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Sökning: WFRF:(Peltola J.)

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1.
  • Aad, G, et al. (författare)
  • 2015
  • swepub:Mat__t
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3.
  • Sliz, E., et al. (författare)
  • Evidence of a causal effect of genetic tendency to gain muscle mass on uterine leiomyomata
  • 2023
  • Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 14:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Uterine leiomyomata (UL) are the most common tumours of the female genital tract and the primary cause of surgical removal of the uterus. Genetic factors contribute to UL susceptibility. To add understanding to the heritable genetic risk factors, we conduct a genome-wide association study (GWAS) of UL in up to 426,558 European women from FinnGen and a previous UL meta-GWAS. In addition to the 50 known UL loci, we identify 22 loci that have not been associated with UL in prior studies. UL-associated loci harbour genes enriched for development, growth, and cellular senescence. Of particular interest are the smooth muscle cell differentiation and proliferation-regulating genes functioning on the myocardin-cyclin dependent kinase inhibitor 1A pathway. Our results further suggest that genetic predisposition to increased fat-free mass may be causally related to higher UL risk, underscoring the involvement of altered muscle tissue biology in UL pathophysiology. Overall, our findings add to the understanding of the genetic pathways underlying UL, which may aid in developing novel therapeutics.
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4.
  • Tabassum, R, et al. (författare)
  • Genetic architecture of human plasma lipidome and its link to cardiovascular disease
  • 2019
  • Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 10:1, s. 4329-
  • Tidskriftsartikel (refereegranskat)abstract
    • Understanding genetic architecture of plasma lipidome could provide better insights into lipid metabolism and its link to cardiovascular diseases (CVDs). Here, we perform genome-wide association analyses of 141 lipid species (n = 2,181 individuals), followed by phenome-wide scans with 25 CVD related phenotypes (n = 511,700 individuals). We identify 35 lipid-species-associated loci (P <5 ×10−8), 10 of which associate with CVD risk including five new loci-COL5A1, GLTPD2, SPTLC3, MBOAT7 and GALNT16 (false discovery rate<0.05). We identify loci for lipid species that are shown to predict CVD e.g., SPTLC3 for CER(d18:1/24:1). We show that lipoprotein lipase (LPL) may more efficiently hydrolyze medium length triacylglycerides (TAGs) than others. Polyunsaturated lipids have highest heritability and genetic correlations, suggesting considerable genetic regulation at fatty acids levels. We find low genetic correlations between traditional lipids and lipid species. Our results show that lipidomic profiles capture information beyond traditional lipids and identify genetic variants modifying lipid levels and risk of CVD.
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5.
  • Brasseur, Z., et al. (författare)
  • Measurement report: Introduction to the HyICE-2018 campaign for measurements of ice-nucleating particles and instrument inter-comparison in the Hyytiala boreal forest
  • 2022
  • Ingår i: Atmospheric Chemistry and Physics. - : Copernicus GmbH. - 1680-7316 .- 1680-7324. ; 22:8, s. 5117-5145
  • Tidskriftsartikel (refereegranskat)abstract
    • The formation of ice particles in Earth's atmosphere strongly influences the dynamics and optical properties of clouds and their impacts on the climate system. Ice formation in clouds is often triggered heterogeneously by ice-nucleating particles (INPs) that represent a very low number of particles in the atmosphere. To date, many sources of INPs, such as mineral and soil dust, have been investigated and identified in the low and mid latitudes. Although less is known about the sources of ice nucleation at high latitudes, efforts have been made to identify the sources of INPs in the Arctic and boreal environments. In this study, we investigate the INP emission potential from high-latitude boreal forests in the mixed-phase cloud regime. We introduce the HyICE-2018 measurement campaign conducted in the boreal forest of Hyytiala, Finland, between February and June 2018. The campaign utilized the infrastructure of the Station for Measuring Ecosystem-Atmosphere Relations (SMEAR) II, with additional INP instruments, including the Portable Ice Nucleation Chamber I and II (PINC and PINCii), the SPectrometer for Ice Nuclei (SPIN), the Portable Ice Nucleation Experiment (PINE), the Ice Nucleation SpEctrometer of the Karlsruhe Institute of Technology (INSEKT) and the Microlitre Nucleation by Immersed Particle Instrument (mu L-NIPI), used to quantify the INP concentrations and sources in the boreal environment. In this contribution, we describe the measurement infrastructure and operating procedures during HyICE-2018, and we report results from specific time periods where INP instruments were run in parallel for inter-comparison purposes. Our results show that the suite of instruments deployed during HyICE-2018 reports consistent results and therefore lays the foundation for forthcoming results to be considered holistically. In addition, we compare measured INP concentrations to INP parameterizations, and we observe good agreement with the Tobo et al. (2013) parameterization developed from measurements conducted in a ponderosa pine forest ecosystem in Colorado, USA.
