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Item Acute Ischemic Stroke After Moderate to Severe Traumatic Brain Injury: Incidence and Impact on Outcome(AHA, 2017-07) Kowalski, Robert G.; Haarbauer-Krupa, Juliet K.; Bell, Jeneita M.; Corrigan, John D.; Hammond, Flora M.; Torbey, Michel T.; Hofmann, Melissa C.; Dams-O'Connor, Kristen; Miller, A. Cate; Whiteneck, Gale G.; Physical Medicine and Rehabilitation, School of MedicineBackground and Purpose—Traumatic brain injury (TBI) leads to nearly 300 000 annual US hospitalizations and increased lifetime risk of acute ischemic stroke (AIS). Occurrence of AIS immediately after TBI has not been well characterized. We evaluated AIS acutely after TBI and its impact on outcome. Methods—A prospective database of moderate to severe TBI survivors, admitted to inpatient rehabilitation at 22 Traumatic Brain Injury Model Systems centers and their referring acute-care hospitals, was analyzed. Outcome measures were AIS incidence, duration of posttraumatic amnesia, Functional Independence Measure, and Disability Rating Scale, at rehabilitation discharge. Results—Between October 1, 2007, and March 31, 2015, 6488 patients with TBI were enrolled in the Traumatic Brain Injury Model Systems National Database. One hundred and fifty-nine (2.5%) patients had a concurrent AIS, and among these, median age was 40 years. AIS was associated with intracranial mass effect and carotid or vertebral artery dissection. High-velocity events more commonly caused TBI with dissection. AIS predicted poorer outcome by all measures, accounting for a 13.3-point reduction in Functional Independence Measure total score (95% confidence interval, −16.8 to −9.7; P<0.001), a 1.9-point increase in Disability Rating Scale (95% confidence interval, 1.3–2.5; P<0.001), and an 18.3-day increase in posttraumatic amnesia duration (95% confidence interval, 13.1–23.4; P<0.001). Conclusions—Ischemic stroke is observed acutely in 2.5% of moderate to severe TBI survivors and predicts worse functional and cognitive outcome. Half of TBI patients with AIS were aged ≤40 years, and AIS patients more often had cervical dissection. Vigilance for AIS is warranted acutely after TBI, particularly after high-velocity events.Item Advanced Therapy in Traumatic Brain Injury Inpatient Rehabilitation: Effects on Outcomes During the First Year after Discharge(Elsevier, 2019) Timpson, Misti; Hade, Erinn M.; Beaulieu, Cynthia; Horn, Susan D.; Hammond, Flora M.; Peng, Juan; Montgomery, Erin; Giuffrida, Clare; Gilchrist, Kamie; Lash, Aubrey; Dijkers, Marcel; Corrigan, John D.; Bogner, Jennifer; Physical Medicine and Rehabilitation, School of MedicineObjective To use causal inference methods to determine if receipt of a greater proportion inpatient rehabilitation treatment focused on higher level functions, e.g. executive functions, ambulating over uneven surfaces (Advanced Therapy, AdvTx) results in better rehabilitation outcomes. Design A cohort study using propensity score methods applied to the TBI-Practice-Based Evidence (TBI-PBE) database, a database consisting of multi-site, prospective, longitudinal observational data. Setting Acute inpatient rehabilitation (IRF). Participants Patients enrolled in the TBI-PBE study (n=1843), aged 14 years or older, who sustained a severe, moderate, or complicated mild TBI, receiving their first IRF admission to one of 9 sites in the US, and consented to follow-up 3 and 9 months post discharge from inpatient rehabilitation. Interventions Not applicable. Main Outcome Measures: Participation Assessment with Recombined Tools-Objective-17, FIMTM Motor and Cognitive scores, Satisfaction with Life Scale, and Patient Health Questionnaire-9. Results Controlling for measured potential confounders, increasing the percentage of AdvTx during inpatient TBI rehabilitation was found to be associated with better community participation, functional independence, life satisfaction, and decreased likelihood of depression during the year following discharge from inpatient rehabilitation. Participants