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  • 1.
    Andersen, Leon
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin.
    Appelblad, Micael
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin.
    Wiklund, Urban
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Radiofysik.
    Sundström, Nina
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Radiofysik.
    Svenmarker, Staffan
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin.
    Our initial experience of monitoring the autoregulation of cerebral blood flow during cardiopulmonary bypass2023Inngår i: The journal of extra-corporeal technology, ISSN 0022-1058, Vol. 55, nr 4, s. 209-217Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    BACKGROUND: Cerebral blood flow (CBF) is believed to be relatively constant within an upper and lower blood pressure limit. Different methods are available to monitor CBF autoregulation during surgery. This study aims to critically analyze the application of the cerebral oxygenation index (COx), one of the commonly used techniques, using a reference to data from a series of clinical registrations.

    METHOD: CBF was monitored using near-infrared spectroscopy, while cerebral blood pressure was estimated by recordings obtained from either the radial or femoral artery in 10 patients undergoing cardiopulmonary bypass. The association between CBF and blood pressure was calculated as a moving continuous correlation coefficient. A COx index > 0.4 was regarded as a sign of abnormal cerebral autoregulation (CA). Recordings were examined to discuss reliability measures and clinical feasibility of the measurements, followed by interpretation of individual results, identification of possible pitfalls, and suggestions of alternative methods.

    RESULTS AND CONCLUSION: Monitoring of CA during cardiopulmonary bypass is intriguing and complex. A series of challenges and limitations should be considered before introducing this method into clinical practice.

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  • 2.
    Andersson, Kennet
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Radiofysik.
    Manchester, Ian R
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Institutionen för tillämpad fysik och elektronik.
    Andersson, Nina
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Radiofysik.
    Shiriaev, Anton
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Institutionen för tillämpad fysik och elektronik.
    Malm, Jan
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Neurologi.
    Eklund, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Radiofysik.
    Assessment of cerebrospinal fluid outflow conductance using an adaptive observer-experimental and clinical evaluation2007Inngår i: Physiological Measurement, ISSN 0967-3334, E-ISSN 1361-6579, Vol. 28, nr 11, s. 1355-1368Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Idiopathic normal pressure hydrocephalus (INPH) patients have a disturbance in the dynamics of the cerebrospinal fluid (CSF) system. The outflow conductance, C, of the CSF system has been suggested to be prognostic for positive outcome after treatment with a CSF shunt. All current methods for estimation of C have drawbacks; these include lack of information on the accuracy and relatively long investigation times. Thus, there is a need for improved methods. To accomplish this, the theoretical framework for a new adaptive observer (OBS) was developed which provides real-time estimation of C. The aim of this study was to evaluate the OBS method and to compare it with the constant pressure infusion (CPI) method. The OBS method was applied to data from infusion investigations performed with the CPI method. These consisted of repeated measurements on an experimental set-up and 30 patients with suspected INPH. There was no significant difference in C between the CPI and the OBS method for the experimental set-up. For the patients there was a significant difference, −0.84 ± 1.25 µl (s kPa)−1, mean ± SD (paired sample t-test, p < 0.05). However, such a difference is within clinically acceptable limits. This encourages further development of this new real-time approach for estimation of the outflow conductance.

  • 3.
    Andersson, Kennet
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Radiofysik.
    Sundström, Nina
    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.
    Effect of resting pressure on the estimate of cerebrospinal fluid outflow conductance2011Inngår i: Fluids and barriers of the CNS, ISSN 2045-8118, Vol. 8, nr 1, s. 15-Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    BACKGROUND: A lumbar infusion test is commonly used as a predictive test for patients with normal pressure hydrocephalus and for evaluation of cerebrospinal fluid (CSF) shunt function. Different infusion protocols can be used to estimate the outflow conductance (Cout) or its reciprocal the outflow resistance, (Rout) with or without using the baseline resting pressure, Pr. Both from a basic physiological research and a clinical perspective, it is important to understand the limitations of the model on which infusion tests are based. By estimating Cout using two different analyses, with or without Pr, the limitations could be explored. The aim of this study was to compare the Cout estimates, and investigate what effect Pr had on the results.

    METHODS: Sixty-three patients that underwent a constant pressure infusion protocol as part of their preoperative evaluation for normal pressure hydrocephalus, were included (age 70.3+/-10.8 years (mean +/-SD). The analysis was performed without (Cexcl Pr) and with (Cincl Pr) Pr. The estimates were compared using Bland-Altman plots and paired sample t-tests (p<0.05 considered significant).

    RESULTS: Mean Cout for the 63 patients was: Cexcl Pr = 7.0+/-4.0 (mean +/-SD) ul/(s kPa) and Cincl Pr = 9.1+/-4.3 ul/(s kPa) and Rout was 19.0+/-9.2 and 17.7+/-11.3 mmHg/ml/min, respectively. There was a positive correlation between methods (r=0.79, n=63, p<0.01). The difference, DeltaCout, -2.1+/-2.7 ul/(s kPa) between methods was significant (p<0.01) and DeltaRout was 1.2 +/- 8.8 mmHg/ml/min). The Bland-Altman plot visualized that the variation around the mean difference was similar all through the range of measured values and there was no correlation between DeltaCout and Cout.

    CONCLUSIONS: The difference between Cout estimates, obtained from analyses with or without Pr, needs to be taken into consideration when comparing results from studies using different infusion test protocols. The study suggests variation in CSF formation rate, variation in venous pressure or a pressure dependent Cout as possible causes for the deviation from the CSF absorption model seen in some patients.

  • 4.
    Andersson, Nina
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper.
    Cerebrospinal fluid infusion methods: development and validation on patients with idiopathic normal pressure hydrocephalus2007Doktoravhandling, med artikler (Annet vitenskapelig)
    Abstract [en]

    Cerebrospinal fluid (CSF) infusion tests can be used to estimate the dynamic properties of the CSF system. Idiopathic normal pressure hydrocephalus (INPH) is a syndrome signified by a disturbance to the CSF system, where the cause is unknown and the diagnosis is difficult to determine. As an aid in identifying patients with INPH who will improve after shunt surgery, infusion tests are commonly used to determine the outflow conductance (Cout), or outflow resistance (Rout=1/Cout), of the CSF system. The tests are also used to determine shunt function in vivo. The general aim of this thesis was to develop and validate CSF infusion methods, to investigate the dynamics of the CSF system. The methods should be applicable to patients with INPH, to aid in the quest to further improve the diagnosis and management of this syndrome.

    An existing mathematical model describing the dynamics of the CSF system was further developed. The characteristics of the model were verified and the effect of expanding intracranial air on the intracranial pressure (ICP) was simulated. The simulations supported the recommendation to maintain sea-level pressure during air ambulance transportation of patients with suspected intracranial air.

    A recently developed infusion apparatus was evaluated, on an experimental model as well as on a patient material. The repetitiveness in estimating Cout was found to be good. A statistically significant difference was found between the repeated Cout estimations in the patient group, indicating that there might have been a small physiological change introduced during the infusion test. A parameter, ∆Cout, was proposed and evaluated. It proved to reflect the reliability of individual Cout investigations in a clinically useful way, as well as to provide easily interpreted information.

    An adaptive algorithm for assessment of Cout was developed and evaluated on a patient group. The new algorithm was shown to reduce the investigation time, from 60 minutes, by 14.3 ± 5.9 minutes (mean ± SD), p<0.01, without reducing the reliability of the estimated Cout below clinically relevant levels.

    The relationship between ICP and CSF outflow was studied in a group of patients investigated for INPH. It was found that in the range of moderate increase from baseline pressure, the assumption of a pressure independent Rout was confirmed (p=0.5). However, at larger pressure increments, the relationship had a non-linear tendency (p<0.05). This indicates that the traditional view of a pressure independent Rout might have to be questioned in the region where ICP exceeds baseline pressure too much.

    Infusion tests can be performed in different ways, where three main categories may be distinguished. The bolus infusion method was compared to the constant pressure and constant flow infusion methods, on an experimental model as well as on a patient material. When physiological pressure fluctuations were added to the model, significant differences were found in the determination of Cout in the range of clinical importance, i.e. low Cout (p<0.05). The finding was supported by the patient investigations, the difference was however not significant.

    With the application of the new methods developed in this thesis, and the increased knowledge concerning relationships between CSF dynamic parameters, the CSF infusion test was further improved with the ability to increase measurement reliability in a reduced time. This constitutes a good basis to perform a large multi-centre study with the main goal to determine the predictive value of the parameter Cout.

