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  • 1.
    Aineskog, Helena
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Neurovetenskaper.
    Johansson, Conny
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Neurovetenskaper.
    Nilsson, Robert
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Neurovetenskaper.
    Koskinen, Lars-Owe D.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Neurovetenskaper.
    Lindvall, Peter
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Neurovetenskaper.
    Serum S100B correlates with health-related quality of life and functional outcome in patients at 1 year after aneurysmal subarachnoid haemorrhage2022Ingår i: Acta Neurochirurgica, ISSN 0001-6268, E-ISSN 0942-0940, Vol. 164, nr 8, s. 2209-2218Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    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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  • 2. Andelic, Nada
    et al.
    Røe, Cecilie
    Brunborg, Cathrine
    Zeldovich, Marina
    Løvstad, Marianne
    Løke, Daniel
    Borgen, Ida M.
    Voormolen, Daphne C.
    Howe, Emilie I.
    Forslund, Marit V.
    Dahl, Hilde M.
    von Steinbuechel, Nicole
    Koskinen, Lars-Owe (Medarbetare/bidragsgivare)
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Neurovetenskaper.
    Frequency of fatigue and its changes in the first 6 months after traumatic brain injury: results from the CENTER-TBI study2021Ingår i: Journal of Neurology, ISSN 0340-5354, E-ISSN 1432-1459, Vol. 268, nr 1, s. 61-73Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    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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  • 3.
    Andersson, Nina
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper.
    Grip, Helena
    Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering, Sjukgymnastik.
    Lindvall, Peter
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Koskinen, Lars-Owe D
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Brändström, Helge
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Anestesiologi och intensivvård.
    Malm, Jan
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Eklund, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Air transport of patients with intracranial air: computer model of pressure effects2003Ingår i: Aviation, Space and Environmental Medicine, ISSN 0095-6562, E-ISSN 1943-4448, Vol. 74, nr 2, s. 138-144Artikel i tidskrift (Refereegranskat)
  • 4. Arango-Lasprilla, Juan Carlos
    et al.
    Zeldovich, Marina
    Olabarrieta-Landa, Laiene
    Vindal Forslund, Marit
    Núñez-Fernández, Silvia
    von Steinbuechel, Nicole
    Isager Howe, Emilie
    Røe, Cecilie
    Andelic, Nada
    Koskinen, Lars-Owe D. (Medarbetare/bidragsgivare)
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Neurovetenskaper.
    Sundström, Nina (Medarbetare/bidragsgivare)
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper.
    Early Predictors of Employment Status One Year Post Injury in Individuals with Traumatic Brain Injury in Europe2020Ingår i: Journal of Clinical Medicine, E-ISSN 2077-0383, Vol. 9, nr 6, artikel-id 2007Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    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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  • 5.
    Arnell, Kai
    et al.
    Department of Paediatric Surgery, University Hospital, Uppsala.
    Koskinen, Lars-Owe D
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Neurokirurgi.
    Malm, Jan
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Neurologi.
    Eklund, Anders
    Evaluation of Strata NSC and Codman Hakim adjustable cerebrospinal fluid shunts and their corresponding antisiphon devices: laboratory investigation2009Ingår i: Journal of Neurosurgery: Pediatrics, ISSN 1933-0707, E-ISSN 1933-0715, Vol. 3, nr 3, s. 166-172Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    OBJECT: The authors investigated and compared the in vitro characteristics of 2 CSF shunts, the Strata NSC and the Codman Hakim, and their corresponding antisiphon devices (ASDs).

    METHODS: Six new CSF shunts and the corresponding ASDs for each model were tested in an automated, computerized experimental setup based on pressure regulation. Opening pressure accuracy, resistance, sensitivity to abdominal pressure, antisiphon effect, and the influence of different ASD positions were determined.

    RESULTS: In general the shunts performed according to the manufacturers' specifications. However, at the lowest setting, the opening pressure of the Strata NSC was close to 0, and in the Codman Hakim shunt, it was higher than specified. The resistance in the Codman Hakim shunt (5.4 mm Hg/ml/min) was much higher than that in the Strata NSC (3.6 mm Hg/ml/min). Abdominal pressure affected opening pressure in both valves. Positioning the Strata ASD above or below the ventricular catheter tip resulted in higher and lower opening pressures, respectively, than when it was placed in line with the catheter. The positioning of the Codman Hakim ASD did not influence the opening pressure.

    CONCLUSIONS: Both CSF shunts work properly, but at the lowest setting the opening pressure of the Strata NSC was near 0 and in the Codman Hakim it was twice the manufacturer's specifications. The resistance in the Strata NSC was below the normal physiological range, and in the Codman Hakim device it was in the lower range of normal. The ASD did not change the shunt characteristics in the lying position and therefore might not do so in children. If this is the case, then a shunt system with an integrated ASD could be implanted at the first shunt insertion, thus avoiding a second operation and the possibility of infection.

  • 6.
    Behrens, Anders
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Neurologi.
    Lenfeldt, Niklas
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Neurologi.
    Ambarki, Khalid
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Radiofysik.
    Malm, Jan
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Neurologi.
    Eklund, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Radiofysik.
    Koskinen, Lars-Owe
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Neurokirurgi.
    Transcranial Doppler pulsatility index: not an accurate method to assess intracranial pressure.2010Ingår i: Neurosurgery, ISSN 0148-396X, E-ISSN 1524-4040, Vol. 66, nr 6, s. 1050-1057Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND: Transcranial Doppler sonography (TCD) assessment of intracranial blood flow velocity has been suggested to accurately determine intracranial pressure (ICP). OBJECTIVE: We attempted to validate this method in patients with communicating cerebrospinal fluid systems using predetermined pressure levels. METHODS: Ten patients underwent a lumbar infusion test, applying 4 to 5 preset ICP levels. On each level, the pulsatility index (PI) in the middle cerebral artery was determined by measuring the blood flow velocity using TCD. ICP was simultaneously measured with an intraparenchymal sensor. ICP and PI were compared using correlation analysis. For further understanding of the ICP-PI relationship, a mathematical model of the intracranial dynamics was simulated using a computer. RESULTS: The ICP-PI regression equation was based on data from 8 patients. For 2 patients, no audible Doppler signal was obtained. The equation was ICP = 23*PI + 14 (R = 0.22, P < .01, N = 35). The 95% confidence interval for a mean ICP of 20 mm Hg was -3.8 to 43.8 mm Hg. Individually, the regression coefficients varied from 42 to 90 and the offsets from -32 to +3. The mathematical simulations suggest that variations in vessel compliance, autoregulation, and arterial pressure have a serious effect on the ICP-PI relationship. CONCLUSIONS: The in vivo results show that PI is not a reliable predictor of ICP. Mathematical simulations indicate that this is caused by variations in physiological parameters.

