| 1. |
- Ntalla, Ioanna, et al.
(författare)
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Multi-ancestry GWAS of the electrocardiographic PR interval identifies 202 loci underlying cardiac conduction
- 2020
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 11:1
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Tidskriftsartikel (refereegranskat)abstract
- The electrocardiographic PR interval reflects atrioventricular conduction, and is associated with conduction abnormalities, pacemaker implantation, atrial fibrillation (AF), and cardiovascular mortality. Here we report a multi-ancestry (N=293,051) genome-wide association meta-analysis for the PR interval, discovering 202 loci of which 141 have not previously been reported. Variants at identified loci increase the percentage of heritability explained, from 33.5% to 62.6%. We observe enrichment for cardiac muscle developmental/contractile and cytoskeletal genes, highlighting key regulation processes for atrioventricular conduction. Additionally, 8 loci not previously reported harbor genes underlying inherited arrhythmic syndromes and/or cardiomyopathies suggesting a role for these genes in cardiovascular pathology in the general population. We show that polygenic predisposition to PR interval duration is an endophenotype for cardiovascular disease, including distal conduction disease, AF, and atrioventricular pre-excitation. These findings advance our understanding of the polygenic basis of cardiac conduction, and the genetic relationship between PR interval duration and cardiovascular disease. On the electrocardiogram, the PR interval reflects conduction from the atria to ventricles and also serves as risk indicator of cardiovascular morbidity and mortality. Here, the authors perform genome-wide meta-analyses for PR interval in multiple ancestries and identify 141 previously unreported genetic loci.
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| 2. |
- Andersen, Leon, et al.
(författare)
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Our initial experience of monitoring the autoregulation of cerebral blood flow during cardiopulmonary bypass
- 2023
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Ingår i: The journal of extra-corporeal technology. - : EDP Sciences. - 0022-1058. ; 55:4, s. 209-217
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Cerebral blood flow (CBF) is believed to be relatively constant within an upper and lower blood pressure limit. Different methods are available to monitor CBF autoregulation during surgery. This study aims to critically analyze the application of the cerebral oxygenation index (COx), one of the commonly used techniques, using a reference to data from a series of clinical registrations.METHOD: CBF was monitored using near-infrared spectroscopy, while cerebral blood pressure was estimated by recordings obtained from either the radial or femoral artery in 10 patients undergoing cardiopulmonary bypass. The association between CBF and blood pressure was calculated as a moving continuous correlation coefficient. A COx index > 0.4 was regarded as a sign of abnormal cerebral autoregulation (CA). Recordings were examined to discuss reliability measures and clinical feasibility of the measurements, followed by interpretation of individual results, identification of possible pitfalls, and suggestions of alternative methods.RESULTS AND CONCLUSION: Monitoring of CA during cardiopulmonary bypass is intriguing and complex. A series of challenges and limitations should be considered before introducing this method into clinical practice.
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| 3. |
- Andersson, Kennet, et al.
(författare)
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Effect of resting pressure on the estimate of cerebrospinal fluid outflow conductance
- 2011
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Ingår i: Fluids and barriers of the CNS. - : Springer Science and Business Media LLC. - 2045-8118. ; 8:1, s. 15-
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: A lumbar infusion test is commonly used as a predictive test for patients with normal pressure hydrocephalus and for evaluation of cerebrospinal fluid (CSF) shunt function. Different infusion protocols can be used to estimate the outflow conductance (Cout) or its reciprocal the outflow resistance, (Rout) with or without using the baseline resting pressure, Pr. Both from a basic physiological research and a clinical perspective, it is important to understand the limitations of the model on which infusion tests are based. By estimating Cout using two different analyses, with or without Pr, the limitations could be explored. The aim of this study was to compare the Cout estimates, and investigate what effect Pr had on the results. METHODS: Sixty-three patients that underwent a constant pressure infusion protocol as part of their preoperative evaluation for normal pressure hydrocephalus, were included (age 70.3+/-10.8 years (mean +/-SD). The analysis was performed without (Cexcl Pr) and with (Cincl Pr) Pr. The estimates were compared using Bland-Altman plots and paired sample t-tests (p<0.05 considered significant). RESULTS: Mean Cout for the 63 patients was: Cexcl Pr = 7.0+/-4.0 (mean +/-SD) ul/(s kPa) and Cincl Pr = 9.1+/-4.3 ul/(s kPa) and Rout was 19.0+/-9.2 and 17.7+/-11.3 mmHg/ml/min, respectively. There was a positive correlation between methods (r=0.79, n=63, p<0.01). The difference, DeltaCout, -2.1+/-2.7 ul/(s kPa) between methods was significant (p<0.01) and DeltaRout was 1.2 +/- 8.8 mmHg/ml/min). The Bland-Altman plot visualized that the variation around the mean difference was similar all through the range of measured values and there was no correlation between DeltaCout and Cout. CONCLUSIONS: The difference between Cout estimates, obtained from analyses with or without Pr, needs to be taken into consideration when comparing results from studies using different infusion test protocols. The study suggests variation in CSF formation rate, variation in venous pressure or a pressure dependent Cout as possible causes for the deviation from the CSF absorption model seen in some patients.
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| 4. |
- Andrén, Kerstin, 1980, et al.
