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1.
  • Bar, N., et al. (författare)
  • A reference map of potential determinants for the human serum metabolome
  • 2020
  • Ingår i: Nature. - : Nature Research. - 0028-0836 .- 1476-4687. ; 588:7836, s. 135-140
  • Tidskriftsartikel (refereegranskat)abstract
    • The serum metabolome contains a plethora of biomarkers and causative agents of various diseases, some of which are endogenously produced and some that have been taken up from the environment1. The origins of specific compounds are known, including metabolites that are highly heritable2,3, or those that are influenced by the gut microbiome4, by lifestyle choices such as smoking5, or by diet6. However, the key determinants of most metabolites are still poorly understood. Here we measured the levels of 1,251 metabolites in serum samples from a unique and deeply phenotyped healthy human cohort of 491 individuals. We applied machine-learning algorithms to predict metabolite levels in held-out individuals on the basis of host genetics, gut microbiome, clinical parameters, diet, lifestyle and anthropometric measurements, and obtained statistically significant predictions for more than 76% of the profiled metabolites. Diet and microbiome had the strongest predictive power, and each explained hundreds of metabolites—in some cases, explaining more than 50% of the observed variance. We further validated microbiome-related predictions by showing a high replication rate in two geographically independent cohorts7,8 that were not available to us when we trained the algorithms. We used feature attribution analysis9 to reveal specific dietary and bacterial interactions. We further demonstrate that some of these interactions might be causal, as some metabolites that we predicted to be positively associated with bread were found to increase after a randomized clinical trial of bread intervention. Overall, our results reveal potential determinants of more than 800 metabolites, paving the way towards a mechanistic understanding of alterations in metabolites under different conditions and to designing interventions for manipulating the levels of circulating metabolites. 
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  • Wilman, H. R., et al. (författare)
  • Genetic studies of abdominal MRI data identify genes regulating hepcidin as major determinants of liver iron concentration
  • 2019
  • Ingår i: Journal of Hepatology. - : Elsevier. - 0168-8278 .- 1600-0641. ; 71:3, s. 594-602
  • Tidskriftsartikel (refereegranskat)abstract
    • Background & Aims: Excess liver iron content is common and is linked to the risk of hepatic and extrahepatic diseases. We aimed to identify genetic variants influencing liver iron content and use genetics to understand its link to other traits and diseases. Methods: First, we performed a genome-wide association study (GWAS) in 8,289 individuals from UK Biobank, whose liver iron level had been quantified by magnetic resonance imaging, before validating our findings in an independent cohort (n = 1,513 from IMI DIRECT). Second, we used Mendelian randomisation to test the causal effects of 25 predominantly metabolic traits on liver iron content. Third, we tested phenome-wide associations between liver iron variants and 770 traits and disease outcomes. Results: We identified 3 independent genetic variants (rs1800562 [C282Y] and rs1799945 [H63D] in HFE and rs855791 [V736A] in TMPRSS6) associated with liver iron content that reached the GWAS significance threshold (p <5 × 10−8). The 2 HFE variants account for ∼85% of all cases of hereditary haemochromatosis. Mendelian randomisation analysis provided evidence that higher central obesity plays a causal role in increased liver iron content. Phenome-wide association analysis demonstrated shared aetiopathogenic mechanisms for elevated liver iron, high blood pressure, cirrhosis, malignancies, neuropsychiatric and rheumatological conditions, while also highlighting inverse associations with anaemias, lipidaemias and ischaemic heart disease. Conclusion: Our study provides genetic evidence that mechanisms underlying higher liver iron content are likely systemic rather than organ specific, that higher central obesity is causally associated with higher liver iron, and that liver iron shares common aetiology with multiple metabolic and non-metabolic diseases. Lay summary: Excess liver iron content is common and is associated with liver diseases and metabolic diseases including diabetes, high blood pressure, and heart disease. We identified 3 genetic variants that are linked to an increased risk of developing higher liver iron content. We show that the same genetic variants are linked to higher risk of many diseases, but they may also be associated with some health advantages. Finally, we use genetic variants associated with waist-to-hip ratio as a tool to show that central obesity is causally associated with increased liver iron content.
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  • Koivula, Robert W., et al. (författare)
  • Discovery of biomarkers for glycaemic deterioration before and after the onset of type 2 diabetes : descriptive characteristics of the epidemiological studies within the IMI DIRECT Consortium
  • 2019
  • Ingår i: Diabetologia. - : Springer. - 0012-186X .- 1432-0428. ; 62:9, s. 1601-1615
  • Tidskriftsartikel (refereegranskat)abstract
    • Aims/hypothesis: Here, we describe the characteristics of the Innovative Medicines Initiative (IMI) Diabetes Research on Patient Stratification (DIRECT) epidemiological cohorts at baseline and follow-up examinations (18, 36 and 48 months of follow-up).Methods: From a sampling frame of 24,682 adults of European ancestry enrolled in population-based cohorts across Europe, participants at varying risk of glycaemic deterioration were identified using a risk prediction algorithm (based on age, BMI, waist circumference, use of antihypertensive medication, smoking status and parental history of type 2 diabetes) and enrolled into a prospective cohort study (n = 2127) (cohort 1, prediabetes risk). We also recruited people from clinical registries with type 2 diabetes diagnosed 6-24 months previously (n = 789) into a second cohort study (cohort 2, diabetes). Follow-up examinations took place at similar to 18 months (both cohorts) and at similar to 48 months (cohort 1) or similar to 36 months (cohort 2) after baseline examinations. The cohorts were studied in parallel using matched protocols across seven clinical centres in northern Europe.Results: Using ADA 2011 glycaemic categories, 33% (n = 693) of cohort 1 (prediabetes risk) had normal glucose regulation and 67% (n = 1419) had impaired glucose regulation. Seventy-six per cent of participants in cohort 1 was male. Cohort 1 participants had the following characteristics (mean +/- SD) at baseline: age 62 (6.2) years; BMI 27.9 (4.0) kg/m(2); fasting glucose 5.7 (0.6) mmol/l; 2 h glucose 5.9 (1.6) mmol/l. At the final follow-up examination the participants' clinical characteristics were as follows: fasting glucose 6.0 (0.6) mmol/l; 2 h OGTT glucose 6.5 (2.0) mmol/l. In cohort 2 (diabetes), 66% (n = 517) were treated by lifestyle modification and 34% (n = 272) were treated with metformin plus lifestyle modification at enrolment. Fifty-eight per cent of participants in cohort 2 was male. Cohort 2 participants had the following characteristics at baseline: age 62 (8.1) years; BMI 30.5 (5.0) kg/m(2); fasting glucose 7.2 (1.4) mmol/l; 2 h glucose 8.6 (2.8) mmol/l. At the final follow-up examination, the participants' clinical characteristics were as follows: fasting glucose 7.9 (2.0) mmol/l; 2 h mixed-meal tolerance test glucose 9.9 (3.4) mmol/l.Conclusions/interpretation: The IMI DIRECT cohorts are intensely characterised, with a wide-variety of metabolically relevant measures assessed prospectively. We anticipate that the cohorts, made available through managed access, will provide a powerful resource for biomarker discovery, multivariate aetiological analyses and reclassification of patients for the prevention and treatment of type 2 diabetes.
