Umeå University's logo

umu.sePublications
Change search
Refine search result
12 1 - 50 of 78
CiteExportLink to result list
Permanent link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
Rows per page
  • 5
  • 10
  • 20
  • 50
  • 100
  • 250
Sort
  • Standard (Relevance)
  • Author A-Ö
  • Author Ö-A
  • Title A-Ö
  • Title Ö-A
  • Publication type A-Ö
  • Publication type Ö-A
  • Issued (Oldest first)
  • Issued (Newest first)
  • Created (Oldest first)
  • Created (Newest first)
  • Last updated (Oldest first)
  • Last updated (Newest first)
  • Disputation date (earliest first)
  • Disputation date (latest first)
  • Standard (Relevance)
  • Author A-Ö
  • Author Ö-A
  • Title A-Ö
  • Title Ö-A
  • Publication type A-Ö
  • Publication type Ö-A
  • Issued (Oldest first)
  • Issued (Newest first)
  • Created (Oldest first)
  • Created (Newest first)
  • Last updated (Oldest first)
  • Last updated (Newest first)
  • Disputation date (earliest first)
  • Disputation date (latest first)
Select
The maximal number of hits you can export is 250. When you want to export more records please use the Create feeds function.
  • 1. Andelic, Nada
    et al.
    Røe, Cecilie
    Brunborg, Cathrine
    Zeldovich, Marina
    Løvstad, Marianne
    Løke, Daniel
    Borgen, Ida M.
    Voormolen, Daphne C.
    Howe, Emilie I.
    Forslund, Marit V.
    Dahl, Hilde M.
    von Steinbuechel, Nicole
    Koskinen, Lars-Owe (Contributor)
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Neurosciences.
    Frequency of fatigue and its changes in the first 6 months after traumatic brain injury: results from the CENTER-TBI study2021In: Journal of Neurology, ISSN 0340-5354, E-ISSN 1432-1459, Vol. 268, no 1, p. 61-73Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Fatigue is one of the most commonly reported subjective symptoms following traumatic brain injury (TBI). The aims were to assess frequency of fatigue over the first 6 months after TBI, and examine whether fatigue changes could be predicted by demographic characteristics, injury severity and comorbidities.

    METHODS: Patients with acute TBI admitted to 65 trauma centers were enrolled in the study Collaborative European NeuroTrauma Effectiveness Research in TBI (CENTER-TBI). Subjective fatigue was measured by single item on the Rivermead Post-Concussion Symptoms Questionnaire (RPQ), administered at baseline, three and 6 months postinjury. Patients were categorized by clinical care pathway: admitted to an emergency room (ER), a ward (ADM) or an intensive care unit (ICU). Injury severity, preinjury somatic- and psychiatric conditions, depressive and sleep problems were registered at baseline. For prediction of fatigue changes, descriptive statistics and mixed effect logistic regression analysis are reported.

    RESULTS: Fatigue was experienced by 47% of patients at baseline, 48% at 3 months and 46% at 6 months. Patients admitted to ICU had a higher probability of experiencing fatigue than those in ER and ADM strata. Females and individuals with lower age, higher education, more severe intracranial injury, preinjury somatic and psychiatric conditions, sleep disturbance and feeling depressed postinjury had a higher probability of fatigue.

    CONCLUSION: A high and stable frequency of fatigue was found during the first 6 months after TBI. Specific socio-demographic factors, comorbidities and injury severity characteristics were predictors of fatigue in this study.

    Download full text (pdf)
    fulltext
  • 2. 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. (Contributor)
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Neurosciences.
    Sundström, Nina (Contributor)
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Early Predictors of Employment Status One Year Post Injury in Individuals with Traumatic Brain Injury in Europe2020In: Journal of Clinical Medicine, E-ISSN 2077-0383, Vol. 9, no 6, article id 2007Article in journal (Refereed)
    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.

    Download full text (pdf)
    fulltext
  • 3. Bockhop, Fabian
    et al.
    Zeldovich, Marina
    Cunitz, Katrin
    Van Praag, Dominique
    van der Vlegel, Marjolein
    Beissbarth, Tim
    Hagmayer, York
    von Steinbuechel, Nicole
    Kondziella, Daniel (Contributor)
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Neurosciences.
    Koskinen, Lars-Owe D. (Contributor)
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Neurosciences.
    Sundström, Nina (Contributor)
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Measurement invariance of six language versions of the post-traumatic stress disorder checklist for DSM-5 in civilians after traumatic brain injury2022In: Scientific Reports, E-ISSN 2045-2322, Vol. 12, no 1, article id 16571Article in journal (Refereed)
    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.

    Download full text (pdf)
    fulltext
  • 4.
    Boström, Petrus
    et al.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Svensson, Johan
    Umeå University, Faculty of Social Sciences, Umeå School of Business and Economics (USBE), Statistics. Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Brorsson, Camilla
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Rutegård, Martin
    Umeå University, Faculty of Medicine, Wallenberg Centre for Molecular Medicine at Umeå University (WCMM). Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Early postoperative pain as a marker of anastomotic leakage in colorectal cancer surgery2021In: International Journal of Colorectal Disease, ISSN 0179-1958, E-ISSN 1432-1262, Vol. 36, no 9, p. 1955-1963Article in journal (Refereed)
    Abstract [en]

    Purpose: Even though anastomotic leakage after colorectal surgery is a major clinical problem in need of a timely diagnosis, early indicators of leakage have been insufficiently studied. We therefore conducted a population-based observational study to determine whether the patient’s early postoperative pain is an independent marker of anastomotic leakage.

    Methods: By combining the Swedish Colorectal Cancer Registry and the Swedish Perioperative Registry, we retrieved prospectively collected data on 3084 patients who underwent anastomotic colorectal surgery for cancer in 2014–2017. Postoperative pain, measured with the numerical rating scale (NRS), was considered exposure, while anastomotic leakage and reoperation due to leakage were outcomes. We performed logistic regression to evaluate associations, estimating odds ratios (ORs) and 95% confidence intervals (CIs), while multiple imputation was used to handle missing data.

    Results: In total, 189 patients suffered from anastomotic leakage, of whom 121 patients also needed a reoperation due to leakage. Moderate or severe postoperative pain (NRS 4–10) was associated with an increased risk of anastomotic leakage (OR 1.69, 95% CI 1.21–2.38), as well as reoperation (OR 2.17, 95% CI 1.41–3.32). Severe pain (NRS 8–10) was more strongly related to leakage (OR 2.38, 95% CI 1.44–3.93). These associations were confirmed in multivariable analyses and when reoperation due to leakage was used as an outcome.

    Conclusion: In this population-based retrospective study on prospectively collected data, increased pain in the post-anaesthesia care unit is an independent marker of anastomotic leakage, possibly indicating a need for further diagnostic measures.

    Download full text (pdf)
    fulltext
  • 5.
    Boström, Petrus
    et al.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Svensson, Johan
    Umeå University, Faculty of Social Sciences, Umeå School of Business and Economics (USBE), Statistics.
    Brorsson, Camilla
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Rutegård, Martin
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery. Umeå University, Faculty of Medicine, Wallenberg Centre for Molecular Medicine at Umeå University (WCMM).
    Early postoperative pain as a predictor of anastomotic leakage in colorectal cancer surgeryManuscript (preprint) (Other academic)
  • 6.
    Brorsson, Camilla
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Trauma - logistics and stress response2014Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Background: Trauma is a major cause of death and disability. Adverse events, such as prolonged prehospital time, hypoxia, hypotension and/or hyperventilation have been reported to correlate to poor outcome.

    Adequate cortisol levels are essential for survival after major trauma. In hypotensive critically ill patients, lack of sufficient amount of cortisol can be suspected, and a concept of critical illness related corticosteroid insufficiency has been proposed. Corticosteroid therapy has many adverse effects in critically ill patients and should only be given if life-saving. Correct measurement of serum cortisol levels is important but difficult in critically ill patients with capillary leakage. Estimation of the free and biologically active cortisol is preferable. In serum less than 10% of cortisol is free and biologically active and not possible to measure with routine laboratory methods. Salivary cortisol can be used as a surrogate for free cortisol, but salivary production is reduced in critically ill patients. Liver resection could reduce cortisol levels due to substrate deficiency.

    Aims: 1. Evaluate the occurrence of early adverse events in patients with traumatic brain injury and relate them to outcome. 2. Assess cortisol levels over time after trauma and correlate to severity of trauma, sedative/analgesic drugs and cardiovascular function. 3. Evaluate if saliva stimulation could be performed without interfering with salivary cortisol levels. 4. Assess cortisol levels over time after liver resection in comparison to other major surgery.

    Results: There was no significant correlation between prehospital time ³60 minutes, hypoxia (saturation <95%), hypotension (systolic blood pressure <90 mmHg), or hyperventilation (ETCO2 <4.5 kPa) and a poor outcome (Glasgow Outcome Scale 1-3) in patients with traumatic brain injury. Cortisol levels decreased significantly over time after trauma, but there was no correlation between low (<200 nmol/L) serum cortisol levels and severity of trauma.

    Infusion of sedative/analgesic drugs was the strongest predictor for a low (<200 nmol/L) serum cortisol. The odds ratio for low serum cortisol levels (<200 nmol/L) was 8.0 for patients receiving continuous infusion of sedative/analgesic drugs. There was no significant difference between unstimulated and stimulated salivary cortisol levels (p=0.06) in healthy volunteers. Liver resection was not associated with significantly lower cortisol levels compared to other major surgery.

    Conclusion: There was no significant correlation between early adverse events and outcome in patients with traumatic brain injury. Cortisol levels decreased significantly over time in trauma patients. Low cortisol levels (<200 nmol/L) were significantly correlated to continuous infusion of sedative/analgesic drugs. Saliva stimulation could be performed without interfering with salivary cortisol levels. Liver resection was not associated with low cortisol levels compared to other major surgery.

    Download full text (pdf)
    fulltext
  • 7.
    Brorsson, Camilla
    et al.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Dahlqvist, Per
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Lundberg, Owe
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Naredi, Peter
    Sahlgrenska University Hospital, Gothenburg, Sweden.
    Naredi, Silvana
    Sahlgrenska University Hospital, Gothenburg, Sweden.
    Liver resection is not associated with decreased cortisol levels.Manuscript (preprint) (Other academic)
    Abstract [en]

    Background: Adrenal hormones are synthesized from cholesterol, produced and stored in the liver. Liver failure has been reported to be associated with adrenal insufficiency. A possible mechanism could be a limited supply of substrate for cortisol synthesis. The aims of this study was to evaluate the occurrence of total serum cortisol <200 nmol/L after major liver resection (≥ 30%) and other major surgery (hemicolectomy) and to assess associations between cholesterol and corti­sol levels after liver resection.