who began rehabilitation with greater disability experienced larger gains on some outcomes than those who began rehabilitation with more intact abilities. Conclusions Increasing the proportion of treatment targeting higher level functions appears to have no detrimental and a small, beneficial effect on outcome. Caution should be exercised when inferring causality given that a large number of potential confounders could not be completely controlled with propensity score methods. Further, the extent to which unmeasured confounders influenced the findings is not known and could be of particular concern due to the potential for the patient’s recovery trajectory to influence therapists’ decisions to provide a greater amount AdvTx.Item Association of Sex and Age With Mild Traumatic Brain Injury-Related Symptoms: A TRACK-TBI Study(American Medical Association, 2021-04-01) Levin, Harvey S.; Temkin, Nancy R.; Barber, Jason; Nelson, Lindsay D.; Robertson, Claudia; Brennan, Jeffrey; Stein, Murray B.; Yue, John K.; Giacino, Joseph T.; McCrea, Michael A.; Diaz-Arrastia, Ramon; Mukherjee, Pratik; Okonkwo, David O.; Boase, Kim; Markowitz, Amy J.; Bodien, Yelena; Taylor, Sabrina; Vassar, Mary J.; Manley, Geoffrey T.; TRACK-TBI Investigators; Adeoye, Opeolu; Badjatia, Neeraj; Bullock, M. Ross; Chesnut, Randall; Corrigan, John D.; Crawford, Karen; Dikmen, Sureyya; Duhaime, Ann-Christine; Ellenbogen, Richard; Feeser, V. Ramana; Ferguson, Adam R.; Foreman, Brandon; Gardner, Raquel; Gaudette, Etienne; Gonzalez, Luis; Gopinath, Shankar; Gullapalli, Rao; Hemphill, J. Claude; Hotz, Gillian; Jain, Sonia; Keene, C. Dirk; Korley, Frederick K.; Kramer, Joel; Kreitzer, Natalie; Lindsell, Chris; Machamer, Joan; Madden, Christopher; Martin, Alastair; McAllister, Thomas; Merchant, Randall; Nolan, Amber; Ngwenya, Laura B.; Noel, Florence; Palacios, Eva; Puccio, Ava; Rabinowitz, Miri; Rosand, Jonathan; Sander, Angelle; Satris, Gabriella; Schnyer, David; Seabury, Seth; Sun, Xiaoying; Toga, Arthur; Valadka, Alex; Wang, Kevin; Yuh, Esther; Zafonte, Ross; Psychiatry, School of MedicineImportance: Knowledge of differences in mild traumatic brain injury (mTBI) recovery by sex and age may inform individualized treatment of these patients. Objective: To identify sex-related differences in symptom recovery from mTBI; secondarily, to explore age differences within women, who demonstrate poorer outcomes after TBI. Design, setting, and participants: The prospective cohort study Transforming Research and Clinical Knowledge in Traumatic Brain Injury (TRACK-TBI) recruited 2000 patients with mTBI from February 26, 2014, to July 3, 2018, and 299 patients with orthopedic trauma (who served as controls) from January 26, 2016, to July 27, 2018. Patients were recruited from 18 level I trauma centers and followed up for 12 months. Data were analyzed from August 19, 2020, to March 3, 2021. Exposures: Patients with mTBI (defined by a Glasgow Coma Scale score of 13-15) triaged to head computed tomography in 24 hours or less; patients with orthopedic trauma served as controls. Main outcomes and measures: Measured outcomes included (1) the Rivermead Post Concussion Symptoms Questionnaire (RPQ), a 16-item self-report scale that assesses postconcussion symptom severity over the past 7 days relative to preinjury; (2) the Posttraumatic Stress Disorder Checklist for the Diagnostic and Statistical Manual of Mental Disorders (Fifth Edition) (PCL-5), a 20-item test that measures the severity of posttraumatic stress disorder symptoms; (3) the Patient Health Questionnaire-9 (PHQ-9), a 9-item scale that measures depression based on symptom frequency over the past 2 weeks; and (4) the Brief Symptom Inventory-18 (BSI-18), an 18-item scale of psychological distress (split into Depression and Anxiety subscales). Results: A total of 2000 patients with mTBI (1331 men [67%; mean (SD) age, 41.0 (17.3) years; 1026 White (78%)] and 669 women [33%; mean (SD) age, 43.0 (18.5) years; 505 (76%) White]). After adjustment of multiple comparisons, significant TBI × sex interactions