Background Limited evidence existed on the comparative effectiveness of decompressive craniectomy (DC) versus craniotomy for evacuation of traumatic acute subdural hematoma (ASDH) until the... Show moreBackground Limited evidence existed on the comparative effectiveness of decompressive craniectomy (DC) versus craniotomy for evacuation of traumatic acute subdural hematoma (ASDH) until the recently published randomised clinical trial RESCUE-ASDH. In this study, that ran concurrently, we aimed to determine current practice patterns and compare outcomes of primary DC versus craniotomy.Methods We conducted an analysis of centre treatment preference within the prospective, multicentre, observational Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (known as CENTER-TBI) and NeuroTraumatology Quality Registry (known as Net-QuRe) studies, which enrolled patients throughout Europe and Israel (2014-2020). We included patients with an ASDH who underwent acute neurosurgical evacuation. Patients with severe pre-existing neurological disorders were excluded. In an instrumental variable analysis, we compared outcomes between centres according to treatment preference, measured by the case-mix adjusted proportion DC per centre. The primary outcome was functional outcome rated by the 6-months Glasgow Outcome Scale Extended, estimated with ordinal regression as a common odds ratio (OR), adjusted for prespecified confounders. Variation in centre preference was quantified with the median odds ratio (MOR). CENTER-TBI is registered with ClinicalTrials.gov, number NCT02210221, and the Resource Identification Portal (Research Resource Identifier SCR_015582).Findings Between December 19, 2014 and December 17, 2017, 4559 patients with traumatic brain injury were enrolled in CENTER-TBI of whom 336 (7%) underwent acute surgery for ASDH evacuation; 91 (27%) underwent DC and 245 (63%) craniotomy. The proportion primary DC within total acute surgery cases ranged from 6 to 67% with an interquartile range (IQR) of 12-26% among 46 centres; the odds of receiving a DC for prognostically similar patients in one centre versus another randomly selected centre were trebled (adjusted median odds ratio 2.7, p < 0.0001). Higher centre preference for DC over craniotomy was not associated with better functional outcome (adjusted common odds ratio (OR) per 14% [IQR increase] more DC in a centre = 0.9 [95% CI 0.7-1.1], n = 200). Primary DC was associated with more follow-on surgeries and complications [secondary cranial surgery 27% vs. 18%; shunts 11 vs. 5%]; and similar odds of in-hospital mortality (adjusted OR per 14% IQR more primary DC 1.3 [95% CI (1.0-3.4), n = 200]).Interpretation We found substantial practice variation in the employment of DC over craniotomy for ASDH. This variation in treatment strategy did not result in different functional outcome. These findings suggest that primary DC should be restricted to salvageable patients in whom immediate replacement of the bone flap is not possible due to intraoperative brain swelling. Show less
Kaplan, Z.L.R.; Vlegel, M. van der; Dijck, J.T.J.M. van; Pisica, D.; Leeuwen, N. van; Lingsma, H.F.; ... ; CENTER TBI Participants Invest 2023
Traumatic brain injury (TBI) is a global public health problem and a leading cause of mortality, morbidity, and disability. The increasing incidence combined with the heterogeneity and complexity... Show moreTraumatic brain injury (TBI) is a global public health problem and a leading cause of mortality, morbidity, and disability. The increasing incidence combined with the heterogeneity and complexity of TBI will inevitably place a substantial burden on health systems. These findings emphasize the importance of obtaining accurate and timely insights into healthcare consumption and costs on a multi-national scale. This study aimed to describe intramural healthcare consumption and costs across the full spectrum of TBI in Europe. The Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) core study is a prospective observational study conducted in 18 countries across Europe and in Israel. The baseline Glasgow Coma Scale (GCS) was used to differentiate patients by brain injury severity in mild (GCS 13-15), moderate (GCS 9-12), or severe (GCS & LE;8) TBI. We analyzed seven main cost categories: pre-hospital care, hospital admission, surgical interventions, imaging, laboratory, blood products, and rehabilitation. Costs were estimated based on Dutch reference prices and converted to country-specific unit prices using gross domestic product (GDP)-purchasing power parity (PPP) adjustment. Mixed linear regression was used to identify between-country differences in length of stay (LOS), as a parameter of healthcare consumption. Mixed generalized linear models with gamma distribution and log link function quantified associations of patient characteristics with higher total costs. We included 4349 patients, of whom 2854 (66%) had mild, 371 (9%) had moderate, and 962 (22%) had severe TBI. Hospitalization accounted for the largest part of the intramural consumption and costs (60%). In the total study population, the mean LOS was 5.1 days at the intensive care unit (ICU) and 6.3 days at the ward. For mild, moderate, and severe TBI, mean LOS was, respectively, 1.8, 8.9, and 13.5 days at the ICU and 4.5, 10.1, and 10.3 days at the ward. Other large contributors to the total costs were rehabilitation (19%) and intracranial surgeries (8%). Total costs increased with higher age and greater trauma severity (mild; euro3,800 [IQR euro1,400-14,000], moderate; euro37,800 [IQR euro14,900-euro74,200], severe; euro60,400 [IQR euro24,400-euro112,700]). The adjusted analysis showed that female patients had lower costs than male patients (odds ratio (OR) 0.80 [CI 0.75-1.85]). Increasing TBI severity was associated with higher costs, OR 1.46 (confidence interval [CI] 1.31-1.63) and OR 1.67 [CI 1.52-1.84] for moderate and severe patients, respectively. A worse pre-morbid overall health state, increasing age and more severe systemic trauma, expressed in the Injury Severity Score (ISS), were also significantly associated with higher costs. Intramural costs of TBI are significant and are profoundly driven by hospitalization. Costs increased with trauma severity and age, and male patients incurred higher costs. Reducing LOS could be targeted with advanced care planning, in order to provide cost-effective care. Show less
BACKGROUND: Investigating neurosurgical interventions for traumatic brain injury (TBI) involves complex methodological and practical challenges. In the present report, we have provided an overview... Show moreBACKGROUND: Investigating neurosurgical interventions for traumatic brain injury (TBI) involves complex methodological and practical challenges. In the present report, we have provided an overview of the current state of neurosurgical TBI research and discussed the key challenges and possible solutions. METHODS: The content of our report was based on an extensive literature review and personal knowledge and expert opinions of senior neurosurgeon researchers and epidemiologists. RESULTS: Current best practice research strategies include randomized controlled trials (RCTs) and comparative effectiveness research. The performance of RCTs has been complicated by the heterogeneity of TBI patient populations with the associated sample size requirements, the traditional eminence-based neurosurgical culture, inadequate research budgets, and the often acutely life-threatening setting of severe TBI. Statistical corrections can mitigate the effects of heterogeneity, and increasing awareness of clinical equipoise and informed consent alternatives can improve trial efficiency. The substantial confounding by indication, which limits the interpretability of observational research, can be circumvented by using an instrumental variable analysis. Traditional TBI outcome measures remain relevant but do not adequately capture the subtleties of well-being, suggesting a need for multidimensional approaches to outcome assessments. CONCLUSIONS: In settings in which traditional RCTs are difficult to conduct and substantial confounding by indication can be present, observational studies using an instrumental variable analysis and "pragmatic" RCTs are promising alternatives. Embedding TBI research into standard clinical practice should be more frequently considered but will require fundamental modifications to the current health care system. Finally, multimodality outcome assessment will be key to improving future surgical and nonsurgical TBI research. Show less
