Longitudinal Recovery Following Repetitive Traumatic Brain Injury

Leila L Etemad; John K Yue; Jason Barber; Lindsay D Nelson; Yelena G Bodien; Gabriela G Satris; Patrick J Belton; Debbie Y Madhok; J Russell Huie; Sabah Hamidi; Joye X Tracey; Bukre C Coskun; Justin C Wong; Esther L Yuh; Pratik Mukherjee; Amy J Markowitz; Michael C Huang; Phiroz E Tarapore; Claudia S Robertson; Ramon Diaz-Arrastia; Murray B Stein; Adam R Ferguson; Ava M Puccio; David O Okonkwo; Joseph T Giacino; Michael A McCrea; Geoffrey T Manley; Nancy R Temkin; Anthony M DiGiorgio

doi:10.1001/jamanetworkopen.2023.35804

. 2023 Sep 26;6(9):e2335804. doi: 10.1001/jamanetworkopen.2023.35804

Longitudinal Recovery Following Repetitive Traumatic Brain Injury

Leila L Etemad ^1,^2,^✉, John K Yue ^1,², Jason Barber ³, Lindsay D Nelson ^4,⁵, Yelena G Bodien ^6,⁷, Gabriela G Satris ^1,², Patrick J Belton ^1,², Debbie Y Madhok ⁸, J Russell Huie ^1,², Sabah Hamidi ^1,², Joye X Tracey ^1,², Bukre C Coskun ^1,², Justin C Wong ^1,², Esther L Yuh ^2,⁹, Pratik Mukherjee ^2,⁹, Amy J Markowitz ^1,², Michael C Huang ^1,², Phiroz E Tarapore ^1,², Claudia S Robertson ¹⁰, Ramon Diaz-Arrastia ¹¹, Murray B Stein ¹², Adam R Ferguson ^1,^2,¹³, Ava M Puccio ¹⁴, David O Okonkwo ¹⁴, Joseph T Giacino ^6,⁷, Michael A McCrea ^4,⁵, Geoffrey T Manley ^1,², Nancy R Temkin ³, Anthony M DiGiorgio ^1,^2,^15,^✉, for the TRACK-TBI Investigators

¹Department of Neurological Surgery, University of California, San Francisco

²Brain and Spinal Injury Center, Zuckerberg San Francisco General Hospital and Trauma Center, San Francisco, California

³Departments of Neurological Surgery and Biostatistics, University of Washington, Seattle

⁴Department of Neurosurgery, Medical College of Wisconsin, Milwaukee

⁵Department of Neurology, Medical College of Wisconsin, Milwaukee

⁶Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston

⁷Department of Physical Medicine and Rehabilitation, Spaulding Rehabilitation Hospital, Harvard Medical School, Charlestown, Massachusetts

⁸Department of Emergency Medicine, University of California, San Francisco

⁹Department of Radiology and Biomedical Imaging, University of California, San Francisco

¹⁰Department of Neurological Surgery, Baylor College of Medicine, Houston, Texas

¹¹Department of Neurology, University of Pennsylvania, Philadelphia

¹²Department of Psychiatry, University of California, San Diego

¹³San Francisco Veterans Affairs Healthcare System, San Francisco, California

¹⁴Department of Neurological Surgery, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania

¹⁵Institute of Health Policy Studies, University of California, San Francisco

Accepted for Publication: August 21, 2023.

Published: September 26, 2023. doi:10.1001/jamanetworkopen.2023.35804

^✉

Corresponding Author: Leila L. Etemad, BA (leila.etemad@ucsf.edu), and Anthony M. DiGiorgio, DO, MHA (anthony.digiorgio@ucsf.edu), Department of Neurological, University of California, San Francisco, 2540 23rd St, Bldg 7, 5th Floor, Room 5212, Box 0899, San Francisco, CA 94143.

Author Contributions: Mr Barber and Dr Temkin had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. Ms Etemad and Dr Yue are co–first authors. Drs Manley, Temkin, and DiGiorgio are co–senior authors.

Concept and design: Etemad, Yue, Madhok, Hamidi, Markowitz, Huang, Diaz-Arrastia, Ferguson, Okonkwo, McCrea, Temkin, DiGiorgio.

Acquisition, analysis, or interpretation of data: Etemad, Yue, Barber, Nelson, Bodien, Satris, Belton, Huie, Tracey, Coskun, Wong, Yuh, Mukherjee, Tarapore, Robertson, Diaz-Arrastia, Stein, Ferguson, Puccio, Okonkwo, Giacino, McCrea, Manley, Temkin, DiGiorgio.

Drafting of the manuscript: Etemad, Yue, Belton, Huie, Hamidi, Okonkwo, DiGiorgio.

Critical review of the manuscript for important intellectual content: Etemad, Yue, Barber, Nelson, Bodien, Satris, Belton, Madhok, Tracey, Coskun, Wong, Yuh, Mukherjee, Markowitz, Huang, Tarapore, Robertson, Diaz-Arrastia, Stein, Ferguson, Puccio, Okonkwo, Giacino, McCrea, Manley, Temkin, DiGiorgio.

Statistical analysis: Etemad, Yue, Barber, Belton, Coskun, Ferguson, Okonkwo, Temkin.

Obtained funding: Yue, Mukherjee, Diaz-Arrastia, Okonkwo, Giacino, Manley, Temkin.

Administrative, technical, or material support: Yue, Bodien, Satris, Hamidi, Tracey, Coskun, Wong, Mukherjee, Tarapore, Robertson, Ferguson, Puccio, Okonkwo, McCrea.

Supervision: Yue, Satris, Huie, Tracey, Huang, Tarapore, Diaz-Arrastia, Ferguson, Okonkwo, McCrea, DiGiorgio.

Conflict of Interest Disclosures: Dr Yue reported grants from the Neurosurgery Research and Education Foundation and the Bagan Family Foundation Research Fellowship during the conduct of the study. Dr Nelson reported grants from the National Institute of Neurological Disorders and Stroke, US Centers for Disease Control and Prevention, the US Department of Defense, Medical Technology Enterprise Consortium, and Medical College of Wisconsin Advancing a Healthier Wisconsin Endowment outside the submitted work. Dr Bodien reported grants from the National Institute of Neurological Disorders and Stroke during the conduct of the study. Dr Yuh reported grants from the National Institutes of Health and the Department of Defense during the conduct of the study. Dr Mukherjee reported grants from the National Institutes of Health during the conduct of the study and has a patent for USPTO 62/269778 issued. Dr Markowitz reported grants from the Department of Defense TBI Endpoints Development Initiative during the conduct of the study. Dr Robertson reported grants from the National Institutes of Health, Department of Defense, and National Football League during the conduct of the study. Dr Diaz-Arrastia reported grants and personal fees from BrainBox Solutions and holds stock options in BrainBox Solutions outside the submitted work. Dr Stein reported personal fees from atai Life Sciences, BigHealth, Biogen, Bionomics, BioXcel Therapeutics, Boehringer Ingelheim, Eisai, EmpowerPharm, Engrail Therapeutics, Janssen, Jazz Pharmaceuticals, NeuroTrauma Sciences, PureTech Health, Roche/Genentech, Sage Therapeutics, and Sumitomo Pharma and holds stock options in Oxeia Biopharmaceuticals and EpiVario outside the submitted work. Dr Ferguson reported grants from the National Institutes of Health, Veterans Affairs, Craig H. Neilsen Foundation, and Wings for Life Foundation during the conduct of the study; grants from Santa Clara Valley Medical Center; personal fees from Neuronasal and Spine X; and nonfinancial support from DataRobot outside the submitted work. Dr Giacino reported grants from the Department of Defense and National Institute of Neurological Disorders and Stroke during the conduct of the study. Dr McCrea reported grants from the National Institutes of Health during the conduct of the study; grants from the National Institutes of Health, Centers for Disease Control and Prevention, Deptartment of Defense, National Collegiate Athletics Association, and National Football League; and has served as a consultant for NeuroTrauma Sciences outside the submitted work. Dr Manley reported grants from the Department of Defense, National Institutes of Health, National Football League, and US Department of Energy during the conduct of the study and has received support from NeuroTrauma Sciences and One Mind outside the submitted work. Dr Temkin reported grants from the US Federal Government and the National Football League Foundation during the conduct of the study. Dr DiGiorgio reported grants from Mercatus Center at George Mason University, DePuy Synthes, and AO Spine as well as personal fees from the National Football League outside the submitted work. No other disclosures were reported.

