_num=A1997XC49900029&link_type=ISI) 15. El Moheb M, Herrera-Escobar JP, Breen K, Orlas C, Haynes AN, Levy-Carrick NC, Nehra D, Sanchez SE, Salim A, Velmahos G, et al. Long-Term outcomes of psychoactive drug use in trauma patients: a multicenter patient-reported outcomes study. J Trauma Acute Care Surg 2021;90:319–24.[doi:10.1097/TA.0000000000003032](http://dx.doi.org/10.1097/TA.0000000000003032) 16. Ramchand R, Marshall GN, Schell TL, Jaycox LH, Hambarsoomians K, Shetty V, Hinika GS, Cryer HG, Meade P, Belzberg H. Alcohol abuse and illegal drug use among Los Angeles County trauma patients: prevalence and evaluation of single item screener. J Trauma 2009;66:1461–7.[doi:10.1097/TA.0b013e318184821d](http://dx.doi.org/10.1097/TA.0b013e318184821d)pmid:http://www.ncbi.nlm.nih.gov/pubmed/19430255 [CrossRef](http://tsaco.bmj.com/lookup/external-ref?access_num=10.1097/TA.0b013e318184821d&link_type=DOI) [PubMed](http://tsaco.bmj.com/lookup/external-ref?access_num=19430255&link_type=MED&atom=%2Ftsaco%2F7%2F1%2Fe000913.atom) [Web of Science](http://tsaco.bmj.com/lookup/external-ref?access_num=000266021700038&link_type=ISI) 17. Shymon SJ, Arthur D'Ann, Keeling P, Rashidi S, Kwong LM, Andrawis JP. Current illicit drug use profile of orthopaedic trauma patients and its effect on hospital length of stay. Injury 2020;51:887–91.[doi:10.1016/j.injury.2020.02.077](http://dx.doi.org/10.1016/j.injury.2020.02.077)pmid:http://www.ncbi.nlm.nih.gov/pubmed/32145902 [PubMed](http://tsaco.bmj.com/lookup/external-ref?access_num=http://www.n&link_type=MED&atom=%2Ftsaco%2F7%2F1%2Fe000913.atom) 18. Michaud-Germain C, Tardif P-A, Nadeau A, Gagnon A-P, Mercier Éric. et al. Contribution of substance use in acute injuries with REGARDS to the intent, nature and context of injury: a CHIRPP database study. Cureus 2020;142:e10282-e.[doi:10.7759/cureus.10282](http://dx.doi.org/10.7759/cureus.10282) 19. Zatzick D, Donovan D, Dunn C, Russo J, Wang J, Jurkovich G, Rivara F, Whiteside L, Ries R, Gentilello L. Substance use and posttraumatic stress disorder symptoms in trauma center patients receiving mandated alcohol screening and brief intervention. J Subst Abuse Treat 2012;43:410–7.[doi:10.1016/j.jsat.2012.08.009](http://dx.doi.org/10.1016/j.jsat.2012.08.009)pmid:http://www.ncbi.nlm.nih.gov/pubmed/22999379 [PubMed](http://tsaco.bmj.com/lookup/external-ref?access_num=22999379&link_type=MED&atom=%2Ftsaco%2F7%2F1%2Fe000913.atom) 20. Warren AM, Foreman ML, Bennett MM, Petrey LB, Reynolds M, Patel S, Roden-Foreman K. Posttraumatic stress disorder following traumatic injury at 6 months: associations with alcohol use and depression. J Trauma Acute Care Surg 2014;76:517–22.[doi:10.1097/TA.0000000000000110](http://dx.doi.org/10.1097/TA.0000000000000110)pmid:http://www.ncbi.nlm.nih.gov/pubmed/24458060 [PubMed](http://tsaco.bmj.com/lookup/external-ref?access_num=http://www.n&link_type=MED&atom=%2Ftsaco%2F7%2F1%2Fe000913.atom) 21. McLaughlin C, Kearns NT, Bennett M, Roden-Foreman JW, Roden-Foreman K, Rainey EE, Funk G, Powers MB, Warren AM. Alcohol and drug toxicology screens at time of hospitalization do not predict PTSD or depression after traumatic injury. Am J Surg 2017;214:390–6.