  • 7.
    Behrens, Anders
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Lenfeldt, Niklas
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Ambarki, Khalid
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Radiofysik.
    Malm, Jan
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Eklund, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Radiofysik. Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Centrum för medicinsk teknik och fysik (CMTF).
    Koskinen, Lars-Owe D
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Neurokirurgi.
    Intracranial Pressure and Pulsatility Index:  2011Ingår i: Neurosurgery, ISSN 0148-396X, E-ISSN 1524-4040, Vol. 69, nr 4, s. E1033-E1034Artikel i tidskrift (Refereegranskat)
  • 8.
    Behrens, Anders
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Lenfeldt, Niklas
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Qvarlander, Sara
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Radiofysik.
    Koskinen, Lars-Owe
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Malm, Jan
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Eklund, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Are intracranial pressure wave amplitudes measurable through lumbar puncture?2013Ingår i: Acta Neurologica Scandinavica, ISSN 0001-6314, E-ISSN 1600-0404, Vol. 127, nr 4, s. 233-241Artikel i tidskrift (Refereegranskat)
    Abstract [en]

     Objective The aim of this study was to investigate whether pulsations measured in the brain correspond to those measured in lumbar space, and subsequently whether lumbar punctures could replace invasive recordings. Methods In ten patients with normal pressure hydrocephalus, simultaneous recordings of the intracranial pressure (ICP; intraparenchymal) and lumbar pressure (LP; cerebrospinal fluid pressure) were performed. During registration, pressure was altered between resting pressure and 45mmHg using an infusion test. Data were analyzed regarding pulsations (i.e., amplitudes). Also, the pressure sensors were compared in a bench test. Results The correlation between intracranial and lumbar amplitudes was 0.98. At resting pressure, and moderately elevated ICP, intracranial pulse amplitudes exceeded that of lumbar space with about 0.9mmHg. At the highest ICP, the difference changed to 0.2mmHg. The bench test showed that the agreement of sensor readings was good at resting pressure, but reduced at higher amplitudes. Conclusions Compared to intracranial registrations, amplitudes measured through lumbar puncture were slightly attenuated. The bench test showed that differences were not attributable to dissimilarities of the sensor systems. A lumbar pressure amplitude measurement is an alternative to ICP recording, but the thresholds for what should be interpreted as elevated amplitudes need to be adjusted.

  • 9. Björkman, Sven
    et al.
    Lewander, Tommy
    Karlsson, Jan-Anders
    Koskinen, Lars-Owe D.
    Psychiatric Research Center, Ulleråker Hospital, University of Uppsala, S‐750 17 Uppsala, Sweden.
    Zetterström, Tyra
    Thermic and tremorogenic effects of thyroliberin (TRH) in reserpine-treated mice--the non-involvement of GABA-ergic mechanisms.1981Ingår i: Journal of Pharmacy and Pharmacology (JPP), ISSN 0022-3573, E-ISSN 2042-7158, Vol. 33, nr 9, s. 580-585Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    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.

  • 10.
    Björnfot, Cecilia
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Radiofysik. Umeå universitet, Medicinska fakulteten, Institutionen för diagnostik och intervention.
    Eklund, Anders
    Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI). Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Radiofysik. Umeå universitet, Medicinska fakulteten, Institutionen för diagnostik och intervention.
    Larsson, Jenny
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Neurovetenskaper.
    Hansson, William
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Neurovetenskaper.
    Birnefeld, Johan
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Neurovetenskaper.
    Garpebring, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för diagnostik och intervention.
    Qvarlander, Sara
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Radiofysik. Umeå universitet, Medicinska fakulteten, Institutionen för diagnostik och intervention.
    Koskinen, Lars-Owe D.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Neurovetenskaper.
    Malm, Jan
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Neurovetenskaper.
    Wåhlin, Anders
    Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI). Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Institutionen för tillämpad fysik och elektronik. Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Radiofysik. Umeå universitet, Medicinska fakulteten, Institutionen för diagnostik och intervention.
    Cerebral arterial stiffness is linked to white matter hyperintensities and perivascular spaces in older adults: a 4D flow MRI study2024Ingår i: Journal of Cerebral Blood Flow and Metabolism, ISSN 0271-678X, E-ISSN 1559-7016Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    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.

  • 11.
    Blomstedt, Patric
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Neurokirurgi.
    Hariz, Gun-Marie
    Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering, Arbetsterapi.
    Hariz, Marwan I
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Neurokirurgi.
    Koskinen, Lars-Owe D
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Neurokirurgi.
    Thalamic deep brain stimulation in the treatment of essential tremor: a long-term follow-up2007Ingår i: British Journal of Neurosurgery, ISSN 0268-8697, E-ISSN 1360-046X, Vol. 21, nr 5, s. 504-509Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Deep brain stimulation (DBS) of the nucleus ventralis intermedius thalami (Vim) in the treatment of essential tremor (ET) is well documented concerning the acute effects. Reports of the long-term effects are, however, few and the aim of the present study was to analyse the long-term efficacy of this treatment. Nineteen patients operated with unilateral Vim-DBS were evaluated with the Essential Tremor Rating Scale (ETRS) before surgery, and after a mean time of 1 and 7 years after surgery. The ETRS score for tremor of the contralateral hand was reduced from 6.8 at baseline to 1.2 and 2.7, respectively, on stimulation at follow-up. For hand function (item 11 – 14) the score was reduced from 12.7 to 4.1 and 8.2, respectively. Vim-DBS is an efficient treatment for ET, also after many years of treatment. There is, however, a decreasing effect over time, most noticeable concerning tremor of action.

    Read More: http://informahealthcare.com/doi/abs/10.1080/02688690701552278

  • 12.
    Blomstedt, Patric
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Neurokirurgi.
    Jabre, Mazen
    Bejjani, Boulos-Paul
    Koskinen, Lars-Owe
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Neurokirurgi.
    Electromagnetic environmental influences on implanted deep brain stimulators2006Ingår i: Neuromodulation, ISSN 1094-7159, E-ISSN 1525-1403, Vol. 9, nr 4, s. 262-269Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objective.  The objective of this study was to report our observations on the external electromagnetic field influences on deep brain stimulation (DBS) in our patient population and how these influences affected our patients’ lives and other healthcare-related conditions.

    Materials and Methods.  We have retrospectively analyzed data concerning the effects of external electromagnetic fields on 172 of our patients implanted with DBS.