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  • 5.
    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 effects2003Inngår i: Aviation, Space and Environmental Medicine, ISSN 0095-6562, E-ISSN 1943-4448, Vol. 74, nr 2, s. 138-144Artikkel i tidsskrift (Fagfellevurdert)
  • 6.
    Andersson, Nina
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Radiofysik.
    Malm, Jan
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Neurologi. Neurologi.
    Bäcklund, Tomas
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Radiofysik.
    Eklund, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Radiofysik.
    Assessment of cerebrospinal fluid outflow conductance using constant-pressure infusion - a method with real time estimation of reliability2005Inngår i: Physiological Measurement, ISSN 0967-3334, E-ISSN 1361-6579, Vol. 26, nr 6, s. 1137-1148Artikkel i tidsskrift (Fagfellevurdert)
  • 7.
    Andersson, Nina
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Radiofysik. Department of Biomedical Engineering and Informatics, Umeå University Hospital.
    Malm, Jan
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Neurologi.
    Eklund, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Radiofysik. Department of Biomedical Engineering and Informatics, Umeå University Hospital.
    Dependency of cerebrospinal fluid outflow resistance on intracranial pressure2008Inngår i: Journal of Neurosurgery, ISSN 0022-3085, E-ISSN 1933-0693, Vol. 109, nr 5, s. 918-922Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    OBJECT: The outflow resistance (Rout) of the cerebrospinal fluid (CSF) system has generally been accepted by most investigators as independent of intracranial pressure (ICP), but there are also those claiming that it is not. The general belief is that this question has been investigated numerous times in the past, but few studies have actually been specifically aimed at looking at this relationship, and no study has been able to provide scientific evidence to elucidate fully this fundamental and important issue. The objective of this study was to investigate the relationship between ICP and CSF outflow in 30 patients investigated for idiopathic normal-pressure hydrocephalus. METHODS: Lumbar infusion tests with constant pressure levels were performed, and ICP and corresponding flow were measured on 6 pressure levels for each patient. All data were standardized for comparison. RESULTS: In the range of moderate increases from baseline pressure (approximately 5-12 mm Hg, mean baseline pressure 11.7 mm Hg), the assumption of a pressure-independent Rout was confirmed (p = 0.5). However, when the pressure increment from baseline pressure was larger (approximately 15-22 mm Hg), the relationship had a nonlinear tendency (p < 0.05). CONCLUSIONS: The results of this study support the classic textbook theory of a pressure-independent Rout in the normal ICP range, where the CSF system is commonly operating. However, the theory might have to be questioned in regions where ICP exceeds baseline pressure by too much.

  • 8.
    Andersson, Nina
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper.
    Malm, Jan
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Neurologi.
    Wiklund, Urban
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper.
    Eklund, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper.
    Adaptive method for assessment of cerebrospinal fluid outflow conductance.2007Inngår i: Medical and Biological Engineering and Computing, ISSN 0140-0118, E-ISSN 1741-0444, Vol. 45, nr 4, s. 337-343Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Outflow conductance (C out) is important for predicting shunt responsiveness in patients with suspected idiopathic adult hydrocephalus syndrome (IAHS). C out is determined by performing an infusion test into the cerebrospinal fluid system, and the reliability of the test is dependent on the measurement time. The objective of this study was to develop an adaptive signal analysis method to reduce the investigation time, by taking the individual intracranial pressure variations of the patient into consideration. The method was evaluated on 28 patients with suspected IAHS. The results from full time investigations (60 min) were compared to the results of the new algorithm. Applying the new adaptive method resulted in a reduction of mean investigation time by 14.3 ± 5.9 min (mean ± SD), p < 0.01. The reduction of reliability in the C out estimation was found clinically negligible. We thus recommend this adaptive method to be used when performing constant pressure infusion tests.

  • 9.
    Andrén, Kerstin
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Wikkelsö, Carsten
    Sundström, Nina
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Radiofysik.
    Agerskov, Simon
    Israelsson, Hanna
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Laurell, Katarina
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Hellström, Per
    Tullberg, Mats
    Long-term effects of complications and vascular comorbidity in idiopathic normal pressure hydrocephalus: a quality registry study2018Inngår i: Journal of Neurology, ISSN 0340-5354, E-ISSN 1432-1459, Vol. 265, nr 1, s. 178-186Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: There is little knowledge about the factors influencing the long-term outcome after surgery for idiopathic normal pressure hydrocephalus (iNPH).

    Objective: To evaluate the effects of reoperation due to complications and of vascular comorbidity (hypertension, diabetes, stroke and heart disease) on the outcome in iNPH patients, 2–6 years after shunt surgery.

    Methods: We included 979 patients from the Swedish Hydrocephalus Quality Registry (SHQR), operated on for iNPH during 2004–2011. The patients were followed yearly by mailed questionnaires, including a self-assessed modified Rankin Scale (smRS) and a subjective comparison between their present and their preoperative health condition. The replies were grouped according to the length of follow-up after surgery. Data on clinical evaluations, vascular comorbidity, and reoperations were extracted from the SHQR.

    Results: On the smRS, 40% (38–41) of the patients were improved 2–6 years after surgery and around 60% reported their general health condition to be better than preoperatively. Reoperation did not influence the outcome after 2–6 years. The presence of vascular comorbidity had no negative impact on the outcome after 2–6 years, assessed as improvement on the smRS or subjective improvement of the health condition, except after 6 years when patients with hypertension and a history of stroke showed a less favorable development on the smRS.

    Conclusion: This registry-based study shows no negative impact of complications and only minor effects of vascular comorbidity on the long-term outcome in iNPH.

    Fulltekst (pdf)
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  • 10. Andrén, Kerstin
    et al.
    Wikkelsø, Carsten
    Sundström, Nina
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Radiofysik.
    Israelsson, Hanna
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Agerskov, Simon
    Laurell, Katarina
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap. Department of Neuroscience, Uppsala University, Uppsala, Sweden.
    Hellström, Per
    Tullberg, Mats
    Survival in treated idiopathic normal pressure hydrocephalus2020Inngår i: Journal of Neurology, ISSN 0340-5354, E-ISSN 1432-1459, Vol. 267, nr 3, s. 640-648Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Objective: To describe survival and causes of death in 979 treated iNPH patients from the Swedish Hydrocephalus Quality Registry (SHQR), and to examine the influence of comorbidities, symptom severity and postoperative outcome.

    Methods: All 979 patients operated for iNPH 2004–2011 and registered in the SHQR were included. A matched control group of 4890 persons from the general population was selected by Statistics Sweden. Data from the Swedish Cause of Death Registry was obtained for patients and controls.

    Results: At a median 5.9 (IQR 4.2–8.1) year follow-up, 37% of the iNPH patients and 23% of the controls had died. Mortality was increased in iNPH patients by a hazard ratio of 1.81, 95% CI 1.61–2.04, p < 0.001. More pronounced symptoms in the preoperative ordinal gait scale and the Mini-mental State Examination were the most important independent predictors of mortality along with the prevalence of heart disease. Patients who improved in both the gait scale and in the modified Rankin Scale postoperatively (n = 144) had a similar survival as the general population (p = 0.391). Deaths due to cerebrovascular disease or dementia were more common in iNPH patients, while more controls died because of neoplasms or disorders of the circulatory system.

    Conclusions: Mortality in operated iNPH patients is 1.8 times increased compared to the general population, a lower figure than previously reported. The survival of iNPH patients who improve in gait and functional independence is similar to that of the general population, indicating that shunt surgery for iNPH, besides improving symptoms and signs, can normalize survival.

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  • 11. 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. ()
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Neurovetenskaper.
    Sundström, Nina ()
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper.
    Early Predictors of Employment Status One Year Post Injury in Individuals with Traumatic Brain Injury in Europe2020Inngår i: Journal of Clinical Medicine, E-ISSN 2077-0383, Vol. 9, nr 6, artikkel-id 2007Artikkel i tidsskrift (Fagfellevurdert)
    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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  • 12. Bockhop, Fabian
    et al.
    Zeldovich, Marina
    Cunitz, Katrin
    Van Praag, Dominique
    van der Vlegel, Marjolein
    Beissbarth, Tim
    Hagmayer, York
    von Steinbuechel, Nicole
    Kondziella, Daniel ()
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Neurovetenskaper.
    Koskinen, Lars-Owe D. ()
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Neurovetenskaper.
    Sundström, Nina ()
    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 injury2022Inngår i: Scientific Reports, E-ISSN 2045-2322, Vol. 12, nr 1, artikkel-id 16571Artikkel i tidsskrift (Fagfellevurdert)
    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.

    Fulltekst (pdf)
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  • 13.
    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 simulation2017Inngår i: Scandinavian Journal of Trauma, Resuscitation and Emergency Medicine, E-ISSN 1757-7241, Vol. 25, artikkel-id 50Artikkel i tidsskrift (Fagfellevurdert)
    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.

    Fulltekst (pdf)
    fulltext
  • 14.
    Bäcklund, Tomas
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper.
    Frankel, Jennifer
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Radiofysik.
    Israelsson, Hanna
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap. Vrinnevi Hospital, Norrköping, Sweden.
    Malm, Jan
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Sundström, Nina
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper.
    Trunk sway in idiopathic normal pressure hydrocephalus: quantitative assessment in clinical practice2017Inngår i: Gait & Posture, ISSN 0966-6362, E-ISSN 1879-2219, s. 62-70, artikkel-id 54Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: In diagnosis and treatment of patients with idiopathic normal pressure hydrocephalus (iNPH), there is need for clinically applicable, quantitative assessment of balance and gait. Using a body worn gyroscopic system, the aim of this study was to assess postural stability of iNPH patients in standing, walking and during sensory deprivation before and after cerebrospinal fluid (CSF) drainage and surgery. A comparison was performed between healthy elderly (HE) and patients with various types of hydrocephalus (ventriculomegaly (VM)).