Funding/Support: This work was supported by the following grants: National Institute of Neurological Disorders and Stroke grants RC2NS069409, U01NS086090, and U01NS1365885 (Dr Manley); National Institute of Neurological Disorders and Stroke grant U01NS114140 (Dr Diaz-Arrastia); US Department of Defense grants W81XWH-13-1-0441, W81XWH-14-2-0176, and W81XWH-18-2-0042 (Dr Manley); the Mercatus Center at George Mason University (University of California, San Francisco grant A139895; Dr DiGiorgio), Neurosurgery Research and Education Foundation and Bagan Family Foundation Research Fellowship (University of California, San Francisco grant A139203; Dr Yue).

Role of the Funder/Sponsor: The funders had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.

Group Information: The TRACK-TBI Investigators are listed in Supplement 2.

Data Sharing Statement: See Supplement 3.

^✉

Corresponding author.

PMCID: PMC10523170 PMID: 37751204

Key Points

Question

What are the functional, postconcussive, mental health, and health-related quality-of-life outcomes at 1 year and 3 to 7 years postinjury among adults with postindex traumatic brain injuries (TBIs)?

Findings

In this cohort study of 2417 patients with TBI, compared with those without postindex TBIs, individuals with postindex TBIs at 1 year and 3 to 7 years were more symptomatic across functional, postconcussive, mental health, and health-related quality of life domains, with greatest symptom burden observed in individuals with multiple postindex TBIs.

Meaning

In this study, participants with postindex TBIs were a symptomatic cohort in long-term recovery, and prevention, education, counseling, and follow-up care is needed for these at-risk patients.

This cohort study evaluates associations between sustaining 1 or more TBIs after study enrollment and functional, postconcussive, mental health, and health-related quality-of-life outcomes at 1 year and 3 to 7 years.

Abstract

Importance

One traumatic brain injury (TBI) increases the risk of subsequent TBIs. Research on longitudinal outcomes of civilian repetitive TBIs is limited.

Objective

To investigate associations between sustaining 1 or more TBIs (ie, postindex TBIs) after study enrollment (ie, index TBIs) and multidimensional outcomes at 1 year and 3 to 7 years.

Design, Setting, and Participants

This cohort study included participants presenting to emergency departments enrolled within 24 hours of TBI in the prospective, 18-center Transforming Research and Clinical Knowledge in Traumatic Brain Injury (TRACK-TBI) study (enrollment years, February 2014 to July 2020). Participants who completed outcome assessments at 1 year and 3 to 7 years were included. Data were analyzed from September 2022 to August 2023.

Exposures

Postindex TBI(s).

Main Outcomes and Measures

Demographic and clinical factors, prior TBI (ie, preindex TBI), and functional (Glasgow Outcome Scale–Extended [GOSE]), postconcussive (Rivermead Post-Concussion Symptoms Questionnaire [RPQ]), psychological distress (Brief Symptom Inventory-18 [BSI-18]), depressive (Patient Health Questionnaire-9 [PHQ-9]), posttraumatic stress disorder (PTSD; PTSD Checklist for DSM-5 [PCL-5]), and health-related quality-of-life (Quality of Life After Brain Injury–Overall Scale [QOLIBRI-OS]) outcomes were assessed. Adjusted mean differences (aMDs) and adjusted relative risks are reported with 95% CIs.

Results

Of 2417 TRACK-TBI participants, 1572 completed the outcomes assessment at 1 year (1049 [66.7%] male; mean [SD] age, 41.6 [17.5] years) and 1084 completed the outcomes assessment at 3 to 7 years (714 [65.9%] male; mean [SD] age, 40.6 [17.0] years). At 1 year, a total of 60 participants (4%) were Asian, 255 (16%) were Black, 1213 (77%) were White, 39 (2%) were another race, and 5 (0.3%) had unknown race. At 3 to 7 years, 39 (4%) were Asian, 149 (14%) were Black, 868 (80%) were White, 26 (2%) had another race, and 2 (0.2%) had unknown race. A total of 50 (3.2%) and 132 (12.2%) reported 1 or more postindex TBIs at 1 year and 3 to 7 years, respectively. Risk factors for postindex TBI were psychiatric history, preindex TBI, and extracranial injury severity. At 1 year, compared with those without postindex TBI, participants with postindex TBI had worse functional recovery (GOSE score of 8: adjusted relative risk, 0.57; 95% CI, 0.34-0.96) and health-related quality of life (QOLIBRI-OS: aMD, −15.9; 95% CI, −22.6 to −9.1), and greater postconcussive symptoms (RPQ: aMD, 8.1; 95% CI, 4.2-11.9), psychological distress symptoms (BSI-18: aMD, 5.3; 95% CI, 2.1-8.6), depression symptoms (PHQ-9: aMD, 3.0; 95% CI, 1.5-4.4), and PTSD symptoms (PCL-5: aMD, 7.8; 95% CI, 3.2-12.4). At 3 to 7 years, these associations remained statistically significant. Multiple (2 or more) postindex TBIs were associated with poorer outcomes across all domains.

Conclusions and Relevance

In this cohort study of patients with acute TBI, postindex TBI was associated with worse symptomatology across outcome domains at 1 year and 3 to 7 years postinjury, and there was a dose-dependent response with multiple postindex TBIs. These results underscore the critical need to provide TBI prevention, education, counseling, and follow-up care to at-risk patients.

Introduction

Traumatic brain injury (TBI) is a leading cause of death and disability in the US and worldwide, generating 2.8 million annual TBI-related emergency department (ED) visits, 280 000 hospitalizations, and 64 000 deaths in the US alone.^1,2,3 Individuals who sustain 1 TBI are at a significantly increased risk of sustaining another.^4,5,6,7 Repetitive TBI is frequently studied in contact-sport athletes and military personnel. History of multiple concussions is correlated with depression,^8,9 delayed recovery,^10,11 cognitive impairment,^12,13 and chronic traumatic encephalopathy.¹⁴ However, research on repetitive TBI and its longitudinal association with outcomes in the general population is limited.

TBI may progress from primary injury to chronic disease. Repetitive TBI rates range from 7% to 23% in civillians.^{4,5,6,15,16,17,18} Prior TBI increases the risks of psychiatric symptoms^4,5 and decreased satisfaction with life.¹⁹ In a 2013 US multicenter study, participants with prior TBI reported worse 6-month postconcussive symptoms (PCS), psychological distress, verbal memory, and processing speed.⁶ A population-based study with matched controls in New Zealand¹⁸ found TBIs sustained after the index TBI of study enrollment within 1 year were associated with worsened PCS.²⁰ In a large TBI Model Systems study, moderate or severe postindex TBI conferred worse disability rating scores and cognitive dependence at 1, 2, and 5 years after index TBI.²¹

To better characterize the association of repetitive TBI with recovery, we investigated the association between postindex TBI and functional, PCS, psychological distress, posttraumatic stress disorder (PTSD), depressive, and health-related quality-of-life (HRQOL) outcomes at 1 year and 3 to 7 years. We hypothesized that postindex TBI would be associated with poorer outcomes and that multiple postindex TBIs would be associated with more adverse outcomes at 3 to 7 years.

Methods

Participants and Study Design

The prospective, observational Transforming Research and Clinical Knowledge in Traumatic Brain Injury (TRACK-TBI) study enrolled participants with TBI at 18 US level I trauma centers between February 26, 2014, and July 3, 2018.^22,23,24 Eligible participants met American Congress of Rehabilitation Medicine TBI diagnostic criteria²⁵ in the ED and received clinically indicated head computed tomography²⁶ within 24 hours of TBI. Exclusion criteria were incarceration, pregnancy, nonsurvivable physical trauma, psychiatric hold, debilitating mental health disorders, neurologic disease, and non-English or non-Spanish speaking, depending on site. The TRACK-TBI study received institutional review board approval at each local site. Participants or their legally authorized representative provided written informed consent prior to enrollment. In 2019, the TRACK-TBI longitudinal substudy was approved to conduct annual phone calls with TRACK-TBI participants 2 years or more postinjury.

Data from participants 17 years and older who completed outcome assessments at 1 and 3 to 7 years were included in this analysis; deaths were excluded. If more than 1 longitudinal assessment was completed 3 to 7 years after study enrollment, the latest outcome assessment was analyzed. Study variables were collected in accordance with the National Institutes of Health TBI Common Data Elements.^27,28,29,30 Functional, PCS, psychological distress, PTSD, depression, and HRQOL outcomes were selected as primary outcomes for our analysis. This study followed the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) reporting guideline.

Baseline Measures

Sociodemographic characteristics (age, sex, race and ethnicity, education, insurance), medical history, and injury characteristics were collected at baseline through self-report and medical record review. Race categories included Asian, Black, White, other race (including American Indian and Alaska Native, Inuit, and Native Hawaiian and Other Pacific Islander), and unknown race. Ethnicity categories included Hispanic and non-Hispanic. We adjusted for participants’ Neighborhood Disadvantage Index (NDI) score (range, 0-100), a socioeconomic disadvantage score based on 4 US census tract indicators by zone improvement plan code tabulation areas.^31,32 Injury-related characteristics included Glasgow Coma Scale (GCS),³³ loss of consciousness, care level, Injury Severity Score,³⁴ and computed tomography scans coded as having positive or negative findings for acute traumatic intracranial lesions. To address generalizability, descriptive characteristics of the TRACK-TBI participants included in our study at 1 year and 3 to 7 years were compared with excluded participants (eTable 1 in Supplement 1).