    Methods: Prospective, observational study. 40 patients were included (major liver resection n=15, hemicolectomy n=25). Serum and salivary cortisol were followed from morning before surgery up to five days postoperatively. Sulphated dehy­droepiandrosterone (DHEAS) and lipids (cholesterol, low density lipoproteins, high density lipoproteins and triglycerides) were obtained in liver resection patients.

    Results: 8/25 (32%, hemicolectomy patients), and 3/15 (20%, liver resection patients) had serum cortisol <200 nmol/L. Neither hemicolectomy nor liver resec­tion was significantly associated with serum cortisol <200 nmol/L, p=0.49. Serum cortisol <200 nmol/L was not significantly associated with lipids below normal limits, (cholesterol; p=1.0 day 1, p=0.46 day 4, LDL; p=0.56 day 1, p=1.0 day 4, and HDL; p=0.27 day 1, p=1.0 day 4). Serum and salivary cortisol correlated sig­nificantly (rs=0.83, p<0.0001, hemicolectomy, rs=0.80, p<0.0001, liver resection).

    Conclusion: Serum cortisol levels <200 nmol/L was found in 32% (hemicolec­tomy) and 20% (liver resection) postoperatively. Compared to after hemicolec­tomy, serum cortisol <200 nmol/L was not significantly more common after liver resection. Lipids below normal limits were not associated with serum cortisol <200 nmol/L after liver resection.

  • 8.
    Brorsson, Camilla
    et al.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Dahlqvist, Per
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Nilsson, Leif
    Umeå University, Faculty of Science and Technology, Department of Mathematics and Mathematical Statistics.
    Naredi, Silvana
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Saliva stimulation with glycerine and citric acid does not affect salivary cortisol levels2014In: Clinical Endocrinology, ISSN 0300-0664, E-ISSN 1365-2265, Vol. 81, no 2, p. 244-248Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE:

    In critically ill patients with hypotension, who respond poorly to fluids and vasoactive drugs, cortisol insufficiency may be suspected. In serum over 90% of cortisol is protein-bound, thus routine measures of total serum cortisol may yield 'false lows' due to hypoproteinaemia. Thus, the occurrence of cortisol insufficiency could be overestimated in critically ill patients. Salivary cortisol can be used as a surrogate for free serum cortisol, but in critically ill patients saliva production is decreased, and insufficient volume of saliva for analysis is a common problem. The aim of this study was to investigate if a cotton-tipped applicator with glycerine and citric acid could be used for saliva stimulation without affecting salivary cortisol levels.

    DESIGN:

    Prospective, observational study.

    PARTICIPANTS:

    Thirty-six volunteers (six males, 30 females), age 49 ± 9 years, without known oral mucus membrane rupture in the mouth.

    MEASUREMENTS:

    Forty-two pairs of saliva samples (22 paired morning samples, 20 paired evening samples) were obtained before and after saliva stimulation with glycerine and citric acid. Salivary cortisol was analysed using Spectria Cortisol RIA (Orion Diagnostica, Finland).

    RESULTS:

    The paired samples correlated significantly (P < 0·0001) and there was no significant difference between un-stimulated and stimulated salivary cortisol levels.

    CONCLUSIONS:

    Saliva stimulation with a cotton-tipped applicator containing glycerine and citric acid did not significantly influence salivary cortisol levels in healthy volunteers. This indicates that salivary cortisol measurement after saliva stimulation may be a useful complement when evaluating cortisol status in critically ill patients.

  • 9.
    Brorsson, Camilla
    et al.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Dahlqvist, Per
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Nilsson, Leif
    Umeå University, Faculty of Science and Technology, Department of Mathematics and Mathematical Statistics.
    Thunberg, Johan
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Sylvan, Anders
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Naredi, Silvana
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Adrenal response after trauma is affected by time after trauma and sedative/analgesic drugs2014In: Injury, ISSN 0020-1383, E-ISSN 1879-0267, Vol. 45, no 8, p. 1149-1155Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: The adrenal response in critically ill patients, including trauma victims, has been debated over the last decade. The aim of this study was to assess the early adrenal response after trauma. METHODS: Prospective, observational study of 50 trauma patients admitted to a level-1-trauma centre. Serum and saliva cortisol were followed from the accident site up to five days after trauma. Corticosteroid binding globulin (CBG), dehydroepiandrosterone (DHEA) and sulphated dehydroepiandrosterone (DHEAS) were obtained twice during the first five days after trauma. The effect of time and associations between cortisol levels and; severity of trauma, infusion of sedative/analgesic drugs, cardiovascular dysfunction and other adrenocorticotropic hormone (ACTH) dependent hormones (DHEA/DHEAS) were studied. RESULTS: There was a significant decrease over time in serum cortisol both during the initial 24 h, and from the 2nd to the 5th morning after trauma. A significant decrease over time was also observed in calculated free cortisol, DHEA, and DHEAS. No significant association was found between an injury severity score >/= 16 (severe injury) and a low (< 200 nmol/L) serum cortisol at any time during the study period. The odds for a serum cortisol < 200 nmol/L was eight times higher in patients with continuous infusion of sedative/analgesic drugs compared to patients with no continuous infusion of sedative/analgesic drugs. CONCLUSION: Total serum cortisol, calculated free cortisol, DHEA and DHEAS decreased significantly over time after trauma. Continuous infusion of sedative/analgesic drugs was independently associated with serum cortisol < 200 nmol/L.

  • 10.
    Brorsson, Camilla
    et al.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Rodling-Wahlström, Marie
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Olivecrona, Magnus
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Koskinen, Lars-Owe
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Naredi, Silvana
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Severe traumatic brain injury: consequences of early adverse events2011In: Acta Anaesthesiologica Scandinavica, ISSN 0001-5172, E-ISSN 1399-6576, Vol. 55, no 8, p. 944-951Article in journal (Refereed)
    Abstract [en]

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

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

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

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

    Download full text (pdf)
    fulltext
  • 11. 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. (Contributor)
    Umeå University, Faculty of Medicine, Department of Clinical Sciences.
    Sundström, Nina (Contributor)
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Extended Coagulation Profiling in Isolated Traumatic Brain Injury: A CENTER-TBI Analysis2022In: Neurocritical Care, ISSN 1541-6933, E-ISSN 1556-0961, Vol. 36, no 3, p. 927-941Article in journal (Refereed)
    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.

    Download full text (pdf)
    fulltext
  • 12. 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. (Contributor)
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Neurosciences.
    Sundström, Nina (Contributor)
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Management of arterial partial pressure of carbon dioxide in the first week after traumatic brain injury: results from the CENTER-TBI study2021In: Intensive Care Medicine, ISSN 0342-4642, E-ISSN 1432-1238, Vol. 47, no 9, p. 961-973Article in journal (Refereed)
    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.

    Download full text (pdf)
    fulltext
  • 13. Cnossen, Maryse C.
    et al.
    Lingsma, Hester F.
    Tenovuo, Olli
    Maas, Andrew I. R.
    Menon, David
    Steyerberg, Ewout W.
    Ribbers, Gerard M.
    Polinder, Suzanne
    Brorsson, Camilla (Contributor)
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Rehabilitation after traumatic brain injury: A survey in 70 European neurotrauma centres participating in the CENTER-TBI study2017In: Journal of Rehabilitation Medicine, ISSN 1650-1977, E-ISSN 1651-2081, Vol. 49, no 5, p. 395-401Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: To describe variation in structural and process characteristics of acute in-hospital rehabilitation and referral to post-acute care for patients with traumatic brain injury across Europe.

    DESIGN: Survey study, of neurotrauma centres.

    METHODS: A 14-item survey about in-hospital rehabilitation and referral to post-acute care was sent to 71 neurotrauma centres participating in a European multicentre study (CENTER-TBI). The questionnaire was developed based on literature and expert opinion and was pilot-tested before sending out to the centres.

    RESULTS: Seventy (99%) centres in 20 countries completed the survey. The included centres were predominately academic level I trauma centres. Among the 70 centres, a multidisciplinary rehabilitation team can be consulted at 41% (n = 29) of the intensive care units and 49% (n = 34) of the wards. Only 13 (19%) centres used rehabilitation guidelines in patients with traumatic brain injury. Age was reported as a major determinant of referral decisions in 32 (46%) centres, with younger patients usually referred to specialized rehabilitation centres, and patients ≥ 65 years also referred to nursing homes or local hospitals.

    CONCLUSION: Substantial variation exists in structural and process characteristics of in-hospital acute rehabilitation and referral to post-acute rehabilitation facilities among neurotrauma centres across Europe.

    Download full text (pdf)
    fulltext
  • 14. 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 (Contributor)
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Neurosciences.
    Sundström, Nina (Contributor)
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Blood biomarkers on admission in acute traumatic brain injury: Relations to severity, CT findings and care path in the CENTER-TBI study2020In: EBioMedicine, E-ISSN 2352-3964, Vol. 56, article id 10275Article in journal (Refereed)
    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.

    Download full text (pdf)
    fulltext
  • 15. 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. (Contributor)
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Neurosciences.
    Sundström, Nina (Contributor)
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Outcome Prediction after Moderate and Severe Traumatic Brain Injury: External Validation of Two Established Prognostic Models in 1742 European Patients2021In: Journal of Neurotrauma, ISSN 0897-7151, E-ISSN 1557-9042, Vol. 38, no 10, p. 1377-1388Article in journal (Refereed)
    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.

  • 16. 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. (Contributor)
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Sundström, Nina (Contributor)
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Comparison of Care System and Treatment Approaches for Patients with Traumatic Brain Injury in China versus Europe: A CENTER-TBI Survey Study2020In: Journal of Neurotrauma, ISSN 0897-7151, E-ISSN 1557-9042, Vol. 37, no 16, p. 1806-1817Article in journal (Refereed)
    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.