    Methods: Trunk sway was measured in 31 iNPH patients, 22 VM patients and 58 HE. Measurements were performed at baseline in all subjects, after CSF drainage in both patient groups and after shunt surgery in the iNPH group.

    Results: Preoperatively, the iNPH patients had significantly higher trunk sway compared to HE, specifically for the standing tasks (p < 0.001). Compared to VM, iNPH patients had significantly lower sway velocity during gait in three of four cases on firm support (p < 0.05). Sway velocity improved after CSF drainage and in forward-backward direction after surgery (p < 0.01). Compared to HE both patient groups demonstrated less reliance on visual input to maintain stable posture.

    Conclusions: INPH patients had reduced postural stability compared to HE, particularly during standing, and for differentiation between iNPH and VM patients sway velocity during gait is a promising parameter. A reversible reduction of visual incorporation during standing was also seen. Thus, the gyroscopic system quantitatively assessed postural deficits in iNPH, making it a potentially useful tool for aiding in future diagnoses, choices of treatment and clinical follow-up. 

  • 15.
    Bäcklund, Tomas
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Radiofysik.
    Grip, Helena
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Radiofysik.
    Öhberg, Fredrik
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Radiofysik.
    Sundström, Nina
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Radiofysik.
    Single sensor measurement of heel-height during the push-off phase of gait2021Inngår i: Physiological Measurement, ISSN 0967-3334, E-ISSN 1361-6579, Vol. 42, nr 10, artikkel-id 105016Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Objective: In healthy gait a forceful push-off is needed to get an efficient leg swing and propulsion, and a high heel lift makes a forceful push-off possible. The power of the push-off is decreased with increased age and in persons with impaired balance and gait. The aim of this study was to evaluate whether a wearable equipment (Striton) and algorithms to estimate vertical heel-height during gait from a single optical distance sensor is reliable and feasible for clinical applications.

    Approach: To assess heel-height with the Striton system an optical distance sensor was used to measure the distance to the floor along the shank. An algorithm was created to transform this measure to a vertical distance. The heel-height was validated in an experimental setup, against a 3D motion capture system (MCS), and test-retest and day-to-day tests were performed on 10 elderly persons. As a reference material 83 elderly persons were included, and heel-height was measured before and after surgery in four patients with the neurological disorder idiopathic normal pressure hydrocephalus (iNPH).

    Main results: In the experimental setup the accuracy was high with a maximum error of 2% at all distances, target colours and inclination angles, and the correlation to the MCS was R = 0.94. Test-retest and day-to-day tests were equal within ±1.2 cm. Mean heel-height of the elderly persons was 16.5 ± 0.6 cm and in the patients with iNPH heel-height was increased from 11.2 cm at baseline to 15.3 cm after surgery.

    Significance: Striton can reliably measure heel-height during gait, with low test-retest and day-to-day variability. The system was easy to attach, and simple to use, which makes it suitable for clinical applications.

    Fulltekst (pdf)
    fulltext
  • 16.
    Bäcklund, Tomas
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Radiofysik.
    Öhberg, Fredrik
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Radiofysik.
    Grip, Helena
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Radiofysik.
    Johansson, Gudrun
    Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering.
    Sundström, Nina
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Radiofysik.
    O 035 - A novel method to measure step width during the swing phase of gait2018Inngår i: Gait & Posture, ISSN 0966-6362, E-ISSN 1879-2219, Vol. 65, s. 71-72Artikkel i tidsskrift (Fagfellevurdert)
  • 17.
    Bäcklund, Tomas
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Radiofysik.
    Öhberg, Fredrik
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Radiofysik.
    Johansson, Gudrun
    Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering.
    Grip, Helena
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Radiofysik.
    Sundström, Nina
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Radiofysik.
    Novel, clinically applicable method to measure step-width during the swing phase of gait2020Inngår i: Physiological Measurement, ISSN 0967-3334, E-ISSN 1361-6579, Vol. 41, nr 6, artikkel-id 065005Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Objective: Step-width during walking is an indicator of stability and balance in patients with neurological disorders, and development of objective tools to measure this clinically would be a great advantage. The aim of this study was to validate an in-house-developed gait analysis system (Striton), based on optical and inertial sensors and a novel method for stride detection, for measuring step-width during the swing phase of gait and temporal parameters.

    Approach: The step-width and stride-time measurements were validated in an experimental setup, against a 3D motion capture system and on an instrumented walkway. Further, test-retest and day-to-day variability were evaluated, and gait parameters were collected from 87 elderly persons (EP) and four individuals with idiopathic normal pressure hydrocephalus (iNPH) before/after surgery.

    Main results: Accuracy of the step-width measurement was high: in the experimental setup mean error was 0.08 +/- 0.25 cm (R = 1.00) and against the 3D motion capture system 0.04 +/- 1.12 cm (R = 0.98). Test-retest and day-to-day measurements were equal within +/- 0.5 cm. Mean difference in stride time was -0.003 +/- 0.008 s between Striton and the instrumented walkway. The Striton system was successfully applied in the clinical setting on individuals with iNPH, which had larger step-width (6.88 cm, n = 4) compared to EP (5.22 cm, n = 87).

    Significance: We conclude that Striton is a valid, reliable and wearable system for quantitative assessment of step-width and temporal parameters during gait. Initial measurements indicate that the newly defined step-width parameter differs between EP and patients with iNPH and before/after surgery. Thus, there is potential for clinical applicability in patients with reduced gait stability.

    Fulltekst (pdf)
    fulltext
  • 18. 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. ()
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap.
    Sundström, Nina ()
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper.
    Extended Coagulation Profiling in Isolated Traumatic Brain Injury: A CENTER-TBI Analysis2022Inngår i: Neurocritical Care, ISSN 1541-6933, E-ISSN 1556-0961, Vol. 36, nr 3, s. 927-941Artikkel i tidsskrift (Fagfellevurdert)
    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.

    Fulltekst (pdf)
    fulltext
  • 19. Carra, Giorgia
    et al.
    Güiza, Fabian
    Depreitere, Bart
    Meyfroidt, Geert
    Sundström, Nina ()
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper.
    Prediction model for intracranial hypertension demonstrates robust performance during external validation on the CENTER-TBI dataset2021Inngår i: Intensive Care Medicine, ISSN 0342-4642, E-ISSN 1432-1238, Vol. 47, nr 1, s. 124-126Artikkel i tidsskrift (Fagfellevurdert)
  • 20.
    Chidiac, Christine
    et al.
    Department of Medical Sciences, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
    Sundström, Nina
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Radiofysik.
    Tullberg, M.
    Hydrocephalus Research Unit, Department of Clinical Neuroscience, Institute of Neuroscience and Physiology, Sahlgrenska Academy, Sahlgrenska University Hospital, University of Gothenburg, Gothenburg, Sweden.
    Arvidsson, L.
    Department of Clinical Neuroscience Karolinska Institutet, Department of Neurosurgery, Karolinska University Hospital, Stockholm, Sweden.
    Olivecrona, M.
    Department of Medical Sciences, Faculty of Medicine and Health, Örebro University, Örebro, Sweden; Department of Neurosurgery, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
    Waiting time for surgery influences the outcome in idiopathic normal pressure hydrocephalus: a population-based study2022Inngår i: Acta Neurochirurgica, ISSN 0001-6268, E-ISSN 0942-0940, Vol. 164, nr 2, s. 469-478Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Introduction: Idiopathic normal pressure hydrocephalus (iNPH) is a disease that comes with a great impact on the patient’s life. The only treatment for iNPH, which is a progressive disease, is shunt surgery. It is previously indicated that early intervention might be of importance for the outcome.

    Aim: To investigate if a longer waiting time for surgery, negatively influences the clinical outcome.

    Methods: Eligible for this study were all iNPH patients (n = 3007) registered in the Swedish Hydrocephalus Quality Registry (SHQR) during 1st of January 2004–12th of June 2019. Waiting time, defined as time between the decision to accept a patient for surgery and shunt surgery, was divided into the intervals ≤ 3, 3.1–5.9 and ≥ 6 months. Clinical outcome was assessed 3 and 12 months after surgery using the modified iNPH scale, the Timed Up and Go (TUG) test and the mini mental state examination (MMSE).

    Results: Three months after surgery, 57% of the patients with ≤ 3 months waiting time showed an improvement in modified iNPH scale (≥ 5 points) whereas 52% and 46% of patients with 3.1–5.9 and ≥ 6 months waiting time respectively improved (p = 0.0115). At 12 months of follow-up, the corresponding numbers were 61%, 52% and 51% respectively (p = 0.0536).

    Conclusions: This population-based study showed that in patients with iNPH, shunt surgery should be performed within 3 months of decision to surgery, to attain the best outcome.

