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Sökning: WFRF:(Koskinen Lars Owe 1955 )

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  • Aineskog, Helena, et al. (författare)
  • Serum S100B correlates with health-related quality of life and functional outcome in patients at 1 year after aneurysmal subarachnoid haemorrhage
  • 2022
  • Ingår i: Acta Neurochirurgica. - : Springer Nature. - 0001-6268 .- 0942-0940. ; 164:8, s. 2209-2218
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Early, objective prognostication after aneurysmal subarachnoid haemorrhage (aSAH) is difficult. A biochemical marker would be desirable. Correlation has been found between levels of the protein S100 beta (S100B) and outcome after aSAH. Timing and clinical usefulness are under investigation.METHODS: Eighty-nine patients admitted within 48 h of aSAH were included. Modified ranking scale (mRS), EuroQoL health-related quality of life measure (EQ-5Dindex) and EuroQoL visual analogue scale (EQ-VAS) values were evaluated after 1 year. S100B was measured in blood samples collected at admission and up to day 10.RESULTS: S100B correlated significantly with EQ-5Dindex and mRS, but not EQ-VAS at 1 year after aSAH. A receiver operating characteristic analysis for peak S100B values (area under the curve 0.898, 95% confidence interval 0.828-0.968, p < 0.0001), with a cutoff of 0.4 μg/l, yielded 95.3% specificity and 68% sensitivity for predicting unfavourable outcome. Dichotomized S100B (> 0.4 μg/l vs ≤ 0.4 μg/l), age and Hunt and Hess grading scale score (HH) were associated with unfavourable mRS outcome in univariate logistic regression analysis. Dichotomized S100B was the only variable independently correlated with unfavourable mRS outcome in a multivariate logistic regression analysis.CONCLUSIONS: For the first time, S100B was shown to correlate with mRS and health-related quality of life at 1 year after aSAH. Peak S100B can be used as a prognostic factor for unfavourable outcome measured as dichotomized mRS after aSAH. A peak value cutoff of 0.4 μg/l is suggested. Ethical approval no: 2013/366-31, 4th of February 2014.
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  • Andelic, Nada, et al. (författare)
  • Frequency of fatigue and its changes in the first 6 months after traumatic brain injury : results from the CENTER-TBI study
  • 2021
  • Ingår i: Journal of Neurology. - : Springer. - 0340-5354 .- 1432-1459. ; 268:1, s. 61-73
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Fatigue is one of the most commonly reported subjective symptoms following traumatic brain injury (TBI). The aims were to assess frequency of fatigue over the first 6 months after TBI, and examine whether fatigue changes could be predicted by demographic characteristics, injury severity and comorbidities.METHODS: Patients with acute TBI admitted to 65 trauma centers were enrolled in the study Collaborative European NeuroTrauma Effectiveness Research in TBI (CENTER-TBI). Subjective fatigue was measured by single item on the Rivermead Post-Concussion Symptoms Questionnaire (RPQ), administered at baseline, three and 6 months postinjury. Patients were categorized by clinical care pathway: admitted to an emergency room (ER), a ward (ADM) or an intensive care unit (ICU). Injury severity, preinjury somatic- and psychiatric conditions, depressive and sleep problems were registered at baseline. For prediction of fatigue changes, descriptive statistics and mixed effect logistic regression analysis are reported.RESULTS: Fatigue was experienced by 47% of patients at baseline, 48% at 3 months and 46% at 6 months. Patients admitted to ICU had a higher probability of experiencing fatigue than those in ER and ADM strata. Females and individuals with lower age, higher education, more severe intracranial injury, preinjury somatic and psychiatric conditions, sleep disturbance and feeling depressed postinjury had a higher probability of fatigue.CONCLUSION: A high and stable frequency of fatigue was found during the first 6 months after TBI. Specific socio-demographic factors, comorbidities and injury severity characteristics were predictors of fatigue in this study.
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  • Arango-Lasprilla, Juan Carlos, et al. (författare)
  • Early Predictors of Employment Status One Year Post Injury in Individuals with Traumatic Brain Injury in Europe
  • 2020
  • Ingår i: Journal of Clinical Medicine. - : MDPI. - 2077-0383. ; 9:6
  • Tidskriftsartikel (refereegranskat)abstract
    • Sustaining a traumatic brain injury (TBI) often affects the individual’s ability to work, reducing employment rates post-injury across all severities of TBI. The objective of this multi-country study was to assess the most relevant early predictors of employment status in individuals after TBI at one-year post-injury in European countries. Using a prospective longitudinal non-randomized observational cohort (The Collaborative European NeuroTrauma Effectiveness Research in TBI (CENTER-TBI) project), data was collected between December 2014–2019 from 63 trauma centers in 18 European countries. The 1015 individuals who took part in this study were potential labor market participants, admitted to a hospital and enrolled within 24 h of injury with a clinical TBI diagnosis and indication for a computed tomography (CT) scan, and followed up at one year. Results from a binomial logistic regression showed that older age, status of part-time employment or unemployment at time of injury, premorbid psychiatric problems, and higher injury severity (as measured with higher Injury severity score (ISS), lower Glasgow Coma Scale (GCS), and longer length of stay (LOS) in hospital) were associated with higher unemployment probability at one-year after injury. The study strengthens evidence for age, employment at time of injury, premorbid psychiatric problems, ISS, GCS, and LOS as important predictors for employment status one-year post-TBI across Europe.
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  • Behzadi, Arvin, 1994- (författare)
  • Biomarkers for diagnosis and prognosis in amyotrophic lateral sclerosis
  • 2024
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • Background: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder characterized by loss of upper and lower motor neurons, leading to paresis, muscle atrophy, and respiratory failure. ALS can be difficult to diagnose and prognosticate early.Aim: To investigate the diagnostic and prognostic characteristics of biomarkers in cerebrospinal fluid (CSF), plasma, and skeletal muscle tissue in patients with ALS.Paper I: Neurofilament light chain (NFL) and phosphorylated neurofilament heavy chain (pNFH) were analyzed in CSF using enzyme-linked immunosorbent assay (ELISA), and NFL in plasma was analyzed using single-molecule array (SIMOA). CSF NFL, CSF pNFH, and plasma NFL concentrations can differentiate ALS patients from ALS mimics, and were significantly negatively correlated with the disease duration in ALS patients.Paper II: Myosin heavy chain (MyHC) isoforms in extraocular muscles were investigated using immunofluorescence. Control donors had significantly higher proportion of myofibers containing MyHCIIa and significantly lower proportion of myofibers containing MyHCeom in the global layer compared to spinal-onset ALS and bulbar-onset ALS donors. Disease duration in the spinal-onset ALS donors was significantly correlated with the proportion of myofibers containing MyHCIIa in the global layer and MyHCeom in the orbital layer.Paper III: The study combined the neurofilament concentrations from Paper I, with cytokines previously analyzed in CSF and plasma using SIMOA, to investigate distinct molecular phenotypes in ALS. Patients with bulbar-onset ALS had significantly higher concentrations of CSF tumor necrosis factor α (TNF-α) compared to ALS mimics. TNF-α and NFL were significantly correlated with each other in both CSF and plasma in ALS patients. Combined analysis of NFL and IL-6 in plasma identified molecular prognostic subgroups in ALS patients.Paper IV: Creatine kinase (CK), high-sensitivity cardiac troponin T (hs-cTnT), hs-cTnI, and cystatin C (CysC) were analyzed in plasma in a fully accredited laboratory. CK and hs-cTnT concentrations were significantly elevated in limb-onset ALS compared to controls and bulbar-onset ALS. hs-cTnT concentrations were significantly elevated in truncal-onset ALS compared to controls and bulbar-onset ALS. Multivariable Cox proportional hazards models indicated elevated concentrations of CysC as a significant marker for worse prognosis in ALS.Conclusions: The papers report diagnostic and prognostic characteristics of biomarkers in CSF, plasma, and muscle tissue in ALS patients. The significant findings for biomarkers in plasma could be of value since plasma sampling does not involve a lumbar puncture.
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7.
  • Björkman, Sven, et al. (författare)
  • Thermic and tremorogenic effects of thyroliberin (TRH) in reserpine-treated mice--the non-involvement of GABA-ergic mechanisms.
  • 1981
  • Ingår i: Journal of Pharmacy and Pharmacology (JPP). - : Oxford University Press (OUP). - 0022-3573 .- 2042-7158. ; 33:9, s. 580-585
  • Tidskriftsartikel (refereegranskat)abstract
    • Administration of thyroliberin (TRH) to reserpinized mice causes tremor and counteracts the hypothermia in a dose-dependent fashion. The thyroliberin response is inhibited by gamma-hydroxybutyric acid (GHB) and baclofen, but not by other, more specific GABA-ergic agents, such as THIP, gamma-acetylenic GABA, and sodium valproate. Picrotoxin neither potentiates nor inhibits the thyroliberin actions. Nor are the thyroliberin effects dependent on cholinergic, monoaminergic or histaminergic mechanisms. The results repudiate a current hypothesis, that the peptide actions may be mediated by GABA-ergic pathways in the brain.
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  • Björnfot, Cecilia, et al. (författare)
  • Cerebral arterial stiffness is linked to white matter hyperintensities and perivascular spaces in older adults : a 4D flow MRI study
  • 2024
  • Ingår i: Journal of Cerebral Blood Flow and Metabolism. - : Sage Publications. - 0271-678X .- 1559-7016.
  • Tidskriftsartikel (refereegranskat)abstract
    • White matter hyperintensities (WMH), perivascular spaces (PVS) and lacunes are common MRI features of small vessel disease (SVD). However, no shared underlying pathological mechanism has been identified. We investigated whether SVD burden, in terms of WMH, PVS and lacune status, was related to changes in the cerebral arterial wall by applying global cerebral pulse wave velocity (gcPWV) measurements, a newly described marker of cerebral vascular stiffness. In a population-based cohort of 190 individuals, 66–85 years old, SVD features were estimated from T1-weighted and FLAIR images while gcPWV was estimated from 4D flow MRI data. Additionally, the gcPWV’s stability to variations in field-of-view was analyzed. The gcPWV was 10.82 (3.94) m/s and displayed a significant correlation to WMH and white matter PVS volume (r = 0.29, p < 0.001; r = 0.21, p = 0.004 respectively from nonparametric tests) that persisted after adjusting for age, blood pressure variables, body mass index, ApoB/A1 ratio, smoking as well as cerebral pulsatility index, a previously suggested early marker of SVD. The gcPWV displayed satisfactory stability to field-of-view variations. Our results suggest that SVD is accompanied by changes in the cerebral arterial wall that can be captured by considering the velocity of the pulse wave transmission through the cerebral arterial network.