(författare)
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Long-term effects of complications and vascular comorbidity in idiopathic normal pressure hydrocephalus: a quality registry study
- 2018
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Ingår i: Journal of Neurology. - : Springer Science and Business Media LLC. - 0340-5354 .- 1432-1459. ; 265:1, s. 178-186
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Tidskriftsartikel (refereegranskat)abstract
- There is little knowledge about the factors influencing the long-term outcome after surgery for idiopathic normal pressure hydrocephalus (iNPH). To evaluate the effects of reoperation due to complications and of vascular comorbidity (hypertension, diabetes, stroke and heart disease) on the outcome in iNPH patients, 2-6 years after shunt surgery. We included 979 patients from the Swedish Hydrocephalus Quality Registry (SHQR), operated on for iNPH during 2004-2011. The patients were followed yearly by mailed questionnaires, including a self-assessed modified Rankin Scale (smRS) and a subjective comparison between their present and their preoperative health condition. The replies were grouped according to the length of follow-up after surgery. Data on clinical evaluations, vascular comorbidity, and reoperations were extracted from the SHQR. On the smRS, 40% (38-41) of the patients were improved 2-6 years after surgery and around 60% reported their general health condition to be better than preoperatively. Reoperation did not influence the outcome after 2-6 years. The presence of vascular comorbidity had no negative impact on the outcome after 2-6 years, assessed as improvement on the smRS or subjective improvement of the health condition, except after 6 years when patients with hypertension and a history of stroke showed a less favorable development on the smRS. This registry-based study shows no negative impact of complications and only minor effects of vascular comorbidity on the long-term outcome in iNPH.
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| 5. |
- Andrén, Kerstin, 1980, et al.
(författare)
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Survival in treated idiopathic normal pressure hydrocephalus
- 2020
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Ingår i: Journal of Neurology. - : Springer Science and Business Media LLC. - 0340-5354 .- 1432-1459. ; 267, s. 640-648
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Tidskriftsartikel (refereegranskat)abstract
- Objective To describe survival and causes of death in 979 treated iNPH patients from the Swedish Hydrocephalus Quality Registry (SHQR), and to examine the influence of comorbidities, symptom severity and postoperative outcome. Methods All 979 patients operated for iNPH 2004-2011 and registered in the SHQR were included. A matched control group of 4890 persons from the general population was selected by Statistics Sweden. Data from the Swedish Cause of Death Registry was obtained for patients and controls. Results At a median 5.9 (IQR 4.2-8.1) year follow-up, 37% of the iNPH patients and 23% of the controls had died. Mortality was increased in iNPH patients by a hazard ratio of 1.81, 95% CI 1.61-2.04, p < 0.001. More pronounced symptoms in the preoperative ordinal gait scale and the Mini-mental State Examination were the most important independent predictors of mortality along with the prevalence of heart disease. Patients who improved in both the gait scale and in the modified Rankin Scale postoperatively (n = 144) had a similar survival as the general population (p = 0.391). Deaths due to cerebrovascular disease or dementia were more common in iNPH patients, while more controls died because of neoplasms or disorders of the circulatory system. Conclusions Mortality in operated iNPH patients is 1.8 times increased compared to the general population, a lower figure than previously reported. The survival of iNPH patients who improve in gait and functional independence is similar to that of the general population, indicating that shunt surgery for iNPH, besides improving symptoms and signs, can normalize survival.
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| 6. |
- Arango-Lasprilla, Juan Carlos, et al.
(författare)
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Early Predictors of Employment Status One Year Post Injury in Individuals with Traumatic Brain Injury in Europe
- 2020
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Ingår i: Journal of Clinical Medicine. - : MDPI. - 2077-0383. ; 9:6
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Tidskriftsartikel (refereegranskat)abstract
- Sustaining a traumatic brain injury (TBI) often affects the individual’s ability to work, reducing employment rates post-injury across all severities of TBI. The objective of this multi-country study was to assess the most relevant early predictors of employment status in individuals after TBI at one-year post-injury in European countries. Using a prospective longitudinal non-randomized observational cohort (The Collaborative European NeuroTrauma Effectiveness Research in TBI (CENTER-TBI) project), data was collected between December 2014–2019 from 63 trauma centers in 18 European countries. The 1015 individuals who took part in this study were potential labor market participants, admitted to a hospital and enrolled within 24 h of injury with a clinical TBI diagnosis and indication for a computed tomography (CT) scan, and followed up at one year. Results from a binomial logistic regression showed that older age, status of part-time employment or unemployment at time of injury, premorbid psychiatric problems, and higher injury severity (as measured with higher Injury severity score (ISS), lower Glasgow Coma Scale (GCS), and longer length of stay (LOS) in hospital) were associated with higher unemployment probability at one-year after injury. The study strengthens evidence for age, employment at time of injury, premorbid psychiatric problems, ISS, GCS, and LOS as important predictors for employment status one-year post-TBI across Europe.
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| 7. |
- Bockhop, Fabian, et al.