[doi:10.1016/j.amjsurg.2017.06.026](http://dx.doi.org/10.1016/j.amjsurg.2017.06.026)pmid:http://www.ncbi.nlm.nih.gov/pubmed/28683894 [PubMed](http://tsaco.bmj.com/lookup/external-ref?access_num=http://www.n&link_type=MED&atom=%2Ftsaco%2F7%2F1%2Fe000913.atom) 22. Zatzick D, Jurkovich G, Heagerty P, Russo J, Darnell D, Parker L, Roberts MK, Moodliar R, Engstrom A, Wang J, et al. Stepped collaborative care targeting posttraumatic stress disorder symptoms and comorbidity for us trauma care systems: a randomized clinical trial. JAMA Surg 2021;156:430.[doi:10.1001/jamasurg.2021.0131](http://dx.doi.org/10.1001/jamasurg.2021.0131)pmid:http://www.ncbi.nlm.nih.gov/pubmed/33688908 [PubMed](http://tsaco.bmj.com/lookup/external-ref?access_num=http://www.n&link_type=MED&atom=%2Ftsaco%2F7%2F1%2Fe000913.atom) 23. Zatzick DF, Russo J, Darnell D, Chambers DA, Palinkas L, Van Eaton E, Wang J, Ingraham LM, Guiney R, Heagerty P, et al. An effectiveness-implementation hybrid trial study protocol targeting posttraumatic stress disorder and comorbidity. Implement Sci 2016;11:58.[doi:10.1186/s13012-016-0424-4](http://dx.doi.org/10.1186/s13012-016-0424-4)pmid:http://www.ncbi.nlm.nih.gov/pubmed/27130272 [PubMed](http://tsaco.bmj.com/lookup/external-ref?access_num=http://www.n&link_type=MED&atom=%2Ftsaco%2F7%2F1%2Fe000913.atom) 24. Roberts MK, Fisher DM, Parker LE, Darnell D, Sugarman J, Carrithers J, Weinfurt K, Jurkovich G, Zatzick D. Ethical and regulatory concerns in pragmatic clinical trial monitoring and oversight. Ethics Hum Res 2020;42:29–37.[doi:10.1002/eahr.500066](http://dx.doi.org/10.1002/eahr.500066)pmid:http://www.ncbi.nlm.nih.gov/pubmed/32937035 [PubMed](http://tsaco.bmj.com/lookup/external-ref?access_num=http://www.n&link_type=MED&atom=%2Ftsaco%2F7%2F1%2Fe000913.atom) 25. Nehra D, Bulger EM, Maier RV, Moloney KE, Russo J, Wang J, Anderson K, Zatzick DF. A prospective US national trauma center study of firearm injury survivors weapon carriage and posttraumatic stress disorder symptoms. Ann Surg 2021;274:e364–9.[doi:10.1097/SLA.0000000000005043](http://dx.doi.org/10.1097/SLA.0000000000005043)pmid:http://www.ncbi.nlm.nih.gov/pubmed/34225296 [PubMed](http://tsaco.bmj.com/lookup/external-ref?access_num=http://www.n&link_type=MED&atom=%2Ftsaco%2F7%2F1%2Fe000913.atom) 26. Engstrom A, Moloney K, Nguyen J, Parker L, Roberts M, Moodliar R, Russo J, Wang J, Scheuer H, Zatzick D. A pragmatic clinical trial approach to assessing and monitoring suicidal ideation: results from a national us trauma care system study. Psychiatry 2022;85:13–29.[doi:10.1080/00332747.2021.1991200](http://dx.doi.org/10.1080/00332747.2021.1991200)pmid:http://www.ncbi.nlm.nih.gov/pubmed/34932440 [PubMed](http://tsaco.bmj.com/lookup/external-ref?access_num=http://www.n&link_type=MED&atom=%2Ftsaco%2F7%2F1%2Fe000913.atom) 27. 