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  • Bockhop, Fabian, et al. (författare)
  • Measurement invariance of six language versions of the post-traumatic stress disorder checklist for DSM-5 in civilians after traumatic brain injury
  • 2022
  • Ingår i: Scientific Reports. - : Springer Nature. - 2045-2322. ; 12:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Traumatic brain injury (TBI) is frequently associated with neuropsychiatric impairments such as symptoms of post-traumatic stress disorder (PTSD), which can be screened using self-report instruments such as the Post-Traumatic Stress Disorder Checklist for DSM-5 (PCL-5). The current study aims to inspect the factorial validity and cross-linguistic equivalence of the PCL-5 in individuals after TBI with differential severity. Data for six language groups (n ≥ 200; Dutch, English, Finnish, Italian, Norwegian, Spanish) were extracted from the CENTER-TBI study database. Factorial validity of PTSD was evaluated using confirmatory factor analyses (CFA), and compared between four concurrent structural models. A multi-group CFA approach was utilized to investigate the measurement invariance (MI) of the PCL-5 across languages. All structural models showed satisfactory goodness-of-fit with small between-model variation. The original DSM-5 model for PTSD provided solid evidence of MI across the language groups. The current study underlines the validity of the clinical DSM-5 conceptualization of PTSD and demonstrates the comparability of PCL-5 symptom scores between language versions in individuals after TBI. Future studies should apply MI methods to other sociodemographic (e.g., age, gender) and injury-related (e.g., TBI severity) characteristics to improve the monitoring and clinical care of individuals suffering from PTSD symptoms after TBI.
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  • Böhm, Julia K., et al. (författare)
  • Extended Coagulation Profiling in Isolated Traumatic Brain Injury : A CENTER-TBI Analysis
  • 2022
  • Ingår i: Neurocritical Care. - : Springer. - 1541-6933 .- 1556-0961. ; 36:3, s. 927-941
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Trauma-induced coagulopathy in traumatic brain injury (TBI) remains associated with high rates of complications, unfavorable outcomes, and mortality. The underlying mechanisms are largely unknown. Embedded in the prospective multinational Collaborative European Neurotrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) study, coagulation profiles beyond standard conventional coagulation assays were assessed in patients with isolated TBI within the very early hours of injury.METHODS: Results from blood samples (citrate/EDTA) obtained on hospital admission were matched with clinical and routine laboratory data of patients with TBI captured in the CENTER-TBI central database. To minimize confounding factors, patients with strictly isolated TBI (iTBI) (n = 88) were selected and stratified for coagulopathy by routine international normalized ratio (INR): (1) INR < 1.2 and (2) INR ≥ 1.2. An INR > 1.2 has been well adopted over time as a threshold to define trauma-related coagulopathy in general trauma populations. The following parameters were evaluated: quick's value, activated partial thromboplastin time, fibrinogen, thrombin time, antithrombin, coagulation factor activity of factors V, VIII, IX, and XIII, protein C and S, plasminogen, D-dimer, fibrinolysis-regulating parameters (thrombin activatable fibrinolysis inhibitor, plasminogen activator inhibitor 1, antiplasmin), thrombin generation, and fibrin monomers.RESULTS: Patients with iTBI with INR ≥ 1.2 (n = 16) had a high incidence of progressive intracranial hemorrhage associated with increased mortality and unfavorable outcome compared with patients with INR < 1.2 (n = 72). Activity of coagulation factors V, VIII, IX, and XIII dropped on average by 15-20% between the groups whereas protein C and S levels dropped by 20%. With an elevated INR, thrombin generation decreased, as reflected by lower peak height and endogenous thrombin potential (ETP), whereas the amount of fibrin monomers increased. Plasminogen activity significantly decreased from 89% in patients with INR < 1.2 to 76% in patients with INR ≥ 1.2. Moreover, D-dimer levels significantly increased from a mean of 943 mg/L in patients with INR < 1.2 to 1,301 mg/L in patients with INR ≥ 1.2.CONCLUSIONS: This more in-depth analysis beyond routine conventional coagulation assays suggests a counterbalanced regulation of coagulation and fibrinolysis in patients with iTBI with hemostatic abnormalities. We observed distinct patterns involving key pathways of the highly complex and dynamic coagulation system that offer windows of opportunity for further research. Whether the changes observed on factor levels may be relevant and explain the worse outcome or the more severe brain injuries by themselves remains speculative.
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11.
  • Böhm, Julia K., et al. (författare)
  • Global Characterisation of Coagulopathy in Isolated Traumatic Brain Injury (iTBI) : A CENTER-TBI Analysis
  • 2020
  • Ingår i: Neurocritical Care. - : Encyclopedia of Global Archaeology/Springer Verlag. - 1541-6933 .- 1556-0961. ; 35:1, s. 184-196
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Trauma-induced coagulopathy in patients with traumatic brain injury (TBI) is associated with high rates of complications, unfavourable outcomes and mortality. The mechanism of the development of TBI-associated coagulopathy is poorly understood.Methods: This analysis, embedded in the prospective, multi-centred, observational Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) study, aimed to characterise the coagulopathy of TBI. Emphasis was placed on the acute phase following TBI, primary on subgroups of patients with abnormal coagulation profile within 4 h of admission, and the impact of pre-injury anticoagulant and/or antiplatelet therapy. In order to minimise confounding factors, patients with isolated TBI (iTBI) (n = 598) were selected for this analysis.Results: Haemostatic disorders were observed in approximately 20% of iTBI patients. In a subgroup analysis, patients with pre-injury anticoagulant and/or antiplatelet therapy had a twice exacerbated coagulation profile as likely as those without premedication. This was in turn associated with increased rates of mortality and unfavourable outcome post-injury. A multivariate analysis of iTBI patients without pre-injury anticoagulant therapy identified several independent risk factors for coagulopathy which were present at hospital admission. Glasgow Coma Scale (GCS) less than or equal to 8, base excess (BE) less than or equal to − 6, hypothermia and hypotension increased risk significantly.Conclusion: Consideration of these factors enables early prediction and risk stratification of acute coagulopathy after TBI, thus guiding clinical management.
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  • Ceyisakar, Iris E., et al. (författare)
  • Can We Cluster ICU Treatment Strategies for Traumatic Brain Injury by Hospital Treatment Preferences?
  • 2022
  • Ingår i: Neurocritical Care. - : Springer. - 1541-6933 .- 1556-0961. ; 36:3, s. 846-856
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: In traumatic brain injury (TBI), large between-center differences in treatment and outcome for patients managed in the intensive care unit (ICU) have been shown. The aim of this study is to explore if European neurotrauma centers can be clustered, based on their treatment preference in different domains of TBI care in the ICU.METHODS: Provider profiles of centers participating in the Collaborative European Neurotrauma Effectiveness Research in TBI study were used to assess correlations within and between the predefined domains: intracranial pressure monitoring, coagulation and transfusion, surgery, prophylactic antibiotics, and more general ICU treatment policies. Hierarchical clustering using Ward's minimum variance method was applied to group data with the highest similarity. Heat maps were used to visualize whether hospitals could be grouped to uncover types of hospitals adhering to certain treatment strategies.RESULTS: Provider profiles were available from 66 centers in 20 different countries in Europe and Israel. Correlations within most of the predefined domains varied from low to high correlations (mean correlation coefficients 0.2-0.7). Correlations between domains were lower, with mean correlation coefficients of 0.2. Cluster analysis showed that policies could be grouped, but hospitals could not be grouped based on their preference.CONCLUSIONS: Although correlations between treatment policies within domains were found, the failure to cluster hospitals indicates that a specific treatment choice within a domain is not a proxy for other treatment choices within or outside the domain. These results imply that studying the effects of specific TBI interventions on outcome can be based on between-center variation without being substantially confounded by other treatments.TRIAL REGISTRATION: We do not report the results of a health care intervention.
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14.
  • Citerio, Giuseppe, et al. (författare)
  • Management of arterial partial pressure of carbon dioxide in the first week after traumatic brain injury : results from the CENTER-TBI study
  • 2021
  • Ingår i: Intensive Care Medicine. - : Springer. - 0342-4642 .- 1432-1238. ; 47:9, s. 961-973
  • Tidskriftsartikel (refereegranskat)abstract
    • PURPOSE: To describe the management of arterial partial pressure of carbon dioxide (PaCO2) in severe traumatic brain-injured (TBI) patients, and the optimal target of PaCO2 in patients with high intracranial pressure (ICP).METHODS: Secondary analysis of CENTER-TBI, a multicentre, prospective, observational, cohort study. The primary aim was to describe current practice in PaCO2 management during the first week of intensive care unit (ICU) after TBI, focusing on the lowest PaCO2 values. We also assessed PaCO2 management in patients with and without ICP monitoring (ICPm), and with and without intracranial hypertension. We evaluated the effect of profound hyperventilation (defined as PaCO2 < 30 mmHg) on long-term outcome.RESULTS: We included 1100 patients, with a total of 11,791 measurements of PaCO2 (5931 lowest and 5860 highest daily values). The mean (± SD) PaCO2 was 38.9 (± 5.2) mmHg, and the mean minimum PaCO2 was 35.2 (± 5.3) mmHg. Mean daily minimum PaCO2 values were significantly lower in the ICPm group (34.5 vs 36.7 mmHg, p < 0.001). Daily PaCO2 nadir was lower in patients with intracranial hypertension (33.8 vs 35.7 mmHg, p < 0.001). Considerable heterogeneity was observed between centers. Management in a centre using profound hyperventilation (HV) more frequently was not associated with increased 6 months mortality (OR = 1.06, 95% CI = 0.77-1.45, p value = 0.7166), or unfavourable neurological outcome (OR 1.12, 95% CI = 0.90-1.38, p value = 0.3138).CONCLUSIONS: Ventilation is manipulated differently among centers and in response to intracranial dynamics. PaCO2 tends to be lower in patients with ICP monitoring, especially if ICP is increased. Being in a centre which more frequently uses profound hyperventilation does not affect patient outcomes.
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15.
  • Cnossen, Maryse C., et al. (författare)
  • Prehospital Trauma Care among 68 European Neurotrauma Centers : Results of the CENTER-TBI Provider Profiling Questionnaires
  • 2018
  • Ingår i: Journal of Neurotrauma. - : Mary Ann Liebert. - 0897-7151 .- 1557-9042. ; 36:1, s. 176-181
  • Tidskriftsartikel (refereegranskat)abstract
    • 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.