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  • Alam, Md. Minhaj, et al. (författare)
  • Analysis of the stress raising action of flaws in laser clad deposits
  • 2013
  • Ingår i: Materials and Design. - : Elsevier BV. - 0261-3069 .- 0264-1275 .- 1873-4197. ; 46, s. 328-337
  • Tidskriftsartikel (refereegranskat)abstract
    • Fatigue cracking of laser clad cylindrical and square section bars depends upon a variety of factors. This paper presents Finite Element Analysis (FEA) of the different macro stress fields generated as well as stress raisers created by laser cladding defects for four different fatigue load conditions. As important as the defect types are their locations and orientations, categorized into zero-, one- and two-dimensional defects. Pores and inclusions become critical close to surfaces. The performance of as-clad surfaces can be governed by the sharpness of surface notches and planar defects like hot cracks or lack-of-fusion (LOF) are most critical if oriented vertically, transverse to the bar axis. The combination of the macro stress field with the defect type and its position and orientation determines whether it is the most critical stress raiser. Based on calculated cases, quantitative and qualitative charts were developed as guidelines to visualize the trends of different combinations.
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8.
  • Kaplan, Alexander, et al. (författare)
  • Stress raising in laser clad components depending on geometry and defects
  • 2013
  • Ingår i: 14th NOLAMP Conference. - Luleå : Luleå tekniska universitet. - 9789174396881 - 9789174396898 ; , s. 281-292
  • Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
    • The fatigue life of laser clad components is basically determined by stress raisers, which arehere studied by Finite Element Analysis. Cylindrical and square section bars are compared foraxial, bending and torsional load conditions, which induces the macro-stress field withcorresponding stress peaks. Defects from laser cladding such as pores, cracks or the surfaceroughness superimpose additional stress raising action on this stress field. The geometricalposition and orientation of the defects has strong impact on the induced maximum stresslevel. For surface pores it is demonstrated by the fractography that their occurrence within acritical azimuthal range can initiate fatigue cracking. The different conditions of samplegeometry, load situations, materials and defects are compared and discussed. In particular,advanced illustration methods are applied for improved and generalized documentation andexplanation of the trends, both qualitatively and quantitatively. Guidelines are presented, inparticular emphasizing critical defects and situations, such as surface pores that are difficult todetect because of inclusions, or pores just underneath the surface that generate particularlyhigh stress.
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9.
  • Franz, D, et al. (författare)
  • Towards long-term standardised carbon and greenhouse gas observations for monitoring Europe´s terrestrial ecosystems: a review
  • 2018
  • Ingår i: International Agrophysics. - : Walter de Gruyter GmbH. - 0236-8722 .- 2300-8725. ; 32, s. 439-455
  • Tidskriftsartikel (refereegranskat)abstract
    • Research infrastructures play a key role in launching a new generation of integrated long-term, geographically distributed observation programmes designed to monitor climate change, better understand its impacts on global ecosystems, and evaluate possible mitigation and adaptation strategies. The pan-European Integrated Carbon Observation System combines carbon and greenhouse gas (GHG; CO2, CH4, N2O, H2O) observations within the atmosphere, terrestrial ecosystems and oceans. High-precision measurements are obtained using standardised methodologies, are centrally processed and openly available in a traceable and verifiable fashion in combination with detailed metadata. The Integrated Carbon Observation System ecosystem station network aims to sample climate and land-cover variability across Europe. In addition to GHG flux measurements, a large set of complementary data (including management practices, vegetation and soil characteristics) is collected to support the interpretation, spatial upscaling and modelling of observed ecosystem carbon and GHG dynamics. The applied sampling design was developed and formulated in protocols by the scientific community, representing a trade-off between an ideal dataset and practical feasibility. The use of open-access, high-quality and multi-level data products by different user communities is crucial for the Integrated Carbon Observation System in order to achieve its scientific potential and societal value.
