Functional Recovery, Symptoms, and Quality of Life 1 to 5 Years After Traumatic Brain Injury

Lindsay D Nelson; Nancy R Temkin; Jason Barber; Benjamin L Brett; David O Okonkwo; Michael A McCrea; Joseph T Giacino; Yelena G Bodien; Claudia Robertson; John D Corrigan; Ramon Diaz-Arrastia; Amy J Markowitz; Geoffrey T Manley; and the TRACK-TBI Investigators

doi:10.1001/jamanetworkopen.2023.3660

. 2023 Mar 20;6(3):e233660. doi: 10.1001/jamanetworkopen.2023.3660

Functional Recovery, Symptoms, and Quality of Life 1 to 5 Years After Traumatic Brain Injury

Lindsay D Nelson ^1,^✉, Nancy R Temkin ², Jason Barber ², Benjamin L Brett ¹, David O Okonkwo ³, Michael A McCrea ¹, Joseph T Giacino ^4,⁵, Yelena G Bodien ^4,⁵, Claudia Robertson ⁶, John D Corrigan ⁷, Ramon Diaz-Arrastia ⁸, Amy J Markowitz ^9,^✉, Geoffrey T Manley ⁹; and the TRACK-TBI Investigators

¹Medical College of Wisconsin, Milwaukee

²University of Washington, Seattle

³University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania

⁴Massachusetts General Hospital and Harvard Medical School, Boston

⁵Spaulding Rehabilitation Hospital, Charlestown, Massachusetts

⁶Baylor College of Medicine, Houston, Texas

⁷The Ohio State University Wexner Medical Center, Columbus

⁸University of Pennsylvania, Philadelphia

⁹University of California, San Francisco

Accepted for Publication: January 21, 2023.

Published: March 20, 2023. doi:10.1001/jamanetworkopen.2023.3660

^✉

Corresponding Authors: Lindsay D. Nelson, PhD, Medical College of Wisconsin, 8701 W Watertown Plank Rd, Milwaukee, WI 53226 (linelson@mcw.edu); Amy J. Markowitz, JD, UCSF Brain and Spinal Injury Center, University of California, San Francisco, 1001 Potrero Ave, San Francisco, CA 94110 (amymarkowitz@gmail.com).

Author Contributions: Dr Temkin and Mr Barber 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.

Concept and design: Nelson, Temkin, Okonkwo, McCrea, Bodien, Corrigan, Diaz-Arrastia, Markowitz, Gaudette, Mukherjee, Zafonte.

Acquisition, analysis, or interpretation of data: Nelson, Temkin, Barber, Brett, Okonkwo, McCrea, Giacino, Bodien, Robertson, Corrigan, Diaz-Arrastia, Manley, Feeser, Gopinath, Grandhi, Jain, Keene, Korley, Madden, Mukherjee, Ngwenya, Schneider, Schnyer, Valadka, Yuh.

Drafting of the manuscript: Nelson, Okonkwo, Bodien, Corrigan, Jain.

Critical revision of the manuscript for important intellectual content: Temkin, Barber, Brett, Okonkwo, McCrea, Giacino, Bodien, Robertson, Corrigan, Diaz-Arrastia, Markowitz, Manley, Feeser, Gaudette, Gopinath, Grandhi, Jain, Keene, Korley, Madden, Mukherjee, Ngwenya, Schneider, Schnyer, Valadka, Yuh, Zafonte.

Statistical analysis: Temkin, Barber, Okonkwo, Corrigan, Jain.

Obtained funding: Okonkwo, Diaz-Arrastia, Mukherjee, Zafonte.

Administrative, technical, or material support: Brett, Okonkwo, McCrea, Giacino, Bodien, Robertson, Corrigan, Diaz-Arrastia, Markowitz, Gopinath, Grandhi, Keene, Mukherjee, Valadka.

Supervision: Nelson, Okonkwo, McCrea, Diaz-Arrastia, Manley, Gopinath, Valadka.

Conflict of Interest Disclosures: Dr Nelson reported grants from the National Institutes of Health (NIH), the US Department of Defense (DoD), US Centers for Disease Control and Prevention (CDC), and the Medical College of Wisconsin (MCW) Advancing a Healthier Wisconsin Endowment outside the submitted work. Dr Brett reported receiving grants from National Institute on Aging and grants from National Institute of Neurological Disorders and Stroke (NINDS) outside the submitted work; and honoraria and travel reimbursement as conference speaker. Dr McCrea reported grants from DoD and the NIH to Medical College of Wisconsin during the conduct of the study; consulting work with Neurotrauma Sciences outside the submitted work; he reported researching funding from NIH, DoD, CDC, National Collegiate Athletics Association (NCAA), National Football League (NFL), and Abbott Laboratories paid to his institution outside the submitted work; he reported receiving book royalties from Oxford University Press; he reported service as a clinical consultant with the Milwaukee Bucks, Milwaukee Brewers, and Green Bay Packers, and as codirector of the NFL Neuropsychology Consultants without compensation. Dr Bodien reported receiving grants from Spaulding Rehabilitation Hospital and Massachusetts General Hospital both during the conduct of the study and outside the submitted work. Dr Robertson reported receiving grants from NIH, DoD, and NFL Charities during the conduct of the study. Dr Corrigan reported grants from University of California San Francisco (UCSF) during the conduct of the study; he reported receiving grant funding from National Institute on Independent Living and Rehabilitation Research, NIH, and Administration on Community Living outside the submitted work. Dr Diaz-Arrastia reported receiving grants from BrainBox, consulting work with MesoScale Discoveries Ischemix Inc, and NeurAegis, and equity held with NovaSignal outside the submitted work. Dr Manley reported receiving grant funding from DoD/Medical Technology Enterprise Consortium Transforming Research and Clinical Knowledge in TBI (TRACK-TBI) Network, grants from National Football League Scientific Advisory Board, US Department of Energy, NeuroTruama Sciences LLC, and One Mind Funding during the conduct of the study; he reported that Abbott Laboratories has provided funding for add-in TRACK-TBI clinical studies; he reported receiving an unrestricted gift from the NFL to the UCSF Foundation to support research efforts of the TRACK-TBI NETWORK. Dr Mukherjee reported grants from NIH and DoD during the conduct of the study; in addition, Dr Mukherjee had a patent (No. USPTO 62/269778) issued to the University of California Regents. Dr Ngwenya reported grants from Abbott Laboratories and grants from Biogen outside the submitted work. Dr Schneider reported serving as associate editor for Neurology, and grants from NIH/NINDS and DoD outside the submitted work. Dr Yuh reported receiving grants from NIH and grants from DoD during the conduct of the study; in addition, Dr Yuh had a patent (No. US PTO 62/269778) issued to University of California Regents. Dr Zafonte reported receiving royalties from Springer/Demos publishing for serving as coeditor of text Brain Injury Medicine. Dr Zafonte serves on the scientific advisory board of Myomo, Kisbee, and NanoDiagnostics. He reported receives funding from the NIH and the DOD. He reported service as principal investigator on a grant entitled the Football Players Health Study at Harvard University, which is funded by the NFL Players Association, and he also evaluates patients in the MGH Brain and Body-TRUST Program, which is funded by the NFL Players Association. Dr Zafonte also evaluates patients for the Massachusetts General Hospital Brain and Body TRUST Center, sponsored in part by the NFLPA, and serves on the Mackey White health committee. No other disclosures were reported.

Funding/Support: We thank the many TRACK-TBI study staff and participants, as well as Sabrina Taylor, PhD, for her enormous contributions to the TRACK-TBI studies. The study was funded by National Institute of Neurological Disorders and Stroke (NINDS) grants Nos. U01 NS086090 and U01 NS114140, the National Football League (NFL) Scientific Advisory Board, and Congressional Directed Medical Research Program (CDMRP) grants Nos. W81XWH-14-2-0176 and W81XWH-19-1-0861. Dr. Nelson’s effort was also supported by NINDS grant No. R01 NS110856.

Role of the Funder/Sponsor: The NIH played an advisory role in the initial U01 grant, which covered subject enrollment through 12-month postinjury follow-up. Otherwise, none of the funders were involved in the design and conduct of this study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.