Preindex and Postindex TBI History

At enrollment, lifetime TBI history was assessed using the Ohio State University TBI Identification Method (OSU TBI-ID), a validated structured interview for detection of prior TBI.^35,36 At follow-up time points, postindex TBI information was collected through the OSU TBI-ID Short-Form to ascertain whether the participant sustained another TBI since the index TBI. The interview at 3 to 7 years added a question regarding the number of postindex TBIs.

Primary Outcome Measures

Glasgow Outcome Scale-Extended

The 8-point Glasgow Outcome Scale–Extended (GOSE)^20,37 assesses functional disability after TBI through a structured interview with the participant or caretaker.^38,39 A score of 1 indicates death; 2, vegetative state; 3, lower severe disability; 4, upper severe disability; 5, lower moderate disability; 6, upper moderate disability; 7, lower good recovery; and 8, upper good recovery. A score of 8 reflects complete return to baseline function; a score less than 8 reflects incomplete functional recovery.

Rivermead Post-Concussion Symptoms Questionnaire

The Rivermead Post-Concussion Symptoms Questionnaire (RPQ) measures the severity of 16 PCS across 4 domains (physical, cognitive, mood, and sleep) compared with preinjury levels (ranging from 0 [not experienced] to 4 [severe problem])⁴⁰; 1 was recoded to 0, per accepted protocol.⁴¹ Scores were summed to a maximum of 64; scores of 0 to 12, 13 to 24, 25 to 32, and 33 or greater indicate minimal, mild, moderate, and severe PCS, respectively.⁴¹

Brief Symptom Inventory-18

The Brief Symptom Inventory-18 (BSI-18)⁴² assesses psychological distress using 18 questions across somatization, depression, and anxiety domains, scored from 0 (not at all) to 4 (extremely). The Global Severity Index T score sums responses in each domain normalized by age and sex (maximum score, 72)^42,43; scores of 63 or more indicate clinically significant distress.

PTSD Checklist for DSM-5

The PTSD Checklist for DSM-5 (PCL-5) measures PTSD symptoms according to Diagnostic and Statistical Manual of Mental Disorders (Fifth Edition) criteria.⁴⁴ Twenty items are scored from 0 (not at all) to 5 (extremely) (maximum score, 80); scores of 33 or higher indicate probable clinically relevant PTSD.^45,46

Patient Health Questionnaire-9

The Patient Health Questionnaire-9 (PHQ-9)⁴⁷ is a self-reported scale measuring depressive symptoms using 9 Diagnostic and Statistical Manual of Mental Disorders (Fifth Edition)–focused items scored from 0 (not at all) to 3 (nearly every day).⁴⁸ Scores range from 0 to 27; scores of 5 to 9, 10 to 14, 15 to 19, and 20 to 27 represent mild, moderate, moderately severe, and severe depression, respectively.

Quality of Life After Brain Injury–Overall Scale

The Quality of Life After Brain Injury–Overall Scale (QOLIBRI-OS)⁴⁹ is a self-reported measure of HRQOL across 6 domains (physical condition, cognition, emotions, daily life function, personal life, and social life) frequently affected by TBI, scored from 1 (not at all) to 5 (very). Scores were converted to QOLIBRI total score (range, 0 to 100); scores less than 52 represent impaired HRQOL.^50,51

Statistical Analysis

Differences in sociodemographic characteristics, medical history, and injury-related characteristics were assessed using Mann-Whitney U tests for continuous variables and Fisher exact tests for categorical variables. Inverse probability weighting was used to account for potential biases due to missing outcomes. A boosted regression algorithm based on all baseline sociodemographic, medical history, and injury-related characteristics was used to model missingness, and statistical weights were derived by inverting and rescaling the resulting propensity estimates (eMethods in Supplement 1). Linear regression was used to model the self-reported outcome measures (RPQ, BSI-18, PCL-5, PHQ-9, and QOLIBRI-OS), and log-binomial regression was used to model probability of complete functional recovery (GOSE score of 8). All regression analyses modeled each time point separately and adjusted for sociodemographic characteristics (age, sex, race, ethnicity, education), GCS, preindex TBI, and psychiatric history. A 2-sided significance threshold of P < .05 was used for all analyses, and results were interpreted after Benjamini-Hochberg adjustment for multiple comparisons.⁵² We evaluated normality using boxplots and plots of the residuals from the primary models for each outcome measure. All outcome measures were clearly unimodal with a general Gaussian shape. Normality could be assumed for BSI-18, while the RPQ, PCL-5, and PHQ-9 demonstrated mild right skew (1 year: 1.04, 1.07, and 1.20, respectively; 3 to 7 years: 0.95, 0.98, and 1.18), and the QOLIBRI-OS demonstrated mild left skew (1 year: −0.47; 3 to 7 years: −0.61). Boosted regression modeling was performed using the Toolkit for Weighting and Analysis of Nonequivalent Groups software from the Rand Corporation.⁵³ Other statistical analyses were performed using SAS version 9.4 (SAS Institute) and SPSS version 26 (IBM).

Results

Baseline and Injury-Related Characteristics

Of 2417 TRACK-TBI participants, 1572 completed the outcomes assessment at 1 year (1049 [66.7%] male; mean [SD] age, 41.6 [17.5] years) and 1084 completed the outcomes assessment at 3 to 7 years (714 [65.9%]; mean [SD] age, 40.6 [17.0] years). At 1 year, a total of 60 participants (4%) were Asian, 255 (16%) were Black, 1213 (77%) were White, 39 (2%) were another race, and 5 (0.3%) had unknown race. At 3 to 7 years, 39 (4%) were Asian, 149 (14%) were Black, 868 (80%) were White, 26 (2%) had another race, and 2 (0.2%) had unknown race. Comparison between included and excluded participants (845 at 1 year and 1315 at 3 to 7 years) showed differences in sex, race and ethnicity, education, and socioeconomic disadvantage (eTable 1 in Supplement 1). The flow diagram is shown in Figure 1. Site-specific enrollment is shown in eTable 9 in Supplement 1. Participants with postindex TBI (50 of 1572 [3.2%] at 1 year; 132 of 1084 [12.2%] at 3 to 7 years) and without postindex TBI (1522 of 1572 [96.8%] at 1 year; 952 of 1084 [87.8%] at 3 to 7 years) were comparable in sociodemographic and injury characteristics (Table 1).

Figure 1. — TBI indicates traumatic brain injury.

Table 1. Baseline and Injury Characteristics.