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10.
  • Tuominen, J., et al. (författare)
  • Fatigue behavior of laser clad round steel bars
  • 2015
  • Ingår i: Journal of laser applications. - : Laser Institute of America. - 1042-346X .- 1938-1387. ; 27:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Laser cladding is an overlay welding method to manufacture high performance, fusion bonded metal, and metal matrix composite coatings on metallic substrates with low dilution. Owing to steep thermal gradients, rapid solidification, and possible mismatch in coefficients of thermal expansion between the coating and the substrate, laser cladding induces large tensile residual stresses in coating layer, potentially affecting the service life of clad component under external load-induced stresses. In this study, four-point bending and torsion fatigue tests were conducted on relatively large round laser clad steel bars to determine the effect of laser cladding on fatigue strength. Quenched and tempered 42CrMo4 steel clad with Inconel 625 and S355 structural steel clad with Stellite 21 were subjected to various stress levels for relatively large number of cycles with and without postweld heat treatment (PWHT). The results indicated that Stellite 21 decreased the fatigue life of S355 at all the applied loads, whereas Inconel 625 increased the fatigue life of 42CrMo4 at high loads but decreased at low loads. Applied PWHT did not show any positive influence on fatigue life.
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11.
  • Alam, Md. Minhaj, et al. (författare)
  • Surface pore initiated fatigue failure in laser clad components
  • 2013
  • Ingår i: Journal of laser applications. - : Laser Institute of America. - 1042-346X .- 1938-1387. ; 25:3
  • Tidskriftsartikel (refereegranskat)abstract
    • A laser clad and machined cylindrical structural steel rod was fatigue tested under four-point bending load. The resulting fracture could be tracked back to a spherical surface pore in the Co-based coating. Due to an oxide inclusion, the pore was not identified by dye penetrant inspection. Two circular buckling strain patterns that were detected beside the pore at the surfaces after fracture confirm local plastic deformation prior to crack initiation. In order to calculate the stress field around the surface pore, linear elastic finite element analysis was carried out. For four-point bending load, a surface pore generally exceeds the maximum stress of a smooth rod as long as the pore is located within an azimuthal angle of ±55°, which was the case for the presented as well as for another pore initiated sample.
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  • Gupta, A., et al. (författare)
  • A four-kallikrein panel for the prediction of repeat prostate biopsy: data from the European Randomized Study of Prostate Cancer Screening in Rotterdam, Netherlands
  • 2010
  • Ingår i: British Journal of Cancer. - : Springer Science and Business Media LLC. - 1532-1827 .- 0007-0920. ; 103:5, s. 708-714
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Most men with elevated levels of prostate-specific antigen (PSA) do not have prostate cancer, leading to a large number of unnecessary biopsies. A statistical model based on a panel of four kallikreins has been shown to predict the outcome of a first prostate biopsy. In this study, we apply the model to an independent data set of men with previous negative biopsy but persistently elevated PSA. METHODS: The study cohort consisted of 925 men with a previous negative prostate biopsy and elevated PSA (>= 3 ngml(-1)), with 110 prostate cancers detected (12%). A previously published statistical model was applied, with recalibration to reflect the lower positive biopsy rates on rebiopsy. RESULTS: The full-kallikrein panel had higher discriminative accuracy than PSA and DRE alone, with area under the curve (AUC) improving from 0.58 (95% confidence interval (CI): 0.52, 0.64) to 0.68 (95% CI: 0.62, 0.74), P<0.001, and high-grade cancer (Gleason >= 7) at biopsy with AUC improving from 0.76 (95% CI: 0.64, 0.89) to 0.87 (95% CI: 0.81, 0.94), P 0.003). Application of the panel to 1000 men with persistently elevated PSA after initial negative biopsy, at a 15% risk threshold would reduce the number of biopsies by 712; would miss (or delay) the diagnosis of 53 cancers, of which only 3 would be Gleason 7 and the rest Gleason 6 or less. CONCLUSIONS: Our data constitute an external validation of a previously published model. The four-kallikrein panel predicts the result of repeat prostate biopsy in men with elevated PSA while dramatically decreasing unnecessary biopsies. British Journal of Cancer (2010) 103, 708-714. doi:10.1038/sj.bjc.6605815 www.bjcancer.com Published online 27 July 2010 (C) 2010 Cancer Research UK
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  • Peltola, J., et al. (författare)
  • Easurement of solids velocity and concentration in a large cold CFB model
  • 2014
  • Ingår i: 11th International Conference on Fluidized Bed Technology, CFB 2014; Beijing; China; 14 May 2014 through 17 May 2014. ; , s. 589-594
  • Konferensbidrag (refereegranskat)abstract
    • This work applies optical probe and particle image velocimetry (PIV) measurements for determining the local characteristics of the solids flow in a CFB riser and discusses benefits and limitations of the two methods. Measurements were carried out in an 8.5 m tall CFB riser with a cross-section of 0.7 m x 0.12 m. The optical probe was used to measure both solids volume fraction and velocity whereas the PIV was limited to solids velocity measurements. In addition, the vertical pressure profile and solids circulation rate were measured by means of pressure transducers. The work demonstrates the challenge of applying detailed solids flow measurements in CFB reactors. Both methods applied are associated with limitations and inaccuracies and it is concluded that a combination of both local measurement methods and the global pressure measurements will improve the interpretation of the solids flow field in CFB risers.
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  • Vickers, Andrew J., et al. (författare)
  • A Four-Kallikrein Panel Predicts Prostate Cancer in Men with Recent Screening: Data from the European Randomized Study of Screening for Prostate Cancer, Rotterdam
  • 2010
  • Ingår i: Clinical Cancer Research. - 1078-0432. ; 16:12, s. 3232-3239
  • Tidskriftsartikel (refereegranskat)abstract
    • Purpose: We have developed a statistical prediction model for prostate cancer based on four kallikrein markers in blood: total, free, and intact prostate-specific antigen ( PSA), and kallikrein-related peptidase 2 ( hK2). Although this model accurately predicts the result of biopsy in unscreened men, its properties for men with a history of PSA screening have not been fully characterized. Experimental Design: A total of 1,501 previously screened men with elevated PSA underwent initial biopsy during rounds 2 and 3 of the European Randomized Study of Screening for Prostate Cancer, Rotterdam, with 388 cancers diagnosed. Biomarker levels were measured in serum samples taken before biopsy. The prediction model developed on the unscreened cohort was then applied and predictions compared with biopsy outcome. Results: The previously developed four-kallikrein prediction model had much higher predictive accuracy than PSA and age alone ( area under the curve of 0.711 versus 0.585, and 0.713 versus 0.557 with and without digital rectal exam, respectively; both P < 0.001). Similar statistically significant enhancements were seen for high-grade cancer. Applying the model with a cutoff of 20% cancer risk as the criterion for biopsy would reduce the biopsy rate by 362 for every 1,000 men with elevated PSA. Although diagnosis would be delayed for 47 cancers, these would be predominately low-stage and low-grade ( 83% Gleason 6 T-1c). Conclusions: A panel of four kallikreins can help predict the result of initial biopsy in previously screened men with elevated PSA. Use of a statistical model based on the panel would substantially decrease rates of unnecessary biopsy. Clin Cancer Res; 16( 12); 3232-9. (C)2010 AACR.