were observed for cognitive symptoms (B = 0.76; 5% false discovery rate-corrected P = .02) and somatic RPQ symptoms (B = 0.80; 5% false discovery rate-corrected P = .02), with worse symptoms in women with mTBI than men, but no sex difference in symptoms in control patients with orthopedic trauma. Within the female patients evaluated, there was a significant TBI × age interaction for somatic RPQ symptoms, which were worse in female patients with mTBI aged 35 to 49 years compared with those aged 17 to 34 years (B = 1.65; P = .02) or older than 50 years (B = 1.66; P = .02). Conclusions and relevance: This study found that women were more vulnerable than men to persistent mTBI-related cognitive and somatic symptoms, whereas no sex difference in symptom burden was seen after orthopedic injury. Postconcussion symptoms were also worse in women aged 35 to 49 years than in younger and older women, but further investigation is needed to corroborate these findings and to identify the mechanisms involved. Results suggest that individualized clinical management of mTBI should consider sex and age, as some women are especially predisposed to chronic postconcussion symptoms even 12 months after injury.Item Demographic and Mental Health Predictors of Arrests Up to 10 Years Post-Traumatic Brain Injury: A Veterans Affairs TBI Model Systems Study(Wolters Kluwer, 2021-07) Miles, Shannon R.; Silva, Marc A.; Neumann, Dawn; Dillahunt-Aspillaga, Christina; Corrigan, John D.; Tang, Xinyu; Eapen, Blessen C.; Nakase-Richardson, Risa; Physical Medicine and Rehabilitation, School of MedicineOBJECTIVE: Examine rates and predictors of arrests in Veterans and Service Members (V/SM) who received inpatient rehabilitation for traumatic brain injury (TBI). SETTING: Veterans Administration (VA) Polytrauma Rehabilitation Centers. PARTICIPANTS: A total of 948 V/SM drawn from the VA TBI Model Systems cohort with arrest data up to 10 years post-TBI. DESIGN: Longitudinal cohort study; secondary analysis of pre-TBI characteristics predicting post-TBI arrests. MAIN MEASURES: Disclosure of arrests pre-TBI and up to10 years post-TBI. RESULTS: Thirty-six percent of the sample had been arrested prior to their TBI; 7% were arrested post-TBI. When considering all variables simultaneously in a multivariate model, pre-TBI mental health treatment (adjusted odds ratio [aOR] = 4.30; 95% confidence interval [CI]: 2.03-9.14), pre-TBI heavy alcohol use (aOR = 3.04; CI: 1.08-8.55), and number of follow-up interviews (aOR = 2.05; CI: 1.39-4.50) were significant predictors of post-TBI arrest. CONCLUSION: Arrest rates of V/SM prior to TBI were consistent with rates of arrest for people of similar ages in the United States. Post-TBI rates were lower for V/SM than published rates of post-TBI arrests in civilians with TBI. As part of rehabilitation planning for V/SM with TBI, providers should assess for preinjury mental health services and alcohol misuse to (1) identify those who may be at risk for postinjury arrests and (2) provide relevant resources and/or supports.Item Family Involvement in Traumatic Brain Injury Inpatient Rehabilitation: A Propensity Score Analysis of Effects on Outcomes During the First Year After Discharge(Elsevier, 2019) Bogner, Jennifer; Peng, Juan; Beaulieu, Cynthia; Horn, Susan D.; Corrigan, John D.; Hammond, Flora M.; Dijkers, Marcel P.; Montgomery, Erin; Gilchrist, Kamie; Giuffrida, Clare; Lash, Aubrey; Timpson, Misti; Physical Medicine and Rehabilitation, School of MedicineObjective To evaluate the effect of family attendance at inpatient rehabilitation therapy sessions on traumatic brain injury (TBI) patient outcomes at discharge and up to 9 months postdischarge. Design Propensity score methods are applied to the TBI Practice-Based Evidence database, a database consisting of multisite, prospective, longitudinal, and observational data. Setting Nine inpatient rehabilitation centers in the United States. Participants Patients (N=1835) admitted for first inpatient rehabilitation after an index TBI. Intervention Family attendance