Background: The rapidly increasing number of elderly (>= 65 years old) with TBI is accompanied by substantial medical and economic consequences. An ASDH is the most common injury in elderly with... Show moreBackground: The rapidly increasing number of elderly (>= 65 years old) with TBI is accompanied by substantial medical and economic consequences. An ASDH is the most common injury in elderly with TBI and the surgical versus conservative treatment of this patient group remains an important clinical dilemma. Current BTF guidelines are not based on high-quality evidence and compliance is low, allowing for large international treatment variation. The RESET-ASDH trial is an international multicenter RCT on the (cost-)effectiveness of early neurosurgical hematoma evacuation versus initial conservative treatment in elderly with a t-ASDHMethods: In total, 300 patients will be recruited from 17 Belgian and Dutch trauma centers. Patients >= 65 years with at first presentation a GCS >= 9 and a t-ASDH > 10 mm or a t-ASDH < 10 mm and a midline shift > 5 mm, or a GCS < 9 with a traumatic ASDH < 10 mm and a midline shift < 5 mm without extracranial explanation for the comatose state, for whom clinical equipoise exists will be randomized to early surgical hematoma evacuation or initial conservative management with the possibility of delayed secondary surgery. When possible, patients or their legal representatives will be asked for consent before inclusion. When obtaining patient or proxy consent is impossible within the therapeutic time window, patients are enrolled using the deferred consent procedure. Medical-ethical approval was obtained in the Netherlands and Belgium. The choice of neurosurgical techniques will be left to the discretion of the neurosurgeon. Patients will be analyzed according to an intention-to-treat design. The primary endpoint will be functional outcome on the GOS-E after 1 year. Patient recruitment starts in 2022 with the exact timing depending on the current COVID-19 crisis and is expected to end in 2024.Discussion: The study results will be implemented after publication and presented on international conferences. Depending on the trial results, the current Brain Trauma Foundation guidelines will either be substantiated by high-quality evidence or will have to be altered. Show less
Mostert, C.Q.B.; Singh, R.D.; Gerritsen, M.; Kompanje, E.J.O.; Ribbers, G.M.; Peul, W.C.; Dijck, J.T.J.M. van 2022
Background: Expectation of long-term outcome is an important factor in treatment decision-making after severe traumatic brain injury (sTBI). Conclusive long-term outcome data substantiating these... Show moreBackground: Expectation of long-term outcome is an important factor in treatment decision-making after severe traumatic brain injury (sTBI). Conclusive long-term outcome data substantiating these decisions is nowadays lacking. This systematic review aimed to provide an overview of the scientific literature on long-term outcome after sTBI. Methods: A systematic search was conducted using PubMed from 2008 to 2020. Studies were included when reporting long-term outcome >= 2 years after sTBI (GCS 3-8 or AIS head score >= 4), using standardized outcome measures. Study quality and risk of bias were assessed using the QUIPS tool. Results: Twenty observational studies were included. Studies showed substantial variation in study objectives and study methodology. GOS-E (n = 12) and GOS (n = 8) were the most frequently used outcome measures. Mortality was reported in 46% of patients (range 18-75%). Unfavourable outcome rates ranged from 29 to 100% and full recovery was seen in 21-27% of patients. Most surviving patients reported SF-36 scores lower than the general population. Conclusion: Literature on long-term outcome after sTBI was limited and heterogeneous. Mortality and unfavourable outcome rates were high and persisting sequelae on multiple domains common. Nonetheless, a considerable proportion of survivors achieved favourable outcome. Future studies should incorporate standardized multidimensional and temporal long-term outcome measures to strengthen the evidence-base for acute and subacute decision-making. Show less
Even after thousands of years of experience in treating patients with TBI, decisions regarding the optimal treatment strategy remain difficult for both healthcare workers as policy makers. The... Show moreEven after thousands of years of experience in treating patients with TBI, decisions regarding the optimal treatment strategy remain difficult for both healthcare workers as policy makers. The first part of this thesis investigated the challenges of the treatment decision-making process in patients with (severe) TBI by focussing on three factors considered to be important in this process: patient outcome, in-hospital healthcare consumption, and in-hospital costs. The second part investigated the procedural difficulties in TBI research efficiency by focussing on the process of institutional review board approval and the use of informed consent procedures in patients with TBI with an inability to provide informed consent. Finally, we elaborate on the role of patient outcome and in-hospital costs in the acute treatment decision-making process in patients with severe TBI and make suggestions to optimize future research initiatives. Show less