(författare)
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Measurement invariance of six language versions of the post-traumatic stress disorder checklist for DSM-5 in civilians after traumatic brain injury
- 2022
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Ingår i: Scientific Reports. - : Springer Nature. - 2045-2322. ; 12:1
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Tidskriftsartikel (refereegranskat)abstract
- Traumatic brain injury (TBI) is frequently associated with neuropsychiatric impairments such as symptoms of post-traumatic stress disorder (PTSD), which can be screened using self-report instruments such as the Post-Traumatic Stress Disorder Checklist for DSM-5 (PCL-5). The current study aims to inspect the factorial validity and cross-linguistic equivalence of the PCL-5 in individuals after TBI with differential severity. Data for six language groups (n ≥ 200; Dutch, English, Finnish, Italian, Norwegian, Spanish) were extracted from the CENTER-TBI study database. Factorial validity of PTSD was evaluated using confirmatory factor analyses (CFA), and compared between four concurrent structural models. A multi-group CFA approach was utilized to investigate the measurement invariance (MI) of the PCL-5 across languages. All structural models showed satisfactory goodness-of-fit with small between-model variation. The original DSM-5 model for PTSD provided solid evidence of MI across the language groups. The current study underlines the validity of the clinical DSM-5 conceptualization of PTSD and demonstrates the comparability of PCL-5 symptom scores between language versions in individuals after TBI. Future studies should apply MI methods to other sociodemographic (e.g., age, gender) and injury-related (e.g., TBI severity) characteristics to improve the monitoring and clinical care of individuals suffering from PTSD symptoms after TBI.
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| 8. |
- Brodin, Nina, et al.
(författare)
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“it’s like listening to the radio with a little interference” : a qualitative study describing pain management among patients with psoriatic arthritis
- 2023
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Ingår i: Journal of Clinical Medicine. - : MDPI. - 2077-0383. ; 12:23
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Tidskriftsartikel (refereegranskat)abstract
- Pain is one of the most important areas to focus on in the assessment and treatment of psoriatic arthritis (PsA), and treatment should be individualized and based on the needs of the patient. Therefore, our aim was to explore and describe the management of pain among patients with PsA. We conducted semi-structured interviews with 11 participants with PsA (3 men and 8 women) and used qualitative content analysis to analyze the text. The results showed a main overarching theme of meaning and three subthemes. They were ‘Taking charge of life despite the constant murmur of pain’ through ‘Sorting out vulnerability’, ‘Reaching acceptance and engagement’, and ‘Directing focus to change’. Nine categories further described the components of pain management: ‘face uncertainty for the future, ‘consider restrictions’, ‘illuminate the invisible’, ‘increase awareness’, ‘find a permissive environment and social support’, ‘enhance inner endurance’, ‘reformulate emotions and thoughts’, ‘use distracting activities’, and ‘adjust activities’. The action components of pain management interpreted from a theoretical perspective highlight the importance for the patients of attaining the satisfaction of three basic psychological needs, i.e., competence, autonomy, and relatedness. Health professionals therefore need to increase the skills required for needs-supportive behaviors as well as facilitating spouse and peer support in the management of pain in PsA.
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| 9. |
- Brändström, Helge, et al.
(författare)
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Risk for intracranial pressure increase related to enclosed air in post-craniotomy patients during air ambulance transport : a retrospective cohort study with simulation
- 2017
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Ingår i: Scandinavian Journal of Trauma, Resuscitation and Emergency Medicine. - : BioMed Central. - 1757-7241. ; 25
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Post-craniotomy intracranial air can be present in patients scheduled for air ambulance transport to their home hospital. We aimed to assess risk for in-flight intracranial pressure (ICP) increases related to observed intracranial air volumes, hypothetical sea level pre-transport ICP, and different potential flight levels and cabin pressures. METHODS: A cohort of consecutive subdural hematoma evacuation patients from one University Medical Centre was assessed with post-operative intracranial air volume measurements by computed tomography. Intracranial pressure changes related to estimated intracranial air volume effects of changing atmospheric pressure (simulating flight and cabin pressure changes up to 8000 ft) were simulated using an established model for intracranial pressure and volume relations. RESULTS: Approximately one third of the cohort had post-operative intracranial air. Of these, approximately one third had intracranial air volumes less than 11 ml. The simulation estimated that the expected changes in intracranial pressure during 'flight' would not result in intracranial hypertension. For intracranial air volumes above 11 ml, the simulation suggested that it was possible that intracranial hypertension could develop 'inflight' related to cabin pressure drop. Depending on the pre-flight intracranial pressure and air volume, this could occur quite early during the assent phase in the flight profile. DISCUSSION: These findings support the idea that there should be radiographic verification of the presence or absence of intracranial air after craniotomy for patients planned for long distance air transport. CONCLUSIONS: Very small amounts of air are clinically inconsequential. Otherwise, air transport with maintained ground-level cabin pressure should be a priority for these patients.
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| 10. |
- Bäcklund, Tomas, et al.
(författare)
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Novel, clinically applicable method to measure step-width during the swing phase of gait
- 2020
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Ingår i: Physiological Measurement. - : Institute of Physics Publishing (IOPP). - 0967-3334 .- 1361-6579. ; 41:6
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Step-width during walking is an indicator of stability and balance in patients with neurological disorders, and development of objective tools to measure this clinically would be a great advantage. The aim of this study was to validate an in-house-developed gait analysis system (Striton), based on optical and inertial sensors and a novel method for stride detection, for measuring step-width during the swing phase of gait and temporal parameters.Approach: The step-width and stride-time measurements were validated in an experimental setup, against a 3D motion capture system and on an instrumented walkway. Further, test-retest and day-to-day variability were evaluated, and gait parameters were collected from 87 elderly persons (EP) and four individuals with idiopathic normal pressure hydrocephalus (iNPH) before/after surgery.Main results: Accuracy of the step-width measurement was high: in the experimental setup mean error was 0.08 +/- 0.25 cm (R = 1.00) and against the 3D motion capture system 0.04 +/- 1.12 cm (R = 0.98). Test-retest and day-to-day measurements were equal within +/- 0.5 cm. Mean difference in stride time was -0.003 +/- 0.008 s between Striton and the instrumented walkway. The Striton system was successfully applied in the clinical setting on individuals with iNPH, which had larger step-width (6.88 cm, n = 4) compared to EP (5.22 cm, n = 87).Significance: We conclude that Striton is a valid, reliable and wearable system for quantitative assessment of step-width and temporal parameters during gait. Initial measurements indicate that the newly defined step-width parameter differs between EP and patients with iNPH and before/after surgery. Thus, there is potential for clinical applicability in patients with reduced gait stability.