    Fulltekst (pdf)
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  • 21. 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. ()
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Neurovetenskaper.
    Sundström, Nina ()
    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 study2021Inngår i: Intensive Care Medicine, ISSN 0342-4642, E-ISSN 1432-1238, Vol. 47, nr 9, s. 961-973Artikkel i tidsskrift (Fagfellevurdert)
    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.

    Fulltekst (pdf)
    fulltext
  • 22. 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 ()
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Neurovetenskaper.
    Sundström, Nina ()
    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 study2020Inngår i: EBioMedicine, E-ISSN 2352-3964, Vol. 56, artikkel-id 10275Artikkel i tidsskrift (Fagfellevurdert)
    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.

    Fulltekst (pdf)
    fulltext
  • 23. 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. ()
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Neurovetenskaper.
    Sundström, Nina ()
    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 Patients2021Inngår i: Journal of Neurotrauma, ISSN 0897-7151, E-ISSN 1557-9042, Vol. 38, nr 10, s. 1377-1388Artikkel i tidsskrift (Fagfellevurdert)
    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.

  • 24.
    Erelund, Sofia
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Klinisk fysiologi.
    Karp, Kjell
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Klinisk fysiologi.
    Arvidsson, Sandra
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Klinisk fysiologi.
    Johansson, Bengt
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Klinisk fysiologi.
    Sundström, Nina
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Radiofysik.
    Wiklund, Urban
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper.
    Pulmonary function in a cohort of heart-healthy individuals from Northern Sweden: a comparison with discordant reference values2023Inngår i: BMC Pulmonary Medicine, E-ISSN 1471-2466, Vol. 23, nr 1, artikkel-id 110Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    BACKGROUND: Dynamic spirometry is an important investigation to differentiate between impaired and normal lung function. This study aimed to evaluate the results of lung function testing in a cohort of subjects from Northern Sweden without any known heart or pulmonary disease. Our focus was to compare with two reference materials that have showed differences in the age-dependency of lung function in Swedish subjects.

    METHODS: The study population consisted of 285 healthy adults (148 males, 52%) between 20-90 years of age. The subjects had been randomly selected from the population register for inclusion in a study investigating cardiac function in heart-healthy subjects, but were also assessed with dynamic spirometry. At least seven percent reported smoking. Sixteen subjects presented with pulmonary functional impairments and were excluded from the current study. The sex-specific age-dependency in lung volumes was estimated using the LMS model, where non-linear equations were derived for the mean value (M), the location (L) or skewness, and the scatter (S) or coefficient of variation. This model of the observed lung function data was compared with reference values given by the original LMS model published by the Global Lung Initiative (GLI), and with the model from the recent Obstructive Lung Disease In Norrbotten (OLIN) study, where higher reference values were presented for Swedish subjects than those given by the GLI model.

    RESULTS: No differences were found in the age-dependency of pulmonary function between the LMS model developed in the study and the OLIN model. Although the study group included smokers, the original GLI reference values suggested significantly lower normal values of FEV1 (forced expiratory volume) and FVC (forced vital capacity), and consequently fewer subjects below the lower limit of normality, than both the rederived LMS and OLIN models.

    CONCLUSIONS: Our results are in line with previous reports and support that the original GLI reference values underestimate pulmonary function in the adult Swedish population. This underestimation could be reduced by updating the coefficients in the underlying LMS model based on a larger cohort of Swedish citizens than was available in this study.

    Fulltekst (pdf)
    fulltext
  • 25.
    Erelund, Sofia
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Klinisk fysiologi.
    Slunga-Järvholm, Lisbeth
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Avdelningen för hållbar hälsa.
    Nordendahl, Maria
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Allmänmedicin.
    Johansson, Bengt
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin. Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap.
    Wiklund, Urban
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper.
    Sundström, Nina
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper.
    Heart rate variability and long-term survival in females with ischemic heart diseaseManuskript (preprint) (Annet vitenskapelig)
  • 26.
    Erelund, Sofia
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap.
    Södergren, Anna
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Reumatologi.
    Wiklund, Urban
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper.
    Sundström, Nina
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Radiofysik.
    Heart rate variability and cardiovascular risk factors in patients with rheumatoid arthritis: a longitudinal study2023Inngår i: Autonomic Neuroscience: Basic & Clinical, ISSN 1566-0702, E-ISSN 1872-7484, Vol. 249, artikkel-id 103119Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: It is established that the risk of cardiovascular disease (CVD) is increased in patients with Rheumatoid Arthritis (RA). Heart rate variability (HRV) is a method for evaluating the activity in the cardiac autonomic nervous system. Our aim was to assess the longitudinal development of HRV in patients with RA and compare with healthy controls. Furthermore, we wanted to investigate associations between HRV, inflammatory disease activity and cardiovascular complications in patients with RA over time.

    Method: HRV was assessed with frequency-domain analysis at baseline and after five years in 50 patients with early RA, all being younger than 60 years. HRV indices were age-adjusted based on the estimated age-dependency in 100 age and sex matched healthy controls. Additionally, clinical data including serological markers, disease activity, and blood pressure were collected from the patients. Eleven years after inclusion CVD was assessed.

    Results: At baseline, patients with RA presented with lower HRV compared to controls during deep breathing (6 breaths/min), paced normal breathing (12 breaths/min) and after passive tilt to the upright position. No significant change in HRV was observed at the five-year follow-up. A significant negative correlation was found between HRV parameters and systolic blood pressure (SBP) at baseline. A significant positive correlation was found between heart rate and inflammatory markers at baseline but not after five years. Nine patients had developed CVD after 11 years, but no significant association was found with baseline HRV data.

    Conclusion: This study showed that patients with RA have autonomic imbalance both at an early stage of the disease and after five years, despite anti-rheumatic medication, but no correlation between HRV and inflammation markers were observed. Reduced HRV was also significantly negatively correlated with increased SBP. Hypertension is a common finding in patients with RA. Thus, significant decline of HRV could be a useful early marker for development of hypertension in patients with RA.

    Fulltekst (pdf)
    fulltext
  • 27. 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. ()
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Sundström, Nina ()
    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 Study2020Inngår i: Journal of Neurotrauma, ISSN 0897-7151, E-ISSN 1557-9042, Vol. 37, nr 16, s. 1806-1817Artikkel i tidsskrift (Fagfellevurdert)
    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.

  • 28. 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. ()
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap.
    Sundström, Nina ()
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper.
    Effect of frailty on 6-month outcome after traumatic brain injury: a multicentre cohort study with external validation2022Inngår i: Lancet Neurology, ISSN 1474-4422, E-ISSN 1474-4465, Vol. 21, nr 2, s. 153-162Artikkel i tidsskrift (Fagfellevurdert)
    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.

  • 29.
    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 hydrocephalus2021Inngår i: Journal of Neurosurgery, ISSN 0022-3085, E-ISSN 1933-0693, Vol. 134, nr 2, s. 668-677Artikkel i tidsskrift (Fagfellevurdert)
    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.

  • 30. 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. ()
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap.
    Sundström, Nina ()
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper.
    Missing Data in Prediction Research: A Five-Step Approach for Multiple Imputation, Illustrated in the CENTER-TBI Study2021Inngår i: Journal of Neurotrauma, ISSN 0897-7151, E-ISSN 1557-9042, Vol. 38, nr 13, s. 1842-1857Artikkel i tidsskrift (Fagfellevurdert)
    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.

  • 31.
    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 positions2018Inngår i: American Journal of Physiology. Regulatory Integrative and Comparative Physiology, ISSN 0363-6119, E-ISSN 1522-1490, Vol. 314, nr 3, s. R377-R385Artikkel i tidsskrift (Fagfellevurdert)
    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.

  • 32. 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. ()
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Neurovetenskaper.
    Sundström, Nina ()
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper.
    Rehabilitation and outcomes after complicated vs uncomplicated mild TBI: results from the CENTER-TBI study2022Inngår i: BMC Health Services Research, E-ISSN 1472-6963, Vol. 22, nr 1, artikkel-id 1536Artikkel i tidsskrift (Fagfellevurdert)
    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.

    Fulltekst (pdf)
    fulltext
  • 33. Huijben, Jilske A
    et al.
    Wiegers, Eveline J A
    Ercole, Ari
    de Keizer, Nicolette F
    Maas, Andrew I R
    Steyerberg, Ewout W
    Citerio, Giuseppe
    Wilson, Lindsay
    Polinder, Suzanne
    Nieboer, Daan
    Menon, David
    Lingsma, Hester F
    van der Jagt, Mathieu
    Sundström, Nina ()
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper.
    Quality indicators for patients with traumatic brain injury in European intensive care units: a CENTER-TBI study.2020Inngår i: Critical Care, ISSN 1364-8535, E-ISSN 1466-609X, Vol. 24, nr 1, artikkel-id 78Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    BACKGROUND: The aim of this study is to validate a previously published consensus-based quality indicator set for the management of patients with traumatic brain injury (TBI) at intensive care units (ICUs) in Europe and to study its potential for quality measurement and improvement.