Variable	No. (%)
	Assessment at 1 y			Assessment at 3-7 y
	Postindex TBI		P value	Postindex TBI		P value
	No	Yes	P value	No	Yes	P value
Total	1522 (96.8)	50 (3.2)	NA	952 (87.8)	132 (12.2)	NA
Age, mean (SD), y	41.6 (17.5)	42.7 (17.4)	.84	40.6 (16.9)	40.7 (17.2)	.92
Sex
Male	1020 (67)	29 (58)	.28	634 (67)	80 (61)	.19
Female	502 (33)	21 (42)	.28	318 (33)	52 (39)	.19
Race^a
Asian	59 (4)	1 (2)	.73	38 (4)	1 (1)	.16
Black	245 (16)	10 (20)		135 (14)	14 (11)
White	1175 (77)	38 (76)		754 (79)	114 (86)
Other race^b	38 (3)	1 (2)		23 (2)	3 (2)
Unknown, No.	5	0	NA	2	0	NA
Ethnicity^a
Hispanic	263 (17)	6 (12)	.16	173 (18)	20 (15)	.19
Non-Hispanic	1253 (83)	44 (88)	.16	776 (82)	111 (85)	.19
Unknown, No.	6	0		3	1
Education
Mean (SD), y	13.7 (2.8)	13.3 (2.2)	.19	13.8 (2.8)	14.0 (2.6)	.46
Unknown, No.	33	0	NA	21	3	NA
Socioeconomic disadvantage^c
Mean (SD)	10.7 (6.4)	11.2 (6.0)	.35	10.9 (6.4)	9.7 (5.4)	.04
Unknown, No.	57	0	NA	27	1	NA
Psychiatric history
No	1178 (77)	31 (62)	.02	738 (78)	87 (66)	.009
Yes	344 (23)	19 (38)	.02	214 (22)	45 (34)	.009
Preindex TBI
Any preindex TBI
No	768 (53)	20 (43)	.09	515 (57)	51 (41)	<.001
Yes, no LOC	392 (27)	13 (28)		230 (25)	37 (30)
Yes, LOC	281 (20)	14 (30)		163 (18)	35 (28)
Unknown, No.	81	3	NA	44	9	NA
Preindex TBIs, No.^d
Mean (SD)	0.46 (0.92)	0.67 (1.14)	.10	0.41 (0.87)	0.67 (1.03)	<.001
0	1047 (70)	29 (59)	.17	691 (74)	72 (56)	<.001
1	308 (21)	13 (27)		178 (19)	41 (32)
≥2	137 (9)	7 (14)		71 (8)	16 (12)
Unknown, No.	30	1	NA	12	3	NA
Age at first preindex TBI
Mean (SD), y	22.3 (15.1)	28.6 (17.9)	.08	21.6 (14.4)	24.3 (15.3)	.19
<15 y	149 (34)	4 (20)	.32	87 (35)	16 (29)	.43
≥15 y	294 (66)	16 (80)	.32	160 (65)	40 (71)	.43
Unknown, No.	30	1	NA	14	4	NA
Highest preindex TBI level of care
None	1144 (81)	28 (61)	.001	739 (83)	82 (67)	<.001
ED only	171 (12)	12 (26)		90 (10)	31 (25)
Hospital admission	101 (7)	6 (13)		59 (7)	10 (8)
Unknown, No.	106	4	NA	64	9	NA
Index injury factors
GCS at ED arrival
Mean (SD)	13.3 (3.5)	13.7 (3.1)	.12	13.1 (3.7)	14.0 (2.6)	.003
Severe (3-8)	184 (12)	5 (10)	.76	131 (14)	8 (6)	.01
Moderate (9-12)	58 (4)	1 (2)		45 (5)	3 (2)
Mild (13-15)	1251 (84)	42 (88)		754 (81)	117 (91)
Unknown, No.	29	2	NA	22	4	NA
LOC
No	179 (12)	4 (8)	.30	109 (12)	15 (12)	.68
Suspected	76 (5)	1 (2)		51 (6)	10 (8)
Yes	1186 (82)	44 (90)		747 (82)	103 (80)
Unknown, No.	81	1	NA	45	4	NA
Highest level of care
ED	350 (23)	7 (14)	.69	209 (22)	31 (23)	.11
Ward	548 (36)	24 (48)		335 (35)	57 (43)
ICU	624 (41)	19 (38)		408 (43)	44 (33)
Initial CT findings
Negative	803 (54)	27 (55)	.88	483 (52)	79 (60)	.25
Positive	682 (46)	22 (45)	.88	438 (48)	53 (40)	.25
Unknown, No.	37	1	NA	31	0	NA
Major extracranial injury
No	1233 (81)	44 (88)	.27	779 (82)	111 (84)	.47
Yes	289 (19)	6 (12)	.27	173 (18)	21 (16)	.47
ISS (all systems)
Mean (SD)	15.0 (10.1)	10.9 (8.5)	.005	15.1 (10.2)	12.2 (9.1)	.002
Median (IQR)	13 (8-21)	10 (5-14)	.005	14 (9-21)	10 (5-17)	.002
Unknown/ED only, No.	377	10	NA	231	35	NA
ISS (head/neck)
Mean (SD)	8.6 (7.8)	6.8 (6.0)	.14	9.0 (8.1)	7.3 (7.1)	.06
Median (IQR)	9 (4-16)	6.5 (3.3-9)	.14	9 (4-16)	4 (1-9)	.06
Unknown/ED only, No.	377	10	NA	231	35	NA
ISS (nonhead/nonneck)
Mean (SD)	6.0 (7.3)	3.5 (5.9)	.002	5.7 (7.3)	4.3 (6.0)	.01
Median (IQR)	4 (1-9)	1 (0-4.25)	.002	4 (1-9)	1 (1-6)	.01
Unknown/ED only, No.	378	10	NA	231	35	NA

Open in a new tab

Abbreviations: CT, computed tomography; ED, emergency department; GCS, Glasgow Coma Scale; ICU, intensive care unit; ISS, Injury Severity Score; LOC, loss of consciousness; NA, not applicable; TBI, traumatic brain injury.

^{^a}

Race and ethnicity were obtained by participant self-report and medical record review.

^{^b}

The other race category included American Indian and Alaska Native, Inuit, and Native Hawaiian and Other Pacific Islander.

^{^c}

Socioeconomic disadvantage scores ranged from 0 to 100, with higher scores indicating greater disadvantage.

^{^d}

Number of preindex TBIs included only preindex TBIs with ED or hospital admission.

Statistically significant differences between participants with vs without postindex TBIs were observed at 1 year and 3 to 7 years for higher proportion with baseline psychiatric history (1 year: 19 of 50 [38%] vs 344 of 1522 [23%], respectively; P = .02; 3 to 7 years: 45 of 132 [34%] vs 214 of 952 [22%]; P = .009), higher number of preindex TBIs requiring ED or hospital admission (1 year: ED admission, 12 of 46 [26%] vs 171 of 1416 [12%]; hospital admission, 6 of 46 [13%] vs 101 of 1416 [7%]; P = .001; 3 to 7 years: ED admission, 31 of 123 [25%] vs 90 of 888 [10%]; hospital admission, 10 of 123 [8%] vs 59 of 888 [7%]; P < .001), and lower mean (SD) Injury Severity Score (1 year: 3.5 [5.9] vs 6.0 [7.3]; P = .002; 3 to 7 years: 4.3 [6.0] vs 5.7 [7.3]; P = .01).

Postindex TBI and Outcomes

Figure 2 summarizes our main results. At 1 year, the postindex TBI group exhibited poorer outcome across domains (Table 2). Compared with those without postindex TBI, participants with postindex TBI were less likely to achieve complete functional recovery (GOSE score of 8; adjusted relative risk [aRR], 0.57; 95% CI, 0.34-0.96), had decreased HRQOL (QOLIBRI-OS: adjusted mean difference [aMD], −15.9; 95% CI, −22.6 to −9.1), and increased symptom severities across other outcomes, including PCS (RPQ: aMD, 8.1; 95% CI, 4.2-11.9), psychological distress (BSI-18: aMD, 5.3; 95% CI, 2.1-8.6), PTSD (PCL-5: aMD, 7.8; 95% CI, 3.2-12.4), and depression (PHQ-9: aMD, 3.0; 95% CI, 1.5-4.4). At 3 to 7 years, participants with postindex TBI remained more symptomatic, at reduced magnitudes (QOLIBRI-OS: aMD, −7.3; 95% CI, −11.4, to −3.2; RPQ: aMD, 4.3; 95% CI, 1.9-6.6; BSI-18: aMD, 3.0; 95% CI, 0.9-5.1; PCL-5: aMD, 6.5; 95% CI, 3.4-9.7; PHQ-9: aMD, 1.8; 95% CI, 0.8-2.8). Likelihood of achieving a GOSE score of 8 was lower in those with postindex TBI (42 of 131 [32%] vs 416 of 917 [45%]), although this finding was not significant at 3 to 7 years (aRR, 0.78; 95% CI, 0.61-1.00). Similar findings were observed for postindex TBI with loss of consciousness vs without (eTables 2 and 3 in Supplement 1). Among participants with preindex TBI, differences between groups with and without postindex TBI in RPQ (aMD, 8.6; 95% CI, 2.1-15.1), BSI-18 (aMD, 6.9; 95% CI, 1.5-12.3), PHQ-9 (aMD, 4.80; 95% CI, 2.26-7.33), and QOLIBRI-OS (aMD, −19.8; 95% CI, −30.9 to −8.8) remained significant at 1 year and in QOLIBRI-OS (aMD, −8.8; 95% CI, −16.1 to −1.6) at 3 to 7 years (eTables 4 and 5 in Supplement 1).

Table 2. Association Between Postindex Traumatic Brain Injury (TBI) and Outcome^a.

