| 1. |
- Pennells, Lisa, et al.
(författare)
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Equalization of four cardiovascular risk algorithms after systematic recalibration : individual-participant meta-analysis of 86 prospective studies
- 2019
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Ingår i: European Heart Journal. - : Oxford University Press (OUP). - 0195-668X .- 1522-9645. ; 40:7, s. 621-
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Tidskriftsartikel (refereegranskat)abstract
- Aims: There is debate about the optimum algorithm for cardiovascular disease (CVD) risk estimation. We conducted head-to-head comparisons of four algorithms recommended by primary prevention guidelines, before and after ‘recalibration’, a method that adapts risk algorithms to take account of differences in the risk characteristics of the populations being studied.Methods and results: Using individual-participant data on 360 737 participants without CVD at baseline in 86 prospective studies from 22 countries, we compared the Framingham risk score (FRS), Systematic COronary Risk Evaluation (SCORE), pooled cohort equations (PCE), and Reynolds risk score (RRS). We calculated measures of risk discrimination and calibration, and modelled clinical implications of initiating statin therapy in people judged to be at ‘high’ 10 year CVD risk. Original risk algorithms were recalibrated using the risk factor profile and CVD incidence of target populations. The four algorithms had similar risk discrimination. Before recalibration, FRS, SCORE, and PCE over-predicted CVD risk on average by 10%, 52%, and 41%, respectively, whereas RRS under-predicted by 10%. Original versions of algorithms classified 29–39% of individuals aged ≥40 years as high risk. By contrast, recalibration reduced this proportion to 22–24% for every algorithm. We estimated that to prevent one CVD event, it would be necessary to initiate statin therapy in 44–51 such individuals using original algorithms, in contrast to 37–39 individuals with recalibrated algorithms.Conclusion: Before recalibration, the clinical performance of four widely used CVD risk algorithms varied substantially. By contrast, simple recalibration nearly equalized their performance and improved modelled targeting of preventive action to clinical need.
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| 2. |
- Hutchinson, Peter J, et al.
(författare)
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Consensus statement from the 2014 International Microdialysis Forum
- 2015
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Ingår i: Intensive Care Medicine. - : Springer Science and Business Media LLC. - 0342-4642 .- 1432-1238. ; 41:9, s. 1517-1528
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Tidskriftsartikel (refereegranskat)abstract
- Microdialysis enables the chemistry of the extracellular interstitial space to be monitored. Use of this technique in patients with acute brain injury has increased our understanding of the pathophysiology of several acute neurological disorders. In 2004, a consensus document on the clinical application of cerebral microdialysis was published. Since then, there have been significant advances in the clinical use of microdialysis in neurocritical care. The objective of this review is to report on the International Microdialysis Forum held in Cambridge, UK, in April 2014 and to produce a revised and updated consensus statement about its clinical use including technique, data interpretation, relationship with outcome, role in guiding therapy in neurocritical care and research applications.
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| 3. |
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| 4. |
- van der Harst, Pim, et al.
(författare)
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Seventy-five genetic loci influencing the human red blood cell
- 2012
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 492:7429, s. 369-375
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Tidskriftsartikel (refereegranskat)abstract
- Anaemia is a chief determinant of global ill health, contributing to cognitive impairment, growth retardation and impaired physical capacity. To understand further the genetic factors influencing red blood cells, we carried out a genome-wide association study of haemoglobin concentration and related parameters in up to 135,367 individuals. Here we identify 75 independent genetic loci associated with one or more red blood cell phenotypes at P < 10(-8), which together explain 4-9% of the phenotypic variance per trait. Using expression quantitative trait loci and bioinformatic strategies, we identify 121 candidate genes enriched in functions relevant to red blood cell biology. The candidate genes are expressed preferentially in red blood cell precursors, and 43 have haematopoietic phenotypes in Mus musculus or Drosophila melanogaster. Through open-chromatin and coding-variant analyses we identify potential causal genetic variants at 41 loci. Our findings provide extensive new insights into genetic mechanisms and biological pathways controlling red blood cell formation and function.