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  • Cnossen, Maryse C., et al. (författare)
  • Rehabilitation after traumatic brain injury : A survey in 70 European neurotrauma centres participating in the CENTER-TBI study
  • 2017
  • Ingår i: Journal of Rehabilitation Medicine. - : Journal of Rehabilitation Medicine. - 1650-1977 .- 1651-2081. ; 49:5, s. 395-401
  • Tidskriftsartikel (refereegranskat)abstract
    • 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.
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17.
  • Cnossen, Maryse C., et al. (författare)
  • Variation in monitoring and treatment policies for intracranial hypertension in traumatic brain injury : a survey in 66 neurotrauma centers participating in the CENTER-TBI study
  • 2017
  • Ingår i: Critical Care. - : Springer. - 1364-8535 .- 1466-609X. ; 21:1
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: No definitive evidence exists on how intracranial hypertension should be treated in patients with traumatic brain injury (TBI). It is therefore likely that centers and practitioners individually balance potential benefits and risks of different intracranial pressure (ICP) management strategies, resulting in practice variation. The aim of this study was to examine variation in monitoring and treatment policies for intracranial hypertension in patients with TBI.METHODS: A 29-item survey on ICP monitoring and treatment was developed on the basis of literature and expert opinion, and it was pilot-tested in 16 centers. The questionnaire was sent to 68 neurotrauma centers participating in the Collaborative European Neurotrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) study.RESULTS: The survey was completed by 66 centers (97% response rate). Centers were mainly academic hospitals (n = 60, 91%) and designated level I trauma centers (n = 44, 67%). The Brain Trauma Foundation guidelines were used in 49 (74%) centers. Approximately 90% of the participants (n = 58) indicated placing an ICP monitor in patients with severe TBI and computed tomographic abnormalities. There was no consensus on other indications or on peri-insertion precautions. We found wide variation in the use of first- and second-tier treatments for elevated ICP. Approximately half of the centers were classified as using a relatively aggressive approach to ICP monitoring and treatment (n = 32, 48%), whereas the others were considered more conservative (n = 34, 52%).CONCLUSIONS: Substantial variation was found regarding monitoring and treatment policies in patients with TBI and intracranial hypertension. The results of this survey indicate a lack of consensus between European neurotrauma centers and provide an opportunity and necessity for comparative effectiveness research.
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18.
  • Cnossen, Maryse C., et al. (författare)
  • Variation in Structure and Process of Care in Traumatic Brain Injury : Provider Profiles of European Neurotrauma Centers Participating in the CENTER-TBI Study
  • 2016
  • Ingår i: PLOS ONE. - : Public Library of Science (PLOS). - 1932-6203. ; 11:8
  • Tidskriftsartikel (refereegranskat)abstract
    • INTRODUCTION: The strength of evidence underpinning care and treatment recommendations in traumatic brain injury (TBI) is low. Comparative effectiveness research (CER) has been proposed as a framework to provide evidence for optimal care for TBI patients. The first step in CER is to map the existing variation. The aim of current study is to quantify variation in general structural and process characteristics among centers participating in the Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) study.METHODS: We designed a set of 11 provider profiling questionnaires with 321 questions about various aspects of TBI care, chosen based on literature and expert opinion. After pilot testing, questionnaires were disseminated to 71 centers from 20 countries participating in the CENTER-TBI study. Reliability of questionnaires was estimated by calculating a concordance rate among 5% duplicate questions.RESULTS: All 71 centers completed the questionnaires. Median concordance rate among duplicate questions was 0.85. The majority of centers were academic hospitals (n = 65, 92%), designated as a level I trauma center (n = 48, 68%) and situated in an urban location (n = 70, 99%). The availability of facilities for neuro-trauma care varied across centers; e.g. 40 (57%) had a dedicated neuro-intensive care unit (ICU), 36 (51%) had an in-hospital rehabilitation unit and the organization of the ICU was closed in 64% (n = 45) of the centers. In addition, we found wide variation in processes of care, such as the ICU admission policy and intracranial pressure monitoring policy among centers.CONCLUSION: Even among high-volume, specialized neurotrauma centers there is substantial variation in structures and processes of TBI care. This variation provides an opportunity to study effectiveness of specific aspects of TBI care and to identify best practices with CER approaches.
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19.
  • Czeiter, Endre, et al. (författare)
  • Blood biomarkers on admission in acute traumatic brain injury : Relations to severity, CT findings and care path in the CENTER-TBI study
  • 2020
  • Ingår i: EBioMedicine. - : Elsevier. - 2352-3964. ; 56
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Serum biomarkers may inform and improve care in traumatic brain injury (TBI). We aimed to correlate serum biomarkers with clinical severity, care path and imaging abnormalities in TBI, and explore their incremental value over clinical characteristics in predicting computed tomographic (CT) abnormalities.METHODS: We analyzed six serum biomarkers (S100B, NSE, GFAP, UCH-L1, NFL and t-tau) obtained <24 h post-injury from 2867 patients with any severity of TBI in the Collaborative European NeuroTrauma Effectiveness Research (CENTER-TBI) Core Study, a prospective, multicenter, cohort study. Univariable and multivariable logistic regression analyses were performed. Discrimination was assessed by the area under the receiver operating characteristic curve (AUC) with 95% confidence intervals.FINDINGS: All biomarkers scaled with clinical severity and care path (ER only, ward admission, or ICU), and with presence of CT abnormalities. GFAP achieved the highest discrimination for predicting CT abnormalities (AUC 0•89 [95%CI: 0•87-0•90]), with a 99% likelihood of better discriminating CT-positive patients than clinical characteristics used in contemporary decision rules. In patients with mild TBI, GFAP also showed incremental diagnostic value: discrimination increased from 0•84 [95%CI: 0•83-0•86] to 0•89 [95%CI: 0•87-0•90] when GFAP was included. Results were consistent across strata, and injury severity. Combinations of biomarkers did not improve discrimination compared to GFAP alone.INTERPRETATION: Currently available biomarkers reflect injury severity, and serum GFAP, measured within 24 h after injury, outperforms clinical characteristics in predicting CT abnormalities. Our results support the further development of serum GFAP assays towards implementation in clinical practice, for which robust clinical assay platforms are required.FUNDING: CENTER-TBI study was supported by the European Union 7th Framework program (EC grant 602150).
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20.
  • Dijkland, Simone A., et al. (författare)
  • Outcome Prediction after Moderate and Severe Traumatic Brain Injury : External Validation of Two Established Prognostic Models in 1742 European Patients
  • 2021
  • Ingår i: Journal of Neurotrauma. - : Mary Ann Liebert. - 0897-7151 .- 1557-9042. ; 38:10, s. 1377-1388
  • Tidskriftsartikel (refereegranskat)abstract
    • The International Mission on Prognosis and Analysis of Clinical Trials in Traumatic Brain Injury (IMPACT) and Corticoid Randomisation After Significant Head injury (CRASH) prognostic models predict functional outcome after moderate and severe traumatic brain injury (TBI). We aimed to assess their performance in a contemporary cohort of patients across Europe. The Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) core study is a prospective, observational cohort study in patients presenting with TBI and an indication for brain computed tomography. The CENTER-TBI core cohort consists of 4509 TBI patients available for analyses from 59 centers in 18 countries across Europe and Israel. The IMPACT validation cohort included 1173 patients with GCS ≤12, age ≥14, and 6-month Glasgow Outcome Scale-Extended (GOSE) available. The CRASH validation cohort contained 1742 patients with GCS ≤14, age ≥16, and 14-day mortality or 6-month GOSE available. Performance of the three IMPACT and two CRASH model variants was assessed with discrimination (area under the receiver operating characteristic curve; AUC) and calibration (comparison of observed vs. predicted outcome rates). For IMPACT, model discrimination was good, with AUCs ranging between 0.77 and 0.85 in 1173 patients and between 0.80 and 0.88 in the broader CRASH selection (n = 1742). For CRASH, AUCs ranged between 0.82 and 0.88 in 1742 patients and between 0.66 and 0.80 in the stricter IMPACT selection (n = 1173). Calibration of the IMPACT and CRASH models was generally moderate, with calibration-in-the-large and calibration slopes ranging between -2.02 and 0.61 and between 0.48 and 1.39, respectively. The IMPACT and CRASH models adequately identify patients at high risk for mortality or unfavorable outcome, which supports their use in research settings and for benchmarking in the context of quality-of-care assessment.
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21.
  • Eklund, Anders, et al. (författare)
  • Infusion technique can be used to distinguish between dysfunction of a hydrocephalus shunt system and a progressive dementia
  • 2004
  • Ingår i: Medical and Biological Engineering and Computing. - : Springer. - 0140-0118 .- 1741-0444. ; 42:5, s. 644-649
  • Tidskriftsartikel (refereegranskat)abstract
    • In a deteriorating shunted patient with hydrocephalus, an investigation of shunt function is often performed to distinguish a dysfunctioning shunt from an aggravated condition of the disease. The paper illustrates how a lumbar cerebrospinal fluid (CSF) infusion method can be used to evaluate post-operative deterioration in a shunted patient in order to give the physician valuable support in the shunt revision decision. A 77-year-old man with hydrocephalus was treated operatively by the insertion of a CSF shunt. Owing to shunt failure, the shunt was revised twice during a 5 year period. Using a computerised infusion technique method, with two needles placed in the lumbar subarachnoid space, the CSF dynamic system was determined pre- and post-operatively with the functioning as well as the dysfunctioning shunts. The data were verified with a bench-test of the extirpated CSF shunt. There was a significant difference in conductance G between CSF systems with an open shunt and CSF systems with no shunt or an occluded shunt (ΔG=38mm3 s−1 kPa−1, p=0.014, n=7, ANOVA). CSF dynamics investigations, with and without a shunt, can give valuable clinical support in the management of a deteriorating hydrocephalus patient. With further development of the lumbar infusion method moving towards easy-to-use equipment, there is potential for widespread clinical use.
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22.