  • 17.
    Fontan, Aurelie
    et al.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB). Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI).
    Lindgren, Lenita
    Umeå University, Faculty of Medicine, Department of Nursing.
    Pedale, Tiziana
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB). Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI).
    Brorsson, Camilla
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Bergström, F.
    Faculty of Psychology and Educational Sciences, University of Coimbra, Portugal.
    Eriksson, Johan
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB). Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI).
    A reduced level of consciousness affects non-conscious processes2021In: NeuroImage, ISSN 1053-8119, E-ISSN 1095-9572, Vol. 244, article id 118571Article in journal (Refereed)
    Abstract [en]

    Being conscious is a profound aspect of human existence, and understanding its function and its inception is considered one of the truly grand scientific challenges. However, the nature of consciousness remains enigmatic, to a large part because “being conscious” can refer to both the content (phenomenology) and the level (arousal) of consciousness, and how these different aspects are related remains unclear. To empirically assess the relation between level and content of consciousness, we manipulated these two aspects by presenting stimuli consciously or non-consciously and by using Propofol sedation, while brain activity was measured using fMRI. We observed that sedation affected both conscious and non-conscious processes but at different hierarchical levels; while conscious processing was altered in higher-order regions (the intraparietal sulcus) and spared sensory areas, the opposite effect was observed for non-conscious processing. The observation that Propofol affected non-conscious processing calls for a reconsideration of what kind of information one can gain on “consciousness” from recording neural responses to sedation without considering both (content) conscious and (content) non-conscious processing.

    Download full text (pdf)
    fulltext
  • 18. Fronczek, Jakub
    et al.
    Polok, Kamil
    de Lange, Dylan W.
    Jung, Christian
    Beil, Michael
    Rhodes, Andrew
    Fjølner, Jesper
    Górka, Jacek
    Andersen, Finn H.
    Artigas, Antonio
    Cecconi, Maurizio
    Christensen, Steffen
    Joannidis, Michael
    Leaver, Susannah
    Marsh, Brian
    Morandi, Alessandro
    Moreno, Rui
    Oeyen, Sandra
    Agvald-Öhman, Christina
    Bollen Pinto, Bernardo
    Schefold, Joerg C.
    Valentin, Andreas
    Walther, Sten
    Watson, Ximena
    Zafeiridis, Tilemachos
    Sviri, Sigal
    van Heerden, Peter Vernon
    Flaatten, Hans
    Guidet, Bertrand
    Szczeklik, Wojciech
    Relationship between the Clinical Frailty Scale and short-term mortality in patients ≥ 80 years old acutely admitted to the ICU: a prospective cohort study2021In: Critical Care, ISSN 1364-8535, E-ISSN 1466-609X, Vol. 25, no 1, article id 231Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: The Clinical Frailty Scale (CFS) is frequently used to measure frailty in critically ill adults. There is wide variation in the approach to analysing the relationship between the CFS score and mortality after admission to the ICU. This study aimed to evaluate the influence of modelling approach on the association between the CFS score and short-term mortality and quantify the prognostic value of frailty in this context.

    METHODS: We analysed data from two multicentre prospective cohort studies which enrolled intensive care unit patients ≥ 80 years old in 26 countries. The primary outcome was mortality within 30-days from admission to the ICU. Logistic regression models for both ICU and 30-day mortality included the CFS score as either a categorical, continuous or dichotomous variable and were adjusted for patient's age, sex, reason for admission to the ICU, and admission Sequential Organ Failure Assessment score.

    RESULTS: The median age in the sample of 7487 consecutive patients was 84 years (IQR 81-87). The highest fraction of new prognostic information from frailty in the context of 30-day mortality was observed when the CFS score was treated as either a categorical variable using all original levels of frailty or a nonlinear continuous variable and was equal to 9% using these modelling approaches (p < 0.001). The relationship between the CFS score and mortality was nonlinear (p < 0.01).

    CONCLUSION: Knowledge about a patient's frailty status adds a substantial amount of new prognostic information at the moment of admission to the ICU. Arbitrary simplification of the CFS score into fewer groups than originally intended leads to a loss of information and should be avoided. Trial registration NCT03134807 (VIP1), NCT03370692 (VIP2).

    Download full text (pdf)
    fulltext
  • 19. 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. (Contributor)
    Umeå University, Faculty of Medicine, Department of Clinical Sciences.
    Sundström, Nina (Contributor)
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Effect of frailty on 6-month outcome after traumatic brain injury: a multicentre cohort study with external validation2022In: Lancet Neurology, ISSN 1474-4422, E-ISSN 1474-4465, Vol. 21, no 2, p. 153-162Article in journal (Refereed)
    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.

  • 20.
    Granvik, Christoffer
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology.
    Andersson, Sara
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Andersson, Linus
    Umeå University, Faculty of Social Sciences, Department of Psychology.
    Brorsson, Camilla
    Umeå University, Faculty of Medicine, Department of Diagnostics and Intervention.
    Forsell, Mattias N. E.
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology.
    Ahlm, Clas
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology.
    Normark, Johan
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology.
    Edin, Alicia
    Umeå University, Faculty of Medicine, Department of Diagnostics and Intervention.
    Olfactory dysfunction as an early predictor for post-COVID condition at 1-year follow-up2024In: Brain and Behavior, E-ISSN 2162-3279, Vol. 14, no 6, article id e3574Article in journal (Refereed)
    Abstract [en]

    Background: Olfactory dysfunction together with neurological and cognitive symptoms are common after COVID-19. We aimed to study whether performance on olfactory and neuropsychological tests following infection predict post-COVID condition (PCC), persisting symptoms, and reduced health-related quality of life.

    Methods: Both hospitalized (N = 10) and non-hospitalized individuals (N = 56) were enrolled in this prospective cohort study. Participants were evaluated 1–3 months after infection with an olfactory threshold test and neuropsychological tests, which was used as predictors of PCC. A questionnaire outlining persisting symptoms and the validated instrument EuroQol five-dimension five-level for health-related quality of life assessment were used as outcome data 1 year after infection (N = 59). Principal component analysis was used to identify relevant predictors for PCC at 1 year.

    Results: Objectively assessed olfactory dysfunction at 1–3 months post infection, but not subjective olfactory symptoms, predicted post-COVID condition with reduced health-related quality of life (PCC+) at 1 year. The PCC+ group scored more often below the cut off for mild cognitive impairment on the Montreal Cognitive Assessment (61.5% vs. 21.7%) and higher on the Multidimensional Fatigue Inventory-20, compared to the group without PCC+.

    Conclusion: Our results indicate that objectively assessed, olfactory dysfunction is a predictor for PCC+. These findings underscore the importance of objective olfactory testing. We propose that olfactory screening in the early post-acute phase of COVID-19 infection might identify individuals that are at higher risk of developing long-term health sequalae.

    Download full text (pdf)
    fulltext
  • 21. Gravesteijn, B. Y.
    et al.
    Sewalt, C. A.
    Ercole, A.
    Lecky, F.
    Menon, D.
    Steyerberg, E. W.
    Maas, A. I. R.
    Lingsma, H. F.
    Klimek, M.
    Brorsson, Camilla (Contributor)
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Variation in the practice of tracheal intubation in Europe after traumatic brain injury: a prospective cohort study2020In: Anaesthesia, ISSN 0003-2409, E-ISSN 1365-2044, Vol. 75, no 1, p. 45-53Article in journal (Refereed)
    Abstract [en]

    Traumatic brain injury patients frequently undergo tracheal intubation. We aimed to assess current intubation practice in Europe and identify variation in practice. We analysed data from patients with traumatic brain injury included in the prospective cohort study collaborative European neurotrauma effectiveness research in traumatic brain injury (CENTER-TBI) in 45 centres in 16 European countries. We included patients who were transported to hospital by emergency medical services. We used mixed-effects multinomial regression to quantify the effects on pre-hospital or in-hospital tracheal intubation of the following: patient characteristics; injury characteristics; centre; and trauma system characteristics. A total of 3843 patients were included. Of these, 1322 (34%) had their tracheas intubated; 839 (22%) pre-hospital and 483 (13%) in-hospital. The fit of the model with only patient characteristics predicting intubation was good (Nagelkerke R2 64%). The probability of tracheal intubation increased with the following: younger age; lower pre-hospital or emergency department GCS; higher abbreviated injury scale scores (head and neck, thorax and chest, face or abdomen abbreviated injury score); and one or more unreactive pupils. The adjusted median odds ratio for intubation between two randomly chosen centres was 3.1 (95%CI 2.1-4.3) for pre-hospital intubation, and 2.7 (95%CI 1.9-3.5) for in-hospital intubation. Furthermore, the presence of an anaesthetist was independently associated with more pre-hospital intubation (OR 2.9, 95%CI 1.3-6.6), in contrast to the presence of ambulance personnel who are allowed to intubate (OR 0.5, 95%CI 0.3-0.8). In conclusion, patient and injury characteristics are key drivers of tracheal intubation. Between-centre differences were also substantial. Further studies are needed to improve the evidence base supporting recommendations for tracheal intubation.

    Download full text (pdf)
    fulltext
  • 22. Gravesteijn, Benjamin Y
    et al.
    Nieboer, Daan
    Ercole, Ari
    Lingsma, Hester F
    Nelson, David
    van Calster, Ben
    Steyerberg, Ewout W
    Machine learning algorithms performed no better than regression models for prognostication in traumatic brain injury2020In: Journal of Clinical Epidemiology, ISSN 0895-4356, E-ISSN 1878-5921, Vol. 122, p. 95-107Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: We aimed to explore the added value of common machine learning (ML) algorithms for prediction of outcome for moderate and severe traumatic brain injury.

    STUDY DESIGN AND SETTING: We performed logistic regression (LR), lasso regression, and ridge regression with key baseline predictors in the IMPACT-II database (15 studies, n = 11,022). ML algorithms included support vector machines, random forests, gradient boosting machines, and artificial neural networks and were trained using the same predictors. To assess generalizability of predictions, we performed internal, internal-external, and external validation on the recent CENTER-TBI study (patients with Glasgow Coma Scale <13, n = 1,554). Both calibration (calibration slope/intercept) and discrimination (area under the curve) was quantified.

    RESULTS: In the IMPACT-II database, 3,332/11,022 (30%) died and 5,233(48%) had unfavorable outcome (Glasgow Outcome Scale less than 4). In the CENTER-TBI study, 348/1,554(29%) died and 651(54%) had unfavorable outcome. Discrimination and calibration varied widely between the studies and less so between the studied algorithms. The mean area under the curve was 0.82 for mortality and 0.77 for unfavorable outcomes in the CENTER-TBI study.

    CONCLUSION: ML algorithms may not outperform traditional regression approaches in a low-dimensional setting for outcome prediction after moderate or severe traumatic brain injury. Similar to regression-based prediction models, ML algorithms should be rigorously validated to ensure applicability to new populations.

