The prognostic importance of traumatic axonal injury on early MRI: the Trondheim TAI-MRI grading and quantitative models.

OBJECTIVES: We analysed magnetic resonance imaging (MRI) findings after traumatic brain injury (TBI) aiming to improve the grading of traumatic axonal injury (TAI) to better reflect the outcome. METHODS: Four-hundred sixty-three patients (8-70 years) with mild (n = 158), moderate (n = 129), or severe (n = 176) TBI and early MRI were prospectively included. TAI presence, numbers, and volumes at predefined locations were registered on fluid-attenuated inversion recovery (FLAIR) and diffusion-weighted imaging, and presence and numbers on T2*GRE/SWI. Presence and volumes of contusions were registered on FLAIR. We assessed the outcome with the Glasgow Outcome Scale Extended. Multivariable logistic and elastic-net regression analyses were performed. RESULTS: The presence of TAI differed between mild (6%), moderate (70%), and severe TBI (95%). In severe TBI, bilateral TAI in mesencephalon or thalami and bilateral TAI in pons predicted worse outcomes and were defined as the worst grades (4 and 5, respectively) in the Trondheim TAI-MRI grading. The Trondheim TAI-MRI grading performed better than the standard TAI grading in severe TBI (pseudo-R2 0.19 vs. 0.16). In moderate-severe TBI, quantitative models including both FLAIR volume of TAI and contusions performed best (pseudo-R2 0.19-0.21). In patients with mild TBI or Glasgow Coma Scale (GCS) score 13, models with the volume of contusions performed best (pseudo-R2 0.25-0.26). CONCLUSIONS: We propose the Trondheim TAI-MRI grading (grades 1-5) with bilateral TAI in mesencephalon or thalami, and bilateral TAI in pons as the worst grades. The predictive value was highest for the quantitative models including FLAIR volume of TAI and contusions (GCS score <13) or FLAIR volume of contusions (GCS score ≥ 13), which emphasise artificial intelligence as a potentially important future tool. CLINICAL RELEVANCE STATEMENT: The Trondheim TAI-MRI grading reflects patient outcomes better in severe TBI than today's standard TAI grading and can be implemented after external validation. The prognostic importance of volumetric models is promising for future use of artificial intelligence technologies. KEY POINTS: Traumatic axonal injury (TAI) is an important injury type in all TBI severities. Studies demonstrating which MRI findings that can serve as future biomarkers are highly warranted. This study proposes the most optimal MRI models for predicting patient outcome at 6 months after TBI; one updated pragmatic model and a volumetric model. The Trondheim TAI-MRI grading, in severe TBI, reflects patient outcome better than today's standard grading of TAI and the prognostic importance of volumetric models in all severities of TBI is promising for future use of AI.

Applicability and clinical utility of the German rivermead post-concussion symptoms questionnaire in proxies of children after traumatic brain injury: an instrument validation study.

BACKGROUND: The German Rivermead Post-Concussion Symptoms Questionnaire (RPQ) can be used to assess post-concussion symptoms (PCS) after traumatic brain injury (TBI) in adults, adolescents, and children. METHODS: In this study, we examined the psychometric properties of the German RPQ proxy version (N = 146) for children (8-12 years) after TBI at the item, total and scale score level. Construct validity was analyzed using rank correlations with the proxy-assessed Post-Concussion Symptoms Inventory (PCSI-P), the Patient Health Questionnaire 9 (PHQ-9), and the Generalized Anxiety Disorder Scale 7 (GAD-7). Furthermore, sensitivity testing was performed concerning subjects' sociodemographic and injury-related characteristics. Differential item functioning (DIF) was analyzed to assess the comparability of RPQ proxy ratings for children with those for adolescents. RESULTS: Good internal consistency was demonstrated regarding Cronbach's α (0.81-0.90) and McDonald's ω (0.84-0.92). The factorial validity of a three-factor model was superior to the original one-factor model. Proxy ratings of the RPQ total and scale scores were strongly correlated with the PCSI-P (ϱ = 0.50-0.69), as well as moderately to strongly correlated with the PHQ-9 (ϱ = 0.49-0.65) and the GAD-7 (ϱ = 0.44-0.64). The DIF analysis revealed no relevant differences between the child and adolescent proxy versions. CONCLUSIONS: The German RPQ proxy is a psychometrically reliable and valid instrument for assessing PCS in children after TBI. Therefore, RPQ self- and proxy-ratings can be used to assess PCS in childhood as well as along the lifespan of an individual after TBI.

The Participation Assessment with Recombined Tools-Objective (PART-O): measurement properties of the Norwegian version after traumatic brain injury.

