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Sökning: WFRF:(Knutsson Mikael) > (2020-2022)

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1.
  • Amarenco, Pierre, et al. (författare)
  • Ticagrelor Added to Aspirin in Acute Ischemic Stroke or Transient Ischemic Attack in Prevention of Disabling Stroke : A Randomized Clinical Trial
  • 2020
  • Ingår i: JAMA Neurology. - : American Medical Association (AMA). - 2168-6149 .- 2168-6157. ; 78:2, s. 177-185
  • Tidskriftsartikel (refereegranskat)abstract
    • Importance: Reduction of subsequent disabling stroke is the main goal of preventive treatment in the acute setting after transient ischemic attack (TIA) or minor ischemic stroke.Objective: To evaluate the superiority of ticagrelor added to aspirin in preventing disabling stroke and to understand the factors associated with recurrent disabling stroke.Design, Setting, and Participants: The Acute Stroke or Transient Ischemic Attack Treated With Ticagrelor and Aspirin for Prevention of Stroke and Death (THALES) was a randomized clinical trial conducted between January 22, 2018, and December 13, 2019, with a 30-day follow-up, at 414 hospitals in 28 countries. The trial included 11 016 patients with a noncardioembolic, nonsevere ischemic stroke or high-risk TIA, including 10 803 with modified Rankin Scale score (mRS) recorded at 30 days.Interventions: Ticagrelor (180-mg loading dose on day 1 followed by 90 mg twice daily for days 2-30) or placebo within 24 hours of symptom onset. All patients received aspirin, 300 to 325 mg on day 1 followed by 75 to 100 mg daily for days 2 to 30.Main Outcomes and Measures: Time to the occurrence of disabling stroke (progression of index event or new stroke) or death within 30 days, as measured by mRS at day 30. Disabling stroke was defined by mRS greater than 1.Results: Among participants with 30-day mRS greater than 1, mean age was 68.1 years, 1098 were female (42.6%), and 2670 had an ischemic stroke (95.8%) as a qualifying event. Among 11 016 patients, a primary end point with mRS greater than 1 at 30 days occurred in 221 of 5511 patients (4.0%) randomized to ticagrelor and in 260 of 5478 patients (4.7%) randomized to placebo (hazard ratio [HR], 0.83; 95% CI, 0.69-0.99, P = .04). A primary end point with mRS 0 or 1 at 30 days occurred in 70 of 5511 patients (1.3%) and 87 of 5478 patients (1.6%) (HR, 0.79; 95% CI, 0.57-1.08; P = .14). The ordinal analysis of mRS in patients with recurrent stroke showed a shift of the disability burden following a recurrent ischemic stroke in favor of ticagrelor (odds ratio, 0.77; 95% CI, 0.65-0.91; P = .002). Factors associated with disability were baseline National Institutes of Health Stroke Scale score 4 to 5, ipsilateral stenosis of at least 30%, Asian race/ethnicity, older age, and higher systolic blood pressure, while treatment with ticagrelor was associated with less disability.Conclusions and Relevance: In patients with TIA and minor ischemic stroke, ticagrelor added to aspirin was superior to aspirin alone in preventing disabling stroke or death at 30 days and reduced the total burden of disability owing to ischemic stroke recurrence.Trial Registration: ClinicalTrials.gov Identifier: NCT03354429.
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2.
