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 The role of glucocorticoids without surgical evacuation in the treatment of chronic subdural hematoma is unclear.METHODS In this multicenter, open-label, controlled, noninferiority trial... Show moreBACKGROUND The role of glucocorticoids without surgical evacuation in the treatment of chronic subdural hematoma is unclear.METHODS In this multicenter, open-label, controlled, noninferiority trial, we randomly assigned symptomatic patients with chronic subdural hematoma in a 1:1 ratio to a 19-day tapering course of dexamethasone or to burr-hole drainage. The primary end point was the functional outcome at 3 months after randomization, as assessed by the score on the modified Rankin scale (range, 0 [no symptoms] to 6 [death]). Non-inferiority was defined by a lower limit of the 95% confidence interval of the odds ratio for a better functional outcome with dexamethasone than with surgery of 0.9 or more. Secondary end points included scores on the Markwalder Grading Scale of symptom severity and on the Extended Glasgow Outcome Scale.RESULTS From September 2016 through February 2021, we enrolled 252 patients of a planned sample size of 420; 127 were assigned to the dexamethasone group and 125 to the surgery group. The mean age of the patients was 74 years, and 77% were men. The trial was terminated early by the data and safety monitoring board owing to safety and outcome concerns in the dexamethasone group. The adjusted common odds ratio for a lower (better) score on the modified Rankin scale at 3 months with dexamethasone than with surgery was 0.55 (95% confidence interval, 0.34 to 0.90), which failed to show noninferiority of dexamethasone. The scores on the Markwalder Grading Scale and Extended Glasgow Outcome Scale were generally supportive of the results of the primary analysis. Complications occurred in 59% of the patients in the dexamethasone group and 32% of those in the surgery group, and additional surgery was performed in 55% and 6%, respectively.CONCLUSIONS In a trial that involved patients with chronic subdural hematoma and that was stopped early, dexamethasone treatment was not found to be noninferior to burrhole drainage with respect to functional outcomes and was associated with more complications and a greater likelihood of later surgery. (Funded by the Netherlands Organization for Health Research and Development and others; DECSA EudraCT number, 2015-001563 -39.) Show less
Duvekot, M.H.C.; Garcia, B.L.; Dekker, L.; Nguyen, T.M.; Wijngaard, I.R. van den; Laat, K.F. de; ... ; Venema, E. 2023
Background and purposeDirect transportation to a thrombectomy-capable intervention center is beneficial for patients with ischemic stroke due to large vessel occlusion (LVO), but can delay... Show moreBackground and purposeDirect transportation to a thrombectomy-capable intervention center is beneficial for patients with ischemic stroke due to large vessel occlusion (LVO), but can delay intravenous thrombolytics (IVT). The aim of this modeling study was to estimate the effect of prehospital triage strategies on treatment delays and overtriage in different regions.MethodsWe used data from two prospective cohort studies in the Netherlands: the Leiden Prehospital Stroke Study and the PRESTO study. We included stroke code patients within 6 h from symptom onset. We modeled outcomes of Rapid Arterial oCclusion Evaluation (RACE) scale triage and triage with a personalized decision tool, using drip-and-ship as reference. Main outcomes were overtriage (stroke code patients incorrectly triaged to an intervention center), reduced delay to endovascular thrombectomy (EVT), and delay to IVT.ResultsWe included 1798 stroke code patients from four ambulance regions. Per region, overtriage ranged from 1-13% (RACE triage) and 3-15% (personalized tool). Reduction of delay to EVT varied by region between 24 ± 5 min (n = 6) to 78 ± 3 (n = 2), while IVT delay increased with 5 (n = 5) to 15 min (n = 21) for non-LVO patients. The personalized tool reduced delay to EVT for more patients (25 ± 4 min [n = 8] to 49 ± 13 [n = 5]), while delaying IVT with 3-14 min (8-24 patients). In region C, most EVT patients were treated faster (reduction of delay to EVT 31 ± 6 min (n = 35), with RACE triage and the personalized tool.ConclusionsIn this modeling study, we showed that prehospital triage reduced time to EVT without disproportionate IVT delay, compared to a drip-and-ship strategy. The effect of triage strategies and the associated overtriage varied between regions. Implementation of prehospital triage should therefore be considered on a regional level. Show less