  • Feng, Junfeng, et al. (författare)
  • Comparison of Care System and Treatment Approaches for Patients with Traumatic Brain Injury in China versus Europe : A CENTER-TBI Survey Study
  • 2020
  • Ingår i: Journal of Neurotrauma. - : Mary Ann Liebert. - 0897-7151 .- 1557-9042. ; 37:16, s. 1806-1817
  • Tidskriftsartikel (refereegranskat)abstract
    • Traumatic brain injury (TBI) poses a huge public health and societal problem worldwide. Uncertainty exists on how care system and treatment approaches for TBI worked in China may differ from those in Europe. Better knowledge on this is important to facilitate interpretation of findings reported by Chinese researchers and to inform opportunities for collaborative studies. We aimed to investigate concordance and variations in TBI care between Chinese and European neurotrauma centers. Investigators from 52 centers in China and 68 in Europe involved in the Collaborative European Neuro Trauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) study were invited to complete provider profiling (PP) questionnaires, which covered the main aspects of care system and treatment approaches of TBI care. Participating Chinese and European centers were mainly publicly funded and academic. More centers in China indicated available dedicated neuro-intensive care than those in Europe (98% vs. 60%), and treatment decisions in the ICU were mainly determined by neurosurgeons (58%) in China while in Europe, (neuro)intensivists often took the lead (61%). The ambulance dispatching system was automatic in half of Chinese centers (49%), whereas selective dispatching was more common in European centers (74%). For treatment of refractory intracranial hypertension, a decompressive craniectomy was more frequently regarded as general policy in China compared with in Europe (89% vs. 45%). We observed both concordance and substantial variations with regard to the various aspects of TBI care between Chinese and European centers. These findings are fundamental to guide future research and offer opportunities for collaborative comparative effectiveness research to identify best practices.
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23.
  • Foks, Kelly A., et al. (författare)
  • 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
  • 2017
  • Ingår i: Journal of Neurotrauma. - : Mary Ann Liebert. - 0897-7151 .- 1557-9042. ; 34:17, s. 2529-2535
  • Tidskriftsartikel (refereegranskat)abstract
    • 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 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 13-15 and 26 (38%) as a GCS score between 14-15. At the ED various guidelines for the use of head 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, while 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 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.
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24.
  • Galimberti, Stefania, et al. (författare)
  • Effect of frailty on 6-month outcome after traumatic brain injury : a multicentre cohort study with external validation
  • 2022
  • Ingår i: Lancet Neurology. - : Elsevier. - 1474-4422 .- 1474-4465. ; 21:2, s. 153-162
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Frailty is known to be associated with poorer outcomes in individuals admitted to hospital for medical conditions requiring intensive care. However, little evidence is available for the effect of frailty on patients' outcomes after traumatic brain injury. Many frailty indices have been validated for clinical practice and show good performance to predict clinical outcomes. However, each is specific to a particular clinical context. We aimed to develop a frailty index to predict 6-month outcomes in patients after a traumatic brain injury.METHODS: A cumulative deficit approach was used to create a novel frailty index based on 30 items dealing with disease states, current medications, and laboratory values derived from data available from CENTER-TBI, a prospective, longitudinal observational study of patients with traumatic brain injury presenting within 24 h of injury and admitted to a ward or an intensive care unit at 65 centres in Europe between Dec 19, 2014, and Dec 17, 2017. From the individual cumulative CENTER-TBI frailty index (range 0-30), we obtained a standardised value (range 0-1), with high scores indicating higher levels of frailty. The effect of frailty on 6-month outcome evaluated with the extended Glasgow Outcome Scale (GOSE) was assessed through a proportional odds logistic model adjusted for known outcome predictors. An unfavourable outcome was defined as death or severe disability (GOSE score ≤4). External validation was performed on data from TRACK-TBI, a prospective observational study co-designed with CENTER-TBI, which enrolled patients with traumatic brain injury at 18 level I trauma centres in the USA from Feb 26, 2014, to July 27, 2018. CENTER-TBI is registered with ClinicalTrials.gov, NCT02210221; TRACK-TBI is registered at ClinicalTrials.gov, NCT02119182.FINDINGS: 2993 participants (median age was 51 years [IQR 30-67], 2058 [69%] were men) were included in this analysis. The overall median CENTER-TBI frailty index score was 0·07 (IQR 0·03-0·15), with a median score of 0·17 (0·08-0·27) in older adults (aged ≥65 years). The CENTER-TBI frailty index score was significantly associated with the probability of an increasingly unfavourable outcome (cumulative odds ratio [OR] 1·03, 95% CI 1·02-1·04; p<0·0001), and the association was stronger for participants admitted to hospital wards (1·04, 1·03-1·06, p<0·0001) compared with those admitted to the intensive care unit (1·02, 1·01-1·03 p<0·0001). External validation of the CENTER-TBI frailty index in data from the TRACK-TBI (n=1667) cohort supported the robustness and reliability of these findings. The overall median TRACK-TBI frailty index score was 0·03 (IQR 0-0·10), with the frailty index score significantly associated with the risk of an increasingly unfavourable outcome in patients admitted to hospital wards (cumulative OR 1·05, 95% CI 1·03-1·08; p<0·0001), but not in those admitted to the intensive care unit (1·01, 0·99-1·03; p=0·43).INTERPRETATION: We developed and externally validated a frailty index specific to traumatic brain injury. Risk of unfavourable outcome was significantly increased in participants with a higher CENTER-TBI frailty index score, regardless of age. Frailty identification could help to individualise rehabilitation approaches aimed at mitigating effects of frailty in patients with traumatic brain injury.FUNDING: European Union, Hannelore Kohl Stiftung, OneMind, Integra LifeSciences Corporation, NeuroTrauma Sciences, NIH-NINDS-TRACK-TBI, US Department of Defense.
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25.
  • Gasslander, Johan, et al. (författare)
  • Risk factors for developing subdural hematoma : a registry-based study in 1457 patients with shunted idiopathic normal pressure hydrocephalus
  • 2021
  • Ingår i: Journal of Neurosurgery. - : American Association of Neurological Surgeons. - 0022-3085 .- 1933-0693. ; 134:2, s. 668-677
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVE: Subdural hematomas and hygromas (SDHs) are common complications in idiopathic normal pressure hydrocephalus (iNPH) patients with shunts. In this registry-based study, patients with shunted iNPH were screened nationwide to identify perioperative variables that may increase the risk of SDH.METHODS: The Swedish Hydrocephalus Quality Registry was reviewed for iNPH patients who had undergone shunt surgery in Sweden in 2004-2014. Potential risk factors for SDH were recorded preoperatively and 3 months after surgery. Drug prescriptions were identified from a national pharmacy database. Patients who developed SDHs were compared with those without SDHs.RESULTS: The study population consisted of 1457 patients, 152 (10.4%) of whom developed an SDH. Men developed an SDH more often than women (OR 2.084, 95% CI 1.421-3.058, p < 0.001). Patients on platelet aggregation inhibitors developed an SDH more often than those who were not (OR 1.733, 95% CI 1.236-2.431, p = 0.001). At surgery, shunt opening pressures had been set 5.9 mm H2O lower in the SDH group than in the no-SDH group (109.6 ± 24.1 vs 115.5 ± 25.4 mm H2O, respectively, p = 0.009). Antisiphoning devices (ASDs) were used in 892 patients but did not prevent SDH. Mean opening pressures at surgery and the follow-up were lower with shunts with an ASD, without causing more SDHs. No other differences were seen between the groups.CONCLUSIONS: iNPH patients in this study were diagnosed and operated on in routine practice; thus, the results represent everyday care. Male sex, antiplatelet medication, and a lower opening pressure at surgery were risk factors for SDH. Physical status and comorbidity were not. ASD did not prevent SDH, but a shunt with an ASD allowed a lower opening pressure without causing more SDHs.
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26.
  • Gravesteijn, Benjamin Yaël, et al. (författare)
  • Missing Data in Prediction Research : A Five-Step Approach for Multiple Imputation, Illustrated in the CENTER-TBI Study
  • 2021
  • Ingår i: Journal of Neurotrauma. - : Mary Ann Liebert. - 0897-7151 .- 1557-9042. ; 38:13, s. 1842-1857
  • Tidskriftsartikel (refereegranskat)abstract
    • In medical research, missing data is common. In acute diseases, such as traumatic brain injury (TBI), even well-conducted prospective studies may suffer from missing data in baseline characteristics and outcomes. Statistical models may simply drop patients with any missing values, potentially leaving a selected subset of the original cohort. Imputation is widely accepted by methodologists as an appropriate way to deal with missing data. We aim to provide practical guidance on handling missing data for prediction modeling. We hereto propose a five-step approach, centered around single and multiple imputation: 1) explore the missing data patterns; 2) choose a method of imputation; 3) perform imputation; 4) assess diagnostics of the imputation; and 5) analyze the imputed data sets. We illustrate these five steps with the estimation and validation of the IMPACT (International Mission on Prognosis and Analysis of Clinical Trials in Traumatic Brain Injury) prognostic model in 1375 patients from the CENTER-TBI database, included in 53 centers across 17 countries, with moderate or severe TBI in the prospective European CENTER-TBI study. Future prediction modeling studies in acute diseases may benefit from following the suggested five steps for optimal statistical analysis and interpretation, after maximal effort has been made to minimize missing data.
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27.
  • Gravesteijn, Benjamin Yael, et al. (författare)
  • Tracheal intubation in traumatic brain injury : a multicentreprospective observational study
  • 2020
  • Ingår i: British Journal of Anaesthesia. - : Elsevier. - 0007-0912 .- 1471-6771. ; 125:4, s. 505-517
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: We aimed to study the associations between pre- and in-hospital tracheal intubation and outcomes intraumatic brain injury (TBI), and whether the association varied according to injury severity.Methods: Data from the international prospective pan-European cohort study, Collaborative European NeuroTraumaEffectiveness Research for TBI (CENTER-TBI), were used (n¼4509). For prehospital intubation, we excluded selfpresenters. For in-hospital intubation, patients whose tracheas were intubated on-scene were excluded. The associationbetween intubation and outcome was analysed with ordinal regression with adjustment for the International Mission forPrognosis and Analysis of Clinical Trials in TBI variables and extracranial injury. We assessed whether the effect ofintubation varied by injury severity by testing the added value of an interaction term with likelihood ratio tests.Results: In the prehospital analysis, 890/3736 (24%) patients had their tracheas intubated at scene. In the in-hospitalanalysis, 460/2930 (16%) patients had their tracheas intubated in the emergency department. There was no adjustedoverall effect on functional outcome of prehospital intubation (odds ratio¼1.01; 95% confidence interval, 0.79e1.28;P¼0.96), and the adjusted overall effect of in-hospital intubation was not significant (odds ratio¼0.86; 95% confidenceinterval, 0.65e1.13; P¼0.28). However, prehospital intubation was associated with better functional outcome in patientswith higher thorax and abdominal Abbreviated Injury Scale scores (P¼0.009 and P¼0.02, respectively), whereas inhospital intubation was associated with better outcome in patients with lower Glasgow Coma Scale scores (P¼0.01): inhospital intubation was associated with better functional outcome in patients with Glasgow Coma Scale scores of 10 orlower.Conclusion: The benefits and harms of tracheal intubation should be carefully evaluated in patients with TBI to optimisebenefit. This study suggests that extracranial injury should influence the decision in the prehospital setting, and level ofconsciousness in the in-hospital setting.Clinical trial registration: NCT02210221.