OBJECTIVE: To translate and evaluate the validity of the Participation Assessment with Recombined Tools-Objective (PART-O) in a Norwegian context. METHODS: One hundred and twenty persons with TBI with verified intracranial lesions and persistent symptoms lasting more than 2 years, included in a randomized controlled trial, rated their participation using the PART-O at baseline. The PART-O with its three subscales (Productivity, Out and About, and Social Relations) was translated to Norwegian. Descriptive statistics, Cronbach's alpha, Rasch analysis, and correlation analysis were applied. RESULTS: The Rasch analysis indicated a unidimensional construct of PART-O and its subscales (χ2 < 12.69, p > 0.28). The internal consistency was moderate (Cronbach's alpha 0.48-0.52) and there was a need to reduce scaling options for most of the items. The Out and About and Productivity subscales had considerable floor effects. PART-O showed moderate positive correlation to TBI-related quality of life and global functioning. CONCLUSIONS: PART-O and its subscales reflect unidimensional aspects of participation. In the present Norwegian TBI population the original scaling of PART-O was too detailed for all subscales. The floor effects and suboptimal targeting between items and subjects participation level of the Out and About subscale is a matter of concern.

Frequency and predictors of headache in the first 12 months after traumatic brain injury: results from CENTER-TBI.

BACKGROUND: Headache is a prevalent and debilitating symptom following traumatic brain injury (TBI). Large-scale, prospective cohort studies are needed to establish long-term headache prevalence and associated factors after TBI. This study aimed to assess the frequency and severity of headache after TBI and determine whether sociodemographic factors, injury severity characteristics, and pre- and post-injury comorbidities predicted changes in headache frequency and severity during the first 12 months after injury. METHODS: A large patient sample from the Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) prospective observational cohort study was used. Patients were stratified based on their clinical care pathway: admitted to an emergency room (ER), a ward (ADM) or an intensive care unit (ICU) in the acute phase. Headache was assessed using a single item from the Rivermead Post-Concussion Symptoms Questionnaire measured at baseline, 3, 6 and 12 months after injury. Mixed-effect logistic regression analyses were applied to investigate changes in headache frequency and associated predictors. RESULTS: A total of 2,291 patients responded to the headache item at baseline. At study enrolment, 59.3% of patients reported acute headache, with similar frequencies across all strata. Female patients and those aged up to 40 years reported a higher frequency of headache at baseline compared to males and older adults. The frequency of severe headache was highest in patients admitted to the ICU. The frequency of headache in the ER stratum decreased substantially from baseline to 3 months and remained from 3 to 6 months. Similar trajectory trends were observed in the ICU and ADM strata across 12 months. Younger age, more severe TBI, fatigue, neck pain and vision problems were among the predictors of more severe headache over time. More than 25% of patients experienced headache at 12 months after injury. CONCLUSIONS: Headache is a common symptom after TBI, especially in female and younger patients. It typically decreases in the first 3 months before stabilising. However, more than a quarter of patients still experienced headache at 12 months after injury. Translational research is needed to advance the clinical decision-making process and improve targeted medical treatment for headache. TRIAL REGISTRATION: ClinicalTrials.gov NCT02210221.

The Effect of Recruitment Maneuver on Static Lung Compliance in Patients Undergoing General Anesthesia for Laparoscopic Cholecystectomy: A Single-Centre Prospective Clinical Intervention Study.

Background and Objectives: The aim of this study was to examine whether the use of an alveolar recruitment maneuver (RM) leads to a significant increase in static lung compliance (Cstat) and an improvement in gas exchange in patients undergoing laparoscopic cholecystectomy. Material and Methods: A clinical prospective intervention study was conducted. Patients were divided into two groups according to their body mass index (BMI): normal-weight (group I) and pre-obese and obese grade I (group II). Lung mechanics were monitored (Cstat, dynamic compliance-Cdin, peak pressure-Ppeak, plateau pressure-Pplat, driving pressure-DP) alongside gas exchange, and hemodynamic changes (heart rate-HR, mean arterial pressure-MAP) at six time points: T1 (induction of anesthesia), T2 (formation of pneumoperitoneum), T3 (RM with a PEEP of 5 cm H2O), T4 (RM with a PEEP of 7 cm H2O), T5 (desufflation), and T6 (RM at the end). The RM was performed by increasing the peak pressure by +5 cm of H2O at an equal inspiration-to-expiration ratio (I/E = 1:1) and applying a PEEP of 5 and 7 cm of H2O. Results: Out of 96 patients, 33 belonged to group I and 63 to group II. An increase in Cstat values occurred after all three RMs. At each time point, the Cstat value was measured higher in group I than in group II. A higher increase in Cstat was observed in group II after the second and third RM. Cstat values were higher at the end of the surgical procedure compared to values after the induction of anesthesia. The RM led to a significant increase in PaO2 in both groups without changes in HR or MAP. Conclusions: During laparoscopic cholecystectomy, the application of RM leads to a significant increase in Cstat and an improvement in gas exchange. The prevention of atelectasis during anesthesia should be initiated immediately after the induction of anesthesia, using protective mechanical ventilation and RM.