Background: Endovascular thrombectomy (EVT) through femoral access is difficult to perform in some patients with acute ischemic stroke due to challenging vasculature. We compared outcomes of EVT... Show moreBackground: Endovascular thrombectomy (EVT) through femoral access is difficult to perform in some patients with acute ischemic stroke due to challenging vasculature. We compared outcomes of EVT through femoral versus alternative arterial access. Methods: In this observational study, we included patients from the MR CLEAN Registry who underwent EVT for acute ischemic stroke in the anterior circulation between 2014 and 2019 in the Netherlands. Patients who underwent EVT through alternative and femoral access were matched on propensity scores in a 1:3 ratio. The primary endpoint was favorable functional outcome (modified Rankin Scale score ≤ 2) at 90 days. Secondary endpoints were early neurologic recovery, mortality, successful intracranial reperfusion and puncture related complications. Results: Of the 5197 included patients, 17 patients underwent EVT through alternative access and were matched to 48 patients who underwent EVT through femoral access. Alternative access was obtained through the common carotid artery (n = 15/17) and brachial artery (n = 2/17). Favorable functional outcome was less often observed after EVT through alternative than femoral access (18% versus 27%; aOR, 0.36; 95% CI, 0.05–2.74). The rate of successful intracranial reperfusion was higher for alternative than femoral access (88% versus 58%), although mortality (59% versus 31%) and puncture related complications (29% versus 0%) were more common after alternative access. Conclusions: EVT through alternative arterial access is rarely performed in the Netherlands and seems to be associated with worse outcomes than standard femoral access. A next step would be to compare the additional value of EVT through alternative arterial access after failure of femoral access. Show less
Background: Guillain-Barre ' syndrome (GBS) has a highly variable clinical course and outcome as indicated by the risk of developing respiratory failure and residual inability to walk. Prognostic... Show moreBackground: Guillain-Barre ' syndrome (GBS) has a highly variable clinical course and outcome as indicated by the risk of developing respiratory failure and residual inability to walk. Prognostic models as Erasmus GBS Respi-ratory Insufficiency Score (EGRIS) developed in adult patients are inaccurate in children. Our aim was to determine the prognostic factors of respiratory failure and inability to walk in children with GBS and to develop a new clinical prognostic model for individual patients (EGRIS-Kids).Methods: A multicenter retrospective cohort study was performed using the data of children (younger than 18 years) fulfilling the diagnostic criteria for GBS from the NINDS. This study was performed in two independent cohorts from centers in Germany, Switzerland, Austria (N = 265, collected 1989-2002) and The Netherlands (N = 156, collected 1987-2016). The predicted main outcomes were occurrence of respiratory failure during the disease course and inability to walk independent at one year after diagnosis. Results: In the combined cohort of 421 children, 79 (19%) required mechanical ventilation and one patient died. The EGRIS-kids was developed including: age, cranial nerve involvement and GBS disability score at admission, resulting in a 9 point score predicting risks of respiratory failure ranging from 4 to 50% (AUC = 0.71). A lower GBS disability score at nadir was the strongest predictor of recovery to independent walking (at one month: OR 0.43 95%CI 0.25-0.74).Conclusions: EGRIS-Kids and GBS disability score at admission accurately predict the risk of respiratory failure and inability to walk respectively in children with GBS, as tools to personalize the monitoring and treatment. Show less
Blaauw, J.; Hertog, H.M.D.; Holl, D.C.; Thuss, N.S.; Gaag, N.A. van der; Jellema, K.; ... ; Naalt, J. van der 2023