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| 11. |
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| 12. |
- Bäcklund, Tomas, 1958-, et al.
(författare)
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Single sensor measurement of heel-height during the push-off phase of gait
- 2021
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Ingår i: Physiological Measurement. - : Institute of Physics (IOP). - 0967-3334 .- 1361-6579. ; 42:10
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Tidskriftsartikel (refereegranskat)abstract
- Objective: In healthy gait a forceful push-off is needed to get an efficient leg swing and propulsion, and a high heel lift makes a forceful push-off possible. The power of the push-off is decreased with increased age and in persons with impaired balance and gait. The aim of this study was to evaluate whether a wearable equipment (Striton) and algorithms to estimate vertical heel-height during gait from a single optical distance sensor is reliable and feasible for clinical applications.Approach: To assess heel-height with the Striton system an optical distance sensor was used to measure the distance to the floor along the shank. An algorithm was created to transform this measure to a vertical distance. The heel-height was validated in an experimental setup, against a 3D motion capture system (MCS), and test-retest and day-to-day tests were performed on 10 elderly persons. As a reference material 83 elderly persons were included, and heel-height was measured before and after surgery in four patients with the neurological disorder idiopathic normal pressure hydrocephalus (iNPH).Main results: In the experimental setup the accuracy was high with a maximum error of 2% at all distances, target colours and inclination angles, and the correlation to the MCS was R = 0.94. Test-retest and day-to-day tests were equal within ±1.2 cm. Mean heel-height of the elderly persons was 16.5 ± 0.6 cm and in the patients with iNPH heel-height was increased from 11.2 cm at baseline to 15.3 cm after surgery.Significance: Striton can reliably measure heel-height during gait, with low test-retest and day-to-day variability. The system was easy to attach, and simple to use, which makes it suitable for clinical applications.
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| 13. |
- Bäcklund, Tomas, et al.
(författare)
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Trunk sway in idiopathic normal pressure hydrocephalus : quantitative assessment in clinical practice
- 2017
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Ingår i: Gait & Posture. - : Elsevier. - 0966-6362 .- 1879-2219. ; , s. 62-70
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Tidskriftsartikel (refereegranskat)abstract
- Background: In diagnosis and treatment of patients with idiopathic normal pressure hydrocephalus (iNPH), there is need for clinically applicable, quantitative assessment of balance and gait. Using a body worn gyroscopic system, the aim of this study was to assess postural stability of iNPH patients in standing, walking and during sensory deprivation before and after cerebrospinal fluid (CSF) drainage and surgery. A comparison was performed between healthy elderly (HE) and patients with various types of hydrocephalus (ventriculomegaly (VM)).Methods: Trunk sway was measured in 31 iNPH patients, 22 VM patients and 58 HE. Measurements were performed at baseline in all subjects, after CSF drainage in both patient groups and after shunt surgery in the iNPH group.Results: Preoperatively, the iNPH patients had significantly higher trunk sway compared to HE, specifically for the standing tasks (p < 0.001). Compared to VM, iNPH patients had significantly lower sway velocity during gait in three of four cases on firm support (p < 0.05). Sway velocity improved after CSF drainage and in forward-backward direction after surgery (p < 0.01). Compared to HE both patient groups demonstrated less reliance on visual input to maintain stable posture.Conclusions: INPH patients had reduced postural stability compared to HE, particularly during standing, and for differentiation between iNPH and VM patients sway velocity during gait is a promising parameter. A reversible reduction of visual incorporation during standing was also seen. Thus, the gyroscopic system quantitatively assessed postural deficits in iNPH, making it a potentially useful tool for aiding in future diagnoses, choices of treatment and clinical follow-up.