1. Stamm BH Weathers F, Ford J. Psychometric review of PTSD Checklist (PCL-C, PCL-S, PCL-M, PCL-PR). Stamm BH, ed. Measurement of stress, trauma, and adaptation. Lutherville, MD: The Sidran Press, 1996:250–1. 28. Moodliar R, Russo J, Bedard-Gilligan M, Moloney K, Johnson P, Seo S, Vaziri N, Zatzick D. A pragmatic approach to psychometric comparisons between the DSM-IV and DSM-5 posttraumatic stress disorder (PTSD) checklists in acutely injured trauma patients. Psychiatry 2020;83:390–401.[doi:10.1080/00332747.2020.1762396](http://dx.doi.org/10.1080/00332747.2020.1762396)pmid:http://www.ncbi.nlm.nih.gov/pubmed/32762319 [PubMed](http://tsaco.bmj.com/lookup/external-ref?access_num=http://www.n&link_type=MED&atom=%2Ftsaco%2F7%2F1%2Fe000913.atom) 29. Babor TF, Grant M. From clinical research to secondary prevention: international collaboration in the development of the alcohol use disorders identification test. Alcohol Health and Research World 1989;13:371–4. 30. Bradley KA, DeBenedetti AF, Volk RJ, Williams EC, Frank D, Kivlahan DR. AUDIT-C as a brief screen for alcohol misuse in primary care. Alcohol Clin Exp Res 2007;31:1208–17.[doi:10.1111/j.1530-0277.2007.00403.x](http://dx.doi.org/10.1111/j.1530-0277.2007.00403.x)pmid:http://www.ncbi.nlm.nih.gov/pubmed/17451397 [CrossRef](http://tsaco.bmj.com/lookup/external-ref?access_num=10.1111/j.1530-0277.2007.00403.x&link_type=DOI) [PubMed](http://tsaco.bmj.com/lookup/external-ref?access_num=17451397&link_type=MED&atom=%2Ftsaco%2F7%2F1%2Fe000913.atom) [Web of Science](http://tsaco.bmj.com/lookup/external-ref?access_num=000247318400014&link_type=ISI) 31. Smith PC, Schmidt SM, Allensworth-Davies D, Saitz R. A single-question screening test for drug use in primary care. Arch Intern Med 2010;170:1155–60.[doi:10.1001/archinternmed.2010.140](http://dx.doi.org/10.1001/archinternmed.2010.140)pmid:http://www.ncbi.nlm.nih.gov/pubmed/20625025 [CrossRef](http://tsaco.bmj.com/lookup/external-ref?access_num=10.1001/archinternmed.2010.140&link_type=DOI) [PubMed](http://tsaco.bmj.com/lookup/external-ref?access_num=20625025&link_type=MED&atom=%2Ftsaco%2F7%2F1%2Fe000913.atom) [Web of Science](http://tsaco.bmj.com/lookup/external-ref?access_num=000279797700014&link_type=ISI) 32. Heinze G, Wallisch C, Dunkler D. Variable selection - A review and recommendations for the practicing statistician. Biom J 2018;60:431–49.[doi:10.1002/bimj.201700067](http://dx.doi.org/10.1002/bimj.201700067)pmid:http://www.ncbi.nlm.nih.gov/pubmed/29292533 [PubMed](http://tsaco.bmj.com/lookup/external-ref?access_num=http://www.n&link_type=MED&atom=%2Ftsaco%2F7%2F1%2Fe000913.atom) 33. McCauley JL, Killeen T, Gros DF, Brady KT, Back SE. Posttraumatic stress disorder and co-occurring substance use disorders: advances in assessment and treatment. Clin Psychol 2012;19:283–304.