# Absence from work in the 12 months following mild traumatic brain injury in Europe: a CENTER-TBI cohort study

Louis Jacob, John Castro, Camille Heslot, Nada Andelic, Olli Tenovuo, Philippe Azouvi

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## To cite this version:

Louis Jacob, John Castro, Camille Heslot, Nada Andelic, Olli Tenovuo, et al.. Absence from work in the 12 months following mild traumatic brain injury in Europe: a CENTER-TBI cohort study. Annals of Physical and Rehabilitation Medicine, 2025, 68 (8), pp.102017. 10.1016/j.rehab.2025.102017. hal-05293361

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Original article

# Absence from work in the 12 months following mild traumatic brain injury in Europe: a CENTER-TBI cohort study

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Louis Jacob<sup>a,b,c,*</sup>, John Castro<sup>d,e</sup>, Camille Heslot<sup>a,f</sup>, Nada Andelic<sup>g</sup>, Olli Tenovuo<sup>h</sup>, CENTER-TBI Participants and Investigators (Appendix) <sup>#</sup>, Philippe Azouvi<sup>d,e</sup>

ARTICLE INFO

Keywords:

Absence from work

Epidemiology

Europe

Mild traumatic brain injury

Trajectories

A B S T R A C T

**Background:** Most of the prior research on absence from work after a mild traumatic brain injury (mTBI) was of a small sample size and had a limited number of follow-up assessments.

**Objectives:** Therefore, this study investigated the prevalence of absence from work, trajectories, and associated factors in the 12 months following mTBI in Europe.

**Methods:** Data from a European cohort (CENTER-TBI) were used. Absence from work was assessed at 2 weeks, 3 months, 6 months, and 12 months after mTBI. Associated factors included sociodemographic factors, current psychoactive substance use, pre-injury medical history, injury-related factors, medical care, complications, and discharge, and 2-week follow-up questionnaires. Inferential analyses relied on generalized estimating equations.

**Results:** This study included 1080 adults with mTBI who were working at the time of the injury (median [IQR] age, 46.0 [23.0] years; 69 % men). Absence from work decreased from 32 % at 2 weeks to 20 % at 12 months after the injury (P < 0.001). Around 76 % of adults returned to work within the first 3 months, whereas > 43 % of those absent from work at 3 months remained absent at 12 months. The 3 factors with the strongest association with absence from work were admission to hospital wards (OR = 2.57) or intensive care units (OR = 4.76), the presence of a pre-injury psychiatric disorder (OR = 2.55), and older age (OR = 1.61).

**Conclusions:** One-fifth of workers with mTBI were absent from work 12 months after the injury. Early identification of those at particular risk for not returning to work should be a clinical priority.

**Study registration:** NCT02210221 (https://clinicaltrials.gov/).

Introduction

Mild traumatic brain injury (mTBI) is defined as a TBI with a Glasgow Coma Scale (GCS) score of ≥ 13 half an hour after the injury and a post-traumatic amnesia duration of < 24 h [1]. Worldwide, there are about 69 million

new cases of TBI each year, and 56 million of them are of mild severity [2]. Delayed diagnosis, persistent symptoms, and impaired mental health may have deleterious effects on the working ability of adults with mTBI.

In previous years, multiple studies have investigated absence from work in the working-age mTBI population [3–13]. For example, a study

**Abbreviations:** AIS, Abbreviated Injury Scale; CENTER-TBI, Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury; CI, confidence interval; GAD-7, Generalized Anxiety Disorder-7; GCS, Glasgow Coma Scale; GOSE, Glasgow Outcome Scale-Extended; IQR, interquartile range; ISS, Injury Severity Score; LASSO, least absolute shrinkage and selection operator; MICE, multiple imputation by chained equation; mTBI, mild traumatic brain injury; OR, odds ratio; PCL-5, Post-traumatic Stress Disorder Checklist for DSM-5; PHQ-9, Patient Health Questionnaire-9; QOLIBRI, Quality of Life after Brain Injury; RPQ, Rivermead Post-concussion Symptoms Questionnaire; SD, standard deviation; SF-12, 12-item Short-Form Health Survey.

*Corresponding author.

E-mail address: louis.jacob@aphp.fr (L. Jacob).

# Details on the CENTER-TBI Participants and Investigators are provided under the Acknowledgments section.

ARTICLE INFO

<footnote><sup>a</sup>Assistance Publique – Hôpitaux de Paris (AP-HP), Université Paris Cité, Lariboisière-Fernand Widal Hospital, Department of Physical Medicine and Rehabilitation, Paris 75010, France</footnote>

<footnote><sup>b</sup>Inserm, Université Paris Cité, U1153, Epidemiology of Ageing and Neurodegenerative Diseases (EpiAgeing), Paris 75010, France</footnote>

<footnote><sup>c</sup>Research and Development Unit, Parc Sanitari Sant Joan de Dèu, CIBERSAM, ISCIII, Dr. Antoni Pujadas, 42, Sant Boi de Llobregat, Barcelona 08830, Spain</footnote>

<footnote><sup>d</sup>Assistance Publique – Hôpitaux de Paris (AP-HP), Université Paris Saclay, Raymond Poincaré Hospital, Department of Physical Medicine and Rehabilitation, Garches 92380, France</footnote>

<footnote><sup>e</sup>Université Paris-Saclay, UVSQ, Inserm, CESP, MOODS research team, Villejuif 94807, France</footnote>

<footnote><sup>f</sup>Sorbonne Université, Paris Brain Institute (ICM), Frontlab, CNRS UMR 7225, INSERM U1127, Paris 75013, France</footnote>

<footnote><sup>g</sup>Department of Physical Medicine and Rehabilitation, Oslo University Hospital and University of Oslo, Oslo 0372, Norway</footnote>

<footnote><sup>h</sup>Turku Brain Injury Centre, Turku University Hospital and University of Turku, Turku FI-20014, Finland</footnote>
of 435 mTBI individuals presenting to emergency departments of trauma centers in the United States revealed that the prevalence of absence from work was 59 % at 2 weeks and 17 % at 12 months after the injury [10]. Although the previous body of scientific literature is of interest, it displays several limitations that should be acknowledged at this point. Most studies included fewer than 200 participants [3,4,7,9,11–13], which may have impacted the generalizability of the findings. Moreover, all, except 1 study, were conducted in a single country [3–7,9–13]. Given that employment and health policies vary by country, results in 1 country may not be extrapolated to another country. In addition, research has frequently included only 1 or 2 follow-up assessments [4,5,8,9,12,13], and hence, it was not possible to investigate detailed trajectories of absence from work following the injury. In this context, more data on work status and its correlates following an mTBI are urgently needed.

Therefore, this study aimed to investigate the prevalence of absence from work, its trajectories, and its associated factors in the 12 months following mTBI in Europe. With the premise that most adults would return to work within the first few months after the injury, we hypothesized that the prevalence of absence from work would gradually decrease in the year following the mTBI. An additional hypothesis was that certain demographic factors (eg, age), health behaviors (eg, alcohol misuse), medical conditions (eg, pre-injury psychiatric disorder), and injury-related factors (eg, baseline GCS) would be statistically associated with absence from work. Although the same dataset has already been used in the literature focusing on all TBIs [14,15] and mTBI [8], it is worth noting that the previous mTBI study focused on a single follow-up assessment (ie, 6 months post-injury), which limits the possibility of studying trajectories and conducting detailed longitudinal analyses.

## Material and methods

### Study design

This study relied on data from the Collaborative European Neuro-Trauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) dataset [16]. The CENTER-TBI dataset included 4509 individuals living in Europe and Israel (18 countries) with mild, moderate, or severe TBI [17]. Data were collected between 2014 and 2017. Adults included in the CENTER-TBI study had to be referred to one of the participating centers within 24 h of the TBI, with an indication to undergo a head computed tomography scan. After being referred to a participating center, there were 3 possible care pathways: direct discharge from the emergency room, admission to hospital wards, and admission to intensive care units. The minimum follow-up was 6 months and lasted for up to 24 months. Data collection relied on medical records and personal interviews. An electronic form was used by research personnel at each participating center to collect the data, which was de-identified before being stored on a secure database [17].

### Regulatory and ethical considerations

Ethics approval for the CENTER-TBI study was obtained from each participating center [17]. Informed consent was mandatory in line with local and national requirements. Details on the ethical approval at each participating center are available online [18]. The study was registered at https://clinicaltrials.gov/ under the number NCT02210221.

### Study participants

The analysis included only participants with a baseline-derived GCS score of ≥ 13, who were working at the time of the injury, and had available follow-up data on absence from work. The baseline-derived GCS score was preferred over the GCS score assessed at the accident scene, as this score was frequently missing (ie, 40 % of the data was missing). The baseline-derived GCS, which was centrally computed, corresponds to the post-stabilization GCS score; if this score was missing, the closest

<figure><img src="image_4.png" /><figcaption>**Fig. 1.** Flowchart of study participants. Abbreviation: CENTER-TBI Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury.</figcaption></figure>

pre-hospital, non-missing GCS score was used. Adults were considered actively working if they reported working ≥ 35 h per week, working 20–34 h per week, working < 20 h per week, or having special employment/sheltered employment. Considering this definition, full-time students were excluded from this research. The flow chart of the study participants is displayed in Fig. 1. The study adhered to the STROBE (Strengthening the Reporting of Observational Studies in Epidemiology) guidelines (Supplementary Table 1).

### Absence from work (dependent variable)

Absence from work was assessed within the year following mTBI. There were 4 assessments at 2 weeks, 3 months, 6 months, and 12 months after the injury. Only absence from work was assessed at these follow-ups in the present research. Not all participants were seen at each of these assessments; however, every participant had at least 1 follow-up assessment regarding their absence from work. Adults were considered absent from work if they reported being unable to work, being retired, or actively seeking employment. The reason for retirement was not documented. In contrast, adults were considered to have returned to work if they returned to the previous job at the same level or hours, returned to the previous job at a reduced level or hours, returned to the previous job at an increased level or hours from pre-injury, changed job/had a different work, or had special employment/sheltered employment.

### Factors associated with 12-month absence from work

Factors assessed at the time of injury, or 2 weeks after the injury, included sociodemographic factors, current psychoactive substance use,
pre-injury medical history, injury-related factors, medical care, compli-
cations and discharge, and 2-week follow-up questionnaires.

Sociodemographic factors

Sociodemographic factors included age, sex, marital status, years of
education, occupational category, and European region.

Current psychoactive substance use

Psychoactive substances included tobacco, alcohol misuse (> 2 units per day), and cannabis, the use of these substances being assessed in the 3 months preceding mTBI. For alcohol misuse, the definition relied on the cutoff frequently chosen in Europe [19].