ObjectiveChronic subdural hematoma (CSDH) is a common neurological condition, often affecting the elderly. Cognitive impairment is frequently observed at presentation. However, the course and... Show moreObjectiveChronic subdural hematoma (CSDH) is a common neurological condition, often affecting the elderly. Cognitive impairment is frequently observed at presentation. However, the course and longer term aspects of the cognitive status of CSDH patients are unknown. In this study, we aim to explore the cognitive status of CSDH patients after treatment.MethodsAn exploratory study in which CSDH patients were assessed 3 months after treatment and compared to healthy controls. A total of 56 CSDH patients (age 72.1 SD +/- 10.8 years with 43 [77%] males) and 60 healthy controls were included (age 67.5 +/- SD 4.8 with 34 [57%] males). Cognitive testing was performed using the Telephonic Interview of Cognitive Status-modified (TICS-m), a 12-item questionnaire in which a total of 50 points can be obtained on several cognitive domains.ResultsMedian time between treatment and cognitive testing was 93 days (range 76-139). TICS-m scores of CSDH patients were significantly lower than healthy controls, after adjusting for age and sex: mean score 34.6 (95% CI: 33.6-35.9) vs. 39.6 (95% CI: 38.5-40.7), p value < 0.001. More than half (54%) of CSDH patients have cognitive scores at follow-up that correspond with cognitive impairment.ConclusionA large number of CSDH patients show significantly worse cognitive status 3 months after treatment compared to healthy controls. This finding underlines the importance of increased awareness for impaired cognition after CSDH. Further research on this topic is warranted. Show less
The main treatment strategy for chronic subdural hematoma is surgical intervention. When a conservative pharmacological approach is considered in symptomatic patients, mainly dexamethasone therapy... Show moreThe main treatment strategy for chronic subdural hematoma is surgical intervention. When a conservative pharmacological approach is considered in symptomatic patients, mainly dexamethasone therapy is applied. Recent trials revealed dexamethasone therapy to be an ineffective treatment in symptomatic patients with chronic subdural hematoma. Whether the efficacy of dexamethasone therapy differs in radiological hematoma subtypes is unknown. The aim of this substudy was to identify which hematoma subtype might be favorable for dexamethasone therapy. As part of a randomized controlled trial, symptomatic chronic subdural hematoma patients received 19-days dexamethasone therapy. The primary outcome measure was the change in hematoma size as measured on follow-up computed tomography (CT) after 2 weeks of dexamethasone in six hematoma (architectural and density) subtypes: homogeneous total, laminar, separated and trabecular architecture types, and hematoma without hyperdense components (homogeneous hypodense, isodense) and with hyperdense components (homogeneous hyperdense, mixed density). We analyzed hematoma thickness, midline shift, and volume using multi-variable linear regression adjusting for age, sex and baseline value of the specific radiological parameter. From September 2016 until February 2021, 85 patients were included with a total of 114 chronic subdural hematoma. The mean age was 76 years and 25% were women. Larger decrease in hematoma thickness and midline shift was revealed in hematoma without hyperdense components compared with hematoma with hyperdense components (adjusted [adj.] b -2.2 mm, 95% confidence interval [CI] -4.1 to -0.3 and adj. b -1.3 mm, 95% CI -2.7 to 0.0 respectively). Additional surgery was performed in 57% of patients with the highest observed rate (81%) in separated hematoma. Largest hematoma reduction and better clinical improvement was observed in chronic subdural hematoma without hyperdense components after dexamethasone therapy. Evaluation of these parameters can be part of an individualized treatment strategy. Show less
Miah, I.P.; Blanter, A.; Tank, Y.; Zwet, E.W. van; Rosendaal, F.R.; Peul, W.C.; ... ; Gaag, N.A. van der 2022