during therapy sessions. Main Outcome Measures Participation Assessment for Recombined Tools-Objective-17 (Total scores and subdomain scores of Productivity, Out and About, and Social Relations), Functional Independence Measure, Satisfaction with Life Scale, and Patient Health Questionnaire-9. Results Participants whose families were in attendance for at least 10% of the treatment time were more out and about in their communities at 3 and 9 months postdischarge than participants whose families attended treatment less than 10% of the time. Although findings varied by propensity score method, improved functional independence in the cognitive area at 9 months was also associated with increased family attendance. Conclusions Family involvement during inpatient rehabilitation may improve community participation and cognitive functioning up to 9 months after discharge. Rehabilitation teams should engage patients’ families in the rehabilitation process to maximize outcomes.Item Functional Change from Five to Fifteen Years after Traumatic Brain Injury(Liebert, 2021-03) Hammond, Flora M.; Perkins, Susan M.; Corrigan, John D.; Nakase-Richardson, Risa; Brown, Allen W.; O’Neil-Pirozzi, Therese M.; Zasler, Nathan D.; Greenwald, Brian D.; Physical Medicine and Rehabilitation, School of MedicineFew studies have assessed the long-term functional outcomes of traumatic brain injury (TBI) in large, well-characterized samples. Using the Traumatic Brain Injury Model Systems cohort, this study assessed the maintenance of independence between years 5 and 15 post-injury and risk factors for decline. The study sample included 1381 persons with TBI who received inpatient rehabilitation, survived to 15 years post-injury, and were available for data collection at 5 or 10 years and 15 years post-injury. The Functional Independence Measure (FIM) and Disability Rating Scale (DRS) were used to measure functional outcomes. The majority of participants had no changes during the 10-year time frame. For FIM, only 4.4% showed decline in Self-Care, 4.9% declined in Mobility, and 5.9% declined in Cognition. Overall, 10.4% showed decline in one or more FIM subscales. Decline was detected by DRS Level of Function (24% with >1-point change) and Employability (6% with >1-point change). Predictors of decline factors across all measures were age >25 years and, across most measures, having less than or equal to a high school education. Additional predictors of FIM decline included male sex (FIM Mobility and Self-Care) and longer rehabilitation length of stay (FIM Mobility and Cognition). In contrast to studies reporting change in the first 5 years post-TBI inpatient rehabilitation, a majority of those who survive to 15 years do not experience functional decline. Aging and cognitive reserve appear to be more important drivers of loss of function than original severity of the injury. Interventions to identify those at risk for decline may be needed to maintain or enhance functional status as persons age with a TBI.Item Functional Outcomes Over the First Year After Moderate to Severe Traumatic Brain Injury in the Prospective, Longitudinal TRACK-TBI Study(American Medical Association, 2021) McCrea, Michael A.; Giacino, Joseph T.; Barber, Jason; Temkin, Nancy R.; Nelson, Lindsay D.; Levin, Harvey S.; Dikmen, Sureyya; Stein, Murray; Bodien, Yelena G.; Boase, Kim; Taylor, Sabrina R.; Vassar, Mary; Mukherjee, Pratik; Robertson, Claudia; Diaz-Arrastia, Ramon; Okonkwo, David O.; Markowitz, Amy J.; Manley, Geoffrey T.; TRACK-TBI Investigators; Adeoye, Opeolu; Badjatia, Neeraj; Bullock, M. Ross; Chesnut, Randall; Corrigan, John D.; Crawford, Karen; Duhaime, Ann-Christine; Ellenbogen, Richard; Feeser, V. Ramana; Ferguson, Adam R.; Foreman, Brandon; Gardner, Raquel; Gaudette, Etienne; Goldman, Dana; Gonzalez, Luis; Gopinath, Shankar; Gullapalli, Rao; Hemphill, J. Claude; Hotz, Gillian; Jain, Sonia; Keene, C. Dirk; Korley, Frederick K.; Kramer, Joel; Kreitzer, Natalie; Lindsell, Chris; Machamer, Joan; Madden, Christopher; Martin, Alastair; McAllister, Thomas; Merchant, Randall; Ngwenya, Laura