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Personal Factors Associated With Postconcussion Symptoms 3 Months After Mild Traumatic Brain Injury

  • Toril Skandsen
    Correspondence
    Corresponding author Toril Skandsen, MD, PhD, NTNU Faculty of Medicine and Heath Sciences, N-7491 Trondheim, Norway.
    Affiliations
    Department of Neuromedicine and Movement Science, Norwegian University of Science and Technology (NTNU), Trondheim, Norway

    Department of Physical Medicine and Rehabilitation, St. Olavs Hospital, Trondheim University Hospital, Trondheim, Norway
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  • Jonas Stenberg
    Affiliations
    Department of Neuromedicine and Movement Science, Norwegian University of Science and Technology (NTNU), Trondheim, Norway

    Department of Neurosurgery, St. Olavs Hospital, Trondheim University Hospital, Trondheim, Norway
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  • Turid Follestad
    Affiliations
    Department of Clinical and Molecular Medicine, Norwegian University of Science and Technology (NTNU), Trondheim, Norway
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  • Migle Karaliute
    Affiliations
    Department of Psychology, Norwegian University of Science and Technology (NTNU), Trondheim, Norway

    Department of Neurology and Clinical Neurophysiology, St. Olavs Hospital, Trondheim University Hospital, Trondheim, Norway
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  • Simen B. Saksvik
    Affiliations
    Department of Physical Medicine and Rehabilitation, St. Olavs Hospital, Trondheim University Hospital, Trondheim, Norway

    Department of Psychology, Norwegian University of Science and Technology (NTNU), Trondheim, Norway
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  • Cathrine E. Einarsen
    Affiliations
    Department of Neuromedicine and Movement Science, Norwegian University of Science and Technology (NTNU), Trondheim, Norway

    Department of Physical Medicine and Rehabilitation, St. Olavs Hospital, Trondheim University Hospital, Trondheim, Norway
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  • Hanna Lillehaug
    Affiliations
    Department of Psychology, Norwegian University of Science and Technology (NTNU), Trondheim, Norway
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  • Asta K. Håberg
    Affiliations
    Department of Neuromedicine and Movement Science, Norwegian University of Science and Technology (NTNU), Trondheim, Norway

    Department of Radiology and Nuclear Medicine, St. Olavs Hospital, Trondheim University Hospital, Trondheim, Norway
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  • Anne Vik
    Affiliations
    Department of Neuromedicine and Movement Science, Norwegian University of Science and Technology (NTNU), Trondheim, Norway

    Department of Neurosurgery, St. Olavs Hospital, Trondheim University Hospital, Trondheim, Norway
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  • Alexander Olsen
    Affiliations
    Department of Physical Medicine and Rehabilitation, St. Olavs Hospital, Trondheim University Hospital, Trondheim, Norway

    Department of Psychology, Norwegian University of Science and Technology (NTNU), Trondheim, Norway
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  • Grant L. Iverson
    Affiliations
    Department of Physical Medicine and Rehabilitation, Harvard Medical School, Boston, Massachusetts

    Spaulding Rehabilitation Hospital and Spaulding Research Institute, Charlestown, Massachusetts

    Home Base, A Red Sox Foundation and Massachusetts General Hospital Program, Charlestown, Massachusetts
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Open AccessPublished:October 27, 2020DOI:https://doi.org/10.1016/j.apmr.2020.10.106

      Abstract

      Objective

      To describe personal factors in patients with mild traumatic brain injury (MTBI) and 2 control groups and to explore how such factors were associated with postconcussion symptoms (PCSs).

      Design

      Prospective cohort study.

      Setting

      Level 1 trauma center and outpatient clinic.

      Participants

      Participants (N=541) included patients with MTBI (n=378), trauma controls (n=82), and community controls (n=81).

      Main Outcome Measures

      Data on preinjury health and work status, personality, resilience, attention deficit/hyperactivity, and substance use. Computed tomography (CT) findings and posttraumatic amnesia were recorded. Symptoms were assessed at 3 months with the British Columbia Postconcussion Symptom Inventory and labeled as PCS+ if ≥3 symptoms were reported or the total score was ≥13. Predictive models were fitted with penalized logistic regression using the least absolute shrinkage and selection operator (lasso) in the MTBI group, and model fit was assessed with optimism-corrected area under the curve (AUC) of the receiver operating characteristic curve.

      Results

      There were few differences in personal factors between the MTBI group and the 2 control groups without MTBI. Rates of PCS+ were 20.8% for the MTBI group, 8.0% for trauma controls, and 1.3% for community controls. In the MTBI group, there were differences between the PCS+ and PCS− group on most personal factors and injury-related variables in univariable comparisons. In the lasso models, the optimism-corrected AUC for the full model was 0.79, 0.73 for the model only including personal factors, and 0.63 for the model only including injury variables. Working less than full time before injury, having preinjury pain and poor sleep quality, and being female were among the selected predictors, but also resilience and some personality traits contributed in the model. Intracranial abnormalities on CT were also a risk factor for PCS.

      Conclusions

      Personal factors convey important prognostic information in patients with MTBI. A vulnerable work status and preinjury health problems might indicate a need for follow-up and targeted interventions.

      Keywords

      List of abbreviations:

      ADHD (attention deficit hyperactivity disorder), AUC (area under the curve), CC (community control), CT (computed tomography), lasso (least absolute shrinkage and selection operator), MTBI (mild traumatic brain injury), PCS (postconcussion symptom), PTA (posttraumatic amnesia), TBI (traumatic brain injury), TC (trauma control)
      After mild traumatic brain injury (MTBI), a significant minority experiences a range of persistent somatic, cognitive, and emotional symptoms over months or even years, a condition here referred to as postconcussion symptoms (PCSs).
      • Polinder S.
      • Cnossen M.C.
      • Real R.G.L.
      • et al.
      A multidimensional approach to post-concussion symptoms in mild traumatic brain injury.
      PCSs are associated with considerable functional limitations and reduced quality of life,
      • McMahon P.
      • Hricik A.
      • Yue J.K.
      • et al.
      Symptomatology and functional outcome in mild traumatic brain injury: results from the prospective TRACK-TBI study.
      ,
      • King N.S.
      • Kirwilliam S.
      Permanent post-concussion symptoms after mild head injury.
      but only weak association has been found between MTBI severity and outcome,
      • Iverson G.L.
      • Lange R.T.
      • Waljas M.
      • et al.
      Outcome from complicated versus uncomplicated mild traumatic brain injury.
      ,
      • Panenka W.J.
      • Lange R.T.
      • Bouix S.
      • et al.
      Neuropsychological outcome and diffusion tensor imaging in complicated versus uncomplicated mild traumatic brain injury.
      and the disability some people experience can therefore seem out of proportion to a TBI that is categorized as mild. The heterogeneity in MTBI outcome, together with the inconsistent findings on the role of injury severity and neuroimaging findings on outcome, suggest that the biopsychosocial model may serve as a framework to understand and treat PCSs.
      • Polinder S.
      • Cnossen M.C.
      • Real R.G.L.
      • et al.
      A multidimensional approach to post-concussion symptoms in mild traumatic brain injury.
      ,
      • Silverberg N.D.
      • Iverson G.L.
      Etiology of the post-concussion syndrome: physiogenesis and psychogenesis revisited.
      ,
      • Iverson G.L.
      Network analysis and precision rehabilitation for the post-concussion syndrome.
      A biopsychosocial treatment approach is likely most effective if initiated early after injury
      • Jover J.
      • Abasolo L.
      Early intervention to restore function and maintain healthy trajectory.
      ; thus identification of patients at risk is important. Personal factors, as conceptualized in the International Classification of Function,
      World Health Organization
      International classification of functioning, disability and health (ICF).
      such as personality and preinjury mental and physical health, have all been associated with PCSs.
      • van der Naalt J.
      • Timmerman M.E.
      • de Koning M.E.
      • et al.
      Early predictors of outcome after mild traumatic brain injury (UPFRONT): an observational cohort study.
      ,
      • Cassidy J.D.
      • Cancelliere C.
      • Carroll L.J.
      • et al.
      Systematic review of self-reported prognosis in adults after mild traumatic brain injury: results of the International Collaboration on Mild Traumatic Brain Injury Prognosis.
      Female sex has been found to be a risk factor in some but not all studies.
      • Merritt V.C.
      • Padgett C.R.
      • Jak A.J.
      A systematic review of sex differences in concussion outcome: what do we know?.
      • Cancelliere C.
      • Donovan J.
      • Cassidy J.D.
      Is sex an indicator of prognosis after mild traumatic brain injury: a systematic analysis of the findings of the World Health Organization Collaborating Centre Task Force on Mild Traumatic Brain Injury and the International Collaboration on Mild Traumatic Brain Injury Prognosis.
      • Bazarian J.J.
      • Blyth B.
      • Mookerjee S.
      • He H.
      • McDermott M.P.
      Sex differences in outcome after mild traumatic brain injury.
      However, more research is needed to explore which personal factors should be included in future prognostic models.
      • Maas A.I.R.
      • Menon D.K.
      • Adelson P.D.
      • et al.
      Traumatic brain injury: integrated approaches to improve prevention, clinical care, and research.
      ,
      • Silverberg N.D.
      • Gardner A.J.
      • Brubacher J.R.
      • Panenka W.J.
      • Li J.J.
      • Iverson G.L.
      Systematic review of multivariable prognostic models for mild traumatic brain injury.
      In the Trondheim MTBI follow-up study, we acquired comprehensive information in patients and control participants without MTBI about a range of personal factors such as personality, resilience, optimism, preinjury somatic and psychological health, experienced life events, and substance use, in addition to measures of injury severity. Our aims were to describe these in patients with MTBI and 2 control groups, and to explore whether such factors were associated with MTBI and PCSs. We built prediction models and explored which of the personal factors were most consistently associated with PCSs after MTBI and to what degree the injury-related variables added to model performance.

      Methods

      Participants

      The patients with MTBI were part of the Trondheim MTBI follow-up study (n=378), a study consisting of patients 16-59 years old presenting from April 2014 to December 2015 at 2 emergency departments: St. Olavs Hospital, Trondheim University Hospital, a level 1 trauma center and the Trondheim Municipal Emergency clinic, a general practitioner-run, outpatient clinic.
      • Skandsen T.
      • Einarsen C.E.
      • Normann I.
      • et al.
      The epidemiology of mild traumatic brain injury: the Trondheim MTBI follow-up study.
      In this cohort, around 60% of all eligible patients were enrolled, and the cohort has been shown to be representative of all young adult and middle-aged patients with MTBI in the catchment area.
      • Skandsen T.
      • Einarsen C.E.
      • Normann I.
      • et al.
      The epidemiology of mild traumatic brain injury: the Trondheim MTBI follow-up study.
      Inclusion criteria were having sustained a TBI
      • Menon D.K.
      • Schwab K.
      • Wright D.W.
      • Maas A.I.
      Position statement: definition of traumatic brain injury.
      categorized as mild according to the World Health Organization Collaborating Centre Task Force on Mild Traumatic Brain Injury criteria. All had Glasgow Coma Scale scores of 13-15 at presentation in the emergency department and either witnessed loss of consciousness <30 minutes, confusion, or posttraumatic amnesia (PTA) <24 hours. Patients that met these criteria and had traumatic lesions on computed tomography (CT) scans were included in the study if the intracranial lesion did not require surgery.
      • Carroll L.J.
      • Cassidy J.D.
      • Holm L.
      • Kraus J.
      • Coronado V.G.
      Methodological issues and research recommendations for mild traumatic brain injury: whe WHO Collaborating Centre Task Force on Mild Traumatic Brain Injury.
      Exclusion criteria were (1) nonfluency in the Norwegian language; (2) pre-existing severe neurologic disorder (eg, stroke, multiple sclerosis) or a prior history of a complicated mild, moderate, or severe TBI; or (3) ongoing psychiatric (eg, psychotic or bipolar disorder), health (eg, cancer), or substance abuse problems determined by the researcher responsible for inclusion and considered to be severe enough to likely interfere with follow-up.
      • Skandsen T.
      • Einarsen C.E.
      • Normann I.
      • et al.
      The epidemiology of mild traumatic brain injury: the Trondheim MTBI follow-up study.
      The control groups were (1) trauma controls (TCs): 82 patients with minor orthopedic injuries, matched on the group level on age and sex, using a procedure ensuring similar numbers of men and women in each 5-year age interval and (2) community controls (CCs): 81 persons recruited among staff, family, and acquaintances of patients and staff, matched on age, sex, and education, using a procedure also ensuring similar years of education in each 5-year age interval. The exclusion criteria applied to the MTBI group were used for the controls, but in addition, the TCs did not have trauma affecting the head, neck, or dominant arm, and the CCs were not receiving treatment for psychiatric disorders.
      The regional committee for research ethics approved the study. Participants and parents of participants younger than 18 years in the cohort study gave informed consent.

      Study procedures

      Patients were consecutively identified based on lists of emergency department visits and CT referrals, and they were approached and enrolled as previously described.
      • Skandsen T.
      • Einarsen C.E.
      • Normann I.
      • et al.
      The epidemiology of mild traumatic brain injury: the Trondheim MTBI follow-up study.
      Data on preinjury characteristics (personal factors) were collected during the first week after injury, considering the situation as it was before their injury. Both a structured interview and questionnaires were used. At 3 months after injury, the patients underwent an outcome evaluation by a telephone interview.