The TRACK-TBI Investigators: V. Ramana Feeser, MD, Virginia Commonwealth University; Etienne Gaudette, PhD, University of Toronto; Shankar Gopinath, MD, Baylor College of Medicine; Ramesh Grandhi, MD, MS, University of Utah; Sonia Jain, PhD, University of California, San Diego; C. Dirk Keene, PhD, University of Washington; Frederick K. Korley, MD, PhD, University of Michigan; Christopher Madden, MD, University of Texas Southwestern; Pratik Mukherjee, MD, PhD, University of California, San Francisco; Laura B. Ngwenya, MD, PhD, University of Cincinnati; Andrea Schneider, MD, PhD, University of Pennsylvania; David Schnyer, PhD, University of Texas, Austin; Alex Valadka, MD, Virginia Commonwealth University; Esther Yuh, MD, PhD, University of California, San Francisco; Ross Zafonte, DO, Harvard Medical School.

Disclaimer: The manuscript’s contents are solely the responsibility of the authors; they do not necessarily represent the official views of the National Institutes of Health and are not necessarily endorsed by the US Department of Defense or NFL.

Data Sharing Statement: See Supplement 2.

^✉

Corresponding author.

PMCID: PMC10028488 PMID: 36939699

Key Points

Question

What is the course of functional, symptom, and quality of life outcomes 1 to 5 years after mild traumatic brain injury (mTBI) and moderate-severe traumatic brain injury (msTBI)?

Findings

In this cohort study of 1196 level I trauma center patients (859 mTBI, 188 msTBI, 152 orthopedic trauma controls) followed 5 years postinjury, msTBI was associated with increased mortality, yet msTBI survivors displayed improved independence from 1 to 5 years. mTBI survivors had poorer outcomes than controls.

Meaning

These results suggest that better understanding of TBI recovery, as well as increased clinical and community support for mTBI and msTBI, are warranted to address long-term risks associated with TBI.

This cohort study of level I trauma center patients compares outcomes for function and quality of life of patients with mild and moderate-severe traumatic brain injury over the course of 5 years following injury.

Abstract

Importance

Many level I trauma center patients experience clinical sequelae at 1 year following traumatic brain injury (TBI). Longer-term outcome data are needed to develop better monitoring and rehabilitation services.

Objective

To examine functional recovery, TBI-related symptoms, and quality of life from 1 to 5 years postinjury.

Design, Setting, and Participants

This cohort study enrolled trauma patients across 18 US level I trauma centers between 2014 and 2018. Eligible participants were enrolled within 24 hours of injury and followed up to 5 years postinjury. Data were analyzed January 2023.

Exposures

Mild TBI (mTBI), moderate-severe TBI (msTBI), or orthopedic traumatic controls (OTC).

Main Outcomes and Measures

Functional independence (Glasgow Outcome Scale-Extended [GOSE] score 5 or higher), complete functional recovery (GOSE score, 8), better (ie, lower) TBI-related symptom burden (Rivermead Post Concussion Symptoms Questionnaire score of 15 or lower), and better (ie, higher) health-related quality of life (Quality of Life After Brain Injury Scale-Overall Scale score 52 or higher); mortality was analyzed as a secondary outcome.

Results

A total 1196 patients were included in analysis (mean [SD] age, 40.8 [16.9] years; 781 [65%] male; 158 [13%] Black, 965 [81%] White). mTBI and OTC groups demonstrated stable, high rates of functional independence (98% to 100% across time). While odds of independence were lower among msTBI survivors, the majority were independent at 1 year (72%), and this proportion increased over time (80% at 5 years; group × year, P = .005; independence per year: odds ratio [OR] for msTBI, 1.28; 95% CI, 1.03-1.58; OR for mTBI, 0.81; 95% CI, 0.64-1.03). For other outcomes, group differences at 1 year remained stable over time (group × year, P ≥ .44). Odds of complete functional recovery remained lower for persons with mTBI vs OTC (OR, 0.39; 95% CI, 0.28-0.56) and lower for msTBI vs mTBI (OR, 0.34; 95% CI, 0.24-0.48). Odds of better TBI-related symptom burden and quality of life were similar for both TBI subgroups and lower than OTCs. Mortality between 1 and 5 years was higher for msTBI (5.5%) than mTBI (1.5%) and OTC (0.7%; P = .02).

Conclusions and Relevance

In this cohort study, patients with previous msTBI displayed increased independence over 5 years; msTBI was also associated with increased mortality. These findings, in combination with the persistently elevated rates of unfavorable outcomes in mTBI vs controls imply that more monitoring and rehabilitation are needed for TBI.

Introduction

Clinical recovery from traumatic brain injury (TBI) typically proceeds most rapidly in the first 3 to 6 months postinjury.^1,2,3,4,5 Most studies have terminated follow-up by 6 months, resulting in limited data on TBI’s long-term natural history.⁶ Smaller, retrospective studies and investigations of restricted subgroups (eg, patients admitted to inpatient rehabilitation) indicate that TBI recovery is dynamic, continuing for years. These findings counter the clinical narrative that recovery is unidirectional (ie, improving) and time-limited.^7,8,9,10,11 Although many persons appear to have an ongoing need for support to overcome and compensate for TBI-related deficits, they rarely receive formal clinical services beyond the first few months postinjury.^12,13,14 Large-scale prospective studies characterizing the long-term outcomes of TBI may inform initiatives to develop systems of postacute care for TBI that better meet the long-term needs of this population,¹⁴ while promoting clinical research aimed at developing disease-modifying therapies.

In recent years, data from large-scale prospective studies^5,8,15,16 have enriched understanding of the natural history of TBI. The multicenter Transforming Research and Clinical Knowledge in TBI (TRACK-TBI) study revealed that, contrary to popular belief that mild TBI (mTBI) (ie, Glasgow Coma Scale [GCS] score, 13-15) is a time-limited condition, the majority of level I trauma center patients with mTBI continue to report symptoms and injury-related problems with daily function at 1 year postinjury.^15,17 Persons with moderate-severe TBI (msTBI) (GCS score, 3-12) in the TRACK-TBI sample have displayed varied outcomes, often achieving functional independence and returning to work but rarely making a complete recovery.⁵ Unlike functional outcomes, which show a clear dose-response association with TBI severity, TBI-related symptoms show elevated rates of persistence in all level I trauma center patients with TBI, with weak and sometimes conflicting associations with TBI severity.^17,18 Similarly, survivors of TBI often report satisfactory quality of life irrespective of their injury severity and functional limitations.^19,20,21 These findings highlight the value of capturing differing outcome measures over time.

Our objective was to examine the degree to which TBI across severities is associated with functional recovery, TBI-related symptoms, and quality of life from 1 to 5 years postinjury. We hypothesized that outcomes would continue to be poorest through the follow-up period post-msTBI, followed by mTBI, followed by orthopedic trauma control (OTC) groups.

Methods

Participants and Study Design

This manuscript follows Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) guidelines for reporting observational studies. TRACK-TBI is a prospective, multicenter study recruiting participants from 18 level I trauma centers. The study was approved by the institutional review board of each enrolling institution. Participants or their legally authorized representatives completed written informed consent. The initial study enrolled participants from February 26, 2014, to July 27, 2018, within 24 of hours of injury with follow-up until 12 months postinjury. The clinical outcomes of the sample at these time points have been reported elsewhere.^5,15,22 In 2019, the study began TRACK-LONG, which aimed to conduct up to 3 annual phone calls for living participants at least 2 years postinjury. The eligible sample for the present study of longer-term clinical outcomes were TBI or OTC participants who were at least 17 years old, had a known admission GCS score, and were not known to have died by 1 year postinjury (eTable 1 in Supplement 1). Of these, primary analyses focused on the participants who were not known to have died through 5 years postinjury and who completed at least 1 primary outcome from 2 to 5 years postinjury. Secondary analyses of mortality included another 20 participants who died between 1 and 5 years postinjury.