Health-care professionals and researchers have a legal and ethical responsibility to inform patients before carrying out diagnostic tests or treatment interventions as part of a clinical study.... Show moreHealth-care professionals and researchers have a legal and ethical responsibility to inform patients before carrying out diagnostic tests or treatment interventions as part of a clinical study. Interventional research in emergency situations can involve patients with some degree of acute cognitive impairment, as is regularly the case in traumatic brain injury and ischaemic stroke. These patients or their proxies are often unable to provide informed consent within narrow therapeutic time windows. International regulations and national laws are criticised for being inconclusive or restrictive in providing solutions. Currently accepted consent alternatives are deferred consent, exception from consent, or waiver of consent. However, these alternatives appear under-utilised despite being ethically permissible, socially acceptable, and regulatorily compliant. We anticipate that, when the requirements for medical urgency are properly balanced with legal and ethical conduct, the increased use of these alternatives has the potential to improve the efficiency and quality of future emergency interventional studies in patients with an inability to provide informed consent. Show less
Wijk, R.P.J. van; Dijck, J.T.J.M. van; Timmers, M.; Veen, E. van; Citerio, G.; Lingsma, H.F.; ... ; CENTER-TB1 Investigators 2020
Purpose: Enrolling traumatic brain injury (731) patients with an inability to provide informed consent in research is challenging. Alternatives to patient consent are not sufficiently embedded in... Show morePurpose: Enrolling traumatic brain injury (731) patients with an inability to provide informed consent in research is challenging. Alternatives to patient consent are not sufficiently embedded in European and national legislation, which allows procedural variation and bias. We aimed to quantify variations in informed consent policy and practice.Methods: Variation was explored in the CENTER-TBI study. Policies were reported by using a questionnaire and national legislation. Data on used informed consent procedures were available for 4498 patients from 57 centres across 17 European countries.Results: Variation in the use of informed consent procedures was found between and within EU member states. Proxy informed consent (N = 1377;64%) was the most frequently used type of consent in the ICU, followed by patient informed consent (N 426;20%) and deferred consent (N 334;16%). Deferred consent was only actively used in 15 centres (26%), although it was considered valid in 47 centres (82%).Conclusions: Alternatives to patient consent are essential for TBI research. While there seems to be concordance amongst national legislations, there is regional variability in institutional practices with respect to the use of different informed consent procedures. Variation could be caused by several reasons, including inconsistencies in clear legislation or knowledge of such legislation amongst researchers. (C) 2020 Published by Elsevier Inc. Show less
AbstractBackground: The high occurrence and acute and chronic sequelae of traumatic brain injury (TBI) cause major healthcare and socioeconomic challenges. This study aimed to describe outcome, in... Show moreAbstractBackground: The high occurrence and acute and chronic sequelae of traumatic brain injury (TBI) cause major healthcare and socioeconomic challenges. This study aimed to describe outcome, in-hospital healthcare consumption and in-hospital costs of patients with TBI.Methods: We used data from hospitalised TBI patients that were included in the prospective observational CENTER-TBI study in three Dutch Level I Trauma Centres from 2015 to 2017. Clinical data was completed with data on in-hospital healthcare consumption and costs. TBI severity was classified using the Glasgow Coma Score (GCS). Patient outcome was measured by in-hospital mortality and Glasgow Outcome Score-Extended (GOSE) at 6 months. In-hospital costs were calculated following the Dutch guidelines for cost calculation.Results: A total of 486 TBI patients were included. Mean age was 56.1 ± 22.4 years and mean GCS was 12.7 ± 3.8. Six-month mortality (4.2%-66.7%), unfavourable outcome (GOSE ≤ 