[doi:10.1111/cpsp.12006](http://dx.doi.org/10.1111/cpsp.12006)pmid:http://www.ncbi.nlm.nih.gov/pubmed/24179316 [CrossRef](http://tsaco.bmj.com/lookup/external-ref?access_num=10.1111/cpsp.12006&link_type=DOI) [PubMed](http://tsaco.bmj.com/lookup/external-ref?access_num=http://www.n&link_type=MED&atom=%2Ftsaco%2F7%2F1%2Fe000913.atom) 34. Dworkin ER, Wanklyn S, Stasiewicz PR, Coffey SF. Ptsd symptom presentation among people with alcohol and drug use disorders: comparisons by substance of abuse. Addict Behav 2018;76:188–94.[doi:10.1016/j.addbeh.2017.08.019](http://dx.doi.org/10.1016/j.addbeh.2017.08.019)pmid:http://www.ncbi.nlm.nih.gov/pubmed/28846939 [PubMed](http://tsaco.bmj.com/lookup/external-ref?access_num=http://www.n&link_type=MED&atom=%2Ftsaco%2F7%2F1%2Fe000913.atom) 35. Bulger EM, Johnson P, Parker L, Moloney KE, Roberts MK, Vaziri N, Seo S, Nehra D, Thomas P, Zatzick D. Nationwide survey of trauma center screening and intervention practices for posttraumatic stress disorder, firearm violence, mental health, and substance use disorders. J Am Coll Surg 2022;234:274–87.[doi:10.1097/XCS.0000000000000064](http://dx.doi.org/10.1097/XCS.0000000000000064)pmid:http://www.ncbi.nlm.nih.gov/pubmed/35213489 [PubMed](http://tsaco.bmj.com/lookup/external-ref?access_num=http://www.n&link_type=MED&atom=%2Ftsaco%2F7%2F1%2Fe000913.atom) 36. Zatzick D, Donovan DM, Jurkovich G, Gentilello L, Dunn C, Russo J, Wang J, Zatzick CD, Love J, McFadden C, et al. Disseminating alcohol screening and brief intervention at trauma centers: a policy-relevant cluster randomized effectiveness trial. Addiction 2014;109:754–65.[doi:10.1111/add.12492](http://dx.doi.org/10.1111/add.12492)pmid:http://www.ncbi.nlm.nih.gov/pubmed/24450612 [CrossRef](http://tsaco.bmj.com/lookup/external-ref?access_num=10.1111/add.12492&link_type=DOI) [PubMed](http://tsaco.bmj.com/lookup/external-ref?access_num=24450612&link_type=MED&atom=%2Ftsaco%2F7%2F1%2Fe000913.atom) 37. Veach LJ, Moro RR, Miller P, Reboussin BA, Ivers NN, Rogers JL, O'Brien MC. et al. Alcohol counseling in hospital trauma: examining two brief interventions. Journal of Counseling & Development 2018;96:243–53.[doi:10.1002/jcad.12199](http://dx.doi.org/10.1002/jcad.12199) 38. Zatzick D, Roy-Byrne P, Russo J, Rivara F, Droesch R, Wagner A, Dunn C, Jurkovich G, Uehara E, Katon W. A randomized effectiveness trial of stepped collaborative care for acutely injured trauma survivors. Arch Gen Psychiatry 2004;61:498–506.[doi:10.1001/archpsyc.61.5.498](http://dx.doi.org/10.1001/archpsyc.61.5.498)pmid:http://www.ncbi.nlm.nih.gov/pubmed/15123495 [CrossRef](http://tsaco.bmj.com/lookup/external-ref?access_num=10.1001/archpsyc.61.5.498&link_type=DOI) [PubMed](http://tsaco.bmj.com/lookup/external-ref?access_num=15123495&link_type=MED&atom=%2Ftsaco%2F7%2F1%2Fe000913.atom) [Web of Science](http://tsaco.bmj.com/lookup/external-ref?access_num=000221178800009&link_type=ISI) 39. Zatzick D, O'Connor SS, Russo J, Wang J, Bush N, Love J, Peterson R, Ingraham L, Darnell D, Whiteside L, et al. Technology-Enhanced stepped collaborative care targeting posttraumatic stress disorder and comorbidity after injury: a randomized controlled trial. J Trauma Stress 2015;28:391–400.