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28.
  • Gravesteijn, B. Y., et al. (författare)
  • Variation in the practice of tracheal intubation in Europe after traumatic brain injury : a prospective cohort study
  • 2020
  • Ingår i: Anaesthesia. - : John Wiley & Sons. - 0003-2409 .- 1365-2044. ; 75:1, s. 45-53
  • Tidskriftsartikel (refereegranskat)abstract
    • Traumatic brain injury patients frequently undergo tracheal intubation. We aimed to assess current intubation practice in Europe and identify variation in practice. We analysed data from patients with traumatic brain injury included in the prospective cohort study collaborative European neurotrauma effectiveness research in traumatic brain injury (CENTER-TBI) in 45 centres in 16 European countries. We included patients who were transported to hospital by emergency medical services. We used mixed-effects multinomial regression to quantify the effects on pre-hospital or in-hospital tracheal intubation of the following: patient characteristics; injury characteristics; centre; and trauma system characteristics. A total of 3843 patients were included. Of these, 1322 (34%) had their tracheas intubated; 839 (22%) pre-hospital and 483 (13%) in-hospital. The fit of the model with only patient characteristics predicting intubation was good (Nagelkerke R2 64%). The probability of tracheal intubation increased with the following: younger age; lower pre-hospital or emergency department GCS; higher abbreviated injury scale scores (head and neck, thorax and chest, face or abdomen abbreviated injury score); and one or more unreactive pupils. The adjusted median odds ratio for intubation between two randomly chosen centres was 3.1 (95%CI 2.1-4.3) for pre-hospital intubation, and 2.7 (95%CI 1.9-3.5) for in-hospital intubation. Furthermore, the presence of an anaesthetist was independently associated with more pre-hospital intubation (OR 2.9, 95%CI 1.3-6.6), in contrast to the presence of ambulance personnel who are allowed to intubate (OR 0.5, 95%CI 0.3-0.8). In conclusion, patient and injury characteristics are key drivers of tracheal intubation. Between-centre differences were also substantial. Further studies are needed to improve the evidence base supporting recommendations for tracheal intubation.
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29.
  • Horton, Lindsay, et al. (författare)
  • Questionnaires vs Interviews for the Assessment of Global Functional Outcomes After Traumatic Brain Injury
  • 2021
  • Ingår i: JAMA Network Open. - : American Medical Association. - 2574-3805. ; 4:11
  • Tidskriftsartikel (refereegranskat)abstract
    • Importance: An interview is considered the gold standard method of assessing global functional outcomes in clinical trials among patients with acute traumatic brain injury (TBI). However, several multicenter clinical trials have used questionnaires completed by a patient or caregiver to assess the primary end point.Objective: To examine agreement between interview and questionnaire formats for assessing TBI outcomes and to consider whether an interview has advantages.Design, Setting, and Participants: This cohort study used data from patients enrolled in the Collaborative European NeuroTrauma Effectiveness Research in TBI (CENTER-TBI) project from December 2014 to December 2017. Data were analyzed from December 2020 to April 2021. Included patients were aged 16 years or older with TBI and a clinical indication for computed tomography imaging. Outcome assessments were completed using both an interview and a questionnaire at follow-up 3 and 6 months after injury.Exposures: Traumatic brain injury of all severities.Main Outcomes and Measures: Ratings on the Glasgow Outcome Scale-Extended (GOSE) administered as a structured interview rated by an investigator and as a questionnaire completed by patients or caregivers and scored centrally were compared, and the strength of agreement was evaluated using weighted κ statistics. Secondary outcomes included comparison of different sections of the GOSE assessments and the association of GOSE ratings with baseline factors and patient-reported mental health, health-related quality of life, and TBI symptoms.Results: Among the 3691 eligible individuals in the CENTER-TBI study, both GOSE assessment formats (interview and questionnaire) were completed by 994 individuals (26.9%) at 3 months after TBI (654 [65.8%] male; median age, 53 years [IQR, 33-66 years]) and 628 (17.0%) at 6 months (409 [65.1%] male; median age, 51 years [IQR, 31-64 years]). Outcomes of the 2 assessment methods agreed well at both 3 months (weighted κ, 0.77; 95% CI, 0.73-0.80) and 6 months (weighted κ, 0.82; 95% CI, 0.78-0.86). Furthermore, item-level agreement between the 2 methods was good for sections regarding independence in everyday activities (κ, 0.70-0.79 across both time points) and moderate for sections regarding subjective aspects of functioning such as relationships and symptoms (κ, 0.41-0.51 across both time points). Compared with questionnaires, interviews recorded more problems with work (294 [30.5%] vs 233 [24.2%] at 3 months and 161 [26.8%] vs 136 [22.7%] at 6 months), fewer limitations in social and leisure activities (330 [33.8%] vs 431 [44.1%] at 3 months and 179 [29.7%] vs 219 [36.4%] at 6 months), and more symptoms (524 [53.6%] vs 324 [33.1%] at 3 months and 291 [48.4%] vs 179 [29.8%] at 6 months). Interviewers sometimes assigned an overall rating based on judgment rather than interview scoring rules, particularly for patients with potentially unfavorable TBI outcomes. However, for both formats, correlations with baseline factors (ρ, -0.13 to 0.42) and patient-reported outcomes (ρ, 0.29 to 0.65) were similar in strength.Conclusions and Relevance: In this cohort study, GOSE ratings obtained by questionnaire and interview methods were in good agreement. The similarity of associations of the ratings obtained by both GOSE methods with baseline factors and other TBI outcome measures suggests that despite some apparent differences, the core information collected by both interviews and questionnaires was similar. The findings support the use of questionnaires in studies in which this form of contact may offer substantial practical advantages compared with interviews.
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30.
  • Howe, Emilie Isager, et al. (författare)
  • Rehabilitation and outcomes after complicated vs uncomplicated mild TBI : results from the CENTER-TBI study
  • 2022
  • Ingår i: BMC Health Services Research. - : BioMed Central (BMC). - 1472-6963. ; 22:1
  • Tidskriftsartikel (refereegranskat)abstract
    • 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.
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31.
  • Hugoson-Seligsohn, Eva E., et al. (författare)
  • TRH-induced blood flow and mean arterial pressure changes in the rabbit are not dependent on the anaesthetic used.
  • 1989
  • Ingår i: British Journal of Pharmacology. - : Macmillan Publishers Ltd.. - 0007-1188 .- 1476-5381. ; 97:1, s. 190-196
  • Tidskriftsartikel (refereegranskat)abstract
    • 1. The effects of thyrotropin releasing hormone (TRH) on regional cerebral blood flow were studied in rabbits anaesthetized with pentobarbitone or ketamine. The blood flow was determined with the labelled microsphere method before and after the i.v. administration of either 50 micrograms kg-1 or 2 mg kg-1 TRH.2. In order to measure the cerebral O2 consumption the arteriovenous difference in oxygen saturation in the brain (CAVOD) was measured before and after the administration of 2 mg kg-1 TRH.3. In animals under pentobarbitone anaesthesia 50 micrograms kg-1 TRH elicited an increase in mean arterial blood pressure (MAP) of about 1 kPa and 2 mg kg-1 TRH elevated the MAP by about 2 kPa. With ketamine as the anaesthetic the corresponding values were 0.5 kPa and 7 kPa, respectively. TRH induced significant vasoconstriction in several peripheral tissues.4. The total cerebral blood flow (CBFtot) increased from 54 +/- 4 to 78 +/- 5 g min-1 100 g-1 after the administration of 50 micrograms kg-1 TRH in pentobarbitone-anaesthetized animals. An even greater effect was elicited by 2 mg kg-1 TRH, from 48 +/- 6 to 113 +/- 19 g min-1 100 g-1. In ketamine-anaesthetized rabbits, 50 micrograms kg-1 TRH tended to enhance the CBFtot and 2 mg kg-1 increased it from 71 +/- 6 to 141 +/- 19 g min-1 100 g-1.5. In animals anaesthetized with pentobarbitone, the CAVOD decreased from 47.3 +/- 1.7% to 35.1 +/- 2.2% at 3 min after TRH delivery, and then gradually increased to the control level. In animals under ketamine anaesthesia the CAVOD decreased from 63.3 + 2.0% to 45.2 + 7.4% after the administration of 2 mg kg'- TRH.6. It is concluded that TRH elicits cerebral vasodilatation in excess of that required by the change in cerebral metabolism which may have taken place. The pattern of responses was similar to that produced in rabbits under urethane anaesthesia.
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32.
  • Huijben, Jilske A., et al. (författare)
  • Use and impact of high intensity treatments in patients with traumatic brain injury across Europe : a CENTER-TBI analysis
  • 2021
  • Ingår i: Critical Care. - : BioMed Central (BMC). - 1364-8535 .- 1466-609X. ; 25:1
  • Tidskriftsartikel (refereegranskat)abstract
    • PURPOSE: To study variation in, and clinical impact of high Therapy Intensity Level (TIL) treatments for elevated intracranial pressure (ICP) in patients with traumatic brain injury (TBI) across European Intensive Care Units (ICUs).METHODS: We studied high TIL treatments (metabolic suppression, hypothermia (< 35 °C), intensive hyperventilation (PaCO2 < 4 kPa), and secondary decompressive craniectomy) in patients receiving ICP monitoring in the ICU stratum of the CENTER-TBI study. A random effect logistic regression model was used to determine between-centre variation in their use. A propensity score-matched model was used to study the impact on outcome (6-months Glasgow Outcome Score-extended (GOSE)), whilst adjusting for case-mix severity, signs of brain herniation on imaging, and ICP.RESULTS: 313 of 758 patients from 52 European centres (41%) received at least one high TIL treatment with significant variation between centres (median odds ratio = 2.26). Patients often transiently received high TIL therapies without escalation from lower tier treatments. 38% of patients with high TIL treatment had favourable outcomes (GOSE ≥ 5). The use of high TIL treatment was not significantly associated with worse outcome (285 matched pairs, OR 1.4, 95% CI [1.0-2.0]). However, a sensitivity analysis excluding high TIL treatments at day 1 or use of metabolic suppression at any day did reveal a statistically significant association with worse outcome.CONCLUSION: Substantial between-centre variation in use of high TIL treatments for TBI was found and treatment escalation to higher TIL treatments were often not preceded by more conventional lower TIL treatments. The significant association between high TIL treatments after day 1 and worse outcomes may reflect aggressive use or unmeasured confounders or inappropriate escalation strategies.TAKE HOME MESSAGE: Substantial variation was found in the use of highly intensive ICP-lowering treatments across European ICUs and a stepwise escalation strategy from lower to higher intensity level therapy is often lacking. Further research is necessary to study the impact of high therapy intensity treatments.TRIAL REGISTRATION: The core study was registered with ClinicalTrials.gov, number NCT02210221, registered 08/06/2014, https://clinicaltrials.gov/ct2/show/NCT02210221?id=NCT02210221&draw=1&rank=1 and with Resource Identification Portal (RRID: SCR_015582).