Pre-injury medical history

Pre-injury medical history included the number of chronic physical conditions, a psychiatric disorder, and a previous TBI. Fourteen chronic physical conditions were assessed; the list of these conditions has been detailed elsewhere [20].

Injury-related factors

Injury-related factors were the geographical area of the accident,
injury intention, baseline-derived GCS score, and Injury Severity Score
(ISS). The ISS corresponds to the sum of the squares of the 3 body
regions displaying the highest Abbreviated Injury Scale (AIS) score; ISS
scores range from 0 to 75 [21].

Medical care, complications, and discharge

Medical care, complications, and discharge-related factors included stratum (ie, direct discharge from the emergency room, admission to hospital wards, or admission to intensive care units), intracranial surgery, extracranial surgery, intracranial complication, extracranial complication, and GCS at discharge.

Two-week follow-up questionnaires

Several questionnaires were undertaken at the 2-week assessment. Not all individuals participated in the 2-week follow-up. These questionnaires were the Generalized Anxiety Disorder-7 (GAD-7), the Glasgow Outcome Scale-Extended (GOSE), the Post-traumatic Stress Disorder Checklist for DSM-5 (PCL-5), the Patient Health Questionnaire-9 (PHQ-9), the Quality of Life after Brain Injury (QOLIBRI), the Rivermead Post-concussion Symptoms Questionnaire (RPQ), the 12-item Short-Form Health Survey (SF-12) mental component, and the SF-12 physical component. The GAD-7 ranges from 0 to 21, and higher scores indicate higher generalized anxiety disorder symptoms [22]. A cutoff of 10 is used to identify moderate-to-severe generalized anxiety disorder symptoms. The GOSE is a measure of disability and recovery after TBI, which ranges from 1 (death) to 8 (upper good recovery) [23]. The PCL-5 measures post-traumatic stress disorder symptoms; the score ranges from 0 to 80, and an increased score corresponds to more severe symptoms [24]. A cutoff around 31–33 is suggestive of post-traumatic stress disorder [25]. The PHQ-9 is a scale aimed at assessing depression (0–27 score; a higher score indicates more depressive symptoms) [26]. A cutoff of 10 is used to define major depression. Regarding the QOLIBRI, this questionnaire assesses the disease-specific quality of life, and the score ranges from 0 to 100, with decreasing scores indicating decreasing quality of life [27]. The RPQ measures post-concussion symptoms, and the score range is 0–64 (higher scores indicate more severe symptoms) [28]. Finally, the SF-12 evaluates generic health-related quality of life, with a mental and a physical component, ranging from 0 (poorest quality of life) to 100 (best quality of life) [29]. Although these variables were also assessed later in the follow-up, the present research focused on the 2-week assessment only to strengthen the potential causality between these variables and the 12-month absence from work, this causality being interpreted cautiously given the observational nature of the study.

Statistical analysis

Missing data

The proportion of missing data ranged from 0 % for age, sex, Euro-
pean region, baseline-derived GCS score, and stratum to 82 % for the SF-
12 (mental and physical components; Table 1). There were 99 % of
mTBI adults working at the time of the injury who had at least 1 missing
value in the independent variables. The median (interquartile range
[IQR]) number of missing data per individual in the independent varia-
bles was 8 (2). Missing data were imputed using multiple imputation by
chained equation (MICE). As previous research has indicated, the num-
ber of imputations should equal the proportion of incomplete cases
[30], 99 datasets were imputed.

Descriptive analysis

The characteristics of individuals with mTBI at the injury and 2 weeks after the injury were described before and after multiple imputation. Categorical variables were described using N (%), and continuous variables were described using median (IQR). For the GAD-7, PCL-5, and PHQ-9 questionnaires, the proportion of participants with scores equal to or higher than 10 for the GAD-7, 32 for the PCL-5, and 10 for the PHQ-9 was estimated. Furthermore, the prevalence of absence from work was analyzed at 2 weeks, 3 months, 6 months, and 12 months after the injury. The change in the prevalence of absence from work was studied using a generalized estimating equation, which relied on the binomial family with a logit link function, with absence from work as the dependent variable and time as the independent variable. Trajectories of absence from work within the year of mTBI were also descriptively analyzed. The same 4 follow-ups were used. For each follow-up except the 2-week follow-up, 4 trajectories were studied using proportions: proportion of participants not working among those not working at the previous follow-up, proportion of participants working among those not working at the previous follow-up, proportion of participants not working among those working at the previous follow-up, and proportion of participants working among those working at the previous follow-up. The different working categories were detailed at each evaluation. The descriptive analyses focusing on the absence from work and its trajectories during the 12 months following the mTBI were repeated in people without any intracranial surgery during the hospitalization (if any) and any intracranial complication at discharge. These sensitivity analyses were motivated by the fact that the definition of mTBI sometimes includes normal structural brain imaging [31].

Inferential analysis

The associations between time since the TBI, the characteristics of the mTBI population at the injury and 2 weeks after the injury (ie, the independent variables), and absence from work in the 12 months following the injury (ie, the dependent variable) were studied using generalized estimating equations relying on the binomial family with a logit link function. The first regression analysis was unadjusted, and each association was analyzed separately. Due to the presence of > 20 independent variables, it was not feasible to include all variables in the adjusted analysis. The selection of the variables relied on the least absolute shrinkage and selection operator (LASSO). The LASSO regression was performed on the 99 imputed datasets. An independent variable was included in the final model only if it had been selected in at least half of the imputed datasets. After this selection, sex, years of education, current tobacco use, current alcohol misuse, the GAD-7, the PHQ-9, and the RPQ were excluded from the analysis. All numerical variables were scaled to allow comparisons of their respective estimates. For the occupational category, due to the small size of the “None” category, it was merged with the “Other” category. For the region of Central and Eastern Europe, which included a small number of participants, a merger was made with Southern Europe. Given that the data assessed at 2 weeks had > 65 % missing data, and although these missing data were imputed, 2 adjusted analyses were conducted: 1 model excluded the 2-
<table><caption>**Table 1**

Characteristics of the mild traumatic brain injury population before and after multiple imputation (N = 1080).</caption><thead><tr><th>Characteristics</th><th>Category</th><th>Before multiple imputation</th><th>Missing data (N [%])</th><th>After multiple imputation</th></tr></thead><tbody><tr><td><strong>Sociodemographic factors</strong></td><td></td><td></td><td></td><td></td></tr><tr><td>Age (in years)</td><td>Median (IQR)</td><td>46.0 (23.0)</td><td>0 (0)</td><td>46.0 (23.0)</td></tr><tr><td rowspan="2">Sex</td><td>Female</td><td>336 (31)</td><td>0 (0)</td><td>336 (31)</td></tr><tr><td>Male</td><td>744 (69)</td><td></td><td>744 (69)</td></tr><tr><td rowspan="2">Marital status</td><td>Married or living together</td><td>625 (60)</td><td>34 (3)</td><td>644 (60)</td></tr><tr><td>Never married, separated, divorced, or widowed</td><td>421 (40)</td><td></td><td>436 (40)</td></tr><tr><td>Years of education</td><td>Median (IQR)</td><td>14.0 (5.0)</td><td>110 (10)</td><td>14.2 (5.0)</td></tr><tr><td rowspan="7">Occupational category</td><td>Manager or professional</td><td>249 (23)</td><td>6 (1)</td><td>250 (23)</td></tr><tr><td>Technician, supervisor, or associate professional</td><td>162 (15)</td><td></td><td>162 (15)</td></tr><tr><td>Clerk or sales</td><td>116 (11)</td><td></td><td>117 (11)</td></tr><tr><td>Skilled manual worker</td><td>171 (16)</td><td></td><td>172 (16)</td></tr><tr><td>Manual worker</td><td>198 (18)</td><td></td><td>199 (18)</td></tr><tr><td>Other</td><td>177 (16)</td><td></td><td>178 (16)</td></tr><tr><td>None</td><td>1 (&lt; 1)</td><td></td><td>1 (&lt; 1)</td></tr><tr><td rowspan="4">European region</td><td>Central and Eastern Europe</td><td>19 (2)</td><td>0 (0)</td><td>19 (2)</td></tr><tr><td>Northern Europe</td><td>315 (29)</td><td></td><td>315 (29)</td></tr><tr><td>Southern Europe</td><td>247 (23)</td><td></td><td>247 (23)</td></tr><tr><td>Western Europe</td><td>499 (46)</td><td></td><td>499 (46)</td></tr><tr><td><strong>Current psychoactive substance use</strong></td><td></td><td></td><td></td><td></td></tr><tr><td rowspan="2">Tobacco</td><td>No</td><td>717 (71)</td><td>65 (6)</td><td>759 (70)</td></tr><tr><td>Yes</td><td>298 (29)</td><td></td><td>321 (30)</td></tr><tr><td rowspan="2">Alcohol (misuse)</td><td>No</td><td>652 (64)</td><td>64 (6)</td><td>694 (64)</td></tr><tr><td>Yes</td><td>364 (36)</td><td></td><td>386 (36)</td></tr><tr><td rowspan="2">Cannabis</td><td>No</td><td>967 (96)</td><td>68 (6)</td><td>1030 (95)</td></tr><tr><td>Yes</td><td>45 (4)</td><td></td><td>50 (5)</td></tr><tr><td><strong>Pre-injury medical history</strong></td><td></td><td></td><td></td><td></td></tr><tr><td>Number of chronic physical conditions</td><td>Median (IQR)</td><td>1.0 (1.0)</td><td>1 (&lt; 1)</td><td>1.0 (1.0)</td></tr><tr><td rowspan="2">Psychiatric disorder</td><td>No</td><td>967 (90)</td><td>11 (1)</td><td>976 (90)</td></tr><tr><td>Yes</td><td>102 (10)</td><td></td><td>104 (10)</td></tr><tr><td rowspan="2">Previous traumatic brain injury</td><td>No</td><td>928 (89)</td><td>39 (4)</td><td>961 (89)</td></tr><tr><td>Yes</td><td>113 (11)</td><td></td><td>119 (11)</td></tr><tr><td><strong>Injury-related factors</strong></td><td></td><td></td><td></td><td></td></tr><tr><td rowspan="2">Geographical area of injury</td><td>Rural</td><td>215 (21)</td><td>45 (4)</td><td>228 (21)</td></tr><tr><td>Urban</td><td>820 (79)</td><td></td><td>852 (79)</td></tr><tr><td rowspan="3">Injury intention</td><td>Intentional</td><td>58 (5)</td><td>2 (&lt; 1)</td><td>58 (5)</td></tr><tr><td>Undetermined</td><td>21 (2)</td><td></td><td>21 (2)</td></tr><tr><td>Unintentional</td><td>999 (93)</td><td></td><td>1001 (93)</td></tr><tr><td>Baseline-derived GCS score</td><td>Median (IQR)</td><td>15.0 (0.0)</td><td>0 (0)</td><td>15.0 (0.0)</td></tr><tr><td>Injury Severity Score</td><td>Median (IQR)</td><td>10.0 (13.0)</td><td>6 (&lt; 1)</td><td>10.0 (13.0)</td></tr><tr><td><strong>Medical care, complications, and discharge</strong></td><td></td><td></td><td></td><td></td></tr><tr><td rowspan="3">Stratum</td><td>Direct discharge from the emergency room</td><td>334 (31)</td><td>0 (0)</td><td>334 (31)</td></tr><tr><td>Admission to hospital wards</td><td>475 (44)</td><td></td><td>475 (44)</td></tr><tr><td>Admission to intensive care units</td><td>271 (25)</td><td></td><td>271 (25)</td></tr><tr><td rowspan="2">Intracranial surgery</td><td>No</td><td>687 (90)</td><td>320 (30)</td><td>798 (74)</td></tr><tr><td>Yes</td><td>73 (10)</td><td></td><td>282 (26)</td></tr><tr><td rowspan="2">Extracranial surgery</td><td>No</td><td>620 (82)</td><td>320 (30)</td><td>796 (74)</td></tr><tr><td>Yes</td><td>140 (18)</td><td></td><td>284 (26)</td></tr><tr><td rowspan="2">Intracranial complication</td><td>No</td><td>697 (95)</td><td>350 (32)</td><td>771 (71)</td></tr><tr><td>Yes</td><td>33 (5)</td><td></td><td>309 (29)</td></tr><tr><td rowspan="2">Extracranial complication</td><td>No</td><td>669 (92)</td><td>350 (32)</td><td>780 (72)</td></tr><tr><td>Yes</td><td>61 (8)</td><td></td><td>300 (28)</td></tr><tr><td>GCS at discharge</td><td>Median (IQR)</td><td>15.0 (0.0)</td><td>465 (33)</td><td>15.0 (0.0)</td></tr><tr><td><strong>Two-week follow-up questionnaires</strong></td><td></td><td></td><td></td><td></td></tr><tr><td>GAD-7<sup>a</sup></td><td>Median (IQR)</td><td>2.0 (6.0)</td><td>723 (67)</td><td>2.7 (6.7)</td></tr><tr><td>GOSE</td><td>Median (IQR)</td><td>7.0 (3.0)</td><td>809 (75)</td><td>6.0 (2.2)</td></tr><tr><td>PCL-5<sup>b</sup></td><td>Median (IQR)</td><td>9.0 (16.0)</td><td>724 (67)</td><td>9.9 (17.4)</td></tr><tr><td>PHQ-9<sup>c</sup></td><td>Median (IQR)</td><td>5.0 (9.0)</td><td>724 (67)</td><td>5.4 (8.3)</td></tr><tr><td>QOLIBRI</td><td>Median (IQR)</td><td>71.0 (29.0)</td><td>710 (66)</td><td>67.4 (31.5)</td></tr><tr><td>RPQ</td><td>Median (IQR)</td><td>6.0 (17.0)</td><td>716 (66)</td><td>7.2 (17.0)</td></tr><tr><td>SF-12 – mental component</td><td>Median (IQR)</td><td>47.4 (15.8)</td><td>888 (82)</td><td>46.4 (15.9)</td></tr><tr><td>SF-12 – physical component</td><td>Median (IQR)</td><td>44.9 (17.5)</td><td>888 (82)</td><td>40.5 (18.4)</td></tr></tbody></table>