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8.
  • Allesøe, Rosa Lundbye, et al. (författare)
  • Discovery of drug–omics associations in type 2 diabetes with generative deep-learning models
  • 2023
  • Ingår i: Nature Biotechnology. - : Springer Nature. - 1087-0156 .- 1546-1696. ; 41:3, s. 399-408
  • Tidskriftsartikel (refereegranskat)abstract
    • The application of multiple omics technologies in biomedical cohorts has the potential to reveal patient-level disease characteristics and individualized response to treatment. However, the scale and heterogeneous nature of multi-modal data makes integration and inference a non-trivial task. We developed a deep-learning-based framework, multi-omics variational autoencoders (MOVE), to integrate such data and applied it to a cohort of 789 people with newly diagnosed type 2 diabetes with deep multi-omics phenotyping from the DIRECT consortium. Using in silico perturbations, we identified drug–omics associations across the multi-modal datasets for the 20 most prevalent drugs given to people with type 2 diabetes with substantially higher sensitivity than univariate statistical tests. From these, we among others, identified novel associations between metformin and the gut microbiota as well as opposite molecular responses for the two statins, simvastatin and atorvastatin. We used the associations to quantify drug–drug similarities, assess the degree of polypharmacy and conclude that drug effects are distributed across the multi-omics modalities.
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  • Gudmundsdottir, Valborg, et al. (författare)
  • Whole blood co-expression modules associate with metabolic traits and type 2 diabetes : an IMI-DIRECT study
  • 2020
  • Ingår i: Genome Medicine. - : BioMed Central. - 1756-994X. ; 12:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: The rising prevalence of type 2 diabetes (T2D) poses a major global challenge. It remains unresolved to what extent transcriptomic signatures of metabolic dysregulation and T2D can be observed in easily accessible tissues such as blood. Additionally, large-scale human studies are required to further our understanding of the putative inflammatory component of insulin resistance and T2D. Here we used transcriptomics data from individuals with (n = 789) and without (n = 2127) T2D from the IMI-DIRECT cohorts to describe the co-expression structure of whole blood that mainly reflects processes and cell types of the immune system, and how it relates to metabolically relevant clinical traits and T2D.Methods: Clusters of co-expressed genes were identified in the non-diabetic IMI-DIRECT cohort and evaluated with regard to stability, as well as preservation and rewiring in the cohort of individuals with T2D. We performed functional and immune cell signature enrichment analyses, and a genome-wide association study to describe the genetic regulation of the modules. Phenotypic and trans-omics associations of the transcriptomic modules were investigated across both IMI-DIRECT cohorts.Results: We identified 55 whole blood co-expression modules, some of which clustered in larger super-modules. We identified a large number of associations between these transcriptomic modules and measures of insulin action and glucose tolerance. Some of the metabolically linked modules reflect neutrophil-lymphocyte ratio in blood while others are independent of white blood cell estimates, including a module of genes encoding neutrophil granule proteins with antibacterial properties for which the strongest associations with clinical traits and T2D status were observed. Through the integration of genetic and multi-omics data, we provide a holistic view of the regulation and molecular context of whole blood transcriptomic modules. We furthermore identified an overlap between genetic signals for T2D and co-expression modules involved in type II interferon signaling.Conclusions: Our results offer a large-scale map of whole blood transcriptomic modules in the context of metabolic disease and point to novel biological candidates for future studies related to T2D.
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  • Jung, Christian, et al. (författare)
  • A comparison of very old patients admitted to intensive care unit after acute versus elective surgery or intervention
  • 2019
  • Ingår i: Journal of critical care. - : W B SAUNDERS CO-ELSEVIER INC. - 0883-9441 .- 1557-8615. ; 52, s. 141-148
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: We aimed to evaluate differences in outcome between patients admitted to intensive care unit (ICU) after elective versus acute surgery in a multinational cohort of very old patients (80 years; VIP). Predictors of mortality, with special emphasis on frailty, were assessed.Methods: In total, 5063 VIPs were induded in this analysis, 922 were admitted after elective surgery or intervention, 4141 acutely, with 402 after acute surgery. Differences were calculated using Mann-Whitney-U test and Wilcoxon test. Univariate and multivariable logistic regression were used to assess associations with mortality.Results: Compared patients admitted after acute surgery, patients admitted after elective surgery suffered less often from frailty as defined as CFS (28% vs 46%; p < 0.001), evidenced lower SOFA scores (4 +/- 5 vs 7 +/- 7; p < 0.001). Presence of frailty (CFS >4) was associated with significantly increased mortality both in elective surgery patients (7% vs 12%; p = 0.01), in acute surgery (7% vs 12%; p = 0.02).Conclusions: VIPs admitted to ICU after elective surgery evidenced favorable outcome over patients after acute surgery even after correction for relevant confounders. Frailty might be used to guide clinicians in risk stratification in both patients admitted after elective and acute surgery. 