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  • Bicak, Mesude, et al. (författare)
  • Genetic signature of prostate cancer mouse models resistant to optimized hK2 targeted α-particle therapy
  • 2020
  • Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 1091-6490. ; 117:26, s. 15172-15181
  • Tidskriftsartikel (refereegranskat)abstract
    • Hu11B6 is a monoclonal antibody that internalizes in cells expressing androgen receptor (AR)-regulated prostate-specific enzyme human kallikrein-related peptidase 2 (hK2; KLK2). In multiple rodent models, Actinium-225-labeled hu11B6-IgG1 ([225Ac]hu11B6-IgG1) has shown promising treatment efficacy. In the present study, we investigated options to enhance and optimize [225Ac]hu11B6 treatment. First, we evaluated the possibility of exploiting IgG3, the IgG subclass with superior activation of complement and ability to mediate FC-γ-receptor binding, for immunotherapeutically enhanced hK2 targeted α-radioimmunotherapy. Second, we compared the therapeutic efficacy of a single high activity vs. fractionated activity. Finally, we used RNA sequencing to analyze the genomic signatures of prostate cancer that progressed after targeted α-therapy. [225Ac]hu11B6-IgG3 was a functionally enhanced alternative to [225Ac]hu11B6-IgG1 but offered no improvement of therapeutic efficacy. Progression-free survival was slightly increased with a single high activity compared to fractionated activity. Tumor-free animals succumbing after treatment revealed no evidence of treatment-associated toxicity. In addition to up-regulation of canonical aggressive prostate cancer genes, such as MMP7, ETV1, NTS, and SCHLAP1, we also noted a significant decrease in both KLK3 (prostate-specific antigen ) and FOLH1 (prostate-specific membrane antigen) but not in AR and KLK2, demonstrating efficacy of sequential [225Ac]hu11B6 in a mouse model.
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20.
  • Carlsson, Sigrid V., et al. (författare)
  • Can one blood draw replace transrectal ultrasonography-estimated prostate volume to predict prostate cancer risk?
  • 2013
  • Ingår i: BJU International. - 1464-4096 .- 1464-410X. ; 112:5, s. 602-609
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective To explore whether a panel of kallikrein markers in blood: total, free and intact prostate-specific antigen (PSA) and kallikrein-related peptidase 2, could be used as a non-invasive alternative for predicting prostate cancer on biopsy in a screening setting. Subjects and Methods The study cohort comprised previously unscreened men who underwent sextant biopsy owing to elevated PSA (3 ng/mL) in two different centres of the European Randomized Study of Screening for Prostate Cancer, Rotterdam (n = 2914) and Gteborg (n = 740). A statistical model, based on kallikrein markers, was compared with one based on established clinical factors for the prediction of biopsy outcome. Results The clinical tests were found to be no better than blood markers, with an area under the curve in favour of the blood measurements of 0.766 vs. 0.763 in Rotterdam and 0.809 vs. 0.774 in Gteborg. Adding digital rectal examination (DRE) or DRE plus transrectal ultrasonography (TRUS) volume to the markers improved discrimination, although the increases were small. Results were similar for predicting high-grade cancer. There was a strong correlation between the blood measurements and TRUS-estimated prostate volume (Spearman's correlation 0.60 in Rotterdam and 0.57 in Gteborg). Conclusions In previously unscreened men, each with indication for biopsy, a statistical model based on kallikrein levels was similar to a clinical model in predicting prostate cancer in a screening setting, outside the day-to-day clinical practice. Whether a clinical approach can be replaced by laboratory analyses or used in combination with decision models (nomograms) is a clinical judgment that may vary from clinician to clinician depending on how they weigh the different advantages and disadvantages (harms, costs, time, invasiveness) of both approaches.
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21.
