| 1. |
- Zamora, Juan Carlos, et al.
(författare)
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Considerations and consequences of allowing DNA sequence data as types of fungal taxa
- 2018
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Ingår i: IMA Fungus. - : INT MYCOLOGICAL ASSOC. - 2210-6340 .- 2210-6359. ; 9:1, s. 167-185
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Tidskriftsartikel (refereegranskat)abstract
- Nomenclatural type definitions are one of the most important concepts in biological nomenclature. Being physical objects that can be re-studied by other researchers, types permanently link taxonomy (an artificial agreement to classify biological diversity) with nomenclature (an artificial agreement to name biological diversity). Two proposals to amend the International Code of Nomenclature for algae, fungi, and plants (ICN), allowing DNA sequences alone (of any region and extent) to serve as types of taxon names for voucherless fungi (mainly putative taxa from environmental DNA sequences), have been submitted to be voted on at the 11th International Mycological Congress (Puerto Rico, July 2018). We consider various genetic processes affecting the distribution of alleles among taxa and find that alleles may not consistently and uniquely represent the species within which they are contained. Should the proposals be accepted, the meaning of nomenclatural types would change in a fundamental way from physical objects as sources of data to the data themselves. Such changes are conducive to irreproducible science, the potential typification on artefactual data, and massive creation of names with low information content, ultimately causing nomenclatural instability and unnecessary work for future researchers that would stall future explorations of fungal diversity. We conclude that the acceptance of DNA sequences alone as types of names of taxa, under the terms used in the current proposals, is unnecessary and would not solve the problem of naming putative taxa known only from DNA sequences in a scientifically defensible way. As an alternative, we highlight the use of formulas for naming putative taxa (candidate taxa) that do not require any modification of the ICN.
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| 2. |
- Bohm, Felix, et al.
(författare)
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FFR-Guided Complete or Culprit-Only PCI in Patients with Myocardial Infarction
- 2024
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Ingår i: New England Journal of Medicine. - : MASSACHUSETTS MEDICAL SOC. - 0028-4793 .- 1533-4406.
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Tidskriftsartikel (refereegranskat)abstract
- Background The benefit of fractional flow reserve (FFR)-guided complete revascularization in patients with ST-segment elevation myocardial infarction (STEMI) and multivessel coronary artery disease remains unclear.Methods In this multinational, registry-based, randomized trial, we assigned patients with STEMI or very-high-risk non-STEMI (NSTEMI) and multivessel disease who were undergoing primary percutaneous coronary intervention (PCI) of the culprit lesion to receive either FFR-guided complete revascularization of nonculprit lesions or no further revascularization. The primary outcome was a composite of death from any cause, myocardial infarction, or unplanned revascularization. The two key secondary outcomes were a composite of death from any cause or myocardial infarction and unplanned revascularization.Results A total of 1542 patients underwent randomization, with 764 assigned to receive FFR-guided complete revascularization and 778 assigned to receive culprit-lesion-only PCI. At a median follow-up of 4.8 years (interquartile range, 4.3 to 5.2), a primary-outcome event had occurred in 145 patients (19.0%) in the complete-revascularization group and in 159 patients (20.4%) in the culprit-lesion-only group (hazard ratio, 0.93; 95% confidence interval [CI], 0.74 to 1.17; P=0.53). With respect to the secondary outcomes, no apparent between-group differences were observed in the composite of death from any cause or myocardial infarction (hazard ratio, 1.12; 95% CI, 0.87 to 1.44) or unplanned revascularization (hazard ratio, 0.76; 95% CI, 0.56 to 1.04). There were no apparent between-group differences in safety outcomes.Conclusions Among patients with STEMI or very-high-risk NSTEMI and multivessel coronary artery disease, FFR-guided complete revascularization was not shown to result in a lower risk of a composite of death from any cause, myocardial infarction, or unplanned revascularization than culprit-lesion-only PCI at 4.8 years. (Funded by the Swedish Research Council and others; FULL REVASC ClinicalTrials.gov number, NCT02862119.) In a registry-based trial, FFR-guided PCI of nonculprit lesions did not result in a lower risk of a composite of death from any cause, myocardial infarction, or unplanned revascularization than culprit-lesion-only PCI.
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| 3. |
- Böhm, Felix, et al.