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  • Aguilar, J., et al. (författare)
  • Study of nonstandard interactions mediated by a scalar field at the ESSnuSB experiment
  • 2024
  • Ingår i: Physical Review D. - : American Physical Society. - 2470-0010 .- 2470-0029. ; 109:11
  • Tidskriftsartikel (refereegranskat)abstract
    • In this paper, we study scalar mediator induced nonstandard interactions (SNSIs) in the context of the ESSnuSB experiment. In particular, we study the capability of ESSnuSB to put bounds on the SNSI parameters and also study the impact of SNSIs in the measurement of the leptonic CP phase δCP. Existence of SNSIs modifies the neutrino mass matrix and this modification can be expressed in terms of three diagonal real parameters (ηee, ημμ, and ηττ) and three off-diagonal complex parameters (ηeμ, ηeτ, and ημτ). Our study shows that the upper bounds on the parameters ημμ and ηττ depend upon how Δm312 is minimized in the theory. However, this is not the case when one tries to measure the impact of SNSIs on δCP. Further, we show that the CP sensitivity of ESSnuSB can be completely lost for certain values of ηee and ημτ for which the appearance channel probability becomes independent of δCP.
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  • Aguilar, J., et al. (författare)
  • Study of nonstandard interactions mediated by a scalar field at the ESSnuSB experiment
  • 2024
  • Ingår i: Physical Review D. - : American Physical Society (APS). - 2470-0010 .- 2470-0029. ; 109:11
  • Tidskriftsartikel (refereegranskat)abstract
    • In this paper, we study scalar mediator induced nonstandard interactions (SNSIs) in the context of the ESSnuSB experiment. In particular, we study the capability of ESSnuSB to put bounds on the SNSI parameters and also study the impact of SNSIs in the measurement of the leptonic ?⁢? phase ??⁢?. Existence of SNSIs modifies the neutrino mass matrix and this modification can be expressed in terms of three diagonal real parameters (??⁢?, ??⁢?, and ??⁢?) and three off-diagonal complex parameters (??⁢?, ??⁢?, and ??⁢?). Our study shows that the upper bounds on the parameters ??⁢? and ??⁢? depend upon how Δ⁢?231 is minimized in the theory. However, this is not the case when one tries to measure the impact of SNSIs on ??⁢?. Further, we show that the ?⁢? sensitivity of ESSnuSB can be completely lost for certain values of ??⁢? and ??⁢? for which the appearance channel probability becomes independent of ??⁢?.
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16.
  • Brorsson, Joakim, 1988, et al. (författare)
  • Efficient Calculation of the Lattice Thermal Conductivity by Atomistic Simulations with Ab Initio Accuracy
  • 2022
  • Ingår i: Advanced Theory and Simulations. - : Wiley. - 2513-0390. ; 5:2
  • Tidskriftsartikel (refereegranskat)abstract
    • High-order force constant expansions can provide accurate representations of the potential energy surface relevant to vibrational motion. They can be efficiently parametrized using quantum mechanical calculations and subsequently sampled at a fraction of the cost of the underlying reference calculations. Here, force constant expansions are combined via the hiphive package with GPU-accelerated molecular dynamics simulations via the GPUMD package to obtain an accurate, transferable, and efficient approach for sampling the dynamical properties of materials. The performance of this methodology is demonstrated by applying it both to materials with very low thermal conductivity (Ba8Ga16Ge30, SnSe) and a material with a relatively high lattice thermal conductivity (monolayer-MoS2). These cases cover both situations with weak (monolayer-MoS2, SnSe) and strong (Ba8Ga16Ge30) pho renormalization. The simulations also enable to access complementary information such as the spectral thermal conductivity, which allows to discriminate the contribution by different phonon modes while accounting for scattering to all orders. The software packages described here are made available to the scientific community as free and open-source software in order to encourage the more widespread use of these techniques as well as their evolution through continuous and collaborative development.
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  • Ejlertsson, Lina, et al. (författare)
  • Customized interventions improved employees' experience of recovery during the workday
  • 2021
  • Ingår i: Work. - 1051-9815. ; 70:2, s. 509-519
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: There is a lack of research regarding factors promoting recovery during the workday and effective interventions. OBJECTIVE: To evaluate how different intervention activities may impact employees' experiences of recovery at the workplace. METHODS: Customized intervention activities based on qualitative results and a participatory approach were integrated among the employees at six primary health care centres (PHCCs; n'='166) during one year. Recovery and workplace factors were measured with a questionnaire at the start and end of intervention, and also in a control group (15 PHCCs; n'='328). Group differences were tested (Chi-2) and explanatory factors compared by logistic regression models. RESULTS: The proportion of employees reporting workday recovery increased in the intervention group (19.9%to 29.1%; p'='0.01), whereas the control group showed no significant change. Recovery was explained by self-reflection and reflection with co-workers. After intervention, having influence on work situation, energy-building experience, and opportunity for laughter also contributed significantly to recovery. CONCLUSIONS: The results contribute to work recovery research by confirming that a customized intervention may have an impact on employees' recovery experiences. The study showed that considering the factors of reflection, influence, and companionship can positively impact workplace recovery.
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  • Ejlertsson, Lina, et al. (författare)
  • Is it possible to gain energy at work? A questionnaire study in primary health care
  • 2020
  • Ingår i: Primary Health Care Research and Development. - 1463-4236. ; 21
  • Tidskriftsartikel (refereegranskat)abstract
    • Abstract Objectives: The area of regenerative work is still close to unexplored. The aim was to explore the possibility for employees to gain energy at work. Methods: Questionnaire to all employees (n = 599) from different professions in public and private primary health care centers in one health care district in Sweden. The questionnaire, which had a salutogenic perspective, included information on self-rated health, psychosocial work environment and experiences, recovery, social climate, and energy. Having an energy-building experience was defined by a positive response to two combined questions regarding energy at work. Analyses were performed with bivariate correlation and multiple logistic regression. Results: The response rate was 84%. Health and energy correlated positively (r = 0.54). In total, 44.5% of the employees reported having an energy-building experience. Predictors for having an energy-building experience were recovery [positive odds ratio (POR) = 2.78], autonomy (POR = 2.26), positive workplace characteristics (POR = 2.09), and internal work experiences (POR = 1.88). Conclusions: The results support the hypothesis that it is possible to gain energy at work, an area that is still close to unexplored. There is a high correlation between energy and health. Employees' energy-building experiences relate to well-being at work and correlates to recovery, autonomy, positive workplace characteristics, and positive internal work experiences. This knowledge can help in improving future work environment development.