Outcome measure	No postindex TBI		Postindex TBI		Effect size^b
Outcome measure	Total, No.	Mean (SD)	Total, No.	Mean (SD)	Measure (95% CI)	P value^c
1 y
GOSE score of 8, No. (%)	1446	638 (44)	48	10 (21)	aRR, 0.57 (0.34 to 0.96)	.03
RPQ	1456	12.1 (13.9)	48	22.7 (16.0)	aMD, 8.1 (4.2 to 11.9)	<.001
BSI-18	1453	49.1 (11.6)	48	56.6 (12.0)	aMD, 5.3 (2.1 to 8.6)	.001
PCL-5	1433	16.1 (16.6)	48	26.9 (16.7)	aMD, 7.8 (3.2 to 12.4)	.001
PHQ-9	1451	4.6 (5.3)	48	8.7 (7.3)	aMD, 2.96 (1.49 to 4.44)	<.001
QOLIBRI-OS	1452	67.6 (24.5)	48	47.0 (28.4)	aMD, −15.9 (−22.6 to −9.1)	<.001
3-7 y
GOSE score of 8, No. (%)	917	416 (45)	131	42 (32)	aRR, 0.78 (0.61 to 1.00)	.06
RPQ	917	10.8 (12.7)	130	16.1 (15.1)	aMD, 4.3 (1.9 to 6.6)	<.001
BSI-18	916	49.3 (11.0)	130	53.3 (12.6)	aMD, 3.0 (0.9 to 5.1)	.004
PCL-5	889	15.5 (16.5)	128	22.8 (20.1)	aMD, 6.5 (3.4 to 9.7)	<.001
PHQ-9	918	4.8 (5.3)	130	7.0 (6.3)	aMD, 1.78 (0.77 to 2.78)	.001
QOLIBRI-OS	919	70.8 (21.9)	130	62.2 (24.5)	aMD, −7.3 (−11.4 to −3.2)	<.001

Open in a new tab

Abbreviations: aMD, adjusted mean difference; aRR, adjusted relative risk; BSI-18, Brief Symptom Inventory-18; GOSE, Glasgow Outcome Scale–Extended; PCL-5, PTSD Checklist for DSM-5; PHQ-9, Patient Health Questionnaire-9; QOLIBRI-OS, Quality of Life After Brain Injury–Overall Scale; RPQ, Rivermead Post-Concussion Symptoms Questionnaire.

^{^a}

Multivariable linear regressions were performed for scalar outcome measures (BSI-18, PCL-5, PHQ-9, QOLIBRI-OS, and RPQ), and multivariable logistic regression was performed for complete functional recovery (GOSE score of 8).

^{^b}

All regressions were adjusted for age, sex, race and ethnicity, education, Glasgow Coma Scale, preindex TBI level of care, and psychiatric history and were propensity weighted for missingness.

^{^c}

All significant P values (P < .05) remained significant after adjustment for multiple comparisons (Benjamini-Hochberg; m = 12).

We evaluated the association between multiple postindex TBIs (26 of 1084 [2.4%]) and outcomes at 3 to 7 years. Number of postindex TBIs (0 vs 1, 1 vs 2 or more, and 2 or more vs 0) showed a dose-dependent association across all outcomes assessed by rank regression (Table 3). Compared with those without postindex TBIs, those with 1 postindex TBI had elevated PCL-5 (aMD, 3.6; 95% CI, 0.2-7.0) and lower QOLIBRI-OS (aMD, −4.8; 95% CI, −9.3 to −0.3). Those with 2 or more vs 1 postindex TBI and those with 2 or more vs 0 postindex TBIs were less likely to attain complete functional recovery (GOSE score of 8; 2 or more vs 1: aRR, 0.31; 95% CI, 0.10-0.96; 2 or more vs 0: aRR, 0.28; 95% CI, 0.09-0.84) and were more symptomatic across outcome domains, including QOLIBRI-OS (2 or more vs 1: aMD, −12.6; 95% CI, −22.2 to −3.0; 2 or more vs 0: aMD, −17.4; 95% CI, −26.1 to −8.7), RPQ (2 or more vs 1: aMD, 10.1; 95% CI, 4.6-15.6; 2 or more vs 0: aMD, 12.4; 95% CI, 7.4-17.4), BSI-18 (2 or more vs 1: aMD, 6.7; 95% CI, 1.8-11.5; 2 or more vs 0: aMD, 8.4; 95% CI, 4.0-12.8), PCL-5 (2 or more vs 1: aMD, 14.7; 95% CI, 7.4-22.0; 2 or more vs 0: aMD, 18.3; 95% CI, 11.7-25.0), and PHQ-9 (2 or more vs 1: aMD, 4.88; 95% CI, 2.53-7.23; 2 or more vs 0: aMD, 5.71; 95% CI, 3.57-7.85).

Table 3. Association of Multiple Postindex Traumatic Brain Injuries (TBIs) with Outcomes at 3 to 7 Years^a.

Outcome measure	No. of postindex TBIs						Effect size^b
	0 TBIs		1 TBI		≥2 TBIs		1 vs 0 TBIs		≥2 vs 1 TBI		≥2 vs 0 TBIs		Overall P value^c^,^d
	Total, No.	Mean (SD)	Total, No.	Mean (SD)	Total, No.	Mean (SD)	Measure (95% CI)	P value^c	Measure (95% CI)	P value^c	Measure (95% CI)	P value^c	Overall P value^c^,^d
GOSE score of 8, No. (%)	917	416 (45)	105	39 (37)	26	3 (12)	aRR, 0.90 (0.70 to 1.15)	.21	aRR, 0.31 (0.10 to 0.96)	.04	aRR, 0.28 (0.09 to 0.84)	.02	.03
RPQ	917	10.8 (12.7)	104	14.1 (14.1)	26	24.0 (16.9)	aMD, 2.3 (−0.3 to 4.9)	.08	aMD, 10.1 (4.6 to 15.6)	<.001	aMD, 12.4 (7.4 to 17.4)	<.001	<.001
BSI-18	916	49.3 (11.0)	104	52.0 (11.6)	26	58.5 (15.1)	aMD, 1.7 (−0.6 to 4.0)	.14	aMD, 6.7 (1.8 to 11.5)	.007	aMD, 8.4 (4.0 to 12.8)	<.001	.003
PCL-5	889	15.5 (16.5)	102	20.1 (18.2)	26	33.5 (24.0)	aMD, 3.6 (0.2 to 7.0)	.04	aMD, 14.7 (7.4 to 22.0)	<.001	aMD, 18.3 (11.7 to 25.0)	<.001	<.001
PHQ-9	918	4.8 (5.3)	104	6.1 (5.8)	26	10.5 (7.0)	aMD, 0.83 (−0.27 to 1.93)	.14	aMD, 4.88 (2.53 to 7.23)	<.001	aMD, 5.71 (3.57 to 7.85)	<.001	<.001
QOLIBRI-OS	919	70.8 (21.9)	104	64.7 (23.3)	26	52.4 (26.9)	aMD, −4.8 (−9.3 to −0.3)	.04	aMD, −12.6 (−22.2 to −3.0)	.01	aMD, −17.4 (−26.1 to −8.7)	<.001	<.001

Open in a new tab

^{^a}

^{^b}

All regressions were adjusted for age, sex, race and ethnicity, education, Glasgow Coma Scale, preindex TBI level of care, and psychiatric history and were propensity weighted for missingness.

^{^c}

Significance was assessed at P < .05. No adjustments were made for multiple comparisons.

^{^d}

Overall significance assumes ordinality of postindex TBI categories and was assessed by rank regression.

We further investigated associations between the timing of postindex TBI and outcomes and observed no difference at 1 year (eTable 6 in Supplement 1). eTable 7 in Supplement 1 summarizes the number of years between postindex TBI and outcomes at 3 to 7 years. An association was observed between the timing of assessment and decreased symptomology (RPQ, BSI-18, PCL-5, PHQ-9, QOLIBRI-OS), and original associations remained significant after adjusting for timing (eTable 8 in Supplement 1).

Discussion

In this multicenter study, participants with postindex TBI were at elevated risk for incomplete functional recovery and greater symptomatology across PCS, mental health, and HRQOL domains at 1 year postinjury. These findings were conserved at 3 to 7 years. Notably, multiple postindex TBIs at 3 to 7 years conferred greater risks of incomplete functional recovery and symptom burden across domains. These results show that participants with postindex TBIs comprise a distinctly symptomatic cohort in long-term recovery, and at-risk patients may benefit from targeted prevention and follow-up care.

Postindex TBI Risk Factors

Risk factors for postindex TBI at both time points included baseline psychiatric history, preindex TBI frequency and severity, and less severe index peripheral injury. Psychiatric history^54,55 and preindex TBI^4,5 are well-known risk factors for TBI. The finding that peripheral injuries were more severe in individuals without postindex TBI suggests these individuals may be too severely injured to resume high-risk activities that would predispose to TBI. Risk factors specific to 3 to 7 years included less-severe index TBI (higher GCS) and socioeconomic disadvantage. Prior research suggests that civilians with preindex and postindex TBI sustain less-severe index TBI.^5,6,17

Postindex TBI and Outcomes

At 1 year, multiple regression analyses controlling for major confounders demonstrated that participants with postindex TBI were at risk for reduced complete functional recovery (GOSE score of 8; aRR, 0.57; 95% CI, 0.34-0.96) and were more symptomatic (PCS, psychological distress, PTSD, depression, and HRQOL). Mean outcome scores indicated clinically significant mild PCS, depression, and impaired HRQOL. In participants with preindex TBI, those with postindex TBI remained more symptomatic across PCS, psychological distress, depressive, and HRQOL outcomes with comparable effect sizes, further supporting the association of postindex TBI with outcome. Our results are consistent with literature demonstrating worsened PCS, PTSD, and mental health in civilians with preindex TBI⁶ and worsened PCS in civilians with postindex TBI.¹⁸

At 3 to 7 years, the postindex TBI group remained more symptomatic (PCS, psychological distress, PTSD, depression, and HRQOL) after multiple regressions, at reduced magnitudes. There was no significant association between functional recovery and postindex TBI after multivariable regressions, which may reflect lower composite symptomatology at 3 to 7 years. Among participants with preindex TBIs, those with postindex TBIs reported worse HRQOL but no difference in other outcomes with reduced effect sizes, suggesting that both preindex and postindex TBIs contribute to outcomes at 3 to 7 years.