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| 14. |
- Bäcklund, Tomas, 1958-
(författare)
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Wearable systems and sensors for the assessment of motor control : Development and validation of methods for clinical assessment of idiopathic normal pressure hydrocephalus
- 2021
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Human gait and balance are controlled by automatic processes in the central nervous system, and in sensory and proprioceptive systems. If a disturbance occurs in any of these complex structures, it may lead to balance and gait problems. Equally important are the systems controlling the upper extremity functions where reach, grasp and manipulation skills may be affected. For the neurodegenerative disease idiopathic normal pressure hydrocephalus (iNPH), balance and gait disturbances are cardinal symptoms. Motor control of the upper extremities is also affected. In clinic today, physical impairment of persons with iNPH is commonly visually assessed using subjective, course tests with ordinal scales with the risk of missing minor changes. There is a lack of objective and quantitative ways to measure motor control in daily patient care. The aim of this thesis was to develop and validate tools for objective assessment of parameters that affect motor control in persons with iNPH.Postural stability in stance and walking was assessed using gyroscopes in patients with iNPH, healthy elderly (HE) and patients with ventriculomegaly (VM). Compared to HE, patients with iNPH had reduced postural stability and relied less on vision. iNPH patients also had a lower trunk sway velocity than VM during walking. The gyroscopic system could quantitatively assess postural deficits in iNPH, making it a potentially useful tool for diagnosis and for clinical follow-up. The differences found during gait also suggests that walking, rather than quiet stance, should be further investigated for facilitating differential diagnosis compared to other patient groups with ventriculomegaly.The gait in patients with iNPH is according to guidelines defined as slow, shuffling with a low foot-lift, and wide based. To objectively quantify the latter two features, a system (Striton) was developed in-house to assess the increased distance between the feet and the peak heel-height at the push-off phase of the gait cycle. It was validated in experimental setups, compared to gold standard motion capture systems (MCS), on healthy elderly (HE), through test-retest and day-to-day evaluations, and in four patients with iNPH. Striton demonstrated high correlations, in step-width and in heel-height, compared with the MCS. The mean step-width in the HE was 5.2 ± 0.9 cm (mean±Standard Deviation) and the heel-height 16.7±0.6 cm. Test-retest and day-to-day variations were small, ±0.5 cm in step-width and ±1.2 cm in heel-height, and differences in the parameters were seen between HE and iNPH both before and after surgery. Thus, Striton has the potential of quantitatively assessing gait parameters in HE and iNPH in a valuable manner.
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| 15. |
- Böhm, Julia K., et al.
(författare)
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Extended Coagulation Profiling in Isolated Traumatic Brain Injury : A CENTER-TBI Analysis
- 2022
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Ingår i: Neurocritical Care. - : Springer. - 1541-6933 .- 1556-0961. ; 36:3, s. 927-941
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Trauma-induced coagulopathy in traumatic brain injury (TBI) remains associated with high rates of complications, unfavorable outcomes, and mortality. The underlying mechanisms are largely unknown. Embedded in the prospective multinational Collaborative European Neurotrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) study, coagulation profiles beyond standard conventional coagulation assays were assessed in patients with isolated TBI within the very early hours of injury.METHODS: Results from blood samples (citrate/EDTA) obtained on hospital admission were matched with clinical and routine laboratory data of patients with TBI captured in the CENTER-TBI central database. To minimize confounding factors, patients with strictly isolated TBI (iTBI) (n = 88) were selected and stratified for coagulopathy by routine international normalized ratio (INR): (1) INR < 1.2 and (2) INR ≥ 1.2. An INR > 1.2 has been well adopted over time as a threshold to define trauma-related coagulopathy in general trauma populations. The following parameters were evaluated: quick's value, activated partial thromboplastin time, fibrinogen, thrombin time, antithrombin, coagulation factor activity of factors V, VIII, IX, and XIII, protein C and S, plasminogen, D-dimer, fibrinolysis-regulating parameters (thrombin activatable fibrinolysis inhibitor, plasminogen activator inhibitor 1, antiplasmin), thrombin generation, and fibrin monomers.RESULTS: Patients with iTBI with INR ≥ 1.2 (n = 16) had a high incidence of progressive intracranial hemorrhage associated with increased mortality and unfavorable outcome compared with patients with INR < 1.2 (n = 72). Activity of coagulation factors V, VIII, IX, and XIII dropped on average by 15-20% between the groups whereas protein C and S levels dropped by 20%. With an elevated INR, thrombin generation decreased, as reflected by lower peak height and endogenous thrombin potential (ETP), whereas the amount of fibrin monomers increased. Plasminogen activity significantly decreased from 89% in patients with INR < 1.2 to 76% in patients with INR ≥ 1.2. Moreover, D-dimer levels significantly increased from a mean of 943 mg/L in patients with INR < 1.2 to 1,301 mg/L in patients with INR ≥ 1.2.CONCLUSIONS: This more in-depth analysis beyond routine conventional coagulation assays suggests a counterbalanced regulation of coagulation and fibrinolysis in patients with iTBI with hemostatic abnormalities. We observed distinct patterns involving key pathways of the highly complex and dynamic coagulation system that offer windows of opportunity for further research. Whether the changes observed on factor levels may be relevant and explain the worse outcome or the more severe brain injuries by themselves remains speculative.
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| 16. |
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| 17. |
- Chidiac, Christine, 1994-, et al.
(författare)
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Waiting time for surgery influences the outcome in idiopathic normal pressure hydrocephalus : a population-based study
- 2022
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Ingår i: Acta Neurochirurgica. - : Springer. - 0001-6268 .- 0942-0940. ; 164:2, s. 469-478
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Tidskriftsartikel (refereegranskat)abstract
- INTRODUCTION: Idiopathic normal pressure hydrocephalus (iNPH) is a disease that comes with a great impact on the patient's life. The only treatment for iNPH, which is a progressive disease, is shunt surgery. It is previously indicated that early intervention might be of importance for the outcome.AIM: To investigate if a longer waiting time for surgery, negatively influences the clinical outcome.METHODS: Eligible for this study were all iNPH patients (n = 3007) registered in the Swedish Hydrocephalus Quality Registry (SHQR) during 1st of January 2004-12th of June 2019. Waiting time, defined as time between the decision to accept a patient for surgery and shunt surgery, was divided into the intervals ≤ 3, 3.1-5.9 and ≥ 6 months. Clinical outcome was assessed 3 and 12 months after surgery using the modified iNPH scale, the Timed Up and Go (TUG) test and the mini mental state examination (MMSE).RESULTS: Three months after surgery, 57% of the patients with ≤ 3 months waiting time showed an improvement in modified iNPH scale (≥ 5 points) whereas 52% and 46% of patients with 3.1-5.9 and ≥ 6 months waiting time respectively improved (p = 0.0115). At 12 months of follow-up, the corresponding numbers were 61%, 52% and 51% respectively (p = 0.0536).CONCLUSIONS: This population-based study showed that in patients with iNPH, shunt surgery should be performed within 3 months of decision to surgery, to attain the best outcome.