The main treatment strategy for chronic subdural hematoma is surgical intervention. When a conservative pharmacological approach is considered in symptomatic patients, mainly dexamethasone therapy... Show moreThe main treatment strategy for chronic subdural hematoma is surgical intervention. When a conservative pharmacological approach is considered in symptomatic patients, mainly dexamethasone therapy is applied. Recent trials revealed dexamethasone therapy to be an ineffective treatment in symptomatic patients with chronic subdural hematoma. Whether the efficacy of dexamethasone therapy differs in radiological hematoma subtypes is unknown. The aim of this substudy was to identify which hematoma subtype might be favorable for dexamethasone therapy. As part of a randomized controlled trial, symptomatic chronic subdural hematoma patients received 19-days dexamethasone therapy. The primary outcome measure was the change in hematoma size as measured on follow-up computed tomography (CT) after 2 weeks of dexamethasone in six hematoma (architectural and density) subtypes: homogeneous total, laminar, separated and trabecular architecture types, and hematoma without hyperdense components (homogeneous hypodense, isodense) and with hyperdense components (homogeneous hyperdense, mixed density). We analyzed hematoma thickness, midline shift, and volume using multi-variable linear regression adjusting for age, sex and baseline value of the specific radiological parameter. From September 2016 until February 2021, 85 patients were included with a total of 114 chronic subdural hematoma. The mean age was 76 years and 25% were women. Larger decrease in hematoma thickness and midline shift was revealed in hematoma without hyperdense components compared with hematoma with hyperdense components (adjusted [adj.] b -2.2 mm, 95% confidence interval [CI] -4.1 to -0.3 and adj. b -1.3 mm, 95% CI -2.7 to 0.0 respectively). Additional surgery was performed in 57% of patients with the highest observed rate (81%) in separated hematoma. Largest hematoma reduction and better clinical improvement was observed in chronic subdural hematoma without hyperdense components after dexamethasone therapy. Evaluation of these parameters can be part of an individualized treatment strategy. Show less
Purpose: Chronic subdural hematoma (CSDH) is a common neurological disease often affecting the elderly. Long-term excess mortality for patients after CSDH has been suggested but causes of death are... Show morePurpose: Chronic subdural hematoma (CSDH) is a common neurological disease often affecting the elderly. Long-term excess mortality for patients after CSDH has been suggested but causes of death are unknown. We hypothesize that excess mortality of CSDH patients is related to frailty. In this article, we describe mortality rates and causes of death of CSDH patients compared with the general population and assess the association of frailty with mortality. Methods: A cohort study in which consecutive CSDH patients were compared to the general population regarding mortality rates. Furthermore, the association of six frailty indicators (cognitive problems, frequent falling, unable to live independently, unable to perform daily self-care, use of benzodiazepines or psychotropic drugs, and number of medications) with mortality was assessed. Results: A total of 1307 CSDH patients were included, with a mean age of 73.7 (SD +/- 11.4) years and 958 (73%) were male. Median follow-up was 56 months (range: 0-213). Compared with controls CSDH patients had a hazard ratio for mortality of 1.34 (95% CI: 1.2-1.5). CSDH patients more often died from cardiovascular diseases (37% vs. 30%) and falls (7.2% vs. 3.7%). Among CSDH patients frequent falling (HR 1.3; 95% CI: 1.0-1.7), inability to live independently (HR 1.4, 95% CI: 1.1-1.8), inability to perform daily self-care (HR 1.5; 95% CI: 1.1-1.9), and number of medications used (HR 1.0; 95% CI: 1.0-1.1) were independently associated with mortality. Conclusions: CSDH patients have higher mortality rates than the general population. Frailty in CSDH patients is associated with higher mortality risk. More attention for the frailty of CSDH patients is warranted. Show less
Steen, W. van der; Ende, N.A.M. van der; Kranendonk, K.R. van; Chalos, V.; Oostenbrugge, R.J. van; Zwam, W.H. van; ... ; MR CLEAN Trial MR CLEAN Registry 2022
BACKGROUND: Symptomatic intracranial hemorrhage (sICH) is a serious complication after endovascular treatment for ischemic stroke. We aimed to identify determinants of its occurrence and location... Show moreBACKGROUND: Symptomatic intracranial hemorrhage (sICH) is a serious complication after endovascular treatment for ischemic stroke. We aimed to identify determinants of its occurrence and location.METHODS: We retrospectively analyzed data from the Dutch MR CLEAN trial (Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands) and MR CLEAN registry. We included adult patients with a large vessel occlusion in the anterior circulation who underwent endovascular treatment within 6.5 hours of stroke onset. We used univariable and multivariable logistic regression analyses