Abbreviations: GAD-7, Generalized Anxiety Disorder-7; GCS, Glasgow Coma Scale; GOSE, Glasgow Outcome Scale—Extended; IQR, interquartile range; ISS, Injury Severity Score; PCL-5, Post-traumatic Stress Disorder Checklist for DSM-5; PHQ-9, Patient Health Questionnaire-9; QOLIBRI, Quality of Life after Brain Injury; RPQ, Rivermead Post-concussion Symptoms Questionnaire; SF-12, 12-item Short-Form Health Survey.

Data are N (%) unless otherwise specified.

Given that the prevalence of participants with at least one missing data point was 99%, 99 datasets were imputed using chained equations. Figures displayed in the table are pooled over the 99 imputed datasets.

<sup>a</sup> 14% and 17% of adults had a GAD-7 score higher than or equal to 10 before and after multiple imputation, which indicates moderate-to-severe generalized anxiety disorder symptoms.

<sup>b</sup> 11% and 14% of adults had a PCL-5 score higher than or equal to 32 before and after multiple imputation, suggesting the presence of post-traumatic stress disorder.

<sup>c</sup> 26% and 28% of adults had a PHQ-9 score higher than or equal to 10 before and after multiple imputation, which defines major depression.
<figure><img src="image_5.png" /><figcaption>**Fig. 2.** Prevalence of absence from work in adults with mild traumatic brain injury in the year following the injury in Europe. The upper bar corresponds to the upper limit of the 95 % confidence interval. There were 64 %, 16 %, 18 %, and 53 % of missing data for absence from work at 2 weeks, 3 months, 6 months, and 12 months, respectively. The *P* value was obtained using a generalized estimating equation, which relied on the binomial family with a logit link function, with absence from work as the dependent variable and time as the numerical independent variable.</figcaption></figure>

week follow-up questionnaires, and 1 model included them. This infer-
ential analysis was repeated in the population of mTBI adults without
any intracranial surgery during the hospitalization (if any) and any
intracranial complication at discharge. The results of the generalized
estimating equations were pooled over the 99 imputed datasets and dis-
played using odds ratios (ORs) and CIs. *P* values < 0.050 were consid-
ered statistically significant. The statistical analysis was conducted using
R version 4.4.2 [32].

Results

Characteristics of the population

A total of 1080 individuals were included in the present study. The characteristics of the population are displayed in Table 1. The median (IQR) age was 46.0 (23.0) years; 69 % of the participants were male. The prevalence of pre-injury psychiatric disorders was 10 %. The median (IQR) baseline-derived GCS score was 15.0 (0.0), while the median (IQR) ISS was 10.0 (13.0). The most frequent stratum was the admission to hospital wards (ie, 44 %). At 2 weeks, 17 % of the population displayed moderate-to-severe generalized anxiety disorder symptoms (ie, a GAD-7 score higher or equal to 10), 14 % had possible post-traumatic stress disorder (ie, a PCL-5 score higher or equal to 32), and 28 % showed major depression (ie, a PHQ-9 score higher or equal to 10).

Trajectories of absence from work in the year following mild traumatic brain injury

Participants with data at 2 weeks numbered 388, at 3 months, 905, at 6 months, 882, and at 12 months, 512. The prevalence of absence from work in the year following mTBI is shown in Fig. 2. The proportion of individuals absent from work was 32 % at 2 weeks and decreased to 20 % at 12 months (P < 0.001). For mTBI adults without intracranial surgery during hospitalization (if any) and any intracranial complication at discharge, the prevalence of absence from work was 51 % at 2 weeks and 17 % at 12 months (P < 0.001; Supplementary Figure 1). Fig. 3 further displays trajectories of absence from work in the year following mTBI. Among people absent from work at 2 weeks, most (ie, 70 %)

returned to work at 3 months, while 99 % of those already working at 2
weeks continued working at 3 months. Overall, 76 % of the population
returned to work within the first 3 months. The trajectory of people
absent from work changed between 3 and 6 months. At the 3-month fol-
low-up, 62 % of those not working remained absent from work at the 6-
month follow-up. Most people who worked at 3 months continued work-
ing at 6 months (ie, 96 %). The trajectories observed between 3 and 6
months persisted between 6 and 12 months. Overall, 43 % of those not
working at 3 months were absent from work at 12 months. These trajec-
tories were corroborated in the mTBI population without intracranial
surgery and any intracranial complication (Supplementary Figure 2).
The only exception is that, as already mentioned, most adults (ie, 51 %)
were absent from work at 2 weeks.

Factors associated with 12-month absence from work in people with mild traumatic brain injury

Table 2 shows the association between time since the TBI, the char-
acteristics of participants (ie, the independent variables), and absence
from work in the 12 months following traumatic brain injury (ie, the
dependent variable). The adjusted analysis, not including 2-week fol-
low-up questionnaires, revealed that absence from work was statistically
associated with time since the TBI (2 weeks: reference; 3 months:
OR = 0.25, 95 % CI = 0.18–0.35; 6 months: OR = 0.16, 95 %
CI = 0.11–0.23; and 12 months: OR = 0.11, 95 % CI = 0.07–0.16),
age (in years; per one-standard deviation [SD] increase: OR = 1.61,
95 % CI = 1.41–1.83), skilled manual occupation (managerial or pro-
fessional occupation: reference; OR = 1.48, 95 % CI = 1.06–2.07),
manual occupation (OR = 1.53, 95 % CI = 1.11–2.12), the number of
chronic physical conditions (per one-SD increase: OR = 1.14, 95 %
CI = 1.02–1.27), a pre-injury psychiatric disorder (OR = 2.41, 95 %
CI = 1.72–3.39), the baseline-derived GCS score (per one-SD increase:
OR = 0.81, 95 % CI = 0.73–0.89), the ISS (per one-SD increase:
OR = 1.52, 95 % CI = 1.31–1.77), and stratum (direct discharge from
the emergency room: reference; admission to hospital wards:
OR = 2.64, 95 % CI = 1.40–4.99; admission to intensive care units:
OR = 4.57, 95 % CI = 2.32–9.02). The adjusted analysis, including 2-
week follow-up questionnaires, corroborated most of these findings.
<figure><img src="image_6.png" /><figcaption>Fig. 3. Trajectories of absence from work in the year following mild traumatic brain injury in Europe.</figcaption></figure>

Table 2

Association between time since the traumatic brain injury, the characteristics of adults, and absence from work in the 12 months following mild traumatic brain injury (generalized estimating equations).