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| 5. |
- Baldvinsdóttir, Bryndís, et al.
(författare)
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Adverse events during endovascular treatment of ruptured aneurysms : A prospective nationwide study on subarachnoid hemorrhage in Sweden
- 2023
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Ingår i: BRAIN AND SPINE. - : Elsevier. - 2772-5294. ; 3
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: A range of adverse events (AEs) may occur in patients with subarachnoid hemorrhage (SAH). Endovascular treatment is commonly used to prevent aneurysm re-rupture.Research question: The aim of this study was to identify AEs related to endovascular treatment, analyze risk factors for AEs and how AEs affect patient outcome.Material and methods: Patients with aneurysmal SAH admitted to all neurosurgical centers in Sweden during a 3.5-year period (2014-2018) were prospectively registered. AEs related to endovascular aneurysm treatment were thromboembolic events, aneurysm re-rupture, vessel dissection and puncture site hematoma. Potential risk factors for the AEs were analyzed using multivariate logistic regression. Functional outcome was assessed at one year using the extended Glasgow outcome scale.Results: In total, 1037 patients were treated for ruptured aneurysms. Of which, 715 patients were treated with endovascular occlusion. There were 115 AEs reported in 113 patients (16%). Thromboembolic events were noted in 78 patients (11%). Aneurysm re-rupture occurred in 28 (4%), vessel dissection in 4 (0.6%) and puncture site hematoma in 5 (0.7%). Blister type aneurysm, aneurysm smaller than 5 mm and endovascular techniques other than coiling were risk factors for treatment-related AEs. At follow-up, 230 (32%) of the patients had unfavorable outcome. Patients suffering intraprocedural aneurysm re-rupture were more likely to have unfavorable outcome (OR 6.9, 95% CI 2.3-20.9).Discussion and conclusion: Adverse events related to endovascular occlusion of a ruptured aneurysm were seen in 16% of patients. Aneurysm re-rupture during endovascular treatment was associated with increased risk of unfavorable functional outcome.
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| 6. |
- Calling, Susanna, et al.
(författare)
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Lung function, respiratory symptoms and incident venous thromboembolism during a 44-year follow-up
- 2023
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Ingår i: Thrombosis Update. - Oxford : Elsevier. - 2666-5727. ; 12
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Tidskriftsartikel (refereegranskat)abstract
- Background: Chronic obstructive pulmonary disease (COPD) and infections are risk factors for venous thromboembolism (VTE), but the reasons behind the associations are not fully known. Few studies have investigated whether lung function and respiratory symptoms in individuals without COPD are associated with VTE. Objectives: To study the incidence of VTE in individuals without COPD and other major VTE risk factors, in relation to baseline lung function and respiratory symptoms, through a 44-year follow-up prospective cohort study. Methods: As part of a health screening program, a total of 20,253 men and 7361 women underwent a baseline examination from 1974 to 1992, including a spirometry test and a self-administered questionnaire about respiratory symptoms, e.g., chronic bronchitis, cough, phlegm, and dyspnoea. Lung function was assessed through quartiles of forced expiratory volume in 1 s/forced vital capacity (FEV1/FVC). Through linkage with national registers, all individuals were followed for incidence of VTE. Results: Respiratory symptoms (cough and dyspnoea) at baseline were associated with an increased risk of incident VTE in women after adjustments for age, height, BMI, smoking status, varicose veins, and FEV1/FVC. The adjusted hazard ratio in relation to chronic bronchitis was 1.57 (95% confidence interval 1.17–2.11). Poor lung function was not associated with an increased risk of VTE after adjustments for potential confounders. Conclusion: Women with respiratory symptoms of cough and dyspnoea without COPD have an increased risk of VTE, independent of lung function and major VTE risk factors. Further studies are needed to confirm the association and to study the clinical applicability of the results. © 2023 The Authors
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| 7. |
- Crespo, Alejandro J., et al.