Sub-symptom threshold aerobic exercise for patients with persisting post-concussion symptoms and exercise intolerance after mild traumatic brain injury - a study protocol with a nested feasibility study for a randomized controlled trial.

BACKGROUND: Persistent post-concussion symptoms (PPCS) affect between 34 and 46% after a mild traumatic brain injury (mTBI). Many also experience exercise intolerance. Sub-symptom threshold aerobic exercise, SSTAE (exercise at an intensity level that does not increase symptoms) is proposed as a treatment to both reduce the symptom burden and increase the exercise tolerance after the injury. It is unclear if this also applies in a more chronic phase after mTBI. MAIN PURPOSE: The main purpose of this study is to evaluate whether SSTAE in addition to ordinary rehabilitation will lead to clinically meaningful improvement of symptom burden, normalize exercise tolerance, increase physical activity, improve health-related quality of life, and reduce patient-specific activity limitations compared to a control group that only receives ordinary rehabilitation. DESIGN: Randomized, controlled, single-blind parallel-group study with three measurement times; T0 at baseline, T1 after the intervention and T2 six months after T1. METHODS: Patients between the ages of 18 and 60 with exercise intolerance and persistent PPCS (> 3 months) will be recruited to the study and randomized to two groups. All patients will receive follow-up at the outpatient TBI clinic. The intervention group will in addition receive SSTAE for 12 weeks with exercise diaries and a retest every 3 weeks for optimal dosage and progression. The Rivermead post-concussion symptoms questionnaire will be the main outcome measure. The secondary outcome measure will be a test of exercise tolerance-the Buffalo Concussion Treadmill Test. Other outcome measures include the patient-specific functional scale that measures patient-specific activity limitations, as well as outcome measures for diagnosis-specific health-related quality of life, anxiety and depression, specific symptoms such as dizziness, headache and fatigue, and physical activity. DISCUSSION: This study will add knowledge about the effect of SSTAE and whether it should be implemented in rehabilitation for the adult population with persistent PPCS after mTBI. The nested feasibility trial showed that the SSTAE intervention was safe and that the study procedures and delivery of the intervention overall were feasible. However, minor amendments to the study protocol were made prior to the commencement of the RCT. TRIAL REGISTRATION: Clinical Trials.gov, NCT05086419. Registered on September 5th, 2021.

Workplace Factors Associated With Return to Work After Mild-to-Moderate Traumatic Brain Injury.

OBJECTIVE: Sociodemographic and injury-related predictors for return to work (RTW) after mild-to-moderate traumatic brain injury (TBI) have been extensively explored. However, there is a knowledge gap regarding work-related predictors of RTW. The main aim of this study was to explore work-related predictors of work participation 6 and 12 months after mild-to-moderate TBI. SETTING: Data were collected at baseline 8 to 12 weeks after injury, and 3, 6, and 12 months after baseline, at a specialized TBI rehabilitation outpatient clinic at Oslo University Hospital, Oslo, Norway. PARTICIPANTS: Eligible patients had suffered a mild-to-moderate TBI 8 to 12 weeks previously, were employed 50% or more at time of injury, were between 18 and 60 years of age, and sick listed 50% or more at time of inclusion due to symptoms of TBI (based on the Rivermead Post-Concussion Symptoms Questionnaire). In total, 116 patients were included in a randomized controlled trial, of whom 113 were included in the 1-year analysis. DESIGN: Patients were originally included in a randomized controlled trial. There were no between-group differences in RTW after 1 year. Thus, the participants were evaluated as one cohort in this study. MAIN MEASURES: The primary outcome measure was work participation 1 year after study inclusion. Work-related predictors were chosen on the basis of previous research and expert opinion and entered into a multivariable linear regression model. The model controlled for sociodemographic and injury-related factors. RESULTS: The best-fitting model explained 25% of variation in work participation at 1 year. Significant predictors were predictability, quantitative demands and rewards (recognition) at the workplace, private or public employment, symptom burden at baseline, and sex. CONCLUSION: In this study, several work-related predictors outperformed some of the established sociodemographic and injury-related predictors of RTW after TBI, thus stressing the need for further focus and research on amendable predictors of RTW after mild-to-moderate TBI.

