Outcome and comparative effectiveness research in traumatic brain injury : a methodological perspective

Traumatic brain injury (TBI) is one of the leading causes of death and disability worldwide. Although research activity in TBI has expanded rapidly, all these endeavors have not yet resulted in major advances in our understanding of TBI. This thesis addresses two important topics in TBI research. First, outcome following TBI including the prevalence and predictors of psychiatric disorders and post-concussion symptoms. Second, this thesis examines whether comparative effectiveness research (CER) could contribute to evidence generation in TBI, with a focus on current guideline adherence, treatment variation and analytical methods. We found that prevalence rates of post-concussion symptoms and psychiatric disorders varied widely and were dependent on pre-injury factors, patient population, assessment, analysis strategy and the diagnostic criteria used. Etiology of TBI sequelae is complex and multifactorial and includes biological, psychological and social factors that might be difficult to capture in a prediction model. When studying prevalence and predictors of psychiatric disorders and post-concussion symptoms following TBI, the role of misattribution, research setting, attrition and the overlap in symptomatology between post-concussion symptoms and psychiatric disorders should be taken into account. Current evidence underpinning TBI guidelines is weak, and consequently, there is large variation in policy and guideline adherence among neurotrauma centers. This variation provides an opportunity for CER. However, the effect estimate obtained in observational CER studies largely depends on the analytical method used. Since all analytical methods have their strengths and limitations and are based on untestable assumptions, it is important that researchers do not consider one particular analytical method as the most appropriate. Different analytical methods that are reasonable for the research question under study should be used as sensitivity analyses and the results of observational CER studies should be confirmed by high-quality RCTs

Rating of pre-injury symptoms over time in patients with mild traumatic brain injury:The good-old-days-bias revisited

Objective Post-concussion syndrome (PCS) occurs following mild traumatic brain injury (mTBI). Patients with mTBI are often assessed using self-report instruments that rely on perception of current symptoms compared to how they felt and functioned pre-injury. The objective was to examine reliability of patients’ post-injury reporting of their pre-injury symptoms. Methods We included two control groups (trauma patients without brain injury history and healthy controls) who were recruited at an outpatient surgical clinic and among the working and social environment of the researchers, respectively. The Head Injury Symptom Checklist (HISC) was used to assess pre-injury and current symptoms at four time points post injury. We included 836 patients with mTBIs, 191 trauma patients without brain injury history, and 100 healthy controls. Results Patients with mTBI reported significantly more pre-injury symptoms than both control groups (p < .001). Forty-five percent of patients with mTBI were inconsistent in their pre-injury ratings across four assessments. Patients with post-injury PCS reported much greater pre-injury symptoms and were more often inconsistent. Conclusion Accurately assessing PCS by comparing pre with post-injury complaints is difficult, and may have implications for diagnosis when using self-report instruments. Therefore, post-injury PCS diagnosis should be interpreted with caution and PCS should ideally be examined using clinical examination

Post-Traumatic Stress Disorder after Civilian Traumatic Brain Injury: A Systematic Review and Meta-Analysis of Prevalence Rates

Post-traumatic stress disorder (PTSD) is a commonly diagnosed psychiatric disorder following traumatic brain injury (TBI). Much research on PTSD and TBI has focused on military conflict settings. Less is known about PTSD in civilian TBI. We conducted a systematic review and meta-analysis on the prevalence of PTSD after mild and moderate/severe TBI in civilian populations. We further aimed to explore the influence of methodological quality and assessment methods. A systematic literature search was performed on studies reporting on PTSD in civilian TBI, excluding studies on military populations. The risk of bias was assessed using the MORE (Methodological evaluation of Observational REsearch) checklist. Meta-analysis was conducted for overall prevalence rates for PTSD with sensitivity analyses for the severity of TBI. Fifty-two studies were included, of which 31 were graded as low risk of bias. Prevalence rates of PTSD in low risk of bias studies varied widely (2.6–36%) with a pooled prevalence rate of 15.6%. Pooled prevalence rates of PTSD for mild TBI (13.5%, 95% confidence interval [CI]: 11.7–15.3; I2 = 2%) did not differ from moderate/severe TBI (11.8, 95% CI: 7.5–16.1; I2 = 63%). Similar rates were reported in studies using different approaches and times of assessment. Although most studies that compared participants with TBI with trauma patients and healthy controls found no difference in prevalence rates of PTSD, a meta-analysis across studies revealed a higher prevalence of PTSD in patients with TBI (odds ratio [OR]: 1.73, 95% CI: 1.21–2.47). This review highlights variability between studies and emphasizes the need for higher-quality studies. Further research is warranted to determine risk factors for the development of PTSD after TBI