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| 18. |
- Citerio, Giuseppe, et al.
(författare)
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Management of arterial partial pressure of carbon dioxide in the first week after traumatic brain injury : results from the CENTER-TBI study
- 2021
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Ingår i: Intensive Care Medicine. - : Springer. - 0342-4642 .- 1432-1238. ; 47:9, s. 961-973
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: To describe the management of arterial partial pressure of carbon dioxide (PaCO2) in severe traumatic brain-injured (TBI) patients, and the optimal target of PaCO2 in patients with high intracranial pressure (ICP).METHODS: Secondary analysis of CENTER-TBI, a multicentre, prospective, observational, cohort study. The primary aim was to describe current practice in PaCO2 management during the first week of intensive care unit (ICU) after TBI, focusing on the lowest PaCO2 values. We also assessed PaCO2 management in patients with and without ICP monitoring (ICPm), and with and without intracranial hypertension. We evaluated the effect of profound hyperventilation (defined as PaCO2 < 30 mmHg) on long-term outcome.RESULTS: We included 1100 patients, with a total of 11,791 measurements of PaCO2 (5931 lowest and 5860 highest daily values). The mean (± SD) PaCO2 was 38.9 (± 5.2) mmHg, and the mean minimum PaCO2 was 35.2 (± 5.3) mmHg. Mean daily minimum PaCO2 values were significantly lower in the ICPm group (34.5 vs 36.7 mmHg, p < 0.001). Daily PaCO2 nadir was lower in patients with intracranial hypertension (33.8 vs 35.7 mmHg, p < 0.001). Considerable heterogeneity was observed between centers. Management in a centre using profound hyperventilation (HV) more frequently was not associated with increased 6 months mortality (OR = 1.06, 95% CI = 0.77-1.45, p value = 0.7166), or unfavourable neurological outcome (OR 1.12, 95% CI = 0.90-1.38, p value = 0.3138).CONCLUSIONS: Ventilation is manipulated differently among centers and in response to intracranial dynamics. PaCO2 tends to be lower in patients with ICP monitoring, especially if ICP is increased. Being in a centre which more frequently uses profound hyperventilation does not affect patient outcomes.
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| 19. |
- Czeiter, Endre, et al.
(författare)
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Blood biomarkers on admission in acute traumatic brain injury : Relations to severity, CT findings and care path in the CENTER-TBI study
- 2020
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Ingår i: EBioMedicine. - : Elsevier. - 2352-3964. ; 56
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Serum biomarkers may inform and improve care in traumatic brain injury (TBI). We aimed to correlate serum biomarkers with clinical severity, care path and imaging abnormalities in TBI, and explore their incremental value over clinical characteristics in predicting computed tomographic (CT) abnormalities.METHODS: We analyzed six serum biomarkers (S100B, NSE, GFAP, UCH-L1, NFL and t-tau) obtained <24 h post-injury from 2867 patients with any severity of TBI in the Collaborative European NeuroTrauma Effectiveness Research (CENTER-TBI) Core Study, a prospective, multicenter, cohort study. Univariable and multivariable logistic regression analyses were performed. Discrimination was assessed by the area under the receiver operating characteristic curve (AUC) with 95% confidence intervals.FINDINGS: All biomarkers scaled with clinical severity and care path (ER only, ward admission, or ICU), and with presence of CT abnormalities. GFAP achieved the highest discrimination for predicting CT abnormalities (AUC 0•89 [95%CI: 0•87-0•90]), with a 99% likelihood of better discriminating CT-positive patients than clinical characteristics used in contemporary decision rules. In patients with mild TBI, GFAP also showed incremental diagnostic value: discrimination increased from 0•84 [95%CI: 0•83-0•86] to 0•89 [95%CI: 0•87-0•90] when GFAP was included. Results were consistent across strata, and injury severity. Combinations of biomarkers did not improve discrimination compared to GFAP alone.INTERPRETATION: Currently available biomarkers reflect injury severity, and serum GFAP, measured within 24 h after injury, outperforms clinical characteristics in predicting CT abnormalities. Our results support the further development of serum GFAP assays towards implementation in clinical practice, for which robust clinical assay platforms are required.FUNDING: CENTER-TBI study was supported by the European Union 7th Framework program (EC grant 602150).
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| 20. |
- Dijkland, Simone A., et al.