    Results.  Identifiable electromagnetic sources turned the implantable pulse generator (IPG) off in 20 patients. In two patients, these episodes necessitated replacement of the Itrel II IPG (Medtronic Inc., Minneapolis, MN, USA) with the magnetically shielded Kinetra IPG (Medtronic Inc.). Six patients received cardiac pacemakers, leading, in two patients, to interference between the systems. Our experience concerning magnetic resonance imaging, electrocardiogram (ECG), heart defibrillation, electro-cautery, and other sources of electromagnetic interference also is described.

    Conclusions.  External electromagnetic interference may, in rare cases, constitute a severe threat to the well-being of the patient implanted with a DBS system. Also, malfunction of a DBS system may constitute a medical emergency. Nevertheless, in spite of these external electromagnetic influences, we consider DBS to be a safe method, provided safety protocols are followed, and provided that provider awareness about potential hazards is present.

  • 13.
    Blomstedt, Patric
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Neurokirurgi.
    Sandvik, Ulrika
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Neurokirurgi.
    Hariz, Marwan
    UCL Insitute of Neurology, Queen Square, London, Uk.
    Fytagoridis, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Neurokirurgi.
    Forsgren, Lars
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Hariz, Gun-Marie
    Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering, Arbetsterapi.
    Koskinen, Lars-Owe
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Neurokirurgi.
    Influence of age, gender and severity of tremor on outcome after thalamic and subthalamic DBS for essential tremor2011Ingår i: Parkinsonism & Related Disorders, ISSN 1353-8020, E-ISSN 1873-5126, Vol. 17, nr 8, s. 617-620Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Deep brain stimulation (DBS) is an established treatment for essential tremor (ET). The nucleus ventralis intermedius thalami (Vim) is the target of choice, but promising results have been presented regarding DBS in the posterior subthalamic area (PSA). The aim of this study was to evaluate the possible influence of gender, age and severity of disease on the outcome of these procedures. Sixty eight patients (34 Vim, 34 PSA) with ET were included in this non-randomised study. Evaluation using the Essential Tremor Rating Scale (ETRS) was performed before, and one year after surgery concerning PSA DBS, and at a mean of 28 ± 24 months concerning Vim DBS. Items 5/6 and 11-14 (hand tremor and hand function) were selected for analysis of tremor outcome. The efficacy of DBS on essential tremor was not related to age or gender. Nor was it associated with the severity of tremor when the percentual reduction of tremor on stimulation was taken into account. However, patients with a more severe tremor at baseline had a higher degree of residual tremor on stimulation. Tremor in the treated hand and hand function were improved with 70% in the Vim group and 89% in the PSA group.

  • 14.
    Bobinski, Lukas
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Koskinen, Lars-Owe D.
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Lindvall, Peter
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Complications following cranioplasty using autologous bone or polymethylmethacrylate-Retrospective experience from a single center2013Ingår i: Clinical neurology and neurosurgery (Dutch-Flemish ed. Print), ISSN 0303-8467, E-ISSN 1872-6968, Vol. 115, nr 9, s. 1788-1791Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objective: A decompressive hemicraniectomy is a potentially life-saving intervention following head trauma. Once performed patients are obliged to undergo a second procedure with cranioplasty. Two of the most commonly used materials are autologous bone and polymethylmethacrylate (PMMA). We have now evaluated complications following a cranioplasty using these materials. Materials and methods: During a 7-year period (2002-2008) 49 patients were operated with a decompressive craniectomy following head trauma. Patients received a cranioplasty consisting of autologous bone (30 patients, 61.2%) or PMMA (19 patients, 38.8%) and were followed at least 24 months. Patient data were collected retrospectively. Results: Twenty patients (20/49, 40.8%) experienced a complication that prompted a re-operation. There was a significantly higher rate of complications leading to a re-operation (53.3% vs. 21.1%, p = 0.03) and a shorter survival time of the cranioplasty (mean 48.1 +/- 7.8 vs. 79.5 +/- 9.0 months, p = 0.035) in patients with autologous bone compared to PMMA. Bone resorption and the presence of postoperative hematomas were significantly more common in patients with autologous bone. The material used for cranioplasty was the only variable that significantly correlated to the rate of complications. Conclusions: In our series we had a high percentage of patients needing re-operation due to complications following a cranioplasty. Though generally considered a straightforward procedure, complications and associated morbidity in patients undergoing cranioplasty should not be underestimated. 

  • 15.
    Bobinski, Lukas
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Olivecrona, Magnus
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Koskinen, Lars-Owe D.
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Dynamics of brain tissue changes induced by traumatic brain injury assessed with the Marshall, Morris-Marshall, and the Rotterdam classifications and its impact on outcome in a prostacyclin placebo-controlled study2012Ingår i: Acta Neurochirurgica, ISSN 0001-6268, E-ISSN 0942-0940, Vol. 154, nr 6, s. 1069-1079Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The present study evaluates the types and dynamics of intracranial pathological changes in patients with severe traumatic brain injury (sTBI) who participated in a prospective, randomized, double-blinded study of add-on treatment with prostacyclin. Further, the changes of brain CT scan and their correlation to Glasgow Coma Scale score (GCS), maximal intracranial pressure (ICPmax), minimal cerebral perfusion pressure (CPPmin), and Glasgow Outcome Score (GOS) at 3, 6, and 12 months were studied. Forty-eight subjects with severe traumatic brain injury were treated according to an ICP-targeted therapy protocol based on the Lund concept with the addition of prostacyclin or placebo. The first available CT scans (CTi) and follow-up scans nearest to 24 h (CT24) were evaluated using the Marshall, Rotterdam, and Morris-Marshall classifications. There was a significant correlation of the initial Marshall, Rotterdam, Morris-Marshall classifications and GOS at 3 and 12 months. The CT24 Marshall classification did not significantly correlate to GOS while the Rotterdam and the Morris-Marshall classification did. The CTi Rotterdam classification predicted outcome evaluated as GOS at 3 and 12 months. Prostacyclin treatment did not influence the dynamic of tissue changes. The Rotterdam classification seems to be appropriate for describing the evolution of the injuries on the CT scans and contributes in predicting of outcome in patients treated with an ICP-targeted therapy. The Morris-Marshall classification can also be used for prognostication of outcome but it describes only the impact of traumatic subarachnoid hemorrhage (tSAH).