to identify determinants of overall sICH occurrence, sICH within infarcted brain tissue, and sICH outside infarcted brain tissue.RESULTS: SICH occurred in 203 (6%) of 3313 included patients and was located within infarcted brain tissue in 50 (25%), outside infarcted brain tissue in 23 (11%), and both within and outside infarcted brain tissue in 116 (57%) patients. In 14 patients (7%), data on location were missing. Prior antiplatelet use, baseline systolic blood pressure, baseline plasma glucose levels, post-endovascular treatment modified treatment in cerebral ischemia score, and duration of procedure were associated with all outcome parameters. In addition, determinants of sICH within infarcted brain tissue included history of myocardial infarction (adjusted odds ratio, 1.65 [95% CI, 1.06-2.56]) and poor collateral score (adjusted odds ratio, 1.42 [95% CI, 1.02-1.95]), whereas determinants of sICH outside infarcted brain tissue included level of occlusion on computed tomography angiography (internal carotid artery or internal carotid artery terminus compared with M1: adjusted odds ratio, 1.79 [95% CI 1.16-2.78]).CONCLUSIONS: Several factors, some potentially modifiable, are associated with sICH occurrence. Further studies should investigate whether modification of baseline systolic blood pressure or plasma glucose level could reduce the risk of sICH. In addition, determinants differ per location of sICH, supporting the hypothesis of varying underlying mechanisms.[GRAPHICS]. Show less
Brand, C.L. van den; Foks, K.A.; Lingsma, H.F.; Naalt, J. van der; Jacobs, B.; Jong, E. de; ... ; Jellema, K. 2022
Objective: To update the existing CHIP (CT in Head Injury Patients) decision rule for detection of (in-tra)cranial findings in adult patients following minor head injury (MHI).Methods: The study is... Show moreObjective: To update the existing CHIP (CT in Head Injury Patients) decision rule for detection of (in-tra)cranial findings in adult patients following minor head injury (MHI).Methods: The study is a prospective multicenter cohort study in the Netherlands. Consecutive MHI pa-tients of 16 years and older were included. Primary outcome was any (intra)cranial traumatic finding on computed tomography (CT). Secondary outcomes were any potential neurosurgical lesion and neuro-surgical intervention. The CHIP model was validated and subsequently updated and revised. Diagnostic performance was assessed by calculating the c-statistic. Results: Among 4557 included patients 3742 received a CT (82%). In 383 patients (8.4%) a traumatic find-ing was present on CT. A potential neurosurgical lesion was found in 73 patients (1.6%) with 26 (0.6%) patients that actually had neurosurgery or died as a result of traumatic brain injury. The original CHIP underestimated the risk of traumatic (intra)cranial findings in low-predicted-risk groups, while in high -predicted-risk groups the risk was overestimated. The c-statistic of the original CHIP model was 0.72 (95% CI 0.69-0.74) and it would have missed two potential neurosurgical lesions and one patient that underwent neurosurgery. The updated model performed similar to the original model regarding trau-matic (intra)cranial findings (c-statistic 0.77 95% CI 0.74-0.79, after crossvalidation c-statistic 0.73). The updated CHIP had the same CT rate as the original CHIP (75%) and a similar sensitivity (92 versus 93%) and specificity (both 27%) for any traumatic (intra)cranial finding. However, the updated CHIP would not have missed any (potential) neurosurgical lesions and had a higher sensitivity for (potential) neurosurgi-cal lesions or death as a result of traumatic brain injury (100% versus 96%).Conclusions: Use of the updated CHIP decision rule is a good alternative to current decision rules for patients with MHI. In contrast to the original CHIP the update identified all patients with (potential) neurosurgical lesions without increasing CT rate.(c) 2022 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY license ( http://creativecommons.org/licenses/by/4.0/ ) Show less