B.; Noel, Florence; Nolan, Amber; Palacios, Eva; Perl, Daniel; Puccio, Ava; Rabinowitz, Miri; Rosand, Jonathan; Sander, Angelle; Satris, Gabriella; Schnyer, David; Seabury, Seth; Sherer, Mark; Toga, Arthur; Valadka, Alex; Wang, Kevin; Yue, John K.; Yuh, Esther; Zafonte, Ross; Psychiatry, School of MedicineImportance: Moderate to severe traumatic brain injury (msTBI) is a major cause of death and disability in the US and worldwide. Few studies have enabled prospective, longitudinal outcome data collection from the acute to chronic phases of recovery after msTBI. Objective: To prospectively assess outcomes in major areas of life function at 2 weeks and 3, 6, and 12 months after msTBI. Design, setting, and participants: This cohort study, as part of the Transforming Research and Clinical Knowledge in TBI (TRACK-TBI) study, was conducted at 18 level 1 trauma centers in the US from February 2014 to August 2018 and prospectively assessed longitudinal outcomes, with follow-up to 12 months postinjury. Participants were patients with msTBI (Glasgow Coma Scale scores 3-12) extracted from a larger group of patients with mild, moderate, or severe TBI who were enrolled in TRACK-TBI. Data analysis took place from October 2019 to April 2021. Exposures: Moderate or severe TBI. Main outcomes and measures: The Glasgow Outcome Scale-Extended (GOSE) and Disability Rating Scale (DRS) were used to assess global functional status 2 weeks and 3, 6, and 12 months postinjury. Scores on the GOSE were dichotomized to determine favorable (scores 4-8) vs unfavorable (scores 1-3) outcomes. Neurocognitive testing and patient reported outcomes at 12 months postinjury were analyzed. Results: A total of 484 eligible patients were included from the 2679 individuals in the TRACK-TBI study. Participants with severe TBI (n = 362; 283 men [78.2%]; median [interquartile range] age, 35.5 [25-53] years) and moderate TBI (n = 122; 98 men [80.3%]; median [interquartile range] age, 38 [25-53] years) were comparable on demographic and premorbid variables. At 2 weeks postinjury, 36 of 290 participants with severe TBI (12.4%) and 38 of 93 participants with moderate TBI (41%) had favorable outcomes (GOSE scores 4-8); 301 of 322 in the severe TBI group (93.5%) and 81 of 103 in the moderate TBI group (78.6%) had moderate disability or worse on the DRS (total score ≥4). By 12 months postinjury, 142 of 271 with severe TBI (52.4%) and 54 of 72 with moderate TBI (75%) achieved favorable outcomes. Nearly 1 in 5 participants with severe TBI (52 of 270 [19.3%]) and 1 in 3 with moderate TBI (23 of 71 [32%]) reported no disability (DRS score 0) at 12 months. Among participants in a vegetative state at 2 weeks, 62 of 79 (78%) regained consciousness and 14 of 56 with available data (25%) regained orientation by 12 months. Conclusions and relevance: In this study, patients with msTBI frequently demonstrated major functional gains, including recovery of independence, between 2 weeks and 12 months postinjury. Severe impairment in the short term did not portend poor outcomes in a substantial minority of patients with msTBI. When discussing prognosis during the first 2 weeks after injury, clinicians should be particularly cautious about making early, definitive prognostic statements suggesting poor outcomes and withdrawal of life-sustaining treatment in patients with msTBI.Item Impact of Level of Effort on the Effects of Compliance with the 3-Hour Rule(Elsevier, 2019) Beaulieu, Cynthia L.; Peng, Juan; Hade, Erinn M.; Corrigan, John D.; Seel, Ronald T.; Dijkers, Marcel P.; Hammond, Flora M.; Horn, Susan D.; Timpson, Misti L.; Swan, Melanie; Bogner, Jennifer; Physical Medicine and Rehabilitation, School of MedicineObjective To determine if patients’ level of effort (LOE) in therapy sessions during traumatic brain injury (TBI) rehabilitation modifies the effect of compliance with the 3-Hour Rule of the Centers for Medicare & Medicaid Services. Design Propensity score methodology applied to the TBI-Practice-Based