(författare)
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FFR-Guided Complete or Culprit-Only PCI in Patients with Myocardial Infarction
- 2024
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Ingår i: New England Journal of Medicine. - : Massachusetts Medical Society. - 0028-4793 .- 1533-4406. ; 390:16, s. 1481-1492
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The benefit of fractional flow reserve (FFR)-guided complete revascularization in patients with ST-segment elevation myocardial infarction (STEMI) and multivessel coronary artery disease remains unclear. METHODS: In this multinational, registry-based, randomized trial, we assigned patients with STEMI or very-high-risk non-STEMI (NSTEMI) and multivessel disease who were undergoing primary percutaneous coronary intervention (PCI) of the culprit lesion to receive either FFR-guided complete revascularization of nonculprit lesions or no further revascularization. The primary outcome was a composite of death from any cause, myocardial infarction, or unplanned revascularization. The two key secondary outcomes were a composite of death from any cause or myocardial infarction and unplanned revascularization. RESULTS: A total of 1542 patients underwent randomization, with 764 assigned to receive FFR-guided complete revascularization and 778 assigned to receive culprit-lesion-only PCI. At a median follow-up of 4.8 years (interquartile range, 4.3 to 5.2), a primary-outcome event had occurred in 145 patients (19.0%) in the complete-revascularization group and in 159 patients (20.4%) in the culprit-lesion-only group (hazard ratio, 0.93; 95% confidence interval [CI], 0.74 to 1.17; P = 0.53). With respect to the secondary outcomes, no apparent between-group differences were observed in the composite of death from any cause or myocardial infarction (hazard ratio, 1.12; 95% CI, 0.87 to 1.44) or unplanned revascularization (hazard ratio, 0.76; 95% CI, 0.56 to 1.04). There were no apparent between-group differences in safety outcomes. CONCLUSIONS: Among patients with STEMI or very-high-risk NSTEMI and multivessel coronary artery disease, FFR-guided complete revascularization was not shown to result in a lower risk of a composite of death from any cause, myocardial infarction, or unplanned revascularization than culprit-lesion-only PCI at 4.8 years. (Funded by the Swedish Research Council and others; FULL REVASC ClinicalTrials.gov number, NCT02862119.).
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| 4. |
- Al-Khatib, Sana M., et al.
(författare)
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Outcomes of apixaban vs. warfarin by type and duration of atrial fibrillation : results from the ARISTOTLE trial
- 2013
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Ingår i: European Heart Journal. - : Oxford University Press (OUP). - 0195-668X .- 1522-9645. ; 34:31, s. 2464-2471
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Tidskriftsartikel (refereegranskat)abstract
- It is uncertain whether the benefit from apixaban varies by type and duration of atrial fibrillation (AF). A total of 18 201 patients with AF [2786 (15.3) with paroxysmal and 15 412 (84.7) with persistent or permanent] were randomized to apixaban or warfarin. In this pre-specified secondary analysis, we compared outcomes and treatment effect of apixaban vs. warfarin by AF type and duration. The primary efficacy endpoint was a composite of ischaemic or haemorrhagic stroke or systemic embolism. The secondary efficacy endpoint was all-cause mortality. There was a consistent reduction in stroke or systemic embolism (P for interaction 0.71), all-cause mortality (P for interaction 0.75), and major bleeding (P for interaction 0.50) with apixaban compared with warfarin for both AF types. Apixaban was superior to warfarin in all studied endpoints, regardless of AF duration at study entry (P for all interactions 0.13). The rate of stroke or systemic embolism was significantly higher in patients with persistent or permanent AF than patients with paroxysmal AF (1.52 vs. 0.98; P 0.003, adjusted P 0.015). There was also a trend towards higher mortality in patients with persistent or permanent AF (3.90 vs. 2.81; P 0.0002, adjusted P 0.066). The risks of stroke, mortality, and major bleeding were lower with apixaban than warfarin regardless of AF type and duration. Although the risk of stroke or systemic embolism was lower in paroxysmal than persistent or permanent AF, apixaban is an attractive alternative to warfarin in patients with AF and at least one other risk factor for stroke, regardless of the type or duration of AF.
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| 5. |
- Alexander, John H., et al.
(författare)
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Apixaban vs. warfarin with concomitant aspirin in patients with atrial fibrillation : insights from the ARISTOTLE trial
- 2014
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Ingår i: European Heart Journal. - : Oxford University Press (OUP). - 0195-668X .- 1522-9645. ; 35:4, s. 224-232
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Tidskriftsartikel (refereegranskat)abstract
- Aims We assessed the effect of concomitant aspirin use on the efficacy and safety of apixaban compared with warfarin in patients with atrial fibrillation (AF). Methods and results In ARISTOTLE, 18 201 patients were randomized to apixaban 5 mg twice daily or warfarin. Concomitant aspirin use was left to the discretion of the treating physician. In this predefined analysis, simple and marginal structured models were used to adjust for baseline and time-dependent confounders associated with aspirin use. Outcome measures included stroke or systemic embolism, ischaemic stroke, myocardial infarction, mortality, major bleeding, haemorrhagic stroke, major or clinically relevant non-major bleeding, and any bleeding. On Day 1, 4434 (24%) patients were taking aspirin. Irrespective of concomitant aspirin use, apixaban reduced stroke or systemic embolism [with aspirin: apixaban 1.12% vs. warfarin 1.91, hazard ratio (HR) 0.58, 95% confidence interval (CI) 0.39-0.85 vs. without aspirin: apixaban 1.11% vs. warfarin 1.32%, HR 0.84, 95% CI 0.66-1.07; P interaction = 0.10] and caused less major bleeding than warfarin (with aspirin: apixaban 3.10 vs. warfarin 3.92%, HR 0.77, 95% CI 0.60-0.99 vs. without aspirin: apixaban 1.82% vs. warfarin 2.78, HR without aspirin 0.65, 95% CI 0.55-0.78; P interaction = 0.29). Similar results were seen in the subgroups of patients with and without arterial vascular disease. Conclusion Apixaban had similar beneficial effects on stroke or systemic embolism and major bleeding compared with warfarin, irrespective of concomitant aspirin use.