<table><thead><tr><th rowspan="2">Characteristics</th><th rowspan="2">Category</th><th colspan="3">Unadjusted analysis</th><th colspan="3">Adjusted analysis (without 2-week follow-up questionnaires)</th><th colspan="3">Adjusted analysis (with 2-week follow-up questionnaires)</th></tr><tr><th>Odds ratio</th><th>95% confidence interval</th><th>P value</th><th>Odds ratio</th><th>95% confidence interval</th><th>P value</th><th>Odds ratio</th><th>95% confidence interval</th><th>P value</th></tr></thead><tbody><tr><td rowspan="4">Time since the traumatic brain injury</td><td>Two weeks</td><td>Reference</td><td></td><td></td><td>Reference</td><td></td><td></td><td>Reference</td><td></td><td></td></tr><tr><td>Three months</td><td>0.69</td><td>0.53-0.89</td><td>0.005</td><td>0.25</td><td>0.18-0.35</td><td>&lt; 0.001</td><td>0.24</td><td>0.17-0.34</td><td>&lt; 0.001</td></tr><tr><td>Six months</td><td>0.52</td><td>0.39-0.68</td><td>&lt; 0.001</td><td>0.16</td><td>0.11-0.23</td><td>&lt; 0.001</td><td>0.15</td><td>0.11-0.22</td><td>&lt; 0.001</td></tr><tr><td>Twelve months</td><td>0.52</td><td>0.39-0.71</td><td>&lt; 0.001</td><td>0.11</td><td>0.07-0.16</td><td>&lt; 0.001</td><td>0.10</td><td>0.07-0.16</td><td>&lt; 0.001</td></tr><tr><td rowspan="2">Sociodemographic factors</td><td>Age (in years)</td><td>Per one-SD increase</td><td>1.40</td><td>1.27-1.55</td><td>&lt; 0.001</td><td>1.61</td><td>1.41-1.83</td><td>&lt; 0.001</td><td>1.61</td><td>1.40-1.85</td><td>&lt; 0.001</td></tr><tr><td>Sex</td><td>Female</td><td>Reference</td><td></td><td></td><td>Not included</td><td></td><td></td><td>Not included</td><td></td><td></td></tr><tr><td rowspan="2">Marital status</td><td>Male</td><td>1.04</td><td>0.85-1.26</td><td>0.726</td><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>Married or living together</td><td>Reference</td><td></td><td></td><td></td><td>Reference</td><td></td><td></td><td>Reference</td><td></td></tr><tr><td rowspan="5">Occupational category</td><td>Never married, separated, divorced, or widowed</td><td>1.04</td><td>0.86-1.26</td><td>0.695</td><td>1.21</td><td>0.95-1.53</td><td>0.122</td><td>1.16</td><td>0.91-1.49</td><td>0.236</td></tr><tr><td>Manager or professional</td><td>Reference</td><td></td><td></td><td></td><td>Reference</td><td></td><td></td><td>Reference</td><td></td></tr><tr><td>Technician, supervisor, or associate professional</td><td>0.91</td><td>0.66-1.24</td><td>0.544</td><td>0.92</td><td>0.65-1.30</td><td>0.641</td><td>0.93</td><td>0.65-1.33</td><td>0.698</td></tr><tr><td>Clerk or salesperson</td><td>1.20</td><td>0.86-1.68</td><td>0.285</td><td>1.06</td><td>0.72-1.57</td><td>0.765</td><td>1.03</td><td>0.69-1.54</td><td>0.874</td></tr><tr><td>Skilled manual worker</td><td>1.49</td><td>1.12-1.99</td><td>0.007</td><td>1.48</td><td>1.06-2.07</td><td>0.023</td><td>1.59</td><td>1.12-2.25</td><td>0.010</td></tr><tr><td rowspan="3">Years of education</td><td>Manual worker</td><td>1.52</td><td>1.16-2.00</td><td>0.003</td><td>1.53</td><td>1.11-2.12</td><td>0.010</td><td>1.59</td><td>1.13-2.24</td><td>0.007</td></tr><tr><td>Other / None</td><td>0.89</td><td>0.66-1.20</td><td>0.436</td><td>0.83</td><td>0.59-1.16</td><td>0.267</td><td>0.84</td><td>0.59-1.19</td><td>0.323</td></tr><tr><td>Per one-SD increase</td><td>0.88</td><td>0.79-0.97</td><td>0.012</td><td>Not included</td><td></td><td></td><td>Not included</td><td></td><td></td></tr><tr><td rowspan="2">European region</td><td>Central and Eastern Europe / Southern Europe</td><td>1.12</td><td>0.90-1.40</td><td>0.323</td><td>1.09</td><td>0.84-1.43</td><td>0.515</td><td>1.11</td><td>0.82-1.50</td><td>0.485</td></tr><tr><td>Northern Europe</td><td>0.89</td><td>0.72-1.11</td><td>0.295</td><td>0.91</td><td>0.71-1.18</td><td>0.481</td><td>0.95</td><td>0.72-1.24</td><td>0.693</td></tr><tr><td rowspan="2">Current psychoactive substance use</td><td>Tobacco</td><td>No</td><td>Reference</td><td></td><td>Not included</td><td></td><td></td><td>Not included</td><td></td><td></td></tr><tr><td>Yes</td><td>1.14</td><td>0.93-1.41</td><td>0.212</td><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td rowspan="2">Alcohol (misuse)</td><td>No</td><td>Reference</td><td></td><td></td><td>Not included</td><td></td><td></td><td>Not included</td><td></td><td></td></tr><tr><td>Yes</td><td>1.09</td><td>0.89-1.33</td><td>0.398</td><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td rowspan="2">Cannabis</td><td>No</td><td>Reference</td><td></td><td></td><td>Reference</td><td></td><td></td><td>Reference</td><td></td><td></td></tr><tr><td>Yes</td><td>1.09</td><td>0.67-1.77</td><td>0.728</td><td>1.29</td><td>0.76-2.21</td><td>0.345</td><td>1.49</td><td>0.81-2.75</td><td>0.201</td></tr><tr><td rowspan="2">Pre-injury medical history</td><td>Number of chronic physical conditions</td><td>Per one-SD increase</td><td>1.27</td><td>1.17-1.39</td><td>&lt; 0.001</td><td>1.14</td><td>1.02-1.27</td><td>0.017</td><td>1.11</td><td>0.99-1.25</td><td>0.075</td></tr><tr><td>Psychiatric disorder</td><td>No</td><td>Reference</td><td></td><td></td><td>Reference</td><td></td><td></td><td>Reference</td><td></td><td></td></tr><tr><td rowspan="2">Previous traumatic brain injury</td><td>Yes</td><td>2.29</td><td>1.75-3.00</td><td>&lt; 0.001</td><td>2.41</td><td>1.72-3.39</td><td>&lt; 0.001</td><td>2.55</td><td>1.69-3.84</td><td>&lt; 0.001</td></tr><tr><td>Yes</td><td>Reference</td><td></td><td></td><td>Reference</td><td></td><td></td><td>Reference</td><td></td><td></td></tr><tr><td rowspan="2">Injury-related factors</td><td>Geographical area of injury</td><td>Rural</td><td>Reference</td><td></td><td>Reference</td><td></td><td></td><td>Reference</td><td></td><td></td></tr><tr><td>Urban</td><td>0.97</td><td>0.77-1.22</td><td>0.800</td><td>1.26</td><td>0.96-1.65</td><td>0.102</td><td>1.31</td><td>0.97-1.77</td><td>0.082</td></tr><tr><td rowspan="3">Injury intention</td><td>Intentional</td><td>Reference</td><td></td><td></td><td>Reference</td><td></td><td></td><td>Reference</td><td></td><td></td></tr><tr><td>Undetermined</td><td>2.36</td><td>1.14-4.86</td><td>0.020</td><td>1.88</td><td>0.83-4.26</td><td>0.133</td><td>2.01</td><td>0.80-5.08</td><td>0.138</td></tr><tr><td>Unintentional</td><td>1.37</td><td>0.87-2.16</td><td>0.176</td><td>1.13</td><td>0.68-1.88</td><td>0.638</td><td>1.12</td><td>0.65-1.96</td><td>0.679</td></tr><tr><td rowspan="2">Baseline-derived GCS score</td><td>Per one-SD increase</td><td>0.70</td><td>0.64-0.75</td><td>&lt; 0.001</td><td>0.81</td><td>0.73-0.89</td><td>&lt; 0.001</td><td>0.81</td><td>0.72-0.91</td><td>&lt; 0.001</td></tr><tr><td>Per one-SD increase</td><td>1.82</td><td>1.66-1.99</td><td>&lt; 0.001</td><td>1.52</td><td>1.31-1.77</td><td>&lt; 0.001</td><td>1.40</td><td>1.17-1.68</td><td>&lt; 0.001</td></tr></tbody></table>