Background The effectiveness of alteplase for ischemic stroke treatment is limited, partly due to the occurrence of intracranial and extracranial hemorrhage. Mutant pro-urokinase (m-proUK) does not... Show moreBackground The effectiveness of alteplase for ischemic stroke treatment is limited, partly due to the occurrence of intracranial and extracranial hemorrhage. Mutant pro-urokinase (m-proUK) does not deplete fibrinogen and lyses fibrin only after induction with alteplase. Therefore, this treatment has the potential to be safer and more efficacious than treatment with alteplase alone. The aim of this study is to assess the safety and efficacy of thrombolytic treatment consisting of a small bolus alteplase followed by m-proUK compared with standard thrombolytic treatment with alteplase in patients presenting with ischemic stroke. Methods DUMAS is a multicenter, phase II trial with a prospective randomized open-label blinded end-point (PROBE) design, and an adaptive design for dose optimization. Patients with ischemic stroke, who meet the criteria for treatment with intravenous (IV) alteplase can be included. Patients eligible for endovascular thrombectomy are excluded. Patients are randomly assigned (1:1) to receive a bolus of IV alteplase (5mg) followed by a continuous IV infusion of m-proUK (40 mg/h during 60 min) or usual care with alteplase (0.9 mg/kg). Depending on the results of interim analyses, the dose of m-proUK may be revised to a lower dose (30 mg/h during 60 min) or a higher dose (50 mg/h during 60 min). We aim to include 200 patients with a final diagnosis of ischemic stroke. The primary outcome is any post-intervention intracranial hemorrhage (ICH) on neuroimaging at 24 h according to the Heidelberg Bleeding Classification, analyzed with binary logistic regression. Efficacy outcomes include stroke severity measured with the National Institutes of Health Stroke Scale (NIHSS) at 24 h and 5-7 days, score on the modified Rankin scale (mRS) assessed at 30 days, change (pre-treatment vs. post-treatment) in abnormal perfusion volume, and blood biomarkers of thrombolysis at 24 h. Secondary safety endpoints include symptomatic intracranial hemorrhage, death, and major extracranial hemorrhage. This trial will use a deferred consent procedure. Discussion When dual thrombolytic therapy with a small bolus alteplase and m-proUK shows the anticipated effect on the outcome, this will lead to a 13% absolute reduction in the occurrence of ICH in patients with ischemic stroke. Show less
Background Treatment choices for individual patients with an inborn bleeding disorder are increasingly challenging due to increasing options and rising costs for society. We have initiated an... Show moreBackground Treatment choices for individual patients with an inborn bleeding disorder are increasingly challenging due to increasing options and rising costs for society. We have initiated an integrated interdisciplinary national research program. Objectives The SYMPHONY consortium strives to orchestrate personalized treatment in patients with an inborn bleeding disorder, by unraveling the mechanisms behind interindividual variations of bleeding phenotype. Patients The SYMPHONY consortium will investigate patients with an inborn bleeding disorder, both diagnosed and not yet diagnosed. Results Research questions are categorized under the themes: (1) diagnosis, (2) treatment, and (3) fundamental research, and consist of work packages addressing specific domains. Importantly, collaborations between patients and talented researchers from different areas of expertise promise to augment the impact of the SYMPHONY consortium, leading to unique interactions and intellectual property. Conclusions SYMPHONY will perform research on all aspects of care, treatment individualization in patients with inborn bleeding disorders, as well as diagnostic innovations and results of molecular genetics and cellular model technology with regard to the hemostatic process. We believe that these research investments will lead to health-care innovations with long-term clinical and societal impact. This consortium has been made possible by a governmental, competitive grant from the Netherlands Organization for Scientific Research (NWO) within the framework of the NWA-ORC Call grant agreement NWA.1160.18.038. Show less