Stability and Change in Biopsychosocial Factors Associated With Fatigue 6 and 12 Months After Traumatic Brain Injury: An Exploratory Multilevel Study.

OBJECTIVE: To explore factors associated with stability and change in fatigue from 6 to 12 months following traumatic brain injury (TBI). SETTING: Combined in- and outpatient acute care and postacute rehabilitation settings. PARTICIPANTS: A total of 103 patients with confirmed intracranial injury were assessed 6 and/or 12 months following TBI. DESIGN: A prospective observational study with repeated measures at 2 time points, analyzed with a hybrid mixed-effects model. MAIN MEASURES: Primary outcomes were the fatigue factor derived from items from several fatigue patient-reported outcome measures (PROMs; Fatigue Severity Scale, Chalder Fatigue Scale, Giessen Subjective Complaints List-fatigue subscale, and Rivermead Post-Concussion Symptoms Questionnaire-fatigue item) Secondary outcomes were PROMs relating to pain, somatic and psychological distress, insomnia, sleepiness, personality traits, optimism, resilience, behavioral activation and inhibition, and loneliness, as well as neuropsychological measures. Demographic variables and injury severity characteristics were included as covariates. RESULTS: In multilevel regression, female sex, years of education, and 3 factors related to injury severity, somatic vulnerability, and psychosocial robustness were all significantly associated with variation in fatigue between subjects, and explained 61% of the variance in fatigue that was due to stable between-subject differences. Fatigue levels declined significantly over time. Changes in pain severity, somatic symptom burden, psychological distress, and behavioral inhibition were positively associated with changes in fatigue, explaining 22% of the variance in fatigue within subjects. CONCLUSIONS: The study demonstrated that several previously implicated factors show robust effects in distinguishing individuals with TBI on levels of fatigue, but only a few show additional within-subject associations across time. Pain severity, somatic symptom burden, psychological distress, and behavioral inhibition correlated with fatigue across time, implicating these factors as crucial targets for rehabilitation of patients with TBI who suffer from persistent fatigue.

Almost half of children and adolescents had unmet need 6 months after their traumatic brain injury.

AIM: Very few studies have focused on how children with traumatic brain injuries (TBI) access and use publicly funded healthcare and educational services. We aimed to compare the symptoms, recovery and service use of children with TBIs and a control group with other traumatic injuries. METHODS: This case-control study was conducted at Oslo University Hospital, Norway, from 2015 to 2020. It focused on 49 patients aged 1-15 years who were hospitalised with TBIs and compared them with 51 matched patients with other traumatic injuries. Unmet needs were based on reports from parents, patients and clinicians 6 months after the injury. RESULTS: Many children hospitalised after TBIs experienced persistent cognitive and emotional symptoms that effected their return to school and subsequent social interactions. These were associated with reduced quality of life. Nearly half (47%) of the children in the TBI group had unmet needs after 6 months, compared to 12% of the controls. Patients with TBIs also had more symptoms and showed less favourable recoveries than the controls. CONCLUSION: Paediatric patients with TBIs had long-term cognitive and emotional symptoms that affected their return to school and social functioning. Almost half of them had unmet needs 6 months after their acute injury.

Discrepancy between disability and reported well-being after traumatic brain injury.

BACKGROUND: Following traumatic brain injury (TBI), the clinical focus is often on disability. However, patients' perceptions of well-being can be discordant with their disability level, referred to as the 'disability paradox'. We aimed to examine the relationship between disability and health-related quality of life (HRQoL) following TBI, while taking variation in personal, injury-related and environment factors into account. METHODS: We used data from the Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury study. Disability was assessed 6 months post-injury by the Glasgow Outcome Scale-Extended (GOSE). HRQoL was assessed by the SF-12v2 physical and mental component summary scores and the Quality of Life after Traumatic Brain Injury overall scale. We examined mean total and domain HRQoL scores by GOSE. We quantified variance in HRQoL explained by GOSE, personal, injury-related and environment factors with multivariable regression. RESULTS: Six-month outcome assessments were completed in 2075 patients, of whom 78% had mild TBI (Glasgow Coma Scale 13-15). Patients with severe disability had higher HRQoL than expected on the basis of GOSE alone, particularly after mild TBI. Up to 50% of patients with severe disability reported HRQoL scores within the normative range. GOSE, personal, injury-related and environment factors explained a limited amount of variance in HRQoL (up to 29%). CONCLUSION: Contrary to the idea that discrepancies are unusual, many patients with poor functional outcomes reported well-being that was at or above the boundary considered satisfactory for the normative sample. These findings challenge the idea that satisfactory HRQoL in patients with disability should be described as 'paradoxical' and question common views of what constitutes 'unfavourable' outcome.