  • 23. Gravesteijn, Benjamin Y
    et al.
    Sewalt, Charlie A
    Ercole, Ari
    Akerlund, Cecilia
    Nelson, David
    Maas, Andrew I R
    Menon, David
    Lingsma, Hester F
    Steyerberg, Ewout W
    Toward a New Multi-Dimensional Classification of Traumatic Brain Injury: A Collaborative European NeuroTrauma Effectiveness Research for Traumatic Brain Injury Study.2020In: Journal of Neurotrauma, ISSN 0897-7151, E-ISSN 1557-9042, Vol. 37, no 7, p. 1002-1010Article in journal (Refereed)
    Abstract [en]

    Traumatic brain injury (TBI) is currently classified as mild, moderate, or severe TBI by trichotomizing the Glasgow Coma Scale (GCS). We aimed to explore directions for a more refined multidimensional classification system. For that purpose, we performed a hypothesis-free cluster analysis in the Collaborative European NeuroTrauma Effectiveness Research for TBI (CENTER-TBI) database: a European all-severity TBI cohort (n = 4509). The first building block consisted of key imaging characteristics, summarized using principal component analysis from 12 imaging characteristics. The other building blocks were demographics, clinical severity, secondary insults, and cause of injury. With these building blocks, the patients were clustered into four groups. We applied bootstrap resampling with replacement to study the stability of cluster allocation. The characteristics that predominantly defined the clusters were injury cause, major extracranial injury, and GCS. The clusters consisted of 1451, 1534, 1006, and 518 patients, respectively. The clustering method was quite stable: the proportion of patients staying in one cluster after resampling and reclustering was 97.4% (95% confidence interval [CI]: 85.6-99.9%). These clusters characterized groups of patients with different functional outcomes: from mild to severe, 12%, 19%, 36%, and 58% of patients had unfavorable 6 month outcome. Compared with the mild and the upper intermediate cluster, the lower intermediate and the severe cluster received more key interventions. To conclude, four types of TBI patients may be defined by injury mechanism, presence of major extracranial injury and GCS. Describing patients according to these three characteristics could potentially capture differences in etiology and care pathways better than with GCS only.

  • 24. Gravesteijn, Benjamin Yaël
    et al.
    Sewalt, Charlie Aletta
    Venema, Esmee
    Nieboer, Daan
    Steyerberg, Ewout W.
    Brorsson, Camilla
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Koskinen, Lars-Owe D. (Contributor)
    Umeå University, Faculty of Medicine, Department of Clinical Sciences.
    Sundström, Nina (Contributor)
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Missing Data in Prediction Research: A Five-Step Approach for Multiple Imputation, Illustrated in the CENTER-TBI Study2021In: Journal of Neurotrauma, ISSN 0897-7151, E-ISSN 1557-9042, Vol. 38, no 13, p. 1842-1857Article in journal (Refereed)
    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.

  • 25. Guidet, Bertrand
    et al.
    de Lange, Dylan W
    Boumendil, Ariane
    Leaver, Susannah
    Watson, Ximena
    Boulanger, Carol
    Szczeklik, Wojciech
    Artigas, Antonio
    Morandi, Alessandro
    Andersen, Finn
    Zafeiridis, Tilemachos
    Jung, Christian
    Moreno, Rui
    Walther, Sten
    Oeyen, Sandra
    Schefold, Joerg C
    Cecconi, Maurizio
    Marsh, Brian
    Joannidis, Michael
    Nalapko, Yuriy
    Elhadi, Muhammed
    Fjølner, Jesper
    Flaatten, Hans
    The contribution of frailty, cognition, activity of daily life and comorbidities on outcome in acutely admitted patients over 80 years in European ICUs: the VIP2 study2020In: Intensive Care Medicine, ISSN 0342-4642, E-ISSN 1432-1238, Vol. 46, no 1, p. 57-69Article in journal (Refereed)
    Abstract [en]

    PURPOSE: Premorbid conditions affect prognosis of acutely-ill aged patients. Several lines of evidence suggest geriatric syndromes need to be assessed but little is known on their relative effect on the 30-day survival after ICU admission. The primary aim of this study was to describe the prevalence of frailty, cognition decline and activity of daily life in addition to the presence of comorbidity and polypharmacy and to assess their influence on 30-day survival.

    METHODS: Prospective cohort study with 242 ICUs from 22 countries. Patients 80 years or above acutely admitted over a six months period to an ICU between May 2018 and May 2019 were included. In addition to common patients' characteristics and disease severity, we collected information on specific geriatric syndromes as potential predictive factors for 30-day survival, frailty (Clinical Frailty scale) with a CFS > 4 defining frail patients, cognitive impairment (informant questionnaire on cognitive decline in the elderly (IQCODE) with IQCODE ≥ 3.5 defining cognitive decline, and disability (measured the activity of daily life with the Katz index) with ADL ≤ 4 defining disability. A Principal Component Analysis to identify co-linearity between geriatric syndromes was performed and from this a multivariable model was built with all geriatric information or only one: CFS, IQCODE or ADL. Akaike's information criterion across imputations was used to evaluate the goodness of fit of our models.

    RESULTS: We included 3920 patients with a median age of 84 years (IQR: 81-87), 53.3% males). 80% received at least one organ support. The median ICU length of stay was 3.88 days (IQR: 1.83-8). The ICU and 30-day survival were 72.5% and 61.2% respectively. The geriatric conditions were median (IQR): CFS: 4 (3-6); IQCODE: 3.19 (3-3.69); ADL: 6 (4-6); Comorbidity and Polypharmacy score (CPS): 10 (7-14). CFS, ADL and IQCODE were closely correlated. The multivariable analysis identified predictors of 1-month mortality (HR; 95% CI): Age (per 1 year increase): 1.02 (1.-1.03, p = 0.01), ICU admission diagnosis, sequential organ failure assessment score (SOFA) (per point): 1.15 (1.14-1.17, p < 0.0001) and CFS (per point): 1.1 (1.05-1.15, p < 0.001). CFS remained an independent factor after inclusion of life-sustaining treatment limitation in the model.

    CONCLUSION: We confirm that frailty assessment using the CFS is able to predict short-term mortality in elderly patients admitted to ICU. Other geriatric syndromes do not add improvement to the prediction model. Since CFS is easy to measure, it should be routinely collected for all elderly ICU patients in particular in connection to advance care plans, and should be used in decision making.

  • 26. Guidet, Bertrand
    et al.
    Flaatten, Hans
    Boumendil, Ariane
    Morandi, Alessandro
    Andersen, Finn H.
    Artigas, Antonio
    Bertolini, Guido
    Cecconi, Maurizio
    Christensen, Steffen
    Faraldi, Loredana
    Fjølner, Jesper
    Jung, Christian
    Marsh, Brian
    Moreno, Rui
    Oeyen, Sandra
    Öhman, Christina Agwald
    Pinto, Bernardo Bollen
    Soliman, Ivo W.
    Szczeklik, Wojciech
    Valentin, Andreas
    Watson, Ximena
    Zafeiridis, Tilemachos
    De Lange, Dylan W.
    Withholding or withdrawing of life-sustaining therapy in older adults (≥ 80 years) admitted to the intensive care unit2018In: Intensive Care Medicine, ISSN 0342-4642, E-ISSN 1432-1238, Vol. 44, no 7, p. 1027-1038Article in journal (Refereed)
    Abstract [en]

    PURPOSE: To document and analyse the decision to withhold or withdraw life-sustaining treatment (LST) in a population of very old patients admitted to the ICU.

    METHODS: This prospective study included intensive care patients aged ≥ 80 years in 309 ICUs from 21 European countries with 30-day mortality follow-up.

    RESULTS: LST limitation was identified in 1356/5021 (27.2%) of patients: 15% had a withholding decision and 12.2% a withdrawal decision (including those with a previous withholding decision). Patients with LST limitation were older, more frail, more severely ill and less frequently electively admitted. Patients with withdrawal of LST were more frequently male and had a longer ICU length of stay. The ICU and 30-day mortality were, respectively, 29.1 and 53.1% in the withholding group and 82.2% and 93.1% in the withdrawal group. LST was less frequently limited in eastern and southern European countries than in northern Europe. The patient-independent factors associated with LST limitation were: acute ICU admission (OR 5.77, 95% CI 4.32-7.7), Clinical Frailty Scale (CFS) score (OR 2.08, 95% CI 1.78-2.42), increased age (each 5 years of increase in age had a OR of 1.22 (95% CI 1.12-1.34) and SOFA score [OR of 1.07 (95% CI 1.05-1.09 per point)]. The frequency of LST limitation was higher in countries with high GDP and was lower in religious countries.

    CONCLUSIONS: The most important patient variables associated with the instigation of LST limitation were acute admission, frailty, age, admission SOFA score and country.

    TRIAL REGISTRATION: ClinicalTrials.gov (ID: NTC03134807).

  • 27. Haas, Lenneke E M
    et al.
    Boumendil, Ariane
    Flaatten, Hans
    Guidet, Bertrand
    Ibarz, Mercedes
    Jung, Christian
    Moreno, Rui
    Morandi, Alessandro
    Andersen, Finn H
    Zafeiridis, Tilemachos
    Walther, Sten
    Oeyen, Sandra
    Leaver, Susannah
    Watson, Ximena
    Boulanger, Carole
    Szczeklik, Wojciech
    Schefold, Joerg C
    Cecconi, Maurizio
    Marsh, Brian
    Joannidis, Michael
    Nalapko, Yuriy
    Elhadi, Muhammed
    Fjølner, Jesper
    Artigas, Antonio
    de Lange, Dylan W
    Frailty is associated with long-term outcome in patients with sepsis who are over 80 years old: results from an observational study in 241 European ICUs2021In: Age and Ageing, ISSN 0002-0729, E-ISSN 1468-2834, Vol. 50, no 5, p. 1719-1727Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Sepsis is one of the most frequent reasons for acute intensive care unit (ICU) admission of very old patients and mortality rates are high. However, the impact of pre-existing physical and cognitive function on long-term outcome of ICU patients ≥ 80 years old (very old intensive care patients (VIPs)) with sepsis is unclear.

    OBJECTIVE: To investigate both the short- and long-term mortality of VIPs admitted with sepsis and assess the relation of mortality with pre-existing physical and cognitive function.

    DESIGN: Prospective cohort study.

    SETTING: 241 ICUs from 22 European countries in a six-month period between May 2018 and May 2019.

    SUBJECTS: Acutely admitted ICU patients aged ≥80 years with sequential organ failure assessment (SOFA) score ≥ 2.