Evidence (TBI-PBE) database, consisting of multi-site, prospective, longitudinal observational data. Setting Acute inpatient rehabilitation facilities (IRF). Participants Patients (n=1820) who received their first IRF admission for TBI in the US and were enrolled for 3 and 9 month follow-up. Main Outcome Measures Participation Assessment with Recombined Tools-Objective-17, FIMTM Motor and Cognitive scores, Satisfaction with Life Scale, and Patient Health Questionnaire-9. Results When the full cohort was examined, no strong main effect of compliance with the 3-Hour Rule was identified and LOE did not modify the effect of compliance with the 3-Hour Rule. In contrast, LOE had a strong positive main effect on all outcomes, except depression. When the sample was stratified by level of disability, LOE modified the effect of compliance, particularly on the outcomes of participants with less severe disability. For these patients, providing 3 hours of therapy for 50%+ of therapy days in the context of low effort resulted in poorer performance on select outcome measures at discharge and up to 9 months post discharge compared to patients with <50% of 3-hr therapy days. Conclusions LOE is an active ingredient in inpatient TBI rehabilitation, while compliance with the 3-Hour Rule was not found to have a substantive impact on the outcomes. The results support matching time in therapy during acute TBI rehabilitation to patients’ LOE in order to optimize long-term benefits on outcomes.Item Improving Transition from Inpatient Rehabilitation following Traumatic Brain Injury: Protocol for the BRITE Pragmatic Comparative Effectiveness Trial(Elsevier, 2021-05) Fann, Jesse R.; Hart, Tessa; Ciol, Marcia A.; Moore, Megan; Bogner, Jennifer; Corrigan, John D.; Dams-O'Connor, Kristen; Driver, Simon; Dubiel, Rosemary; Hammond, Flora M.; Kajankova, Maria; Watanabe, Thomas K.; Hoffman, Jeanne M.; Physical Medicine and Rehabilitation, School of MedicineModerate to severe traumatic brain injury (TBI) is a common cause of long-term disability. Due to challenges that include inconsistent access to follow-up care, persons with TBI being discharged from inpatient rehabilitation facilities (IRFs) are at risk for rehospitalization, poor reintegration into the community, family stress, and other unfavorable outcomes resulting from unmet needs. In a six-center randomized pragmatic comparative effectiveness study, the BRITE trial (Brain Injury Rehabilitation: Improving the Transition Experience, ClinicalTrials.gov NCT03422276), we compare the effectiveness of two existing methods for transition from IRF to community living or long-term nursing care. The Rehabilitation Discharge Plan (RDP) includes patient/family education and referrals for continued care. The Rehabilitation Transition Plan (RTP) provides RDP plus individualized, manualized care management via phone or videoconference, for 6 months. Nine hundred patients will be randomized (1:1) to RDP or RTP, with caregivers also invited to participate and contribute caregiver-reported outcomes. Extensive stakeholder input, including active participation of persons with TBI and their families, has informed all aspects of trial design and implementation planning. We hypothesize that RTP will result in better patient- and caregiver-reported outcomes (societal participation, quality of life, caregiver well-being) and more efficient use of healthcare resources at 6-months (primary outcome) and 12-months post-discharge, compared to RDP alone. Planned analyses will explore which participants benefit most from each transition model. With few exclusion criteria and other pragmatic features, the findings of this trial are expected to have a broad impact on improving transitions from inpatient TBI rehabilitation.Item Latent Profile Analysis of Neuropsychiatric Symptoms and Cognitive Function of Adults 2 Weeks After Traumatic Brain Injury: Findings From the TRACK-TBI Study(American Medical Association, 2021-03-01) Brett, Benjamin L.; Kramer, Mark D.; Whyte, John; McCrea, Michael A.; Stein, Murray