Community-Based Interventions After Acquired Brain Injury-A Systematic Review of Intervention Types and Their Effectiveness.

OBJECTIVES: Comprehensive review of existing types and effectiveness of community-based interventions delivered to adults (mean age 18-65 years) with long-lasting (≥6 months) difficulties following acquired brain injury (ABI). DESIGN: Systematic review of controlled intervention studies published until February 2021. MAIN MEASURES: Systematic searches in databases (MEDLINE, PsycINFO, Database of Abstracts of Reviews of Effects [Cochrane Library], and Cochrane Central Register of Controlled Trials [Cochrane Library]) and inclusion of English peer-reviewed full-text articles; randomized or controlled community-based intervention studies; sample size of 20 or more participants; and 3 or more intervention sessions. Two reviewers independently extracted data for the synthesis and assessed the methodological quality. Data extraction included study characteristics, demographics of participants, content and dose of intervention, outcome measures, and findings. RESULT: The search returned 7386 publications, of which 49 eligible studies were included, revealing a diverse range of community-based interventions and a myriad of outcome measures applied for assessing functional capacities, participation, and quality of life in the chronic phase of ABI. Intervention types encompassed 14 holistic, 23 physical, and 12 specific interventions. A large heterogeneity regarding intervention frequency and intensity was found. Meta-analyses performed on the holistic, physical, and specific interventions did not indicate any significant pooled effects but showed highly variable effects between individuals, both in persons with traumatic and nontraumatic brain injuries. CONCLUSIONS: Because of lack of pooled effects within types of community-based interventions, specific evidence-based recommendations within holistic, physical, and specific interventions designed to mitigate long-lasting ABI problems cannot be made. This review highlights the need for future studies to address methodological issues concerning larger sample size, lack of clear description interventions and comparator, missing reports of effects in change scores, need for consistent use of recommended outcome measures, and investigating the wide variety in intervention responsiveness among participants with ABI. Systematic review registration: PROSPERO (CRD42019124949).

Patient-Reported Problem Areas in Chronic Traumatic Brain Injury.

OBJECTIVE: The aims of this study were to (1) assess self-reported main problem areas reported by patients with traumatic brain injury (TBI) and their family members in the chronic phase, and (2) compare the self-prioritized problems with difficulties captured by questionnaires and neuropsychological screening through linking to the International Classification of Functioning, Disability and Health (ICF). SETTING: Outpatient clinic at the Oslo University Hospital, Norway. PARTICIPANTS: In total, 120 patients with TBI were recruited, of whom, 78 had a participating family member. Eligibility criteria were a clinical TBI diagnosis with verified intracranial injury, living at home, aged 18 to 72 years, 2 years or more postinjury, and experiencing perceived TBI-related difficulties, reduced physical and mental health, or difficulties with participation in everyday life. Patients with severe psychiatric or neurological disorders or inability to participate in goal-setting processes were excluded. DESIGN: Cross-sectional. MAIN MEASURES: Target Outcomes, that is, 3 main TBI-related problem areas reported by patients and family members, collected in a semistructured interview; standardized questionnaires of TBI-related symptoms, anxiety, depression, functioning, and health-related quality of life; neuropsychological screening battery. RESULTS: Target Outcomes were related to cognitive, physical, emotional, and social difficulties. Target Outcomes were linked to 12 chapters and 112 distinct categories in the ICF, while standardized measures only covered 10 chapters and 28 categories. Some aspects of post-TBI adjustment were found to be insufficiently covered by the ICF classification, such as identity issues, lack of meaningful activities, and feeling lonely. CONCLUSION: The Target Outcomes approach is a useful assessment method in a population with chronic TBI. The standardized questionnaires capture the spectrum of problems, whereas the Target Outcomes approach captures the prioritized individual problems hindering everyday life after TBI. While the standardized measures are an irreplaceable part of the assessment, Target Outcomes ensures patient involvement and may help clinicians better tailor relevant rehabilitation efforts.

Health related quality of life, service utilization and costs for patients with Huntington's disease in Norway.