(författare)
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On the state-of-the-art of CFD simulations for wave energy converters within the open-source numerical framework of DualSPHysics
- 2023
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Ingår i: Proceedings of the 15th European Wave and Tidal Energy Conference, Bilbao, 3-7 September 2023. - : European Wave and Tidal Energy Conference.
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Konferensbidrag (refereegranskat)abstract
- There are currently several types of devices capable of harnessing wave energy, exploiting a broad variety of physical transformation processes. These devices – known as Wave Energy Converters (WECs) – are developed to maximize their power output. However, there are still uncertainties about their response and survivability to loads induced by adverse environmental conditions, with a consequent increase of the Levelized Cost of Energy (LCOE), which prevents in fact their commercial diffusion. As evidenced by a large body of research, marine renewable energy devices need to have more robust design practices. To address this issue, we propose the CFD-based DualSPHysics toolbox as a support in the design stages. DualSPHysics is high-fidelity software inherently suited to numerically address most challenges posed by multiphysics simulations, which are required to reliably predict WEC response in situations well beyond operational conditions. It should be noted that WECs, generally, may be connected to the seabed and comprise mechanical systems named Power Take-Offs (PTO) used to convert the energy from waves into electricity or other usable energies. To reproduce these features, DualSPHysics benefits from coupling with the multiphysics library Project Chrono and the dynamic mooring model Moordyn+. In this work, the augmented DualSPHysics framework is utilised to simulate a range of very different types of WECs with a variety of elements, such as catenary connections, taut mooring lines, or linear and nonlinear PTO actuators. Version 5.2 of the open-source licensed code was recently released, making the numerical framework publicly available as one unit. This work aims to provide a numerical review of past applications, and to demonstrate how the same open-source code is able to simulate very different technologies.Specifically, this paper proposes routine modeling and validation procedures using the SPH-based solver DualSPHysics applied to five different WEC types: i) a moored point absorber (PA); ii) an oscillating wave surge converter (OWSC); iii) a floating OWSC (so called FOSWEC); iv) a wave energy hyperbaric converter (WEHC); and v) a multi-body attenuator (so called Multi-float M4). For each device listed above, we provide validation proof against physical model data for various components of the floater(s) and PTO related quantities, performed under specific sea conditions that aim to challenge their survivability. Within the scope of this research, we present the WEC response with respect to the degrees of freedom that really matter for each of the floatings due to hydrodynamic interactions (i.e., heave, surge, and pitch), along with quantities more intimately connected to the anchoring systems (e.g., line tension) or the mechanical apparatus (e.g., end-stopper force). The quality of the results, the discussion built upon them and the demonstrated solver exploitability to a wide range of WECs show that one software model can run all cases using the exact same methodology, which is of great value for the marine energy R&D community. Finally, we discuss future research objectives, which include the implementation of automation to apply open control systems and possible applications to subsets of WEC farm arrays and other floating energy harnessing devices.
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| 8. |
- Fagman, Johan Bourghardt, 1980, et al.
(författare)
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EGFR, but not COX-2, protein in resected pancreatic ductal adenocarcinoma is associated with poor survival.