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33.
  • Huijben, Jilske A., et al. (författare)
  • Variation in Blood Transfusion and Coagulation Management in Traumatic Brain Injury at the Intensive Care Unit : A Survey in 66 Neurotrauma Centers Participating in the Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury Study
  • 2017
  • Ingår i: Journal of Neurotrauma. - : Mary Ann Liebert. - 0897-7151 .- 1557-9042. ; 35:2, s. 323-332
  • Tidskriftsartikel (refereegranskat)abstract
    • Our aim was to describe current approaches and to quantify variability between European intensive care units (ICUs) in patients with traumatic brain injury (TBI). Therefore, we conducted a provider profiling survey as part of the Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) study. The ICU Questionnaire was sent to 68 centers from 20 countries across Europe and Israel. For this study, we used ICU questions focused on 1) hemoglobin target level (Hb-TL), 2) coagulation management, and 3) deep venous thromboembolism (DVT) prophylaxis. Seventy-eight participants, mostly intensivists and neurosurgeons of 66 centers, completed the ICU questionnaire. For ICU-patients, half of the centers (N = 34; 52%) had a defined Hb-TL in their protocol. For patients with TBI, 26 centers (41%) indicated an Hb-TL between 70 and 90 g/L and 38 centers (59%) above 90 g/L. To treat trauma-related hemostatic abnormalities, the use of fresh frozen plasma (N = 48; 73%) or platelets (N = 34; 52%) was most often reported, followed by the supplementation of vitamin K (N = 26; 39%). Most centers reported using DVT prophylaxis with anticoagulants frequently or always (N = 62; 94%). In the absence of hemorrhagic brain lesions, 14 centers (21%) delayed DVT prophylaxis until 72 h after trauma. If hemorrhagic brain lesions were present, the number of centers delaying DVT prophylaxis for 72 h increased to 29 (46%). Overall, a lack of consensus exists between European ICUs on blood transfusion and coagulation management. The results provide a baseline for the CENTER-TBI study, and the large between-center variation indicates multiple opportunities for comparative effectiveness research.
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34.
  • Huijben, Jilske A., et al. (författare)
  • Variation in general supportive and preventive intensive care management of traumatic brain injury : a survey in 66 neurotrauma centers participating in the Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) study
  • 2018
  • Ingår i: Critical Care. - : Springer. - 1364-8535 .- 1466-609X. ; 22:1
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: General supportive and preventive measures in the intensive care management of traumatic brain injury (TBI) aim to prevent or limit secondary brain injury and optimize recovery. The aim of this survey was to assess and quantify variation in perceptions on intensive care unit (ICU) management of patients with TBI in European neurotrauma centers.METHODS: We performed a survey as part of the Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) study. We analyzed 23 questions focused on: 1) circulatory and respiratory management; 2) fever control; 3) use of corticosteroids; 4) nutrition and glucose management; and 5) seizure prophylaxis and treatment.RESULTS: The survey was completed predominantly by intensivists (n = 33, 50%) and neurosurgeons (n = 23, 35%) from 66 centers (97% response rate). The most common cerebral perfusion pressure (CPP) target was > 60 mmHg (n = 39, 60%) and/or an individualized target (n = 25, 38%). To support CPP, crystalloid fluid loading (n = 60, 91%) was generally preferred over albumin (n = 15, 23%), and vasopressors (n = 63, 96%) over inotropes (n = 29, 44%). The most commonly reported target of partial pressure of carbon dioxide in arterial blood (PaCO2) was 36-40 mmHg (4.8-5.3 kPa) in case of controlled intracranial pressure (ICP) < 20 mmHg (n = 45, 69%) and PaCO2 target of 30-35 mmHg (4-4.7 kPa) in case of raised ICP (n = 40, 62%). Almost all respondents indicated to generally treat fever (n = 65, 98%) with paracetamol (n = 61, 92%) and/or external cooling (n = 49, 74%). Conventional glucose management (n = 43, 66%) was preferred over tight glycemic control (n = 18, 28%). More than half of the respondents indicated to aim for full caloric replacement within 7 days (n = 43, 66%) using enteral nutrition (n = 60, 92%). Indications for and duration of seizure prophylaxis varied, and levetiracetam was mostly reported as the agent of choice for both seizure prophylaxis (n = 32, 49%) and treatment (n = 40, 61%).CONCLUSIONS: Practice preferences vary substantially regarding general supportive and preventive measures in TBI patients at ICUs of European neurotrauma centers. These results provide an opportunity for future comparative effectiveness research, since a more evidence-based uniformity in good practices in general ICU management could have a major impact on TBI outcome.
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35.
  • Hägglund, Linda, et al. (författare)
  • Correlation of Cerebral and Subcutaneous Glycerol in Severe Traumatic Brain Injury and Association with Tissue Damage
  • 2022
  • Ingår i: Neurocritical Care. - : Humana Press. - 1541-6933 .- 1556-0961. ; 36:3, s. 993-1001
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: This study is a substudy of a prospective consecutive double-blinded randomized study on the effect of prostacyclin in severe traumatic brain injury (sTBI). The aims of the present study were to investigate whether there was a correlation between brain and subcutaneous glycerol levels and whether the ratio of interstitial glycerol in the brain and subcutaneous tissue (glycerolbrain/sc) was associated with tissue damage in the brain, measured by using the Rotterdam score, S-100B, neuron-specific enolase (NSE), the Injury Severity Score (ISS), the Acute Physiology and Chronic Health Evaluation Score (APACHE II), and trauma type. A potential association with clinical outcome was explored.METHODS: Patients with sTBI aged 15-70 years presenting with a Glasgow Coma Scale Score ≤ 8 were included. Brain and subcutaneous adipose tissue glycerol levels were measured through microdialysis in 48 patients, of whom 42 had complete data for analysis. Brain tissue damage was also evaluated by using the Rotterdam classification of brain computed tomography scans and the biochemical biomarkers S-100B and NSE.RESULTS: In 60% of the patients, a positive relationship in glycerolbrain/sc was observed. Patients with a positive correlation of glycerolbrain/sc had slightly higher brain glycerol levels compared with the group with a negative correlation. There was no significant association between the computed tomography Rotterdam score and glycerolbrain/sc. S-100B and NSE were associated with the profile of glycerolbrain/sc. Our results cannot be explained by the general severity of the trauma as measured by using the Injury Severity Score or Acute Physiology and Chronic Health Evaluation Score.CONCLUSIONS: We have shown that peripheral glycerol may flux into the brain. This effect is associated with worse brain tissue damage. This flux complicates the interpretation of brain interstitial glycerol levels. We remind the clinicians that a damaged blood-brain barrier, as seen in sTBI, may alter the concentrations of various substances, including glycerol in the brain. Awareness of this is important in the interpretation of the data bedside as well in research.
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36.
  • Jacob, Louis, et al. (författare)
  • Predictors of Access to Rehabilitation in the Year Following Traumatic Brain Injury : A European Prospective and Multicenter Study
  • 2020
  • Ingår i: Neurorehabilitation and Neural Repair. - : Sage Publications. - 1545-9683 .- 1552-6844. ; 34:9, s. 814-830
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Although rehabilitation is beneficial for individuals with traumatic brain injury (TBI), a significant proportion of them do not receive adequate rehabilitation after acute care.Objective: Therefore, the goal of this prospective and multicenter study was to investigate predictors of access to rehabilitation in the year following injury in patients with TBI.Methods: Data from a large European study (CENTER-TBI), including TBIs of all severities between December 2014 and December 2017 were used (N = 4498 patients). Participants were dichotomized into those who had and those who did not have access to rehabilitation in the year following TBI. Potential predictors included sociodemographic factors, psychoactive substance use, preinjury medical history, injury-related factors, and factors related to medical care, complications, and discharge.Results: In the year following traumatic injury, 31.4% of patients received rehabilitation services. Access to rehabilitation was positively and significantly predicted by female sex (odds ratio [OR] = 1.50), increased number of years of education completed (OR = 1.05), living in Northern (OR = 1.62; reference: Western Europe) or Southern Europe (OR = 1.74), lower prehospital Glasgow Coma Scale score (OR = 1.03), higher Injury Severity Score (OR = 1.01), intracranial (OR = 1.33) and extracranial (OR = 1.99) surgery, and extracranial complication (OR = 1.75). On contrast, significant negative predictors were lack of preinjury employment (OR = 0.80), living in Central and Eastern Europe (OR = 0.42), and admission to hospital ward (OR = 0.47; reference: admission to intensive care unit) or direct discharge from emergency room (OR = 0.24).Conclusions: Based on these findings, there is an urgent need to implement national and international guidelines and strategies for access to rehabilitation after TBI.
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37.
  • Johansson, Conny, et al. (författare)
  • Serum Levels of Myo-inositol Predicts Clinical Outcome 1 Year After Aneurysmal Subarachnoid Hemorrhage
  • 2022
  • Ingår i: Neurosurgery. - : Lippincott Williams & Wilkins. - 0148-396X .- 1524-4040. ; 91:5, s. 790-798
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Early prognostication of long-term outcome in patients suffering from spontaneous subarachnoid hemorrhage (SAH) remains a challenge. No biomarkers are routinely used for prognostication. A previous study has indicated that the metabolite myo-inositol (MI) may be used to predict long-term outcome.OBJECTIVE: To investigate if MI measured in serum correlates with long-term clinical outcome in patients suffering from SAH.METHODS: We conducted an observational cohort study including 88 patients treated for SAH at Umeå University Hospital. Serum samples were collected in the hospital, and a gas chromatography/mass spectroscopy method was used to quantitatively measure MI. Patients were assessed after 1 year using the Glasgow Outcome Scale Extended and dichotomized to favorable or unfavorable outcome. Differences in MI levels between the 2 groups were analyzed.RESULTS: There was no difference in MI levels between the groups upon admission. Myo-inositol levels decreased over time in the entire study population. The decrease was significantly larger in the unfavorable outcome group. A receiver operating characteristics analysis yielded an area under the curve of 0.903 (CI 0.8-1.0, P < .001) for the MI value on day 7 to predict favorable outcome after 1 year.CONCLUSION: Myo-inositol measured in serum may aid prognostication of outcome in patients with SAH. The mechanism behind this remains unclear, although it can be theorized to reflect processes leading to delayed cerebral ischemia, which affects long-term outcome. This is the first study to quantitively measure MI in serum for prognostication of outcome in patients with SAH.