BACKGROUND: Huntington's disease (HD) is a progressive genetic neurodegenerative disease accompanied by mental and neurocognitive disabilities, which requires long-term and comprehensive treatment and care. Information on the health and economic burden of HD is scarce, but essential for conducting health economic analyses, in light of the prospect of new therapies for HD. In this study, we aim to identify values for Health-Related Quality of Life (HRQoL), describe service utilization and costs, and their associations with clinical and socio-demographic variables across all phases of HD. METHODS: A cross-sectional study including 86 patients across all phases of HD. Values of HRQoL were calculated based on EQ-5D-3L index scores. Additionally, health care and societal costs were estimated based on service utilization collected using the Client Service Receipt Inventory (CSRI) and data from the patients' interviews. Total societal costs included costs of primary and secondary health care services, informal care and productivity loss of the patients. Multiple regression analyses were used to investigate associations between socio-demographic and clinical variables on HRQoL and costs. RESULTS: HRQoL values declined, while total costs increased across disease severity. Total six-month healthcare costs and total societal costs were € 18,538 and € 66,789 respectively. Healthcare and societal costs doubled from early to middle phase, and tripled from middle to advanced disease phase. Main six-month cost components for the three disease phases were informal care costs (€ 30,605) accounting for approximately half the total societal costs, and costs due to production loss (€ 18,907) being slightly higher than the total healthcare costs. Disease severity and gender were found to have the strongest effect on both values of HRQoL and costs. CONCLUSIONS: Reported values of HRQoL and costs including costs for production loss may be used in modelling the cost-effectiveness of treatment for HD. Our results highlight the crucial role the informal caregivers play in the care provided to HD patients in all disease phases. Future research should focus on the estimation of productivity loss among informal caregivers.

Cost-effectiveness analysis of combined cognitive and vocational rehabilitation in patients with mild-to-moderate TBI: results from a randomized controlled trial.

BACKGROUND: Traumatic brain injury (TBI) represents a financial burden to the healthcare system, patients, their families and society. Rehabilitation interventions with the potential for reducing costs associated with TBI are demanded. This study evaluated the cost-effectiveness of a randomized, controlled, parallel group trial that compared the effectiveness of a combined cognitive and vocational intervention to treatment as usual (TAU) on vocational outcomes. METHODS: One-hundred sixteen participants with mild-to-moderate TBI were recruited from an outpatient clinic at Oslo University Hospital, Norway. They were randomized to a cognitive rehabilitation intervention (Compensatory Cognitive Training, CCT) and Supported Employment (SE) or TAU in a 1:1 ratio. Costs of CCT-SE and TAU, healthcare services, informal care and productivity loss were assessed 3, 6 and 12 months after study inclusion. Cost-effectiveness was evaluated from the difference in number of days until return to pre-injury work levels between CCT-SE and TAU and quality-adjusted life years (QALYs) derived from the EQ-5D-5L across 12 months follow-up. Cost-utility was expressed in incremental cost-effectiveness ratio (ICER). RESULTS: The mean total costs of healthcare services was € 3,281 in the CCT-SE group and € 2,300 in TAU, informal care was € 2,761 in CCT-SE and € 3,591 in TAU, and productivity loss was € 30,738 in CCT-SE and € 33,401 in TAU. Costs related to productivity loss accounted for 84% of the total costs. From a healthcare perspective, the ICER was € 56 per day earlier back to work in the CCT-SE group. Given a threshold of € 27,500 per QALY gained, adjusting for baseline difference in EQ-5D-5L index values revealed a net monetary benefit (NMB) of € -561 (0.009*27,500-979) from the healthcare perspective, indicating higher incremental costs for the CCT-SE group. From the societal perspective, the NMB was € 1,566 (0.009*27,500-(-1,319)), indicating that the CCT-SE intervention was a cost-effective alternative to TAU. CONCLUSIONS: Costs associated with productivity loss accounted for the majority of costs in both groups and were lower in the CCT-SE group. The CCT-SE intervention was a cost-effective alternative to TAU when considering the societal perspective, but not from a healthcare perspective. TRIAL REGISTRATION: ClinicalTrails.gov NCT03092713 .

Rehabilitation and outcomes after complicated vs uncomplicated mild TBI: results from the CENTER-TBI study.