- 2019
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Ingår i: Oncology letters. - : Spandidos Publications. - 1792-1074 .- 1792-1082. ; 17:6, s. 5361-5368
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Tidskriftsartikel (refereegranskat)abstract
- The effects of EGFR and COX-2 protein overexpression on clinical outcomes in pancreatic ductal adenocarcinoma (PDAC) patients remains unclear. Therefore, the aim of the present study was to evaluate the protein expression of epithelial growth factor receptor (EGFR) and cyclooxygenase-2 (COX-2) in tumor cells in surgically resected PDAC, in comparison with clinicopathological characteristics and clinical outcomes. Immunohistochemical staining of formalin-fixed paraffin-embedded tissue derived from surgically resected tumors was performed. Tissue slides were evaluated for membrane wild-type EGFR and cytoplasmic COX-2 staining using a histoscore system. Statistical associations between EGFR and COX-2 staining and clinicopathological characteristics were examined to predict survival. In a cohort of 32 resected PDAC patients, high EGFR protein expression in tumor cells was significantly associated with shorter median overall survival (7.9 vs. 39.2 months, P=0.0038). The corresponding hazard ratio (HR) for patients with high EGFR protein expression in tumor cells was 3.12 [95% confidence interval (CI): 1.39-7.00, P=0.006]. COX-2 protein expression was not associated with survival (22.6 vs. 24.5 months P=0.60; HR 1.22 95% CI: 0.59-2.51, P=0.60). Following multivariate Cox regression analysis, high EGFR protein expression in tumor cells (P=0.043) remained as significant independent prognostic factor for survival. In conclusion, high wild-type EGFR protein expression, but not COX-2 protein expression, in tumor cells is a prognostic factor for reduced overall survival following pancreatic tumor resection, supporting a role for EGFR in identifying resected patients that may benefit from EGFR-targeted therapy.
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| 9. |
- Fava, Cristiano, et al.
(författare)
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Cardiovascular consequences of a polygenetic component of blood pressure in an urban-based longitudinal study: the Malmö Diet and Cancer.
- 2014
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Ingår i: Journal of Hypertension. - 1473-5598. ; 32:7, s. 1424-1428
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Tidskriftsartikel (refereegranskat)abstract
- A recently published genome wide association study identified 29 single nucleotide polymorphisms (SNPs) influencing blood pressure (BP). Case-control studies suggest that a genetic risk score (GRS) based on these 29 SNPs affect the risk of cardiovascular disease (CVD), but its role for CVD at population level is unknown. Here, we prospectively evaluate the impact of this polygenetic BP component on CVD morbidity and mortality in a large urban-based middle-aged population.
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| 10. |
- Fava, Cristiano, et al.
(författare)
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Prediction of Blood Pressure Changes Over Time and Incidence of Hypertension by a Genetic Risk Score in Swedes.
- 2012
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Ingår i: Hypertension. - 1524-4563.
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Tidskriftsartikel (refereegranskat)abstract
- Recent Genome-Wide Association Studies (GWAS) have pinpointed different single nucleotide polymorphisms consistently associated with blood pressure (BP) and hypertension prevalence. However, little data exist regarding single nucleotide polymorphisms predicting BP variation over time and hypertension incidence. The aim of this study was to confirm the association of a genetic risk score (GRS), based on 29 independent single nucleotide polymorphisms, with cross-sectional BP and hypertension prevalence and to challenge its prediction of BP change over time and hypertension incidence in >17 000 middle-aged Swedes participating in a prospective study, the Malmö Preventive Project, investigated at baseline and over a 23-year average period of follow-up. The GRS was associated with higher systolic and diastolic BP values both at baseline (β±SEM, 0.968±0.102 mm Hg and 0.585±0.064 mm Hg; P<1E-19 for both) and at reinvestigation (β±SEM, 1.333±0.161 mm Hg and 0.724±0.086 mm Hg; P<1E-15 for both) and with increased hypertension prevalence (odds ratio [95% CI], 1.192 [1.140-1.245] and 1.144 [1.107-1.183]; P<1E-15 for both). The GRS was positively associated with change (Δ) in BP (β±SEM, 0.033±0.008 mm Hg/y and 0.023±0.004 mm Hg/y; P<1E-04 for both) and hypertension incidence (odds ratio [95% CI], 1.110 [1.065-1.156]; P=6.7 E-07), independently from traditional risk factors. The relative weight of the GRS was lower in magnitude than obesity or prehypertension, but comparable with diabetes mellitus or a positive family history of hypertension. A C-statistics analysis does not show any improvement in the prediction of incident hypertension on top of traditional risk factors. Our data from a large cohort study show that a GRS is independently associated with BP increase and incidence of hypertension.
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