  • 16.
    Bobinski, Lukas
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Olivecrona, Magnus
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Koskinen, Lars-Owe D.
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Rotterdam score, ICP, CPP, S-100B, NSE and their association with Decompressive Craniectomy in severe Traumatic Brain InjuryManuskript (preprint) (Övrigt vetenskapligt)
  • 17. Bockhop, Fabian
    et al.
    Zeldovich, Marina
    Cunitz, Katrin
    Van Praag, Dominique
    van der Vlegel, Marjolein
    Beissbarth, Tim
    Hagmayer, York
    von Steinbuechel, Nicole
    Kondziella, Daniel (Medarbetare/bidragsgivare)
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Neurovetenskaper.
    Koskinen, Lars-Owe D. (Medarbetare/bidragsgivare)
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Neurovetenskaper.
    Sundström, Nina (Medarbetare/bidragsgivare)
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper.
    Measurement invariance of six language versions of the post-traumatic stress disorder checklist for DSM-5 in civilians after traumatic brain injury2022Ingår i: Scientific Reports, E-ISSN 2045-2322, Vol. 12, nr 1, artikel-id 16571Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    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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  • 18.
    Brorsson, Camilla
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Anestesiologi och intensivvård.
    Rodling-Wahlström, Marie
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Anestesiologi och intensivvård.
    Olivecrona, Magnus
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Koskinen, Lars-Owe
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Naredi, Silvana
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Anestesiologi och intensivvård.
    Severe traumatic brain injury: consequences of early adverse events2011Ingår i: Acta Anaesthesiologica Scandinavica, ISSN 0001-5172, E-ISSN 1399-6576, Vol. 55, nr 8, s. 944-951Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Several factors associated with an unfavourable outcome after severe traumatic brain injury (TBI) have been described: prolonged pre-hospital time, secondary referral to a level 1 trauma centre, the occurrence of secondary insults such as hypoxia, hypotension or low end-tidal carbon dioxide (ETCO(2)). To determine whether adverse events were linked to outcome, patients with severe TBI were studied before arrival at a level 1 trauma centre.

    Methods: Prospective, observational study design. Patients with severe TBI (n = 48), admitted to Umea University Hospital between January 2002 to December 2005 were included. All medical records from the site of the accident to arrival at the level 1 trauma centre were collected and evaluated.

    Results: A pre-hospital time of >60 min, secondary referral to a level 1 trauma centre, documented hypoxia (oxygen saturation <95%), hypotension (systolic blood pressure <90 mmHg), hyperventilation (ETCO(2) <4.5 kPa) or tachycardia (heart rate >100 beats/min) at any time before arrival at a level 1 trauma centre were not significantly related to an unfavourable outcome (Glasgow Outcome Scale 1-3).

    Conclusion: Early adverse events before arrival at a level 1 trauma centre were without significance for outcome after severe TBI in the trauma system studied.

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  • 19.
    Brändström, Helge
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Anestesiologi och intensivvård.
    Sundelin, Anna
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Anestesiologi och intensivvård.
    Hoseason, Daniela
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Anestesiologi och intensivvård.
    Sundström, Nina
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper.
    Birgander, Richard
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Diagnostisk radiologi.
    Johansson, Göran
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Anestesiologi och intensivvård.
    Winsö, Ola
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Anestesiologi och intensivvård.
    Koskinen, Lars-Owe
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Haney, Michael
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Anestesiologi och intensivvård.
    Risk for intracranial pressure increase related to enclosed air in post-craniotomy patients during air ambulance transport: a retrospective cohort study with simulation2017Ingår i: Scandinavian Journal of Trauma, Resuscitation and Emergency Medicine, E-ISSN 1757-7241, Vol. 25, artikel-id 50Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND: Post-craniotomy intracranial air can be present in patients scheduled for air ambulance transport to their home hospital. We aimed to assess risk for in-flight intracranial pressure (ICP) increases related to observed intracranial air volumes, hypothetical sea level pre-transport ICP, and different potential flight levels and cabin pressures. METHODS: A cohort of consecutive subdural hematoma evacuation patients from one University Medical Centre was assessed with post-operative intracranial air volume measurements by computed tomography. Intracranial pressure changes related to estimated intracranial air volume effects of changing atmospheric pressure (simulating flight and cabin pressure changes up to 8000 ft) were simulated using an established model for intracranial pressure and volume relations. RESULTS: Approximately one third of the cohort had post-operative intracranial air. Of these, approximately one third had intracranial air volumes less than 11 ml. The simulation estimated that the expected changes in intracranial pressure during 'flight' would not result in intracranial hypertension. For intracranial air volumes above 11 ml, the simulation suggested that it was possible that intracranial hypertension could develop 'inflight' related to cabin pressure drop. Depending on the pre-flight intracranial pressure and air volume, this could occur quite early during the assent phase in the flight profile. DISCUSSION: These findings support the idea that there should be radiographic verification of the presence or absence of intracranial air after craniotomy for patients planned for long distance air transport. CONCLUSIONS: Very small amounts of air are clinically inconsequential. Otherwise, air transport with maintained ground-level cabin pressure should be a priority for these patients.

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  • 20. Böhm, Julia K.
    et al.
    Güting, Helge
    Thorn, Sophie
    Schäfer, Nadine
    Rambach, Victoria
    Schöchl, Herbert
    Grottke, Oliver
    Rossaint, Rolf
    Stanworth, Simon
    Curry, Nicola
    Lefering, Rolf
    Maegele, Marc
    Vámos, Zoltán
    Brorsson, Camilla
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Anestesiologi och intensivvård.
    Global Characterisation of Coagulopathy in Isolated Traumatic Brain Injury (iTBI): A CENTER-TBI Analysis2020Ingår i: Neurocritical Care, ISSN 1541-6933, E-ISSN 1556-0961, Vol. 35, nr 1, s. 184-196Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    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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  • 21. Böhm, Julia K.
    et al.
    Schaeben, Victoria
    Schäfer, Nadine
    Güting, Helge
    Lefering, Rolf
    Thorn, Sophie
    Schöchl, Herbert
    Zipperle, Johannes
    Grottke, Oliver
    Rossaint, Rolf
    Stanworth, Simon
    Curry, Nicola
    Maegele, Marc
    Koskinen, Lars-Owe D. (Medarbetare/bidragsgivare)
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap.
    Sundström, Nina (Medarbetare/bidragsgivare)
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper.
    Extended Coagulation Profiling in Isolated Traumatic Brain Injury: A CENTER-TBI Analysis2022Ingår i: Neurocritical Care, ISSN 1541-6933, E-ISSN 1556-0961, Vol. 36, nr 3, s. 927-941Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    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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  • 22. Carra, Giorgia
    et al.
    Güiza, Fabian
    Depreitere, Bart
    Meyfroidt, Geert
    Sundström, Nina (Medarbetare/bidragsgivare)
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper.
    Prediction model for intracranial hypertension demonstrates robust performance during external validation on the CENTER-TBI dataset2021Ingår i: Intensive Care Medicine, ISSN 0342-4642, E-ISSN 1432-1238, Vol. 47, nr 1, s. 124-126Artikel i tidskrift (Refereegranskat)
  • 23. Ceyisakar, Iris E.
    et al.
    Huijben, Jilske A.
    Maas, Andrew I. R.
    Lingsma, Hester F.
    van Leeuwen, Nikki
    CENTER-TBI participants and investigators, (Medarbetare/bidragsgivare)
    Can We Cluster ICU Treatment Strategies for Traumatic Brain Injury by Hospital Treatment Preferences?2022Ingår i: Neurocritical Care, ISSN 1541-6933, E-ISSN 1556-0961, Vol. 36, nr 3, s. 846-856Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    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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  • 24. Citerio, Giuseppe
    et al.
    Robba, Chiara
    Rebora, Paola
    Petrosino, Matteo
    Rossi, Eleonora
    Malgeri, Letterio
    Stocchetti, Nino
    Galimberti, Stefania
    Menon, David K
    Koskinen, Lars-Owe D. (Medarbetare/bidragsgivare)
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Neurovetenskaper.
    Sundström, Nina (Medarbetare/bidragsgivare)
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper.
    Management of arterial partial pressure of carbon dioxide in the first week after traumatic brain injury: results from the CENTER-TBI study2021Ingår i: Intensive Care Medicine, ISSN 0342-4642, E-ISSN 1432-1238, Vol. 47, nr 9, s. 961-973Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    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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  • 25. Cnossen, Maryse C.
    et al.
    Huijben, Jilske A.
    van der Jagt, Mathieu
    Volovici, Victor
    van Essen, Thomas
    Polinder, Suzanne
    Nelson, David
    Ercole, Ari
    Stocchetti, Nino
    Citerio, Giuseppe
    Peul, Wilco C.
    Maas, Andrew I. R.
    Menon, David
    Steyerberg, Ewout W.
    Lingsma, Hester F.
    Brorsson, Camilla
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Anestesiologi och intensivvård.
    Variation in monitoring and treatment policies for intracranial hypertension in traumatic brain injury: a survey in 66 neurotrauma centers participating in the CENTER-TBI study2017Ingår i: Critical Care, ISSN 1364-8535, E-ISSN 1466-609X, Vol. 21, nr 1, artikel-id 233Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    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.