      Study variables

      PTA was defined as the self-reported time after injury for which the patient had no memory. From a pilot study, we knew that many participants would not be able to provide a valid estimate in minutes; therefore, a predefined option was to record PTA as either <1 hour or 1-24 hours. Intracranial traumatic findings were obtained from the radiology report of the acute head CT, here recorded as yes/no. Fractures of the cranium, face, or other bones were obtained from the radiology report and recorded as yes/no.
      Personal factors assessed were all preinjury: age, sex, education, school marks, reading difficulties, work status, previous MTBI, headache, other pain, psychiatric problems, substance use, alcohol use, sleep quality, attention deficit hyperactivity disorder (ADHD) symptoms, personality traits, life orientation (optimism/pessimism), threatening events, and resilience. Measures, definitions, and cutoff criteria are shown in table 1.
      Table 1Personal factors in the study describing preinjury status
      VariablesMeasures and CategorizationsCollection Methods and Measure Details
      AgeYearsMedical records
      SexMan or womanMedical records
      EducationYears of completed education. Starting from the first year of school, at 6 y of age.Self-report, interview
      School marksAverage high school marks on a 1-6 scale.Self-report, interview
      Reading difficultiesRecorded as “yes” if the person had been diagnosed as having reading difficulties.Self-report, interview
      Reduced workRecorded as “yes” if the person was working or studying <80% (of a 37.5-hr wk).Self-report, interview
      Previous MTBIRecorded as “yes” if the person had sustained ≥1 head traumas likely to have fulfilled the same criteria for MTBI as applied in this study.Self-report, interview
      Preinjury painRecorded as “yes” if the person had nonheadache pain in any part of the body graded ≥3 on a 0-10 NRSPain map and NRS
      Preinjury headacheRecorded as “yes” or “no”Item from self-report questionnaire.

      “Have you suffered from headache during the last year?”
      Psychiatric historyRecorded “yes” if the person reported a history of psychiatric illness.Self-report, interview
      Substance useRecorded “yes” if the person reported using drugs other than alcohol.Self-report, interview
      Poor preinjury sleep qualityISI
      • Bastien C.H.
      • Vallieres A.
      • Morin C.M.
      Validation of the insomnia severity index as an outcome measure for insomnia research.
      the first 3 items: difficulties falling asleep, staying asleep, and waking up to early.
      ISI is a questionnaire, but the first 3 questions were administered as an interview. Self-report questionnaire. A 5-point Likert scale, higher scores indicate greater sleep problems/poor sleep quality.
      ADHD symptomsAdult ADHD Self-Report Scale version 1.1.
      • Kessler R.C.
      • Adler L.
      • Ames M.
      • et al.
      The World Health Organization Adult ADHD Self-Report Scale (ASRS): a short screening scale for use in the general population.
      ,
      • Kessler R.C.
      • Adler L.A.
      • Gruber M.J.
      • Sarawate C.A.
      • Spencer T.
      • Van Brunt D.L.
      Validity of the World Health Organization Adult ADHD Self-Report Scale (ASRS) screener in a representative sample of health plan members.
      Individual scores for inattention, hyperactivity, and total symptom burden. The scores were calculated both for the screening part of the questionnaire (the first 6 items) and the full scale (all 18 items). The total score was calculated for each scale. A likely diagnosis of ADHD was defined as scoring at or above a threshold (“sometimes” on questions 1-3 and “often” on questions 4-6) on at least 4 of the first 6 items.
      • Able S.L.
      • Johnston J.A.
      • Adler L.A.
      • Swindle R.W.
      Functional and psychosocial impairment in adults with undiagnosed ADHD.
      Self-report questionnaire. Higher scores indicate more attention/hyperactivity problems. Two missing items were accepted.
      Alcohol useThe Alcohol Use Disorders Identification Test.
      • Saunders J.B.
      • Aasland O.G.
      • Babor T.F.
      • de la Fuente J.R.
      • Grant M.
      Development of the Alcohol Use Disorders Identification Test (AUDIT): WHO collaborative project on early detection of persons with harmful alcohol consumption--II.
      The total score of the 10 items, and “high use” if total scores ≥8.
      • Saunders J.B.
      • Aasland O.G.
      • Babor T.F.
      • de la Fuente J.R.
      • Grant M.
      Development of the Alcohol Use Disorders Identification Test (AUDIT): WHO collaborative project on early detection of persons with harmful alcohol consumption--II.
      Self-report questionnaire. Higher scores indicate higher consumption. Two missing items were accepted.
      Personality traitsBig Five Inventory (BFI-44),
      • John O.P.
      • Srivastava S.
      History, measurement, and theoretical perspectives.
      ,
      • John O.P.
      • Naumann L.P.
      • Soto C.J.
      Paradigm shift to the integrative big-five trait taxonomy: history, measurement, and conceptual issues.
      a short form of the BFI including 44 items. The mean score for each scale was calculated.
      Self-report questionnaire yielding individual scores on extroversion, agreeableness, conscientiousness, neuroticism, and openness. Higher scores indicate higher levels of that personality trait. At least 50% of the items on each personality domain had to be answered for that scale to be calculated.
      PessimismLife Orientation Test-Revised.
      • Scheier M.F.
      • Carver C.S.
      • Bridges M.W.
      Distinguishing optimism from neuroticism (and trait anxiety, self-mastery, and self-esteem): a re-evaluation of the life orientation test.
      ,
      • Carver C.S.
      • Scheier M.F.
      • Segerstrom S.C.
      Self-report questionnaire with ten items, 6 of them measuring optimism/pessimism and 4 fillers (not scored items). Lower scores indicate higher optimism and the variable is therefore referred to as “pessimism.” Two missing items were accepted.
      Threatening life eventsLTE-Q.
      • Brugha T.S.
      • Cragg D.
      The list of threatening experiences: the reliability and validity of a brief life events questionnaire.
      ,
      • Rosmalen J.G.
      • Bos E.H.
      • de Jonge P.
      Validation of the Long-term Difficulties Inventory (LDI) and the List of Threatening Experiences (LTE) as measures of stress in epidemiological population-based cohort studies.
      The total number of events was calculated.
      Self-report questionnaire measuring experience of environmental stressful events during the last year. The Norwegian version comprised 13 items. Two missing items were accepted on LTE-Q.
      ResilienceRSA.
      • Friborg O.
      • Barlaug D.
      • Martinussen M.
      • Rosenvinge J.H.
      • Hjemdal O.
      Resilience in relation to personality and intelligence.
      • Friborg O.
      • Hjemdal O.
      • Martinussen M.
      • Rosenvinge J.H.
      Empirical support for resilience as more than the counterpart and absence of vulnerability and symptoms of mental disorder.
      • Friborg O.
      • Hjemdal O.
      • Rosenvinge J.H.
      • Martinussen M.
      A new rating scale for adult resilience: what are the central protective resources behind healthy adjustment?.
      The mean score was calculated for all dimensions separately, and total resilience score was the mean of all item scores.
      Self-report questionnaire with 33 items measuring 6 dimensions (perception of self, planned future, social competence, family cohesion, social resources, structured style) and a score of total resilience. Higher scores indicate higher resilience. Three missing items were accepted on RSA.
      Abbreviations: ISI, Insomnia Severity Index; LTE-Q, List of Threatening Events Questionnaire; NRS, Numeric Rating Scale; RSA, Resilience Scale for Adults.
      Outcome was assessed at 3 months after injury with the British Columbia Postconcussion Symptom Inventory.
      • Iverson G.L.
      • Lange R.T.
      Examination of "postconcussion-like" symptoms in a healthy sample.
      The British Columbia Postconcussion Symptom Inventory consists of 13 core symptoms distributed over 4 symptom categories and 3 life problems. In the current study, the 13 core symptoms were used to calculate the total score. PCSs were defined as having at least 3 core symptoms rated as at least moderate (score ≥3) or a total score ≥13. PCSs were assessed both in the MTBI and control groups and refer to a high level of postconcussion/postconcussion-like symptoms. The MTBI group was accordingly divided into a PCS+ and a PCS− group.