  • Amarenco, Pierre, et al. (författare)
  • Ticagrelor Added to Aspirin in Acute Nonsevere Ischemic Stroke or Transient Ischemic Attack of Atherosclerotic Origin
  • 2020
  • Ingår i: Stroke. - 0039-2499 .- 1524-4628. ; 51:12, s. 3504-3513
  • Tidskriftsartikel (refereegranskat)abstract
    • Background and Purpose:Among patients with a transient ischemic attack or minor ischemic strokes, those with ipsilateral atherosclerotic stenosis of cervicocranial vasculature have the highest risk of recurrent vascular events.Methods:In the double-blind THALES (The Acute Stroke or Transient Ischemic Attack Treated With Ticagrelor and ASA for Prevention of Stroke and Death) trial, we randomized patients with a noncardioembolic, nonsevere ischemic stroke, or high-risk transient ischemic attack to ticagrelor (180 mg loading dose on day 1 followed by 90 mg twice daily for days 2–30) or placebo added to aspirin (300–325 mg on day 1 followed by 75–100 mg daily for days 2–30) within 24 hours of symptom onset. The present paper reports a prespecified analysis in patients with and without ipsilateral, potentially causal atherosclerotic stenosis ≥30% of cervicocranial vasculature. The primary end point was time to the occurrence of stroke or death within 30 days.Results:Of 11 016 randomized patients, 2351 (21.3%) patients had an ipsilateral atherosclerotic stenosis. After 30 days, a primary end point occurred in 92/1136 (8.1%) patients with ipsilateral stenosis randomized to ticagrelor and in 132/1215 (10.9%) randomized to placebo (hazard ratio 0.73 [95% CI, 0.56–0.96], P=0.023) resulting in a number needed to treat of 34 (95% CI, 19–171). In patients without ipsilateral stenosis, the corresponding event rate was 211/4387 (4.8%) and 230/4278 (5.4%), respectively (hazard ratio, 0.89 [95% CI, 0.74–1.08]; P=0.23, Pinteraction=0.245). Severe bleeding occurred in 4 (0.4%) and 3 (0.2%) patients with ipsilateral atherosclerotic stenosis on ticagrelor and on placebo, respectively (P=NS), and in 24 (0.5%) and 4 (0.1%), respectively, in 8665 patients without ipsilateral stenosis (hazard ratio=5.87 [95% CI, 2.04–16.9], P=0.001).Conclusions:In this exploratory analysis comparing ticagrelor added to aspirin to aspirin alone, we found no treatment by ipsilateral atherosclerosis stenosis subgroup interaction but did identify a higher absolute risk and a greater absolute risk reduction of stroke or death at 30 days in patients with ipsilateral atherosclerosis stenosis than in those without. In this easily identified population, ticagrelor added to aspirin provided a clinically meaningful benefit with a number needed to treat of 34 (95% CI, 19–171).
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3.
  • Cardinale, Daniele A., 1982-, et al. (författare)
  • Enhanced Skeletal Muscle Oxidative Capacity and Capillary-to-Fiber Ratio Following Moderately Increased Testosterone Exposure in Young Healthy Women
  • 2020
  • Ingår i: Frontiers in Physiology. - : Frontiers Media S.A.. - 1664-042X. ; 11
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Recently, it was shown that exogenously administered testosterone enhances endurance capacity in women. In this study, our understanding on the effects of exogenous testosterone on key determinants of oxygen transport and utilization in skeletal muscle is expanded.Methods: In a double-blinded, randomized, placebo-controlled trial, 48 healthy active women were randomized to 10 weeks of daily application of 10 mg of testosterone cream or placebo. Before and after the intervention, VO2 max, body composition, total hemoglobin (Hb) mass and blood volumes were assessed. Biopsies from the vastus lateralis muscle were obtained before and after the intervention to assess mitochondrial protein abundance, capillary density, capillary-to-fiber (C/F) ratio, and skeletal muscle oxidative capacity.Results: Maximal oxygen consumption per muscle mass, Hb mass, blood, plasma and red blood cell volumes, capillary density, and the abundance of mitochondrial protein levels (i.e., citrate synthase, complexes I, II, III, IV-subunit 2, IV-subunit 4, and V) were unchanged by the intervention. However, the C/F ratio, specific mitochondrial respiratory flux activating complex I and linked complex I and II, uncoupled respiration and electron transport system capacity, but not leak respiration or fat respiration, were significantly increased following testosterone administration compared to placebo.Conclusion: This study provides novel insights into physiological actions of increased testosterone exposure on key determinants of oxygen diffusion and utilization in skeletal muscle of women. Our findings show that higher skeletal muscle oxidative capacity coupled to higher C/F ratio could be major contributing factors that improve endurance performance following moderately increased testosterone exposure.
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4.
  • Dahlberg, Anders, et al. (författare)
  • Svampar Fungi
  • 2020
  • Ingår i: Rödlistade arter i Sverige 2020. - 9789187853548 ; , s. 67-88
  • Bokkapitel (övrigt vetenskapligt/konstnärligt)
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5.