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  • Ejlertsson, Lina, et al. (författare)
  • Strengthened workplace relationships facilitate recovery at work – qualitative experiences of an intervention among employees in primary health care
  • 2021
  • Ingår i: BMC Family Practice. - : Springer Science and Business Media LLC. - 1471-2296. ; 22:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: The literature on workplace interventions focusing on recovery is scarce; hence this study intends to expand that knowledge. An intervention was run for one year, aiming at increasing the experience of recovery during the workday among primary health care employees. During the intervention, different forms of recovery activities were integrated into the daily work at six primary health care centres. The aim of this study was to explore the intervention process and its effects. Methods: After completion of an intervention, 39 employees in seven focus groups were interviewed about their experiences of the intervention. A semi-structured interview guide was used, and the qualitative analysis was conducted by systematic text condensation. Results: Despite different conditions and attitudes when the project was launched, the participants portrayed a positive outcome of the intervention at all six workplaces. Four promoting factors for intervention success were identified: support, legitimacy, customization, and simplicity. Also, three areas of improvement during the intervention period were described: the workplace climate, employee well-being, and recovery awareness, which in turn became promoting factors. Conclusions: An intervention aiming at increasing workplace recovery can be promoted by support, legitimacy, customization, and simplicity. By using these promoting factors, health care workplaces can implement activity models which could increase employees’ experiences of recovery during the workday. Positive effects on workplace climate and employee well-being can also be achieved.
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  • Fronczek, Jakub, et al. (författare)
  • Relationship between the Clinical Frailty Scale and short-term mortality in patients ≥ 80 years old acutely admitted to the ICU : a prospective cohort study
  • 2021
  • Ingår i: Critical Care. - : BioMed Central (BMC). - 1364-8535 .- 1466-609X. ; 25:1
  • Tidskriftsartikel (refereegranskat)abstract
    • 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).
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  • Gaber, Sophie, et al. (författare)
  • Social Citizenship Through Out-of-Home Participation Among Older Adults With and Without Dementia
  • 2022
  • Ingår i: Journal of Applied Gerontology. - : Sage Publications. - 0733-4648 .- 1552-4523. ; 41:11, s. 2362-2373
  • Tidskriftsartikel (refereegranskat)abstract
    • There is limited empirical knowledge about how older adults living with dementia enact their social citizenship through out-of-home participation. This study aimed: (a) to investigate out-of-home participation among older adults with and without dementia in four countries and (b) to compare aspects of stability or change in out-of-home participation. Using a cross-sectional design, older adults with mild-to-moderate dementia and without dementia, aged 55 years and over, were interviewed using the Participation in ACTivities and Places OUTside the Home questionnaire in Canada (n = 58), Sweden (n = 69), Switzerland (n = 70), and the United Kingdom (n = 128). Data were analyzed using descriptive statistics and a two-way analysis of variance. After adjustment for age, diagnosis of dementia and country of residence had significant effects on total out-of-home participation (p <.01). The results contribute to policies and development of programs to facilitate social citizenship by targeting specific activities and places.
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  • Gravesteijn, B. Y., et al. (författare)
  • Variation in the practice of tracheal intubation in Europe after traumatic brain injury : a prospective cohort study
  • 2020
  • Ingår i: Anaesthesia. - : John Wiley & Sons. - 0003-2409 .- 1365-2044. ; 75:1, s. 45-53
  • Tidskriftsartikel (refereegranskat)abstract
    • Traumatic brain injury patients frequently undergo tracheal intubation. We aimed to assess current intubation practice in Europe and identify variation in practice. We analysed data from patients with traumatic brain injury included in the prospective cohort study collaborative European neurotrauma effectiveness research in traumatic brain injury (CENTER-TBI) in 45 centres in 16 European countries. We included patients who were transported to hospital by emergency medical services. We used mixed-effects multinomial regression to quantify the effects on pre-hospital or in-hospital tracheal intubation of the following: patient characteristics; injury characteristics; centre; and trauma system characteristics. A total of 3843 patients were included. Of these, 1322 (34%) had their tracheas intubated; 839 (22%) pre-hospital and 483 (13%) in-hospital. The fit of the model with only patient characteristics predicting intubation was good (Nagelkerke R2 64%). The probability of tracheal intubation increased with the following: younger age; lower pre-hospital or emergency department GCS; higher abbreviated injury scale scores (head and neck, thorax and chest, face or abdomen abbreviated injury score); and one or more unreactive pupils. The adjusted median odds ratio for intubation between two randomly chosen centres was 3.1 (95%CI 2.1-4.3) for pre-hospital intubation, and 2.7 (95%CI 1.9-3.5) for in-hospital intubation. Furthermore, the presence of an anaesthetist was independently associated with more pre-hospital intubation (OR 2.9, 95%CI 1.3-6.6), in contrast to the presence of ambulance personnel who are allowed to intubate (OR 0.5, 95%CI 0.3-0.8). In conclusion, patient and injury characteristics are key drivers of tracheal intubation. Between-centre differences were also substantial. Further studies are needed to improve the evidence base supporting recommendations for tracheal intubation.
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24.
  • Guidet, Bertrand, et al. (författare)
  • Withholding or withdrawing of life-sustaining therapy in older adults (≥ 80 years) admitted to the intensive care unit
  • 2018
  • Ingår i: Intensive Care Medicine. - : Springer Science and Business Media LLC. - 0342-4642 .- 1432-1238. ; 44:7, s. 1027-1038
  • Tidskriftsartikel (refereegranskat)abstract
    • 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).
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25.