      Statistical analyses

      Missing values on single questionnaire items were replaced by that individual’s mean of the answered questions on the scale/questionnaire. The proportion of missing items across questionnaires ranged from 0.12%-0.44%. Very few participants had more than 1 item missing on a returned questionnaire: Adult ADHD Self-Report Scale, respondents with ≥1 missing items 3.10% and respondents with 2 missing items 0.48%; the Alcohol Use Disorders Identification Test, respondents with 1 missing item 1.17% and none had ≥2 missing items; the Big Five Inventory, respondents with ≥1 missing items 10.88% and respondents with ≥2 missing items 3.98%; Life Orientation Test-Revised, respondents with 1 missing item 1.64% and none had ≥2 missing items; List of Threatening Events Questionnaire, respondents with ≥1 missing item 2.36% and respondents with 2 missing items 0.23%; the Resilience Scale for Adults, respondents with ≥1 missing items 4.00% and respondents with ≥2 missing items 0.24%.
      Group differences between the MTBI group, the TC group, and the CC group were evaluated with Kruskal-Wallis tests and chi-square tests. Whether personal and injury-related factors predicted PCSs in patients with MTBI was evaluated with logistic regression models. First, univariable analyses for each variable of interest were conducted. To reduce the number of comparisons, we only analyzed 1 measure from most questionnaires (eg, from the Adult ADHD Self-Report Scale only the total score was analyzed). Odds ratios with 95% CIs are reported. For the group comparisons and the univariable analyses, P values uncorrected for multiple comparisons are reported as well as differences that remained statistically significant after Bonferroni correction. Second, models were fitted by penalized logistic regression using the least absolute shrinkage and selection operator (lasso) as implemented in the Stata command lasso logit. To account for many predictors, lasso shrinks the values of the coefficients to less extreme values, thereby improving the external validity of the model. For variables with low predictive value, the coefficients could be shrunk (set) to 0 and be left out of the final model. The degree of shrinkage was determined by 10-fold cross-validation. In effect, the method performs estimation of the coefficients and variable selection simultaneously and provides estimates of overall fit rather than statistical significance of the individual predictors. Stata handles factor variables by including all dummy variables (ie, none is initially left out as reference category), and the lasso procedure then shrinks 1 or more of the dummy variables to 0. The uncertainty of the coefficients from the lasso was assessed by repeating the penalized regression procedure in 1000 bootstrap samples. The uncertainty for each of the variables was assessed by the proportion of the 1000 bootstrap samples when its coefficient was set to 0. The lower proportion, the higher is the probability that a variable contributes to outcome prediction. The area under the curve (AUC) of the receiver operating characteristic curves was used to assess performance of the models. Optimism-corrected AUCs with 95% CIs were obtained from bootstrapping with 1000 replications. In this internal validation procedure, the model is estimated in the bootstrap samples and then tested in the original sample. The mean difference between the AUCs obtained in the bootstrap samples and the original sample is referred to as the “optimism,” which is subtracted from the AUC obtained in the original model.
      • Steyerberg E.W.
      • Harrell Jr., F.E.
      • Borsboom G.J.
      • Eijkemans M.J.
      • Vergouwe Y.
      • Habbema J.D.
      Internal validation of predictive models: efficiency of some procedures for logistic regression analysis.
      In the univariable analyses, we allowed for a different number of observations between analyses (ie, all available data were used), while in the lasso models only complete cases were included.

      Results

      Overall characteristics of the MTBI group and the control groups

      There were small and mostly statistically nonsignificant differences between the MTBI, TC, and CC groups (table 2). More people in the MTBI group reported prior MTBI, reading difficulties, and a psychiatric history, and the higher frequency of prior MTBI remained statistically significant after Bonferroni correction.
      Table 2Comparisons between the MTBI group, the trauma control group, and the community control group
      VariablesnMTBInTrauma ControlsnCommunity ControlsP Value
      Age (y)3788281
       Mean ± SD31.23±12.9932.60±13.0433.23±13.12
       Median (IQR)25.10 (20.80-40.95)28.02 (21.85-45.58)28.16 (22.90-44.21).208
      Sex, female, n (%)378131 (34.7)8231 (37.8)8131 (38.3).752
      CT findings, yes/not performed, n (%)37822 (5.8)/79 (20.9)-----
      PTA (long), n (%)378107 (28.3)-----
      Other injuries (fractures), yes, n (%)37858 (15.3)8248 (58.5)---
      Cause of injury, n (%)37882---
       Fall135 (35.7)26 (31.7)---
       Violence65 (17.2)1 (1.2)---
       Bicycle58 (15.3)7 (8.5)---
       Sports accident54 (14.3)30 (36.6)---
       Motor vehicle collision43 (11.4)3 (3.7)---
       Struck object17 (4.5)6 (7.3)---
       Other/unknown6 (1.6)9 (11.0)---
      Education years, median (IQR)37513.00 (12.00-16.00)8114.00 (12.00-16.00)8113.00 (12.00-16.00).063
      School marks, median (IQR)3644.50 (3.50-4.50)814.50 (4.50-5.50)804.50 (3.50-5.50).090
      Reading difficulties, yes, n (%)37343 (11.5)813 (3.7)813 (3.7).016
      Reduced work37645 (12.0)817 (8.6)814 (4.9).146
       Part time not working, yes, n (%)
      Not working or studying at the time of injury at all (“full time not working”), or working or studying to some extent but <80% (“part time not working.”)
      22 (5.9)5 (6.2)1 (1.2)-
       Full time not working, yes, n (%)23 (6.1)2 (2.4)3 (3.7)-
      Previous MTBI, yes, n (%)37482 (21.9)816 (7.4)818 (9.9).001
      The comparisons remained statistically significant after Bonferroni correction for multiple comparisons (critical P value=.002).
      Preinjury pain, yes, n (%)37271 (19.1)819 (11.1)7414 (18.9).228
      Preinjury headache, yes, n (%)27283 (30.5)7621 (27.6)7629 (38.2).331
      Psychiatric history, yes, n (%)37661 (16.2)819 (11.1)815 (6.2).044
      Substance use, yes, n (%)36929 (7.9)815 (6.2)8012 (15.0).083
      Poor preinjury sleep quality (ISI), median (IQR)3700.00 (0.00-0.33)810.00 (0.00-0.33)810.00 (0.00-0.67).538
      ADHD symptoms (ASRS), median (IQR)2648076
       Screener inattention5.00 (3.00-5.00)5.00 (3.00-6.00)5.00 (4.00-6.75).315
       Screener hyperactivity3.00 (2.00-5.00)3.00 (2.00-5.00)3.00 (2.00-4.00).726
       Screener total8.00 (6.00-10.00)7.00 (5.00-10.00)8.00 (6.00-10.75).392
       Full scale inattention12.00 (9.00-14.00)11.00 (8.25-14.75)12.00 (9.25-15.00).406
       Full scale hyperactivity10.00 (7.00-14.00)9.00 (7.00-13.75)11.00 (7.25-13.75).425
       Full scale22.50 (17.00-27.75)21.00 (16.00-26.00)23.50 (18.25-28.00).345
       Probable ADHD diagnosis, n (%)24 (9.1)7 (8.8)10 (13.2).543
      Alcohol use (AUDIT)2728076
       Full scale, median (IQR)6.00 (3.00-10.00)5.00 (4.00-8.00)6.00 (4.00-9.00).371
       ≥8, n (%)107 (39.3)24 (30.0)26 (34.2).277
      Personality (BFI), median (IQR)2718076
       Extroversion4.75 (4.00-5.38)4.63 (3.88-5.25)4.63 (4.00-5.25).469
       Agreeableness5.33 (4.89-5.89)5.44 (4.89-6.11)5.39 (4.78-6.00).722
       Conscientiousness5.00 (4.44-5.67)5.11 (4.33-5.78)5.06 (4.11-5.53).389
       Neuroticism3.00 (2.38-3.75)3.12 (2.13-3.75)3.00 (2.41-3.63).812
       Openness4.60 (4.00-5.30)4.70 (4.03-5.20)4.65 (4.03-5.30).875
      Pessimism (LOT-R), median (IQR)2701.17 (0.83-1.67)801.17 (0.83-1.83)761.17 (0.80-1.67).796
      Threatening Life events (LTE-Q), median (IQR)2691.00 (0.00-2.00)791.00 (0.00-2.00)761.00 (0.00-2.00).355
      Resilience (RSA), median (IQR)2698076
       Perception of self5.33 (4.36-6.00)5.50 (4.21-6.00)5.33 (4.38-5.83).907
       Planned future5.75 (4.37-6.00)5.75 (4.75-6.25)5.50 (4.83-6.33).757
       Social competence5.33 (4.50-6.00)5.33 (4.50-6.17)5.50 (4.83-6.33).215
       Family cohesion5.67 (4.83-6.17)5.83 (5.17-6.17)5.67 (4.83-6.33).822
       Social resources6.14 (5.71-6.71)6.28 (5.75-6.71)6.07 (5.57-6.68).464
       Structured style5.00 (4.25-5.75)5.25 (4.50-6.00)5.00 (4.06-5.75).498
       Total resilience5.51 (5.00-5.94)5.66 (5.08-5.96)5.56 (4.89-6.06).765
      Abbreviations: ASRS, Adult ADHD Self-Report Scale; AUDIT, Alcohol Use Disorders Identification Test; BFI, Big Five Inventory; IQR, interquartile range; ISI, mean of the first 3 items of Insomnia Severity Index; LOT-R, Life Orientation Test-Revised; LTE-Q, List of Threatening Events Questionnaire; RSA, Resilience Scale for Adult.
      The comparisons remained statistically significant after Bonferroni correction for multiple comparisons (critical P value=.002).
      Not working or studying at the time of injury at all (“full time not working”), or working or studying to some extent but <80% (“part time not working.”)
      There were 70 patients (20.8%) in the MTBI group with PCSs (the PCS+ group) 3 months after injury. In the control groups, 6 (8%) of the TCs and 1 (1.3%) of the CCs met PCS criteria.

      Correlations between personal factors

      A bivariate correlation matrix illustrating associations between the preinjury personal characteristics is presented in fig 1. There were very small correlations for many of the variables, such as age, previous MTBI, pain, headache, alcohol use, and experienced life events. Resilience correlated positively with extroversion, agreeableness, and conscientiousness and negatively with pessimism, ADHD symptoms, and neuroticism. School marks correlated positively with education, psychiatric history correlated with reduced employment, ADHD symptoms correlated positively with neuroticism and negatively with conscientiousness, and female sex correlated positively with neuroticism.
      Figure thumbnail gr1
      Fig 1Spearman correlations (continuous-continuous associations), rank-biserial correlations (nominal-continuous associations), and phi coefficients (nominal-nominal associations) between the personal factors in the MTBI group.; Abbreviations: ADHD symptoms, full scale of the Adult ADHD Self-Report Scale; alcohol use, full scale of the Alcohol Use Disorders Identification Test; Extroversion, Agreeableness, Conscientiousness, Neuroticism, and Openness, subscales from the Big Five Inventory; pessimism, full scale of the Life Orientation Test-Revised; poor preinjury sleep quality, mean of the 3 first items in Insomnia Severity Index; threatening life events, List of Threatening Events Questionnaire, total nos. of events; resilience, full scale from the Resilience Scale for Adults.

      Comparison of the PCS+ and PCS− groups in univariable analyses

      More individuals in the PCS+ group had intracranial lesions on CT and long PTA duration. Regarding the personal factors, many statistically significant differences were revealed. In the PCS+ group, there were more women; more worked less than full time before the injury; and more reported preinjury pain, psychiatric problems, poor sleep quality, and headache. They had higher scores on the measure of ADHD symptoms and neuroticism, and they had lower scores on extroversion. The PCS+ group also reported lower resilience, higher pessimism, and more threatening life events (table 3).
      Table 3Associations between PCSs and personal and injury-related factors at 3 mo in patients with MTBI (univariate logistic analyses)
      VariablesnPCS+nPCS−ORCI 95%P Value
      Age (y), median (IQR)7026.27 (20.83-42.47)26725.70 (21.06-42.51)1.000.98-1.02.847
      Sex, female, n (%)7038 (54.3)26776 (28.5)2.981.74-5.12<.001
      Statistically significant after Bonferroni correction for multiple comparisons (critical P value=.002).
      CT findings70267<.001
      Statistically significant after Bonferroni correction for multiple comparisons (critical P value=.002).
       Findings, yes, n (%)11 (15.7)8 (3.0)5.181.98-13.54.001
       Not performed, yes, n (%)7 (10.0)63 (23.6)0.420.18-0.97.042
       No findings, yes, n (%)52 (74.3)196 (73.4)Ref-
      PTA (long), n (%)7029 (41.4)26765 (24.3)2.201.27-3.82.005
      Other injuries (fractures), yes, n (%)7014 (20.0)26739 (14.6)1.460.74-2.88.272
      Education, years, median (IQR)7012.00 (12.00-15.25)26413.00 (12.00-16.00)0.890.80-1.00.054
      School marks, median (IQR)664.50 (3.50-4.50)2574.50 (3.50-4.50)0.660.48-0.92.013
      Reading difficulties, yes, n (%)6911 (15.9)26325 (9.5)1.810.84-3.88.130
      Reduced work, yes, n (%)7023 (32.9)26516 (6.0)7.623.74-15.49<.001
      Statistically significant after Bonferroni correction for multiple comparisons (critical P value=.002).
      Previous MTBI, yes, n (%)7018 (25.7)26454 (20.5)1.350.73-2.49.343
      Preinjury pain, yes, n (%)6928 (40.6)26236 (13.7)4.292.36-7.78<.001
      Statistically significant after Bonferroni correction for multiple comparisons (critical P value=.002).
      Preinjury headache, yes, n (%)4923 (46.9)21158 (27.5)2.331.23-4.41.009
      Psychiatric history, yes, n (%)7023 (32.9)26533 (12.5)3.441.85-6.38<.001
      Statistically significant after Bonferroni correction for multiple comparisons (critical P value=.002).
      Substance use, yes, n (%)684 (5.9)26120 (7.7)0.750.25-2.28.616
      Poor preinjury sleep quality (ISI), median (IQR)690.33 (0.0-1.0)2610.0 (0.0-0.33)2.151.49-3.10<.001
      Statistically significant after Bonferroni correction for multiple comparisons (critical P value=.002).
      ADHD symptoms (ASRS), median (IQR)4823.65 (19.25-32.75)20422.00 (16.00-27.75)1.041.01-1.08.016
      Alcohol use (AUDIT), median (IQR)496.00 (3.00-10.50)2116.00 (4.00-10.00)0.990.93-1.05.703
      Personality (BFI), median (IQR)49210
       Extroversion4.38 (3.75-5.13)4.88 (4.13-5.45)0.670.48-0.93.019
       Agreeableness5.33 (4.83-6.00)5.33 (4.89-5.89)0.930.60-1.43.733
       Conscientiousness4.89 (4.28-5.61)5.00 (4.44-5.69)0.800.56-1.16.246
       Neuroticism3.63 (2.81-4.19)2.88 (2.25-3.75)1.701.25-2.31.001
      Statistically significant after Bonferroni correction for multiple comparisons (critical P value=.002).
       Openness4.80 (4.05-5.45)4.60 (4.08-5.30)1.160.81-1.64.415
      Pessimism (LOT-R), median (IQR)491.50 (0.92-2.00)2091.17 (0.83-1.50)1.811.17-2.81.008
      Threatening Life events (LTE-Q), median (IQR)491.00 (0.00-3.00)2081.00 (0.00-2.00)1.251.05-1.47.010
      Resilience (RSA), median (IQR)495.27 (4.48-5.79)2085.57 (5.07-5.97)0.470.31-0.71<.001
      Statistically significant after Bonferroni correction for multiple comparisons (critical P value=.002).
      Abbreviations: ASRS, full scale of the Adult ADHD Self-Report Scale; AUDIT, full scale of the Alcohol Use Disorders Identification Test; BFI, Big Five Inventory; Extroversion, Agreeableness, Conscientiousness, Neuroticism, and Openness, subscales from the Big Five Inventory; IQR, interquartile range; ISI, mean of the 3 first items in Insomnia Severity Index; LOT-R, full scale of the Life Orientation Test-Revised; LTE-Q, List of Threatening Events Questionnaire, total nos. of events; OR, odds ratio; RSA, full scale from the Resilience Scale for Adults.
      Statistically significant after Bonferroni correction for multiple comparisons (critical P value=.002).

      Prediction of PCS in multivariable analyses

      Table 4 shows the predictors selected and their penalized coefficients from the full lasso model. The AUC for the selected model was 0.864 (optimism-corrected, 0.790; 95% CI, 0.724-0.857). In the 1000 bootstrap samples, working less than full time, preinjury pain, CT findings, not being triaged to CT, female sex, preinjury headache, poor preinjury sleep quality, openness, long PTA, and total resilience were the 10 predictors most often not set to 0 (ie, the most important variables in predicting PCSs) (fig 2).
      Table 4Penalized coefficients from a lasso model predicting PCSs (complete case analysis: PCS+ n=42; PCS− n=192)
      VariablesEstimateOR (95% CI)Percentage Coefficient=0
      Age01 (0.99-1.04)56.4
      Sex (female)
      Variables selected by lasso. A coefficient of 0 means that the variable was not selected by lasso. 95% CIs and the proportion of times the variables were set to 0 and were obtained from bootstrapping with 1000 replications. CT-no findings was not selected by lasso and is therefore reference category for this factor variable.
      0.381.46 (1.00-4.28)13.4
      CT
       No findings01 (1.00-1.00)99.5
       Findings
      Variables selected by lasso. A coefficient of 0 means that the variable was not selected by lasso. 95% CIs and the proportion of times the variables were set to 0 and were obtained from bootstrapping with 1000 replications. CT-no findings was not selected by lasso and is therefore reference category for this factor variable.
      1.534.59 (1.00-33.45)3.9
       Not performed
      Variables selected by lasso. A coefficient of 0 means that the variable was not selected by lasso. 95% CIs and the proportion of times the variables were set to 0 and were obtained from bootstrapping with 1000 replications. CT-no findings was not selected by lasso and is therefore reference category for this factor variable.
      −0.850.43 (0.05-1.00)8.3
      PTA (long)
      Variables selected by lasso. A coefficient of 0 means that the variable was not selected by lasso. 95% CIs and the proportion of times the variables were set to 0 and were obtained from bootstrapping with 1000 replications. CT-no findings was not selected by lasso and is therefore reference category for this factor variable.
      0.251.28 (1.00-3.71)27.6
      Other injuries (fractures)01 (0.50-2.72)50.0
      Education01 (0.89-1.19)64.7
      School marks01 (0.52-1.48)53.4
      Reading difficulties01 (0.54-3.46)58.9
      Reduced work
      Variables selected by lasso. A coefficient of 0 means that the variable was not selected by lasso. 95% CIs and the proportion of times the variables were set to 0 and were obtained from bootstrapping with 1000 replications. CT-no findings was not selected by lasso and is therefore reference category for this factor variable.
      1.806.07 (1.64-41.01)0.8
      Previous MTBI01 (0.31-1.35)55.7
      Preinjury pain
      Variables selected by lasso. A coefficient of 0 means that the variable was not selected by lasso. 95% CIs and the proportion of times the variables were set to 0 and were obtained from bootstrapping with 1000 replications. CT-no findings was not selected by lasso and is therefore reference category for this factor variable.
      0.882.42 (1.00-10.78)3.5
      Preinjury headache
      Variables selected by lasso. A coefficient of 0 means that the variable was not selected by lasso. 95% CIs and the proportion of times the variables were set to 0 and were obtained from bootstrapping with 1000 replications. CT-no findings was not selected by lasso and is therefore reference category for this factor variable.
      0.361.43 (1.00-4.18)21.0
      Psychiatric history
      Variables selected by lasso. A coefficient of 0 means that the variable was not selected by lasso. 95% CIs and the proportion of times the variables were set to 0 and were obtained from bootstrapping with 1000 replications. CT-no findings was not selected by lasso and is therefore reference category for this factor variable.
      0.001.00 (0.11-1.29)48.0
      Substance use01 (0.18-1.12)60.9
      Poor preinjury sleep quality (ISI)
      Variables selected by lasso. A coefficient of 0 means that the variable was not selected by lasso. 95% CIs and the proportion of times the variables were set to 0 and were obtained from bootstrapping with 1000 replications. CT-no findings was not selected by lasso and is therefore reference category for this factor variable.
      0.181.12 (1.00-2.40)21.9
      ADHD symptoms (ASRS)
      Variables selected by lasso. A coefficient of 0 means that the variable was not selected by lasso. 95% CIs and the proportion of times the variables were set to 0 and were obtained from bootstrapping with 1000 replications. CT-no findings was not selected by lasso and is therefore reference category for this factor variable.
      0.011.01 (1.00-1.07)42.5
      Alcohol use (AUDIT)01 (0.92-1.01)62.9
      Personality (BFI)
       Extroversion
      Variables selected by lasso. A coefficient of 0 means that the variable was not selected by lasso. 95% CIs and the proportion of times the variables were set to 0 and were obtained from bootstrapping with 1000 replications. CT-no findings was not selected by lasso and is therefore reference category for this factor variable.
      −0.010.99 (0.52-1.00)47.7
       Agreeableness01 (0.70-2.06)60.5
       Conscientiousness01 (0.50-1.00)59.2
       Neuroticism
      Variables selected by lasso. A coefficient of 0 means that the variable was not selected by lasso. 95% CIs and the proportion of times the variables were set to 0 and were obtained from bootstrapping with 1000 replications. CT-no findings was not selected by lasso and is therefore reference category for this factor variable.
      0.111.12 (1.00-1.85)34.5
       Openness
      Variables selected by lasso. A coefficient of 0 means that the variable was not selected by lasso. 95% CIs and the proportion of times the variables were set to 0 and were obtained from bootstrapping with 1000 replications. CT-no findings was not selected by lasso and is therefore reference category for this factor variable.
      0.151.16 (1.00-2.45)24.5
      Pessimism (LOT-R)01 (0.80-2.19)61.5
      Threatening life events (LTE-Q)01 (0.95-1.33)50.2
      Resilience (RSA)
      Variables selected by lasso. A coefficient of 0 means that the variable was not selected by lasso. 95% CIs and the proportion of times the variables were set to 0 and were obtained from bootstrapping with 1000 replications. CT-no findings was not selected by lasso and is therefore reference category for this factor variable.
      −0.330.72 (0.33-1.00)28.7
      Abbreviations: ASRS, full scale of the Adult ADHD Self-Report Scale; AUDIT, full scale of the Alcohol Use Disorders Identification Test; BFI, Big Five Inventory; Extroversion, Agreeableness, Conscientiousness, Neuroticism, and Openness, subscales from the Big Five Inventory; ISI, mean of the 3 first items in Insomnia Severity Index; LOT-R, full scale of the Life Orientation Test-Revised; LTE-Q, List of Threatening Events Questionnaire, total nos. of events; OR, odds ratio; Resilience, full scale from the Resilience Scale for Adults; RSA, Resilience Scale for Adults.
      Variables selected by lasso. A coefficient of 0 means that the variable was not selected by lasso. 95% CIs and the proportion of times the variables were set to 0 and were obtained from bootstrapping with 1000 replications. CT-no findings was not selected by lasso and is therefore reference category for this factor variable.
      Figure thumbnail gr2
      Fig 2Factors most often set to 0. NOTE. The histogram shows the percentage of the 1000 bootstrap samples that gave coefficients equal to 0 for each variable. Proportions closer to 0 indicate greater probability for the variable to be included in the model. Abbreviations: ASRS, full scale of the Adult ADHD Self-Report Scale; AUDIT, full scale of the Alcohol Use Disorders Identification Test; Extroversion, Agreeableness, Conscientiousness, Neuroticism, and Openness, subscales from the Big Five Inventory; ISI, mean of the 3 first items in Insomnia Severity Index; LOT-R, full scale of the Life Orientation Test-Revised; LTE-Q, List of Threatening Events Questionnaire, total nos. of events; resilience, full scale from the Resilience Scale for Adults.
      In a model excluding the injury-related variables, female sex, working less than full time, preinjury pain, poor sleep quality, headache, ADHD symptoms, higher neuroticism and openness, and lower extroversion and resilience were selected as predictive of PCSs, and the AUC was 0.805 (optimism-corrected, 0.734; 95% CI, 0.657-0.814). In a model that only included the injury-related variables, selected predictors for PCSs were intracranial lesions on CT, not being triaged to CT, and longer PTA duration, and the AUC was lower at 0.661 (optimism-corrected, 0.631; 95% CI, 0.551-0.700).
      In a subgroup of patients without intracranial lesions on CT, female sex, working less than full time, preinjury pain, poor sleep quality, headache, ADHD symptoms, openness, and resilience were predictors, and the AUC was 0.818 (optimism-corrected, 0.734; 95% CI, 0.647-0.814).

      Discussion

      This study illustrates that a diverse range of personal factors are associated with having persistent symptoms 3 months after an MTBI. Women were more likely than men to have persistent symptoms, and being unemployed or working less than full time before the injury was a predictor for having persistent symptoms, as were preinjury health problems and personality characteristics. Having intracranial traumatic lesions on head CT was also associated with PCSs but was less important than the personal factors in the multivariable model.
      Female sex was one of the factors most often included in the multivariable PCS prediction model. Thus, sex was a predictor for PCSs, even when some possibly confounding variables were controlled for. Previous reviews have concluded that the literature is inconclusive when it comes to female sex being a risk factor for PCSs
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      Importantly, we found that reduced employment was a strong and unique predictor of PCSs, even when possibly confounding variables were controlled for in the multivariable lasso model (eg, poor sleep quality and psychiatric history, which correlated moderately with reduced employment). Unemployment has previously been found to predict PCS after MTBI
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      Preinjury health factors, such as having a psychiatric history, symptoms of ADHD, headaches, and sleep problems, were all significant predictors. Having preinjury bodily pain emerged as a particularly strong predictor. Preinjury health problems as a risk factor for PCSs have also been reported in other studies,
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      Some injury severity indicators were associated with outcome. In the present study, head CT had been performed in 79% of the sample, and of those, only 6% had intracranial traumatic lesions (ie, complicated MTBI). Patients with complicated MTBI had higher risk for PCSs, which is in line with 1 previous study
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      • Tinawi S.
      • et al.
      Comprehensive clinical picture of patients with complicated vs uncomplicated mild traumatic brain injury.
      PTA duration >1 hour was also associated with PCSs, albeit weakly and not in the uncomplicated MTBI group. Interestingly, not being triaged for CT, which probably can be considered a proxy for having fewer symptoms and an overall better clinical presentation in the emergency department, was associated with a reduced risk of PCSs.
      One aim of this study was to report the discriminative ability of different models using the AUC of the receiver operating characteristic curve and to explore how a broad range of personal factors contributed to model performance. In the full model, we found an AUC value of 0.79 after optimism correction, which is high compared with other reported multivariable models in MTBI.
      • Silverberg N.D.
      • Gardner A.J.
      • Brubacher J.R.
      • Panenka W.J.
      • Li J.J.
      • Iverson G.L.
      Systematic review of multivariable prognostic models for mild traumatic brain injury.
      When injury-related variables were removed, the AUC was only modestly reduced to 0.73. In contrast, a model with only injury severity variables performed poorly (AUC, 0.63). In the subsample with uncomplicated MTBI, the full model also performed adequately (AUC, 0.73), and interestingly, PTA duration was not selected in this model. Positive CT findings were clearly related to having persistent symptoms, but because it is uncommon to have an abnormal head CT after MTBI, combining this and other injury severity variables did not produce a useful prediction model.

      Study limitations

      This study has several limitations. First, preinjury personal factors were all based on self-report, and they were all collected after the injury, making them susceptible to some degree of reporting bias or inaccuracy. This limitation is, for the most part, unavoidable. Second, there was a low rate of complicated MTBIs in this study, which reduces the statistical power of that variable for predicting persistent symptoms. Importantly, however, we consider that a natural consequence of recruiting a more representative cohort of people with MTBIs from both ambulatory clinics and the emergency department. Third, although our sample size was large (N=378), the prevalence of some potentially important preinjury predictor variables in the cohort was small, and thus, power was reduced in analyses of the influence of those predictors (eg, reading difficulties, reduced employment, possible ADHD). Fourth, the number of people with PCSs was modest, and a larger sample of people with PCSs would have allowed for analyses on how prognostic factors moderate each other. Fifth, in the multivariable models, only complete cases were included. Using multiple imputation in lasso models is less straightforward than in ordinary regression models because lasso performs variable selection. However, in the univariable analyses, we could use all data available (ie, the number of observations differed between analyses), and the most important factors for predicting PCSs in the lasso models were also strongly associated with PCSs in the univariable models, further supporting their role in the development of PCSs. Sixth, the CC group was not population-based, and the rate of PCSs in the CC group should be interpreted with caution. However, the groups were matched, not only on age and sex but also on education, and there were only small differences between the MTBI group, the TC group, and the CC group on the factors that predicted PCSs. Seventh, litigation is associated with PCSs in other studies and countries, and we did not collect information on this variable.
      • Hanks R.A.
      • Rapport L.J.
      • Seagly K.
      • Millis S.R.
      • Scott C.
      • Pearson C.
      Outcomes after concussion recovery education: effects of litigation and disability status on maintenance of symptoms.
      ,
      • Lange R.T.
      • Iverson G.L.
      • Rose A.
      Post-concussion symptom reporting and the "good-old-days" bias following mild traumatic brain injury.
      However, in our study, conducted in a country where health care is free and people have access to sickness and disability benefits from the government, a litigation process is seldom initiated in the first few months, when our study was conducted. Also, results from this study were solely for research purposes, not available for anyone else; hence, no financial gain could be obtained through participation. Finally, the relative strength of risk factors may differ in other settings and in other countries, as illustrated in a study of moderate TBI in Norway and the Netherlands,
      • Einarsen C.E.
      • van der Naalt J.
      • Jacobs B.
      • et al.
      Moderate traumatic brain injury: clinical characteristics and a prognostic model of 12-month outcome.
      and our findings need to be replicated.

      Conclusions

      We collected a wider range of personal factors than prior studies and found that several of these factors contributed in large, important, and unique ways to predicting persistent symptoms after MTBI. Particularly important preinjury personal factors relating to persistent symptoms were reduced employment, bodily pain, and headaches, and women were more likely than men to have persistent symptoms. Other important preinjury characteristics included poor sleep quality, symptoms of ADHD, a tendency toward neuroticism, and lower resilience. The common injury-related variables, CT abnormalities, and longer duration of PTA were also predictive of worse outcome but much less so than a combination of personal factors. The results of this study, illustrated in fig 3, highlight the value of taking a broad approach and using the biopsychosocial model as a framework to understand and treat PCSs.
      • Polinder S.
      • Cnossen M.C.
      • Real R.G.L.
      • et al.
      A multidimensional approach to post-concussion symptoms in mild traumatic brain injury.
      ,
      • van der Naalt J.
      • Timmerman M.E.
      • de Koning M.E.
      • et al.
      Early predictors of outcome after mild traumatic brain injury (UPFRONT): an observational cohort study.
      ,
      • Cassidy J.D.
      • Cancelliere C.
      • Carroll L.J.
      • et al.
      Systematic review of self-reported prognosis in adults after mild traumatic brain injury: results of the International Collaboration on Mild Traumatic Brain Injury Prognosis.
      The study represents an important step in the development of practical and feasible prognostic models for adults with MTBI, with the ultimate goal of using these models to identify at-risk individuals and refer them for earlier evidence-informed treatment and rehabilitation.
      Figure thumbnail gr3
      Fig 3Biopsychosocial factors related to symptom reporting at 3 months after MTBI.

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