The number of postindex TBIs (0, 1, or 2 or more) at 3 to 7 years exhibited a dose-dependent association across all domains (functional, PCS, mental health, and HRQOL). A lower proportion of participants with 2 or more postindex TBIs reported complete functional recovery (GOSE score of 8; aRR, 0.31; 95% CI, 0.10-0.96) compared with participants with 1 postindex TBI and exhibited mean outcome scores that exceeded the clinical thresholds for PTSD, mild PCS, and moderate depression. Our findings are consistent with the contact-sport literature, which demonstrates that sustaining multiple TBIs contributes to worsened PCS, mental health symptoms, and delayed recovery.^10,11,56,57

Our analyses of postindex TBI timing further strengthen these results. While no significant associations were observed at 1 year, shorter-interval injuries were associated with poorer recovery in RPQ, BSI-18, PCL-5, PHQ-9, and QOLIBRI-OS at 3 to 7 years. Importantly, all associations between postindex TBI and outcomes remained significant after adjusting for timing via sensitivity analyses at 3 to 7 years. These results impel the need for prevention, education, and follow-up care efforts to decrease the risk of short-interval injuries.

Implications for Clinical Practice

Lack of follow-up care is detrimental to employment and economic outcomes.^58,59 Standardized TBI education, counseling, screening, triage, and referral to care system of patients at risk of repetitive injuries may reduce reinjury and improve likelihood of recovery. Our results show the importance of collecting preindex and postindex TBI histories, as repetitive TBI is a risk factor for poorer multidimensional outcomes.

Utilization of the biopsychosocial-ecological model will inform prevention and follow-up care efforts.^60,61 A combination of biological factors, preinjury and postinjury mental health, social determinants of health (race and ethnicity as well as education), and access to postacute care intersect to influence each patient’s recovery. Risk factors for and sequelae of experiencing 1 or more postindex TBIs encompass biological (eg, the TBI), psychological (eg, postinjury psychological symptomatology, preinjury modifiers), and social/socioeconomic factors (eg, neighborhood disadvantage index), in addition to ecological and other factors not evaluated by the current study. Accordingly, postindex TBIs may be part and parcel of an overall phenotype of protracted recovery and/or poor outcome after TBI, and more in-depth understanding of the mediating factors for these repetitive injuries can mitigate these risks and reduce morbidity after a single TBI. Concurrent application of the biopsychosocial-ecological model by clinicians during counseling and in subsequent research may enable more comprehensive evaluation of underlying risk factors and amplify the impact of prevention, education, and outpatient care interventions.

Limitations

This study has limitations. Our findings are applicable to populations where cranial imaging is indicated to rule out traumatic intracranial hemorrhage but may not be generalizable to patients who do not present to the ED. Participants with assessments at 1 and 3 to 7 years were more likely to be female, non-Hispanic, have greater educational attainment, and less socioeconomic disadvantage, which limit overall generalizability. The OSU TBI-ID is a validated and reliable self-reported measure for lifetime TBI history; however, self-reported measures are inherently limited by recall bias. While out of scope of our study, between-center variability in outcomes is another factor worth examining for comparative effectiveness research in this burdened population. We were unable to evaluate associations between multiple postindex TBIs and outcomes at 1 year, as these data were not captured until 3 to 7 years. Because we sought to review the largest sample size at each time point, the cohorts with assessments at 1 year and 3 to 7 years have slightly different baseline characteristics. Future hypothesis-driven analyses may consider using a common sample across time points. We did not assess associations between postindex TBI and deaths due to small numbers, which warrant future investigation in larger and more diverse samples. While we controlled for major confounders of outcomes, residual confounding related to procedural interventions, complications, and postdischarge care may remain. These limitations constitute relevant next steps.

Using linear regressions to model scalar outcome measures constituted another limitation. While the BSI-18 conformed to normality, the other measures demonstrated some degree of skew. Given that skews were generally mild, we proceeded with linear regression to prioritize the reporting of coefficient units in their original interpretable outcome scores, which aligns with the methodology in prior published reports on outcome measures in large multicenter TBI studies. We recognize that skew may decrease the validity of linear regression models. As such, our results should be interpreted with a commensurate level of caution and await validation studies in this understudied and at-risk population.

Conclusions

In a prospective multicenter cohort of patients with acute TBI, postindex TBI was associated with functional, PCS, mental health, and HRQOL symptomatology at 1 year and 3 to 7 years postinjury. Sustaining multiple postindex TBIs was associated with additional increases in symptomatology compared with sustaining 1 postindex TBI. These results highlight the profound cumulative deficits acquired after repetitive TBI and underscore the imperative need to establish institutional programs to support TBI prevention, education, counseling, and follow-up for at-risk patients.

Supplement 1.

eMethods. Inverse Probability Weighting Methods

eTable 1. Predictors of Being Followed at 1 Year and 3 to 7 Years

eTable 2. Postindex TBI with LOC at Baseline and Injury Characteristics

eTable 3. Association Between Postindex TBI with LOC and Outcome

eTable 4. Association of Postindex TBI and Outcome Among Participants With Preindex TBI

eTable 5. Association of Postindex TBI With LOC and Outcome Among Participants With Preindex TBI

eTable 6. Association Between Postindex TBI Timing and Outcome at 1 Year

eTable 7. Timing of Postindex TBI Relative to Outcomes at 3 to 7 Years

eTable 8. Association Between Postindex TBI Timing and Outcome at 3 to 7 Years

eTable 9. Number of Patients Enrolled by Site

Click here for additional data file.^{(427.8KB, pdf)}

Supplement 2.

Group Information. TRACK-TBI Investigators

Click here for additional data file.^{(158KB, pdf)}

Supplement 3.

Data Sharing Statement

Click here for additional data file.^{(16.4KB, pdf)}

References

1.Taylor CA, Bell JM, Breiding MJ, Xu L. Traumatic brain injury-related emergency department visits, hospitalizations, and deaths—United States, 2007 and 2013. MMWR Surveill Summ. 2017;66(9):1-16. doi: 10.15585/mmwr.ss6609a1 [DOI] [PMC free article] [PubMed] [Google Scholar]
2.Thurman DJ, Alverson C, Dunn KA, Guerrero J, Sniezek JE. Traumatic brain injury in the United States: a public health perspective. J Head Trauma Rehabil. 1999;14(6):602-615. doi: 10.1097/00001199-199912000-00009 [DOI] [PubMed] [Google Scholar]
3.Johnson WD, Griswold DP. Traumatic brain injury: a global challenge. Lancet Neurol. 2017;16(12):949-950. doi: 10.1016/S1474-4422(17)30362-9 [DOI] [PubMed] [Google Scholar]
4.Saunders LL, Selassie AW, Hill EG, et al. A population-based study of repetitive traumatic brain injury among persons with traumatic brain injury. Brain Inj. 2009;23(11):866-872. doi: 10.1080/02699050903283213 [DOI] [PubMed] [Google Scholar]
5.Corrigan JD, Bogner J, Mellick D, et al. Prior history of traumatic brain injury among persons in the Traumatic Brain Injury Model Systems National Database. Arch Phys Med Rehabil. 2013;94(10):1940-1950. doi: 10.1016/j.apmr.2013.05.018 [DOI] [PMC free article] [PubMed] [Google Scholar]
6.Dams-O’Connor K, Spielman L, Singh A, et al. ; TRACK-TBI Investigators . The impact of previous traumatic brain injury on health and functioning: a TRACK-TBI study. J Neurotrauma. 2013;30(24):2014-2020. doi: 10.1089/neu.2013.3049 [DOI] [PMC free article] [PubMed] [Google Scholar]
7.Hayward RD, Fessler MM, Buck J, Fessler RD. Risk factors for recurrent neurotrauma: a population-based study in Southeastern Michigan. Brain Inj. 2018;32(11):1373-1376. doi: 10.1080/02699052.2018.1487584 [DOI] [PubMed] [Google Scholar]
8.Decq P, Gault N, Blandeau M, et al. Long-term consequences of recurrent sports concussion. Acta Neurochir (Wien). 2016;158(2):289-300. doi: 10.1007/s00701-015-2681-4 [DOI] [PubMed] [Google Scholar]
9.Kerr ZY, Evenson KR, Rosamond WD, Mihalik JP, Guskiewicz KM, Marshall SW. Association between concussion and mental health in former collegiate athletes. Inj Epidemiol. 2014;1(1):28. doi: 10.1186/s40621-014-0028-x [DOI] [PMC free article] [PubMed] [Google Scholar]
10.Guskiewicz KM, McCrea M, Marshall SW, et al. Cumulative effects associated with recurrent concussion in collegiate football players: the NCAA Concussion Study. JAMA. 2003;290(19):2549-2555. doi: 10.1001/jama.290.19.2549 [DOI] [PubMed] [Google Scholar]
11.Benson BW, Meeuwisse WH, Rizos J, Kang J, Burke CJ. A prospective study of concussions among National Hockey League players during regular season games: the NHL-NHLPA Concussion Program. CMAJ. 2011;183(8):905-911. doi: 10.1503/cmaj.092190 [DOI] [PMC free article] [PubMed] [Google Scholar]
12.Guskiewicz KM, Marshall SW, Bailes J, et al. Association between recurrent concussion and late-life cognitive impairment in retired professional football players. Neurosurgery. 2005;57(4):719-726. doi: 10.1227/01.NEU.0000175725.75780.DD [DOI] [PubMed] [Google Scholar]
13.Montenigro PH, Alosco ML, Martin BM, et al. Cumulative head impact exposure predicts later-life depression, apathy, executive dysfunction, and cognitive impairment in former high school and college football players. J Neurotrauma. 2017;34(2):328-340. doi: 10.1089/neu.2016.4413 [DOI] [PMC free article] [PubMed] [Google Scholar]
14.Stern RA, Riley DO, Daneshvar DH, Nowinski CJ, Cantu RC, McKee AC. Long-term consequences of repetitive brain trauma: chronic traumatic encephalopathy. PM R. 2011;3(10)(suppl 2):S460-S467. doi: 10.1016/j.pmrj.2011.08.008 [DOI] [PubMed] [Google Scholar]
15.Dams-O’Connor K, Gibbons LE, Bowen JD, McCurry SM, Larson EB, Crane PK. Risk for late-life re-injury, dementia and death among individuals with traumatic brain injury: a population-based study. J Neurol Neurosurg Psychiatry. 2013;84(2):177-182. doi: 10.1136/jnnp-2012-303938 [DOI] [PMC free article] [PubMed] [Google Scholar]
16.Winqvist S, Luukinen H, Jokelainen J, Lehtilahti M, Näyhä S, Hillbom M. Recurrent traumatic brain injury is predicted by the index injury occurring under the influence of alcohol. Brain Inj. 2008;22(10):780-785. doi: 10.1080/02699050802339397 [DOI] [PubMed] [Google Scholar]
17.Bannon SM, Kumar RG, Bogner J, et al. Reinjury after moderate to severe TBI: rates and risk factors in the NIDILRR traumatic brain injury model systems. J Head Trauma Rehabil. 2021;36(1):E50-E60. doi: 10.1097/HTR.0000000000000586 [DOI] [PubMed] [Google Scholar]
18.Theadom A, Parmar P, Jones K, et al. ; BIONIC Research Group . Frequency and impact of recurrent traumatic brain injury in a population-based sample. J Neurotrauma. 2015;32(10):674-681. doi: 10.1089/neu.2014.3579 [DOI] [PubMed] [Google Scholar]
19.Davis LC, Sherer M, Sander AM, et al. Preinjury predictors of life satisfaction at 1 year after traumatic brain injury. Arch Phys Med Rehabil. 2012;93(8):1324-1330. doi: 10.1016/j.apmr.2012.02.036 [DOI] [PubMed] [Google Scholar]
20.Wilson JT, Pettigrew LE, Teasdale GM. Structured interviews for the Glasgow Outcome Scale and the extended Glasgow Outcome Scale: guidelines for their use. J Neurotrauma. 1998;15(8):573-585. doi: 10.1089/neu.1998.15.573 [DOI] [PubMed] [Google Scholar]
21.Rabinowitz AR, Chervoneva I, Hart T, et al. Influence of prior and intercurrent brain injury on 5-year outcome trajectories after moderate to severe traumatic brain injury. J Head Trauma Rehabil. 2020;35(4):E342-E351. doi: 10.1097/HTR.0000000000000556 [DOI] [PMC free article] [PubMed] [Google Scholar]
22.Nelson LD, Temkin NR, Dikmen S, et al. ; and the TRACK-TBI Investigators . Recovery after mild traumatic brain injury in patients presenting to US level I trauma centers: a Transforming Research and Clinical Knowledge in Traumatic Brain Injury (TRACK-TBI) study. JAMA Neurol. 2019;76(9):1049-1059. doi: 10.1001/jamaneurol.2019.1313 [DOI] [PMC free article] [PubMed] [Google Scholar]
23.McCrea MA, Giacino JT, Barber J, et al. ; TRACK-TBI Investigators . Functional outcomes over the first year after moderate to severe traumatic brain injury in the prospective, longitudinal TRACK-TBI study. JAMA Neurol. 2021;78(8):982-992. doi: 10.1001/jamaneurol.2021.2043 [DOI] [PMC free article] [PubMed] [Google Scholar]
24.Madhok DY, Rodriguez RM, Barber J, et al. ; TRACK-TBI Investigators . Outcomes in patients with mild traumatic brain injury without acute intracranial traumatic injury. JAMA Netw Open. 2022;5(8):e2223245. doi: 10.1001/jamanetworkopen.2022.23245 [DOI] [PMC free article] [PubMed] [Google Scholar]
25.Kay T. Definition of mild traumatic brain injury. J Head Trauma Rehabil. 1993;8(3):86-87. doi: 10.1097/00001199-199309000-00009 [DOI] [Google Scholar]
26.Jagoda AS, Bazarian JJ, Bruns JJ Jr, et al. Clinical policy: neuroimaging and decisionmaking in adult mild traumatic brain injury in the acute setting. J Emerg Nurs. 2009;35(2):e5-e40. doi: 10.1016/j.jen.2008.12.010 [DOI] [PubMed] [Google Scholar]
27.Wilde EA, Whiteneck GG, Bogner J, et al. Recommendations for the use of common outcome measures in traumatic brain injury research. Arch Phys Med Rehabil. 2010;91(11):1650-1660.e17. doi: 10.1016/j.apmr.2010.06.033 [DOI] [PubMed] [Google Scholar]
28.Maas AI, Harrison-Felix CL, Menon D, et al. Common data elements for traumatic brain injury: recommendations from the interagency working group on demographics and clinical assessment. Arch Phys Med Rehabil. 2010;91(11):1641-1649. doi: 10.1016/j.apmr.2010.07.232 [DOI] [PubMed] [Google Scholar]
29.Manley GT, Diaz-Arrastia R, Brophy M, et al. Common data elements for traumatic brain injury: recommendations from the biospecimens and biomarkers working group. Arch Phys Med Rehabil. 2010;91(11):1667-1672. doi: 10.1016/j.apmr.2010.05.018 [DOI] [PubMed] [Google Scholar]
30.Duhaime A-C, Gean AD, Haacke EM, et al. ; Common Data Elements Neuroimaging Working Group Members, Pediatric Working Group Members . Common data elements in radiologic imaging of traumatic brain injury. Arch Phys Med Rehabil. 2010;91(11):1661-1666. doi: 10.1016/j.apmr.2010.07.238 [DOI] [PubMed] [Google Scholar]