  • Forslund, Tommie, et al. (författare)
  • Attachment goes to court : child protection and custody issues
  • 2022
  • Ingår i: Attachment & Human Development. - : Taylor & Francis Group. - 1461-6734 .- 1469-2988. ; 24:1, s. 1-52
  • Tidskriftsartikel (refereegranskat)abstract
    • Attachment theory and research are drawn upon in many applied settings, including family courts, but misunderstandings are widespread and sometimes result in misapplications. The aim of this consensus statement is, therefore, to enhance understanding, counter misinformation, and steer family-court utilisation of attachment theory in a supportive, evidence-based direction, especially with regard to child protection and child custody decision-making. The article is divided into two parts. In the first, we address problems related to the use of attachment theory and research in family courts, and discuss reasons for these problems. To this end, we examine family court applications of attachment theory in the current context of the best-interest-of-the-child standard, discuss misunderstandings regarding attachment theory, and identify factors that have hindered accurate implementation. In the second part, we provide recommendations for the application of attachment theory and research. To this end, we set out three attachment principles: the child’s need for familiar, non-abusive caregivers; the value of continuity of good-enough care; and the benefits of networks of attachment relationships. We also discuss the suitability of assessments of attachment quality and caregiving behaviour to inform family court decision-making. We conclude that assessments of caregiver behaviour should take center stage. Although there is dissensus among us regarding the use of assessments of attachment quality to inform child custody and child-protection decisions, such assessments are currently most suitable for targeting and directing supportive interventions. Finally, we provide directions to guide future interdisciplinary research collaboration.
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22.
  • Forslund, Tommie, et al. (författare)
  • El Apego Va a Juicio: Problemas de Custodia y Protección Infantil : [Attachment goes to court: Child protection and custody issues]
  • 2021
  • Ingår i: Anuario de psicología jurídica. - : Colegio Oficial de la Psicologia de Madrid. - 1133-0740 .- 2174-0542. ; 32:1, s. 115-139
  • Tidskriftsartikel (refereegranskat)abstract
    • Attachment theory and research are drawn upon in many applied settings, including family courts, but misunderstandings are widespread and sometimes result in misapplications. The aim of this consensus statement is, therefore, to enhance understanding, counter misinformation, and steer family-court utilisation of attachment theory in a supportive, evidence-based direction, especially with regard to child protection and child custody decision-making. This article is divided into two parts. In the first part, we address problems related to the use of attachment theory and research in family courts, and discuss reasons for these problems. To this end, we examine family court applications of attachment theory in the current context of the best-interest-of-the-child standard, discuss misunderstandings regarding attachment theory, and identify factors that have hindered accurate implementation. In the second part, we provide recommendations for the application of attachment theory and research. To this end, we set out three attachment principles: the child's need for familiar, non-abusive caregivers; the value of continuity of good-enough care; and the benefits of networks of attachment relationships. We also discuss the suitability of assessments of attachment quality and caregiving behaviour to inform family court decision-making. We conclude that assessments of caregiver behaviour should take center stage. Although there is dissensus among us regarding the use of assessments of attachment quality to inform child custody and child-protection decisions, such assessments are currently most suitable for targeting and directing supportive interventions. Finally, we provide directions to guide future interdisciplinary research collaboration.
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  • Shorvon, S. D., et al. (författare)
  • Eslicarbazepine acetate: its effectiveness as adjunctive therapy in clinical trials and open studies
  • 2017
  • Ingår i: Journal of Neurology. - : Springer Science and Business Media LLC. - 0340-5354 .- 1432-1459. ; 264:3, s. 421-431
  • Forskningsöversikt (refereegranskat)abstract
    • Eslicarbazepine acetate (ESL) is a once-daily antiepileptic drug that is approved as adjunctive therapy in adults with focal-onset seizures. Following oral administration, ESL is rapidly metabolized to its active metabolite, eslicarbazepine, which acts primarily by enhancing slow inactivation of voltage-gated sodium channels. The efficacy and safety/tolerability of ESL in the adjunctive setting were established in a comprehensive Phase III program (n = 1702 randomized patients) and this evidence has been supported by several open studies (n = 864). ESL treatment has demonstrated improvements in health-related quality of life, in both randomized clinical trials and open studies. ESL has also been shown to be usually well tolerated and efficacious when used in the adjunctive setting in elderly patients. The effectiveness of ESL as the only add-on to antiepileptic drug monotherapy has been demonstrated in a multinational study (n = 219), subgroup analyses of which have also shown it to be efficacious and generally well tolerated in patients who had previously not responded to carbamazepine therapy. Open studies have also demonstrated improvements in tolerability in patients switched overnight from oxcarbazepine to ESL. Due to differences in pharmacokinetics, pharmacodynamics, and metabolism, there may be clinical situations in which it is appropriate to consider switching patients from oxcarbazepine or carbamazepine to ESL.
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