Comparing health-related quality of life of Dutch and Chinese patients with traumatic brain injury: Do cultural differences play a role?

Background: There is growing interest in health related quality of life (HRQoL) as an outcome measure in international trials. However, there might be differences in the conceptualization of HRQoL across different socio-cultural groups. The objectives of current study were: (I) to compare HRQoL, measured with the short form (SF)-36 of Dutch and Chinese traumatic brain injury (TBI) patients 1 year after injury and; (II) to assess whether differences in SF-36 profiles could be explained by cultural differences in HRQoL conceptualization. TBI patients are of particular interest because this is an important cause of diverse impairments and disabilities in functional, physical, emotional, cognitive, and social domains that may drastically reduce HRQoL. Methods: A prospective cohort study on adult TBI patients in the Netherlands (RUBICS) and a retrospective cohort study in China were used to compare HRQoL 1 year post-injury. Differences on subscales were assessed with the Mann-Whitney U-test. The internal consistency, interscale correlations, item-internal consistency and item-discriminate validity of Dutch and Chinese SF-36 profiles were examined. Confirmatory factor analysis was performed to assess whether Dutch and Chinese data fitted the SF-36 two factor-model (physical and mental construct). Results: Four hundred forty seven Dutch and 173 Chinese TBI patients were included. Dutch patients obtained significantly higher scores on role limitations due to emotional problems (p < .001) and general health (p < .001), while Chinese patients obtained significantly higher scores on physical functioning (p < .001) and bodily pain (p = .001). Scores on these subscales were not explained by cultural differences in conceptualization, since item- and scale statistics were all sufficient. However, differences among Dutch and Chinese patients were found in the conceptualization of the domains vitality, mental health and social functioning. Conclusions: One year after TBI, Dutch and Chinese patients reported a different pattern of HRQoL. Further, there might be cultural differences in the conceptualization of some of the SF-36 subscales, which has implications for outcome evaluation in multi-national trials

Variation in neurosurgical management of traumatic brain injury : a survey in 68 centers participating in the CENTER-TBI study

Correction: Volume: 161 Issue: 3 Pages: 451-455 DOI: 10.1007/s00701-019-03815-6 Accession Number: WOS:000460607500003BackgroundNeurosurgical management of traumatic brain injury (TBI) is challenging, with only low-quality evidence. We aimed to explore differences in neurosurgical strategies for TBI across Europe.MethodsA survey was sent to 68 centers participating in the Collaborative European Neurotrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) study. The questionnaire contained 21 questions, including the decision when to operate (or not) on traumatic acute subdural hematoma (ASDH) and intracerebral hematoma (ICH), and when to perform a decompressive craniectomy (DC) in raised intracranial pressure (ICP).ResultsThe survey was completed by 68 centers (100%). On average, 10 neurosurgeons work in each trauma center. In all centers, a neurosurgeon was available within 30min. Forty percent of responders reported a thickness or volume threshold for evacuation of an ASDH. Most responders (78%) decide on a primary DC in evacuating an ASDH during the operation, when swelling is present. For ICH, 3% would perform an evacuation directly to prevent secondary deterioration and 66% only in case of clinical deterioration. Most respondents (91%) reported to consider a DC for refractory high ICP. The reported cut-off ICP for DC in refractory high ICP, however, differed: 60% uses 25mmHg, 18% 30mmHg, and 17% 20mmHg. Treatment strategies varied substantially between regions, specifically for the threshold for ASDH surgery and DC for refractory raised ICP. Also within center variation was present: 31% reported variation within the hospital for inserting an ICP monitor and 43% for evacuating mass lesions.ConclusionDespite a homogeneous organization, considerable practice variation exists of neurosurgical strategies for TBI in Europe. These results provide an incentive for comparative effectiveness research to determine elements of effective neurosurgical care.Peer reviewe