31.Melendez R, Clarke P, Khan A, Gomez-Lopez I, Li M, Chenoweth M. National Neighborhood Data Archive (NaNDA): socioeconomic status and demographic characteristics of Census tracts, United States, 2008-2017. Accessed August 16, 2023. https://www.openicpsr.org/openicpsr/project/119451/version/V2/view;jsessionid=A226577023171CFCD3CC5858690F62B8
32.Clarke P, Melendez R. National Neighborhood Data Archive (NaNDA): neighborhood socioeconomic and demographic characteristics of Census tracts, United States, 2000-2010. Accessed August 16, 2023. https://www.openicpsr.org/openicpsr/project/111107/version/V1/view
33.Teasdale G, Jennett B. Assessment of coma and impaired consciousness. a practical scale. Lancet. 1974;2(7872):81-84. doi: 10.1016/S0140-6736(74)91639-0 [DOI] [PubMed] [Google Scholar]
34.Baker SP, O’Neill B, Haddon W Jr, Long WB. The injury severity score: a method for describing patients with multiple injuries and evaluating emergency care. J Trauma. 1974;14(3):187-196. doi: 10.1097/00005373-197403000-00001 [DOI] [PubMed] [Google Scholar]
35.Corrigan JD, Bogner J. Initial reliability and validity of the Ohio State University TBI Identification Method. J Head Trauma Rehabil. 2007;22(6):318-329. doi: 10.1097/01.HTR.0000300227.67748.77 [DOI] [PubMed] [Google Scholar]
36.Bogner J, Corrigan JD. Reliability and predictive validity of the Ohio State University TBI identification method with prisoners. J Head Trauma Rehabil. 2009;24(4):279-291. doi: 10.1097/HTR.0b013e3181a66356 [DOI] [PubMed] [Google Scholar]
37.Jennett B, Snoek J, Bond MR, Brooks N. Disability after severe head injury: observations on the use of the Glasgow Outcome Scale. J Neurol Neurosurg Psychiatry. 1981;44(4):285-293. doi: 10.1136/jnnp.44.4.285 [DOI] [PMC free article] [PubMed] [Google Scholar]
38.Pettigrew LE, Wilson JT, Teasdale GM. Assessing disability after head injury: improved use of the Glasgow Outcome Scale. J Neurosurg. 1998;89(6):939-943. doi: 10.3171/jns.1998.89.6.0939 [DOI] [PubMed] [Google Scholar]
39.McMillan T, Wilson L, Ponsford J, Levin H, Teasdale G, Bond M. The Glasgow Outcome Scale—40 years of application and refinement. Nat Rev Neurol. 2016;12(8):477-485. doi: 10.1038/nrneurol.2016.89 [DOI] [PubMed] [Google Scholar]
40.King NS, Crawford S, Wenden FJ, Moss NE, Wade DT. The Rivermead Post Concussion Symptoms Questionnaire: a measure of symptoms commonly experienced after head injury and its reliability. J Neurol. 1995;242(9):587-592. doi: 10.1007/BF00868811 [DOI] [PubMed] [Google Scholar]
41.Potter S, Leigh E, Wade D, Fleminger S. The Rivermead Post Concussion Symptoms Questionnaire: a confirmatory factor analysis. J Neurol. 2006;253(12):1603-1614. doi: 10.1007/s00415-006-0275-z [DOI] [PubMed] [Google Scholar]
42.Derogatis L. Brief Symptom Inventory 18: Administration, Scoring and Procedures Manual. Pearson; 2001. [Google Scholar]
43.Meachen SJ, Hanks RA, Millis SR, Rapport LJ. The reliability and validity of the Brief Symptom Inventory-18 in persons with traumatic brain injury. Arch Phys Med Rehabil. 2008;89(5):958-965. doi: 10.1016/j.apmr.2007.12.028 [DOI] [PubMed] [Google Scholar]
44.American Psychiatric Association . Diagnostic and Statistical Manual of Mental Disorders. 5th ed. American Psychiatric Association; 2013. [Google Scholar]
45.Bovin MJ, Marx BP, Weathers FW, et al. Psychometric properties of the PTSD Checklist for Diagnostic and Statistical Manual of Mental Disorders-Fifth Edition (PCL-5) in veterans. Psychol Assess. 2016;28(11):1379-1391. doi: 10.1037/pas0000254 [DOI] [PubMed] [Google Scholar]
46.Stein MB, Jain S, Giacino JT, et al. ; TRACK-TBI Investigators . Risk of posttraumatic stress disorder and major depression in civilian patients after mild traumatic brain injury: a TRACK-TBI study. JAMA Psychiatry. 2019;76(3):249-258. doi: 10.1001/jamapsychiatry.2018.4288 [DOI] [PMC free article] [PubMed] [Google Scholar]
47.Kroenke K, Spitzer RL, Williams JB. The PHQ-9: validity of a brief depression severity measure. J Gen Intern Med. 2001;16(9):606-613. doi: 10.1046/j.1525-1497.2001.016009606.x [DOI] [PMC free article] [PubMed] [Google Scholar]
48.Kroenke K, Spitzer RL, Williams JB, Löwe B. The Patient Health Questionnaire Somatic, Anxiety, and Depressive Symptom Scales: a systematic review. Gen Hosp Psychiatry. 2010;32(4):345-359. doi: 10.1016/j.genhosppsych.2010.03.006 [DOI] [PubMed] [Google Scholar]
49.von Steinbuechel N, Wilson L, Gibbons H, et al. QOLIBRI overall scale: a brief index of health-related quality of life after traumatic brain injury. J Neurol Neurosurg Psychiatry. 2012;83(11):1041-1047. doi: 10.1136/jnnp-2012-302361 [DOI] [PubMed] [Google Scholar]
50.Wilson L, Marsden-Loftus I, Koskinen S, et al. Interpreting quality of life after brain injury scores: cross-walk with the Short Form-36. J Neurotrauma. 2017;34(1):59-65. doi: 10.1089/neu.2015.4287 [DOI] [PubMed] [Google Scholar]
51.Steyerberg EW, Wiegers E, Sewalt C, et al. ; CENTER-TBI Participants and Investigators . Case-mix, care pathways, and outcomes in patients with traumatic brain injury in CENTER-TBI: a European prospective, multicentre, longitudinal, cohort study. Lancet Neurol. 2019;18(10):923-934. doi: 10.1016/S1474-4422(19)30232-7 [DOI] [PubMed] [Google Scholar]
52.Benjamini Y, Hochberg Y. Controlling the false discovery rate: a practical and powerful approach to multiple testing. J R Stat Soc B. 1995;57(1):289-300. doi: 10.1111/j.2517-6161.1995.tb02031.x [DOI] [Google Scholar]
53.Griffin BA, Ridgeway G, Morral AR, et al. Toolkit for Weighting and Analysis of Nonequivalent Groups (TWANG). Accessed April 4, 2023. https://www.rand.org/statistics/twang.html
54.Vassallo JL, Proctor-Weber Z, Lebowitz BK, Curtiss G, Vanderploeg RD. Psychiatric risk factors for traumatic brain injury. Brain Inj. 2007;21(6):567-573. doi: 10.1080/02699050701426832 [DOI] [PubMed] [Google Scholar]
55.Silverberg ND, Gardner AJ, Brubacher JR, Panenka WJ, Li JJ, Iverson GL. Systematic review of multivariable prognostic models for mild traumatic brain injury. J Neurotrauma. 2015;32(8):517-526. doi: 10.1089/neu.2014.3600 [DOI] [PubMed] [Google Scholar]
56.Rice SM, Parker AG, Rosenbaum S, Bailey A, Mawren D, Purcell R. Sport-related concussion and mental health outcomes in elite athletes: a systematic review. Sports Med. 2018;48(2):447-465. doi: 10.1007/s40279-017-0810-3 [DOI] [PMC free article] [PubMed] [Google Scholar]
57.Manley G, Gardner AJ, Schneider KJ, et al. A systematic review of potential long-term effects of sport-related concussion. Br J Sports Med. 2017;51(12):969-977. doi: 10.1136/bjsports-2017-097791 [DOI] [PMC free article] [PubMed] [Google Scholar]
58.Gaudette É, Seabury SA, Temkin N, et al. ; TRACK-TBI Investigators . Employment and economic outcomes of participants with mild traumatic brain injury in the TRACK-TBI study. JAMA Netw Open. 2022;5(6):e2219444. doi: 10.1001/jamanetworkopen.2022.19444 [DOI] [PMC free article] [PubMed] [Google Scholar]
59.Seabury SA, Gaudette É, Goldman DP, et al. ; TRACK-TBI Investigators . Assessment of follow-up care after emergency department presentation for mild traumatic brain injury and concussion: results from the TRACK-TBI study. JAMA Netw Open. 2018;1(1):e180210. doi: 10.1001/jamanetworkopen.2018.0210 [DOI] [PMC free article] [PubMed] [Google Scholar]
60.National Academies of Sciences, Engineering, and Medicine; Health and Medicine Division; Board on Health Sciences Policy; Board on Health Care Services; Committee on Accelerating Progress in Traumatic Brain Injury Research and Care ; Berwick D, Bowman K, Matney C, eds. Traumatic Brain Injury: A Roadmap for Accelerating Progress. National Academies Press; 2022. [PubMed] [Google Scholar]
61.Maas AIR, Menon DK, Manley GT, et al. ; InTBIR Participants and Investigators . Traumatic brain injury: progress and challenges in prevention, clinical care, and research. Lancet Neurol. 2022;21(11):1004-1060. doi: 10.1016/S1474-4422(22)00309-X [DOI] [PMC free article] [PubMed] [Google Scholar]

Associated Data

This section collects any data citations, data availability statements, or supplementary materials included in this article.

Supplementary Materials