Inclusion Criteria

Inclusion criteria for TBI participants in the parent study were presentation within 24 hours of injury to a participating level I trauma center with clinical suspicion of TBI (ie, head computed tomography [CT] scan ordered) and either showing objective evidence of brain injury (eg, positive results from head CT) or displaying or reporting altered consciousness (American Congress of Rehabilitation Medicine TBI definition).²³ OTCs presented within 24 hours of injury with orthopedic injuries and were excluded if they had physical signs of head trauma or met any criteria for TBI. Exclusions for all participants were being in custody of law enforcement, pregnancy, having nonsurvivable physical trauma, history of debilitating mental health disorders or neurological disease, and being non-English speaking (except for sites that enrolled Spanish-speaking individuals).

Outcome Measures

Glasgow Outcome Scale-Extended

The Glasgow Outcome Scale-Extended (GOSE) estimates how injuries have affected daily function (eg, home independence and return to work, social, and other areas of preinjury daily functioning). Respondents (participants or informants) report on new or worsened difficulties since injury^24,25; responses considered were given a score on an 8-point scale (with 1 indicating 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). Deaths were identified through research assistants’ contact with secondary contacts when pursuing follow-up visits. For the present study, GOSE scores reflected disability due to TBI and accompanying peripheral injuries, when present. Based on nonlinearity of the scale and differing traditional cut points for mTBI and msTBI, we dichotomized the GOSE to reflect both functional independence (GOSE score 5 or above) and complete functional recovery (GOSE score of 8).

Rivermead Post Concussion Symptoms Questionnaire

The Rivermead Post Concussion Symptoms Questionnaire (RPQ) assesses the presence and severity of 16 symptoms that are new or worsened since the injury.²⁶ These diverse physical, cognitive, and emotional symptoms occur in all populations,²⁷ but are especially common after TBI.²⁸ Injury-related symptoms are rated by participants as 2 (mild problem relative to preinjury), 3 (moderate), or 4 (severe); summed ratings yield a symptom severity score ranging from 0 to 64. Following a previously established threshold to project persistent postconcussion symptoms, we defined better (ie, lower) TBI symptom burden as RPQ of 15 or lower.^29,30

Quality of Life After Brain Injury-Overall Scale

The 6-item Quality of Life After Brain Injury-Overall Scale (QOLIBRI-OS) assesses health-related quality of life (QoL) in domains of cognitive, emotional, and physical function³¹ on a 5-point scale (from not at all satisfied to very satisfied). Summed ratings (self-reported by participants) are transformed to produce a total score (100-point scale, with higher equaling better QoL). Scores were dichotomized as 52 or higher (better QoL) vs below 52 (worse QoL), a recommended cut score to indicate probable emotional distress and impaired health-related quality of life.^32,33

Statistical Analysis

Characteristics of subsamples with vs without outcome data were compared descriptively (percentages, means) and with Mann-Whitney U tests and Fisher exact tests. To facilitate drawing inferences for the full enrolled sample, all primary analyses incorporated inverse probability weighting. This approach more heavily weights data from groups who disproportionately did not have follow-up data to estimate parameters for the fully enrolled sample (eMethods in Supplement 1). Analyses were also performed without weighting, with a trivial effect on results.

Preliminary analyses also compared the mTBI, msTBI, and OTC groups on demographic and injury variables using Kruskal-Wallis H tests and Fisher exact tests to inform selection of covariates in multivariable regression models. For the primary analyses, we first computed the percentage of persons within each group who met each outcome at 1, 2, 3, 4, and 5 years. Second, we used mixed effects logistic regression models to evaluate the degree to which group, year since injury (treated linearly), and group × year estimated odds of each outcome, controlling for relevant sociodemographic and injury covariates (age, sex, race, ethnicity, insurance type, education, prior TBI, cause of injury). Categories for race included Alaskan Native or Inuit, Asian, Black, Native Hawaiian or Pacific Islander, Indian, White, and unknown; the source from which examiners collected racial and ethnic data was not documented. Groups with insufficient numbers of individuals who were functionally dependent (OTC group in primary analyses, and additionally the mTBI group without acute intracranial findings in supplemental analyses) were excluded from logistic regression analysis of functional independence (GOSE score 5 or above). Contrasts of within-group changes in outcome measures over time were calculated to interpret group × year interactions. Nonsignificant interaction terms were dropped to facilitate interpretability of main effects. In secondary analyses, we computed percentages for each GOSE domain to further describe the groups’ impairment or function. Supplemental analyses examined (1) the outcomes of the mTBI group stratifying the group by the presence or absence of acute intracranial findings on clinical head CT scans performed upon hospital admission and (2) outcomes for a subset of individuals who were followed from year 1 through year 4 or 5.

Finally, we computed cumulative mortality (ie, not known to have died at 1 year) for participants who died between 1 and 5 years postinjury, and compared groups on cumulative mortality using the log rank test. Tests were 2-tailed with α = .05; no adjustments were made for multiple comparisons. Inverse probability weights were derived using the TWANG Shiny App software package for Windows developed by RAND Corporation (downloaded in December 2019).³⁴ Mixed-effects regression modeling was conducted using SAS statistical software version 9.4 (SAS Institute), and other statistical analyses were conducted in SPSS Statistics for Windows version 26 (IBM Corp).

Results

Sample Characteristics

The full enrolled sample included 2661 participants (mean [SD] age, 41.0 [17.0] years; 1814 male [68%]; 436 Black [16%], 2034 White [76%], 191 other [7%]); 1196 participants were in the sample with outcome data vs 1465 participants without outcome data (eTable 2 in Supplement 1). A total 856 individuals were in the mTBI group, 188 in the msTBI group, and 152 in the OTC group, with statistically significant differences in demographics (age, sex), socioeconomic factors (eg, insurance type, educational history), prior TBI history, and cause of injury (Table 1). The percentage of participants with acute intracranial findings on admission head CT scans was 39% (322 of 832) in the mTBI group and 91% (162 of 178) in the msTBI group.

Table 1. Sample Characteristics and Group Comparisons.

Demographics	Patients, No. (%)			P value^a
Demographics	msTBI (n = 188)	mTBI (n = 856)	OTC (n = 152)	P value^a
Age, mean (SD), y	35.5 (14.4)	41.9 (17.3)	41.4 (15.7)	<.001
Sex
Female	45 (24)	309 (36)	61 (40)	.002
Male	143 (76)	547 (64)	91 (60)	.002
Race^b
Black	21 (11)	113 (13)	24 (16)	.59
White	152 (81)	693 (81)	120 (79)
Other/unknown^c	15 (8)	50 (6)	8 (5)
Hispanic ethnicity	36 (19)	155 (18)	34 (23)	.40
Insurance
Medicaid/uninsured	73 (40)	223 (26)	35 (23)	.001
Other insured^d	110 (60)	619 (74)	115 (77)	.001
Education, mean (SD), y	13.0 (2.7)	14.0 (2.8)	14.4 (2.8)	<.001
Previous TBI
No	152 (87)	636 (79)	117 (83)	.03
Yes, with hospitalization	16 (9)	102 (13)	20 (14)
Yes, without hospitalization	6 (3)	63 (8)	4 (3)
Neurodevelopmental disorder	13 (7)	72 (8)	11 (7)	.78
Mental health history	41 (22)	203 (24)	33 (22)	.80
Injury characteristics
Injury cause
MVC (occupant)	55 (29)	251 (29)	24 (16)	<.001
MCC	23 (12)	56 (7)	16 (11)
MVC (cyclist or pedestrian)	26 (14)	151 (18)	10 (7)
Fall	38 (20)	243 (28)	52 (34)
Assault	12 (6)	46 (5)	2 (1)
Other/unknown^e	34 (18)	109 (13)	48 (32)
CT results positive (vs negative)	162 (91)	322 (39)	0	<.001
Loss of consciousness^f	178 (98)	706 (86)	0	<.001
Posttraumatic amnesia^f	124 (94)	635 (80)	0	<.001
AIS head/neck ≥3	169 (90)	257 (30)	2 (1)	<.001
Maximum non-head/neck AIS ≥3	56 (30)	135 (16)	29 (19)	<.001
Highest level of care
Emergency department	0	216 (25)	60 (39)	<.001
Inpatient unit	4 (2)	384 (45)	85 (56)
Intensive care unit	184 (98)	256 (30)	7 (5)
Injury-related litigation	32 (22)	159 (22)	18 (15)	.22

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Abbreviations: AIS, Abbreviated Injury Severity score; CT, computed tomography; MCC, motorcycle crash; msTBI, moderate-severe traumatic brain injury; mTBI, mild traumatic brain injury; MVC, motor vehicle crash; OTC, orthopedic trauma control; TBI, traumatic brain injury.

