| 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. |
- 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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| 4. |
- 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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| 5. |
- 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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| 6. |
- 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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| 7. |
- 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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| 8. |
- 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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| 9. |
- 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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| 10. |
- 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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