(continued)
<table><caption>**Table 2 (Continued)**</caption><thead><tr><th rowspan="2">Characteristics</th><th rowspan="2">Category</th><th colspan="3">Unadjusted analysis</th><th colspan="3">Adjusted analysis (without 2-week follow-up questionnaires)</th><th colspan="3">Adjusted analysis (with 2-week follow-up questionnaires)</th></tr><tr><th>Odds ratio</th><th>95% confidence interval</th><th>P value</th><th>Odds ratio</th><th>95% confidence interval</th><th>P value</th><th>Odds ratio</th><th>95% confidence interval</th><th>P value</th></tr></thead><tbody><tr><td colspan="11"><strong>Medical care, complications, and discharge</strong></td></tr><tr><td rowspan="2">Stratum</td><td>Admission to hospital wards</td><td>1.43</td><td>1.12–1.82</td><td>0.004</td><td>2.64</td><td>1.40–4.99</td><td>0.003</td><td>2.57</td><td>1.35–4.89</td><td>0.004</td></tr><tr><td>Admission to intensive care units</td><td>3.97</td><td>3.09–5.08</td><td>&lt; 0.001</td><td>4.57</td><td>2.32–9.02</td><td>&lt; 0.001</td><td>4.76</td><td>2.36–9.59</td><td>&lt; 0.001</td></tr><tr><td colspan="2">Direct discharge from the emergency room</td><td>Reference</td><td></td><td></td><td>Reference</td><td></td><td></td><td>Reference</td><td></td><td></td></tr><tr><td rowspan="2">Intracranial surgery</td><td>No</td><td>Reference</td><td></td><td></td><td>Reference</td><td></td><td></td><td>Reference</td><td></td><td></td></tr><tr><td>Yes</td><td>0.79</td><td>0.56–1.12</td><td>0.184</td><td>0.88</td><td>0.53–1.46</td><td>0.628</td><td>0.96</td><td>0.58–1.58</td><td>0.874</td></tr><tr><td rowspan="2">Extracranial surgery</td><td>No</td><td>Reference</td><td></td><td></td><td>Reference</td><td></td><td></td><td>Reference</td><td></td><td></td></tr><tr><td>Yes</td><td>1.58</td><td>1.07–2.34</td><td>0.022</td><td>1.39</td><td>0.96–2.00</td><td>0.079</td><td>1.45</td><td>1.01–2.08</td><td>0.047</td></tr><tr><td rowspan="2">Intracranial complication</td><td>No</td><td>Reference</td><td></td><td></td><td>Reference</td><td></td><td></td><td>Reference</td><td></td><td></td></tr><tr><td>Yes</td><td>0.63</td><td>0.49–0.82</td><td>&lt; 0.001</td><td>1.03</td><td>0.53–2.00</td><td>0.932</td><td>1.18</td><td>0.61–2.30</td><td>0.623</td></tr><tr><td rowspan="2">Extracranial complication</td><td>No</td><td>Reference</td><td></td><td></td><td>Reference</td><td></td><td></td><td>Reference</td><td></td><td></td></tr><tr><td>Yes</td><td>1.03</td><td>0.75–1.42</td><td>0.862</td><td>1.41</td><td>0.91–2.18</td><td>0.122</td><td>1.28</td><td>0.82–1.99</td><td>0.277</td></tr><tr><td colspan="2">GCS at discharge</td><td>0.97</td><td>0.82–1.15</td><td>0.708</td><td>1.02</td><td>0.89–1.17</td><td>0.796</td><td>1.01</td><td>0.88–1.17</td><td>0.850</td></tr><tr><td colspan="11"><strong>Two-week follow-up questionnaires</strong></td></tr><tr><td>GAD-7</td><td>Per one-SD increase</td><td>1.35</td><td>1.13–1.60</td><td>&lt; 0.001</td><td>Not included</td><td></td><td></td><td>Not included</td><td></td><td></td></tr><tr><td>GOSE</td><td>Per one-SD increase</td><td>0.66</td><td>0.53–0.82</td><td>&lt; 0.001</td><td></td><td></td><td></td><td>0.74</td><td>0.57–0.97</td><td>0.031</td></tr><tr><td>PCL-5</td><td>Per one-SD increase</td><td>1.31</td><td>1.12–1.54</td><td>&lt; 0.001</td><td></td><td></td><td></td><td>0.96</td><td>0.78–1.19</td><td>0.724</td></tr><tr><td>PHQ-9</td><td>Per one-SD increase</td><td>1.37</td><td>1.14–1.64</td><td>&lt; 0.001</td><td></td><td></td><td></td><td>Not included</td><td></td><td></td></tr><tr><td>QOLIBRI</td><td>Per one-SD increase</td><td>0.69</td><td>0.56–0.85</td><td>&lt; 0.001</td><td></td><td></td><td></td><td>0.93</td><td>0.71–1.22</td><td>0.601</td></tr><tr><td>RPQ</td><td>Per one-SD increase</td><td>1.25</td><td>1.04–1.50</td><td>0.019</td><td></td><td></td><td></td><td>Not included</td><td></td><td></td></tr><tr><td>SF-12 – mental component</td><td>Per one-SD increase</td><td>0.83</td><td>0.64–1.08</td><td>0.169</td><td></td><td></td><td></td><td>0.96</td><td>0.76–1.22</td><td>0.760</td></tr><tr><td>SF-12 – physical component</td><td>Per one-SD increase</td><td>0.69</td><td>0.54–0.88</td><td>0.003</td><td></td><td></td><td></td><td>0.95</td><td>0.72–1.24</td><td>0.685</td></tr></tbody></table>

Abbreviations: GAD-7, Generalized Anxiety Disorder-7; GOSE, Glasgow Outcome Scale-Extended; ISS, Injury Severity Score; LASSO, least absolute shrinkage and selection operator; mTBI, mild traumatic brain injury; PCL-5, Post-traumatic Stress Disorder Checklist for DSM-5; PHQ-9, Patient Health Questionnaire-9; QOLIBRI, Quality of Life after Brain Injury; RPQ, Rivermead Post-concussion Symptoms Questionnaire; SD, standard deviation; SF-12, 12-item Short-Form Health Survey. Statistically significant results are displayed in bold.

Unadjusted and adjusted generalized estimating equations, relying on the binomial family with a logit link function, were conducted on each imputed dataset, and the results were pooled across the 99 datasets. The dependent variable was absence from work within the 12 months following mTBI. Absence from work was assessed at 2 weeks, 3 months, 6 months, and 12 months. Regarding the independent variables, there was a small number of participants in the occupational category “None,” and this category was, therefore, merged with the category “Other”. Moreover, the region was recoded as a three-category variable, given the small sample size for the category “Central and Eastern Europe” (ie, the category “Central and Eastern Europe” was merged with the category “Southern Europe”). Additionally, given the relatively small population size (ie, 1080 adults) and the presence of more than 25 independent variables, it was decided to select a subset of independent variables for inclusion in the adjusted generalized estimating equations. After applying LASSO regression, the following variables were excluded from the analysis: sex, years of education, current tobacco use, current alcohol misuse, the two-week GAD-7, the two-week PHQ-9, and the two-week RPQ. Moreover, given that two-week follow-up questionnaires had > 65% missing data, a first adjusted model was conducted without these variables. The second adjusted model included the following variables: GOSE, PCL-5, QOLIBRI, SF-12 (mental component), and SF-12 (physical component). Finally, all numerical variables were standardized.

However, the association was no longer statistically significant for the number of chronic physical conditions (per one-SD increase: OR = 1.11, 95% CI = 0.99–1.25), while extracranial surgery (OR = 1.45, 95% CI = 1.01–2.08) and the GOSE (per one-SD increase: OR = 0.74, 95% CI = 0.57–0.97) were statistically associated with the absence from work. Results were similar in participants with mTBI who had not undergone intracranial surgery during their hospitalization (if any) and did not display any intracranial complications at discharge (Supplementary Table 2). Minor changes were observed, such as a lack of statistically significant association for the stratum and the GOSE, and a statistically significant relationship for the number of chronic physical conditions in the sensitivity analyses, including the 2-week questionnaires.

## Discussion

### Main findings

This European study of 1080 adults with mTBI revealed that the absence from work significantly decreased from 32% at 2 weeks to 20% at 12 months after the injury. Two trajectories were identified within the 12 months following the mTBI. During the first 3 months, most participants returned to work, even those who were not working 2 weeks after the injury. In contrast, most people absent from work at 3 months

continued to be absent from work at 6 months, and the same pattern was observed between 6 and 12 months. Several variables were statistically associated with the absence from work in the 12 months following the mTBI: time since the injury (ie, the odds of absence decreased with time), older age, manual occupation, the presence of a pre-injury psychiatric disorder, a lower baseline-derived GCS score, a higher ISS score, admission to hospital wards or intensive care units (compared with direct discharge from the emergency room), extracranial surgery, and a lower GOSE score. Relatively similar results were obtained in the sensitivity analyses focusing on adults without intracranial surgery during hospitalization and any intracranial complication at discharge. To the best of the authors’ knowledge, this research is one of the first multi-country studies on this topic, while it is also one of the first studies to investigate detailed trajectories of absence from work following a mTBI.

### Interpretation of the findings

Before going further, it should be acknowledged that 69% of this mTBI population was either admitted to hospital wards or intensive care units after multiple imputation of missing data, and a substantial proportion of the sample had intracranial surgery. These care pathways and healthcare utilization are uncommon in people with mTBI, which raises questions about the generalizability of the present results. The fact that the proportion of people undergoing surgery (either intracranial or
extracranial surgery) and those with complications (either intracranial or extracranial) was higher after than before the multiple imputation of missing data likely reflects the fact that the missingness of the data was related to the severity of the underlying TBI, a pattern already reported in the literature [33].

A critical finding of the study is that 20 % of adults with mTBI were absent from work 12 months after the injury. This result aligns with some of the previous research published on the topic. For example, a cohort of 152 adults with mTBI from the United States found that the absence from work was 22 % at 3 months and 21 % at 6 months [9]. The present study not only corroborates these results but also shows that absence from work is common in the 12 months following mTBI in a European population. This body of research further shows that most adults with mTBI who return to work do so within the first 3 months, while those absent from work at 3 months are less likely to return to work later. Although figures and trajectories were similar in the mTBI population without intracranial surgery or intracranial complications, the 2-week absence from work was 51 % in this sample. This result may seem counterintuitive, as people with intracranial abnormalities were excluded from this analysis. That said, the 2-week follow-up is an early assessment that may not accurately depict absence from work following mTBI. The 3-month absence from work was comparable between the overall population (ie, 24 %) and the population without intracranial surgery or intracranial complications (ie, 28 %).

The generalized estimating equations corroborate the above findings, as time since mTBI was associated with decreased odds of absence from work. Moreover, in line with a previous study [3], older participants were more likely to be absent from work than their younger counterparts. Older adults with mTBI may face substantial barriers to returning to work early. These barriers may involve persistent symptoms and delayed referral to rehabilitation. Additional barriers include issues with the organization and the psychosocial work environment, such as a lack of knowledge in the workplace on how to handle complex and non-linear return-to-work processes. These circumstances may lead to deficient employer engagement, insufficient workplace accommodations, and a lack of co-worker support [34]. Interestingly, a manual occupation was associated with a higher likelihood of a 12-month absence from work compared with a non-manual occupation. Other research has identified a similar pattern, suggesting that balance and fine motor skill impairments, as well as a less accommodating workplace environment, could compromise the return to work in manual workers [35,36].

Regarding behavioral factors, there was no statistically significant relationship between current alcohol misuse and the 12-month absence from work. Although this lack of statistical significance may be surprising, similar research findings have been obtained on alcohol misuse and the 12-month absence from work [3–13], as well as in terms of overall recovery following a mild-to-moderate traumatic brain injury [37]. However, this prior body of research investigated alcohol consumption and not specifically alcohol misuse, which warrants caution when interpreting the absence of a significant relationship in the present study.

In terms of the pre-injury medical history, the presence of a pre-injury psychiatric disorder increased the odds of absence from work in the year following mTBI. This result should be cautiously interpreted, as psychiatric disorders did not significantly affect the return to work after mTBI in a previous sample of 103 adults [38]. Nonetheless, the lack of statistically significant findings in this prior study could be partially explained by its relatively small sample size. People with psychiatric disorders may experience more difficulties in coping with mTBI than those without these disorders. Based on data obtained outside the field of mTBI (ie, stroke), there is evidence that emotion-focused coping strategies play a substantial role in the return to work after a significant health event [39]. In people with psychiatric disorders, such strategies focusing on emotions might be altered, potentially impairing a successful return to work. Moreover, anxiety and depression are risk factors for increased cognitive impairments and functional difficulties after a TBI [40]. Adults with mTBI and anxiety and depression may have persistent difficulties in using coping strategies that

rely on solving problems. In addition, psychiatric disorders and TBI share some genetic and epigenetic vulnerability [41,42]. In terms of epigenetic vulnerability, there is some preliminary evidence obtained in a rat model showing that the deleterious effects of mTBI on post-traumatic stress disorder are potentially mediated via an alteration of the methylation of the hippocampal DNA [42]. mTBI could also be a trigger for an increase in the intensity of psychiatric symptoms in people with a pre-injury mental health disorder. In the present sample, it should be noted that 17 % of participants had moderate-to-severe generalized anxiety disorder symptoms, while 28 % had major depression.