^{^a}

Unweighted P values reported from Mann-Whitney and Fisher exact tests.

^{^b}

The source of race and ethnicity (eg, medical records vs participant report) was not collected.

^{^c}

Other or unknown race categories included Alaska Native or Inuit, Asian, American Indian, mixed race, Native Hawaiian or Pacific Islander, and unknown.

^{^d}

Other insurance categories included: insurance purchased directly from an insurance company or on the health insurance exchange (this person or family member); insurance through a current or former employer (of this person or another family member); Medicare, for people aged 65 years and older or people with certain disabilities; TRICARE (the US military’s health care program), Department of Veterans Affairs, or other military health care; and other.

^{^e}

Injury cause categories included act of mass violence, other, other nonintentional injury, other road traffic incident, suicide attempt, and unknown.

^{^f}

Witnessed and suspected categories collapsed.

Prevalence and Group Differences in Clinical Outcomes from 1 to 5 Years Postinjury

Figure 1 illustrates the unweighted percentage (95% CI) of each primary outcome by group (eTable 3 for accompanying numbers, eTable 4 for primary analyses using propensity weighting, and eTable 5 for sensitivity analyses verifying results in a subset of individuals who were followed from year 1 to years 4 and 5 in Supplement 1). Table 2 provides results of propensity-weighted mixed effects logistic regression models evaluating the effects of group, year, and group × year on the odds of each outcome, controlling for several sociodemographic and injury variables. Covariates were selected because they demonstrated different distributions across groups (Table 1) or were of substantive interest as potential social determinants of TBI outcomes. Unadjusted, unweighted regression models revealed quite similar group and year effects as the more complex multivariable models (eTable 6 in Supplement 1).

Table 2. Multivariable Mixed Effects Logistic Model Depicting Effects of Group, Year, and Other Variables on Odds of Favorable Outcome From 1 to 5 Years Postinjury With Propensity Weighting^a.

Variable	GOSE score ≥5		GOSE score of 8		RPQ score ≤15		QOLIBRI-OS score ≥52
Variable	OR (95% CI)	P value	OR (95% CI)	P value	OR (95% CI)	P value	OR (95% CI)	P value
Group	NA	<.001	NA	<.001	NA	<.001	NA	.004
msTBI vs mTBI	0.01 (0-0.04)	<.001	0.34 (0.24-0.48)	<.001	0.78 (0.54-1.12)	.18	0.81 (0.56-1.17)	.26
msTBI vs OTC	NA	NA	0.13 (0.08-0.21)	<.001	0.22 (0.13-0.37)	<.001	0.43 (0.26-0.72)	.001
mTBI vs OTC	NA	NA	0.39 (0.28-0.56)	<.001	0.28 (0.19-0.43)	<.001	0.54 (0.36-0.81)	.003
Year (per 1 y)	0.81 (0.64-1.03)	.08	1.01 (0.95-1.07)	.72	1.06 (1.00-1.13)	.06	1.05 (0.99-1.13)	.11
Group × year	NA	.005
msTBI (per 1 y)	1.28 (1.03-1.58)	.02	NA	NA	NA	NA	NA	NA
mTBI (per 1 y)	0.81 (0.64-1.03)	.08	NA	NA	NA	NA	NA	NA
OTC (per 1 y)
Age (per 10 y)	0.67 (0.55-0.82)	<.001	0.89 (0.82-0.96)	.002	0.98 (0.90-1.06)	.56	0.84 (0.78-0.91)	<.001
Female	0.56 (0.30-1.06)	.07	0.64 (0.50-0.82)	<.001	0.54 (0.42-0.71)	<.001	0.64 (0.49-0.84)	.001
Race	NA	.20	NA	.96	NA	.07	NA	.09
Black (vs White)	0.49 (0.22-1.10)	.08	1.00 (0.70-1.43)	.99	0.72 (0.50-1.03)	.08	0.75 (0.52-1.07)	.11
Other/unknown (vs White)	1.20 (0.31-4.68)	.80	1.07 (0.66-1.73)	.78	1.41 (0.83-2.40)	.21	1.47 (0.83-2.62)	.19
Hispanic ethnicity	0.79 (0.35-1.80)	.58	1.01 (0.73-1.40)	.95	0.83 (0.59-1.17)	.30	1.02 (0.72-1.45)	.91
Non-Medicaid insurance (vs Medicaid or uninsured)	2.35 (1.24-4.46)	.009	1.38 (1.05-1.82)	.02	1.58 (1.19-2.10)	.002	1.84 (1.39-2.45)	<.001
Years of education (per 4 y)	1.11 (0.99-1.25)	.06	1.09 (1.04-1.15)	<.001	1.11 (1.06-1.17)	<.001	1.14 (1.08-1.20)	<.001
Previous TBI	NA	.56	NA	.04	NA	.001	NA	<.001
Yes (vs no)	0.67 (0.31-1.47)	.32	0.68 (0.50-0.92)	.01	0.53 (0.39-0.73)	<.001	0.50 (0.37-0.69)	<.001
Unknown (vs no)	0.73 (0.23-2.33)	.59	1.04 (0.64-1.69)	.88	0.98 (0.58-1.64)	.93	0.99 (0.58-1.71)	.98
Injury cause	NA	.50	NA	.47	NA	.46	NA	.48
Fall (vs MVC)	0.73 (0.34-1.56)	.42	1.20 (0.90-1.59)	.22	1.15 (0.85-1.56)	.38	1.02 (0.75-1.40)	.89
Other/unknown (vs MVC)	0.66 (0.31-1.40)	.28	1.09 (0.80-1.49)	.59	0.91 (0.66-1.27)	.59	0.83 (0.60-1.16)	.28

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Abbreviations: GOSE, Glasgow Outcome Scale-Extended; msTBI, moderate-severe traumatic brain injury; mTBI, mild traumatic brain injury; MVC, motor vehicle/traffic crash; NA, not applicable; OTC, orthopedic trauma control; QOLIBRI-OS, Quality of Life After Brain Injury Scale-Overall Scale; RPQ, Rivermead Post Concussion Symptoms Questionnaire; TBI, traumatic brain injury.

^{^a}

Nonsignificant interactions were dropped from models reported (group × year P value was as follows: GOSE, P = .72; RPQ, P = .91; QOLIBRI-OS, P = .20).

The percentage of mTBI and OTC participants with recovery of functional independence (GOSE score 5 or higher) was 98% (95% CI, 96%-99%) to 100% (95% CI, 99%-100%) across time (Figure; eTables 3, 4, and 5 in Supplement 1). Because secondary analyses stratifying mTBI with vs without positive findings on CT scan demonstrated no significant differences between groups, all reported results collapse these groups (eTables 4, 5, and 7 in Supplement 1). Rates were lower for those with msTBI, although most individuals with msTBI achieved independence at 1 year (72%; 95% CI, 64%-79%), and this group showed increasing odds of independence over time (5 years: 80%; 95% CI, 69%-89%; group × year P = .005; msTBI per year: OR, 1.28; 95% CI, 1.03-1.58; P = .02; mTBI per year: OR, 0.81; 95% CI, 0.64-1.03; P = .08) (Table 2). Beyond group and year, odds of functional independence were lower in persons who were older (OR per age 10 years, 0.67; 95% CI, 0.55-0.82) and were higher in those with non-Medicaid insurance (vs Medicaid or no insurance: OR, 2.38; 95% CI, 1.26-4.50). When comparing participants in each group who were dependent vs independent within each GOSE domain (eg, home independence, travel, work, social functioning) across the 5 years of follow-up, domains of independence in the home and independence outside the home (eg, shopping, travel) displayed the largest increases in the percentage of persons demonstrating recovery from 1 to 5 years, as well as the highest rates of complete recovery compared with work, leisure, and relationship functioning, which displayed higher rates of limitations up to 5 years postinjury (Table 3; eTable 8 in Supplement 1).