    METHODS: Our analysis was based on 2006 adult patients admitted to 54 ICUs between 2014 and 2018, enrolled in the CENTER-TBI study. Indicator scores were calculated as percentage adherence for structure and process indicators and as event rates or median scores for outcome indicators. Feasibility was quantified by the completeness of the variables. Discriminability was determined by the between-centre variation, estimated with a random effect regression model adjusted for case-mix severity and quantified by the median odds ratio (MOR). Statistical uncertainty of outcome indicators was determined by the median number of events per centre, using a cut-off of 10.

    RESULTS: A total of 26/42 indicators could be calculated from the CENTER-TBI database. Most quality indicators proved feasible to obtain with more than 70% completeness. Sub-optimal adherence was found for most quality indicators, ranging from 26 to 93% and 20 to 99% for structure and process indicators. Significant (p < 0.001) between-centre variation was found in seven process and five outcome indicators with MORs ranging from 1.51 to 4.14. Statistical uncertainty of outcome indicators was generally high; five out of seven had less than 10 events per centre.

    CONCLUSIONS: Overall, nine structures, five processes, but none of the outcome indicators showed potential for quality improvement purposes for TBI patients in the ICU. Future research should focus on implementation efforts and continuous reevaluation of quality indicators.

    TRIAL REGISTRATION: The core study was registered with ClinicalTrials.gov, number NCT02210221, registered on August 06, 2014, with Resource Identification Portal (RRID: SCR_015582).

  • 34. Jacob, Louis
    et al.
    Cogné, Mélanie
    Tenovuo, Olli
    Røe, Cecilie
    Andelic, Nada
    Majdan, Marek
    Ranta, Jukka
    Ylen, Peter
    Dawes, Helen
    Azouvi, Philippe
    Koskinen, Lars-Owe D. ()
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Neurovetenskaper.
    Sundström, Nina ()
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper.
    Predictors of Access to Rehabilitation in the Year Following Traumatic Brain Injury: A European Prospective and Multicenter Study2020Inngår i: Neurorehabilitation and Neural Repair, ISSN 1545-9683, E-ISSN 1552-6844, Vol. 34, nr 9, s. 814-830Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: Although rehabilitation is beneficial for individuals with traumatic brain injury (TBI), a significant proportion of them do not receive adequate rehabilitation after acute care.

    Objective: Therefore, the goal of this prospective and multicenter study was to investigate predictors of access to rehabilitation in the year following injury in patients with TBI.

    Methods: Data from a large European study (CENTER-TBI), including TBIs of all severities between December 2014 and December 2017 were used (N = 4498 patients). Participants were dichotomized into those who had and those who did not have access to rehabilitation in the year following TBI. Potential predictors included sociodemographic factors, psychoactive substance use, preinjury medical history, injury-related factors, and factors related to medical care, complications, and discharge.

    Results: In the year following traumatic injury, 31.4% of patients received rehabilitation services. Access to rehabilitation was positively and significantly predicted by female sex (odds ratio [OR] = 1.50), increased number of years of education completed (OR = 1.05), living in Northern (OR = 1.62; reference: Western Europe) or Southern Europe (OR = 1.74), lower prehospital Glasgow Coma Scale score (OR = 1.03), higher Injury Severity Score (OR = 1.01), intracranial (OR = 1.33) and extracranial (OR = 1.99) surgery, and extracranial complication (OR = 1.75). On contrast, significant negative predictors were lack of preinjury employment (OR = 0.80), living in Central and Eastern Europe (OR = 0.42), and admission to hospital ward (OR = 0.47; reference: admission to intensive care unit) or direct discharge from emergency room (OR = 0.24).

    Conclusions: Based on these findings, there is an urgent need to implement national and international guidelines and strategies for access to rehabilitation after TBI.

  • 35. Kals, Mart
    et al.
    Kunzmann, Kevin
    Parodi, Livia
    Radmanesh, Farid
    Wilson, Lindsay
    Izzy, Saef
    Anderson, Christopher D.
    Puccio, Ava M.
    Okonkwo, David O.
    Temkin, Nancy
    Steyerberg, Ewout W.
    Stein, Murray B.
    Manley, Geoff T.
    Maas, Andrew I. R.
    Richardson, Sylvia
    Diaz-Arrastia, Ramon
    Palotie, Aarno
    Ripatti, Samuli
    Rosand, Jonathan
    Menon, David K.
    Koskinen, Lars-Owe D. ()
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap.
    Sundström, Nina ()
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper.
    A genome-wide association study of outcome from traumatic brain injury2022Inngår i: EBioMedicine, E-ISSN 2352-3964, Vol. 77, artikkel-id 103933Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    BACKGROUND: Factors such as age, pre-injury health, and injury severity, account for less than 35% of outcome variability in traumatic brain injury (TBI). While some residual outcome variability may be attributable to genetic factors, published candidate gene association studies have often been underpowered and subject to publication bias.

    METHODS: We performed the first genome- and transcriptome-wide association studies (GWAS, TWAS) of genetic effects on outcome in TBI. The study population consisted of 5268 patients from prospective European and US studies, who attended hospital within 24 h of TBI, and satisfied local protocols for computed tomography.

    FINDINGS: The estimated heritability of TBI outcome was 0·26. GWAS revealed no genetic variants with genome-wide significance (p < 5 × 10-8), but identified 83 variants in 13 independent loci which met a lower pre-specified sub-genomic statistical threshold (p < 10-5). Similarly, none of the genes tested in TWAS met tissue-wide significance. An exploratory analysis of 75 published candidate variants associated with 28 genes revealed one replicable variant (rs1800450 in the MBL2 gene) which retained significance after correction for multiple comparison (p = 5·24 × 10-4).

    INTERPRETATION: While multiple novel loci reached less stringent thresholds, none achieved genome-wide significance. The overall heritability estimate, however, is consistent with the hypothesis that common genetic variation substantially contributes to inter-individual variability in TBI outcome. The meta-analytic approach to the GWAS and the availability of summary data allows for a continuous extension with additional cohorts as data becomes available.

    FUNDING: A full list of funding bodies that contributed to this study can be found in the Acknowledgements section.

    Fulltekst (pdf)
    fulltext
  • 36.
    Koskinen, Lars-Owe D.
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Eklund, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper.
    Sundström, Nina
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper.
    Olivecrona, Magnus
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Prostacyclin Influences the Pressure Reactivity in Patients with Severe Traumatic Brain Injury Treated with an ICP-Targeted Therapy2015Inngår i: Neurocritical Care, ISSN 1541-6933, E-ISSN 1556-0961, Vol. 22, nr 1, s. 26-33Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    This prospective consecutive double-blinded randomized study investigated the effect of prostacyclin on pressure reactivity (PR) in severe traumatic brain injured patients. Other aims were to describe PR over time and its relation to outcome. Blunt head trauma patients, Glasgow coma scale a parts per thousand currency sign8, age 15-70 years were included and randomized to prostacyclin treatment (n = 23) or placebo (n = 25). Outcome was assessed using the extended Glasgow outcome scale (GOSE) at 3 months. PR was calculated as the regression coefficient between the hourly mean values of ICP versus MAP. Pressure active/stable was defined as PR a parts per thousand currency sign0. Mean PR over 96 h (PRtot) was 0.077 +/- A 0.168, in the prostacyclin group 0.030 +/- A 0.153 and in the placebo group 0.120 +/- A 0.173 (p < 0.02). There was a larger portion of pressure-active/stable patients in the prostacyclin group than in the placebo group (p < 0.05). Intra-individual changes over time were common. PRtot correlated negatively with GOSE score (p < 0.04). PRtot was 0.117 +/- A 0.182 in the unfavorable (GOSE 1-4) and 0.029 +/- A 0.140 in the favorable outcome group (GOSE 5-8). Area under the curve for prediction of death (ROC) was 0.742 and for favorable outcome 0.628. Prostacyclin influenced the PR in a direction of increased pressure stability and a lower PRtot was associated with improved outcome. The individual PR varied substantially over time. The predictive value of PRtot for outcome was not solid enough to be used in the clinical situation.

  • 37.
    Koskinen, Lars-Owe D.
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Sundström, Nina
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Radiofysik.
    Hägglund, Linda
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Eklund, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Radiofysik.
    Olivecrona, Magnus
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap. Department of Anaesthesia and Intensive Care, Section for Neurosurgery, Faculty of Health and Medicine, Department for Medical Sciences, Örebro University, Örebro, Sweden. .
    Prostacyclin Affects the Relation Between Brain Interstitial Glycerol and Cerebrovascular Pressure Reactivity in Severe Traumatic Brain Injury2019Inngår i: Neurocritical Care, ISSN 1541-6933, E-ISSN 1556-0961, Vol. 31, nr 3, s. 494-500Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: Cerebral injury may alter the autoregulation of cerebral blood flow. One index for describing cerebrovascular state is the pressure reactivity (PR). Little is known of whether PR is associated with measures of brain metabolism and indicators of ischemia and cell damage. The aim of this investigation was to explore whether increased interstitial levels of glycerol, a marker of cell membrane damage, are associated with PR, and if prostacyclin, a membrane stabilizer and regulator of the microcirculation, may affect this association in a beneficial way.