  • Johnston, S. Claiborne, et al. (författare)
  • Ischemic Benefit and Hemorrhage Risk of Ticagrelor-Aspirin Versus Aspirin in Patients With Acute Ischemic Stroke or Transient Ischemic Attack
  • 2021
  • Ingår i: Stroke. - : Wolters Kluwer. - 0039-2499 .- 1524-4628. ; 52:11, s. 3482-3489
  • Tidskriftsartikel (refereegranskat)abstract
    • Background and Purpose: In patients with acute mild-moderate ischemic stroke or high-risk transient ischemic attack, the THALES trial (Acute Stroke or Transient Ischemic Attack Treated With Ticagrelor and Aspirin for Prevention of Stroke and Death) demonstrated that when added to aspirin, ticagrelor reduced stroke or death but increased risk of severe hemorrhage compared with placebo. The primary efficacy outcome of THALES included hemorrhagic stroke and death, events also counted in the primary safety outcome. We sought to disentangle risk and benefit, assess their relative impact, and attempt to identify subgroups with disproportionate risk or benefit. Methods: In a randomized, placebo-controlled, double-blind trial of patients with mild-to-moderate acute noncardioembolic ischemic stroke or high-risk transient ischemic attack, patients were randomized within 24 hours after symptom onset to a 30-day regimen of either ticagrelor plus aspirin or matching placebo plus aspirin. For the present analyses, we defined the efficacy outcome, major ischemic events, as the composite of ischemic stroke or nonhemorrhagic death, and defined the safety outcome, major hemorrhage, as intracranial hemorrhage or hemorrhagic death. Net clinical impact was defined as the combination of these 2 end points. Results: In 11 016 patients (5523 ticagrelor-aspirin and 5493 aspirin), a major ischemic event occurred in 294 patients (5.3%) in the ticagrelor-aspirin group and in 359 patients (6.5%) in the aspirin group (absolute risk reduction 1.19% [95% CI, 0.31%-2.07%]). Major hemorrhage occurred in 22 patients (0.4%) in the ticagrelor-aspirin group and 6 patients (0.1%) in the aspirin group (absolute risk increase 0.29% [95% CI, 0.10%-0.48%]). Net clinical impact favored ticagrelor-aspirin (absolute risk reduction 0.97% [95% CI, 0.08%-1.87%]). Findings were similar when different thresholds for disability were applied and over a range of predefined subgroups. Conclusions: In patients with mild-moderate ischemic stroke or high-risk transient ischemic attack, ischemic benefits of 30-day treatment with ticagrelor-aspirin outweigh risks of hemorrhage. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03354429.
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6.
  • Johnston, S. Claiborne, et al. (författare)
  • Ticagrelor and Aspirin or Aspirin Alone in Acute Ischemic Stroke or TIA
  • 2020
  • Ingår i: New England Journal of Medicine. - : Massachusetts Medical Society. - 0028-4793 .- 1533-4406. ; 383:3, s. 207-217
  • Tidskriftsartikel (refereegranskat)abstract
    • BackgroundTrials have evaluated the use of clopidogrel and aspirin to prevent stroke after an ischemic stroke or transient ischemic attack (TIA). In a previous trial, ticagrelor was not better than aspirin in preventing vascular events or death after stroke or TIA. The effect of the combination of ticagrelor and aspirin on prevention of stroke has not been well studied.MethodsWe conducted a randomized, placebo-controlled, double-blind trial involving patients who had had a mild-to-moderate acute noncardioembolic ischemic stroke, with a National Institutes of Health Stroke Scale (NIHSS) score of 5 or less (range, 0 to 42, with higher scores indicating more severe stroke), or TIA and who were not undergoing thrombolysis or thrombectomy. The patients were assigned within 24 hours after symptom onset, in a 1:1 ratio, to receive a 30-day regimen of either ticagrelor (180-mg loading dose followed by 90 mg twice daily) plus aspirin (300 to 325 mg on the first day followed by 75 to 100 mg daily) or matching placebo plus aspirin. The primary outcome was a composite of stroke or death within 30 days. Secondary outcomes were first subsequent ischemic stroke and the incidence of disability within 30 days. The primary safety outcome was severe bleeding.ResultsA total of 11,016 patients underwent randomization (5523 in the ticagrelor–aspirin group and 5493 in the aspirin group). A primary-outcome event occurred in 303 patients (5.5%) in the ticagrelor–aspirin group and in 362 patients (6.6%) in the aspirin group (hazard ratio, 0.83; 95% confidence interval [CI], 0.71 to 0.96; P=0.02). Ischemic stroke occurred in 276 patients (5.0%) in the ticagrelor–aspirin group and in 345 patients (6.3%) in the aspirin group (hazard ratio, 0.79; 95% CI, 0.68 to 0.93; P=0.004). The incidence of disability did not differ significantly between the two groups. Severe bleeding occurred in 28 patients (0.5%) in the ticagrelor–aspirin group and in 7 patients (0.1%) in the aspirin group (P=0.001).ConclusionsAmong patients with a mild-to-moderate acute noncardioembolic ischemic stroke (NIHSS score ≤5) or TIA who were not undergoing intravenous or endovascular thrombolysis, the risk of the composite of stroke or death within 30 days was lower with ticagrelor–aspirin than with aspirin alone, but the incidence of disability did not differ significantly between the two groups. Severe bleeding was more frequent with ticagrelor.