  • Gylvin, T., et al. (författare)
  • Functional SOCS1 polymorphisms are associated with variation in obesity in whites
  • 2009
  • Ingår i: Diabetes, Obesity and Metabolism. - : Wiley. - 1462-8902 .- 1463-1326. ; 11:3, s. 196-203
  • Tidskriftsartikel (refereegranskat)abstract
    • The suppressor of cytokine signalling 1 (SOCS1) is a natural inhibitor of cytokine and insulin signalling pathways and may also play a role in obesity. In addition, SOCS1 is considered a candidate gene in the pathogenesis of both type 1 diabetes (T1D) and type 2 diabetes (T2D). The objective was to perform mutation analysis of SOCS1 and to test the identified variations for association to T2D-related quantitative traits, T2D or T1D. Mutation scanning was performed by direct sequencing in 27 white Danish subjects. Genotyping was carried out by TaqMan allelic discrimination. A total of more than 8100 individuals were genotyped. Eight variations were identified in the 5' untranslated region (UTR) region. Two of these had allele frequencies below 1% and were not further examined. The six other variants were analysed in groups of T1D families (n = 1461 subjects) and T2D patients (n = 1430), glucose tolerant first-degree relatives of T2D patients (n = 212) and normal glucose tolerant (NGT) subjects. The rs33977706 polymorphism (-820G > T) was associated with a lower body mass index (BMI) (p = 0.004). In a second study (n = 4625 NGT subjects), significant associations of both the rs33977706 and the rs243330 (-1656G > A) variants to obesity were found (p = 0.047 and p = 0.015) respectively. The rs33977706 affected both binding of a nuclear protein to and the transcriptional activity of the SOCS1 promoter, indicating a relationship between this polymorphism and gene regulation. This study demonstrates that functional variations in the SOCS1 promoter may associate with alterations in BMI in the general white population.
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26.
  • Haas, Lenneke E M, et al. (författare)
  • 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 ICUs
  • 2021
  • Ingår i: Age and Ageing. - : Oxford University Press. - 0002-0729 .- 1468-2834. ; 50:5, s. 1719-1727
  • Tidskriftsartikel (refereegranskat)abstract
    • 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.
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27.
  • Howe, Emilie Isager, et al. (författare)
  • Rehabilitation and outcomes after complicated vs uncomplicated mild TBI : results from the CENTER-TBI study
  • 2022
  • Ingår i: BMC Health Services Research. - : BioMed Central (BMC). - 1472-6963. ; 22:1
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Despite existing guidelines for managing mild traumatic brain injury (mTBI), evidence-based treatments are still scarce and large-scale studies on the provision and impact of specific rehabilitation services are needed. This study aimed to describe the provision of rehabilitation to patients after complicated and uncomplicated mTBI and investigate factors associated with functional outcome, symptom burden, and TBI-specific health-related quality of life (HRQOL) up to six months after injury.METHODS: Patients (n = 1379) with mTBI from the Collaborative European NeuroTrauma Effectiveness Research in TBI (CENTER-TBI) study who reported whether they received rehabilitation services during the first six months post-injury and who participated in outcome assessments were included. Functional outcome was measured with the Glasgow Outcome Scale - Extended (GOSE), symptom burden with the Rivermead Post Concussion Symptoms Questionnaire (RPQ), and HRQOL with the Quality of Life after Brain Injury - Overall Scale (QOLIBRI-OS). We examined whether transition of care (TOC) pathways, receiving rehabilitation services, sociodemographic (incl. geographic), premorbid, and injury-related factors were associated with outcomes using regression models. For easy comparison, we estimated ordinal regression models for all outcomes where the scores were classified based on quantiles.RESULTS: Overall, 43% of patients with complicated and 20% with uncomplicated mTBI reported receiving rehabilitation services, primarily in physical and cognitive domains. Patients with complicated mTBI had lower functional level, higher symptom burden, and lower HRQOL compared to uncomplicated mTBI. Rehabilitation services at three or six months and a higher number of TOC were associated with unfavorable outcomes in all models, in addition to pre-morbid psychiatric problems. Being male and having more than 13 years of education was associated with more favorable outcomes. Sustaining major trauma was associated with unfavorable GOSE outcome, whereas living in Southern and Eastern European regions was associated with lower HRQOL.CONCLUSIONS: Patients with complicated mTBI reported more unfavorable outcomes and received rehabilitation services more frequently. Receiving rehabilitation services and higher number of care transitions were indicators of injury severity and associated with unfavorable outcomes. The findings should be interpreted carefully and validated in future studies as we applied a novel analytic approach.
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28.
  • Huijben, Jilske A., et al. (författare)
  • Variation in Blood Transfusion and Coagulation Management in Traumatic Brain Injury at the Intensive Care Unit : A Survey in 66 Neurotrauma Centers Participating in the Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury Study
  • 2017
  • Ingår i: Journal of Neurotrauma. - : Mary Ann Liebert. - 0897-7151 .- 1557-9042. ; 35:2, s. 323-332
  • Tidskriftsartikel (refereegranskat)abstract
    • Our aim was to describe current approaches and to quantify variability between European intensive care units (ICUs) in patients with traumatic brain injury (TBI). Therefore, we conducted a provider profiling survey as part of the Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) study. The ICU Questionnaire was sent to 68 centers from 20 countries across Europe and Israel. For this study, we used ICU questions focused on 1) hemoglobin target level (Hb-TL), 2) coagulation management, and 3) deep venous thromboembolism (DVT) prophylaxis. Seventy-eight participants, mostly intensivists and neurosurgeons of 66 centers, completed the ICU questionnaire. For ICU-patients, half of the centers (N = 34; 52%) had a defined Hb-TL in their protocol. For patients with TBI, 26 centers (41%) indicated an Hb-TL between 70 and 90 g/L and 38 centers (59%) above 90 g/L. To treat trauma-related hemostatic abnormalities, the use of fresh frozen plasma (N = 48; 73%) or platelets (N = 34; 52%) was most often reported, followed by the supplementation of vitamin K (N = 26; 39%). Most centers reported using DVT prophylaxis with anticoagulants frequently or always (N = 62; 94%). In the absence of hemorrhagic brain lesions, 14 centers (21%) delayed DVT prophylaxis until 72 h after trauma. If hemorrhagic brain lesions were present, the number of centers delaying DVT prophylaxis for 72 h increased to 29 (46%). Overall, a lack of consensus exists between European ICUs on blood transfusion and coagulation management. The results provide a baseline for the CENTER-TBI study, and the large between-center variation indicates multiple opportunities for comparative effectiveness research.
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29.
  • Ibarz, Mercedes, et al. (författare)
  • Sepsis at ICU admission does not decrease 30-day survival in very old patients : a post-hoc analysis of the VIP1 multinational cohort study
  • 2020
  • Ingår i: Annals of Intensive Care. - : Springer. - 2110-5820. ; 10:1
  • Tidskriftsartikel (refereegranskat)abstract
    • 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.
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30.