  • 26. Cnossen, Maryse C.
    et al.
    Lingsma, Hester F.
    Tenovuo, Olli
    Maas, Andrew I. R.
    Menon, David
    Steyerberg, Ewout W.
    Ribbers, Gerard M.
    Polinder, Suzanne
    Brorsson, Camilla (Medarbetare/bidragsgivare)
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Anestesiologi och intensivvård.
    Rehabilitation after traumatic brain injury: A survey in 70 European neurotrauma centres participating in the CENTER-TBI study2017Ingår i: Journal of Rehabilitation Medicine, ISSN 1650-1977, E-ISSN 1651-2081, Vol. 49, nr 5, s. 395-401Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    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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  • 27. Cnossen, Maryse C.
    et al.
    Polinder, Suzanne
    Lingsma, Hester F.
    Maas, Andrew I. R.
    Menon, David
    Steyerberg, Ewout W.
    Variation in Structure and Process of Care in Traumatic Brain Injury: Provider Profiles of European Neurotrauma Centers Participating in the CENTER-TBI Study2016Ingår i: PLOS ONE, E-ISSN 1932-6203, Vol. 11, nr 8, artikel-id e0161367Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    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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  • 28. Cnossen, Maryse C.
    et al.
    van der Brande, Ruben
    Lingsma, Hester F.
    Polinder, Suzanne
    Lecky, Fiona
    Maas, Andrew I. R.
    Prehospital Trauma Care among 68 European Neurotrauma Centers: Results of the CENTER-TBI Provider Profiling Questionnaires2018Ingår i: Journal of Neurotrauma, ISSN 0897-7151, E-ISSN 1557-9042, Vol. 36, nr 1, s. 176-181Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    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.

  • 29. Czeiter, Endre
    et al.
    Amrein, Krisztina
    Gravesteijn, Benjamin Y.
    Lecky, Fiona
    Menon, David K.
    Mondello, Stefania
    Newcombe, Virginia F. J.
    Richter, Sophie
    Steyerberg, Ewout W.
    Vyvere, Thijs Vande
    Verheyden, Jan
    Xu, Haiyan
    Yang, Zhihui
    Maas, Andrew I. R.
    Wang, Kevin K. W.
    Büki, Andràs
    Koskinen, Lars-Owe (Medarbetare/bidragsgivare)
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Neurovetenskaper.
    Sundström, Nina (Medarbetare/bidragsgivare)
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper.
    Blood biomarkers on admission in acute traumatic brain injury: Relations to severity, CT findings and care path in the CENTER-TBI study2020Ingår i: EBioMedicine, E-ISSN 2352-3964, Vol. 56, artikel-id 10275Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    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.

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  • 30.
    Dahlqvist, Per
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Koskinen, Lars-Owe D
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Neurokirurgi.
    Brännström, Thomas
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Hägg, Erik
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Testicular enlargement in a patient with a FSH-secreting pituitary adenoma2010Ingår i: Endocrine, ISSN 1355-008X, E-ISSN 1559-0100, Vol. 37, nr 2, s. 289-293Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Clinically non-functional pituitary adenomas are often derived from gonadotropin producing cells. However, gonadotropinomas causing elevated serum levels of follicle-stimulating hormone (FSH) and clinical signs of FSH hypersecretion are very rarely described. Our patient, a 56-year-old man, was referred to our clinic with signs of hypogonadism. Magnetic resonance imaging (MRI) and biochemical examinations showed a large pituitary adenoma and excessive levels of serum FSH. Clinical examination and ultrasound measurement revealed bilaterally enlarged testes. After pituitary surgery, serum FSH levels normalized and there was a decrease in testicular volume. This case suggests that supraphysiological levels of FSH from a gonadotropinoma can cause a clinically observable effect, i.e. testicular enlargement. This is in line with experimental studies showing biological effect of FSH from pituitary adenomas and previous occasional reports of ovarian hyperstimulation and testicular enlargement in patients with FSH-secreting gonadotropinomas.

  • 31. Dijkland, Simone A.
    et al.
    Retel Helmrich, Isabel R. A.
    Nieboer, Daan
    van der Jagt, Mathieu
    Dippel, Diederik W. J.
    Menon, David K.
    Stocchetti, Nino
    Maas, Andrew I. R.
    Lingsma, Hester F.
    Steyerberg, Ewout W.
    Koskinen, Lars-Owe D. (Medarbetare/bidragsgivare)
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Neurovetenskaper.
    Sundström, Nina (Medarbetare/bidragsgivare)
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper.
    Outcome Prediction after Moderate and Severe Traumatic Brain Injury: External Validation of Two Established Prognostic Models in 1742 European Patients2021Ingår i: Journal of Neurotrauma, ISSN 0897-7151, E-ISSN 1557-9042, Vol. 38, nr 10, s. 1377-1388Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    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.