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7.
  • Lai, Y., et al. (författare)
  • Study of Installation Effects on Automotive Cooling Fan Noise
  • 2022
  • Ingår i: SAE Technical Papers. - 400 Commonwealth Drive, Warrendale, PA, United States : SAE International. - 0148-7191.
  • Konferensbidrag (refereegranskat)abstract
    • Vehicle electrification is one of the biggest trends in the automotive industry. Without the presence of combustion engine, which is the main noise source on conventional vehicles, noise from other components becomes more perceivable; among these components, the cooling fan is one of the major noise sources, especially during battery charging. The design of cooling fan modules is usually carried out in the early stage before building prototype vehicles. Therefore, understanding the installation effects of the cooling fan on the radiated sound is essential to secure good customer satisfaction. In this study, three different measurement setups of cooling fans are carried out: free field, wall mounted, and in-vehicle measurement. Four cooling fan prototypes with different fan blade designs are used in each measurement. Correlations of these measurements are investigated through comparisons of the measurement results. The installation effects are identified through spectrum difference between free field and in-vehicle measurement. A spectral decomposition method is implemented to enable the separation of source strength and propagation effect in the results. One variable is introduced to represent the installation effects of vehicles tested in the present study. 
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8.
  • Manninen, Mikael A., et al. (författare)
  • First encounters in the north : cultural diversity and gene flow in Early Mesolithic Scandinavia
  • 2021
  • Ingår i: Antiquity. - : Antiquity Publications. - 0003-598X .- 1745-1744. ; 95:380, s. 310-328
  • Tidskriftsartikel (refereegranskat)abstract
    • Population genetic studies often overlook the evidence for variability and change in past material culture. Here, the authors use a Mesolithic example to demonstrate the importance of integrating archaeological evidence into the interpretation of the Scandinavian hunter-gatherer genetic group. Genetic studies conclude that this group resulted from two single-event dispersals into Scandinavia before 7500 BC. Archaeological evidence, however, shows at least six immigration events pre-dating the earliest DNA, and that the first incoming groups arrived in Scandinavia before 9000 BC. The findings underline the importance of conducting careful archaeological analysis of prehistoric human dispersal in tandem with the study of ancient population genomics.
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9.
  • Ramberg, Ulf, et al. (författare)
  • Att lära av varandra för att styra och leda bättre tillsammans : Case för politikens genomslag
  • 2022
  • Bok (populärvet., debatt m.m.)abstract
    • How do elected officials and managers in municipalities and regions manage and lead together in the best way? In order to deal with society's challenges and get impact and results from political decisions, well-functioning cooperation is a necessity.In the book, leading elected representatives and managers share their experiences and success factors. The book contains both theory and practice, in the form of, among other things, 13 different cases that highlight various strategic issues, structural changes and organizational challenges in municipalities and regions. The book can be seen as a knowledge-based discussion material to support leading politicians and civil servants in the work of implementing political decisions. It also aims to stimulate new perspectives to tackle challenges within individual municipalities and regions.
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10.
  • Ramberg, Ulf, et al. (författare)
  • Praktiska case för politikens genomslag
  • 2022
  • Ingår i: Kommunal ekonomi. - 0282-0099. ; 2022:6, s. 41-42
  • Tidskriftsartikel (populärvet., debatt m.m.)abstract
    • Practicing interaction between politics and administration can be a good idea after elections. One way to do this is to discuss cases together. Based on research on governance and control of the public sector and the advantages of case pedagogy, the authors discuss what can facilitate or hinder the realization of political decisions
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