    METHODS: Sepsis was defined according to the sepsis 3.0 criteria. Patients with sepsis as an admission diagnosis were compared with other acutely admitted patients. In addition to patients' characteristics, disease severity, information about comorbidity and polypharmacy and pre-existing physical and cognitive function were collected.

    RESULTS: Out of 3,596 acutely admitted VIPs with SOFA score ≥ 2, a group of 532 patients with sepsis were compared to other admissions. Predictors for 6-month mortality were age (per 5 years): Hazard ratio (HR, 1.16 (95% confidence interval (CI), 1.09-1.25, P < 0.0001), SOFA (per one-point): HR, 1.16 (95% CI, 1.14-1.17, P < 0.0001) and frailty (CFS > 4): HR, 1.34 (95% CI, 1.18-1.51, P < 0.0001).

    CONCLUSIONS: There is substantial long-term mortality in VIPs admitted with sepsis. Frailty, age and disease severity were identified as predictors of long-term mortality in VIPs admitted with sepsis.

  • 28. 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. (Contributor)
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Neurosciences.
    Sundström, Nina (Contributor)
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Rehabilitation and outcomes after complicated vs uncomplicated mild TBI: results from the CENTER-TBI study2022In: BMC Health Services Research, E-ISSN 1472-6963, Vol. 22, no 1, article id 1536Article in journal (Refereed)
    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.

    Download full text (pdf)
    fulltext
  • 29. Huie, J Russell
    et al.
    Mondello, Stefania
    Lindsell, Christopher J
    Antiga, Luca
    Yuh, Esther L
    Zanier, Elisa R
    Masson, Serge
    Rosario, Bedda L
    Ferguson, Adam R
    Biomarkers for Traumatic Brain Injury: Data Standards and Statistical Considerations2020In: Journal of Neurotrauma, ISSN 0897-7151, E-ISSN 1557-9042Article in journal (Refereed)
    Abstract [en]

    Recent biomarker innovations hold potential for transforming diagnosis, prognostic modeling, and precision therapeutic targeting of traumatic brain injury (TBI). However, many biomarkers, including brain imaging, genomics, and proteomics, involve vast quantities of high-throughput and high-content data. Management, curation, analysis, and evidence synthesis of these data are not trivial tasks. In this review, we discuss data management concepts and statistical and data sharing strategies when dealing with biomarker data in the context of TBI research. We propose that application of biomarkers involves three distinct steps-discovery, evaluation, and evidence synthesis. First, complex/big data has to be reduced to useful data elements at the stage of biomarker discovery. Second, inferential statistical approaches must be applied to these biomarker data elements for assessment of biomarker clinical utility and validity. Last, synthesis of relevant research is required to support practice guidelines and enable health decisions informed by the highest quality, up-to-date evidence available. We focus our discussion around recent experiences from the International Traumatic Brain Injury Research (InTBIR) initiative, with a specific focus on four major clinical projects (Transforming Research and Clinical Knowledge in TBI, Collaborative European NeuroTrauma Effectiveness Research in TBI, Collaborative Research on Acute Traumatic Brain Injury in Intensive Care Medicine in Europe, and Approaches and Decisions in Acute Pediatric TBI Trial), which are currently enrolling subjects in North America and Europe. We discuss common data elements, data collection efforts, data-sharing opportunities, and challenges, as well as examine the statistical techniques required to realize successful adoption and use of biomarkers in the clinic as a foundation for precision medicine in TBI.

  • 30. Huijben, Jilske A.
    et al.
    Volovici, Victor
    Cnossen, Maryse C.
    Haitsma, Iain K.
    Stocchetti, Nino
    Maas, Andrew I. R.
    Menon, David K.
    Ercole, Ari
    Citerio, Giuseppe
    Nelson, David
    Polinder, Suzanne
    Steyerberg, Ewout W.
    Lingsma, Hester F.
    van der Jagt, Mathieu
    Brorsson, Camilla (Contributor)
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Variation in general supportive and preventive intensive care management of traumatic brain injury: a survey in 66 neurotrauma centers participating in the Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) study2018In: Critical Care, ISSN 1364-8535, E-ISSN 1466-609X, Vol. 22, no 1, article id 90Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: General supportive and preventive measures in the intensive care management of traumatic brain injury (TBI) aim to prevent or limit secondary brain injury and optimize recovery. The aim of this survey was to assess and quantify variation in perceptions on intensive care unit (ICU) management of patients with TBI in European neurotrauma centers.

    METHODS: We performed a survey as part of the Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) study. We analyzed 23 questions focused on: 1) circulatory and respiratory management; 2) fever control; 3) use of corticosteroids; 4) nutrition and glucose management; and 5) seizure prophylaxis and treatment.

    RESULTS: The survey was completed predominantly by intensivists (n = 33, 50%) and neurosurgeons (n = 23, 35%) from 66 centers (97% response rate). The most common cerebral perfusion pressure (CPP) target was > 60 mmHg (n = 39, 60%) and/or an individualized target (n = 25, 38%). To support CPP, crystalloid fluid loading (n = 60, 91%) was generally preferred over albumin (n = 15, 23%), and vasopressors (n = 63, 96%) over inotropes (n = 29, 44%). The most commonly reported target of partial pressure of carbon dioxide in arterial blood (PaCO2) was 36-40 mmHg (4.8-5.3 kPa) in case of controlled intracranial pressure (ICP) < 20 mmHg (n = 45, 69%) and PaCO2 target of 30-35 mmHg (4-4.7 kPa) in case of raised ICP (n = 40, 62%). Almost all respondents indicated to generally treat fever (n = 65, 98%) with paracetamol (n = 61, 92%) and/or external cooling (n = 49, 74%). Conventional glucose management (n = 43, 66%) was preferred over tight glycemic control (n = 18, 28%). More than half of the respondents indicated to aim for full caloric replacement within 7 days (n = 43, 66%) using enteral nutrition (n = 60, 92%). Indications for and duration of seizure prophylaxis varied, and levetiracetam was mostly reported as the agent of choice for both seizure prophylaxis (n = 32, 49%) and treatment (n = 40, 61%).

    CONCLUSIONS: Practice preferences vary substantially regarding general supportive and preventive measures in TBI patients at ICUs of European neurotrauma centers. These results provide an opportunity for future comparative effectiveness research, since a more evidence-based uniformity in good practices in general ICU management could have a major impact on TBI outcome.

  • 31. 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 (Contributor)
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Quality indicators for patients with traumatic brain injury in European intensive care units: a CENTER-TBI study.2020In: Critical Care, ISSN 1364-8535, E-ISSN 1466-609X, Vol. 24, no 1, article id 78Article in journal (Refereed)
    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).

  • 32. Huijben, Jilske A
    et al.
    Wiegers, Eveline J A
    Lingsma, Hester F
    Citerio, Giuseppe
    Maas, Andrew I R
    Menon, David K
    Ercole, Ari
    Nelson, David
    van der Jagt, Mathieu
    Steyerberg, Ewout W
    Helbok, Raimund
    Lecky, Fiona
    Peul, Wilco
    Birg, Tatiana
    Zoerle, Tommaso
    Carbonara, Marco
    Stocchetti, Nino
    Changing care pathways and between-center practice variations in intensive care for traumatic brain injury across Europe: a CENTER-TBI analysis2020In: Intensive Care Medicine, ISSN 0342-4642, E-ISSN 1432-1238, Vol. 46, no 5, p. 995-1004Article in journal (Refereed)
    Abstract [en]

    PURPOSE: To describe ICU stay, selected management aspects, and outcome of Intensive Care Unit (ICU) patients with traumatic brain injury (TBI) in Europe, and to quantify variation across centers.

    METHODS: This is a prospective observational multicenter study conducted across 18 countries in Europe and Israel. Admission characteristics, clinical data, and outcome were described at patient- and center levels. Between-center variation in the total ICU population was quantified with the median odds ratio (MOR), with correction for case-mix and random variation between centers.

    RESULTS: A total of 2138 patients were admitted to the ICU, with median age of 49 years; 36% of which were mild TBI (Glasgow Coma Scale; GCS 13-15). Within, 72 h 636 (30%) were discharged and 128 (6%) died. Early deaths and long-stay patients (> 72 h) had more severe injuries based on the GCS and neuroimaging characteristics, compared with short-stay patients. Long-stay patients received more monitoring and were treated at higher intensity, and experienced worse 6-month outcome compared to short-stay patients. Between-center variations were prominent in the proportion of short-stay patients (MOR = 2.3, p < 0.001), use of intracranial pressure (ICP) monitoring (MOR = 2.5, p < 0.001) and aggressive treatments (MOR = 2.9, p < 0.001); and smaller in 6-month outcome (MOR = 1.2, p = 0.01).

    CONCLUSIONS: Half of contemporary TBI patients at the ICU have mild to moderate head injury. Substantial between-center variations exist in ICU stay and treatment policies, and less so in outcome. It remains unclear whether admission of short-stay patients represents appropriate prudence or inappropriate use of clinical resources.

    Download full text (pdf)
    fulltext
  • 33. Ibarz, Mercedes
    et al.
    Boumendil, Ariane
    Haas, Lenneke E. M.
    Irazabal, Marian
    Flaatten, Hans
    de Lange, Dylan W.
    Morandi, Alessandro
    Andersen, Finn H.
    Bertolini, Guido
    Cecconi, Maurizio
    Christensen, Steffen
    Faraldi, Loredana
    Fjølner, Jesper
    Jung, Christian
    Marsh, Brian
    Moreno, Rui
    Oeyen, Sandra
    Öhman, Christina Agwald
    Bollen Pinto, Bernardo
    Soliman, Ivo W.
    Szczeklik, Wojciech
    Valentin, Andreas
    Watson, Ximena
    Zaferidis, Tilemachos
    Guidet, Bertrand
    Artigas, Antonio
    Sepsis at ICU admission does not decrease 30-day survival in very old patients: a post-hoc analysis of the VIP1 multinational cohort study2020In: Annals of Intensive Care, E-ISSN 2110-5820, Vol. 10, no 1, article id 56Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: The number of intensive care patients aged ≥ 80 years (Very old Intensive Care Patients; VIPs) is growing. VIPs have high mortality and morbidity and the benefits of ICU admission are frequently questioned. Sepsis incidence has risen in recent years and identification of outcomes is of considerable public importance. We aimed to determine whether VIPs admitted for sepsis had different outcomes than those admitted for other acute reasons and identify potential prognostic factors for 30-day survival.