  • Jonsdottir, Unnur Saedis, 1982, et al. (författare)
  • Factors That Affect Return to Sports After an Achilles Tendon Rupture: A Qualitative Content Analysis
  • 2023
  • Ingår i: Orthopaedic Journal of Sports Medicine. - : SAGE Publications. - 2325-9671. ; 11:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Achilles tendon rupture is common among physically active individuals, yet a high percentage fail to return to their former activity after the injury. Quantifiable factors such as type of treatment, hours of rehabilitation, and age have not been associated with return-to-play rates. A factor that influences recovery is the participant’s experience before and throughout the rehabilitation process, which can be explored using a qualitative content analysis. Purpose: To explore and describe what influences the participant to return to physical activity after an Achilles tendon rupture. Study Design: Cross-sectional study; Level of evidence, 3. Methods: Twenty participants (14 men; mean age, 46 years) were interviewed as part of this study. All participants had ruptured their Achilles tendon 4 to 6 years before the interviews. From the interviews, codes were extracted that evolved into 19 subcategories, 6 categories, and 1 theme. Results: The overarching theme that emerged was “Help me and then I can fix this.” The 6 categories were (1) one’s own drive to succeed, (2) having a supportive social network, (3) trusting the support from the health and social systems, (4) receiving and adapting information from others drives persistence in returning to activity, (5) impact of the injury on psychological factors; and (6) influence of physiological aspects. Conclusion: To be able to recover properly from an Achilles tendon rupture and return to activity, the study participants described the importance of obtaining the support needed to be able to gain optimal rehabilitation. In the participants’ opinion, for a greater chance of successful treatment and rehabilitation, it was vital to be provided with good support.
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31.
  • Powell, H. C., et al. (författare)
  • Individuals post achilles tendon rupture exhibit asymmetrical knee and ankle kinetics and loading rates during a drop countermovement jump
  • 2018
  • Ingår i: Journal of Orthopaedic and Sports Physical Therapy. - : Journal of Orthopaedic & Sports Physical Therapy (JOSPT). - 0190-6011 .- 1938-1344. ; 48:1, s. 34-43
  • Tidskriftsartikel (refereegranskat)abstract
    • STUDY DESIGN: Cross-sectional laboratory study. BACKGROUND: Asymmetrical knee loading during jogging and hopping has been reported in individuals who have ruptured their Achilles tendon. No studies have examined knee loads in individuals post Achilles tendon rupture during high-demand tasks, such as single-limb landings. OBJECTIVES: We sought to determine whether individuals post Achilles tendon rupture demonstrated asymmetrical knee loads and impact forces during drop countermovement jumps (CMJs). METHODS: Achilles tendon length and the single-leg heel-rise test for endurance were assessed in 34 individuals (31 male) 6.1 ± 2.0 years post Achilles tendon rupture. Movement patterns were assessed during a drop CMJ. Data were analyzed via repeated-measures analyses of variance, with comparisons between limbs and prior treatment history (surgery versus nonsurgery). RESULTS: An 8.6% longer Achilles tendon (P<.001) was found in the involved limb. During the single-leg heel-rise test, the involved limb demonstrated 22.4% less endurance and 14.6% lower heel-rise height (all, P<.001). During the landing phase of the drop CMJ, the involved limb exhibited 39.6% greater loading rate (P<.001), 16.8% greater eccentric knee power (P = .048), but 21.6% lower eccentric ankle power (P<.001). During the take-off phase, the involved limb exhibited 12.1% lower jump height and 19.9% lower concentric ankle power (both, P<.001). CONCLUSION: Elevated eccentric knee joint power and higher loading rates during a drop CMJ in individuals who experienced Achilles tendon rupture several years earlier may be a compensation pattern for reduced plantar flexor function. This movement pattern may place individuals who have had an Achilles tendon rupture at greater risk for knee injuries. © 2018 Journal of Orthopaedic & Sports Physical Therapy®.
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32.
  • Ringborg, U, et al. (författare)
  • The Swedish Council on Technology Assessment in Health Care (SBU) systematic overview of radiotherapy for cancer including a prospective survey of radiotherapy practice in Sweden 2001 - Summary and conclusions
  • 2003
  • Ingår i: Acta Oncologica. - : Informa UK Limited. - 1651-226X .- 0284-186X. ; 42:5-6, s. 357-365
  • Tidskriftsartikel (refereegranskat)abstract
    • A systematic assessment of radiotherapy for cancer was conducted by The Swedish Council on Technology Assessment in Health Care (SBU) and published in 1996. The assessment reviewed the scientific literature up to 1993 on the use of radiotherapy in the treatment of solid tumours. and estimated the costs associated with radiotherapy It also described the current practise of radiotherapy in Sweden 1992 and compared practise with scientific knowledge. The SBU has now conducted a follow-up study on radiotherapy for cancer, including a review of the scientific literature from 1994 and a prospective survey of radiotherapy practise in Sweden 2001. The following conclusions were drawn: The role of radiotherapy as an important form of treatment for cancer with both curative and palliative intent has been further confirmed. The use of radiotherapy in Sweden has increased and is now at the internationally recommended level. Radiotherapy in Sweden is mostly given in accordance with the scientific evidence but may still be underutilized in certain situations. The resources for radiotherapy are being utilized more efficiently The costs of radiotherapy are still 5% of the total cost of cancer care, while the cost of an individual treatment (fraction) has decreased. The need for radiotherapy capacity will increase. In addition, half of the treatment equipment will have to be replaced in the next few years.
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34.
  • Sorensen, J. S., et al. (författare)
  • Islet autoantibodies and residual beta cell function in type 1 diabetes children followed for 3-6 years
  • 2012
  • Ingår i: Diabetes Research and Clinical Practice. - : Elsevier BV. - 1872-8227 .- 0168-8227. ; 96:2, s. 204-210
  • Tidskriftsartikel (refereegranskat)abstract
    • Aims: To test if islet autoantibodies at diagnosis of type 1 diabetes (T1DM) and after 3-6 years with T1D predict residual beta-cell function (RBF) after 3-6 years with T1D. Methods: T1D children (n = 260, median age at diagnosis 9.4, range 0.9-14.7 years) were tested for GAD65, IA-2, ZnT8R, ZnT8W and ZnT8Q autoantibodies (A) at diagnosis, and 3-6 years after diagnosis when also fasting and stimulated RBF were determined. Results: For every 1-year increase in age at diagnosis of TID, the odds of detectable C-peptide increased 1.21 (1.09, 1.34) times for fasting C-peptide and 1.28 (1.15, 1.42) times for stimulated C-peptide. Based on a linear model for subjects with no change in IA-2A levels, the odds of detectable C-peptide were 35% higher than for subjects whose IA-2A levels decreased by half (OR = 1.35 (1.09, 1.67), p = 0.006); similarly for ZnT8WA (OR = 1.39 (1.09, 1.77), p = 0.008) and ZnT8QA (OR = 1.55 (1.06, 2.26) p = 0.024). Such relationship was not detected for GADA or ZnT8RA. All OR adjusted for confounders. Conclusions: Age at diagnosis with T1D was the major predictor of detectable C-peptide 3-6 years post-diagnosis. Decreases in IA-2A, and possibly ZnT8A, levels between diagnosis and post-diagnosis were associated with a reduction in RBF post-diagnosis. (C) 2012 Elsevier Ireland Ltd. All rights reserved.
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35.
  • Stenström, P., et al. (författare)
  • Boosting the performance of shared memory multiprocessors
  • 1997
  • Ingår i: Computer. - : Institute of Electrical and Electronics Engineers (IEEE). - 0018-9162 .- 1558-0814. ; 30, s. 63-70
  • Tidskriftsartikel (refereegranskat)abstract
    • Proposed hardware optimizations to CC-NUMA machines-shared memory multiprocessors that use cache consistency protocols-can shorten the time processors lose because of cache misses and invalidations. The authors look at cost-performance trade-offs for each
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36.
  • van Essen, Thomas A., et al. (författare)
  • Surgery versus conservative treatment for traumatic acute subdural haematoma : a prospective, multicentre, observational, comparative effectiveness study
  • 2022
  • Ingår i: Lancet Neurology. - : Elsevier. - 1474-4422 .- 1474-4465. ; 21:7, s. 620-631
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Despite being well established, acute surgery in traumatic acute subdural haematoma is based on low-grade evidence. We aimed to compare the effectiveness of a strategy preferring acute surgical evacuation with one preferring initial conservative treatment in acute subdural haematoma.METHODS: We did a prospective, observational, comparative effectiveness study using data from participants enrolled in the Collaborative European Neurotrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) cohort. We included patients with no pre-existing severe neurological disorders who presented with acute subdural haematoma within 24 h of traumatic brain injury. Using an instrumental variable analysis, we compared outcomes between centres according to treatment preference for acute subdural haematoma (acute surgical evacuation or initial conservative treatment), measured by the case-mix-adjusted percentage of acute surgery per centre. The primary endpoint was functional outcome at 6 months as rated with the Glasgow Outcome Scale Extended, which was estimated with ordinal regression as a common odds ratio (OR) and adjusted for prespecified confounders. Variation in centre preference was quantified with the median OR (MOR). CENTER-TBI is registered with ClinicalTrials.gov, number NCT02210221, and the Resource Identification Portal (Research Resource Identifier SCR_015582).FINDINGS: Between Dec 19, 2014 and Dec 17, 2017, 4559 patients with traumatic brain injury were enrolled in CENTER-TBI, of whom 1407 (31%) presented with acute subdural haematoma and were included in our study. Acute surgical evacuation was done in 336 (24%) patients, by craniotomy in 245 (73%) of those patients and by decompressive craniectomy in 91 (27%). Delayed decompressive craniectomy or craniotomy after initial conservative treatment (n=982) occurred in 107 (11%) patients. The percentage of patients who underwent acute surgery ranged from 5·6% to 51·5% (IQR 12·3-35·9) between centres, with a two-times higher probability of receiving acute surgery for an identical patient in one centre versus another centre at random (adjusted MOR for acute surgery 1·8; p<0·0001]). Centre preference for acute surgery over initial conservative treatment was not associated with improvements in functional outcome (common OR per 23·6% [IQR increase] more acute surgery in a centre 0·92, 95% CI 0·77-1·09).INTERPRETATION: Our findings show that treatment for patients with acute subdural haematoma with similar characteristics differed depending on the treating centre, because of variation in the preferred approach. A treatment strategy preferring an aggressive approach of acute surgical evacuation over initial conservative treatment was not associated with better functional outcome. Therefore, in a patient with acute subdural haematoma for whom a neurosurgeon sees no clear superiority for acute surgery over conservative treatment, initial conservative treatment might be considered.FUNDING: The Hersenstichting Nederland (also known as the Dutch Brain Foundation), the European Commission Seventh Framework Programme, the Hannelore Kohl Stiftung (Germany), OneMind (USA), Integra LifeSciences Corporation (USA), and NeuroTrauma Sciences (USA).
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40.
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41.
  • Wandell, PE, et al. (författare)
  • Psychic and socioeconomic consequences with diabetes compared to other chronic conditions
  • 1997
  • Ingår i: Scandinavian journal of social medicine. - : SAGE Publications. - 0300-8037. ; 25:1, s. 39-43
  • Tidskriftsartikel (refereegranskat)abstract
    • The present study relies on data for the years 1988 and 1989 from the Swedish continuous Surveys of Living Conditions (SLC), which are based on random samples from the population among individuals aged 16 through 84 years. We compared the rates of self-reported mental health for subjects reporting diabetes ( n = 361), a musculoskeletal condition but without diabetes ( n = 2187), hypertension but without diabetes ( n = 980), and healthy free from any medical condition ( n = 6654). Comparisons are based on age- and gender-standardized rates, using the diabetes group as standard. The results show that more diabetic respondents had psychic symptoms and long-standing psychiatric disorders than the healthy respondents, with otherwise no differences compared to the other chronic conditions. The diabetic respondents had lower mean disposable income, and a higher rate of disability pension than the respondents with hypertension, and than the healthy. They also reported more sick leave days than the healthy respondents.
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42.
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46.