4) (14.6%-80.4%) and full recovery (GOSE = 8) (32.5%-5.9%) rates varied from patients with mild TBI (GCS13-15) to very severe TBI (GCS3-5). Length of stay (8 ± 13 days) and in-hospital costs (€11,920) were substantial and increased with higher TBI severity, presence of intracranial abnormalities, extracranial injury and surgical intervention. Costs were primarily driven by admission (66%) and surgery (13%).Conclusion: In-hospital mortality and unfavourable outcome rates were rather high, but many patients also achieved full recovery. Hospitalised TBI patients show substantial in-hospital healthcare consumption and costs, even in patients with mild TBI. Because these costs are likely to be an underestimation of the actual total costs, more research is required to investigate the actual costs-effectiveness of TBI care.Keywords: Functional outcome; In-hospital costs; Mortality; Traumatic brain injury. Show less
AbstractBackground: The European Union (EU) aims to optimize patient protection and efficiency of health-care research by harmonizing procedures across Member States. Nonetheless, further... Show moreAbstractBackground: The European Union (EU) aims to optimize patient protection and efficiency of health-care research by harmonizing procedures across Member States. Nonetheless, further improvements are required to increase multicenter research efficiency. We investigated IRB procedures in a large prospective European multicenter study on traumatic brain injury (TBI), aiming to inform and stimulate initiatives to improve efficiency.Methods: We reviewed relevant documents regarding IRB submission and IRB approval from European neurotrauma centers participating in the Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI). Documents included detailed information on IRB procedures and the duration from IRB submission until approval(s). They were translated and analyzed to determine the level of harmonization of IRB procedures within Europe.Results: From 18 countries, 66 centers provided the requested documents. The primary IRB review was conducted centrally (N = 11, 61%) or locally (N = 7, 39%) and primary IRB approval was obtained after one (N = 8, 44%), two (N = 6, 33%) or three (N = 4, 23%) review rounds with a median duration of respectively 50 and 98 days until primary IRB approval. Additional IRB approval was required in 55% of countries and could increase duration to 535 days. Total duration from submission until required IRB approval was obtained was 114 days (IQR 75-224) and appeared to be shorter after submission to local IRBs compared to central IRBs (50 vs. 138 days, p = 0.0074).Conclusion: We found variation in IRB procedures between and within European countries. There were differences in submission and approval requirements, number of review rounds and total duration. Research collaborations could benefit from the implementation of more uniform legislation and regulation while acknowledging local cultural habits and moral values between countries.Keywords: CENTER-TBI; European Union; Harmonization; Health-care research; Research ethic committees. Show less
Background Traumatic brain injury is associated with high rates of mortality and morbidity. Trauma patients with a coagulopathy have a 10-fold increased mortality risk compared to patients without... Show moreBackground Traumatic brain injury is associated with high rates of mortality and morbidity. Trauma patients with a coagulopathy have a 10-fold increased mortality risk compared to patients without a coagulopathy. The aim of this study was to identify the incidence of coagulopathy and relate early coagulopathy to clinical outcome in patients with traumatic intracranial hemorrhages. Methods Between September 2015 and December 2016, 108 consecutive cranial trauma patients with traumatic intracranial hemorrhages were included in this study. To assess the relationship between patients with a coagulopathy and outcome, a chi-squared test was performed. Results A total of 29 out of the 108 patients (27%) with a traumatic intracranial hemorrhage developed a coagulopathy within 72 h after admission. Overall, a total of 22 patients (20%) died after admission of which ten were coagulopathic at emergency department presentation. Early coagulopathy in patients with traumatic brain injury is associated with progression of hemorrhagic injury (odds ratio 2.4 (95% confidence interval 0.8-8.0)), surgical intervention (odds ratio 2.8 (95% confidence interval 0.87-9.35)), and increased in-hospital mortality (odds ratio 23.06 (95% confidence interval 5.5-95.9)). Conclusion Patients who sustained a traumatic intracranial hemorrhage remained at risk for developing a coagulopathy until 72 h after trauma. Patients who developed a coagulopathy had a worse clinical outcome than patients who did not develop a coagulopathy. Show less
