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Sökning: WFRF:(Herrmann Joerg) > Karolinska Institutet

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1.
  • Borg, Jorgen, et al. (författare)
  • RATIONALE AND DESIGN OF A MULTICENTRE, DOUBLE-BLIND, PROSPECTIVE, RANDOMIZED, EUROPEAN AND CANADIAN STUDY: EVALUATING PATIENT OUTCOMES AND COSTS OF MANAGING ADULTS WITH POST-STROKE FOCAL SPASTICITY
  • 2011
  • Ingår i: JOURNAL OF REHABILITATION MEDICINE. - : Foundation for Rehabilitation Information. - 1650-1977 .- 1651-2081. ; 43:1, s. 15-22
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective: This report describes the design of a study aiming to provide evidence for the extended use of botulinum toxin A (BOTOX(R), Allergan Inc.) in focal post-stroke upper and lower limb spasticity and to evaluate the impact of incorporating botulinum toxin A treatment into the rehabilitation of patients with spasticity. Design: International, prospective, randomized, double-blind, placebo-controlled study with an open-label extension. Methods: Approximately 300 adults with a stroke occurring 23 months before screening, presenting with symptoms and signs of an upper motor neuron syndrome and focal spasticity-related functional impairment, were randomized to botulinum toxin A+standard care or placebo+standard care. Study medication was administered at baseline and again at Week 12 if required, with follow-up to 52 weeks. The primary endpoint was the number of patients who achieved their investigator-rated principal active functional goal (as measured by Goal Attainment Scaling), at 10 weeks after the second injection (Weeks 22-34) or at the 24-week visit if no second injection was administered. Secondary endpoints included changes from baseline in level of goal achievement, health-related quality of life and resource utilization. Conclusion: The BOTOX(R) Economic Spasticity Trial (BEST) will provide information regarding clinical and cost-effectiveness of botulinum toxin+standard care vs standard care alone in patients with upper and/or lower limb post-stroke spasticity typically seen in clinical practice.
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2.
  • Forteza, Maria J., et al. (författare)
  • Pyruvate dehydrogenase kinase regulates vascular inflammation in atherosclerosis and increases cardiovascular risk
  • 2023
  • Ingår i: Cardiovascular Research. - : Oxford University Press (OUP). - 0008-6363 .- 1755-3245. ; 119:7, s. 1524-1536
  • Tidskriftsartikel (refereegranskat)abstract
    • Recent studies have revealed a close connection between cellular metabolism and the chronic inflammatory process of atherosclerosis. While the link between systemic metabolism and atherosclerosis is well established, the implications of altered metabolism in the artery wall are less understood. Pyruvate dehydrogenase kinase (PDK)-dependent inhibition of pyruvate dehydrogenase (PDH) has been identified as a major metabolic step regulating inflammation. Whether the PDK/PDH axis plays a role in vascular inflammation and atherosclerotic cardiovascular disease remains unclear. Methods and results Gene profiling of human atherosclerotic plaques revealed a strong correlation between PDK1 and PDK4 transcript levels and the expression of pro-inflammatory and destabilizing genes. Remarkably, the PDK1 and PDK4 expression correlated with a more vulnerable plaque phenotype, and PDK1 expression was found to predict future major adverse cardiovascular events. Using the small-molecule PDK inhibitor dichloroacetate (DCA) that restores arterial PDH activity, we demonstrated that the PDK/PDH axis is a major immunometabolic pathway, regulating immune cell polarization, plaque development, and fibrous cap formation in Apoe−/− mice. Surprisingly, we discovered that DCA regulates succinate release and mitigates its GPR91-dependent signals promoting NLRP3 inflammasome activation and IL-1β secretion by macrophages in the plaque. Conclusions We have demonstrated for the first time that the PDK/PDH axis is associated with vascular inflammation in humans and particularly that the PDK1 isozyme is associated with more severe disease and could predict secondary cardiovascular events. Moreover, we demonstrate that targeting the PDK/PDH axis with DCA skews the immune system, inhibits vascular inflammation and atherogenesis, and promotes plaque stability features in Apoe−/− mice. These results point toward a promising treatment to combat atherosclerosis.
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4.
  • Wissel, Joerg, et al. (författare)
  • OnabotulinumtoxinA Improves Pain in Patients With Post-Stroke Spasticity: Findings From a Randomized, Double-Blind, Placebo-Controlled Trial
  • 2016
  • Ingår i: Journal of Pain and Symptom Management. - : ELSEVIER SCIENCE INC. - 0885-3924 .- 1873-6513. ; 52:1, s. 17-26
  • Tidskriftsartikel (refereegranskat)abstract
    • Context. Patients with post-stroke spasticity (PSS) commonly experience pain in affected limbs, which may impact quality of life. Objectives. To assess onabotulinumtoxinA for pain in patients with PSS from the BOTOX (R) Economic Spasticity Trial, a multicenter, randomized, double-blind, placebo-controlled trial. Methods. Patients with PSS (N = 273) were randomized to 22- to 34-week double-blind treatment with onabotulinumtoxinA + standard care (SC) or placebo injection + SC and were eligible to receive open-label onabotulinumtoxinA up to 52 weeks. Assessments included change from baseline on the 11-point pain numeric rating scale, proportion of patients with baseline pain amp;gt;= 4 achieving amp;gt;= 30% and amp;gt;= 50% improvement in pain, and pain interference with work at Week 12, end of double-blind treatment, and Week 52. Results. At baseline, most patients (74.3%) experienced pain and 47.4% had pain amp;gt;= 4 (pain subgroup). Mean pain reduction from baseline at Week 12 was significantly greater with onabotulinumtoxinA + SC (-0.77, 95% CI -1.14 to -0.40) than placebo + SC (-0.13, 95% CI -0.51 to 0.24; P amp;lt; 0.05). Higher proportions of patients in the pain subgroup achieved amp;gt;= 30% and amp;gt;= 50% reductions in pain at Week 12 with onabotulinumtoxinA + SC (53.7% and 37.0%, respectively) compared with placebo (28.8% and 18.6%, respectively; P amp;lt; 0.05). Reductions in pain were sustained through Week 52. Compared with placebo + SC, onabotulinumtoxinA consistently reduced pain interference with work. Conclusion. This is the first randomized, placebo-controlled trial demonstrating statistically significant and clinically meaningful reductions in pain and pain interference with work with onabotulinumtoxinA in patients with PSS. (C) 2016 The Authors. Published by Elsevier Inc. on behalf of American Academy of Hospice and Palliative Medicine. This is an open access article under the CC BY-NC-ND license.
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