Table 3. Frequencies of Each Glasgow Outcome Scale-Extended Domain.

Characteristic	Participants, No./total No. (%) [95% CI]
	msTBI					mTBI
	1 y (n = 145)	2 y (n = 55)	3 y (n = 112)	4 y (n = 100)	5 y (n = 69)	1 y (n = 707)	2 y (n = 210)	3 y (n = 350)	4 y (n = 410)	5 y (n = 461)
Independence in the home
No assistance	111/145 (76) [69-83]	48/55 (87) [75-95]	95/112 (84) [76-91]	86/100 (86) [77-92]	57/69 (82) [71-90]	704/707 (99) [99-100]	206/210 (98) [95-100]	347/350 (99) [97-100]	403/410 (98) [96-99]	454/461 (98) [97-99]
Infrequent assistance	7/145 (5) [2-10]	2/55 (4) [0-12]	4/112 (3) [1-8]	3/100 (3) [0-8]	2/69 (3) [0-10]	2/707 (0) [0-1]	0/210 (0) [0-2]	1/350 (0) [0-2]	3/410 (1) [0-2]	2/461 (0) [0-2]
Frequent assistance	27/145 (19) [13-26]	5/55 (9) [3-20]	14/112 (12) [7-20]	11/100 (11) [6-19]	10/69 (15) [7-25]	1/707 (0) [0-1]	3/210 (2) [0-5]	2/350 (1) [0-2]	4/410 (1) [0-3]	5/461 (1) [0-3]
Independence in shopping
No assistance	108/145 (74) [66-81]	46/55 (82) [70-91]	93/112 (82) [74-89]	85/100 (85) [77-92]	58/69 (83) [72-91]	704/707 (100) [99-100]	204/210 (98) [94-99]	347/350 (99) [97-100]	403/410 (98) [96-99]	453/461 (98) [97-99]
Assistance	37/145 (26) [19-34]	10/55 (18) [9-30]	20/112 (18) [11-26]	15/100 (15) [8-23]	12/69 (17) [9-28]	4/707 (0) [0-1]	5/210 (2) [1-6]	3/350 (1) [0-3]	7/410 (2) [1-4]	8/461 (2) [1-3]
Independent in traveling
No assistance	107/145 (74) [66-81]	45/55 (81) [68-90]	95/112 (84) [76-91]	87/100 (87) [78-93]	58/69 (84) [73-92]	701/707 (99) [98-100]	204/210 (98) [94-99]	345/350 (98) [96-99]	401/410 (98) [96-99]	451/461 (98) [96-99]
Assistance	38/145 (26) [19-34]	11/55 (19) [10-32]	17/112 (16) [9-24]	13/100 (13) [7-22]	11/69 (16) [8-27]	6/707 (1) [0-2]	5/210 (2) [1-6]	5/350 (2) [1-4]	9/410 (2) [1-4]	10/461 (2) [1-4]
Work
No deficit	66/136 (49) [40-57]	29/52 (56) [42-70]	57/102 (55) [45-65]	48/93 (52) [41-62]	31/66 (48) [35-61]	479/595 (80) [77-84]	134/167 (80) [73-86]	239/290 (82) [78-87]	286/339 (84) [80-88]	350/399 (88) [84-91]
Reduced capacity	17/136 (13) [8-20]	8/52 (16) [7-29]	16/102 (16) [9-25]	13/93 (14) [7-22]	9/66 (14) [7-25]	75/595 (13) [10-15]	20/167 (12) [8-18]	29/290 (10) [7-14]	36/339 (10) [7-14]	26/399 (6) [4-9]
Noncompetitive/unable to work	53/136 (39) [30-47]	14/52 (27) [16-42]	29/102 (29) [20-38]	32/93 (35) [25-45]	25/66 (38) [26-51]	42/595 (7) [5-9]	13/167 (8) [4-13]	22/290 (8) [5-11]	17/339 (5) [3-8]	23/399 (6) [4-9]
Social/leisure functioning
No deficit	80/145 (55) [46-63]	33/55 (59) [45-72]	58/112 (51) [42-61]	52/100 (52) [42-62]	32/69 (46) [34-59]	573/707 (81) [78-84]	143/210 (68) [62-75]	252/350 (72) [67-77]	284/410 (69) [65-74]	347/461 (75) [71-79]
A bit less	26/145 (18) [12-25]	9/55 (16) [7-28]	17/112 (15) [9-23]	13/100 (13) [7-21]	7/69 (10) [4-20]	75/707 (11) [8-13]	30/210 (14) [10-20]	50/350 (14) [11-19]	52/410 (13) [10-16]	46/461 (10) [7-13]
Much less	20/145 (14) [8-20]	7/55 (13) [5-25]	20/112 (17) [11-26]	23/100 (23) [15-32]	20/69 (30) [19-42]	42/707 (6) [4-8]	30/210 (14) [10-20]	39/350 (11) [8-15]	51/410 (12) [9-16]	49/461 (11) [8-14]
Unable	20/145 (14) [9-20]	7/55 (13) [5-25]	18/112 (16) [10-24]	12/100 (12) [7-21]	10/69 (14) [7-25]	17/707 (2) [1-4]	7/210 (3) [1-7]	9/350 (2) [1-5]	23/410 (6) [4-8]	19/461 (4) [3-7]
Family disruption
No disruption	86/145 (59) [51-67]	32/55 (58) [44-71]	66/112 (59) [49-68]	60/100 (60) [50-70]	40/69 (57) [45-69]	510/707 (72) [69-75]	128/210 (61) [54-68]	236/350 (67) [62-72]	293/410 (71) [67-76]	345/461 (75) [71-79]
Occasional	12/145 (8) [4-14]	12/55 (22) [12-36]	13/112 (12) [6-19]	18/100 (18) [11-27]	10/69 (15) [7-25]	73/707 (10) [8-13]	39/210 (18) [13-24]	48/350 (14) [10-18]	38/410 (9) [7-12]	59/461 (13) [10-16]
Frequent	34/145 (23) [17-31]	6/55 (10) [4-21]	23/112 (20) [13-29]	14/100 (14) [8-23]	13/69 (18) [10-30]	94/707 (13) [11-16]	27/210 (13) [9-18]	49/350 (14) [11-18]	55/410 (13) [10-17]	47/461 (10) [8-13]
Constant	14/145 (9) [5-15]	5/55 (9) [3-20]	10/112 (9) [4-16]	8/100 (8) [3-15]	7/69 (10) [4-19]	30/707 (4) [3-6]	17/210 (8) [5-12]	17/350 (5) [3-8]	25/410 (6) [4-9]	10/461 (2) [1-4]
Other disabling symptoms
No impact	46/145 (32) [24-40]	18/55 (32) [20-46]	33/112 (29) [21-39]	30/100 (30) [21-40]	21/69 (30) [20-42]	345/706 (49) [45-53]	93/210 (45) [38-52]	152/350 (43) [38-49]	182/410 (44) [40-49]	243/461 (53) [48-57]
Some impact	99/145 (68) [60-76]	38/55 (68) [54-80]	79/112 (71) [61-79]	70/100 (70) [60-79]	48/69 (70) [58-80]	360/706 (51) [47-55]	116/210 (55) [48-62]	198/350 (57) [51-62]	228/410 (56) [51-60]	218/461 (47) [43-52]

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Abbreviations: msTBI, moderate-severe traumatic brain injury; mTBI, mild traumatic brain injury; OTC, orthopedic trauma control.

Other outcomes had nonsignificant results of year and group × year (consequently, interaction terms were dropped from the remaining models). Odds of complete functional recovery (GOSE score of 8) were lower for msTBI vs mTBI (17% vs 47% in year 5; group main effect: OR, 0.34; 95% CI, 0.24-0.48) and lower for mTBI vs OTC (47% vs 62% in year 5; group main effect: OR, 0.39 95% CI, 0.28-0.56). Odds of complete functional recovery were also lower vs OTC for persons with older age (per age 10 years: OR, 0.89; 95% CI, 0.82-0.96; P = .002), female sex (OR, 0.64; 95% CI, 0.50-0.82; P < .001), Medicaid or no insurance (OR for non-Medicaid insurance, 1.38; 95% CI, 1.05-1.82; P = .02), lower education (per 4 years: OR, 1.09; 95% CI, 1.04-1.15; P < .001), and prior TBI history (yes vs no: OR, 0.68; 95% CI, 0.50-0.92; P = .01).