    Materials and Methods: Patients suffering severe traumatic brain injury (sTBI) were treated according to an intracranial pressure (ICP)-targeted therapy based on the Lund concept and randomized to an add-on treatment with prostacyclin or placebo. Inclusion criteria were verified blunt head trauma, Glasgow Coma Score <= 8, age 15-70 years, and a first measured cerebral perfusion pressure of >= 10 mmHg. Multimodal monitoring was applied. A brain microdialysis catheter was placed on the worst affected side, close to the penumbra zone. Mean (glycerol(mean)) and maximal glycerol (glycerol(max)) during the 96-h sampling period were calculated. The mean PR was calculated as the ICP/mean arterial pressure (MAP) regression coefficient based on hourly mean ICP and MAP during the first 96 h.

    Results: Of the 48 included patients, 45 had valid glycerol and PR measurements available. PR was higher in the placebo group as compared to the prostacyclin group (p = 0.0164). There was a positive correlation between PR and the glycerol(mean) (rho = 0.503, p = 0.01) and glycerol(max) (rho = 0.490, p = 0.015) levels in the placebo group only.

    Conclusions: PR is correlated to the glycerol level in patients suffering from sTBI, a relationship that is not seen in the group treated with prostacyclin. Glycerol has been associated with membrane degradation and may support glycerol as a biomarker for vascular endothelial breakdown. Such a breakdown may impair the regulation of cerebrovascular PR.

    Fulltekst (pdf)
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  • 38.
    Koskinen, Lars-Owe D.
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Sundström, Nina
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Radiofysik.
    Hägglund, Linda
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Eklund, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Radiofysik.
    Olivecrona, Magnus
    The relation between brain interstitial clycerol and pressure reactivity in TBI is prostacyclin dependent2018Inngår i: Journal of Neurotrauma, ISSN 0897-7151, E-ISSN 1557-9042, Vol. 35, nr 16, s. A185-A185Artikkel i tidsskrift (Annet vitenskapelig)
  • 39.
    Koskinen, Lars-Owe
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Sundstrom, Nina
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper. Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Centrum för medicinsk teknik och fysik (CMTF).
    Brorsson, Camilla
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap.
    Olivecrona, M.
    SECONDARY PEAK OF S-100B IS ASSOCIATED WITH DECOMPRESSIVE HEMICRANIECTOMY2016Inngår i: Journal of Neurotrauma, ISSN 0897-7151, E-ISSN 1557-9042, Vol. 33, nr 3, s. A27-A27Artikkel i tidsskrift (Annet vitenskapelig)
    Abstract [en]

    S-100B is a tissue biomarker for brain injury and secondary peak of S-100B (SP) is associated with outcome. Little is known whether SP is associated with decompressive hemicraniectomy (DC).

  • 40.
    Lenfeldt, Niklas
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Neurologi. Neurologi.
    Andersson, Nina
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper.
    Ågren-Wilsson, Aina
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Neurologi. Neurologi.
    Bergenheim, A Tommy
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Neurokirurgi. Neurokirurgi.
    Koskinen, Lars-Owe D
    Neurokirurgi.
    Eklund, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper.
    Malm, Jan
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Neurologi. Neurologi.
    Cerebrospinal fluid pulse pressure method: a possible substitute for the examination of B waves2004Inngår i: Journal of Neurosurgery, ISSN 0022-3085, E-ISSN 1933-0693, Vol. 101, nr 6, s. 944-950Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Object. The appearance of numerous B waves during intracranial pressure (ICP) registration in patients with idiopathic adult hydrocephalus syndrome (IAHS) is considered to predict good outcome after shunt surgery. The aim of this study was to describe which physical parameters of the cerebrospinal fluid (CSF) system B-waves reflect and to find a method that could replace long-term B-wave analysis.

    Methods. Ten patients with IAHS were subjected to long-term registration of ICP and a lumbar constant-pressure infusion test. The B-wave presence, CSF outflow resistance (Rout), and relative pulse pressure coefficient (RPPC) were assessed using computerized analysis. The RPPC was introduced as a parameter reflecting the joint effect of elastance and pulsatory volume changes on ICP and was determined by relating ICP pulse amplitudes to mean ICP.

    Conclusions. The B-wave presence on ICP registration correlates strongly with RPPC (r = 0.91, p < 0.001, 10 patients) but not with CSF Rout. This correlation indicates that B waves—like RPPC—primarily reflect the ability of the CSF system to reallocate and store liquid rather than absorb it. The RPPC-assessing lumbar short-term CSF pulse pressure method could replace the intracranial long-term B-wave analysis.

  • 41.
    Liljegren, Axel Risinger
    et al.
    Department of Clinical Science-Neurosciences, Sweden.
    Brorsson, Camilla
    Department of Surgery and Perioperative Sciences, Sweden.
    Karlsson, Marcus
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Radiofysik.
    Koskinen, Lars-Owe D.
    Department of Clinical Science-Neurosciences, Sweden.
    Sundström, Nina
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Radiofysik.
    Cerebrovascular pressure reactivity measures: index comparison and clinical outcome in patients with traumatic brain injury treated according to an intracranial pressure–focused management2023Inngår i: Neurotrauma Reports, E-ISSN 2689-288X, Vol. 4, nr 1, s. 848-856Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The aim was to investigate whether the pressure reactivity indices PRx, long-PRx (L-PRx), and pressure reactivity (PR) are interchangeable as measures of vascular reactivity, and whether they correlate with clinical outcome when an intracranial pressure (ICP)-targeted treatment regimen is applied in patients with traumatic brain injury (TBI). Patients with TBI (n = 29) that arrived at the hospital within 24 h of injury were included. PRx and L-PRx were derived from Pearson correlations between mean arterial pressure (MAP) and ICP over a short- and long-time interval. PR was the regression coefficient between the hourly mean values of ICP and MAP. Indices were compared to each other, parameters at admission, and outcome assessed by the extended Glasgow Outcome Scale-Extended (GOSE) at 6 and 12 months. PRx and L-PRx had the strongest correlation with each other (R = 0.536, p < 0.01). A correlation was also noted between L-PRx and PR (R = 0.475, p < 0.01), but not between PRx and PR. A correlation was found between age and PRx (R = 0.482, p = 0.01). No association with outcome for any of the indices was found. PRx/L-PRx and L-PRx/PR were moderately correlated with each other. Age was associated with PRx. None of the indices correlated with outcome when our ICP treatment regime was applied. Part of our null hypothesis, that the three indices are associated with outcome, must be rejected. There was, however, an association between some of the indices. To further understand the relation of treatment regimes and pressure reactivity indices, a larger, randomized study is warranted.

    Fulltekst (pdf)
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  • 42.
    Malm, Jan
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Sundström, Nina
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Radiofysik.
    Cesarini, Kristina G
    Department of Neuroscience, Uppsala University, Uppsala, Sweden.
    Edsbagge, Mikael
    Institute of Neuroscience and Physiology, University of Gothenburg, Göteborg, Sweden.
    Kristensen, B
    Department of Neurology, Aalborg University, Aalborg, Denmark.
    Leijon, Göran
    Division of Neurology, Faculty of Health Sciences, University Hospital, Linköping, Sweden.
    Eklund, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Radiofysik.
    Implementation of a new CSF dynamic device: a multicenter feasibility study in 562 patients2012Inngår i: Acta Neurologica Scandinavica, ISSN 0001-6314, E-ISSN 1600-0404, Vol. 125, nr 3, s. 199-205Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Objectives: The cerebrospinal fluid (CSF) infusion test is frequently used when selecting hydrocephalus patients for shunt surgery. Very little has been reported regarding adverse events. We present a prospective feasibility study.

    Methods: Standardized devices for measuring CSF dynamics were built and 562 patients investigated: Needles were placed by lumbar puncture (LP). An automatic CSF infusion protocol was performed. Course of events during the investigation as well as adverse events were registered.

    Results: Preoperative evaluation of normal-pressure hydrocephalus was the most common indication (63%), followed by evaluation of shunt function (23%) and intracranial pressure recordings (14%). The LP was successfully performed in all but nine cases with 24 patients (4.3%) reporting major discomfort. Ringer infusion was performed in 474 investigations, and a valid measurement of the outflow resistance was received in 439 (93%). During the infusion phase, 17 (4%) patients reported severe headache. Infusion volume was significantly higher in patients having subjective symptoms during the infusion phase compared with those without adverse events. During 269 preoperative CSF tap tests, six (2%) patients had severe headache. Post-investigational headache was reported by 83 (15%) patients at the 24-h follow-up. No serious adverse events were observed.

    Conclusion: Infusion testing was safe and without serious adverse events with a high rate of successful procedures. The investigation was associated with expected mild to moderate discomfort.