BACKGROUND: Despite existing guidelines for managing mild traumatic brain injury (mTBI), evidence-based treatments are still scarce and large-scale studies on the provision and impact of specific rehabilitation services are needed. This study aimed to describe the provision of rehabilitation to patients after complicated and uncomplicated mTBI and investigate factors associated with functional outcome, symptom burden, and TBI-specific health-related quality of life (HRQOL) up to six months after injury. METHODS: Patients (n = 1379) with mTBI from the Collaborative European NeuroTrauma Effectiveness Research in TBI (CENTER-TBI) study who reported whether they received rehabilitation services during the first six months post-injury and who participated in outcome assessments were included. Functional outcome was measured with the Glasgow Outcome Scale - Extended (GOSE), symptom burden with the Rivermead Post Concussion Symptoms Questionnaire (RPQ), and HRQOL with the Quality of Life after Brain Injury - Overall Scale (QOLIBRI-OS). We examined whether transition of care (TOC) pathways, receiving rehabilitation services, sociodemographic (incl. geographic), premorbid, and injury-related factors were associated with outcomes using regression models. For easy comparison, we estimated ordinal regression models for all outcomes where the scores were classified based on quantiles. RESULTS: Overall, 43% of patients with complicated and 20% with uncomplicated mTBI reported receiving rehabilitation services, primarily in physical and cognitive domains. Patients with complicated mTBI had lower functional level, higher symptom burden, and lower HRQOL compared to uncomplicated mTBI. Rehabilitation services at three or six months and a higher number of TOC were associated with unfavorable outcomes in all models, in addition to pre-morbid psychiatric problems. Being male and having more than 13 years of education was associated with more favorable outcomes. Sustaining major trauma was associated with unfavorable GOSE outcome, whereas living in Southern and Eastern European regions was associated with lower HRQOL. CONCLUSIONS: Patients with complicated mTBI reported more unfavorable outcomes and received rehabilitation services more frequently. Receiving rehabilitation services and higher number of care transitions were indicators of injury severity and associated with unfavorable outcomes. The findings should be interpreted carefully and validated in future studies as we applied a novel analytic approach. TRIAL REGISTRATION: ClinicalTrials.gov NCT02210221.

Incidence of emergency neurosurgical TBI procedures: a population-based study.

BACKGROUND: The rates of emergency neurosurgery in traumatic brain injury (TBI) patients vary between populations and trauma centers. In planning acute TBI treatment, knowledge about rates and incidence of emergency neurosurgery at the population level is of importance for organization and planning of specialized health care services. This study aimed to present incidence rates and patient characteristics for the most common TBI-related emergency neurosurgical procedures. METHODS: Oslo University Hospital is the only trauma center with neurosurgical services in Southeast Norway, which has a population of 3 million. We extracted prospectively collected registry data from the Oslo TBI Registry - Neurosurgery over a five-year period (2015-2019). Incidence was calculated in person-pears (crude) and age-adjusted for standard population. We conducted multivariate multivariable logistic regression models to assess variables associated with emergency neurosurgical procedures. RESULTS: A total of 2151 patients with pathological head CT scans were included. One or more emergency neurosurgical procedure was performed in 27% of patients. The crude incidence was 3.9/100,000 person-years. The age-adjusted incidences in the standard population for Europe and the world were 4.0/100,000 and 3.3/100,000, respectively. The most frequent emergency neurosurgical procedure was the insertion of an intracranial pressure monitor, followed by evacuation of the mass lesion. Male sex, road traffic accidents, severe injury (low Glasgow coma score) and CT characteristics such as midline shift and compressed/absent basal cisterns were significantly associated with an increased probability of emergency neurosurgery, while older age was associated with a decreased probability. CONCLUSIONS: The incidence of emergency neurosurgery in the general population is low and reflects neurosurgery procedures performed in patients with severe injuries. Hence, emergency neurosurgery for TBIs should be centralized to major trauma centers.

The effectiveness of a family-centred intervention after traumatic brain injury: A pragmatic randomised controlled trial.

OBJECTIVES: To determine the effectiveness of a family-centred intervention for patients with traumatic brain injury and family members. DESIGN: Open-labelled, two-armed randomised controlled trial. SETTINGS: Outpatient clinic and family residences. PARTICIPANTS: Sixty-one patients (33 women) with traumatic brain injury, with mean (SD) age 43.8 (12.2), and 63 family members (33 women), with mean (SD) age 42.6 (11.3), were assign to intervention (n = 30 families) and control group (n = 31 families). INTERVENTION: An eight-session single-family intervention to improve individual and family functioning. OUTCOME MEASURES: Self-reported questionnaires at start-of-treatment, median (IQR) 11.4 (8.4, 15.9) months post-injury, and at two follow-ups, 2.7 (2.3, 3.8) and 9.2 (8.2, 9.9) months after start-of-treatment. Primary outcome measures were the SF-36 Mental Component Summary (MCS) and Caregiver Burden Scale (CGB). Secondary outcome measures were the Family Adaptability and Cohesion Evaluation Scale (FACES) and Quality of Life after Brain Injury Questionnaire (QOLIBRI). Group differences were analysed with linear mixed-model analysis for repeated measurements. RESULTS: No significant between-group differences were found. The intervention group significantly improved on the MCS, the CGB and FACES in the treatment period, whereas the controls did not. The mean (SD) MCS change in the treatment period was 2.4 (1.1) points P = 0.028 in the intervention group. Mean (SE) MCS scores were 47.9 (1.26) and 47.3 (1.27) in the intervention and control group at last follow-up. CONCLUSIONS: Receiving an eight-session family intervention, in addition to specialised rehabilitation for the patients, was not superior to rehabilitation at a specialised traumatic brain injury outpatient clinic.

Post-concussion symptoms three months after mild-to-moderate TBI: characteristics of sick-listed patients referred to specialized treatment and consequences of intracranial injury.

Objective: To present pre-injury, injury-related, work-related and post-injury characteristics, and to compare patients with and without traumatic intracranial abnormalities, in a treatment-seeking sample with persistent post-concussion symptoms (PPCS) after mild-to-moderate TBI.Methods: Cross-sectional design in the context of a specialized TBI outpatient clinic. Eligible patients were aged 18-60 years, employed ≥ 50% at time of injury, and sick listed ≥ 50% at inclusion due to PPCS. Data were collected 8-12 weeks after injury through review of medical records, semi-structured interviews, questionnaires, and neuropsychological screening.Results: The study included 116 patients, of whom 60% were women, and predominantly white-collar workers in full-time positions. Ninety-four percent had a mild TBI, and 23% had intracranial abnormalities. The full sample reported high somatic, emotional, and cognitive symptom burden, and decreased health-related quality of life. Patients with normal CT/MRI results reported higher overall symptom burden, while patients with intracranial abnormalities had worse memory function.Conclusion: Injury severity and traumatic intracranial radiological findings should not be the sole ground for planning of rehabilitation service provision in patients with PPCS, as subjective complaints do not necessarily co-vary with these variables.

Pre- and in-hospital mortality for moderate-to-severe traumatic brain injuries: an analysis of the National Trauma Data Bank (2008-2014).

Objectives: This study aimed to: (1) evaluate pre- and in-hospital mortality for moderate-to-severe TBI in the U.S. by injury type (blunt vs. penetrating) and (2) estimate annual regression-adjusted mortality from 2008-2014.Methods: Data were analyzed from the National Trauma Data Bank (N=247,648). Multivariable logistic regression analyses were performed by injury type to assess changes in mortality between study periods (early period: 2008-2010; late period: 2011-2014) and to estimate annual regression-adjusted mortality. Mortality odds ratios and 95% confidence intervals were calculated.Results: Total observed mortality was 18.8%. After covariate adjustment, patients in the late period had an increased odds of prehospital mortality compared to patients in the early period for blunt (OR: 4.69; 95%CI: 4.41-4.98) and penetrating trauma (OR: 4.71; 95%CI: 4.39-5.06). In contrast, patients in the late period had a decreased odds of in-hospital mortality compared to patients in the early period for blunt (OR: 0.95; 95%CI: 0.91-0.98) and penetrating trauma (OR: 0.92; 95%CI: 0.85-0.98).Conclusions: The decreasing in-hospital mortality trend is consistent with previous literature. Additional research is warranted to validate the observed increase in prehospital mortality and to identify best practices that can improve prehospital outcomes for patients with moderate-to-severe TBI.

Trajectory of 10-Year Neurocognitive Functioning After Moderate-Severe Traumatic Brain Injury: Early Associations and Clinical Application.

OBJECTIVE: This study aimed to explore the 10-year trajectories of neurocognitive domains after moderate-severe traumatic brain injury (TBI), to identify factors related to long-term neurocognitive functioning, and to investigate whether performance remained stable or changed over time. METHOD: Seventy-nine patients with moderate-severe TBI between the ages of 16 and 55 years were assessed at 3 months, 1, 5, and 10 years postinjury using neuropsychological tests and functional outcomes. Three hierarchical linear models were used to investigate the relationships of domain-specific neurocognitive trajectories (Memory, Executive function, and Reasoning) with injury severity, demographics, functional outcome at 3 months (Glasgow Outcome Scale-Extended) and emotional distress at 1 year (Symptom Checklist 90-Revised). RESULTS: Education, injury severity measures, functional outcome, and emotional distress were significantly associated with both Memory and Executive function. Education and emotional distress were related to Reasoning. The interaction effects between time and these predictors in predicting neurocognitive trajectories were nonsignificant. Among patients with data at 1 and 10 year follow-ups (n = 47), 94-96% exhibited stable scores on Executive function and Reasoning tasks, and 83% demonstrated stable scores on Memory tasks. Significant memory decline was presented in 11% of patients. CONCLUSIONS: The findings highlight the differential contribution of variables in their relationships with long-term neurocognitive functioning after moderate-severe TBI. Injury severity was important for Memory outcomes, whereas emotional distress influenced all neurocognitive domains. Reasoning (intellectual) abilities were relatively robust after TBI. While the majority of patients appeared to be cognitively stable beyond the first year, a small subset demonstrated a significant memory decline over time.