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| 6. |
- Böhm, Felix, et al.
(författare)
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The Full Revasc (Ffr-gUidance for compLete non-cuLprit REVASCularization) Registry-based randomized clinical trial
- 2021
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Ingår i: American Heart Journal. - : Elsevier. - 0002-8703 .- 1097-6744. ; 241, s. 92-100
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Tidskriftsartikel (refereegranskat)abstract
- Background Complete revascularization in ST elevation myocardial infarction (STEMI) patients with multivessel disease has resulted in reduction in composite clinical endpoints in medium sized trials. Only one trial showed an effect on hard clinical endpoints, but the revascularization procedure was guided by angiographic evaluation of stenosis severity. Consequently, it is not clear how Fractional Flow Reserve (FFR)-guided percutaneous coronary intervention (PCI) affects hard clinical endpoints in STEMI. Methods and Results The Ffr-gUidance for compLete non-cuLprit REVASCularization (FULL REVASC) - is a pragmatic, multicenter, international, registry-based randomized clinical trial designed to evaluate whether a strategy of FFR-guided complete revascularization of non-culprit lesions, reduces the combined primary endpoint of total mortality, non-fatal MI and unplanned revascularization. 1,545 patients were randomized to receive FFR-guided PCI during the index hospitalization or initial conservative management of non-culprit lesions. We found that in angiographically severe non-culprit lesions of 90-99% severity, 1 in 5 of these lesions were re-classified as non-flow limiting by FFR. Considering lesions of intermediate severity (70%-89%), half were re-classified as non-flow limiting by FFR. The study is event driven for an estimated follow-up of at least 2.75 years to detect a 9.9%/year >7.425%/year difference (HR = 0.74 at 80% power (alpha = .05)) for the combined primary endpoint. Conclusion This large randomized clinical trial is designed and powered to evaluate the effect of complete revascularization with FFR-guided PCI during index hospitalization on total mortality, non-fatal MI and unplanned revascularization following primary PCI in STEMI patients with multivessel disease. Enrollment completed in September 2019 and follow-up is ongoing.
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| 7. |
- Durheim, Michael T., et al.
(författare)
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Chronic obstructive pulmonary disease in patients with atrial fibrillation : Insights from the ARISTOTLE trial
- 2016
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Ingår i: International Journal of Cardiology. - : Elsevier BV. - 0167-5273 .- 1874-1754. ; 202, s. 589-594
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Tidskriftsartikel (refereegranskat)abstract
- Background: Comorbid chronic obstructive pulmonary disease (COPD) is associated with poor outcomes among patients with cardiovascular disease. The risks of stroke and mortality associated with COPD among patients with atrial fibrillation are not well understood. Methods: We analyzed patients from ARISTOTLE, a randomized trial of 18,201 patients with atrial fibrillation comparing the effects of apixaban versus warfarin on the risk of stroke or systemic embolism. Using Cox proportional hazards models, we assessed the associations between comorbid COPD and risk of stroke or systemic embolism and of mortality, adjusting for treatment allocation, smoking history and other risk factors. Results: COPD was present in 1950 (10.8%) of 18,134 patients with data on pulmonary disease history. After multivariable adjustment, COPD was not associated with risk of stroke or systemic embolism (adjusted HR 0.85 [95% CI 0.60, 1.21], p = 0.356). However, COPD was associated with a higher risk of all-cause mortality (adjusted HR 1.60 [95% CI 1.36, 1.88], p < 0.001) and both cardiovascular and non-cardiovascular mortality. The benefit of apixaban over warfarin on stroke or systemic embolism was consistent among patients with and without COPD (HR 0.92 [95% CI 0.52, 1.63] versus 0.78 [95% CI 0.65, 0.95], interaction p = 0.617). Conclusions: COPD was independently associated with increased risk of cardiovascular and non-cardiovascular mortality among patients with atrial fibrillation, but was not associated with risk of stroke or systemic embolism. The effect of apixaban on stroke or systemic embolism in COPD patients was consistent with its effect in the overall trial population.
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| 8. |
- Fellman, Daniel, et al.
(författare)
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The role of strategy use in working memory training outcomes
- 2020
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Ingår i: Journal of memory and language (Print). - : Elsevier. - 0749-596X .- 1096-0821. ; 110
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Tidskriftsartikel (refereegranskat)abstract
- Cognitive mechanisms underlying the limited transfer effects of working memory (WM) training remain poorly understood. We tested in detail the Strategy Mediation hypothesis, according to which WM training generates task-specific strategies that facilitate performance on the trained task and its untrained variants. This large-scale pre-registered randomized controlled trial (n = 258) used a 4-week adaptive WM training with a single digit n-back task. Strategy use was probed with open-ended strategy reports. We employed a Strategy training group (n = 73) receiving external strategy instruction, a Traditional training group (n = 118) practicing without strategy instruction, and Passive controls (n = 67). Both training groups showed emerging transfer to untrained n-back task variants already at intermediate test after 3 training sessions, extending to all untrained n-back task variants at posttest after 12 training sessions. The Strategy training group outperformed the Traditional training group only at the beginning of training, indicating short-lived strategy manipulation effects. Importantly, in the Traditional training group, strategy evolvement modulated the gains in the trained and untrained n -back tasks, supporting the Strategy Mediation hypothesis. Our results concur with the view of WM training as cognitive skill learning.
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| 9. |
- Flaker, Greg, et al.
(författare)
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Amiodarone, Anticoagulation, and Clinical Events in Patients With Atrial Fibrillation Insights From the ARISTOTLE Trial
- 2014
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Ingår i: Journal of the American College of Cardiology. - : Elsevier BV. - 0735-1097 .- 1558-3597. ; 64:15, s. 1541-1550
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND Amiodarone is an effective medication in preventing atrial fibrillation (AF), but it interferes with the metabolism of warfarin. OBJECTIVES This study sought to examine the association of major thrombotic clinical events and bleeding with the use of amiodarone in the ARISTOTLE (Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation) trial. METHODS Baseline characteristics of patients who received amiodarone at randomization were compared with those who did not receive amiodarone. The interaction between randomized treatment and amiodarone was tested using a Cox model, with main effects for randomized treatment and amiodarone and their interaction. Matching on the basis of a propensity score was used to compare patients who received and who did not receive amiodarone at the time of randomization. RESULTS In ARISTOTLE, 2,051 (11.4%) patients received amiodarone at randomization. Patients on warfarin and amiodarone had time in the therapeutic range that was lower than patients not on amiodarone (56.5% vs. 63.0%; p < 0.0001). More amiodarone-treated patients had a stroke or a systemic embolism (1.58%/year vs. 1.19%/year; adjusted hazard ratio [HR]: 1.47, 95% confidence interval [CI]: 1.03 to 2.10; p = 0.0322). Overall mortality and major bleeding rates were elevated, but were not significantly different in amiodarone-treated patients and patients not on amiodarone. When comparing apixaban with warfarin, patients who received amiodarone had a stroke or a systemic embolism rate of 1.24%/year versus 1.85%/year (HR: 0.68, 95% CI: 0.40 to 1.15), death of 4.15%/year versus 5.65%/year (HR: 0.74, 95% CI: 0.55 to 0.98), and major bleeding of 1.86%/year versus 3.06%/year (HR: 0.61, 95% CI: 0.39 to 0.96). In patients who did not receive amiodarone, the stroke or systemic embolism rate was 1.29%/year versus 1.57%/year (HR: 0.82, 95% CI: 0.68 to 1.00), death was 3.43%/year versus 3.68%/year (HR: 0.93, 95% CI: 0.83 to 1.05), and major bleeding was 2.18%/year versus 3.03%/year (HR: 0.72, 95% CI: 0.62 to 0.84). The interaction p values for amiodarone use by apixaban treatment effects were not significant. CONCLUSIONS Amiodarone use was associated with significantly increased stroke and systemic embolism risk and a lower time in the therapeutic range when used with warfarin. Apixaban consistently reduced the rate of stroke and systemic embolism, death, and major bleeding compared with warfarin in amiodarone-treated patients and patients who were not on amiodarone.
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| 10. |
- Focks, Jeroen Jaspers, et al.
(författare)
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Polypharmacy and effects of apixaban versus warfarin in patients with atrial fibrillation : post hoc analysis of the ARISTOTLE trial
- 2016
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Ingår i: BMJ-BRITISH MEDICAL JOURNAL. - : BMJ. - 1756-1833. ; 353
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE To determine whether the treatment effect of apixaban versus warfarin differs with increasing numbers of concomitant drugs used by patients with atrial fibrillation. DESIGN Post hoc analysis performed in 2015 of results from ARISTOTLE (apixaban for reduction in stroke and other thromboembolic events in atrial fibrillation)-a multicentre, double blind, double dummy trial that started in 2006 and ended in 2011. PARTICIPANTS 18 201 ARISTOTLE trial participants. INTERVENTIONS In the ARISTOTLE trial, patients were randomised to either 5 mg apixaban twice daily (n=9120) or warfarin (target international normalised ratio range 2.0-3.0; n=9081). In the post hoc analysis, patients were divided into groups according to the number of concomitant drug treatments used at baseline (0-5, 6-8, >= 9 drugs) with a median follow-up of 1.8 years. MAIN OUTCOME MEASURES Clinical outcomes and treatment effects of apixaban versus warfarin (adjusted for age, sex, and country). RESULTS Each patient used a median of six drugs (interquartile range 5-9); polypharmacy (>= 5 drugs) was seen in 13 932 (76.5%) patients. Greater numbers of concomitant drugs were used in older patients, women, and patients in the United States. The number of comorbidities increased across groups of increasing numbers of drugs (0-5, 6-8, >= 9 drugs), as did the proportions of patients treated with drugs that interact with warfarin or apixaban. Mortality also rose significantly with the number of drug treatments (P<0.001), as did rates of stroke or systemic embolism (1.29, 1.48, and 1.57 per 100 patient years, for 0-5, 6-8, and >= 9 drugs, respectively) and major bleeding (1.91, 2.46, and 3.88 per 100 patient years, respectively). Relative risk reductions in stroke or systemic embolism for apixaban versus warfarin were consistent, regardless of the number of concomitant drugs (P-interaction=0.82). A smaller reduction in major bleeding was seen with apixaban versus warfarin with increasing numbers of concomitant drugs (P-interaction=0.017). Patients with interacting (potentiating) drugs for warfarin or apixaban had similar outcomes and consistent treatment effects of apixaban versus warfarin. CONCLUSIONS In the ARISTOTLE trial, three quarters of patients had polypharmacy; this subgroup had an increased comorbidity, more interacting drugs, increased mortality, and higher rates of thromboembolic and bleeding complications. In terms of a potential differential response to anticoagulation therapy in patients with atrial fibrillation and polypharmacy, apixaban was more effective than warfarin, and is at least just as safe.
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| 11. |
- Garcia, David A., et al.
(författare)
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Apixaban versus warfarin in patients with atrial fibrillation according to prior warfarin use : Results from the Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation trial
- 2013
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Ingår i: American Heart Journal. - : Elsevier BV. - 0002-8703 .- 1097-6744. ; 166:3, s. 549-558
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Tidskriftsartikel (refereegranskat)abstract
- Background Patients with atrial fibrillation who are vitamin K antagonist (VKA)-naive may have a higher risk of thrombosis and/or bleeding than VKA-experienced patients. Methods and results Using data from ARISTOTLE, we assessed baseline characteristics and the treatment effect of apixaban versus warfarin in the VKA-naive and VKA-experienced cohorts. We compared rates of study drug discontinuation and time-in-therapeutic range. Overall, 7,800 (43%) were VKA naive, and 10,401 were VKA experienced. At baseline, both groups were similar with respect to age and congestive heart failure, hypertension, age, diabetes, stroke score (CHADS(2)). Fewer VKA-naive patients had a history of prior stroke (18% vs 21%) or prior bleeding (10% vs 22%) and were more often female (39% vs 33%). The effect of apixaban on the primary efficacy and safety outcomes was similar in VKA-naive (stroke/systemic embolism: hazard ratio [ HR] 0.86, 95% CI 0.67-1.11 and major bleeding: HR 0.73, 95% CI 0.59-0.91) and VKA-experienced populations (stroke/systemic embolism: HR 0.73, 95% CI 0.57-0.95, P value for interaction = 0.39 and major bleeding: HR 0.66, 95% CI 0.55-0.80, P value for interaction = 0.50). Permanent study drug discontinuation was numerically less likely in patients receiving apixaban whether they were VKA naive (HR for discontinuation: 0.87, 95% CI 0.79-0.95) or VKA experienced (HR for discontinuation: 0.93, 95% CI 0.85-1.02). Among patients receiving warfarin, the mean/median times in therapeutic range were lower in the VKA-naive group (VKA-naive: 57.5/61.4, VKA-experienced: 66.0/69.1, P < .001). Conclusion The treatment effects of apixaban (vs warfarin) were not modified by VKA naivety. The rates of stroke/systemic embolism and major bleeding were numerically lower among the patients assigned to apixaban, irrespective of prior VKA use.
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| 12. |
- Garcia, David, et al.
(författare)
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Management and clinical outcomes in patients treated with apixaban versus warfarin undergoing procedures
- 2014
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Ingår i: Blood. - : American Society of Hematology. - 0006-4971 .- 1528-0020. ; 124:25, s. 3692-3698
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Tidskriftsartikel (refereegranskat)abstract
- Using data from ARISTOTLE, we describe the periprocedural management of anticoagulation and rates of subsequent clinical outcomes among patients chronically anticoagulated with warfarin or apixaban. We recorded whether (and for how long) anticoagulant therapy was interrupted pre-procedure; whether bridging therapy was used; and the proportion of patients who experienced important clinical outcomes during the 30 days post-procedure. Of 10,674 procedures performed during follow-up in 5924 patients, 9260 were included in this analysis. Anticoagulant treatment was not interrupted pre-procedure 37.5% of the time. During the 30 days post-procedure, stroke or systemic embolism occurred after 16/4624 (0.35%) procedures among apixaban-treated patients and 26/4530 (0.57%) procedures among warfarin-treated patients (OR 0.601; 95% CI 0.322–1.120). Major bleeding occurred in 74/4560 (1.62%) procedures in the apixaban arm and 86/4454 (1.93%) in the warfarin arm (OR 0.846; 95% CI 0.614–1.166). The risk of death was similar with apixaban (54/4624 [1.17%]) and warfarin (49/4530 [1.08%]) (OR 1.082; 95% CI 0.733–1.598). Among patients in ARISTOTLE, the 30-day post-procedure stroke, death, and major bleeding rates were low and similar in apixaban- and warfarin-treated patients, regardless of whether anticoagulation was stopped beforehand. Our findings suggest that many patients on chronic anticoagulation can safely undergo procedures; some will not require a pre-procedure interruption of anticoagulation. ARISTOTLE ClinicalTrials.gov number (NCT00412984).
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| 13. |
- Granger, CB, et al.
(författare)
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Clinical events after transitioning from apixaban versus warfarin to warfarin at the end of the Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation (ARISTOTLE) trial
- 2015
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Ingår i: American Heart Journal. - : Elsevier BV. - 0002-8703 .- 1097-6744. ; 169:1, s. 25-30
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Tidskriftsartikel (refereegranskat)abstract
- Background We sought to assess the occurrence of events after blinded study drug discontinuation and transition to open-label vitamin K antagonist (VKA) in ARISTOTLE.Methods At the end of ARISTOTLE, blinded study drug was stopped, and open-label VKA was recommended. For patients completing the trial on blinded study drug, a 2-day bridging period with apixaban or apixaban placebo was recommended (while beginning open-label VKA). Outcomes were assessed during the 30 days after stopping blinded study drug.Results Of the 6,809 patients in the apixaban group and 6,588 in the warfarin group who completed the trial on study drug, there were 21 strokes or systemic emboli (4.02%/year) and 26 major bleeding (4.97%/year) events in the apixaban group (transitioning to VKA) and 5 strokes or systemic emboli (0.99%/year) and 10 major bleeding (1.97%/year) events in the warfarin group (continuing on VKA), with most of the imbalance between groups being after the first week. Similar results were seen in the first 30 days of the trial where warfarin-naive patients starting warfarin had a higher rate of stroke or systemic emboli (5.41%/year) than warfarin-experienced patients (1.42%/year), a pattern not seen when starting apixaban. No similar increase in events with apixaban versus warfarin was seen during temporary or permanent study drug discontinuation during the trial.Conclusions The excess in thrombotic and bleeding events in the apixaban group after study drug discontinuation appears to be related to an increased risk associated with the initiation of a VKA rather than a direct effect of apixaban. Whether >= 2 days of apixaban bridging improves outcomes during VKA transition is unknown and deserves further evaluation.
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| 14. |
- Guimaraes, Patricia O., et al.
(författare)
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Anticoagulation therapy and clinical outcomes in patients with recently diagnosed atrial fibrillation : Insights from the ARISTOTLE trial
- 2017
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Ingår i: International Journal of Cardiology. - : Elsevier BV. - 0167-5273 .- 1874-1754. ; 227, s. 443-449
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Tidskriftsartikel (refereegranskat)abstract
- Background: Evidence supporting use of antithrombotic therapy in atrial fibrillation (AF) is based mainly on data from patients with permanent, persistent, or paroxysmal AF. Less is known about the risk following a new diagnosis of AF and the efficacy and safety of apixaban in these patients. Methods: Using data from ARISTOTLE, we assessed the relationship between timing of AF diagnosis and clinical outcomes and the efficacy and safety of apixaban versus warfarin in these patients. Recently diagnosed AF was defined as a new diagnosis of AF within 30 days prior to enrollment. Cox proportional hazards models were used to determine the association between recently diagnosed AF and clinical outcomes. We also assessed the efficacy and safety of apixaban versus warfarin according to time since AF diagnosis. Results: In ARISTOTLE, 1899 (10.5%) patients had recently diagnosed AF. After adjustment, patients with recently versus remotely diagnosed Al' had a similar risk of stroke/systemic embolism (HR = 1.07, 95% CI = 0.80-1.42; p 0.67), but higher mortality was seen in patients with recently diagnosed AF (adjusted HR = 1.21, 95% Cl 1.02-1.43; p 0.03). The beneficial effects of apixaban, compared with warfarin, on clinical outcomes were consistent, irrespective of timing of AI' diagnosis (all interaction p-values >0.12). Conclusion: Patients with recently diagnosed AF had a similar risk of stroke but higher mortality than patients with remotely diagnosed AF, suggesting that they are not at "low risk" and warrant stroke prevention strategies. The benefits of apixaban over warfarin were preserved, irrespective of timing of AF diagnosis.
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| 15. |
- Guimaraes, Patricia O., et al.
(författare)
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International normalized ratio control and subsequent clinical outcomes in patients with atrial fibrillation using warfarin
- 2019
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Ingår i: Journal of Thrombosis and Thrombolysis. - : Springer Science and Business Media LLC. - 0929-5305 .- 1573-742X. ; 48:1, s. 27-34
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Tidskriftsartikel (refereegranskat)abstract
- We explored associations between INR measures and clinical outcomes in patients with AF using warfarin, and whether INR history predicted future INR measurements. We included patients in ARISTOTLE who were randomized to and received warfarin. Among patients who had events, we included those with ≥ 3 INR values in the 180 days prior to the event, with the most recent ≤ 60 days prior to the event, who were on warfarin at the time of event (n = 545). Non-event patients were included in the control group if they had ≥ 180 days of warfarin exposure with ≥ 3 INR measurements (n = 7259). The median (25th, 75th) number of INR values per patient was 29 (21, 38) over a median follow-up of 1.8 years. A total of 87% had at least one INR value < 1.5; 49% had at least one value > 4.0. The last INRs before events (median 14 [24, 7] days) were < 3.0 for at least 75% of patients with major bleeding and > 2.0 for half of patients with ischemic stroke. Historic time in therapeutic range (TTR) was weakly associated with future TTR (R2 = 0.212). Historic TTR ≥ 80% had limited predictive ability to discriminate future TTR ≥ 80% (C index 0.61). In patients with AF receiving warfarin, most bleeding events may not have been preventable despite careful INR control. Our findings suggest that INRs collected through routine management are not sufficiently predictive to provide reassurance about future time in therapeutic range or to prevent subsequent outcomes, and might be over-interpreted in clinical practice.
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| 16. |
- Halvorsen, Sigrun, et al.
(författare)
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Efficacy and safety of apixaban compared with warfarin according to age for stroke prevention in atrial fibrillation : observations from the ARISTOTLE trial
- 2014
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Ingår i: European Heart Journal. - : Oxford University Press (OUP). - 0195-668X .- 1522-9645. ; 35:28, s. 1864-1872
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Tidskriftsartikel (refereegranskat)abstract
- Aims The risk of stroke in patients with atrial fibrillation (AF) increases with age. In the ARISTOTLE trial, apixaban when compared with warfarin reduced the rate of stroke, death, and bleeding. We evaluated these outcomes in relation to patient age. Methods and results A total of 18 201 patients with AF and a raised risk of stroke were randomized to warfarin or apixaban 5 mg b.d. with dose reduction to 2.5 mg b.d. or placebo in 831 patients with >= 2 of the following criteria: age >= 80 years, body weight <= 60 kg, or creatinine >= 133 mu mol/L. We used Cox models to compare outcomes in relation to patient age during 1.8 years median follow-up. Of the trial population, 30% were <65 years, 39% were 65 to <75, and 31% were >= 75 years. The rates of stroke, all-cause death, and major bleeding were higher in the older age groups (P < 0.001 for all). Apixaban was more effective than warfarin in preventing stroke and reducing mortality across all age groups, and associated with less major bleeding, less total bleeding, and less intracranial haemorrhage regardless of age (P interaction >0.11 for all). Results were also consistent for the 13% of patients >= 80 years. No significant interaction with apixaban dose was found with respect to treatment effect on major outcomes. Conclusion The benefits of apixaban vs. warfarin were consistent in patients with AF regardless of age. Owing to the higher risk at older age, the absolute benefits of apixaban were greater in the elderly.