(författare)
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Outcome Prediction after Moderate and Severe Traumatic Brain Injury : External Validation of Two Established Prognostic Models in 1742 European Patients
- 2021
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Ingår i: Journal of Neurotrauma. - : Mary Ann Liebert. - 0897-7151 .- 1557-9042. ; 38:10, s. 1377-1388
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Tidskriftsartikel (refereegranskat)abstract
- The International Mission on Prognosis and Analysis of Clinical Trials in Traumatic Brain Injury (IMPACT) and Corticoid Randomisation After Significant Head injury (CRASH) prognostic models predict functional outcome after moderate and severe traumatic brain injury (TBI). We aimed to assess their performance in a contemporary cohort of patients across Europe. The Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) core study is a prospective, observational cohort study in patients presenting with TBI and an indication for brain computed tomography. The CENTER-TBI core cohort consists of 4509 TBI patients available for analyses from 59 centers in 18 countries across Europe and Israel. The IMPACT validation cohort included 1173 patients with GCS ≤12, age ≥14, and 6-month Glasgow Outcome Scale-Extended (GOSE) available. The CRASH validation cohort contained 1742 patients with GCS ≤14, age ≥16, and 14-day mortality or 6-month GOSE available. Performance of the three IMPACT and two CRASH model variants was assessed with discrimination (area under the receiver operating characteristic curve; AUC) and calibration (comparison of observed vs. predicted outcome rates). For IMPACT, model discrimination was good, with AUCs ranging between 0.77 and 0.85 in 1173 patients and between 0.80 and 0.88 in the broader CRASH selection (n = 1742). For CRASH, AUCs ranged between 0.82 and 0.88 in 1742 patients and between 0.66 and 0.80 in the stricter IMPACT selection (n = 1173). Calibration of the IMPACT and CRASH models was generally moderate, with calibration-in-the-large and calibration slopes ranging between -2.02 and 0.61 and between 0.48 and 1.39, respectively. The IMPACT and CRASH models adequately identify patients at high risk for mortality or unfavorable outcome, which supports their use in research settings and for benchmarking in the context of quality-of-care assessment.
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| 21. |
- Erelund, Sofia, 1983-
(författare)
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Heart and lung function - in health and disease : methodological studies in clinical physiology
- 2023
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The human heart and lungs constitute an intricate and dynamic system. Various clinical physiological examinations can be used to evaluate cardio-pulmonary function and identify abnormalities. Thus, it is important to understand how normal physiology presents, to be able to identify pathological findings. To distinguish normal from abnormal findings in a patient population compared to healthy controls, adequate, accurate and up-to-date reference materials are required. There is currently a lack of well-established sex and age specific reference materials that clearly state boundaries of normality for electrocardiography (ECG) variables. For lung function examinations there are several different reference materials available, being discordant between ethnicities. In addition, the relation between lung function, age, sex, and height has generally been difficult to model in an optimal way. This highlights the need for more adequate sex-specific models regarding age- and height-dependency of spirometry variables. Heart rate variability (HRV) is a method for evaluating the autonomic nervous system (ANS) and its influence on heart rate and blood pressure. Autonomic disturbances are characterized by an imbalance between the sympathetic and the parasympathetic nervous systems. It is well known that decreased HRV is associated with increased mortality. Autonomic imbalances are also associated with various pathological conditions, of which rheumatoid arthritis (RA) and ischemic heart disease (IHD) are studied in this thesis.The purpose of this thesis was to describe the properties of different clinical physiological examinations and to investigate reference values relating to cardiovascular and pulmonary function in healthy individuals regarding age and sex. In addition, the aim was to assess the relationship between HRV, RA and CVD both cross sectionally and longitudinally. In a subjectively healthy population (n=219) of varying age, there were age and sex-dependent differences in ECG examinations. This emphasizes former findings and supports the need to establish age- and sex-specific reference values in the future. Lung function examinations in subjectively healthy persons (n=285) support and emphasize that the reference values presented by the Global Lung function Initiative (GLI) underestimate the pulmonary function in the adult Swedish population. The study showed that the model used in GLI can be updated with new values that are specific for the Caucasian population in Sweden. Patients with RA (n=50) presented with lower HRV than healthy controls (n=100) during autonomic provocation tests, both at baseline examinations and after five years. This indicates a cardiac autonomic imbalance. Furthermore, increased systolic blood pressure was associated with reduced HRV, thus a decrease in HRV could be a risk marker for developing arterial hypertension in this patient group.Females with IHD (n=197) presented with lower HRV compared to controls (n=141) at baseline, and a higher mortality rate after 15 years. The higher mortality rate was only present in females < 60 years of age. For measurements obtained in the upright position, HRV was higher in females that died during follow-up compared to those who were alive. This thesis emphasizes the importance of validated and updated sex- and age- specific reference materials, and models that are well suited for different clinical physiological examinations. Additionally, HRV examinations exposed changes in the ANS related to RA as well as IHD, where findings were shown to be persistent over time and particularly pronounced during provocations. In the future, HRV assessment could be a useful tool to identify the increased risk of developing hypertension in patients with RA, or to customize treatment based on ANS response as the field of personalized medicine continues to evolve.
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| 22. |
- Erelund, Sofia, et al.