  • 43.
    Manchester, Ian
    et al.
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Institutionen för tillämpad fysik och elektronik.
    Andersson, Kennet
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Radiofysik. Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Centrum för medicinsk teknik och fysik (CMTF).
    Andersson, Nina
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Radiofysik. Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Centrum för medicinsk teknik och fysik (CMTF).
    Shiriaev, Anton S
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Institutionen för tillämpad fysik och elektronik.
    Eklund, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Radiofysik. Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Centrum för medicinsk teknik och fysik (CMTF).
    A nonlinear observer for on-line estimation of the cerebrospinal fluid outflow resistance.2008Inngår i: Automatica, ISSN 0005-1098, E-ISSN 1873-2836, Vol. 44, nr 5, s. 1426-1430Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Accurate estimates of the outflow resistance of the human cerebrospinal fluid system are important for the diagnosis of a medical condition known as hydrocephalus. In this paper we design a nonlinear observer which provides on-line estimates of the outflow resistance, to the best of our knowledge the first method to do so. The output of the observer is proven to globally converge to an unbiased estimate. Its performance is experimentally verified using the same apparatus used to perform actual patient diagnoses and a specially-designed physical model of the human cerebrospinal fluid system.

  • 44. Mikolić, Ana
    et al.
    Polinder, Suzanne
    Steyerberg, Ewout W.
    Retel Helmrich, Isabel R. A.
    Giacino, Joseph T.
    Maas, Andrew I. R.
    van der Naalt, Joukje
    Voormolen, Daphne C.
    von Steinbüchel, Nicole
    Wilson, Lindsay
    Lingsma, Hester F.
    van Klaveren, David
    Koskinen, Lars-Owe ()
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Neurovetenskaper.
    Sundström, Nina ()
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper.
    Prediction of Global Functional Outcome and Post-Concussive Symptoms after Mild Traumatic Brain Injury: External Validation of Prognostic Models in the Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) Study2021Inngår i: Journal of Neurotrauma, ISSN 0897-7151, E-ISSN 1557-9042, Vol. 38, nr 2, s. 196-209Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The majority of traumatic brain injuries (TBIs) are categorized as mild, according to a baseline Glasgow Coma Scale (GCS) score of 13-15. Prognostic models that were developed to predict functional outcome and persistent post-concussive symptoms (PPCS) after mild TBI have rarely been externally validated. We aimed to externally validate models predicting 3-12-month Glasgow Outcome Scale Extended (GOSE) or PPCS in adults with mild TBI. We analyzed data from the Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) project, which included 2862 adults with mild TBI, with 6-month GOSE available for 2374 and Rivermead Post-Concussion Symptoms Questionnaire (RPQ) results available for 1605 participants. Model performance was evaluated based on calibration (graphically and characterized by slope and intercept) and discrimination (C-index). We validated five published models for 6-month GOSE and three for 6-month PPCS scores. The models used different cutoffs for outcome and some included symptoms measured 2 weeks post-injury. Discriminative ability varied substantially (C-index between 0.58 and 0.79). The models developed in the Corticosteroid Randomisation After Significant Head Injury (CRASH) trial for prediction of GOSE <5 discriminated best (C-index 0.78 and 0.79), but were poorly calibrated. The best performing models for PPCS included 2-week symptoms (C-index 0.75 and 0.76). In conclusion, none of the prognostic models for early prediction of GOSE and PPCS has both good calibration and discrimination in persons with mild TBI. In future studies, prognostic models should be tailored to the population with mild TBI, predicting relevant end-points based on readily available predictors.

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  • 45. Mikolić, Ana
    et al.
    van Klaveren, David
    Oude Groeniger, Joost
    Wiegers, Eveline J. A.
    Lingsma, Hester F.
    Zeldovich, Marina
    von Steinbüchel, Nicole
    Maas, Andrew I. R.
    Roeters van Lennep, Jeanine E.
    Polinder, Suzanne
    Koskinen, Lars-Owe D. ()
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Neurovetenskaper.
    Sundström, Nina ()
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper.
    Differences between Men and Women in Treatment and Outcome after Traumatic Brain Injury2021Inngår i: Journal of Neurotrauma, ISSN 0897-7151, E-ISSN 1557-9042, Vol. 38, nr 2, s. 235-251Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Traumatic brain injury (TBI) is a significant cause of disability, but little is known about sex and gender differences after TBI. We aimed to analyze the association between sex/gender, and the broad range of care pathways, treatment characteristics, and outcomes following mild and moderate/severe TBI. We performed mixed-effects regression analyses in the prospective multi-center Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) study, stratified for injury severity and age, and adjusted for baseline characteristics. Outcomes were various care pathway and treatment variables, and 6-month measures of functional outcome, health-related quality of life (HRQoL), post-concussion symptoms (PCS), and mental health symptoms. The study included 2862 adults (36% women) with mild (mTBI; Glasgow Coma Scale [GCS] score 13–15), and 1333 adults (26% women) with moderate/severe TBI (GCS score 3–12). Women were less likely to be admitted to the intensive care unit (ICU; odds ratios [OR] 0.6, 95% confidence interval [CI]: 0.4-0.8) following mTBI. Following moderate/severe TBI, women had a shorter median hospital stay (OR 0.7, 95% CI: 0.5-1.0). Following mTBI, women had poorer outcomes; lower Glasgow Outcome Scale Extended (GOSE; OR 1.4, 95% CI: 1.2-1.6), lower generic and disease-specific HRQoL, and more severe PCS, depression, and anxiety. Among them, women under age 45 and above age 65 years showed worse 6-month outcomes compared with men of the same age. Following moderate/severe TBI, there was no difference in GOSE (OR 0.9, 95% CI: 0.7-1.2), but women reported more severe PCS (OR 1.7, 95% CI: 1.1-2.6). Men and women differ in care pathways and outcomes following TBI. Women generally report worse 6-month outcomes, but the size of differences depend on TBI severity and age. Future studies should examine factors that explain these differences.

    Fulltekst (pdf)
    fulltext
  • 46.
    Qvarlander, Sara
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Radiofysik. Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Centrum för medicinsk teknik och fysik (CMTF).
    Sundström, Nina
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Radiofysik. Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Centrum för medicinsk teknik och fysik (CMTF).
    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).
    Postural effects on intracranial pressure: modeling and clinical evaluation2013Inngår i: Journal of applied physiology, ISSN 8750-7587, E-ISSN 1522-1601, Vol. 115, nr 10, s. 1474-1480Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Introduction The physiological effect of posture on intracranial pressure (ICP) is not well described. This study defined and evaluated three mathematical models describing the postural effects on ICP, designed to predict ICP at different head-up tilt-angles from the supine ICP value.

    Methods Model I was based on a hydrostatic indifference point for the cerebrospinal fluid (CSF) system, i.e. the existence of a point in the system where pressure is independent of body position. Models II and III were based on Davson's equation for CSF absorption, which relates ICP to venous pressure, and postulated that gravitational effects within the venous system are transferred to the CSF system. Model II assumed a fully communicating venous system and model III that collapse of the jugular veins at higher tilt-angles creates two separate hydrostatic compartments. Evaluation of the models was based on ICP measurements at seven tilt-angles (0-71°)in 27 normal pressure hydrocephalus patients.

    Results ICP decreased with tilt-angle (ANOVA, p<0.01). The reduction was well predicted by model III (ANOVA lack-of-fit: p=0.65), which showed excellent fit against measured ICP. Neither model I nor II adequately described the reduction in ICP (ANOVA lack-of-fit: p<0.01).

    Conclusion Postural changes in ICP could not be predicted based on the currently accepted theory of a hydrostatic indifference point for the CSF system, but a new model combining Davson's equation for CSF absorption and hydrostatic gradients in a collapsible venous system performed well and can be useful in future research on gravity and CSF physiology.

  • 47. Retel Helmrich, Isabel Rosalie Arianne
    et al.
    van Klaveren, David
    Andelic, Nada
    Lingsma, Hester
    Maas, Andrew
    Menon, David
    Polinder, Suzanne
    Røe, Cecilie
    Steyerberg, Ewout W
    Van Veen, Ernest
    Wilson, Lindsay
    Koskinen, Lars-Owe D. ()
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Neurovetenskaper.
    Sundström, Nina ()
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper.
    Discrepancy between disability and reported well-being after traumatic brain injury2022Inngår i: Journal of Neurology, Neurosurgery and Psychiatry, ISSN 0022-3050, E-ISSN 1468-330X, Vol. 93, nr 7, s. 785-96Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    BACKGROUND: Following traumatic brain injury (TBI), the clinical focus is often on disability. However, patients' perceptions of well-being can be discordant with their disability level, referred to as the 'disability paradox'. We aimed to examine the relationship between disability and health-related quality of life (HRQoL) following TBI, while taking variation in personal, injury-related and environment factors into account.

    METHODS: We used data from the Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury study. Disability was assessed 6 months post-injury by the Glasgow Outcome Scale-Extended (GOSE). HRQoL was assessed by the SF-12v2 physical and mental component summary scores and the Quality of Life after Traumatic Brain Injury overall scale. We examined mean total and domain HRQoL scores by GOSE. We quantified variance in HRQoL explained by GOSE, personal, injury-related and environment factors with multivariable regression.