Prehospital Trauma Care among 68 European Neurotrauma Centers: Results of the CENTER-TBI Provider Profiling Questionnaires

The first hour following traumatic brain injury (TBI) is considered crucial to prevent death and disability. It is, however, not established yet how the prehospital care should be organized to optimize recovery during the first hour. The objective of the current study was to examine variation in prehospital trauma care across Europe aiming to inform comparative effectiveness analyses on care for neurotrauma patients. A survey on prehospital trauma care was sent to 68 neurotrauma centers from 20 European countries participating in the Collaborative European NeuroTrauma Effectiveness Research in TBI (CENTER-TBI) study. The survey was developed using literature review and expert opinion and was pilot tested in 16 centers. All participants completed the questionnaire. Advanced life support was used in half of the centers (n = 35; 52%), whereas the other centers used mainly basic life support (n = 26; 38%). A mobile medical team (MMT) could be dispatched 24/7 in most centers (n = 66; 97%). Helicopters were used in approximately half of the centers to transport the MMT to the scene (n = 39; 57%) and the patient to the hospital (n = 31, 46%). Half of the centers used a stay-and-play approach at the scene (n = 37; 55%), while the others used a scoop-and-run approach or another policy. We found wide variation in prehospital trauma care across Europe. This may reflect differences in socio-economic situations, geographic differences, and a general lack of strong evidence for some aspects of prehospital care. The current variation provides the opportunity to study the effectiveness of prehospital interventions and systems of care in comparative effectiveness research

Management of Mild Traumatic Brain Injury at the Emergency Department and Hospital Admission in Europe: A Survey of 71 Neurotrauma Centers Participating in the CENTER-TBI Study.

Previous studies have indicated that there is no consensus about management of mild traumatic brain injury (mTBI) at the emergency department (ED) and during hospital admission. We aim to study variability between management policies for TBI patients at the ED and at the hospital ward across Europe. Centers participating in the Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) study received questionnaires about different phases of TBI care. These questionnaires included 71 questions about TBI management at the ED and at the hospital ward. We found differences in how centers defined mTBI. For example, 40 centers (59%) defined mTBI as a Glasgow Coma Scale (GCS) score between 13 and 15 and 26 (38%) defined it as a GCS score between 14 and 15. At the ED various guidelines for the use of head computed tomography (CT) in mTBI patients were used; 32 centers (49%) used national guidelines, 10 centers (15%) local guidelines, and 14 centers (21%) used no guidelines at all. Also, differences in indication for admission between centers were found. After ED discharge, 7 centers (10%) scheduled a routine follow-up appointment, whereas 38 (54%) did so only after ward admission. In conclusion, large between-center variation exists in policies for diagnostics, admission, and discharge decisions in patients with mTBI at the ED and in the hospital. Guidelines are not always operational in centers, and reported policies systematically diverge from what is recommended in those guidelines. The results of this study may be useful in the understanding of mTBI care in Europe and show the need for further studies on the effectiveness of different policies on outcome

Prehospital Trauma Care among 68 European Neurotrauma Centers: Results of the CENTER-TBI Provider Pr

