| 1. |
- Amarenco, Pierre, et al.
(author)
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Ticagrelor Added to Aspirin in Acute Ischemic Stroke or Transient Ischemic Attack in Prevention of Disabling Stroke : A Randomized Clinical Trial
- 2020
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In: JAMA Neurology. - : American Medical Association (AMA). - 2168-6149 .- 2168-6157. ; 78:2, s. 177-185
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Journal article (peer-reviewed)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.
(author)
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Ticagrelor Added to Aspirin in Acute Nonsevere Ischemic Stroke or Transient Ischemic Attack of Atherosclerotic Origin
- 2020
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In: Stroke. - 0039-2499 .- 1524-4628. ; 51:12, s. 3504-3513
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Journal article (peer-reviewed)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. |
- Bhatt, Deepak L., et al.
(author)
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Rationale, design and baseline characteristics of the effect of ticagrelor on health outcomes in diabetes mellitus patients Intervention study
- 2019
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In: Clinical Cardiology. - : Wiley. - 0160-9289 .- 1932-8737. ; 42:5, s. 498-505
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Journal article (peer-reviewed)abstract
- In the setting of prior myocardial infarction, the oral antiplatelet ticagrelor added to aspirin reduced the risk of recurrent ischemic events, especially, in those with diabetes mellitus. Patients with stable coronary disease and diabetes are also at elevated risk and might benefit from dual antiplatelet therapy. The Effect of Ticagrelor on Health Outcomes in diabEtes Mellitus patients Intervention Study (THEMIS, NCT01991795) is a Phase 3b randomized, double-blinded, placebo-controlled trial of ticagrelor vs placebo, on top of low dose aspirin. Patients >= 50 years with type 2 diabetes receiving anti-diabetic medications for at least 6 months with stable coronary artery disease as determined by a history of previous percutaneous coronary intervention, bypass grafting, or angiographic stenosis of >= 50% of at least one coronary artery were enrolled. Patients with known prior myocardial infarction (MI) or stroke were excluded. The primary efficacy endpoint is a composite of cardiovascular death, myocardial infarction, or stroke. The primary safety endpoint is Thrombolysis in Myocardial Infarction major bleeding. A total of 19 220 patients worldwide have been randomized and at least 1385 adjudicated primary efficacy endpoint events are expected to be available for analysis, with an expected average follow-up of 40 months (maximum 58 months). Most of the exposure is on a 60 mg twice daily dose, as the dose was lowered from 90 mg twice daily partway into the study. The results may revise the boundaries of efficacy for dual antiplatelet therapy and whether it has a role outside acute coronary syndromes, prior myocardial infarction, or percutaneous coronary intervention.
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| 4. |
- Cardinale, Daniele A., 1982-, et al.
(author)
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Enhanced Skeletal Muscle Oxidative Capacity and Capillary-to-Fiber Ratio Following Moderately Increased Testosterone Exposure in Young Healthy Women
- 2020
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In: Frontiers in Physiology. - : Frontiers Media S.A.. - 1664-042X. ; 11
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Journal article (peer-reviewed)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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| 5. |
- Connolly, Stuart J., et al.