    RESULTS: Six-month outcome assessments were completed in 2075 patients, of whom 78% had mild TBI (Glasgow Coma Scale 13-15). Patients with severe disability had higher HRQoL than expected on the basis of GOSE alone, particularly after mild TBI. Up to 50% of patients with severe disability reported HRQoL scores within the normative range. GOSE, personal, injury-related and environment factors explained a limited amount of variance in HRQoL (up to 29%).

    CONCLUSION: Contrary to the idea that discrepancies are unusual, many patients with poor functional outcomes reported well-being that was at or above the boundary considered satisfactory for the normative sample. These findings challenge the idea that satisfactory HRQoL in patients with disability should be described as 'paradoxical' and question common views of what constitutes 'unfavourable' outcome.

    Fulltekst (pdf)
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  • 48. Rezoagli, Emanuele
    et al.
    Petrosino, Matteo
    Rebora, Paola
    Menon, David K.
    Mondello, Stefania
    Cooper, D. James
    Maas, Andrew I. R.
    Wiegers, Eveline J. A.
    Galimberti, Stefania
    Citerio, Giuseppe
    Koskinen, Lars-Owe D. ()
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap.
    Sundström, Nina ()
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper.
    High arterial oxygen levels and supplemental oxygen administration in traumatic brain injury: insights from CENTER-TBI and OzENTER-TBI.2022Inngår i: Intensive Care Medicine, ISSN 0342-4642, E-ISSN 1432-1238, Vol. 48, nr 12, s. 1709-1725Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    PURPOSE: The effect of high arterial oxygen levels and supplemental oxygen administration on outcomes in traumatic brain injury (TBI) is debated, and data from large cohorts of TBI patients are limited. We investigated whether exposure to high blood oxygen levels and high oxygen supplementation is independently associated with outcomes in TBI patients admitted to the intensive care unit (ICU) and undergoing mechanical ventilation.

    METHODS: This is a secondary analysis of two multicenter, prospective, observational, cohort studies performed in Europe and Australia. In TBI patients admitted to ICU, we describe the arterial partial pressure of oxygen (PaO2) and the oxygen inspired fraction (FiO2). We explored the association between high PaO2 and FiO2 levels within the first week with clinical outcomes. Furthermore, in the CENTER-TBI cohort, we investigate whether PaO2 and FiO2 levels may have differential relationships with outcome in the presence of varying levels of brain injury severity (as quantified by levels of glial fibrillary acidic protein (GFAP) in blood samples obtained within 24 h of injury).

    RESULTS: The analysis included 1084 patients (11,577 measurements) in the CENTER-TBI cohort, of whom 55% had an unfavorable outcome, and 26% died at a 6-month follow-up. Median PaO2 ranged from 93 to 166 mmHg. Exposure to higher PaO2 and FiO2 in the first seven days after ICU admission was independently associated with a higher mortality rate. A trend of a higher mortality rate was partially confirmed in the OzENTER-TBI cohort (n = 159). GFAP was independently associated with mortality and functional neurologic outcome at follow-up, but it did not modulate the outcome impact of high PaO2 levels, which remained independently associated with 6-month mortality.

    CONCLUSIONS: In two large prospective multicenter cohorts of critically ill patients with TBI, levels of PaO2 and FiO2 varied widely across centers during the first seven days after ICU admission. Exposure to high arterial blood oxygen or high supplemental oxygen was independently associated with 6-month mortality in the CENTER-TBI cohort, and the severity of brain injury did not modulate this relationship. Due to the limited sample size, the findings were not wholly validated in the external OzENTER-TBI cohort. We cannot exclude the possibility that the worse outcomes associated with higher PaO2 were due to use of higher FiO2 in patients with more severe injury or physiological compromise. Further, these findings may not apply to patients in whom FiO2 and PaO2 are titrated to brain tissue oxygen monitoring (PbtO2) levels. However, at minimum, these findings support the need for caution with oxygen therapy in TBI, particularly since titration of supplemental oxygen is immediately applicable at the bedside.

    Fulltekst (pdf)
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  • 49. Riemann, Lennart
    et al.
    Alhalabi, Obada T
    Unterberg, Andreas W
    Younsi, Alexander
    Koskinen, Lars-Owe D. ()
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Neurovetenskaper.
    Sundström, Nina ()
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper.
    Concomitant spine trauma in patients with traumatic brain injury: Patient characteristics and outcomes2022Inngår i: Frontiers in Neurology, E-ISSN 1664-2295, Vol. 13, artikkel-id 861688Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    OBJECTIVE: Spine injury is highly prevalent in patients with poly-trauma, but data on the co-occurrence of spine trauma in patients with traumatic brain injury (TBI) are scarce. In this study, we used the Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) database to assess the prevalence, characteristics, and outcomes of patients with TBI and a concurrent traumatic spinal injury (TSI).

    METHODS: Data from the European multi-center CENTER-TBI study were analyzed. Adult patients with TBI (≥18 years) presenting with a concomitant, isolated TSI of at least serious severity (Abbreviated Injury Scale; AIS ≥3) were included. For outcome analysis, comparison groups of TBI patients with TSI and systemic injuries (non-isolated TSI) and without TSI were created using propensity score matching. Rates of mortality, unfavorable outcomes (Glasgow Outcome Scale Extended; GOSe < 5), and full recovery (GOSe 7-8) of all patients and separately for patients with only mild TBI (mTBI) were compared between groups at 6-month follow-up.

    RESULTS: A total of 164 (4%) of the 4,254 CENTER-TBI core study patients suffered from a concomitant isolated TSI. The median age was 53 [interquartile range (IQR): 37-66] years and 71% of patients were men. mTBI was documented in 62% of cases, followed by severe TBI (26%), and spine injuries were mostly cervical (63%) or thoracic (31%). Surgical spine stabilization was performed in 19% of cases and 57% of patients were admitted to the ICU. Mortality at 6 months was 11% and only 36% of patients regained full recovery. There were no significant differences in the 6-month rates of mortality, unfavorable outcomes, or full recovery between TBI patients with and without concomitant isolated TSI. However, concomitant non-isolated TSI was associated with an unfavorable outcome and a higher mortality. In patients with mTBI, a negative association with full recovery could be observed for both concomitant isolated and non-isolated TSI.

    CONCLUSION: Rates of mortality, unfavorable outcomes, and full recovery in TBI patients with and without concomitant, isolated TSIs were comparable after 6 months. However, in patients with mTBI, concomitant TSI was a negative predictor for a full recovery. These findings might indicate that patients with moderate to severe TBI do not necessarily exhibit worse outcomes when having a concomitant TSI, whereas patients with mTBI might be more affected.

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  • 50. Riemann, Lennart
    et al.
    Beqiri, Erta
    Smielewski, Peter
    Czosnyka, Marek
    Stocchetti, Nino
    Sakowitz, Oliver
    Zweckberger, Klaus
    Unterberg, Andreas
    Younsi, Alexander
    Sundström, Nina ()
    Department of Radiation Sciences, Biomedical Engineering, Umeå University Hospital, Umeå, Sweden.
    Low-resolution pressure reactivity index and its derived optimal cerebral perfusion pressure in adult traumatic brain injury: a CENTER-TBI study2020Inngår i: Critical Care, ISSN 1364-8535, E-ISSN 1466-609X, Vol. 24, nr 1, artikkel-id 266Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: After traumatic brain injury (TBI), brain tissue can be further damaged when cerebral autoregulation is impaired. Managing cerebral perfusion pressure (CPP) according to computed "optimal CPP" values based on cerebrovascular reactivity indices might contribute to preventing such secondary injuries. In this study, we examined the discriminative value of a low-resolution long pressure reactivity index (LPRx) and its derived "optimal CPP" in comparison to the well-established high-resolution pressure reactivity index (PRx).

    Methods: Using the Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) study dataset, the association of LPRx (correlation between 1-min averages of intracranial pressure and arterial blood pressure over a moving time frame of 20 min) and PRx (correlation between 10-s averages of intracranial pressure and arterial blood pressure over a moving time frame of 5 min) to outcome was assessed and compared using univariate and multivariate regression analysis. "Optimal CPP" values were calculated using a multi-window algorithm that was based on either LPRx or PRx, and their discriminative ability was compared.

    Results: LPRx and PRx were both significant predictors of mortality in univariate and multivariate regression analysis, but PRx displayed a higher discriminative ability. Similarly, deviations of actual CPP from "optimal CPP" values calculated from each index were significantly associated with outcome in univariate and multivariate analysis. "Optimal CPP" based on PRx, however, trended towards more precise predictions.

    Conclusions: LPRx and its derived "optimal CPP" which are based on low-resolution data were significantly associated with outcome after TBI. However, they did not reach the discriminative ability of the high-resolution PRx and its derived "optimal CPP." Nevertheless, LPRx might still be an interesting tool to assess cerebrovascular reactivity in centers without high-resolution signal monitoring.

    Trial registration: ClinicalTrials.gov Identifier: NCT02210221. First submitted July 29, 2014. First posted August 6, 2014.

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