  • 32.
    Eklund, Anders
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper. Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Centrum för medicinsk teknik och fysik (CMTF).
    Jóhannesson, Gauti
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Oftalmiatrik.
    Johansson, Elias
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Farmakologi.
    Holmlund, Petter
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper.
    Qvarlander, Sara
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper.
    Ambarki, Khalid
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper.
    Wåhlin, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper. Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI).
    Koskinen, Lars-Owe D.
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Farmakologi.
    Malm, Jan
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    The Pressure Difference between Eye and Brain Changes with Posture2016Ingår i: Annals of Neurology, ISSN 0364-5134, E-ISSN 1531-8249, Vol. 80, nr 2, s. 269-276Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objective: The discovery of a posture-dependent effect on the difference between intraocular pressure (IOP) and intracranial pressure (ICP) at the level of lamina cribrosa could have important implications for understanding glaucoma and idiopathic intracranial hypertension and could help explain visual impairments in astronauts exposed to microgravity. The aim of this study was to determine the postural influence on the difference between simultaneously measured ICP and IOP.

    Methods: Eleven healthy adult volunteers (age = 46 ± 10 years) were investigated with simultaneous ICP, assessed through lumbar puncture, and IOP measurements when supine, sitting, and in 9° head-down tilt (HDT). The trans–lamina cribrosa pressure difference (TLCPD) was calculated as the difference between the IOP and ICP. To estimate the pressures at the lamina cribrosa, geometrical distances were estimated from magnetic resonance imaging and used to adjust for hydrostatic effects.

    Results: The TLCPD (in millimeters of mercury) between IOP and ICP was 12.3 ± 2.2 for supine, 19.8 ± 4.6 for sitting, and 6.6 ± 2.5 for HDT. The expected 24-hour average TLCPD on earth—assuming 8 hours supine and 16 hours upright—was estimated to be 17.3mmHg. By removing the hydrostatic effects on pressure, a corresponding 24-hour average TLCPD in microgravity environment was simulated to be 6.7mmHg.

    Interpretation: We provide a possible physiological explanation for how microgravity can cause symptoms similar to those seen in patients with elevated ICP. The observed posture dependency of TLCPD also implies that assessment of the difference between IOP and ICP in upright position may offer new understanding of the pathophysiology of idiopathic intracranial hypertension and glaucoma. 

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  • 33.
    Eklund, Anders
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Radiofysik.
    Koskinen, Lars-Owe D
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Neurokirurgi.
    Williams, Michael A
    Luciano, Mark G
    Dombrowski, Stephen M
    Malm, Jan
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Hydrodynamics of the CertasTM programmable valve for the treatment of hydrocephalus2012Ingår i: Fluids and barriers of the CNS, ISSN 2045-8118, Vol. 9, nr 1, s. 12-Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND: The new CertasTM shunt for the treatment of hydrocephalus has seven standard pressure settings that according to the manufacturer range from 36 to 238 mmH2O, and an additional "Virtual Off" setting with an opening pressure >400 mmH2O. Information on actual pressure response and reliability of shunt performance is important in clinical application, especially the "Virtual Off" setting as a non-surgical replacement for shunt ligation. The objective of this study was to evaluate the in-vitro hydrodynamic performance of the CertasTM shunt.

    METHODS: Six new CertasTM shunts with proximal and distal catheters were tested with an automated, computerized test system that raised the pressure from zero to a maximum pressure and back to zero at each valve setting. Opening pressure and flow resistance were determined.

    RESULTS: For settings 1-7 the measured opening pressure range was 26 to 247 mmH2O, and the mean change in opening pressure for a one-step adjustment was between 33 and 38 mmH2O. For setting 8 ("Virtual Off") the measured mean opening pressure was 494 +/- 34 mmH2O (range 451 to 556 mmH2O). The mean outflow resistance was 7.0 mmHg/ml/min (outflow conductance 17.9 ul/s/kPa).

    CONCLUSIONS: The six shunts had similar characteristics and closely matched the manufacturer's specifications for opening pressure at settings 1-7. The opening pressure for the "Virtual Off" setting was nearly 500 mmH2O, which is 100 mmH2O higher than the manufacturer's specification of ">400" and should be functionally off for most patients with communicating hydrocephalus. Clinical studies are needed to evaluate if the CSF dynamic profile persists after implantation in patients.

  • 34.
    Eklund, Anders
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper.
    Lundkvist, B.
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Neurologi.
    Koskinen, Lars-Owe D.
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Neurokirurgi.
    Malm, J
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Neurologi.
    Infusion technique can be used to distinguish between dysfunction of a hydrocephalus shunt system and a progressive dementia2004Ingår i: Medical and Biological Engineering and Computing, ISSN 0140-0118, E-ISSN 1741-0444, Vol. 42, nr 5, s. 644-649Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    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.

  • 35. Feng, Junfeng
    et al.
    van Veen, Ernest
    Yang, Chun
    Huijben, Jilske A.
    Lingsma, Hester F.
    Gao, Guoyi
    Jiang, Jiyao
    Maas, Andrew I. R.
    Koskinen, Lars-Owe D. (Medarbetare/bidragsgivare)
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Sundström, Nina (Medarbetare/bidragsgivare)
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper.
    Comparison of Care System and Treatment Approaches for Patients with Traumatic Brain Injury in China versus Europe: A CENTER-TBI Survey Study2020Ingår i: Journal of Neurotrauma, ISSN 0897-7151, E-ISSN 1557-9042, Vol. 37, nr 16, s. 1806-1817Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    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.

  • 36. Foks, Kelly A.
    et al.
    Cnossen, Maryse C.
    Dippel, Diederik W. J.
    Maas, Andrew I.R.
    Menon, David
    van der Naalt, Joukje
    Steyerberg, Ewout W.
    Lingsma, Hester F.
    Polinder, Suzanne
    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 study2017Ingår i: Journal of Neurotrauma, ISSN 0897-7151, E-ISSN 1557-9042, Vol. 34, nr 17, s. 2529-2535Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    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.

  • 37. Galimberti, Stefania
    et al.
    Graziano, Francesca
    Maas, Andrew I. R.
    Isernia, Giulia
    Lecky, Fiona
    Jain, Sonia
    Sun, Xiaoying
    Gardner, Raquel C.
    Taylor, Sabrina R.
    Markowitz, Amy J.
    Manley, Geoffrey T.
    Valsecchi, Maria Grazia
    Bellelli, Giuseppe
    Citerio, Giuseppe
    Koskinen, Lars-Owe D. (Medarbetare/bidragsgivare)
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap.
    Sundström, Nina (Medarbetare/bidragsgivare)
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper.
    Effect of frailty on 6-month outcome after traumatic brain injury: a multicentre cohort study with external validation2022Ingår i: Lancet Neurology, ISSN 1474-4422, E-ISSN 1474-4465, Vol. 21, nr 2, s. 153-162Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    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.