    RESULTS: This prospective study included VIPs with Sequential Organ Failure Assessment (SOFA) scores ≥ 2 acutely admitted to 307 ICUs in 21 European countries. Of 3869 acutely admitted VIPs, 493 (12.7%) [53.8% male, median age 83 (81-86) years] were admitted for sepsis. Sepsis was defined according to clinical criteria; suspected or demonstrated focus of infection and SOFA score ≥ 2 points. Compared to VIPs admitted for other acute reasons, VIPs admitted for sepsis were younger, had a higher SOFA score (9 vs. 7, p < 0.0001), required more vasoactive drugs [82.2% vs. 55.1%, p < 0.0001] and renal replacement therapies [17.4% vs. 9.9%; p < 0.0001], and had more life-sustaining treatment limitations [37.3% vs. 32.1%; p = 0.02]. Frailty was similar in both groups. Unadjusted 30-day survival was not significantly different between the two groups. After adjustment for age, gender, frailty, and SOFA score, sepsis had no impact on 30-day survival [HR 0.99 (95% CI 0.86-1.15), p = 0.917]. Inverse-probability weight (IPW)-adjusted survival curves for the first 30 days after ICU admission were similar for acute septic and non-septic patients [HR: 1.00 (95% CI 0.87-1.17), p = 0.95]. A matched-pair analysis in which patients with sepsis were matched with two control patients of the same gender with the same age, SOFA score, and level of frailty was also performed. A Cox proportional hazard regression model stratified on the matched pairs showed that 30-day survival was similar in both groups [57.2% (95% CI 52.7-60.7) vs. 57.1% (95% CI 53.7-60.1), p = 0.85].

    CONCLUSIONS: After adjusting for organ dysfunction, sepsis at admission was not independently associated with decreased 30-day survival in this multinational study of 3869 VIPs. Age, frailty, and SOFA score were independently associated with survival.

    Download full text (pdf)
    fulltext
  • 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. (Contributor)
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Neurosciences.
    Sundström, Nina (Contributor)
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Predictors of Access to Rehabilitation in the Year Following Traumatic Brain Injury: A European Prospective and Multicenter Study2020In: Neurorehabilitation and Neural Repair, ISSN 1545-9683, E-ISSN 1552-6844, Vol. 34, no 9, p. 814-830Article in journal (Refereed)
    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. (Contributor)
    Umeå University, Faculty of Medicine, Department of Clinical Sciences.
    Sundström, Nina (Contributor)
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    A genome-wide association study of outcome from traumatic brain injury2022In: EBioMedicine, E-ISSN 2352-3964, Vol. 77, article id 103933Article in journal (Refereed)
    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.

    Download full text (pdf)
    fulltext
  • 36.
    Koskinen, Lars-Owe
    et al.
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Sundstrom, Nina
    Umeå University, Faculty of Medicine, Department of Radiation Sciences. Umeå University, Faculty of Science and Technology, Centre for Biomedical Engineering and Physics (CMTF).
    Brorsson, Camilla
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences.
    Olivecrona, M.
    SECONDARY PEAK OF S-100B IS ASSOCIATED WITH DECOMPRESSIVE HEMICRANIECTOMY2016In: Journal of Neurotrauma, ISSN 0897-7151, E-ISSN 1557-9042, Vol. 33, no 3, p. A27-A27Article in journal (Other academic)
    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).

  • 37. Maas, Andrew I. R.
    et al.
    Menon, David K.
    Adelson, P. David
    Andelic, Nada
    Bell, Michael J.
    Belli, Antonio
    Bragge, Peter
    Brazinova, Alexandra
    Büki, András
    Chesnut, Randall M.
    Citerio, Giuseppe
    Coburn, Mark
    Cooper, D. Jamie
    Crowder, A. Tamara
    Czeiter, Endre
    Czosnyka, Marek
    Diaz-Arrastia, Ramon
    Dreier, Jens P.
    Duhaime, Ann-Christine
    Ercole, Ari
    van Essen, Thomas A.
    Feigin, Valery L.
    Gao, Guoyi
    Giacino, Joseph
    Gonzalez-Lara, Laura E.
    Gruen, Russell L.
    Gupta, Deepak
    Hartings, Jed A.
    Hill, Sean
    Jiang, Ji-Yao
    Ketharanathan, Naomi
    Kompanje, Erwin J. O.
    Lanyon, Linda
    Laureys, Steven
    Lecky, Fiona
    Levin, Harvey
    Lingsma, Hester F.
    Maegele, Marc
    Majdan, Marek
    Manley, Geoffrey
    Marsteller, Jill
    Mascia, Luciana
    McFadyen, Charles
    Mondello, Stefania
    Newcombe, Virginia
    Palotie, Aarno
    Parizel, Paul M.
    Peul, Wilco
    Piercy, James
    Polinder, Suzanne
    Puybasset, Louis
    Rasmussen, Todd E.
    Rossaint, Rolf
    Smielewski, Peter
    Söderberg, Jeannette
    Stanworth, Simon J.
    Stein, Murray B.
    von Steinbüchel, Nicole
    Stewart, William
    Steyerberg, Ewout W.
    Stocchetti, Nino
    Synnot, Anneliese
    Te Ao, Braden
    Tenovuo, Olli
    Theadom, Alice
    Tibboel, Dick
    Videtta, Walter
    Wang, Kevin K. W.
    Williams, W. Huw
    Wilson, Lindsay
    Yaffe, Kristine
    Traumatic brain injury: integrated approaches to improve prevention, clinical care, and research2017In: Lancet Neurology, ISSN 1474-4422, E-ISSN 1474-4465, Vol. 16, no 12, p. 987-1048Article in journal (Refereed)
  • 38. 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 (Contributor)
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Neurosciences.
    Sundström, Nina (Contributor)
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    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) Study2021In: Journal of Neurotrauma, ISSN 0897-7151, E-ISSN 1557-9042, Vol. 38, no 2, p. 196-209Article in journal (Refereed)
    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.

    Download full text (pdf)
    fulltext
  • 39.
    Mikolić, Ana
    et al.
    Department of Public Health, Erasmus MC-University Medical Center Rotterdam, Rotterdam, the Netherlands..
    Steyerberg, Ewout W.
    Department of Public Health, Erasmus MC-University Medical Center Rotterdam, Rotterdam, the Netherlands.;Department of Biomedical Data Sciences, Leiden University Medical Center, Leiden, the Netherlands..
    Polinder, Suzanne
    Department of Public Health, Erasmus MC-University Medical Center Rotterdam, Rotterdam, the Netherlands..
    Wilson, Lindsay
    Division of Psychology, University of Stirling, Stirling, United Kingdom..
    Zeldovich, Marina
    Institute of Medical Psychology and Medical Sociology, University Medical Center Göttingen, Georg-August-University, Göttingen, Germany..
    von Steinbuechel, Nicole
    Institute of Medical Psychology and Medical Sociology, University Medical Center Göttingen, Georg-August-University, Göttingen, Germany..
    Newcombe, Virginia F.J.
    Division of Anesthesia, Department of Medicine, University of Cambridge, Cambridge, United Kingdom..
    Menon, David K.
    Division of Anesthesia, Department of Medicine, University of Cambridge, Cambridge, United Kingdom..
    van der Naalt, Joukje
    Department of Neurology, University of Groningen, University Medical Center Groningen, the Netherlands..
    Lingsma, Hester F.
    Department of Public Health, Erasmus MC-University Medical Center Rotterdam, Rotterdam, the Netherlands..
    Maas, Andrew I.R.
    Department of Neurosurgery, Antwerp University Hospital and University of Antwerp, Edegem, Belgium..
    van Klaveren, David
    Department of Public Health, Erasmus MC-University Medical Center Rotterdam, Rotterdam, the Netherlands.;Predictive Analytics and Comparative Effectiveness Center, Institute for Clinical Research and Health Policy Studies/Tufts Medical Center, Boston, Massachusetts, USA..
    Koskinen, Lars-Owe D. (Contributor)
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Neurosciences.
    Prognostic models for global functional outcome and post-concussion symptoms following mild traumatic brain injury: a collaborative european neurotrauma effectiveness research in traumatic brain injury (CENTER-TBI) study2023In: Journal of Neurotrauma, ISSN 0897-7151, E-ISSN 1557-9042, Vol. 40, no 15-16, p. 1651-1670Article in journal (Refereed)
    Abstract [en]

    After mild traumatic brain injury (mTBI), a substantial proportion of individuals do not fully recover on the Glasgow Outcome Scale Extended (GOSE) or experience persistent post-concussion symptoms (PPCS). We aimed to develop prognostic models for the GOSE and PPCS at 6 months after mTBI and to assess the prognostic value of different categories of predictors (clinical variables; questionnaires; computed tomography [CT]; blood biomarkers). From the Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) study, we included participants aged 16 or older with Glasgow Coma Score (GCS) 13-15. We used ordinal logistic regression to model the relationship between predictors and the GOSE, and linear regression to model the relationship between predictors and the Rivermead Post-concussion Symptoms Questionnaire (RPQ) total score. First, we studied a pre-specified Core model. Next, we extended the Core model with other clinical and sociodemographic variables available at presentation (Clinical model). The Clinical model was then extended with variables assessed before discharge from hospital: early post-concussion symptoms, CT variables, biomarkers, or all three categories (extended models). In a subset of patients mostly discharged home from the emergency department, the Clinical model was extended with 2-3-week post-concussion and mental health symptoms. Predictors were selected based on Akaike's Information Criterion. Performance of ordinal models was expressed as a concordance index (C) and performance of linear models as proportion of variance explained (R2). Bootstrap validation was used to correct for optimism. We included 2376 mTBI patients with 6-month GOSE and 1605 patients with 6-month RPQ. The Core and Clinical models for GOSE showed moderate discrimination (C = 0.68 95% confidence interval 0.68 to 0.70 and C = 0.70[0.69 to 0.71], respectively) and injury severity was the strongest predictor. The extended models had better discriminative ability (C = 0.71[0.69 to 0.72] with early symptoms; 0.71[0.70 to 0.72] with CT variables or with blood biomarkers; 0.72[0.71 to 0.73] with all three categories). The performance of models for RPQ was modest (R2 = 4% Core; R2 = 9% Clinical), and extensions with early symptoms increased the R2 to 12%. The 2-3-week models had better performance for both outcomes in the subset of participants with these symptoms measured (C = 0.74 [0.71 to 0.78] vs. C = 0.63[0.61 to 0.67] for GOSE; R2 = 37% vs. 6% for RPQ). In conclusion, the models based on variables available before discharge have moderate performance for the prediction of GOSE and poor performance for the prediction of PPCS. Symptoms assessed at 2-3 weeks are required for better predictive ability of both outcomes. The performance of the proposed models should be examined in independent cohorts.