  • Willy, R. W., et al. (författare)
  • Elevated Knee Joint Kinetics and Reduced Ankle Kinetics Are Present During Jogging and Hopping After Achilles Tendon Ruptures
  • 2017
  • Ingår i: American Journal of Sports Medicine. - : SAGE Publications. - 0363-5465 .- 1552-3365. ; 45:5, s. 1124-1133
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Deficits in plantarflexor function are common after an Achilles tendon rupture. These deficits may result in an altered distribution of joint loads during lower extremity tasks. Hypothesis: We hypothesized that, regardless of treatment, the Achilles tendon-ruptured limb would exhibit deficits in ankle kinematics and joint power while exhibiting elevated knee joint power and patellofemoral joint loads during walking, jogging, and hopping. We further hypothesized that this loading pattern would be most evident during jogging and hopping. Methods: Thirty-four participants (17 participants treated surgically, 17 treated nonsurgically) were tested at a mean 6.1 +/- 2.0 years after an Achilles tendon rupture. Lower extremity kinematics and kinetics were assessed while participants completed walking, jogging, and single-legged hopping trials. Patellofemoral joint stress was calculated via a musculoskeletal model. Data were analyzed via mixed-model repeated analyses of variance (alpha = .05) and the limb symmetry index (LSI). Results: No differences (P >= .05) were found between the surgical and nonsurgical groups. In both groups, large side-to-side deficits in the plantarflexion angle at toeoff (LSI: 53.5%-73.9%) were noted during walking, jogging, and hopping in the involved limb. Side-to-side deficits in the angular velocity were only present during jogging (LSI: 93.5%) and hopping (LSI: 92.5%). This pattern was accompanied by large deficits in eccentric (LSI: 80.8%-94.7%) and concentric (LSI: 82.2%-84.7%) ankle joint powers in the involved limb during all tasks. Interestingly, only jogging and hopping demonstrated greater knee joint loads when compared with the uninvolved limb. Concentric knee power was greater during jogging (LSI: 117.2%) and hopping (LSI: 115.9%) compared with the uninvolved limb. Similarly, peak patellofemoral joint stress was greater in the involved limb during jogging (LSI: 107.5%) and hopping (LSI: 107.1%), while only hopping had a greater loading rate of patellofemoral joint stress (LSI: 110.9%). Conclusion: Considerable side-to-side deficits in plantarflexor function were observed during walking, jogging, and hopping in patients after an Achilles tendon rupture. As a possible compensation, increased knee joint loads were present but only during jogging and hopping. Clinical Relevance: These data suggest that after an Achilles tendon rupture, patients may be susceptible to greater mechanical loading of the knee during sporting tasks, regardless of surgical or nonsurgical treatment.
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47.
  • Yuh, Esther L, et al. (författare)
  • Pathological computed tomography features associated with adverse outcomes after mild traumatic brain injury : A TRACK-TBI study with external validation in CENTER-TBI.
  • 2021
  • Ingår i: JAMA Neurology. - : American Medical Association (AMA). - 2168-6149 .- 2168-6157. ; 78:9, s. 1137-1148
  • Tidskriftsartikel (refereegranskat)abstract
    • IMPORTANCE: A head computed tomography (CT) with positive results for acute intracranial hemorrhage is the gold-standard diagnostic biomarker for acute traumatic brain injury (TBI). In moderate to severe TBI (Glasgow Coma Scale [GCS] scores 3-12), some CT features have been shown to be associated with outcomes. In mild TBI (mTBI; GCS scores 13-15), distribution and co-occurrence of pathological CT features and their prognostic importance are not well understood.OBJECTIVE: To identify pathological CT features associated with adverse outcomes after mTBI.DESIGN, SETTING, AND PARTICIPANTS: The longitudinal, observational Transforming Research and Clinical Knowledge in Traumatic Brain Injury (TRACK-TBI) study enrolled patients with TBI, including those 17 years and older with GCS scores of 13 to 15 who presented to emergency departments at 18 US level 1 trauma centers between February 26, 2014, and August 8, 2018, and underwent head CT imaging within 24 hours of TBI. Evaluations of CT imaging used TBI Common Data Elements. Glasgow Outcome Scale-Extended (GOSE) scores were assessed at 2 weeks and 3, 6, and 12 months postinjury. External validation of results was performed via the Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) study. Data analyses were completed from February 2020 to February 2021.EXPOSURES: Acute nonpenetrating head trauma.MAIN OUTCOMES AND MEASURES: Frequency, co-occurrence, and clustering of CT features; incomplete recovery (GOSE scores <8 vs 8); and an unfavorable outcome (GOSE scores <5 vs ≥5) at 2 weeks and 3, 6, and 12 months.RESULTS: In 1935 patients with mTBI (mean [SD] age, 41.5 [17.6] years; 1286 men [66.5%]) in the TRACK-TBI cohort and 2594 patients with mTBI (mean [SD] age, 51.8 [20.3] years; 1658 men [63.9%]) in an external validation cohort, hierarchical cluster analysis identified 3 major clusters of CT features: contusion, subarachnoid hemorrhage, and/or subdural hematoma; intraventricular and/or petechial hemorrhage; and epidural hematoma. Contusion, subarachnoid hemorrhage, and/or subdural hematoma features were associated with incomplete recovery (odds ratios [ORs] for GOSE scores <8 at 1 year: TRACK-TBI, 1.80 [95% CI, 1.39-2.33]; CENTER-TBI, 2.73 [95% CI, 2.18-3.41]) and greater degrees of unfavorable outcomes (ORs for GOSE scores <5 at 1 year: TRACK-TBI, 3.23 [95% CI, 1.59-6.58]; CENTER-TBI, 1.68 [95% CI, 1.13-2.49]) out to 12 months after injury, but epidural hematoma was not. Intraventricular and/or petechial hemorrhage was associated with greater degrees of unfavorable outcomes up to 12 months after injury (eg, OR for GOSE scores <5 at 1 year in TRACK-TBI: 3.47 [95% CI, 1.66-7.26]). Some CT features were more strongly associated with outcomes than previously validated variables (eg, ORs for GOSE scores <5 at 1 year in TRACK-TBI: neuropsychiatric history, 1.43 [95% CI .98-2.10] vs contusion, subarachnoid hemorrhage, and/or subdural hematoma, 3.23 [95% CI 1.59-6.58]). Findings were externally validated in 2594 patients with mTBI enrolled in the CENTER-TBI study.CONCLUSIONS AND RELEVANCE: In this study, pathological CT features carried different prognostic implications after mTBI to 1 year postinjury. Some patterns of injury were associated with worse outcomes than others. These results support that patients with mTBI and these CT features need TBI-specific education and systematic follow-up.
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