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38.
  • Johansson, Conny, et al. (författare)
  • Serum neurofilament light as a predictor of outcome in subarachnoid haemorrhage
  • 2023
  • Ingår i: Acta Neurochirurgica. - : Springer. - 0001-6268 .- 0942-0940. ; 165:10, s. 2793-2800
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Prognostication of clinical outcome in patients suffering from aneurysmal subarachnoid haemorrhage (SAH) is a challenge. There are no biochemical markers in routine use that can aid in prognostication. Neurofilament light (NFL) measured in cerebrospinal fluid (CSF) has been associated with clinical outcome in previous studies.Objective: To investigate if serum levels of NFL correlate with CSF levels and long-term clinical outcome in patients suffering from SAH.Methods: We conducted an observational cohort study of 88 patients treated for SAH at Umeå University Hospital in 2014–2018. Serum and CSF samples were analysed using an enzyme-linked immunosorbent assay to quantify NFL levels. Outcome was assessed using Glasgow Outcome Scale Extended and dichotomised as favourable or unfavourable. Differences in NFL levels between outcome groups were analysed using repeated measurements ANOVA. Relationship between CSF and serum NFL levels was analysed using Pearson’s correlation. A multivariate binary logistic regression model and a receiver operation characteristic curve were used to assess the predictive value of serum NFL.Results: A significant correlation between serum and CSF-NFL levels could be seen (Pearson’s correlation coefficient = 0.7, p <.0001). Mean level of serum NFL was higher in the unfavourable outcome group than the favourable outcome group (p <.0001), in all epochs of SAH, and correlated with initial disease severity on the World Federation of Neurosurgical Societies scale. Serum NFL in the late phase displayed the best predictive potential in a receiver operation characteristic curve analysis (AUC=0.845, p <.0001).Conclusion: Levels of NFL in serum and CSF are correlated. Early serum NFL levels seem to reflect initial tissue damage and serum NFL levels in the late phase may reflect secondary events such as vasospasm or delayed cerebral ischemia. Serum NFL may be used as a prognostic marker of clinical outcome in SAH.
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39.
  • Johansson, M., et al. (författare)
  • Interleukin-2 and histamine in combination inhibit tumour growth and angiogenesis in malignant glioma
  • 2000
  • Ingår i: British Journal of Cancer. - : Cancer Research Campaign. - 0007-0920 .- 1532-1827. ; 83:6, s. 826-832
  • Tidskriftsartikel (refereegranskat)abstract
    • Biotherapy including interleukin-2 (IL-2) treatment seems to be more effective outside the central nervous system when compared to the effects obtained when the same tumour is located intracerebrally. Recently published studies suggest that reduced activity of NK cells in tumour tissue can be increased by histamine. The present study was designed to determine whether IL-2 and histamine, alone or in combination, can induce anti-tumour effects in an orthotopic rat glioma model. One group of rats was treated with histamine alone (4 mg kg(-1)s.c. as daily injections from day 6 after intracranial tumour implantation), another group with IL-2 alone as a continuous subcutaneous infusion and a third group with both histamine and IL-2. The animals were sacrificed at day 24 after tumour implantation. IL-2 and histamine in combination significantly reduced tumour growth. The microvessel density was significantly reduced, an effect mainly affecting the small vessels. No obvious alteration in the pattern of VEGF mRNA expression was evident and no significant changes in apoptosis were observed. Neither IL-2 nor histamine alone caused any detectable effects on tumour growth. Histamine caused an early and pronounced decline in tumour blood flow compared to normal brain. The results indicate that the novel combination of IL-2 and histamine can be of value in reducing intracerebral tumour growth and, thus, it might be of interest to re-evaluate the therapeutic potential of biotherapy in malignant glioma.
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40.
  • Johansson, Mikael, et al. (författare)
  • Tumor blood flow and the cytotoxic effects of estramustine and its constituents in a rat glioma model
  • 1997
  • Ingår i: Neurosurgery. - : Oxford University Press. - 0148-396X .- 1524-4040. ; 41:1, s. 237-244
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVE: Estramustine (EaM) is a conjugate of nor-nitrogen mustard (NNM) and 17 beta-estradiol (E2) that has cytotoxic and radiosensitizing effects on experimental malignant glioma. Its mechanism of action is only partly understood. To further investigate the mechanism in vivo, the effects on tumor blood flow (TBF) and tumor growth were analyzed.METHODS: TBF was measured by radioactive microspheres, and tumor growth was measured by weight. Apoptosis was evaluated by in situ end labeling and gel electrophoresis. The effects of the constituents NNM and E2 were also evaluated.RESULTS: EaM increased TBF to 153.8 ml/100 g/min after 3 days and to 153.9 ml/100 g/min after 10 days of treatment, compared with 94.0 ml/100 g/min in untreated controls. Cerebral blood flow did not change after EaM treatment. NNM increased TBF but also showed a tendency to increase cerebral blood flow. E2 increased TBF, whereas cerebral blood flow was unchanged. EaM resulted in a rapid reduction in tumor weight from 230 mg in untreated animals to 146 mg after 3 days of treatment. EaM induced an early transient fragmentation of deoxyribonucleic acid in glioma but not in the normal brain. Neither NNM nor E2 affected tumor weight.CONCLUSION: EaM increases TBF in the BT4C rat glioma model with a concomitant rapid antitumoral effect. The increase in TBF could partially be induced by an estrogen-like action of EaM, but the rapid cytotoxic effect of the drug is obviously attributed to the intact EaM compound. This cytotoxic effect might be attributable to the induction of programmed cell death.
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41.
  • Kals, Mart, et al. (författare)
  • A genome-wide association study of outcome from traumatic brain injury
  • 2022
  • Ingår i: EBioMedicine. - : Elsevier. - 2352-3964. ; 77
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Factors such as age, pre-injury health, and injury severity, account for less than 35% of outcome variability in traumatic brain injury (TBI). While some residual outcome variability may be attributable to genetic factors, published candidate gene association studies have often been underpowered and subject to publication bias.METHODS: We performed the first genome- and transcriptome-wide association studies (GWAS, TWAS) of genetic effects on outcome in TBI. The study population consisted of 5268 patients from prospective European and US studies, who attended hospital within 24 h of TBI, and satisfied local protocols for computed tomography.FINDINGS: The estimated heritability of TBI outcome was 0·26. GWAS revealed no genetic variants with genome-wide significance (p < 5 × 10-8), but identified 83 variants in 13 independent loci which met a lower pre-specified sub-genomic statistical threshold (p < 10-5). Similarly, none of the genes tested in TWAS met tissue-wide significance. An exploratory analysis of 75 published candidate variants associated with 28 genes revealed one replicable variant (rs1800450 in the MBL2 gene) which retained significance after correction for multiple comparison (p = 5·24 × 10-4).INTERPRETATION: While multiple novel loci reached less stringent thresholds, none achieved genome-wide significance. The overall heritability estimate, however, is consistent with the hypothesis that common genetic variation substantially contributes to inter-individual variability in TBI outcome. The meta-analytic approach to the GWAS and the availability of summary data allows for a continuous extension with additional cohorts as data becomes available.FUNDING: A full list of funding bodies that contributed to this study can be found in the Acknowledgements section.
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42.
  • Karlsson, Britt M., et al. (författare)
  • Nimodipine affects the microcirculation and modulates the vascular effects of acetylcholinesterase inhibition
  • 2003
  • Ingår i: Upsala Journal of Medical Sciences. - : Taylor & Francis. - 0300-9734 .- 2000-1967. ; 108:2, s. 141-149
  • Tidskriftsartikel (refereegranskat)abstract
    • The present investigation was undertaken in order to study whether microvascular effects of the calcium antagonist nimodipine induces changes that can explain an increased detoxification of the highly toxic cholinesterase inhibitor soman. Anaesthetised, tracheotomised and artificially ventilated rats were treated intra-peritoneally (ip) with nimodipine, 10 mg kg(-1) or vehicle followed one hour later by the exposure to 45 microg kg(-1) soman (iv). Nimodipine per se induced a vasodilation in the intestine, myocardium and other muscles. In the abdominal skin soman elicited a significant vasoconstriction that was turned into an increased blood flow after nimodipine pre-treatment. A slight vasoconstriction in diaphragm of soman intoxicated rats was turned into a significant vasodilation by nimodipine pre-treatment. In the intestinal parts no effect of soman was detected. However, in nimodipine pretreated animals soman induced a significant vasoconstriction. The capacity of soman detoxifying processes, i.e. enzymatic hydrolysis and covalent binding to different esterases, is unequally distributed throughout the body. Together with the knowledge of the detoxifying processes of cholinesterase inhibition the results support our theory, that nimodipine alters the peripheral blood flow in a beneficial way resulting in improved detoxification ability.
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43.
  • Karlsson, Britt M., et al. (författare)
  • The effect of the calcium antagonist nimodipine on the detoxification of soman in anaesthetized rabbits.
  • 1997
  • Ingår i: Journal of Pharmacy and Pharmacology (JPP). - : Oxford University Press (OUP). - 0022-3573 .- 2042-7158. ; 49:3, s. 296-300
  • Tidskriftsartikel (refereegranskat)abstract
    • The effect of nimodipine, a vasoactive calcium antagonist, on the disappearance of soman from blood was studied in anaesthetized rabbits intoxicated with soman (10.8 micrograms kg-1 i.v.). Blood samples from the left heart ventricle and femoral artery were used to investigate soman detoxification. The concentrations of the soman isomers C+P- and C-P- in blood samples were determined by gas chromatography coupled with high-resolution mass spectrometry. During the sampling, 15-300 s after soman injection, the soman concentration in control animals decreased from 50 to 0.029 ng mL-1; in animals pre-treated with nimodipine (10 mg kg-1) it decreased from 15 to 0.033 ng mL-1. In animals pre-treated with nimodipine the soman concentration was significantly reduced during the first minute of sampling. No differences were detected between soman concentrations in samples from the heart and femoral artery. Acetylcholinesterase inhibition was also used as an indicator of soman activity; there was no difference between the activity of this enzyme in different peripheral organs of control and nimodipine-treated animals. Nimodipine reduces the initial concentration of soman in the blood, which might be of significance in the treatment of soman intoxication.
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44.
  • Koch, Bo L., et al. (författare)
  • Inhalation of substance P and thiorphan : acute toxicity and effects on respiration in conscious guinea pigs.
  • 1999
  • Ingår i: Journal of Applied Toxicology. - 0260-437X .- 1099-1263. ; 19:1, s. 19-23
  • Tidskriftsartikel (refereegranskat)abstract
    • Substance P is a tachykinin and a biologically active neuropeptide. The peptide produces salivation, neuronal excitation, vasodilatation, increased vascular permeability and contraction of smooth muscles in the respiratory tract. The study was designed to evaluate the acute effects in guinea pigs of inhaled aerosolized Substance P (SP). Apart from the acute toxic effect of the peptide, the distribution in different organs was also investigated. The acute inhalation toxicity of SP (LC50, 15 min) when co-administrated with the neutral endopeptidase inhibitor thiorphan was 368 microg m(-3). The peptide caused an increase in respiratory rate proceeding a decrease in tidal volume. As the exposure proceeded, a decrease in both respiratory rate and further decreases in tidal volume were observed until either the animal died or the exposure was terminated. The decreases in respiratory rate and tidal volume were probably due to bronchoconstriction caused by SP. Eighteen per cent of the inhaled amount of radioactive SP was retained in the body, and the highest concentrations of radioactivity were found in the kidney, lung and liver. Substance P in combination with thiorphan administered as an aerosol is extremely toxic and highly potent. Exposure to the substance at extremely low air concentrations may result in incapacitation in humans.
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45.
  • Koskinen, Lars-Owe D., Professor, 1955- (författare)
  • Cerebral and peripheral blood flow effects of TRH in the rat : a role of vagal nerves
  • 1989
  • Ingår i: Peptides. - : Elsevier BV. - 0196-9781 .- 1873-5169. ; 10:5, s. 933-938
  • Tidskriftsartikel (refereegranskat)abstract
    • The cardiovascular effects of the IV infusion of TRH were studied in the rat. TRH tended to increase the MAP and markedly increased the CBF(tot) in the control group, in vagotomized animals and in methylatropine-pretreated rats. A marked vasodilation was noted in the pancreas, gastric mucosa, duodenum and cardiac muscle. This effect was turned to vasoconstriction, the heart excluded, in vagotomized animals. Muscarinic blockade attenuated the vasodilating effect of TRH in the duodenum and gastric mucosa. The results indicate that TRH elicits cerebral vasodilation and a partly nonmuscarinic parasympathetically mediated vasodilation in several gastrointestinal organs in parallel with a vasoconstriction which is unmasked by vagotomy.
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46.
  • Koskinen, Lars-Owe D., Professor, 1955-, et al. (författare)
  • Cerebrovascular effects of the TRH analogues pGlu-3-methyl-His-Pro amide and pGlu-Glu-Pro amide : a comparison with TRH.
  • 2000
  • Ingår i: Upsala Journal of Medical Sciences. - : Upsala Medical Society. - 0300-9734 .- 2000-1967. ; 105:1, s. 73-83
  • Tidskriftsartikel (refereegranskat)abstract
    • The goal of the study was to assess whether TRH analogues possess cerebrovascular effects similar to the native peptide. The neuropeptide thyrotropin releasing hormone (TRH) elicits cerebrovasodilation in several species under various conditions. The laser-Doppler method was employed to study the effects of TRH and the analogues pGlu-3-methyl-His-Pro amid (M-TRH) and pGlu-Glu-Pro amide. Intravenous (i.v.) injection of 300 microg kg(-1) of TRH elicited cerebrovasodilation and a 62% increase in blood flow within 1 minute. M-TRH, in a dose of 300 microg kg(-1) i.v., elicited a 80% increase in cerebral blood flow. Even a minute dose of M-TRH (625 ng kg(-1)) caused an increase in cerebral blood flow. No clear difference in effects on the cerebral blood flow was observed between spontaneously and mechanically ventilated animals, pGlu-Glu-Pro amide had no cerebrovascular effect.
  •  
47.
  • Koskinen, Lars-Owe D., Professor, 1955-, et al. (författare)
  • Cigarette smoke and hypoxia induce acute changes in the testicular and cerebral microcirculation
  • 2000
  • Ingår i: Upsala Journal of Medical Sciences. - : Taylor & Francis. - 0300-9734 .- 2000-1967. ; 105:3, s. 215-226
  • Tidskriftsartikel (refereegranskat)abstract
    • The acute effects of cigarette smoking and hypoxia on the cerebral and testicular microcirculation were studied in anestethised adult rats. Smoking for 2 min did not influence arterial pO2, pCO2 or pH but it induced an increase in cerebral blood flow by 34% and inhibited vasomotion in the testis for about 1 h. One hour after smoke exposure apnea induced a slight increase in arterial pCO2, a significant decrease in pO2, and an increase in cerebral blood flow (CBF) by 54%. In animals not previously exposed to cigarette smoke apnea increased CBF by 121%, demonstrating that a short-term exposure to tobacco smoke influences the cerebrovascular reactivity for more than one hour. In the testis, apnea resulted in a decreased blood flow by 39% and a complete depression of vasomotion. Breathing 10% O2/90% N2 resulted in moderate hypoxia, a total disappearance of the vasomotion in the testis, a 24% decrease in testicular blood flow, but a 23% increase in CBF.Our results indicate that short-term exposure to tobacco smoke induces marked acute vascular effects in both the brain and the testis. Apnea and moderate hypoxia elicited totyally different effects in the brain and testis, inicating different vascular control mechanisms. 
  •  
48.
  • Koskinen, Lars-Owe D., Professor, 1955- (författare)
  • CSF drainage
  • 2012
  • Ingår i: Management of severe traumatic brain injury. - Berlin, Heidelberg : Springer Berlin/Heidelberg. - 9783642281266 - 9783642281259 - 9783662505533 ; , s. 285-287
  • Bokkapitel (refereegranskat)abstract
    • In an early retrospective study in 39 patients, intermittent or continuous CSF drainage was applied, and it was concluded that early drainage was of little use in influencing ICP while later CSF removal had a more pronounced effect (Papo et al. 1981). In a prospective study on 31 patients, it was shown that various volumes of CSF intermittent drainage significantly decreased the ICP with a few mmHg, but in only 6/31 subjects, the decrease was more than 3 mmHg and lasting for more than 10 min (Kerr et al. 2000). A prospective study in 24 subjects, with sustained elevated ICP after other ICP decreasing measures, showed that in about 50% of the cases, the ICP was brought under control after continuous drainage (Timofeev et al. 2008). In a prospective study of 45 patients with sTBI and 55 patients with SAH and presenting refractory ICP elevation, a combination of ventriculostomy and lumbar drainage was shown to reduce the ICP but not to affect outcome (Tuettenberg et al. 2009). In that same study, 12% presented with cerebral herniation and 6% died due to herniation. Some studies have shown an improved outcome after using CSF drainage (Timofeev et al. 2008; Ghajar et al. 1993).
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49.
  • Koskinen, Lars-Owe D., Professor, 1955- (författare)
  • Effect of low intravenous doses of TRH, acid-TRH and cyclo(His-Pro) on cerebral and peripheral blood flows.
  • 1986
  • Ingår i: British Journal of Pharmacology. - : Wiley. - 0007-1188 .- 1476-5381. ; 87:3, s. 509-519
  • Tidskriftsartikel (refereegranskat)abstract
    • Local cerebral and peripheral blood flow in conscious and anaesthetized rabbits were investigated with the microsphere method, before and after the i.v. administration of 25 or 50 micrograms kg-1 thyrotropin-releasing hormone (TRH). Before the experiment, the cervical sympathetic chain was sectioned on one side in order to evaluate the possible effect of the sympathetic nerves on cranial and extracranial blood flows. Blood flow was also determined in anaesthetized rabbits before and after the administration of the TRH metabolites cyclo(His-Pro) and acid-TRH and after subsequent administration of 50 micrograms kg-1 TRH. TRH caused an increase in mean arterial blood pressure (MAP) of about 1 to 2 kPa whereas cyclo(His-Pro) and acid-TRH had no effect on MAP. In the anaesthetized animal an increase in total cerebral blood flow (CBFtot), from 71 +/- 7 to 107 +/- 12 g min-1 100 g-1 (P less than 0.05) was observed on the sympathetic intact side after 25 micrograms kg-1 TRH and a further increase to 130 +/- 9 g min-1 100g-1 (P less than 0.01) after 50 micrograms kg-1 TRH. A similar effect was observed on the sympathotomized side. An effect on CBF in the conscious animal was not detected. The control CBFtot (104 +/- 8 g min-1 100g-1) was higher in these animals than in the anaesthetized animals (P less than 0.02). Neither cyclo(His-Pro) nor acid-TRH mimicked the effect of TRH on CBF. In several peripheral tissues, e.g. skin, pancreas and gastric mucosa, a reduction in blood flow was noted after the administration of TRH in both anaesthetized and conscious rabbits. It was concluded that TRH can induce cerebral vasodilatation in animals with a depressed CBF, whereas the vasoconstrictor effect of TRH in peripheral organs is not markedly affected by the state of consciousness.
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50.
  • Koskinen, Lars-Owe D., Professor, 1955- (författare)
  • Effects of raised intracranial pressure on regional cerebral blood flow : a comparison of effects of naloxone and TRH on the microcirculation in partial cerebral ischaemia.
  • 1985
  • Ingår i: British Journal of Pharmacology. - : Wiley. - 0007-1188 .- 1476-5381. ; 85:2, s. 489-497
  • Tidskriftsartikel (refereegranskat)abstract
    • The effects on regional cerebral blood flow (rCBF) of raised intracranial pressure (ICP) and of naloxone and thyrotropin releasing hormone (TRH) during this condition were studied in anaesthetized rabbits. The ICP was elevated until a central ischaemic response was observed. The regional blood flow was determined with the microsphere technique before and during elevation of the ICP (ICPe) and after drug treatment. Total CBF was reduced by about 70% during ICPe while the uveal blood flow increased slightly and some other peripheral tissue blood flows remained unaffected. The administration of TRH caused an increase in mean arterial blood pressure (MAP) from 11.9 +/- 0.6 to 14.6 +/- 0.7 kPa and a normalization of the rCBF. In some peripheral tissues, e.g. gastric mucosa and spleen, TRH reduced the blood flow by 53% and 76%, respectively. In blood pressure stabilized animals no effect on rCBF was seen after TRH. Naloxone had no consistent effect on MAP or local blood flow. It was concluded that in the range of cerebral perfusion pressure studied there was a passive relationship between cerebral blood flow and perfusion pressure. The lack of effect of naloxone and the marked effect of TRH during cerebral ischaemia are consistent with a mechanism of action of TRH not related to a 'physiological' antagonism of opioids.
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