Odds of better symptom outcome (RPQ score 15 or lower) were lower in both mTBI (vs OTC: OR, 0.28; 95% CI, 0.19-0.43) and msTBI (vs OTC: OR, 0.22; 95% CI, 0.13-0.37) groups, and nonsignificant between subgroups (msTBI vs mTBI: OR, 0.78; 95% CI, 0.54-1.12). Odds of better symptom outcome were lower in persons with female sex (OR, 0.54; 95% CI, 0.42-0.71; P < .001), Medicaid or no insurance (OR for non-Medicaid insurance, 1.58; 95% CI, 1.19-2.10; P = .002), less education (per 4 years: OR, 1.11; 95% CI, 1.06-1.17; P < .001), and prior TBI (yes vs no: OR, 0.53; 95% CI, 0.39-0.73; P < .001).

Odds of better quality of life (QOLIBRI-OS score 52 or above) were lower in both TBI subgroups relative to OTCs (mTBI: OR, 0.54; 95% CI, 0.36-0.81; msTBI: OR, 0.43; 95% CI, 0.26-0.72) but were comparable with each other (msTBI vs mTBI: OR, 0.81; 95% CI, 0.56-1.17). Odds of better quality of life were lower in persons with older age (per age 10 years: OR, 0.84; 95% CI, 0.78-0.91; P < .001), female sex (OR, 0.64; 95% CI, 0.49-0.84; P = .001), Medicaid or no insurance (OR for non-Medicaid insurance, 1.84; 95% CI, 1.39-2.45; P < .001), lower education (per 4 years: OR, 1.14; 95% CI, 1.08-1.20; P < .001), and prior TBI (yes vs no: OR, 0.50; 95% CI, 0.37-0.69; P < .001). Persons with msTBI displayed higher rates of death (7 individuals [5.5%] at 5 years) than the mTBI and OTC groups (12 [1.5%] and 1 [0.7%] individuals at 5 years, respectively; log rank P = .02) (Table 4).

Table 4. Cumulative Mortality From 1 to 5 Years Postinjury Among Persons Believed to Be Living at 1 Year^a.

Year	Deaths, No. (%)			P value
Year	msTBI	mTBI	OTC	P value
1	0	0	0	.02
2	4 (2.2)	2 (0.2)	1 (0.7)
3	5 (2.8)	6 (0.7)	1 (0.7)
4	5 (2.8)	11 (1.3)	1 (0.7)
5	7 (5.5)	12 (1.5)	1 (0.7)

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Abbreviations: OTC, orthopedic trauma control; msTBI, moderate-severe TBI; mTBI, mild traumatic brain injury.

^{^a}

Cells report cumulative mortality and number of deaths (cumulative). P value from log rank test.

Discussion

In this prospective, longitudinal study of former level I trauma center patients at 1 to 5 years post-TBI, we found both potential for continued functional recovery and persistently elevated rates of clinical impairment up to 5 years across all TBI severities. Survivors of msTBI demonstrated, on average, increasing odds of recovery of functional independence over time. As defined in this study, independence (ie, GOSE scores of 5 or above) reflected sufficient independence in home activities to be safely left alone for at least 24 hours, as well as the ability to conduct simple shopping tasks and arrange or provide one’s own transportation. This important milestone indicates that persons with TBI, as well as individuals providing support to them, reclaim some autonomy in daily life.

Yet persons who reach this level of function may experience myriad symptoms, cognitive impairments, and physical limitations that disrupt life function and perceived life quality. For example, 83% of msTBI and 53% of mTBI participants reported incomplete functional recovery (ie, GOSE score below 8) at 5 years postinjury, reflecting stable odds of incomplete recovery from 1 to 5 years (ie, no interaction with year) that remained higher than the OTC group (38% at 5 years).^5,15 Similarly, the proportion of persons with lesser TBI-related symptom burden and better health-related quality of life was stable for all groups over time. The TBI groups showed comparable symptom and quality of life outcomes. Yet, both TBI groups experienced less favorable symptom and quality of life outcomes than the OTC group. These findings illustrate the differing relevance of injury variables across clinical outcomes and highlight the need to investigate the causal factors that drive long-term impairments captured by diverse outcomes.

Our findings align with those of the TBI Model Systems (TBI-MS) study, finding higher rates of functional improvement than decline from 1 to 5 years post-msTBI.³⁵ However, the TBI-MS study also illustrated the variable recovery trajectories across individuals, with most demonstrating static functional outcome and a minority declining. Like the TBI-MS study, we also found that despite potential for clinical improvements from 1 to 5 years, persons with msTBI have increased mortality rates relative to mTBI or OTC participants.^36,37 It is unclear what factors contributed to the outcomes of the msTBI group in our sample. Other studies point to depression, physical comorbidities, cognitive functioning, and age as prognostic of long-term functional and quality of life outcomes after TBI.^{8,11,35,38,39} In light of the relative dearth of rehabilitation services and community supports beyond the first several months postinjury,¹² our findings justify intensifying efforts to provide longer-term rehabilitation, mental health treatment, and community services for persons with TBI. The elevated rates of incomplete recovery among mTBI participants demonstrates the need for more comprehensive systems of care for level I trauma center patients irrespective of TBI severity and time since injury.

This study also revealed several social determinants of long-term TBI outcomes. Independent of injury group and time since injury, odds of less favorable outcomes manifested in persons who were older, female, and who had less baseline education, Medicaid or no insurance at the time of injury, and histories of prior TBI. Although cause of injury was not associated with outcomes, other research points to assaultive injury as prognostic of some outcomes.⁴⁰ (Our sample had insufficient cases of assault to treat this category separately.) Taken together, our findings support the consensus that TBI recovery is influenced by multiple factors.^{14,41,42,43,44,45,46,47,48,49} Nuanced interrogation of the biological mechanisms by which age and sex affect TBI recovery will fuel the design of more effective treatments. Additionally, efforts to provide follow-up care for TBI must account for difficulties accessing health care that result from insufficient health insurance coverage for many Americans with TBI.⁵⁰

Within individuals with TBI and GCS scores between 13 and 15, abnormal results on a head CT at hospital admission was not associated with clinical outcomes. This is consistent with research finding small or conflicting associations between TBI severity and self-report outcomes of symptoms and quality of life,^17,18,22 while contributing to knowledge on long-term functional outcome. These findings are likely to reflect the relatively severe grade of CT- GCS 13 to 15 TBI in level I trauma centers (eg, 27% of this subgroup of the TRACK-TBI sample have acute intracranial findings on magnetic resonance imaging around 2 weeks postinjury).^51,52

Limitations

This study had several limitations. Our group-level comparisons could not illustrate the varied trajectories of long-term recovery that are known to occur after TBI. Because TRACK-TBI only enrolled level I trauma center patients with TBI who underwent a clinical head CT scan, the findings cannot be generalized beyond these characteristics. Additionally, the study design precluded annual follow-up assessment for every patient during the entire 1-to-5-year follow-up period (eTable 1 in Supplement 1). However, our comparison of weighted and unweighted analysis and sensitivity analyses in a subset of persons followed from 1 to 5 years supports the robustness of our findings. Additionally, because outcomes were gathered from research contact rather than public death databases, mortality may be underestimated.

Conclusions

This study was unique in its long-term follow-up of persons with mTBI, msTBI, and orthopedic injury. That msTBI survivors at 1 year postinjury experienced both greater increases in functional independence and elevated rates of mortality relative to mTBI and OTC groups demonstrates the need to advance understanding of factors that contribute to long-term TBI outcomes. That mTBI was also associated with persistently elevated rates of adverse clinical outcomes from 1 to 5 years postinjury demonstrates that all level I trauma center patients with TBI should be more closely monitored and treated for injury sequelae, from the acute through chronic recovery period. Finally, the urgency of providing better clinical and community support is paramount.