  • 38.
    Gasslander, Johan
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap. Departments of Cardiology and Health, Medicine and Caring Services, Linkoping University, Vrinnevi General Hospital Norrköping.
    Sundström, Nina
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Radiofysik.
    Eklund, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Radiofysik.
    Koskinen, Lars-Owe D.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Neurovetenskaper.
    Malm, Jan
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Neurovetenskaper.
    Risk factors for developing subdural hematoma: a registry-based study in 1457 patients with shunted idiopathic normal pressure hydrocephalus2021Ingår i: Journal of Neurosurgery, ISSN 0022-3085, E-ISSN 1933-0693, Vol. 134, nr 2, s. 668-677Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    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.

  • 39. Gravesteijn, B. Y.
    et al.
    Sewalt, C. A.
    Ercole, A.
    Lecky, F.
    Menon, D.
    Steyerberg, E. W.
    Maas, A. I. R.
    Lingsma, H. F.
    Klimek, M.
    Brorsson, Camilla (Medarbetare/bidragsgivare)
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Anestesiologi och intensivvård.
    Variation in the practice of tracheal intubation in Europe after traumatic brain injury: a prospective cohort study2020Ingår i: Anaesthesia, ISSN 0003-2409, E-ISSN 1365-2044, Vol. 75, nr 1, s. 45-53Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    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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  • 40. Gravesteijn, Benjamin Yael
    et al.
    Sewalt, Charlie Aletta
    Nieboer, Daan
    Menon, David Krishna
    Maas, Andrew
    Lecky, Fiona
    Klimek, Markus
    Lingsma, Hester Floor
    Brorsson, Camilla
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Anestesiologi och intensivvård.
    Tracheal intubation in traumatic brain injury: a multicentreprospective observational study2020Ingår i: British Journal of Anaesthesia, ISSN 0007-0912, E-ISSN 1471-6771, Vol. 125, nr 4, s. 505-517Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    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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  • 41. Gravesteijn, Benjamin Yaël
    et al.
    Sewalt, Charlie Aletta
    Venema, Esmee
    Nieboer, Daan
    Steyerberg, Ewout W.
    Brorsson, Camilla
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Anestesiologi och intensivvård.
    Koskinen, Lars-Owe D. (Medarbetare/bidragsgivare)
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap.
    Sundström, Nina (Medarbetare/bidragsgivare)
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper.
    Missing Data in Prediction Research: A Five-Step Approach for Multiple Imputation, Illustrated in the CENTER-TBI Study2021Ingår i: Journal of Neurotrauma, ISSN 0897-7151, E-ISSN 1557-9042, Vol. 38, nr 13, s. 1842-1857Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    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.

  • 42. Grenander, A.
    et al.
    Bredbacka, S.
    Rydvall, A.
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Anestesiologi och intensivvård.
    Aroch, R.
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Anestesiologi och intensivvård.
    Edner, G.
    Koskinen, Lars-Owe D.
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Olivecrona, M.
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Antithrombin treatment in patients with traumatic brain injury: a pilot study2001Ingår i: J Neurosurg Anesthesiol, Vol. 13, nr 1, s. 49-56Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    This study will determine if early administration of antithrombin concentrate to patients with traumatic brain injury (TBI) can inhibit or significantly shorten the time of coagulopathy. The progress of brain injury monitored by computed tomographic scan (CT) was also assessed, as was the time needed for intensive care and outcome related to Glasgow outcome scale (GOS). Twenty-eight patients with isolated brain trauma verified with CT were included in either of two parallel groups. The Glasgow coma score (GCS) was mean 7.5, and median 7.0; signifying a moderate to severe traumatic brain injury but with a mortality of only 3.5%. The patients randomized to antithrombin treatment received a total of 100 U/kg BW during 24 hours. To measure hypercoagulability, soluble fibrin (SF), D-dimer (D-d), and thrombin-antithrombin complex (TAT) were assessed together with antithrombin (AT) and routine coagulation tests. Before treatment, SF, D-d, and TAT were markedly increased in both groups. Soluble fibrin and D-dimer (measured after treatment began) appeared to decrease faster in the AT group, and there was a statistically significant difference between the groups at 36 hours for SF and at 36 hours, 48 hours, and at Day 3 for D-d. Thrombin-antithrombin complex levels were very high in both groups but, surprisingly, showed no significant difference between the groups. The authors conclude that antithrombin concentrate administered to patients with severe TBI resulted in a marginal reduction of hypercoagulation. We could not detect any obvious influence by antithrombin on brain injury progress, on CT, or on outcome or time needed for intensive care.

  • 43. Grände, P-O
    et al.
    Koskinen, L-O
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Neurokirurgi.
    Naredi, S
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Anestesiologi och intensivvård.
    Reinstrup, P
    Romner, B
    Conventional treatments for severe head injury: are they effective, ineffective, or even harmful?2007Ingår i: Acta Anaesthesiologica Scandinavica, ISSN 0001-5172, E-ISSN 1399-6576, Vol. 51, nr 10, s. 1294-1296Artikel i tidskrift (Övrigt vetenskapligt)
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  • 44.
    Hariz, Gun-Marie
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering, Arbetsterapi. Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Blomstedt, Patric
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Neurokirurgi.
    Koskinen, Lars-Owe D
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Neurokirurgi.
    Long-term effect of deep brain stimulation for essential tremor on activities of daily living and health-related quality of life2008Ingår i: Acta Neurologica Scandinavica, ISSN 0001-6314, E-ISSN 1600-0404, Vol. 118, nr 6, s. 387-394Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    OBJECTIVES: To report long-term effects of thalamic deep brain stimulation (DBS) on activities of daily living (ADL) and health-related quality of life (HRQoL) in patients with essential tremor (ET).

    MATERIALS AND METHODS: Nineteen consecutive patients were evaluated at baseline, at a mean of 1 year, then at a mean of 7 years after DBS using Tremor Rating Scale, Mini Mental Test, ADL Taxonomy, Nottingham Health Profile, Life Satisfaction Checklist, Visual Analogue Scale and interview.

    RESULTS: There was a decrease of DBS efficacy on tremor between 1 and 7 years post-operatively. The marked improvement in ADL at 1 year was no longer sustained at long-term, except for the ability to eat. Social life remained improved.