(författare)
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Heart rate variability and cardiovascular risk factors in patients with rheumatoid arthritis : a longitudinal study
- 2023
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Ingår i: Autonomic Neuroscience. - : Elsevier. - 1566-0702 .- 1872-7484. ; 249
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Tidskriftsartikel (refereegranskat)abstract
- Background: It is established that the risk of cardiovascular disease (CVD) is increased in patients with Rheumatoid Arthritis (RA). Heart rate variability (HRV) is a method for evaluating the activity in the cardiac autonomic nervous system. Our aim was to assess the longitudinal development of HRV in patients with RA and compare with healthy controls. Furthermore, we wanted to investigate associations between HRV, inflammatory disease activity and cardiovascular complications in patients with RA over time.Method: HRV was assessed with frequency-domain analysis at baseline and after five years in 50 patients with early RA, all being younger than 60 years. HRV indices were age-adjusted based on the estimated age-dependency in 100 age and sex matched healthy controls. Additionally, clinical data including serological markers, disease activity, and blood pressure were collected from the patients. Eleven years after inclusion CVD was assessed.Results: At baseline, patients with RA presented with lower HRV compared to controls during deep breathing (6 breaths/min), paced normal breathing (12 breaths/min) and after passive tilt to the upright position. No significant change in HRV was observed at the five-year follow-up. A significant negative correlation was found between HRV parameters and systolic blood pressure (SBP) at baseline. A significant positive correlation was found between heart rate and inflammatory markers at baseline but not after five years. Nine patients had developed CVD after 11 years, but no significant association was found with baseline HRV data.Conclusion: This study showed that patients with RA have autonomic imbalance both at an early stage of the disease and after five years, despite anti-rheumatic medication, but no correlation between HRV and inflammation markers were observed. Reduced HRV was also significantly negatively correlated with increased SBP. Hypertension is a common finding in patients with RA. Thus, significant decline of HRV could be a useful early marker for development of hypertension in patients with RA.
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| 23. |
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| 24. |
- Erelund, Sofia, et al.
(författare)
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Pulmonary function in a cohort of heart-healthy individuals from Northern Sweden : a comparison with discordant reference values
- 2023
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Ingår i: BMC Pulmonary Medicine. - : BioMed Central (BMC). - 1471-2466. ; 23:1
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Dynamic spirometry is an important investigation to differentiate between impaired and normal lung function. This study aimed to evaluate the results of lung function testing in a cohort of subjects from Northern Sweden without any known heart or pulmonary disease. Our focus was to compare with two reference materials that have showed differences in the age-dependency of lung function in Swedish subjects.METHODS: The study population consisted of 285 healthy adults (148 males, 52%) between 20-90 years of age. The subjects had been randomly selected from the population register for inclusion in a study investigating cardiac function in heart-healthy subjects, but were also assessed with dynamic spirometry. At least seven percent reported smoking. Sixteen subjects presented with pulmonary functional impairments and were excluded from the current study. The sex-specific age-dependency in lung volumes was estimated using the LMS model, where non-linear equations were derived for the mean value (M), the location (L) or skewness, and the scatter (S) or coefficient of variation. This model of the observed lung function data was compared with reference values given by the original LMS model published by the Global Lung Initiative (GLI), and with the model from the recent Obstructive Lung Disease In Norrbotten (OLIN) study, where higher reference values were presented for Swedish subjects than those given by the GLI model.RESULTS: No differences were found in the age-dependency of pulmonary function between the LMS model developed in the study and the OLIN model. Although the study group included smokers, the original GLI reference values suggested significantly lower normal values of FEV1 (forced expiratory volume) and FVC (forced vital capacity), and consequently fewer subjects below the lower limit of normality, than both the rederived LMS and OLIN models.CONCLUSIONS: Our results are in line with previous reports and support that the original GLI reference values underestimate pulmonary function in the adult Swedish population. This underestimation could be reduced by updating the coefficients in the underlying LMS model based on a larger cohort of Swedish citizens than was available in this study.
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| 25. |
- Feng, Junfeng, et al.
(författare)
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Comparison of Care System and Treatment Approaches for Patients with Traumatic Brain Injury in China versus Europe : A CENTER-TBI Survey Study
- 2020
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Ingår i: Journal of Neurotrauma. - : Mary Ann Liebert. - 0897-7151 .- 1557-9042. ; 37:16, s. 1806-1817
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Tidskriftsartikel (refereegranskat)abstract
- Traumatic brain injury (TBI) poses a huge public health and societal problem worldwide. Uncertainty exists on how care system and treatment approaches for TBI worked in China may differ from those in Europe. Better knowledge on this is important to facilitate interpretation of findings reported by Chinese researchers and to inform opportunities for collaborative studies. We aimed to investigate concordance and variations in TBI care between Chinese and European neurotrauma centers. Investigators from 52 centers in China and 68 in Europe involved in the Collaborative European Neuro Trauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) study were invited to complete provider profiling (PP) questionnaires, which covered the main aspects of care system and treatment approaches of TBI care. Participating Chinese and European centers were mainly publicly funded and academic. More centers in China indicated available dedicated neuro-intensive care than those in Europe (98% vs. 60%), and treatment decisions in the ICU were mainly determined by neurosurgeons (58%) in China while in Europe, (neuro)intensivists often took the lead (61%). The ambulance dispatching system was automatic in half of Chinese centers (49%), whereas selective dispatching was more common in European centers (74%). For treatment of refractory intracranial hypertension, a decompressive craniectomy was more frequently regarded as general policy in China compared with in Europe (89% vs. 45%). We observed both concordance and substantial variations with regard to the various aspects of TBI care between Chinese and European centers. These findings are fundamental to guide future research and offer opportunities for collaborative comparative effectiveness research to identify best practices.
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