Furthermore, the baseline-derived GCS score, the ISS score, being hospitalized in hospital wards or intensive care units (compared with direct discharge from the emergency room), and extracranial surgery were positively and statistically associated with absence from work. Similarly, another research identified multiple bodily injuries and intracranial abnormalities, which can be viewed as indirect markers of the injury severity, as risk factors for delayed return to work after mTBI [3]. More severe mTBI may be associated with longer disability and a persisting need for specialized rehabilitation, and such trends may favor the absence from work. Finally, there was an inverse relationship between the 2-week GOSE score and 12-month absence from work. This finding, which is in line with the literature [43], highlights the fact that disability following mTBI may undermine the return to work.

## Clinical and public health implications and directions for future research

Older age, a manual occupation, the presence of a pre-injury psychiatric disorder, several injury-related factors, and a post-injury disability were identified as positively associated with higher odds of absence from work after a mTBI. From a clinical perspective, these identifiers may help clinicians distinguish individuals with mTBI at an increased risk for not returning to work. Older workers may be followed more regularly after mTBI to identify early barriers to returning to work and facilitate such a return. In terms of occupational category, it is essential to mitigate the deleterious effects of the complex interplay between persisting symptoms and insufficient occupational support on the return to work among manual workers. Early intervention vocational rehabilitation [44] and coordinated, personalized programs [45] could help mitigate these deleterious effects. Such interventions could be implemented in both inpatient and outpatient settings, depending on the individual's clinical profile, occupational background, and objectives [46]. Regarding the presence of a pre-injury psychiatric disorder, the psychological and psychiatric management of people with mTBI is critical, and those with impaired mental health should be referred to mental health specialists to discuss the introduction of supportive interventions and the initiation of a dedicated follow-up. Beyond the factors above associated with returning to work, clinicians could also attempt to characterize the coping strategies used by adults with mTBI who did return to work after the injury. These coping strategies (eg, emotion- and problem-focused strategies) may vary within the mTBI population [39], highlighting the need for personalized and tailored interventions (eg, cognitive training, neuropsychological training, and psychotherapy) [47,48]. From a public health perspective, the fact that 20 % of adults with mTBI were absent from work at 12 months from the injury calls for the implementation of measures aiming at favoring a gradual return to work in this population when symptoms are no longer disabling. These measures align with recent recommendations from experts, which suggest improving care pathways for people with mTBI to better structure their follow-up [49]. For future research, it is crucial to corroborate these findings in other cohorts of mTBI adults. At the same time, there is a need for further studies based on data collected more than a year after the injury.

## Limitations

The study findings should be interpreted in the light of several limitations. First, a substantial proportion of missing data on absence from
work was present at each follow-up assessment, and although some anal-
yses relied on generalized estimating equations, these missing data may
have impacted the results. The rate of missing data was also particularly
high for 2-week questionnaires, and this rate may have affected the
results of the generalized estimating equations that included question-
naires assessed at 2 weeks. Second, having more data on the occupa-
tional environment (eg, detailed job types, physical job demands, and
work-related stress) and occupational status would have enabled more
detailed analyses. More specifically, the reason for retirement was
undocumented. Given that retirement may be unrelated to the injury in
some cases, absence from work in people with mTBI may have been
overestimated. Moreover, some adults may be outside the workforce for
reasons unrelated to the mTBI (eg, job loss due to economic reasons).
Third, data collection relied on medical records and personal interviews,
and some of the independent variables were likely self-reported (eg, a
previous traumatic brain injury), potentially introducing recall and
social desirability biases. At the same time, psychoactive substance use
(eg, alcohol misuse) was assessed in the last 3 months. In terms of pre-
injury psychiatric disorders, as these conditions are associated with
stigma [50], their presence may have been underreported. Moreover,
there was no data on the specific type of psychiatric disorder. Fourth,
mTBI does not usually require hospitalization and is often managed in
outpatient settings. The present sample, which was observed in level-1
trauma centers and hospitalized in almost 70 % of cases (ie, 44 % in hos-
pital wards and 25 % in intensive care units), may not accurately repre-
sent the population with mTBI. Fifth, although the definition of mTBI
requires information on post-traumatic amnesia, such amnesia and its
duration were not recorded.

Conclusions

The present study of 1080 workers with mTBI from Europe showed that the absence from work decreased in the year following the injury, reaching 20 % at 12 months post-injury. Older age, a manual occupation, the presence of a pre-injury psychiatric disorder, several injury-related factors, and a lower 2-week GOSE score were positively and statistically associated with higher odds of absence from work within the 12 months following mTBI. Further studies are warranted to corroborate the present results in other regions of the world. At the same time, additional data are needed on the absence from work for > 12 months after mTBI.

Data and code statement

The CENTER-TBI data are accessible to interested researchers after
sending a proposal on the online platform (https://www.center-tbi.eu/).
The code used for this study is available from the corresponding author
upon reasonable request.

Declaration of competing interest

The authors declare that they have no known competing financial
interests or personal relationships that could have appeared to influence
the work reported in this paper.

CRediT authorship contribution statement

**Louis Jacob:** Formal analysis, Investigation, Methodology, Supervi-
sion, Visualization, Writing – original draft, Writing – review & editing.
**John Castro:** Formal analysis, Methodology, Visualization, Writing –
review & editing. **Camille Heslot:** Visualization, Writing – review &
editing. **Nada Andelic:** Visualization, Writing – review & editing. **Olli
Tenovuo:** Visualization, Writing – review & editing. **Philippe Azouvi:**
Investigation, Methodology, Supervision, Visualization, Writing –
review & editing.

Acknowledgments

The authors would like to thank the CENTER-TBI consortium for hav-
ing approved the present study and for their support while the data were
analyzed.

The center-TBI participants and investigators: Cecilia Akerlund¹,
Krisztina Amrein², Nada Andelic³, Lasse Andreassen⁴, Audny Anke⁵,
Anna Antoni⁶, Gérard Audibert⁷, Philippe Azouvi⁸, Maria Luisa Azzo-
lini⁹, Ronald Bartels¹⁰, Pál Barzó¹¹, Romuald Beauvais¹², Ronny Beer¹³,
Bo-Michael Bellander¹⁴, Antonio Belli¹⁵, Habib Benali¹⁶, Maurizio
Berardino¹⁷, Luigi Beretta⁹, Morten Blaabjerg¹⁸, Peter Bragge¹⁹, Alexan-
dra Brazinova²⁰, Vibeke Brinck²¹, Joanne Brooker²², Camilla Brors-
son²³, Andras Buki²⁴, Monika Bullinger²⁵, Manuel Cabeleira²⁶, Alessio
Caccioppola²⁷, Emiliana Calappi²⁷, Maria Rosa Calvi²⁹, Peter Cameron²⁸,
Guillermo Carbayo Lozano²⁹, Marco Carbonara²⁷, Simona Cavallo¹⁷,
Giorgio Chevallard³⁰, Arturo Chieregato³⁰, Giuseppe Citerio³¹, ³², Hans
Clusmann³³, Mark Coburn³⁴, Jonathan Coles³⁵, Jamie D. Cooper³⁶,
Marta Correia³⁷, Amra Covi´c³⁸, Nicola Curry³⁹, Endre Czeiter²⁴, Marek
Czosnyka²⁶, Claire Dahyot-Fizelier⁴⁰, Paul Dark⁴¹, Helen Dawes⁴²,
Véronique De Keyser⁴³, Vincent Degos¹⁶, Francesco Della Corte⁴⁴, Hugo
den Boogert¹⁰, Bart Depreitere⁴⁵, Dula Dîlvesi⁴⁶, Abhishek Dixit⁴⁷,
Emma Donoghue²², Jens Dreier⁴⁸, Guy-Loup Dulière⁴⁹, Ari Ercole⁴⁷, Pat-
rick Esser⁴², Erzsébet Ezer⁵⁰, Martin Fabricius⁵¹, Valery L. Feigin⁵²,
Kelly Foks⁵³, Shirin Frisvold⁵⁴, Alex Furmanov⁵⁵, Pablo Gagliardo⁵⁶,
Damien Galanaud¹⁶, Dashiell Gantner²⁸, Guoyi Gao⁵⁷, Pradeep
George⁵⁸, Alexandre Ghuysen⁵⁹, Lelde Giga⁶⁰, Ben Glocker⁶¹, Jagoš
Golubovic⁴⁶, Pedro A. Gomez⁶², Johannes Gratz⁶³, Benjamin Grave-
steijn⁶⁴, Francesca Grossi⁴⁴, Russell L. Gruen⁶⁵, Deepak Gupta⁶⁶, Juanita
A. Haagsma⁶⁴, Iain Haittsma⁶⁷, Raimund Helbok⁶⁸,⁶⁹, Eirik Helseth⁷⁰,
Lindsay Horton ⁷¹, Jilske Huijben⁶⁴, Peter J. Hutchinson⁷², Bram
Jacobs⁷³, Stefan Jankowski⁷⁴, Mike Jarrett²¹, Ji-yao Jiang⁵⁸, Faye John-
son⁷⁵, Kelly Jones⁵², Mladen Karan⁴⁶, Angelos G. Kolias⁷², Erwin Kom-
panje⁷⁶, Daniel Kondziella⁵¹, Evgenios Kornaropoulos⁴⁷, Lars-Owe
Koskinen⁷⁷, Noémi Kovács⁷⁸, Ana Kowark⁷⁹, Alfonso Lagares⁶², Linda
Lanyon⁵⁸, Steven Laureys⁸⁰, Fiona Lecky⁸¹, ⁸², Didier Ledoux⁸⁰, Rolf
Lefering⁸³, Valerie Legrand⁸⁴, Aurelie Lejeune⁸⁵, Leon Levi⁸⁶, Roger
Lightfoot⁸⁷, Hester Lingsma⁶⁴, Andrew I.R. Maas⁴³,⁸⁸, Ana M. Castaño-
León⁶², Marc Maegele⁸⁹, Marek Majdan²⁰, Alex Manara⁹⁰, Geoffrey
Manley⁹¹, Costanza Martino⁹², Hugues Maréchal⁴⁹, Julia Mattern⁹³,
Catherine McMahon⁹⁴, Béla Melegh⁹⁵, David Menon⁴⁷, Tomas Menov-
sky⁴³,⁸⁸, Ana Mikolic⁶⁴, Benoit Misset⁸⁰, Visakh Muraleedharan⁵⁸, Lyn-
nette Murray²⁸, Ancuta Negru⁹⁶, David Nelson¹, Virginia Newcombe⁴⁷,
Daan Nieboer⁶⁴, József Nyirádi², Otesile Olubukola⁸¹, Matej Oresic⁹⁷,
Fabrizio Ortolano²⁷, Aarno Palotie⁹⁸, ⁹⁹, ¹⁰⁰, Paul M. Parizel¹⁰¹, Jean-
François Payen¹⁰², Natascha Perera¹², Vincent Perlbarg¹⁶, Paolo Per-
sona¹⁰³, Wilco Peul¹⁰⁴, Anna Piippo-Karjalainen¹⁰⁵, Matti Pirinen⁹⁸,
Dana Pisica⁶⁴, Horia Ples⁹⁶, Suzanne Polinder⁶⁴, Inigo Pomposo²⁹, Jussi
P. Posti¹⁰⁶, Louis Puybasset¹⁰⁷, Andreea Radoi¹⁰⁸, Arminas Ragaus-
kas¹⁰⁹, Rahul Raj¹⁰⁵, Malinka Rambadagalla¹¹⁰, Isabel Retel Helmrich⁶⁴,
Jonathan Rhodes¹¹¹, Sylvia Richardson¹¹², Sophie Richter⁴⁷, Samuli
Ripatti⁹⁸, Saulius Rocka¹⁰⁹, Cecilie Roe¹¹³, Olav Roise¹¹⁴,¹¹⁵, Jonathan
Rosand¹¹⁶, Jeffrey V. Rosenfeld¹¹⁷, Christina Rosenlund¹¹⁸, Guy Rosen-
thal⁵⁵, Rolf Rossaint⁷⁹, Sandra Rossi¹⁰³, Daniel Rueckert⁶¹ Martin
Rusnák¹¹⁹, Juan Sahuquillo¹⁰⁸, Oliver Sakowitz²⁹, ¹²⁰, Renan Sanchez-
Porras¹²⁰, Janos Sandor¹²¹, Nadine Schäfer⁸³, Silke Schmidt¹²², Herbert
Schoechl¹²³, Guus Schoonman¹²⁴, Rico Frederik Schou¹²⁵, Elisabeth
Schwendenwein⁶, Charlie Sewalt⁶⁴, Ranjit D. Singh¹⁰⁴, Toril Skand-
sen¹²⁶, ¹²⁷, Peter Smielewski²⁶, Abayomi Sorinola¹²⁸, Emmanuel Stama-
takis⁴⁷, Simon Stanworth³⁹, Robert Stevens¹²⁹, William Stewart¹³⁰,
Ewout W. Steyerberg⁶⁴, ¹³¹, Nino Stocchetti¹³², Nina Sundström¹³³,
Riikka Takala¹³⁴, Viktória Tamás¹²⁸, Tomas Tamosuitis¹³⁵, Mark Steven
Taylor²⁰, Aurore Thibaut⁸⁰, Braden Te Ao⁵², Olli Tenovuo¹⁰⁶, Alice
Theadom⁵², Matt Thomas⁹⁰, Dick Tibboel¹³⁶, Marjolein Timmers⁷⁶,
Christos Tolias¹³⁷, Tony Trapani²⁸, Cristina Maria Tudora⁹⁶, Andreas
Unterberg⁹³, Peter Vajkoczy ¹³⁸, Shirley Vallance²⁸, Egils Valeinis⁶⁰,
Zoltán Vámos⁵⁰, Mathieu van der Jagt¹³⁹, Gregory Van der Steen⁴³,
Joukje van der Naalt⁷³, Jeroen T.J.M. van Dijck¹⁰⁴, Inge A. M. van Erp¹⁰⁴, Thomas A. van Essen¹⁰⁴, Wim Van Hecke¹⁴⁰, Caroline van Heugten¹⁴¹, Ernest van Veen⁶⁴, Thijs Vande Vyvere¹⁴², Roel P. J. van Wijk¹⁰⁴, Alessia Vargiolu³², Emmanuel Vega⁸⁵, Kimberley Velt⁶⁴, Jan Verheyden¹⁴⁰, Paul M. Vespa¹⁴³, Anne Vik¹²⁶, ¹⁴⁴, Rimantas Vilcinis¹³⁵, Victor Volovici⁶⁷, Nicole von Steinbüchel³⁸, Daphne Voormolen⁶⁴, Petar Vulekovic⁴⁶, Kevin K.W. Wang¹⁴⁵, Daniel Whitehouse⁴⁷, Eveline Wiegers⁶⁴, Guy Williams⁴⁷, Lindsay Wilson⁷¹, Stefan Winzeck⁴⁷, Stefan Wolf¹⁴⁶, Zhihui Yang¹¹⁶, Peter Ylén¹⁴⁷, Alexander Younsi⁹³, Frederick A. Zeiler⁴⁷,¹⁴⁸, Veronika Zelinkova²⁰, Agate Ziverte⁶⁰, Tommaso Zuerle²⁷

¹Department of Physiology and Pharmacology, Section of Perioperative Medicine and Intensive Care, Karolinska Institutet, Stockholm, Sweden

²János Szentágothai Research Centre, University of Pécs, Pécs, Hungary

³Division of Clinical Neuroscience, Department of Physical Medicine and Rehabilitation, Oslo University Hospital and University of Oslo, Oslo, Norway

⁴Department of Neurosurgery, University Hospital Northern Norway, Tromso, Norway

⁵Department of Physical Medicine and Rehabilitation, University Hospital Northern Norway, Tromso, Norway

⁶Trauma Surgery, Medical University Vienna, Vienna, Austria

⁷Department of Anesthesiology & Intensive Care, University Hospital Nancy, Nancy, France

⁸Raymond Poincare hospital, Assistance Publique – Hopitaux de Paris, Paris, France

⁹Department of Anesthesiology & Intensive Care, S Raffaele University Hospital, Milan, Italy

¹⁰Department of Neurosurgery, Radboud University Medical Center, Nijmegen, The Netherlands

¹¹Department of Neurosurgery, University of Szeged, Szeged, Hungary

¹²International Projects Management, ARTTIC, Munchen, Germany

¹³Department of Neurology, Neurological Intensive Care Unit, Medical University of Innsbruck, Innsbruck, Austria

¹⁴Department of Neurosurgery & Anesthesia & intensive care medicine, Karolinska University Hospital, Stockholm, Sweden

¹⁵NIHR Surgical Reconstruction and Microbiology Research Centre, Birmingham, UK

¹⁶Anesthesie-Réanimation, Assistance Publique – Hopitaux de Paris, Paris, France

¹⁷Department of Anesthesia & ICU, AOU Città della Salute e della Scienza di Torino - Orthopedic and Trauma Center, Torino, Italy

¹⁸Department of Neurology, Odense University Hospital, Odense, Denmark

¹⁹BehaviourWorks Australia, Monash Sustainability Institute, Monash University, Victoria, Australia

²⁰Department of Public Health, Faculty of Health Sciences and Social Work, Trnava University, Trnava, Slovakia

²¹Quesgen Systems Inc., Burlingame, California, USA

²²Australian & New Zealand Intensive Care Research Centre, Department of Epidemiology and Preventive Medicine, School of Public Health and Preventive Medicine, Monash University, Melbourne, Australia

²³Department of Surgery and Perioperative Science, Umea University, Umea, Sweden

²⁴Department of Neurosurgery, Medical School, University of Pécs, Hungary and Neurotrauma Research Group, János Szentágothai Research Centre, University of Pécs, Hungary

²⁵Department of Medical Psychology, Universitätsklinikum Hamburg-Eppendorf, Hamburg, Germany

²⁶Brain Physics Lab, Division of Neurosurgery, Dept of Clinical Neurosciences, University of Cambridge, Addenbrooke's Hospital, Cambridge, UK

²⁷Neuro ICU, Fondazione IRCCS Cà Granda Ospedale Maggiore Polyclinico, Milan, Italy

²⁸ANZIC Research Centre, Monash University, Department of Epidemiology and Preventive Medicine, Melbourne, Victoria, Australia

²⁹Department of Neurosurgery, Hospital of Cruces, Bilbao, Spain

³⁰NeuroIntensive Care, Niguarda Hospital, Milan, Italy

³¹School of Medicine and Surgery, Università Milano Bicocca, Milano, Italy

³²NeuroIntensive Care Unit, Department Neuroscience, IRCCS Fondazione San Gerardo dei Tintori, Monza, Italy

³³Department of Neurosurgery, Medical Faculty RWTH Aachen University, Aachen, Germany

³⁴Department of Anesthesiology and Intensive Care Medicine, University Hospital Bonn, Bonn, Germany

³⁵Department of Anesthesia & Neurointensive Care, Cambridge University Hospital NHS Foundation Trust, Cambridge, UK

³⁶School of Public Health & PM, Monash University and The Alfred Hospital, Melbourne, Victoria, Australia

³⁷Radiology/MRI department, MRC Cognition and Brain Sciences Unit, Cambridge, UK

³⁸Institute of Medical Psychology and Medical Sociology, Universitätsmedizin Göttingen, Göttingen, Germany

³⁹Oxford University Hospitals NHS Trust, Oxford, UK

⁴⁰Intensive Care Unit, CHU Poitiers, Poitiers, France

⁴¹University of Manchester NIHR Biomedical Research Centre, Critical Care Directorate, Salford Royal Hospital NHS Foundation Trust, Salford, UK

⁴²Movement Science Group, Faculty of Health and Life Sciences, Oxford Brookes University, Oxford, UK

⁴³Department of Neurosurgery, Antwerp University Hospital, Edegem, Belgium

⁴⁴Department of Anesthesia & Intensive Care, Maggiore Della Carità Hospital, Novara, Italy

⁴⁵Department of Neurosurgery, University Hospitals Leuven, Leuven, Belgium

⁴⁶Department of Neurosurgery, Clinical centre of Vojvodina, Faculty of Medicine, University of Novi Sad, Novi Sad, Serbia

⁴⁷Division of Anaesthesia, University of Cambridge, Addenbrooke's Hospital, Cambridge, UK

⁴⁸Center for Stroke Research Berlin, Charité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany

⁴⁹Intensive Care Unit, CHR Citadelle, Liège, Belgium

⁵⁰Department of Anaesthesiology and Intensive Therapy, University of Pécs, Pécs, Hungary

⁵¹Departments of Neurology, Clinical Neurophysiology and Neuroanaesthesiology, Region Hovedstaden Rigshospitalet, Copenhagen, Denmark

⁵²National Institute for Stroke and Applied Neurosciences, Faculty of Health and Environmental Studies, Auckland University of Technology, Auckland, New Zealand

⁵³Department of Neurology, Erasmus MC, Rotterdam, the Netherlands

⁵⁴Department of Anesthesiology and Intensive care, University Hospital Northern Norway, Tromso, Norway

⁵⁵Department of Neurosurgery, Hadassah-hebrew University Medical center, Jerusalem, Israel

⁵⁶Fundación Instituto Valenciano de Neurorrehabilitación (FIVAN), Valencia, Spain

⁵⁷Department of Neurosurgery, Shanghai Renji hospital, Shanghai Jiaotong University/school of medicine, Shanghai, China

⁵⁸Karolinska Institutet, INCF International Neuroinformatics Coordinating Facility, Stockholm, Sweden

⁵⁹Emergency Department, CHU, Liège, Belgium

⁶⁰Neurosurgery clinic, Pauls Stradins Clinical University Hospital, Riga, Latvia

⁶¹Department of Computing, Imperial College London, London, UK

⁶²Department of Neurosurgery, Hospital Universitario 12 de Octubre, Madrid, Spain
⁶³Department of Anesthesia, Critical Care and Pain Medicine, Medical University of Vienna, Austria

⁶⁴Department of Public Health, Erasmus Medical Center-University Medical Center, Rotterdam, The Netherlands

⁶⁵College of Health and Medicine, Australian National University, Canberra, Australia

⁶⁶Department of Neurosurgery, Neurosciences Centre & JPN Apex trauma centre, All India Institute of Medical Sciences, New Delhi-110029, India

⁶⁷Department of Neurosurgery, Erasmus MC, Rotterdam, the Netherlands

⁶⁸Department of Neurology, Kepler University Hospital, Johannes Kepler University Linz, Linz, Austria.

⁶⁹Clinical Research Institute for Neuroscience, Johannes Kepler University Linz, Linz, Austria

⁷⁰Department of Neurosurgery, Oslo University Hospital, Oslo, Norway

⁷¹Division of Psychology, University of Stirling, Stirling, UK

⁷²Division of Neurosurgery, Department of Clinical Neurosciences, Addenbrooke's Hospital & University of Cambridge, Cambridge, UK

⁷³Department of Neurology, University of Groningen, University Medical Center Groningen, Groningen, Netherlands

⁷⁴Neurointensive Care, Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, UK

⁷⁵Salford Royal Hospital NHS Foundation Trust Acute Research Delivery Team, Salford, UK

⁷⁶Department of Intensive Care and Department of Ethics and Philosophy of Medicine, Erasmus Medical Center, Rotterdam, The Netherlands

⁷⁷Department of Clinical Neuroscience, Neurosurgery, Umeå University, Umeå, Sweden

⁷⁸Hungarian Brain Research Program - Grant No KTIA_13_NAP-A-II/8, University of Pécs, Pécs, Hungary

⁷⁹Department of Anaesthesiology, University Hospital of Aachen, Aachen, Germany

⁸⁰Cyclotron Research Center, University of Liège, Liège, Belgium

⁸¹Centre for Urgent and Emergency Care Research (CURE), Health Services Research Section, School of Health and Related Research (SchHARR), University of Sheffield, Sheffield, UK

⁸²Emergency Department, Salford Royal Hospital, Salford UK

⁸³Institute of Research in Operative Medicine (IFOM), Witten/Herdecke University, Cologne, Germany

⁸⁴VP Global Project Management CNS, ICON, Paris, France

⁸⁵Department of Anesthesiology-Intensive Care, Lille University Hospital, Lille, France

⁸⁶Department of Neurosurgery, Rambam Medical Center, Haifa, Israel

⁸⁷Department of Anesthesiology & Intensive Care, University Hospitals Southampton NHS Trust, Southampton, UK

⁸⁸Department of Translational Neuroscience, Faculty of Medicine and Health Science, University of Antwerp, Antwerp, Belgium

⁸⁹Cologne-Merheim Medical Center (CMMC), Department of Traumatology, Orthopedic Surgery and Sportmedicine, Witten/Herdecke University, Cologne, Germany

⁹⁰Intensive Care Unit, Southmead Hospital, Bristol, Bristol, UK

⁹¹Department of Neurological Surgery, University of California, San Francisco, California, USA

⁹²Department of Anesthesia & Intensive Care, M. Bufalini Hospital, Cesena, Italy

⁹³Department of Neurosurgery, University Hospital Heidelberg, Heidelberg, Germany

⁹⁴Department of Neurosurgery, The Walton centre NHS Foundation Trust, Liverpool, UK

⁹⁵Department of Medical Genetics, University of Pécs, Pécs, Hungary

⁹⁶Department of Neurosurgery, Emergency County Hospital Timisoara, Timisoara, Romania

⁹⁷School of Medical Sciences, Örebro University, Örebro, Sweden

⁹⁸Institute for Molecular Medicine Finland, University of Helsinki, Helsinki, Finland

⁹⁹Analytic and Translational Genetics Unit, Department of Medicine; Psychiatric & Neurodevelopmental Genetics Unit, Department of Psychiatry; Department of Neurology, Massachusetts General Hospital, Boston, MA, USA

¹⁰⁰Program in Medical and Population Genetics; The Stanley Center for Psychiatric Research, The Broad Institute of MIT and Harvard, Cambridge, MA, USA

¹⁰¹Department of Radiology, University of Antwerp, Edegem, Belgium

¹⁰²Department of Anesthesiology & Intensive Care, University Hospital of Grenoble, Grenoble, France

¹⁰³Department of Anesthesia & Intensive Care, Azienda Ospedaliera Università di Padova, Padova, Italy

¹⁰⁴Dept. of Neurosurgery, Leiden University Medical Center, Leiden, The Netherlands and Dept. of Neurosurgery, Medical Center Haaglanden, The Hague, The Netherlands

¹⁰⁵Department of Neurosurgery, Helsinki University Central Hospital

¹⁰⁶Division of Clinical Neurosciences, Department of Neurosurgery and Turku Brain Injury Centre, Turku University Hospital and University of Turku, Turku, Finland

¹⁰⁷Department of Anesthesiology and Critical Care, Pitié-Salpêtrière Teaching Hospital, Assistance Publique, Hôpitaux de Paris and University Pierre et Marie Curie, Paris, France

¹⁰⁸Neurotraumatology and Neurosurgery Research Unit (UNINN), Vall d'Hebron Research Institute, Barcelona, Spain

¹⁰⁹Department of Neurosurgery, Kaunas University of technology and Vilnius University, Vilnius, Lithuania

¹¹⁰Department of Neurosurgery, Rezekne Hospital, Latvia

¹¹¹Department of Anaesthesia, Critical Care & Pain Medicine NHS Lothian & University of Edinburgh, Edinburgh, UK

¹¹²Director, MRC Biostatistics Unit, Cambridge Institute of Public Health, Cambridge, UK

¹¹³Department of Physical Medicine and Rehabilitation, Oslo University Hospital/University of Oslo, Oslo, Norway

¹¹⁴Division of Orthopedics, Oslo University Hospital, Oslo, Norway

¹¹⁵Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway

¹¹⁶Broad Institute, Cambridge MA Harvard Medical School, Boston MA, Massachusetts General Hospital, Boston MA, USA

¹¹⁷National Trauma Research Institute, The Alfred Hospital, Monash University, Melbourne, Victoria, Australia

¹¹⁸Department of Neurosurgery, Odense University Hospital, Odense, Denmark

¹¹⁹International Neurotrauma Research Organisation, Vienna, Austria

¹²⁰Klinik für Neurochirurgie, Klinikum Ludwigsburg, Ludwigsburg, Germany

¹²¹Division of Biostatistics and Epidemiology, Department of Preventive Medicine, University of Debrecen, Debrecen, Hungary

¹²²Department Health and Prevention, University Greifswald, Greifswald, Germany

¹²³Department of Anaesthesiology and Intensive Care, AUVA Trauma Hospital, Salzburg, Austria

¹²⁴Department of Neurology, Elisabeth-TweeSteden Ziekenhuis, Tilburg, the Netherlands

¹²⁵Department of Neuroanesthesia and Neurointensive Care, Odense University Hospital, Odense, Denmark

¹²⁶Department of Neuromedicine and Movement Science, Norwegian University of Science and Technology, NTNU, Trondheim, Norway

¹²⁷Department of Physical Medicine and Rehabilitation, St.Olavs Hospital, Trondheim University Hospital, Trondheim, Norway

¹²⁸Department of Neurosurgery, University of Pécs, Pécs, Hungary

¹²⁹Division of Neuroscience Critical Care, John Hopkins University School of Medicine, Baltimore, USA

¹³⁰Department of Neuropathology, Queen Elizabeth University Hospital and University of Glasgow, Glasgow, UK
¹³¹Dept. of Department of Biomedical Data Sciences, Leiden University Medical Center, Leiden, The Netherlands

¹³²Department of Pathophysiology and Transplantation, Milan University, and Neuroscience ICU, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, Milano, Italy

¹³³Department of Radiation Sciences, Biomedical Engineering, Umeå University, Umeå, Sweden

¹³⁴Perioperative Services, Intensive Care Medicine and Pain Management, Turku University Hospital and University of Turku, Turku, Finland

¹³⁵Department of Neurosurgery, Kaunas University of Health Sciences, Kaunas, Lithuania

¹³⁶Intensive Care and Department of Pediatric Surgery, Erasmus Medical Center, Sophia Children's Hospital, Rotterdam, The Netherlands

¹³⁷Department of Neurosurgery, Kings college London, London, UK

¹³⁸Neurologie, Neurochirurgie und Psychiatrie, Charité – Universitätsmedizin Berlin, Berlin, Germany

¹³⁹Department of Intensive Care Adults, Erasmus MC – University Medical Center Rotterdam, Rotterdam, the Netherlands

¹⁴⁰Icometrix NV, Leuven, Belgium

¹⁴¹Movement Science Group, Faculty of Health and Life Sciences, Oxford Brookes University, Oxford, UK

¹⁴²Radiology Department, Antwerp University Hospital and University of Antwerp, Edegem, Belgium

¹⁴³Director of Neurocritical Care, University of California, Los Angeles, USA

¹⁴⁴Department of Neurosurgery, St. Olav's Hospital, Trondheim University Hospital, Trondheim, Norway

¹⁴⁵Department of Emergency Medicine, University of Florida, Gainesville, Florida, USA

¹⁴⁶Department of Neurosurgery, Charité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany

¹⁴⁷VTT Technical Research Centre, Tampere, Finland

¹⁴⁸Section of Neurosurgery, Department of Surgery, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, MB, Canada

## Funding

This study relied on data that were collected from the CENTER-TBI Consortium. The FP7 program of the European Union (grant 602150) did financially support the CENTER-TBI project.

## Supplementary materials

Supplementary material associated with this article can be found in the online version at doi:10.1016/j.rehab.2025.102017.

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