    CONCLUSION: Although there is a decrease of DBS effect on tremor at 7 years, and even though further ageing and co-morbidities may impact on the well-being of patients, there is still relevant benefit of DBS on few aspects of ADL and HRQoL in patients with ET.

  • 45.
    Holmlund, Petter
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Radiofysik.
    Eklund, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Radiofysik.
    Koskinen, Lars-Owe D.
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Johansson, Elias
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Sundström, Nina
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Radiofysik.
    Malm, Jan
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Qvarlander, Sara
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Radiofysik.
    Venous collapse regulates intracranial pressure in upright body positions2018Ingår i: American Journal of Physiology. Regulatory Integrative and Comparative Physiology, ISSN 0363-6119, E-ISSN 1522-1490, Vol. 314, nr 3, s. R377-R385Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Recent interest in intracranial pressure (ICP) in the upright posture has revealed that the mechanisms regulating postural changes in ICP are not fully understood. We have suggested an explanatory model where the postural changes in ICP depend on well-established hydrostatic effects in the venous system and where these effects are interrupted by collapse of the internal jugular veins (IJVs) in more upright positions. The aim of this study was to investigate this relationship by simultaneous invasive measurements of ICP, venous pressure and IJV collapse in healthy volunteers. ICP (monitored via the lumbar route), central venous pressure (PICC-line) and IJV cross-sectional area (ultrasound) were measured in 11 healthy volunteers (47±10 years) in seven positions, from supine to sitting (0°-69°). Venous pressure and anatomical distances were used to predict ICP in accordance with the explanatory model, and IJV area was used to assess IJV collapse. The hypothesis was tested by comparing measured ICP to predicted ICP. Our model accurately described the general behavior of the observed postural ICP changes (mean difference: -0.03±2.7 mmHg). No difference was found between predicted and measured ICP for any tilt-angle (p-values: 0.65 - 0.94). The results support the hypothesis that postural ICP changes are governed by hydrostatic effects in the venous system and IJV collapse. This improved understanding of the postural ICP regulation may have important implications for the development of better treatments for neurological and neurosurgical conditions affecting ICP.

  • 46.
    Holmlund, Petter
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper.
    Johansson, Elias
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Qvarlander, Sara
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper.
    Wåhlin, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper. Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI).
    Ambarki, Khalid
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper.
    Koskinen, Lars-Owe D.
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Malm, Jan
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Eklund, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper.
    Human jugular vein collapse in the upright posture: implications for postural intracranial pressure regulation2017Ingår i: Fluids and Barriers of the CNS, E-ISSN 2045-8118, Vol. 14, artikel-id 17Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Intracranial pressure (ICP) is directly related to cranial dural venous pressure (P-dural). In the upright posture, P-dural is affected by the collapse of the internal jugular veins (IJVs) but this regulation of the venous pressure has not been fully understood. A potential biomechanical description of this regulation involves a transmission of surrounding atmospheric pressure to the internal venous pressure of the collapsed IJVs. This can be accomplished if hydrostatic effects are cancelled by the viscous losses in these collapsed veins, resulting in specific IJV cross-sectional areas that can be predicted from flow velocity and vessel inclination. Methods: We evaluated this potential mechanism in vivo by comparing predicted area to measured IJV area in healthy subjects. Seventeen healthy volunteers (age 45 +/- 9 years) were examined using ultrasound to assess IJV area and flow velocity. Ultrasound measurements were performed in supine and sitting positions. Results: IJV area was 94.5 mm(2) in supine and decreased to 6.5 +/- 5.1 mm(2) in sitting position, which agreed with the predicted IJV area of 8.7 +/- 5.2 mm(2) (equivalence limit +/- 5 mm(2), one-sided t tests, p = 0.03, 33 IJVs). Conclusions: The agreement between predicted and measured IJV area in sitting supports the occurrence of a hydrostatic-viscous pressure balance in the IJVs, which would result in a constant pressure segment in these collapsed veins, corresponding to a zero transmural pressure. This balance could thus serve as the mechanism by which collapse of the IJVs regulates P-dural and consequently ICP in the upright posture.

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  • 47.
    Holmlund, Petter
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Radiofysik.
    Johansson, Elias
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Avdelningen för medicin.
    Qvarlander, Sara
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper.
    Wåhlin, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper.
    Ambarki, Khalid
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper.
    Koskinen, Lars-Owe D.
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Malm, Jan
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Eklund, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Radiofysik.
    Jugular vein collapse in upright and its relation to intracranial pressure regulation2017Ingår i: Journal of Cerebral Blood Flow and Metabolism, ISSN 0271-678X, E-ISSN 1559-7016, Vol. 37, s. 297-297Artikel i tidskrift (Refereegranskat)
  • 48. Horton, Lindsay
    et al.
    Rhodes, Jonathan
    Menon, David K.
    Maas, Andrew I. R.
    Wilson, Lindsay
    Questionnaires vs Interviews for the Assessment of Global Functional Outcomes After Traumatic Brain Injury2021Ingår i: JAMA Network Open, E-ISSN 2574-3805, Vol. 4, nr 11, artikel-id e2134121Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    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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  • 49. Howe, Emilie Isager
    et al.
    Zeldovich, Marina
    Andelic, Nada
    von Steinbuechel, Nicole
    Fure, Silje C. R.
    Borgen, Ida M. H.
    Forslund, Marit V.
    Hellstrøm, Torgeir
    Søberg, Helene L.
    Sveen, Unni
    Rasmussen, Mari
    Kleffelgaard, Ingerid
    Tverdal, Cathrine
    Helseth, Eirik
    Løvstad, Marianne
    Lu, Juan
    Arango-Lasprilla, Juan Carlos
    Tenovuo, Olli
    Azouvi, Philippe
    Dawes, Helen
    Roe, Cecilie
    Koskinen, Lars-Owe D. (Medarbetare/bidragsgivare)
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Neurovetenskaper.
    Sundström, Nina (Medarbetare/bidragsgivare)
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper.
    Rehabilitation and outcomes after complicated vs uncomplicated mild TBI: results from the CENTER-TBI study2022Ingår i: BMC Health Services Research, E-ISSN 1472-6963, Vol. 22, nr 1, artikel-id 1536Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    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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  • 50. Hugoson-Seligsohn, Eva E.
    et al.
    Koskinen, Lars-Owe D.
    Department of Physiology and Medical Biophysics, Biomedical Centre, University of Uppsala, Uppsala, Sweden.
    TRH-induced blood flow and mean arterial pressure changes in the rabbit are not dependent on the anaesthetic used.1989Ingår i: British Journal of Pharmacology, ISSN 0007-1188, E-ISSN 1476-5381, Vol. 97, nr 1, s. 190-196Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    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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