Background Despite being well established, acute surgery in traumatic acute subdural haematoma is based on low-grade evidence. We aimed to compare the effectiveness of a strategy preferring acute... Show moreBackground Despite being well established, acute surgery in traumatic acute subdural haematoma is based on low-grade evidence. We aimed to compare the effectiveness of a strategy preferring acute surgical evacuation with one preferring initial conservative treatment in acute subdural haematoma.Methods We did a prospective, observational, comparative effectiveness study using data from participants enrolled in the Collaborative European Neurotrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) cohort. We included patients with no pre-existing severe neurological disorders who presented with acute subdural haematoma within 24 h of traumatic brain injury. Using an instrumental variable analysis, we compared outcomes between centres according to treatment preference for acute subdural haematoma (acute surgical evacuation or initial conservative treatment), measured by the case-mix-adjusted percentage of acute surgery per centre. The primary endpoint was functional outcome at 6 months as rated with the Glasgow Outcome Scale Extended, which was estimated with ordinal regression as a common odds ratio (OR) and adjusted for prespecified confounders. Variation in centre preference was quantified with the median OR (MOR). CENTER-TBI is registered with ClinicalTrials.gov , number NCT02210221, and the Resource Identification Portal (Research Resource Identifier SCR_015582).Findings Between Dec 19, 2014 and Dec 17, 2017, 4559 patients with traumatic brain injury were enrolled in CENTER-TBI, of whom 1407 (31%) presented with acute subdural haematoma and were included in our study. Acute surgical evacuation was done in 336 (24%) patients, by craniotomy in 245 (73%) of those patients and by decompressive craniectomy in 91 (27%). Delayed decompressive craniectomy or craniotomy after initial conservative treatment (n=982) occurred in 107 (11%) patients. The percentage of patients who underwent acute surgery ranged from 5.6% to 51.5% (IQR 12.3-35.9) between centres, with a two-times higher probability of receiving acute surgery for an identical patient in one centre versus another centre at random (adjusted MOR for acute surgery 1.8; p<0.0001]). Centre preference for acute surgery over initial conservative treatment was not associated with improvements in functional outcome (common OR per 23.6% [IQR increase] more acute surgery in a centre 0.92, 95% CI 0.77-1.09).Interpretation Our findings show that treatment for patients with acute subdural haematoma with similar characteristics differed depending on the treating centre, because of variation in the preferred approach. A treatment strategy preferring an aggressive approach of acute surgical evacuation over initial conservative treatment was not associated with better functional outcome. Therefore, in a patient with acute subdural haematoma for whom a neurosurgeon sees no clear superiority for acute surgery over conservative treatment, initial conservative treatment might be considered. Copyright (C) 2022 Published by Elsevier Ltd. All rights reserved. Show less
Objective: To compare outcomes between patients with primary external ventricular device (EVD)-driven treatment of intracranial hypertension and those with primary intraparenchymal monitor (IP)... Show moreObjective: To compare outcomes between patients with primary external ventricular device (EVD)-driven treatment of intracranial hypertension and those with primary intraparenchymal monitor (IP)-driven treatment.Methods: The CENTER-TBI study is a prospective, multicenter, longitudinal observational cohort study that enrolled patients of all TBI severities from 62 participating centers (mainly level I trauma centers) across Europe between 2015 and 2017. Functional outcome was assessed at 6 months and a year. We used multivariable adjusted instrumental variable (IV) analysis with "center" as instrument and logistic regression with covariate adjustment to determine the effect estimate of EVD on 6-month functional outcome. Results: A total of 878 patients of all TBI severities with an indication for intracranial pressure (ICP) monitoring were included in the present study, of whom 739 (84%) patients had an IP monitor and 139 (16%) an EVD. Patients included were predominantly male (74% in the IP monitor and 76% in the EVD group), with a median age of 46 years in the IP group and 48 in the EVD group. Six-month GOS-E was similar between IP and EVD patients (adjusted odds ratio (aOR) and 95% confidence interval [CI] OR 0.74 and 95% CI [0.36-1.52], adjusted IV analysis). The length of intensive care unit stay was greater in the EVD group than in the IP group (adjusted rate ratio [95% CI] 1.70 [1.34-2.12], IV analysis). One hundred eighty-seven of the 739 patients in the IP group (25%) required an EVD due to refractory ICPs. Conclusion: We found no major differences in outcomes of patients with TBI when comparing EVD-guided and IP monitor-guided ICP management. In our cohort, a quarter of patients that initially received an IP monitor required an EVD later for ICP control. The prevalence of complications was higher in the EVD group. Show less
BACKGROUND: We aimed to quantify the need for additional surgery in patients with chronic subdural hematoma (CSDH) primarily treated with dexamethasone and to identify patient characteristics... Show moreBACKGROUND: We aimed to quantify the need for additional surgery in patients with chronic subdural hematoma (CSDH) primarily treated with dexamethasone and to identify patient characteristics associated with additional surgery.METHODS: Data were retrospectively collected from 283 patients with CSDH, primarily treated with dexamethasone, in 3 hospitals from 2008 to 2018. Primary outcome was the need for additional surgery. The association between baseline characteristics and additional surgery was analyzed with univariable and multivariable logistic regression analysis and presented as adjusted odds ratios (aOR).RESULTS: In total, 283 patients with CSDH were included: 146 patients (51.6%) received 1 dexamethasone course (DXM group), 30 patients (10.6%) received 2 dexamethasone courses (DXM-DXM group), and 107 patients (37.8%) received additional surgery (DXM-SURG group). Patients who underwent surgery more often had a Mark-walder Grading Scale of 2 (as compared with 1, aOR 2.05; 95% confidence interval [CI] 0.90-4.65), used statins (aOR 2.09; 95% CI 1.01-4.33), had a larger midline shift (aOR 1.10 per mm; 95% CI 1.01-1.21) and had larger hematoma thickness (aOR 1.16 per mm; 95% CI 1.09-1.23), had a bilateral hematoma (aOR 1.85; 95% CI 0.90-3.79), and had a separated hematoma (as compared with homogeneous, aOR 1.77; 95% CI 0.72-4.38). Antithrombotics (aOR 0.45; 95% CI 0.21-0.95) and trabecular hematoma (as compared with homogeneous, aOR 0.31; 95% CI 0.12-0.77) were associated with a lower likelihood of surgery.CONCLUSIONS: More than one-third of patients with CSDH primarily treated with dexamethasone received additional surgery. These patients were more severely affected amongst others with larger hematomas. Show less
Large and complex data sets are increasingly available for research in critical care. To analyze these data, researchers use techniques commonly referred to as statistical learning or machine... Show moreLarge and complex data sets are increasingly available for research in critical care. To analyze these data, researchers use techniques commonly referred to as statistical learning or machine learning (ML). The latter is known for large successes in the field of diagnostics, for example, by identification of radiological anomalies. In other research areas, such as clustering and prediction studies, there is more discussion regarding the benefit and efficiency of ML techniques compared with statistical learning. In this viewpoint, we aim to explain commonly used statistical learning and ML techniques and provide guidance for responsible use in the case of clustering and prediction questions in critical care. Clustering studies have been increasingly popular in critical care research, aiming to inform how patients can be characterized, classified, or treated differently. An important challenge for clustering studies is to ensure and assess generalizability. This limits the application of findings in these studies toward individual patients. In the case of predictive questions, there is much discussion as to what algorithm should be used to most accurately predict outcome. Aspects that determine usefulness of ML, compared with statistical techniques, include the volume of the data, the dimensionality of the preferred model, and the extent of missing data. There are areas in which modern ML methods may be preferred. However, efforts should be made to implement statistical frameworks (e.g., for dealing with missing data or measurement error, both omnipresent in clinical data) in ML methods. To conclude, there are important opportunities but also pitfalls to consider when performing clustering or predictive studies with ML techniques. We advocate careful valuation of new data-driven findings. More interaction is needed between the engineer mindset of experts in ML methods, the insight in bias of epidemiologists, and the probabilistic thinking of statisticians to extract as much information and knowledge from data as possible, while avoiding harm. Show less