    Download full text (pdf)
    fulltext
  • 40. 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. (Contributor)
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Neurosciences.
    Sundström, Nina (Contributor)
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Differences between Men and Women in Treatment and Outcome after Traumatic Brain Injury2021In: Journal of Neurotrauma, ISSN 0897-7151, E-ISSN 1557-9042, Vol. 38, no 2, p. 235-251Article in journal (Refereed)
    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.

    Download full text (pdf)
    fulltext
  • 41.
    Milton, A
    et al.
    Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden.
    Schandl, A
    Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden.
    Soliman, I W
    Department of Intensive Care Medicine, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands.
    Meijers, K
    Department of Anaesthesiology and Intensive Care, Sodersjukhuset, Stockholm, Sweden.
    van den Boogaard, M
    Department of Intensive Care Medicine, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands.
    Larsson, I M
    Department of Surgical Sciences, Uppsala University, Uppsala, Sweden.
    Brorsson, Camilla
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Östberg, U
    Department of Anaesthesiology and Intensive Care, Östersund Hospital, Östersund, Sweden.
    Oxenbøll-Collet, M
    Department of Intensive Care, Rigshospitalet Copenhagen, Copenhagen, Denmark.
    Savilampi, J
    Department of Anaesthesiology and Intensive Care, Örebro University Hospital, Örebro, Sweden.
    Paskins, S
    Department of Intensive Care, Odense University Hospital, Odense, Denmark.
    Bottai, M
    Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
    Sackey, P V
    Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden.
    Development of an ICU discharge instrument predicting psychological morbidity: a multinational study2018In: Intensive Care Medicine, ISSN 0342-4642, E-ISSN 1432-1238, Vol. 44, no 12, p. 2038-2047Article in journal (Refereed)
    Abstract [en]

    PURPOSE: To develop an instrument for use at ICU discharge for prediction of psychological problems in ICU survivors.

    METHODS: Multinational, prospective cohort study in ten general ICUs in secondary and tertiary care hospitals in Sweden, Denmark and the Netherlands. Adult patients with an ICU stay ≥ 12 h were eligible for inclusion. Patients in need of neurointensive care, with documented cognitive impairment, unable to communicate in the local language, without a home address or with more than one limitation of therapy were excluded. Primary outcome was psychological morbidity 3 months after ICU discharge, defined as Hospital Anxiety and Depression Scale (HADS) subscale score ≥ 11 or Post-traumatic Stress Symptoms Checklist-14 (PTSS-14) part B score > 45.

    RESULTS: A total of 572 patients were included and 78% of patients alive at follow-up responded to questionnaires. Twenty percent were classified as having psychological problems post-ICU. Of 18 potential risk factors, four were included in the final prediction model after multivariable logistic regression analysis: symptoms of depression [odds ratio (OR) 1.29, 95% confidence interval (CI) 1.10-1.50], traumatic memories (OR 1.44, 95% CI 1.13-1.82), lack of social support (OR 3.28, 95% CI 1.47-7.32) and age (age-dependent OR, peak risk at age 49-65 years). The area under the receiver operating characteristics curve (AUC) for the instrument was 0.76 (95% CI 0.70-0.81).

    CONCLUSIONS: We developed an instrument to predict individual patients' risk for psychological problems 3 months post-ICU, http://www.imm.ki.se/biostatistics/calculators/psychmorb/ . The instrument can be used for triage of patients for psychological ICU follow-up.

    TRIAL REGISTRATION: The study was registered at clinicaltrials.gov, NCT02679157.

    Download full text (pdf)
    fulltext
  • 42. Milton, Anna
    et al.
    Schandl, Anna
    Soliman, Iwo
    Joelsson-Alm, Eva
    van den Boogaard, Mark
    Wallin, Ewa
    Brorsson, Camilla
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Östberg, Ulrika
    Latocha, Kristine
    Savilampi, Johanna
    Paskins, Stinne
    Bottai, Matteo
    Sackey, Peter
    ICU discharge screening for prediction of new-onset physical disability: A multinational cohort study2020In: Acta Anaesthesiologica Scandinavica, ISSN 0001-5172, E-ISSN 1399-6576, Vol. 64, no 6, p. 789-797Article in journal (Refereed)
    Abstract [en]

    Background: Methods to identify patients at risk for incomplete physical recovery after intensive care unit (ICU) stay are lacking. Our aim was to develop a method for prediction of new‐onset physical disability at ICU discharge.

    Methods: Multinational prospective cohort study in 10 general ICUs in Sweden, Denmark, and the Netherlands. Adult patients with an ICU stay ≥12 hours were eligible for inclusion. Sixteen candidate predictors were analyzed with logistic regression for associations with the primary outcome; new‐onset physical disability 3 months post‐ICU, defined as a ≥10 score reduction in the Barthel Index (BI) compared to baseline.

    Results: Of the 572 included patients, follow‐up data are available on 78% of patients alive at follow‐up. The incidence of new‐onset physical disability was 19%. Univariable and multivariable modeling rendered one sole predictor for the outcome: physical status at ICU discharge, assessed with the five first items of the Chelsea critical care physical assessment tool (CPAx) (odds ratio 0.87, 95% confidence interval (CI) 0.81‐0.93), a higher score indicating a lower risk, with an area under the receiver operating characteristics curve of 0.68 (95% CI 0.61‐0.76). Negative predictive value for a low‐risk group (CPAx score >18) was 0.88, and positive predictive value for a high‐risk group (CPAx score ≤18) was 0.32.

    Conclusion: The ICU discharge assessment described in this study had a moderate AUC but may be useful to rule out patients unlikely to need physical interventions post‐ICU. For high‐risk patients, research to determine post‐ICU risk factors for an incomplete rehabilitation is mandated.

    Download full text (pdf)
    fulltext
  • 43. 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. (Contributor)
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Neurosciences.
    Sundström, Nina (Contributor)
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Discrepancy between disability and reported well-being after traumatic brain injury2022In: Journal of Neurology, Neurosurgery and Psychiatry, ISSN 0022-3050, E-ISSN 1468-330X, Vol. 93, no 7, p. 785-96Article in journal (Refereed)
    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.

    Download full text (pdf)
    fulltext
  • 44. 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. (Contributor)
    Umeå University, Faculty of Medicine, Department of Clinical Sciences.
    Sundström, Nina (Contributor)
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    High arterial oxygen levels and supplemental oxygen administration in traumatic brain injury: insights from CENTER-TBI and OzENTER-TBI.2022In: Intensive Care Medicine, ISSN 0342-4642, E-ISSN 1432-1238, Vol. 48, no 12, p. 1709-1725Article in journal (Refereed)
    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.

    Download full text (pdf)
    fulltext
  • 45. Riemann, Lennart
    et al.
    Alhalabi, Obada T
    Unterberg, Andreas W
    Younsi, Alexander
    Koskinen, Lars-Owe D. (Contributor)
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Neurosciences.
    Sundström, Nina (Contributor)
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Concomitant spine trauma in patients with traumatic brain injury: Patient characteristics and outcomes2022In: Frontiers in Neurology, E-ISSN 1664-2295, Vol. 13, article id 861688Article in journal (Refereed)
    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.

    Download full text (pdf)
    fulltext
  • 46. Riemann, Lennart
    et al.
    Mikolic, Ana
    Maas, Andrew
    Unterberg, Andreas
    Younsi, Alexander
    Koskinen, Lars-Owe D. (Contributor)
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Neurosciences.
    Sundström, Nina (Contributor)
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Computed tomography lesions and their association with global outcome in young people with mild traumatic brain injury2023In: Journal of Neurotrauma, ISSN 0897-7151, E-ISSN 1557-9042, Vol. 40, no 11-12, p. 1243-1254Article in journal (Refereed)
    Abstract [en]

    Mild traumatic brain injury (mTBI) can be accompanied by structural damage to the brain. Here, we investigated how the presence of intracranial traumatic computed tomography (CT) pathologies relates to the global functional outcome in young patients one year after mTBI. All patients with mTBI (Glasgow Coma Scale: 13-15) ≤24 years in the multi-center, prospective, observational Collaborative European NeuroTrauma Effectiveness Research in TBI (CENTER-TBI) study were included. Patient demographics and CT findings were assessed at admission, and the Glasgow Outcome Scale Extended (GOSE) was evaluated at 12 months follow-up. The association between a "positive CT" (at least one of the following: epidural hematoma, subdural hematoma, traumatic subarachnoid hemorrhage (tSAH), intraventricular hemorrhage, subdural collection mixed density, contusion, traumatic axonal injury) and functional outcome (GOSE) was assessed using multi-variable mixed ordinal and logistic regression models. A total of 462 patients with mTBI and initial brain CT from 46 study centers were included. The median age was 19 (17-22) years, and 322 (70%) were males. CT imaging showed a traumatic intracranial pathology in 171 patients (37%), most commonly tSAH (48%), contusions (40%), and epidural hematomas (37%). Patients with a positive CT scan were less likely to achieve a complete recovery 12 months post-injury. The presence of any CT abnormality was associated with both lower GOSE scores (odds ratio [OR]: 0.39 [0.24-0.63]) and incomplete recovery (GOSE <8; OR: 0.41 [0.25-0.68]), also when adjusted for demographical and clinical baseline factors. The presence of intracranial traumatic CT pathologies was predictive of outcome 12 months after mTBI in young patients, which might help to identify candidates for early follow-up and additional care.

  • 47. Riemann, Lennart
    et al.
    Zweckberger, Klaus
    Unterberg, Andreas
    Damaty, Ahmed El
    Younsi, Alexander
    Koskinen, Lars-Owe D. (Contributor)
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Neurosciences.
    Sundström, Nina (Contributor)
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Injury Causes and Severity in Pediatric Traumatic Brain Injury Patients Admitted to the Ward or Intensive Care Unit: A Collaborative European Neurotrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) Study2020In: Frontiers in Neurology, E-ISSN 1664-2295, Vol. 11, article id 345Article in journal (Refereed)
    Abstract [en]

    Background: Traumatic brain injury (TBI) is the leading cause of death and disability in children. It includes a range of different pathologies that differ considerably from adult TBI. Analyzing and understanding injury patterns of pediatric TBI is essential to establishing new preventive efforts as well as to improve clinical management.

