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Sökning: WFRF:(Eriksson Bengt I.) > Forskningsöversikt

  • Resultat 1-4 av 4
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1.
  • Eriksson, Ulf G, et al. (författare)
  • Pharmacokinetics of melagatran and the effect on ex vivo coagulation time in orthopaedic surgery patients receiving subcutaneous melagatran and oral ximelagatran : a population model analysis
  • 2003
  • Ingår i: Clinical Pharmacokinetics. - 0312-5963 .- 1179-1926. ; 42:7, s. 687-701
  • Forskningsöversikt (refereegranskat)abstract
    • OBJECTIVE: Ximelagatran, an oral direct thrombin inhibitor, is rapidly bioconverted to melagatran, its active form. The objective of this population analysis was to characterise the pharmacokinetics of melagatran and its effect on activated partial thromboplastin time (APTT), an ex vivo measure of coagulation time, in orthopaedic surgery patients sequentially receiving subcutaneous melagatran and oral ximelagatran as prophylaxis for venous thromboembolism. To support the design of a pivotal dose-finding study, the impact of individualised dosage based on bodyweight and calculated creatinine clearance was examined. DESIGN AND METHODS: Pooled data obtained in three small dose-guiding studies were analysed. The patients received twice-daily administration, with either subcutaneous melagatran alone or a sequential regimen of subcutaneous melagatran followed by oral ximelagatran, for 8-11 days starting just before initiation of surgery. Nonlinear mixed-effects modelling was used to evaluate rich data of melagatran pharmacokinetics (3326 observations) and the pharmacodynamic effect on APTT (2319 observations) in samples from 216 patients collected in the three dose-guiding trials. The pharmacokinetic and pharmacodynamic models were validated using sparse data collected in a subgroup of 319 patients enrolled in the pivotal dose-finding trial. The impact of individualised dosage on pharmacokinetic and pharmacodynamic variability was evaluated by simulations of the pharmacokinetic-pharmacodynamic model. RESULTS: The pharmacokinetics of melagatran were well described by a one-compartment model with first-order absorption after both subcutaneous melagatran and oral ximelagatran. Melagatran clearance was correlated with renal function, assessed as calculated creatinine clearance. The median population clearance (creatinine clearance 70 mL/min) was 5.3 and 22.9 L/h for the subcutaneous and oral formulations, respectively. The bioavailability of melagatran after oral ximelagatran relative to subcutaneous melagatran was 23%. The volume of distribution was influenced by bodyweight. For a patient with a bodyweight of 75kg, the median population estimates were 15.5 and 159L for the subcutaneous and oral formulations, respectively. The relationship between APTT and melagatran plasma concentration was well described by a power function, with a steeper slope during and early after surgery but no influence by any covariates. Simulations demonstrated that individualised dosage based on creatinine clearance or bodyweight had no clinically relevant impact on the variability in melagatran pharmacokinetics or on the effect on APTT. CONCLUSIONS: The relatively low impact of individualised dosage on the pharmacokinetic and pharmacodynamic variability of melagatran supported the use of a fixed-dose regimen in the studied population of orthopaedic surgery patients, including those with mild to moderate renal impairment.
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2.
  • Aad, G., et al. (författare)
  • The ATLAS Experiment at the CERN Large Hadron Collider
  • 2008
  • Ingår i: Journal of Instrumentation. - 1748-0221. ; 3:S08003
  • Forskningsöversikt (refereegranskat)abstract
    • The ATLAS detector as installed in its experimental cavern at point 1 at CERN is described in this paper. A brief overview of the expected performance of the detector when the Large Hadron Collider begins operation is also presented.
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3.
  • Halme, P., et al. (författare)
  • Challenges of ecological restoration : Lessons from forests in northern Europe
  • 2013
  • Ingår i: Biological Conservation. - : Elsevier BV. - 0006-3207 .- 1873-2917. ; 167, s. 248-256
  • Forskningsöversikt (refereegranskat)abstract
    • The alarming rate of ecosystem degradation has raised the need for ecological restoration throughout different biomes and continents. North European forests may appear as one of the least vulnerable ecosystems from a global perspective, since forest cover is not rapidly decreasing and many ecosystem services remain at high level. However, extensive areas of northern forests are heavily exploited and have lost a major part of their biodiversity value. There is a strong requirement to restore these areas towards a more natural condition in order to meet the targets of the Convention on Biological Diversity. Several northern countries are now taking up this challenge by restoring forest biodiversity with increasing intensity. The ecology and biodiversity of boreal forests are relatively well understood making them a good model for restoration activities in many other forest ecosystems. Here we introduce northern forests as an ecosystem, discuss the historical and recent human impact and provide a brief status report on the ecological restoration projects and research already conducted there. Based on this discussion, we argue that before any restoration actions commence, the ecology of the target ecosystem should be established with the need for restoration carefully assessed and the outcome properly monitored. Finally, we identify the most important challenges that need to be solved in order to carry out efficient restoration with powerful and long-term positive impacts on biodiversity: coping with unpredictability, maintaining connectivity in time and space, assessment of functionality, management of conflicting interests and social restrictions and ensuring adequate funding. © 2013 Elsevier Ltd.
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4.
  • Nilsson-Helander, Katarina, 1957, et al. (författare)
  • Individualiserad behandling viktig vid akut hälseneruptur. : Individualized treatment important in acute Achilles tendon ruptures
  • 2014
  • Ingår i: Läkartidningen. - 0023-7205. ; 111:34-35
  • Forskningsöversikt (refereegranskat)abstract
    • An acute Achilles tendon rupture is a common sports-related injury in middle-aged men. The diagnosis is always clinical and it is very important that the diagnosis is not missed or delayed. The time period for tendon healing and rehabilitation is long and commonly results in functional deficits. Only half of the patients return to the preinjury lev-el of physical activity. There is no consensus in terms of the optimal treatment for patients with acute Achilles tendon rupture. Both surgical and non-surgical treatment with modern rehabilitation protocols are valid alternatives in the clinical day-by-day work. There is a need for future studies to optimize the treatment and identify predictors in order to individualize the optimal treatment.
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  • Resultat 1-4 av 4

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