(author)
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Andexanet for Factor Xa Inhibitor-Associated Acute Intracerebral Hemorrhage
- 2024
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In: New England Journal of Medicine. - 0028-4793. ; 390:19, s. 1745-1755
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Journal article (peer-reviewed)abstract
- Background Patients with acute intracerebral hemorrhage who are receiving factor Xa inhibitors have a risk of hematoma expansion. The effect of andexanet alfa, an agent that reverses the effects of factor Xa inhibitors, on hematoma volume expansion has not been well studied. Methods We randomly assigned, in a 1:1 ratio, patients who had taken factor Xa inhibitors within 15 hours before having an acute intracerebral hemorrhage to receive andexanet or usual care. The primary end point was hemostatic efficacy, defined by expansion of the hematoma volume by 35% or less at 12 hours after baseline, an increase in the score on the National Institutes of Health Stroke Scale of less than 7 points (scores range from 0 to 42, with higher scores indicating worse neurologic deficit) at 12 hours, and no receipt of rescue therapy between 3 hours and 12 hours. Safety end points were thrombotic events and death. Results A total of 263 patients were assigned to receive andexanet, and 267 to receive usual care. Efficacy was assessed in an interim analysis that included 452 patients, and safety was analyzed in all 530 enrolled patients. Atrial fibrillation was the most common indication for factor Xa inhibitors. Of the patients receiving usual care, 85.5% received prothrombin complex concentrate. Hemostatic efficacy was achieved in 150 of 224 patients (67.0%) receiving andexanet and in 121 of 228 (53.1%) receiving usual care (adjusted difference, 13.4 percentage points; 95% confidence interval [CI], 4.6 to 22.2; P=0.003). The median reduction from baseline to the 1-to-2-hour nadir in anti-factor Xa activity was 94.5% with andexanet and 26.9% with usual care (P<0.001). Thrombotic events occurred in 27 of 263 patients (10.3%) receiving andexanet and in 15 of 267 (5.6%) receiving usual care (difference, 4.6 percentage points; 95% CI, 0.1 to 9.2; P=0.048); ischemic stroke occurred in 17 patients (6.5%) and 4 patients (1.5%), respectively. There were no appreciable differences between the groups in the score on the modified Rankin scale or in death within 30 days. Conclusions Among patients with intracerebral hemorrhage who were receiving factor Xa inhibitors, andexanet resulted in better control of hematoma expansion than usual care but was associated with thrombotic events, including ischemic stroke. (Funded by Alexion AstraZeneca Rare Disease and others; ANNEXA-I ClinicalTrials.gov number, NCT03661528.).
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| 6. |
- Dahlberg, Anders, et al.
(author)
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Svampar Fungi
- 2015
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In: Rödlistade arter i Sverige 2015. - 9789187853104 ; , s. 53-71
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Book chapter (other academic/artistic)
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| 7. |
- Du, Lin, et al.
(author)
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Modelling of Acoustic Resonators Using the Linearized Navier Stokes Equations
- 2016
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In: SAE Technical Paper Series. - 400 Commonwealth Drive, Warrendale, PA, United States : SAE International. - 0148-7191.
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Conference paper (peer-reviewed)abstract
- To tune the acoustics of intake systems resonators are often used. A problem with this solution is that the performance of these resonators can be affected a lot by flow. First, for low frequencies (Strouhal-numbers) the acoustic induced vorticity across a resonator inlet opening will create damping, which can reduce the efficiency. Secondly, the vorticity across the opening can also change the end-correction (added mass) for the resonator, which can modify the resonance frequency. However, the largest problem that can occur is whistling. This happens since the vortex-sound interaction across a resonator opening for certain Strouhal-numbers will amplify incoming sound waves. A whistling can then be created if this amplified sound forms a feedback loop, e.g., via reflections from system boundaries or the resonator. To analyse this kind of problem it is necessary to have a model that allows for both sound and vorticity and their interaction. This means using a convected wave equation type of model is not sufficient. A better approach is to apply the linearized Navier Stokes equations, which will give a full model of the vortex-sound effects. In this paper an effort to apply this approach on a set of generic resonators is described. Besides the numerical results comparisons with experiments are also presented.
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| 8. |
- Friman, Ola, 1975-, et al.
(author)
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Recognizing emphysema - A neural network approach
- 2002
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In: Pattern Recognition, 2002. Proceedings. 16th International Conference on (Volume:1). - : IEEE Computer Society. ; , s. 512-515
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Conference paper (peer-reviewed)abstract
- An accurate and fully automatic method for detecting and quantifying emphysema in CT-images is presented. The method is based on an image preprocessing step followed by a neural network classifier trained to separate true emphysema from artifacts. The proposed approach is shown to be superior to an established method when applied on real patient data.
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| 9. |
- Fritzell, Peter, et al.