[doi:10.1002/jts.22041](http://dx.doi.org/10.1002/jts.22041)pmid:http://www.ncbi.nlm.nih.gov/pubmed/26467327 [PubMed](http://tsaco.bmj.com/lookup/external-ref?access_num=http://www.n&link_type=MED&atom=%2Ftsaco%2F7%2F1%2Fe000913.atom) 40. Rothbaum BO, Kearns MC, Price M, Malcoun E, Davis M, Ressler KJ, Lang D, Houry D. Early intervention may prevent the development of posttraumatic stress disorder: a randomized pilot civilian study with modified prolonged exposure. Biol Psychiatry 2012;72:957–63.[doi:10.1016/j.biopsych.2012.06.002](http://dx.doi.org/10.1016/j.biopsych.2012.06.002)pmid:http://www.ncbi.nlm.nih.gov/pubmed/22766415 [PubMed](http://tsaco.bmj.com/lookup/external-ref?access_num=22766415&link_type=MED&atom=%2Ftsaco%2F7%2F1%2Fe000913.atom) 41. O'Donnell ML, Lau W, Tipping S, Holmes ACN, Ellen S, Judson R, Varker T, Elliot P, Bryant RA, Creamer MC, et al. Stepped early psychological intervention for posttraumatic stress disorder, other anxiety disorders, and depression following serious injury. J Trauma Stress 2012;25:125–33.[doi:10.1002/jts.21677](http://dx.doi.org/10.1002/jts.21677)pmid:http://www.ncbi.nlm.nih.gov/pubmed/22522725 [CrossRef](http://tsaco.bmj.com/lookup/external-ref?access_num=10.1002/jts.21677&link_type=DOI) [PubMed](http://tsaco.bmj.com/lookup/external-ref?access_num=22522725&link_type=MED&atom=%2Ftsaco%2F7%2F1%2Fe000913.atom) [Web of Science](http://tsaco.bmj.com/lookup/external-ref?access_num=000303041500001&link_type=ISI) 42. Larsen SE, Hunt JC, Geier T, Heyrman K, Schumann N, Brandolino A, Timmer-Murillo S, Bergner C, Larson C, deRoon-Cassini TA. A randomized trial of modified prolonged exposure to prevent the development of posttraumatic stress disorder in patients hospitalized with traumatic injuries. J Trauma Stress 2021;34:104–15.[doi:10.1002/jts.22580](http://dx.doi.org/10.1002/jts.22580)pmid:http://www.ncbi.nlm.nih.gov/pubmed/33269808 [PubMed](http://tsaco.bmj.com/lookup/external-ref?access_num=http://www.n&link_type=MED&atom=%2Ftsaco%2F7%2F1%2Fe000913.atom) 43. Skogstad L, Hem E, Sandvik L, Ekeberg O. Nurse-Led psychological intervention after physical traumas: a randomized controlled trial. J Clin Med Res 2015;7:339–47.[doi:10.14740/jocmr2082w](http://dx.doi.org/10.14740/jocmr2082w)pmid:http://www.ncbi.nlm.nih.gov/pubmed/25780483 [PubMed](http://tsaco.bmj.com/lookup/external-ref?access_num=http://www.n&link_type=MED&atom=%2Ftsaco%2F7%2F1%2Fe000913.atom) 44. Wade DM, Mouncey PR, Richards-Belle A, Wulff J, Harrison DA, Sadique MZ, Grieve RD, Emerson LM, Mason AJ, Aaronovitch D, et al. Effect of a nurse-led preventive psychological intervention on symptoms of posttraumatic stress disorder among critically ill patients: a randomized clinical trial. JAMA 2019;321:665–75.[doi:10.1001/jama.2019.0073](http://dx.doi.org/10.1001/jama.2019.0073)pmid:http://www.ncbi.nlm.nih.gov/pubmed/30776295 [PubMed](http://tsaco.bmj.com/lookup/external-ref?access_num=http://www.n&link_type=MED&atom=%2Ftsaco%2F7%2F1%2Fe000913.atom) 45. Giummarra MJ, Lennox A, Dali G, Costa B, Gabbe BJ. Early psychological interventions for posttraumatic stress, depression and anxiety after traumatic injury: a systematic review and meta-analysis. Clin Psychol Rev 2018;62:11–36.