Supplement 1.

eMethods. Inverse Probability Weighting Methods

eTable 1. Summary of Participants From the Initial TRACK-TBI Study Considered for the Present Study Who Were Eligible for TRACK-LONG Follow-up Appointments by Year Post-injury and Number Followed

eTable 2. Overview of Sample of Interest and Predictors of Being Followed 1-5 Years

eTable 3. Percentage of Individuals With Favorable Recovery From 1-5 Years Post-injury (Unweighted)

eTable 4. Percentage of Individuals With Favorable Outcome From 1-5 Years Post-injury (Weighted)

eTable 5. Percentage of Individuals Who Completed Both a Year 1 and Year 4 or 5 Outcome Assessment With Favorable Outcome at Year 1 and Year 4/5 Post-injury (Weighted)

eTable 6. Mixed Effects Logistic Model Depicting Group, Year, and Group × Year Effects on Favorable Outcome (Without Propensity Weighting or Additional Covariates)

eTable 7. Multivariable Mixed Effects Logistic Model Depicting Effects of Group, Year, and Other Variables on Odds of Favorable Outcome From 1-5 Years Post-injury (With Propensity Weighting)

eTable 8. Frequencies of Each Glasgow Outcome Scale-Extended Domain in the Control Group

Click here for additional data file.^{(409.8KB, pdf)}

Supplement 2.