(author)
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Bacteria : back pain, leg pain and Modic sign—a surgical multicentre comparative study
- 2019
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In: European spine journal. - : Springer. - 0940-6719 .- 1432-0932. ; 28:12, s. 2981-2989
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Journal article (peer-reviewed)abstract
- Purpose: To compare bacterial findings in pain-generating degenerated discs in adults operated on for lumbar disc herniation (LDH), and mostly also suffering from low back pain (LBP), with findings in adolescent patients with non-degenerated non-pain-generating discs operated on for scoliosis, and to evaluate associations with Modic signs on magnetic resonance imaging (MRI). Cutibacterium acnes (Propionibacterium acnes) has been found in painful degenerated discs, why it has been suggested treating patients with LDH/LBP with antibiotics. As multidrug-resistant bacteria are a worldwide concern, new indications for using antibiotics should be based on solid scientific evidence.Methods: Between 2015 and 2017, 40 adults with LDH/LBP (median age 43, IQR 33–49) and 20 control patients with scoliosis (median age 17, IQR 15–20) underwent surgery at seven Swedish hospitals. Samples were cultured from skin, surgical wound, discs and vertebrae. Genetic relatedness of C. acnes isolates was investigated using single-nucleotide polymorphism analysis. DNA samples collected from discs/vertebrae were analysed using 16S rRNA-based PCR sequencing. MRI findings were assessed for Modic changes.Results: No bacterial growth was found in 6/40 (15%) LDH patients, compared with 3/20 (15%) scoliosis patients. Most positive samples in both groups were isolated from the skin and then from subcutis or deep within the wound. Of the four disc and vertebral samples from each of the 60 patients, 235/240 (98%) were DNA negative by bacterial PCR. A single species, C. acnes, was found exclusively in the disc/vertebra from one patient in each group. In the LDH group, 29/40 (72%) patients had at least one sample with growth of C. acnes, compared to 14/20 (70%) in the scoliosis group. Bacterial findings and Modic changes were not associated.Conclusions: Cutibacterium acnes found in discs and vertebrae during surgery for disc herniation in adults with degenerated discs may be caused by contamination, as findings in this group were similar to findings in a control group of young patients with scoliosis and non-degenerated discs. Furthermore, such findings were almost always combined with bacterial findings on the skin and/or in the wound. There was no association between preoperative Modic changes and bacterial findings. Antibiotic treatment of lumbar disc herniation with sciatica and/or low back pain, without signs of clinical discitis/spondylitis, should be seriously questioned.
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| 10. |
- Johansson, Lotta, 1965, et al.
(author)
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Evaluation of a sound environment intervention in an ICU : A feasibility study
- 2018
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In: Australian Critical Care. - Amsterdam : Elsevier. - 1036-7314 .- 1878-1721. ; 31:2, s. 59-70
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Journal article (peer-reviewed)abstract
- Background: Currently, it is well known that the sound environment in intensive care units (ICU) is substandard. Therefore, there is a need of interventions investigating possible improvements. Unfortunately, there are many challenges to consider in the design and performance of clinical intervention studies including sound measurements and clinical outcomes.Objectives: (1) explore whether it is possible to implement a full-scale intervention study in the ICU concerning sound levels and their impact on the development of ICU delirium; (2) discuss methodological challenges and solutions for the forthcoming study; (3) conduct an analysis of the presence of ICU delirium in the study group; and (4) describe the sound pattern in the intervention rooms.Methods: A quasi-randomized clinical trial design was chosen. The intervention consisted of a refurbished two-bed ICU patient room (experimental) with a new suspended wall-to-wall ceiling and a low frequency absorber. An identical two-bed room (control) remained unchanged.Inclusion criteria: Patients >18 years old with ICU lengths of stay (LoS) >48. h. The final study group consisted of 31 patients: six from the rebuilt experimental room and 25 from the control room. Methodological problems and possible solutions were continuously identified and documented.Results: Undertaking a full-scale intervention study with continuous measurements of acoustic data in an ICU is possible. However, this feasibility study demonstrated some aspects to consider before start. The randomization process and the sound measurement procedure must be developed. Furthermore, proper education and training are needed for determining ICU delirium.Conclusion: This study raises a number of points that may be helpful for future complex interventions in an ICU. For a full-scale study to be completed a continuously updated cost calculation is necessary. Furthermore, representatives from the clinic need to be involved in all stages during the project.
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