B.; Giacino, Joseph T.; Sherer, Mark; Markowitz, Amy J.; Manley, Geoffrey T.; Nelson, Lindsay D.; TRACK-TBI Investigators; Adeoye, Opeolu; Badjatia, Neeraj; Boase, Kim; Barber, Jason; Bodien, Yelena; Bullock, M. Ross; Chesnut, Randall; Corrigan, John D.; Crawford, Karen; Diaz-Arrastia, Ramon; Dikmen, Sureyya; Duhaime, Ann-Christine; Ellenbogen, Richard; Feeser, V. Ramana; Ferguson, Adam R.; Foreman, Brandon; Gardner, Raquel; Gaudette, Etienne; Gonzalez, Luis; Gopinath, Shankar; Gullapalli, Rao; Hemphill, J. Claude; Hotz, Gillian; Jain, Sonia; Keene, C. Dirk; Korley, Frederick K.; Kramer, Joel; Kreitzer, Natalie; Levin, Harvey; Lindsell, Chris; Machamer, Joan; Madden, Christopher; Martin, Alastair; McAllister, Thomas; Merchant, Randall; Mukherjee, Pratik; Ngwenya, Laura B.; Noel, Florence; Okonkwo, David; Palacios, Eva; Puccio, Ava; Rabinowitz, Miri; Robertson, Claudia; Rosand, Jonathan; Sander, Angelle; Satris, Gabriella; Schnyer, David; Seabury, Seth; Taylor, Sabrina; Temkin, Nancy; Toga, Arthur; Valadka, Alex; Vassar, Mary; Wang, Kevin; Yue, John K.; Yuh, Esther; Zafonte, Ross; Psychiatry, School of MedicineImportance: Heterogeneity across patients with traumatic brain injury (TBI) presents challenges for clinical care and intervention design. Identifying distinct clinical phenotypes of TBI soon after injury may inform patient selection for precision medicine clinical trials. Objective: To investigate whether distinct neurobehavioral phenotypes can be identified 2 weeks after TBI and to characterize the degree to which early neurobehavioral phenotypes are associated with 6-month outcomes. Design, setting, and participants: This prospective cohort study included patients presenting to 18 US level 1 trauma centers within 24 hours of TBI from 2014 to 2019 as part of the Transforming Research and Clinical Knowledge in TBI (TRACK-TBI) study. Data were analyzed from January 28, 2020, to January 11, 2021. Exposures: TBI. Main outcomes and measures: Latent profiles (LPs) were derived from common dimensions of neurobehavioral functioning at 2 weeks after injury, assessed through National Institutes of Health TBI Common Data Elements (ie, Brief Symptom Inventory-18, Patient Health Questionnaire-9 Depression checklist, Posttraumatic Stress Disorder Checklist for DSM-5, PROMIS Pain Intensity scale, Insomnia Severity Index, Rey Auditory Verbal Learning Test, Wechsler Adult Intelligence Scale-Fourth Edition Coding and Symbol Search subtests, Trail Making Test, and NIH Toolbox Cognitive Battery Pattern Comparison Processing Speed, Dimensional Change Card Sort, Flanker Inhibitory Control and Attention, and Picture Sequence Memory subtests). Six-month outcomes were the Satisfaction With Life Scale (SWLS), Quality of Life after Brain Injury-Overall Scale (QOLIBRI-OS), Glasgow Outcome Scale-Extended (GOSE), and Rivermead Post-Concussion Symptoms Questionnaire (RPQ). Results: Among 1757 patients with TBI included, 1184 (67.4%) were men, and the mean (SD) age was 39.9 (17.0) years. LP analysis revealed 4 distinct neurobehavioral phenotypes at 2 weeks after injury: emotionally resilient (419 individuals [23.8%]), cognitively impaired (368 individuals [20.9%]), cognitively resilient (620 individuals [35.3%]), and neuropsychiatrically distressed (with cognitive weaknesses; 350 individuals [19.9%]). Adding LP group to models including demographic characteristics, medical history, Glasgow Coma Scale score, and other injury characteristics was associated with significantly improved estimation of association with 6-month outcome (GOSE R2 increase = 0.09-0.19; SWLS R2 increase = 0.12-0.22; QOLIBRI-OS R2 increase = 0.14-0.32; RPQ R2 = 0.13-0.34). Conclusions and relevance: In this cohort study of patients with TBI presenting to US level-1 trauma centers, qualitatively distinct profiles of symptoms and cognitive functioning were identified at 2 weeks after TBI. These distinct phenotypes may help optimize clinical decision-making regarding prognosis, as well as selection and stratification for randomized clinical trials.