    Methods: The multi-center, prospectively collected CENTER-TBI core and registry databases were screened and patients were included when younger than 18 years at enrollment and admitted to the regular ward (admission stratum) or intensive care unit (ICU stratum) following TBI. Patient demographics, injury causes, clinical findings, brain CT imaging details, and outcome (GOSE at 6 months follow-up) were retrieved and analyzed. Injury characteristics were compared between patients admitted to the regular ward and ICU and multivariate analysis of factors predicting an unfavorable outcome (GOSE 1-4) was performed.

    Results: from the core study were compared to the registry dataset which includes larger patient numbers but no follow-up data. Results: Two hundred and twenty seven patients in the core dataset and 687 patients in the registry dataset were included in this study. In the core dataset, road-traffic incidents were the most common cause of injury overall and in the ICU stratum, while incidental falls were most common in the admission stratum. Brain injury was considered serious to severe in the majority of patients and concurrent injuries in other body parts were very common. Intracranial abnormalities were detected in 60% of initial brain CTs. Intra- and extracranial surgical interventions were performed in one-fifth of patients. The overall mortality rate was 3% and the rate of unfavorable outcome 10%, with those numbers being considerably higher among ICU patients. GCS and the occurrence of secondary insults could be identified as independent predictors for an unfavorable outcome. Injury characteristics from the core study could be confirmed in the registry dataset.

    Conclusion: Our study displays the most common injury causes and characteristics of pediatric TBI patients that are treated in the regular ward or ICU in Europe. Road-traffic incidents were especially common in ICU patients, indicating that preventive efforts could be effective in decreasing the incidence of severe TBI in children. 

    Download full text (pdf)
    fulltext
  • 48. Robba, Chiara
    et al.
    Banzato, Erika
    Rebora, Paola
    Iaquaniello, Carolina
    Huang, Chao-Yuan
    Wiegers, Eveline J. A.
    Meyfroidt, Geert
    Citerio, Giuseppe
    Koskinen, Lars-Owe (Contributor)
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Neurosciences.
    Sundström, Nina (Contributor)
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Acute Kidney Injury in Traumatic Brain Injury Patients: Results From the Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury Study2020In: Critical Care Medicine, ISSN 0090-3493, E-ISSN 1530-0293, Vol. 49, no 1, p. 112-126Article in journal (Refereed)
    Abstract [en]

    OBJECTIVES: Acute kidney injury is frequent in polytrauma patients, and it is associated with increased mortality and extended hospital length of stay. However, the specific prevalence of acute kidney injury after traumatic brain injury is less recognized. The present study aims to describe the occurrence rate, risk factors, timing, and association with outcome of acute kidney injury in a large cohort of traumatic brain injury patients.

    DESIGN: The Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury is a multicenter, prospective observational, longitudinal, cohort study.

    SETTING: Sixty-five ICUs across Europe.

    PATIENTS: For the present study, we selected 4,509 traumatic brain injury patients with an ICU length of stay greater than 72 hours and with at least two serum creatinine values during the first 7 days of ICU stay.

    MEASUREMENTS AND MAIN RESULTS: We classified acute kidney injury in three stages according to the Kidney Disease Improving Global Outcome criteria: acute kidney injury stage 1 equals to serum creatinine × 1.5–1.9 times from baseline or an increase greater than or equal to 0.3 mg/dL in 48 hours; acute kidney injury stage 2 equals to serum creatinine × 2–2.9 times baseline; acute kidney injury stage 3 equals to serum creatinine × three times baseline or greater than or equal to 4 mg/dL or need for renal replacement therapy. Standard reporting techniques were used to report incidences. A multivariable Cox regression analysis was performed to model the cause-specific hazard of acute kidney injury and its association with the long-term outcome. We included a total of 1,262 patients. The occurrence rate of acute kidney injury during the first week was as follows: acute kidney injury stage 1 equals to 8% (n = 100), acute kidney injury stage 2 equals to 1% (n = 14), and acute kidney injury stage 3 equals to 3% (n = 36). Acute kidney injury occurred early after ICU admission, with a median of 2 days (interquartile range 1–4 d). Renal history (hazard ratio = 2.48; 95% CI, 1.39–4.43; p = 0.002), insulin-dependent diabetes (hazard ratio = 2.52; 95% CI, 1.22–5.197; p = 0.012), hypernatremia (hazard ratio = 1.88; 95% CI, 1.31–2.71; p = 0.001), and osmotic therapy administration (hazard ratio = 2.08; 95% CI, 1.45–2.99; p < 0.001) were significantly associated with the risk of developing acute kidney injury. Acute kidney injury was also associated with an increased ICU length of stay and with a higher probability of 6 months unfavorable Extended Glasgow Outcome Scale and mortality.

    CONCLUSIONS: Acute kidney injury after traumatic brain injury is an early phenomenon, affecting about one in 10 patients. Its occurrence negatively impacts mortality and neurologic outcome at 6 months. Osmotic therapy use during ICU stay could be a modifiable risk factor.

  • 49. Robba, Chiara
    et al.
    Galimberti, Stefania
    Graziano, Francesca
    Wiegers, Eveline J. A.
    Lingsma, Hester F.
    Iaquaniello, Carolina
    Stocchetti, Nino
    Menon, David
    Citerio, Giuseppe
    Brorsson, Camilla (Contributor)
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Tracheostomy practice and timing in traumatic brain-injured patients: a CENTER-TBI study2020In: Intensive Care Medicine, ISSN 0342-4642, E-ISSN 1432-1238, Vol. 46, p. 983-994Article in journal (Refereed)
    Abstract [en]

    PURPOSE: Indications and optimal timing for tracheostomy in traumatic brain-injured (TBI) patients are uncertain. This study aims to describe the patients' characteristics, timing, and factors related to the decision to perform a tracheostomy and differences in strategies among different countries and assess the effect of the timing of tracheostomy on patients' outcomes.

    METHODS: We selected TBI patients from CENTER-TBI, a prospective observational longitudinal cohort study, with an intensive care unit stay ≥ 72 h. Tracheostomy was defined as early (≤ 7 days from admission) or late (> 7 days). We used a Cox regression model to identify critical factors that affected the timing of tracheostomy. The outcome was assessed at 6 months using the extended Glasgow Outcome Score.

    RESULTS: Of the 1358 included patients, 433 (31.8%) had a tracheostomy. Age (hazard rate, HR = 1.04, 95% CI = 1.01-1.07, p = 0.003), Glasgow coma scale ≤ 8 (HR = 1.70, 95% CI = 1.22-2.36 at 7; p < 0.001), thoracic trauma (HR = 1.24, 95% CI = 1.01-1.52, p = 0.020), hypoxemia (HR = 1.37, 95% CI = 1.05-1.79, p = 0.048), unreactive pupil (HR = 1.76, 95% CI = 1.27-2.45 at 7; p < 0.001) were predictors for tracheostomy. Considerable heterogeneity among countries was found in tracheostomy frequency (7.9-50.2%) and timing (early 0-17.6%). Patients with a late tracheostomy were more likely to have a worse neurological outcome, i.e., mortality and poor neurological sequels (OR = 1.69, 95% CI = 1.07-2.67, p = 0.018), and longer length of stay (LOS) (38.5 vs. 49.4 days, p = 0.003).

    CONCLUSIONS: Tracheostomy after TBI is routinely performed in severe neurological damaged patients. Early tracheostomy is associated with a better neurological outcome and reduced LOS, but the causality of this relationship remains unproven.

  • 50. Robba, Chiara
    et al.
    Rebora, Paola
    Banzato, Erika
    Wiegers, Eveline J. A.
    Stocchetti, Nino
    Menon, David K.
    Citerio, Giuseppe
    Koskinen, Lars-Owe D. (Contributor)
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Neurosciences.
    Sundström, Nina (Contributor)
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Incidence, Risk Factors, and Effects on Outcome of Ventilator-Associated Pneumonia in Patients With Traumatic Brain Injury: Analysis of a Large, Multicenter, Prospective, Observational Longitudinal Study2020In: Chest, ISSN 0012-3692, E-ISSN 1931-3543, Vol. 158, no 6, p. 2292-2303Article in journal (Refereed)
    Abstract [en]

    Background: No large prospective data, to our knowledge, are available on ventilator-associated pneumonia (VAP) in patients with traumatic brain injury (TBI).

    Research Question: To evaluate the incidence, timing, and risk factors of VAP after TBI and its effect on patient outcome.

    Study Design and Methods: This analysis is of the Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury data set, from a large, multicenter, prospective, observational study including patients with TBI admitted to European ICUs, receiving mechanical ventilation for ≥ 48 hours and with an ICU length of stay (LOS) ≥ 72 hours. Characteristics of patients with VAP vs characteristics of patients without VAP were compared, and outcome was assessed at 6 months after injury by using the Glasgow Outcome Scale Extended.

    Results: The study included 962 patients: 196 (20.4%) developed a VAP at a median interval of 5 days (interquartile range [IQR], 3-7 days) after intubation. Patients who developed VAP were younger (median age, 39.5 [IQR, 25-55] years vs 51 [IQR, 30-66] years; P < .001), with a higher incidence of alcohol abuse (36.6% vs 27.6%; P = .026) and drug abuse (10.1% vs 4.2%; P = .009), more frequent thoracic trauma (53% vs 43%; P = .014), and more episodes of respiratory failure during ICU stay (69.9% vs 28.1%; P < .001). Age (hazard ratio [HR], 0.99; 95% CI, 0.98-0.99; P = .001), chest trauma (HR, 1.4; 95% CI, 1.03-1.90; P = .033), histamine-receptor antagonist intake (HR, 2.16; 95% CI, 1.37-3.39; P = .001), and antibiotic prophylaxis (HR, 0.69; 95% CI, 0.50-0.96; P = .026) were associated with the risk of VAP. Patients with VAP had a longer duration of mechanical ventilation (median, 15 [IQR, 10-22] days vs 8 [IQR, 5-14] days; P < .001) and ICU LOS (median, 20 [IQR, 14-29] days vs 13 [IQR, 8-21] days; P < .001). However, VAP was not associated with increased mortality or worse neurological outcome. Overall mortality at 6 months was 22%.

    Interpretation: VAP occurs less often than previously described in patients after TBI and has a detrimental effect on ICU LOS but not on mortality and neurological outcome.

    Clinical Trial Registration: ClinicalTrials.gov; No.: NCT02210221; URL: www.clinicaltrials.gov

12 1 - 50 of 78
CiteExportLink to result list
Permanent link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf