Dataset Information

Association of Sex and Age With Mild Traumatic Brain Injury-Related Symptoms: A TRACK-TBI Study.

ABSTRACT:

Importance

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.

SUBMITTER: Levin HS

PROVIDER: S-EPMC8025125 | biostudies-literature | 2021 Apr

REPOSITORIES: biostudies-literature

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Publications

Association of Sex and Age With Mild Traumatic Brain Injury-Related Symptoms: A TRACK-TBI Study.

Levin Harvey S HS Temkin Nancy R NR Barber Jason J Nelson Lindsay D LD Robertson Claudia C Brennan Jeffrey J Stein Murray B MB Yue John K JK Giacino Joseph T JT McCrea Michael A MA Diaz-Arrastia Ramon R Mukherjee Pratik P Okonkwo David O DO Boase Kim K Markowitz Amy J AJ Bodien Yelena Y Taylor Sabrina S Vassar Mary J MJ Manley Geoffrey T GT Adeoye Opeolu O Badjatia Neeraj N Bullock M Ross MR Chesnut Randall R Corrigan John D JD Crawford Karen K Dikmen Sureyya S Duhaime Ann-Christine AC Ellenbogen Richard R Feeser V Ramana VR Ferguson Adam R AR Foreman Brandon B Gardner Raquel R Gaudette Etienne E Gonzalez Luis L Gopinath Shankar S Gullapalli Rao R Hemphill J Claude JC Hotz Gillian G Jain Sonia S Keene C Dirk CD Korley Frederick K FK Kramer Joel J Kreitzer Natalie N Lindsell Chris C Machamer Joan J Madden Christopher C Martin Alastair A McAllister Thomas T Merchant Randall R Nolan Amber A Ngwenya Laura B LB Noel Florence F Palacios Eva E Puccio Ava A Rabinowitz Miri M Rosand Jonathan J Sander Angelle A Satris Gabriella G Schnyer David D Seabury Seth S Sun Xiaoying X Toga Arthur A Valadka Alex A Wang Kevin K Yuh Esther E Zafonte Ross R

JAMA network open 20210401 4

<h4>Importance</h4>Knowledge of differences in mild traumatic brain injury (mTBI) recovery by sex and age may inform individualized treatment of these patients.<h4>Objective</h4>To identify sex-related differences in symptom recovery from mTBI; secondarily, to explore age differences within women, who demonstrate poorer outcomes after TBI.<h4>Design, setting, and participants</h4>The prospective cohort study Transforming Research and Clinical Knowledge in Traumatic Brain Injury (TRACK-TBI) recru ...[more]

PMID: 33822070

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Project description:ImportanceMild traumatic brain injury (mTBI) may impair the ability to work. Strategies to facilitate return to work are understudied.ObjectiveTo assess employment and economic outcomes for employed, working-age adults with mTBI in the 12 months after injury and the association between return to work and employer assistance.Design, setting, and participantsUsing data from the Transforming Research and Clinical Knowledge in Traumatic Brain Injury (TRACK-TBI) study, a cohort study of patients with mTBI presenting to emergency departments of 11 level I US trauma centers was performed. Patients with mTBI enrolled in the TRACK-TBI cohort study from February 26, 2014, to May 4, 2016, were followed up at 2 weeks and 3, 6, and 12 months after injury. Work status and income decline of participants were documented in the first year after injury. Associations between work status, injury characteristics, and offer of employer assistance and associations between follow-up care and employer assistance were investigated. Results were adjusted for unobserved outcomes using inverse probability weighting. Data were extracted July 12, 2020; analyses were completed March 24, 2021. Analyses included 435 participants aged 18 to 64 years who were working before the injury, had a Glasgow Coma Scale score of 13 to 15, and completed all postinjury follow-up surveys.Main outcomes and measuresPrimary outcomes were work status (working or not working) at each study follow-up milestone. Employer assistance included sick leave, reduced hours, modified schedule, transfer to different tasks, assistive technology, and coaching offered during the first 3 months after injury.ResultsOf 435 participants (147 [34%] female; 320 [74%] White; mean [SD] age 37.3 [12.9] years), 258 (59%) reported not working at 2 weeks after injury and 74 (17%) reported not working at 12 months after injury. More than one-fifth (92 [21%]) experienced a decline in annual income. Work status at 12 months was significantly associated with postconcussion symptoms experienced at 3 months after injury (73% of patients with 3 or more symptoms reported working at 12 months after injury vs 89% of patients with 2 or fewer symptoms; P < .001) but not with other injury characteristics. Participants offered employer assistance in the first 3 months after injury were more likely to report working after injury than those not offered such assistance (at 6 months: 88% vs 78%; P = .02; at 12 months: 86% vs 72%; P = .005).Conclusions and relevanceIn this cohort study, mTBI was associated with substantial employment and economic consequences for some patients. Clinicians should systematically follow up with patients with mTBI and coordinate with employers to promote successful return to work.

Project description:Older adults have the highest incidence of traumatic brain injury globally. Accurate blood-based biomarkers are needed to assist with diagnosis of patients across the spectrum of age and time post-injury. Several reports have suggested lower accuracy for blood-based biomarkers in older adults, and there is a paucity of data beyond day-1 post-injury. Our aims were to investigate age-related differences in diagnostic accuracy and 2-week evolution of four leading candidate blood-based traumatic brain injury biomarkers-plasma glial fibrillary acidic protein, ubiquitin carboxy-terminal hydrolase L1, S100 calcium binding protein B and neuron-specific enolase-among participants in the 18-site prospective cohort study Transforming Research And Clinical Knowledge in Traumatic Brain Injury. Day-1 biomarker data were available for 2602 participants including 2151 patients with traumatic brain injury, 242 orthopedic trauma controls and 209 healthy controls. Participants were stratified into 3 age categories (young: 17-39 years, middle-aged: 40-64 years, older: 65-90 years). We investigated age-stratified biomarker levels and biomarker discriminative abilities across three diagnostic groups: head CT-positive/negative; traumatic brain injury/orthopedic controls; and traumatic brain injury/healthy controls. The difference in day-1 glial fibrillary acidic protein, ubiquitin carboxy-terminal hydrolase L1 and neuron-specific enolase levels across most diagnostic groups was significantly smaller for older versus younger adults, resulting in a narrower range within which a traumatic brain injury diagnosis may be discriminated in older adults. Despite this, day-1 glial fibrillary acidic protein had good to excellent performance across all age-categories for discriminating all three diagnostic groups (area under the curve 0.84-0.96; lower limit of 95% confidence intervals all >0.78). Day-1 S100 calcium-binding protein B and ubiquitin carboxy-terminal hydrolase L1 showed good discrimination of CT-positive versus negative only among adults under age 40 years within 6 hours of injury. Longitudinal blood-based biomarker data were available for 522 hospitalized patients with traumatic brain injury and 24 hospitalized orthopaedic controls. Glial fibrillary acidic protein levels maintained good to excellent discrimination across diagnostic groups until day 3 post-injury irrespective of age, until day 5 post-injury among middle-aged or younger patients and until week 2 post-injury among young patients only. In conclusion, the blood-based glial fibrillary acidic protein assay tested here has good to excellent performance across all age-categories for discriminating key traumatic brain injury diagnostic groups to at least 3 days post-injury in this trauma centre cohort. The addition of a blood-based diagnostic to the evaluation of traumatic brain injury, including geriatric traumatic brain injury, has potential to streamline diagnosis.

Project description:BackgroundPost-traumatic stress disorder (PTSD) and depression are common after mild traumatic brain injury (mTBI), but their biological drivers are uncertain. We therefore explored whether polygenic risk scores (PRS) derived for PTSD and major depressive disorder (MDD) are associated with the development of cognate TBI-related phenotypes.MethodsMeta-analyses were conducted using data from two multicenter, prospective observational cohort studies of patients with mTBI: the CENTER-TBI study (ClinicalTrials.gov ID NCT02210221) in Europe (December 2014-December 2017) and the TRACK-TBI study in the US (March 2014-July 2018). In both cohorts, the most common causes of injury were road traffic accidents and falls. Primary outcomes, specifically probable PTSD and depression, were defined at 6 months post-injury using scores ≥33 on the PTSD Checklist-5 and ≥15 on the Patient Health Questionnaire-9, respectively. We calculated PTSD-PRS and MDD-PRS for patients aged ≥17 years who had a Glasgow Coma Scale score of 13-15 upon hospital arrival and assessed their association with PTSD and depression following TBI. We also evaluated the transferability of the findings in a cohort of African Americans.FindingsOverall, 11.8% (219/1869) and 6.7% (124/1869) patients were classified as having probable PTSD and depression, respectively. The PTSD-PRS was significantly associated with higher adjusted odds of PTSD in both cohorts, with a pooled odds ratio (OR) of 1.55 [95% confidence interval (CI) 1.30-1.84, p < 0.001, I 2 = 20.8%]. Although the MDD-PRS increased the risk of depression after TBI, it did not reach significance in the individual cohorts. However, in a combined analysis, the risk was significantly elevated with a pooled OR of 1.26 [95% CI 1.03-1.53, p = 0.02, I 2 = 0%]. The addition of PRSs improved the proportion of outcome variance explained in the two study cohorts from 19.5% and 30.3% to 21.6% and 34.0% for PTSD; and from 11.0% and 22.5% to 12.8% and 22.6% for depression. Patients in the highest cognate PRS quintile had increased odds of 3.16 [95% CI 1.80-5.55] and 2.03 [95% CI 1.04-3.94] of developing PTSD or depression compared to the lowest quintile, respectively.InterpretationAssociations of PRSs with PTSD and depression following TBI are not disorder-specific. However, the overlap between MDD-PRS and depression following TBI is less robust compared to PTSD-PRS and PTSD. PRSs could improve risk prediction, and permit enrichment for interventional trials.FundingThis study was supported by funding by an FP7 grant from the European Union, Hannelore Kohl Stiftung, Integra LifeSciences Corporation, NeuroTrauma Sciences, US National Institutes of Health, US Department of Defense, National Football League Advisory Board, US Department of Energy, and One Mind.

Project description:Introduction: Over 70% of traumatic brain injuries (TBI) are classified as mild (mTBI), which present heterogeneously. Associations between pre-injury comorbidities and outcomes are not well-understood, and understanding their status as risk factors may improve mTBI management and prognostication. Methods: mTBI subjects (GCS 13-15) from TRACK-TBI Pilot completing 3- and 6-month functional [Glasgow Outcome Scale-Extended (GOSE)] and post-concussive outcomes [Acute Concussion Evaluation (ACE) physical/cognitive/sleep/emotional subdomains] were extracted. Pre-injury comorbidities >10% incidence were included in regressions for functional disability (GOSE ≤ 6) and post-concussive symptoms by subdomain. Odds ratios (OR) and mean differences (B) were reported. Significance was assessed at p < 0.0083 (Bonferroni correction). Results: In 260 subjects sustaining blunt mTBI, mean age was 44.0-years and 70.4% were male. Baseline comorbidities >10% incidence included psychiatric-30.0%, cardiac (hypertension)-23.8%, cardiac (structural/valvular/ischemic)-20.4%, gastrointestinal-15.8%, pulmonary-15.0%, and headache/migraine-11.5%. At 3- and 6-months separately, 30.8% had GOSE ≤ 6. At 3-months, psychiatric (GOSE ≤ 6: OR = 2.75, 95% CI [1.44-5.27]; ACE-physical: B = 1.06 [0.38-1.73]; ACE-cognitive: B = 0.72 [0.26-1.17]; ACE-sleep: B = 0.46 [0.17-0.75]; ACE-emotional: B = 0.64 [0.25-1.03]), headache/migraine (GOSE ≤ 6: OR = 4.10 [1.67-10.07]; ACE-sleep: B = 0.57 [0.15-1.00]; ACE-emotional: B = 0.92 [0.35-1.49]), and gastrointestinal history (ACE-physical: B = 1.25 [0.41-2.10]) were multivariable predictors of worse outcomes. At 6-months, psychiatric (GOSE ≤ 6: OR = 2.57 [1.38-4.77]; ACE-physical: B = 1.38 [0.68-2.09]; ACE-cognitive: B = 0.74 [0.28-1.20]; ACE-sleep: B = 0.51 [0.20-0.83]; ACE-emotional: B = 0.93 [0.53-1.33]), and headache/migraine history (ACE-physical: B = 1.81 [0.79-2.84]) predicted worse outcomes. Conclusions: Pre-injury psychiatric and pre-injury headache/migraine symptoms are risk factors for worse functional and post-concussive outcomes at 3- and 6-months post-mTBI. mTBI patients presenting to acute care should be evaluated for psychiatric and headache/migraine history, with lower thresholds for providing TBI education/resources, surveillance, and follow-up/referrals. Clinical Trial Registration: www.ClinicalTrials.gov, identifier NCT01565551.

Dataset Information

Association of Sex and Age With Mild Traumatic Brain Injury-Related Symptoms: A TRACK-TBI Study.

Importance

Objective

Design, setting, and participants

Exposures

Main outcomes and measures

Results

Conclusions and relevance

Publications

Association of Sex and Age With Mild Traumatic Brain Injury-Related Symptoms: A TRACK-TBI Study.

Similar Datasets

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