Purpose of reviewThere is an urgent need to discuss the uncertainties and paradoxes in clinical decision-making after severe traumatic brain injury (s-TBI). This could improve transparency, reduce... Show morePurpose of reviewThere is an urgent need to discuss the uncertainties and paradoxes in clinical decision-making after severe traumatic brain injury (s-TBI). This could improve transparency, reduce variability of practice and enhance shared decision-making with proxies.Recent findingsClinical decision-making on initiation, continuation and discontinuation of medical treatment may encompass substantial consequences as well as lead to presumed patient benefits. Such decisions, unfortunately, often lack transparency and may be controversial in nature. The very process of decision- making is frequently characterized by both a lack of objective criteria and the absence of validated prognostic models that could predict relevant outcome measures, such as long-term quality and satisfaction with life. In practice, while treatment-limiting decisions are often made in patients during the acute phase immediately after s-TBI, other such severely injured TBI patients have been managed with continued aggressive medical care, and surgical or other procedural interventions have been undertaken in the context of pursuing a more favorable patient outcome. Given this spectrum of care offered to identical patient cohorts, there is clearly a need to identify and decrease existing selectivity, and better ascertain the objective criteria helpful towards more consistent decision-making and thereby reduce the impact of subjective valuations of predicted patient outcome.SummaryRecent efforts by multiple medical groups have contributed to reduce uncertainty and to improve care and outcome along the entire chain of care. Although an unlimited endeavor for sustaining life seems unrealistic, treatment-limiting decisions should not deprive patients of a chance on achieving an outcome they would have considered acceptable. Show less
BackgroundThe in-hospital treatment of patients with traumatic brain injury (TBI) is considered to be expensive, especially in patients with severe TBI (s-TBI). To improve future treatment deci-... Show moreBackgroundThe in-hospital treatment of patients with traumatic brain injury (TBI) is considered to be expensive, especially in patients with severe TBI (s-TBI). To improve future treatment deci- sion-making, resource allocation and research initiatives, this study reviewed the in-hospital costs for patients with s-TBI and the quality of study methodology.MethodsA systematic search was performed using the following databases: PubMed, MEDLINE, Embase, Web of Science, Cochrane library, CENTRAL, Emcare, PsychINFO, Academic Search Premier and Google Scholar. Articles published before August 2018 reporting in- hospital acute care costs for patients with s-TBI were included. Quality was assessed by using a 19-item checklist based on the CHEERS statement.ResultsTwenty-five out of 2372 articles were included. In-hospital costs per patient were generally high and ranged from $2,130 to $401,808. Variation between study results was primarily caused by methodological heterogeneity and variable patient and treatment characteristics. The quality assessment showed variable study quality with a mean total score of 71% (range 48% - 96%). Especially items concerning cost data scored poorly (49%) because data source, cost calculation methodology and outcome reporting were regularly unmen- tioned or inadequately reported.ConclusionsHealthcare consumption and in-hospital costs for patients with s-TBI were high and varied widely between studies. Costs were primarily driven by the length of stay and surgical inter- vention and increased with higher TBI severity. However, drawing firm conclusions on the actual in-hospital costs of patients sustaining s-TBI was complicated due to variation and inadequate quality of the included studies. Future economic evaluations should focus on the long-term cost-effectiveness of treatment strategies and use guideline recommendations and common data elements to improve study quality. Show less
Veen, E. van; Jagt, M. van der; Cnossen, M.C.; Maas, A.I.R.; Beaufort, I.D. de; Menon, D.K.; ... ; CENTER-TBI Investigators 2018