The first hour following traumatic brain injury (TBI) is considered crucial to prevent death and disability. It is, however, not established yet how the prehospital care should be organized to optimize recovery during the first hour. The objective of the current study was to examine variation in prehospital trauma care across Europe aiming to inform comparative effectiveness analyses on care for neurotrauma patients. A survey on prehospital trauma care was sent to 68 neurotrauma centers from 20 European countries participating in the Collaborative European NeuroTrauma Effectiveness Research in TBI (CENTER-TBI) study. The survey was developed using literature review and expert opinion and was pilot tested in 16 centers. All participants completed the questionnaire. Advanced life support was used in half of the centers (n = 35; 52%), whereas the other centers used mainly basic life support (n = 26; 38%). A mobile medical team (MMT) could be dispatched 24/7 in most centers (n = 66; 97%). Helicopters were used in approximately half of the centers to transport the MMT to the scene (n = 39; 57%) and the patient to the hospital (n = 31, 46%). Half of the centers used a stay-and-play approach at the scene (n = 37; 55%), while the others used a scoop-and-run approach or another policy. We found wide variation in prehospital trauma care across Europe. This may reflect differences in socio-economic situations, geographic differences, and a general lack of strong evidence for some aspects of prehospital care. The current variation provides the opportunity to study the effectiveness of prehospital interventions and systems of care in comparative effectiveness research

Rehabilitation after traumatic brain injury: A survey in 70 European neurotrauma centres participating in the CENTER-TBI study.

OBJECTIVE: To describe variation in structural and process characteristics of acute in-hospital rehabilitation and referral to post-acute care for patients with traumatic brain injury across Europe. DESIGN: Survey study, of neurotrauma centres. METHODS: A 14-item survey about in-hospital rehabilitation and referral to post-acute care was sent to 71 neurotrauma centres participating in a European multicentre study (CENTER-TBI). The questionnaire was developed based on literature and expert opinion and was pilot-tested before sending out to the centres. RESULTS: Seventy (99%) centres in 20 countries completed the survey. The included centres were predominately academic level I trauma centres. Among the 70 centres, a multidisciplinary rehabilitation team can be consulted at 41% (n = 29) of the intensive care units and 49% (n = 34) of the wards. Only 13 (19%) centres used rehabilitation guidelines in patients with traumatic brain injury. Age was reported as a major determinant of referral decisions in 32 (46%) centres, with younger patients usually referred to specialized rehabilitation centres, and patients ≥ 65 years also referred to nursing homes or local hospitals. CONCLUSION: Substantial variation exists in structural and process characteristics of in-hospital acute rehabilitation and referral to post-acute rehabilitation facilities among neurotrauma centres across Europe

Variation in neurosurgical management of traumatic brain injury: a survey in 68 centers participating in the CENTER-TBI study.

BACKGROUND: Neurosurgical management of traumatic brain injury (TBI) is challenging, with only low-quality evidence. We aimed to explore differences in neurosurgical strategies for TBI across Europe. METHODS: A survey was sent to 68 centers participating in the Collaborative European Neurotrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) study. The questionnaire contained 21 questions, including the decision when to operate (or not) on traumatic acute subdural hematoma (ASDH) and intracerebral hematoma (ICH), and when to perform a decompressive craniectomy (DC) in raised intracranial pressure (ICP). RESULTS: The survey was completed by 68 centers (100%). On average, 10 neurosurgeons work in each trauma center. In all centers, a neurosurgeon was available within 30 min. Forty percent of responders reported a thickness or volume threshold for evacuation of an ASDH. Most responders (78%) decide on a primary DC in evacuating an ASDH during the operation, when swelling is present. For ICH, 3% would perform an evacuation directly to prevent secondary deterioration and 66% only in case of clinical deterioration. Most respondents (91%) reported to consider a DC for refractory high ICP. The reported cut-off ICP for DC in refractory high ICP, however, differed: 60% uses 25 mmHg, 18% 30 mmHg, and 17% 20 mmHg. Treatment strategies varied substantially between regions, specifically for the threshold for ASDH surgery and DC for refractory raised ICP. Also within center variation was present: 31% reported variation within the hospital for inserting an ICP monitor and 43% for evacuating mass lesions. CONCLUSION: Despite a homogeneous organization, considerable practice variation exists of neurosurgical strategies for TBI in Europe. These results provide an incentive for comparative effectiveness research to determine elements of effective neurosurgical care