Data Sharing Statement

Click here for additional data file.^{(16.5KB, pdf)}

References

1.Carroll LJ, Cassidy JD, Peloso PM, et al. ; WHO Collaborating Centre Task Force on Mild Traumatic Brain Injury . Prognosis for mild traumatic brain injury: results of the WHO Collaborating Centre Task Force on Mild Traumatic Brain Injury. J Rehabil Med. 2004;(43)(suppl):84-105. doi: 10.1080/16501960410023859 [DOI] [PubMed] [Google Scholar]
2.Schretlen DJ, Shapiro AM. A quantitative review of the effects of traumatic brain injury on cognitive functioning. Int Rev Psychiatry. 2003;15(4):341-349. doi: 10.1080/09540260310001606728 [DOI] [PubMed] [Google Scholar]
3.McCrea M, Iverson GL, McAllister TW, et al. An integrated review of recovery after mild traumatic brain injury (MTBI): implications for clinical management. Clin Neuropsychol. 2009;23(8):1368-1390. doi: 10.1080/13854040903074652 [DOI] [PubMed] [Google Scholar]
4.Pagulayan KF, Temkin NR, Machamer J, Dikmen SS. A longitudinal study of health-related quality of life after traumatic brain injury. Arch Phys Med Rehabil. 2006;87(5):611-618. doi: 10.1016/j.apmr.2006.01.018 [DOI] [PubMed] [Google Scholar]
5.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]
6.Maas AI, Stocchetti N, Bullock R. Moderate and severe traumatic brain injury in adults. Lancet Neurol. 2008;7(8):728-741. doi: 10.1016/S1474-4422(08)70164-9 [DOI] [PubMed] [Google Scholar]
7.Corrigan JD, Hammond FM. Traumatic brain injury as a chronic health condition. Arch Phys Med Rehabil. 2013;94(6):1199-1201. doi: 10.1016/j.apmr.2013.01.023 [DOI] [PubMed] [Google Scholar]
8.Corrigan JD, Cuthbert JP, Harrison-Felix C, et al. US population estimates of health and social outcomes 5 years after rehabilitation for traumatic brain injury. J Head Trauma Rehabil. 2014;29(6):E1-E9. doi: 10.1097/HTR.0000000000000020 [DOI] [PubMed] [Google Scholar]
9.Masel BE, DeWitt DS. Traumatic brain injury: a disease process, not an event. J Neurotrauma. 2010;27(8):1529-1540. doi: 10.1089/neu.2010.1358 [DOI] [PubMed] [Google Scholar]
10.Vanderploeg RD, Curtiss G, Luis CA, Salazar AM. Long-term morbidities following self-reported mild traumatic brain injury. J Clin Exp Neuropsychol. 2007;29(6):585-598. doi: 10.1080/13803390600826587 [DOI] [PubMed] [Google Scholar]
11.Kumar RG, Ketchum JM, Corrigan JD, Hammond FM, Sevigny M, Dams-O’Connor K. The longitudinal effects of comorbid health burden on functional outcomes for adults with moderate to severe traumatic brain injury. J Head Trauma Rehabil. 2020;35(4):E372-E381. doi: 10.1097/HTR.0000000000000572 [DOI] [PMC free article] [PubMed] [Google Scholar]
12.Andelic N, Forslund MV, Perrin PB, et al. Long-term follow-up of use of therapy services for patients with moderate-to-severe traumatic brain injury. J Rehabil Med. 2020;52(3):jrm00034. doi: 10.2340/16501977-2662 [DOI] [PubMed] [Google Scholar]
13.Mahoney EJ, Silva MA, Reljic T, et al. Rehabilitation needs at 5 years post-traumatic brain injury: a VA TBI Model Systems study. J Head Trauma Rehabil. 2021;36(3):175-185. doi: 10.1097/HTR.0000000000000629 [DOI] [PubMed] [Google Scholar]
14.National Academy of Sciences, Engineering, and Medicine . Traumatic Brain Injury: A Roadmap for Accelerating Progress. The National Academies Press; 2022. [PubMed] [Google Scholar]
15.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]
16.Maas AI, Menon DK, Steyerberg EW, et al. ; CENTER-TBI Participants and Investigators . Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI): a prospective longitudinal observational study. Neurosurgery. 2015;76(1):67-80. doi: 10.1227/NEU.0000000000000575 [DOI] [PubMed] [Google Scholar]
17.Machamer J, Temkin N, Dikmen S, et al. ; TRACK-TBI Investigators . Symptom frequency and persistence in the first year after traumatic brain injury: a TRACK-TBI study. J Neurotrauma. 2022;39(5-6):358-370. doi: 10.1089/neu.2021.0348 [DOI] [PMC free article] [PubMed] [Google Scholar]
18.Nelson LD, Kramer MD, Joyner KJ, et al. ; TRACK-TBI Investigators . Relationship between transdiagnostic dimensions of psychopathology and traumatic brain injury (TBI): a TRACK-TBI study. J Abnorm Psychol. 2021;130(5):423-434. doi: 10.1037/abn0000672 [DOI] [PMC free article] [PubMed] [Google Scholar]
19.Rauen K, Reichelt L, Probst P, et al. Quality of life up to 10 years after traumatic brain injury: a cross-sectional analysis. Health Qual Life Outcomes. 2020;18(1):166. doi: 10.1186/s12955-020-01391-3 [DOI] [PMC free article] [PubMed] [Google Scholar]
20.von Steinbüchel N, Wilson L, Gibbons H, et al. ; QOLIBRI Task Force . Quality of Life after Brain Injury (QOLIBRI): scale validity and correlates of quality of life. J Neurotrauma. 2010;27(7):1157-1165. doi: 10.1089/neu.2009.1077 [DOI] [PubMed] [Google Scholar]
21.Born K, Amsler F, Gross T. Prospective evaluation of the Quality of Life after Brain Injury (QOLIBRI) score: minor differences in patients with major versus no or mild traumatic brain injury at one-year follow up. Health Qual Life Outcomes. 2018;16(1):136. doi: 10.1186/s12955-018-0966-z [DOI] [PMC free article] [PubMed] [Google Scholar]
22.Kreitzer N, Jain S, Young JS, et al. ; Transforming Research and Clinical Knowledge in Traumatic Brain Injury (TRACK-TBI) Investigators . Comparing the Quality of Life after Brain Injury-Overall Scale and Satisfaction with Life Scale as outcome measures for traumatic brain injury research. J Neurotrauma. 2021;38(23):3352-3363. doi: 10.1089/neu.2020.7546 [DOI] [PMC free article] [PubMed] [Google Scholar]
23.Kay T, Harrington D, Adams R, Anderson T, et al. Mild traumatic brain injury committee of the head injury interdisciplinary special interest group of the American Congress of Rehabilitation Medicine—definition of mild traumatic brain injury. J Head Trauma Rehabil. 1993;8(3):86-87. [Google Scholar]
24.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]
25.Wilson L, Boase K, Nelson LD, et al. A manual for the Glasgow Outcome Scale-Extended Interview. J Neurotrauma. 2021;38(17):2435-2446. doi: 10.1089/neu.2020.7527 [DOI] [PMC free article] [PubMed] [Google Scholar]
26.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]
27.Iverson GL, Lange RT. Examination of “postconcussion-like” symptoms in a healthy sample. Appl Neuropsychol. 2003;10(3):137-144. doi: 10.1207/S15324826AN1003_02 [DOI] [PubMed] [Google Scholar]
28.Rees PM. Contemporary issues in mild traumatic brain injury. Arch Phys Med Rehabil. 2003;84(12):1885-1894. doi: 10.1016/j.apmr.2003.03.001 [DOI] [PubMed] [Google Scholar]
29.Temkin N, Machamer J, Dikmen S, et al. Risk factors for high symptom burden 3 months after traumatic brain injury and implications for clinical trial: a TRACK-TBI study. J Neurotrauma. 2022;39(21-22):1524-1532. doi: 10.1089/neu.2022.0113 [DOI] [PMC free article] [PubMed] [Google Scholar]
30.Thompson C, Davies P, Herrmann L, Summers M, Potter S. Approaches to establishing validated cut-off scores on the Rivermead Post-Concussion Symptoms Questionnaire (RPQ). Brain Inj. 2016;30(5-6):770. [Google Scholar]
31.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]
32.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]
33.Truelle JL, Koskinen S, Hawthorne G, et al. ; Qolibri Task Force . Quality of life after traumatic brain injury: the clinical use of the QOLIBRI, a novel disease-specific instrument. Brain Inj. 2010;24(11):1272-1291. doi: 10.3109/02699052.2010.506865 [DOI] [PubMed] [Google Scholar]
34.Griffon BA, Ridgeway G, Morral AR, Ramchand R, Jaycox JH, McCaffrey DF. Toolkit for Weighting and Analysis of Nonequivalent Groups (TWANG) website. RAND Corporation . Published online 2014. Accessed October 9, 2022. https://www.rand.org/statistics/twang
35.Hammond FM, Hart T, Bushnik T, Corrigan JD, Sasser H. Change and predictors of change in communication, cognition, and social function between 1 and 5 years after traumatic brain injury. J Head Trauma Rehabil. 2004;19(4):314-328. doi: 10.1097/00001199-200407000-00006 [DOI] [PubMed] [Google Scholar]
36.Brooks JC, Strauss DJ, Shavelle RM, Paculdo DR, Hammond FM, Harrison-Felix CL. Long-term disability and survival in traumatic brain injury: results from the National Institute on Disability and Rehabilitation Research Model Systems. Arch Phys Med Rehabil. 2013;94(11):2203-2209. doi: 10.1016/j.apmr.2013.07.005 [DOI] [PubMed] [Google Scholar]
37.Harrison-Felix C, Kolakowsky-Hayner SA, Hammond FM, et al. Mortality after surviving traumatic brain injury: risks based on age groups. J Head Trauma Rehabil. 2012;27(6):E45-E56. doi: 10.1097/HTR.0b013e31827340ba [DOI] [PubMed] [Google Scholar]
38.Juengst SB, Adams LM, Bogner JA, et al. Trajectories of life satisfaction after traumatic brain injury: influence of life roles, age, cognitive disability, and depressive symptoms. Rehabil Psychol. 2015;60(4):353-364. doi: 10.1037/rep0000056 [DOI] [PMC free article] [PubMed] [Google Scholar]
39.Azouvi P, Ghout I, Bayen E, et al. Disability and health-related quality-of-life 4 years after a severe traumatic brain injury: a structural equation modelling analysis. Brain Inj. 2016;30(13-14):1665-1671. doi: 10.1080/02699052.2016.1201593 [DOI] [PubMed] [Google Scholar]
40.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]
41.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]
42.Nelson LD, Furger RE, Ranson J, et al. Acute clinical predictors of symptom recovery in emergency department patients with uncomplicated mild traumatic brain injury or non-traumatic brain injuries. J Neurotrauma. 2018;35(2):249-259. doi: 10.1089/neu.2017.4988 [DOI] [PMC free article] [PubMed] [Google Scholar]
43.Cnossen MC, van der Naalt J, Spikman JM, et al. Prediction of persistent post-concussion symptoms after mild traumatic brain injury. J Neurotrauma. 2018;35(22):2691-2698. doi: 10.1089/neu.2017.5486 [DOI] [PubMed] [Google Scholar]
44.Booker J, Sinha S, Choudhari K, Dawson J, Singh R. Description of the predictors of persistent post-concussion symptoms and disability after mild traumatic brain injury: the SHEFBIT cohort. Br J Neurosurg. 2019;33(4):367-375. doi: 10.1080/02688697.2019.1598542 [DOI] [PubMed] [Google Scholar]
45.Rabinowitz AR, Li X, McCauley SR, et al. Prevalence and predictors of poor recovery from mild traumatic brain injury. J Neurotrauma. 2015;32(19):1488-1496. doi: 10.1089/neu.2014.3555 [DOI] [PMC free article] [PubMed] [Google Scholar]
46.Ponsford J, Cameron P, Fitzgerald M, Grant M, Mikocka-Walus A, Schönberger M. Predictors of postconcussive symptoms 3 months after mild traumatic brain injury. Neuropsychology. 2012;26(3):304-313. doi: 10.1037/a0027888 [DOI] [PubMed] [Google Scholar]
47.Roozenbeek B, Lingsma HF, Lecky FE, et al. ; International Mission on Prognosis Analysis of Clinical Trials in Traumatic Brain Injury (IMPACT) Study Group; Corticosteroid Randomisation After Significant Head Injury (CRASH) Trial Collaborators; Trauma Audit and Research Network (TARN) . Prediction of outcome after moderate and severe traumatic brain injury: external validation of the International Mission on Prognosis and Analysis of Clinical Trials (IMPACT) and Corticoid Randomisation After Significant Head injury (CRASH) prognostic models. Crit Care Med. 2012;40(5):1609-1617. doi: 10.1097/CCM.0b013e31824519ce [DOI] [PMC free article] [PubMed] [Google Scholar]
48.Dijkland SA, Helmrich IRAR, Nieboer D, et al. ; CENTER-TBI Participants and Investigators . Outcome prediction after moderate and severe traumatic brain injury: external validation of two established prognostic models in 1742 European patients. J Neurotrauma. 2021;38(10):1377-1388. doi: 10.1089/neu.2020.7300 [DOI] [PubMed] [Google Scholar]
49.Miller T, Kallenbach MD, Huber DL, Brett BL, Nelson LD. Relationship between neighborhood disadvantage and mild traumatic brain injury symptoms. J Head Trauma Rehabil. Published online October 14, 2022. doi: 10.1097/HTR.0000000000000809 [DOI] [PMC free article] [PubMed] [Google Scholar]
50.Asemota AO, George BP, Cumpsty-Fowler CJ, Haider AH, Schneider EB. Race and insurance disparities in discharge to rehabilitation for patients with traumatic brain injury. J Neurotrauma. 2013;30(24):2057-2065. doi: 10.1089/neu.2013.3091 [DOI] [PMC free article] [PubMed] [Google Scholar]
51.Yuh EL, Mukherjee P, Lingsma HF, et al. ; TRACK-TBI Investigators . Magnetic resonance imaging improves 3-month outcome prediction in mild traumatic brain injury. Ann Neurol. 2013;73(2):224-235. doi: 10.1002/ana.23783 [DOI] [PMC free article] [PubMed] [Google Scholar]
52.Yue JK, Yuh EL, Korley FK, et al. ; TRACK-TBI Investigators . Association between plasma GFAP concentrations and MRI abnormalities in patients with CT-negative traumatic brain injury in the TRACK-TBI cohort: a prospective multicentre study. Lancet Neurol. 2019;18(10):953-961. doi: 10.1016/S1474-4422(19)30282-0 [DOI] [PubMed] [Google Scholar]

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