[doi:10.1016/j.cpr.2018.05.001](http://dx.doi.org/10.1016/j.cpr.2018.05.001)pmid:http://www.ncbi.nlm.nih.gov/pubmed/29754102 [CrossRef](http://tsaco.bmj.com/lookup/external-ref?access_num=10.1016/j.cpr.2018.05.001&link_type=DOI) [PubMed](http://tsaco.bmj.com/lookup/external-ref?access_num=http://www.n&link_type=MED&atom=%2Ftsaco%2F7%2F1%2Fe000913.atom) 46. Koepsell TD, Zatzick DF, Rivara FP. Estimating the population impact of preventive interventions from randomized trials. Am J Prev Med 2011;40:191–8.[doi:10.1016/j.amepre.2010.10.022](http://dx.doi.org/10.1016/j.amepre.2010.10.022)pmid:http://www.ncbi.nlm.nih.gov/pubmed/21238868 [CrossRef](http://tsaco.bmj.com/lookup/external-ref?access_num=10.1016/j.amepre.2010.10.022&link_type=DOI) [PubMed](http://tsaco.bmj.com/lookup/external-ref?access_num=21238868&link_type=MED&atom=%2Ftsaco%2F7%2F1%2Fe000913.atom) 47. D'Onofrio G, O'Connor PG, Pantalon MV, Chawarski MC, Busch SH, Owens PH, Bernstein SL, Fiellin DA. Emergency department-initiated buprenorphine/naloxone treatment for opioid dependence: a randomized clinical trial. JAMA 2015;313:1636–44.[doi:10.1001/jama.2015.3474](http://dx.doi.org/10.1001/jama.2015.3474)pmid:http://www.ncbi.nlm.nih.gov/pubmed/25919527 [CrossRef](http://tsaco.bmj.com/lookup/external-ref?access_num=10.1001/jama.2015.3474&link_type=DOI) [PubMed](http://tsaco.bmj.com/lookup/external-ref?access_num=25919527&link_type=MED&atom=%2Ftsaco%2F7%2F1%2Fe000913.atom) 48. Whiteside LK, Huynh L, Morse S, Hall J, Meurer W, Banta-Green CJ, Scheuer H, Cunningham R, McGovern M, Zatzick DF. The emergency department longitudinal integrated care (ED-LINC) intervention targeting opioid use disorder: a pilot randomized clinical trial. J Subst Abuse Treat 2022;136:108666.[doi:10.1016/j.jsat.2021.108666](http://dx.doi.org/10.1016/j.jsat.2021.108666)pmid:http://www.ncbi.nlm.nih.gov/pubmed/34952745 [PubMed](http://tsaco.bmj.com/lookup/external-ref?access_num=http://www.n&link_type=MED&atom=%2Ftsaco%2F7%2F1%2Fe000913.atom) 49. Breslau N, Davis GC, Schultz LR. Posttraumatic stress disorder and the incidence of nicotine, alcohol, and other drug disorders in persons who have experienced trauma. Arch Gen Psychiatry 2003;60:289–94.[doi:10.1001/archpsyc.60.3.289](http://dx.doi.org/10.1001/archpsyc.60.3.289)pmid:http://www.ncbi.nlm.nih.gov/pubmed/12622662 [CrossRef](http://tsaco.bmj.com/lookup/external-ref?access_num=10.1001/archpsyc.60.3.289&link_type=DOI) [PubMed](http://tsaco.bmj.com/lookup/external-ref?access_num=12622662&link_type=MED&atom=%2Ftsaco%2F7%2F1%2Fe000913.atom) [Web of Science](http://tsaco.bmj.com/lookup/external-ref?access_num=000181572200009&link_type=ISI) 50. American College of Surgeons Committee on Trauma. Resources for optimal care of the injured patient: 2006. 4th ed. Chicago, IL: American College of Surgeons, 2006.