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| 17. |
- Held, Claes, et al.
(författare)
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Clinical outcomes and management associated with major bleeding in patients with atrial fibrillation treated with apixaban or warfarin : insights from the ARISTOTLE trial
- 2015
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Ingår i: European Heart Journal. - : Oxford University Press (OUP). - 0195-668X .- 1522-9645. ; 36:20, s. 1264-1272
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Tidskriftsartikel (refereegranskat)abstract
- Aim In the Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation (ARISTOTLE) trial, apixaban compared with warfarin reduced the risk of stroke, major bleed, and death in patients with atrial fibrillation. In this ancillary study, we evaluated clinical consequences of major bleeds, as well as management and treatment effects of warfarin vs. apixaban.Methods and results Major International Society on Thrombosis and Haemostasis bleeding was defined as overt bleeding accompanied by a decrease in haemoglobin (Hb) of ≥2 g/dL or transfusion of ≥2 units of packed red cells, occurring at a critical site or resulting in death. Time to event [death, ischaemic stroke, or myocardial infarction (MI)] was evaluated by Cox regression models. The excess risk associated with bleeding was evaluated by separate time-dependent indicators for intracranial (ICH) and non-intracranial haemorrhage. Major bleeding occurred in 848 individuals (4.7%), of whom 126 (14.9%) died within 30 days. Of 176 patients with an ICH, 76 (43.2%) died, and of the 695 patients with major non-ICH, 64 (9.2%) died within 30 days of the bleeding. The risk of death, ischaemic stroke, or MI was increased roughly 12-fold after a major non-ICH bleeding event within 30 days. Corresponding risk of death following an ICH was markedly increased, with HR 121.5 (95% CI 91.3–161.8) as was stroke or MI with HR 21.95 (95% CI 9.88–48.81), respectively. Among patients with major bleeds, 20.8% received vitamin K and/or related medications (fresh frozen plasma, coagulation factors, factor VIIa) to stop bleeding within 3 days, and 37% received blood transfusion. There was no interaction between apixaban and warfarin and major bleeding on the risk of death, stroke, or MI.Conclusion Major bleeding was associated with substantially increased risk of death, ischaemic stroke, or MI, especially following ICH, and this risk was similarly elevated regardless of treatment with apixaban or warfarin. These results underscore the importance of preventing bleeding in anti-coagulated patients.
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| 18. |
- Hohnloser, Stefan H., et al.
(författare)
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Efficacy of apixaban when compared with warfarin in relation to renal function in patients with atrial fibrillation : insights from the ARISTOTLE trial
- 2012
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Ingår i: European Heart Journal. - : Oxford University Press (OUP). - 0195-668X .- 1522-9645. ; 33:22, s. 2821-2830
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Tidskriftsartikel (refereegranskat)abstract
- AimsAtrial fibrillation (AF) is common among patients with impaired renal function. Apixaban, a novel oral anticoagulant with partial renal excretion, was compared with warfarin and reduced the rate stroke, death and bleeding in the ARISTOTLE trial. We evaluated these outcomes in relation to renal function.Methods and resultsBaseline glomerular filtration rate (GFR) was estimated using the Cockcroft–Gault and Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations as well as cystatin C measurements. According to baseline Cockcroft–Gault, there were 7518 patients (42%) with an estimated GFR (eGFR) of >80 mL/min, 7587 (42%) between >50 and 80 mL/min, and 3017 (15%) with an eGFR of ≤50 mL/min. The rate of cardiovascular events and bleeding was higher at impaired renal function (≤80 mL/min). Apixaban was more effective than warfarin in preventing stroke or systemic embolism and reducing mortality irrespective of renal function. These results were consistent, regardless of methods for GFR estimation. Apixaban was associated with less major bleeding events across all ranges of eGFRs. The relative risk reduction in major bleeding was greater in patients with an eGFR of ≤50 mL/min using Cockcroft–Gault {hazard ratio (HR) 0.50 [95% confidence interval (CI) 0.38–0.66], interaction P = 0.005} or CKD-EPI equations [HR 0.48 (95% CI 0.37–0.64), interaction P = 0.003].ConclusionIn patients with AF, renal impairment was associated with increased risk of cardiovascular events and bleeding. When compared with warfarin, apixaban treatment reduced the rate of stroke, death, and major bleeding, regardless of renal function. Patients with impaired renal function seemed to have the greatest reduction in major bleeding with apixaban.
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| 19. |
- Holmqvist, Fredrik, et al.
(författare)
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Heart rate is associated with progression of atrial fibrillation, independent of rhythm
- 2015
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Ingår i: Heart. - : BMJ. - 1355-6037 .- 1468-201X. ; 101:11, s. 894-899
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Tidskriftsartikel (refereegranskat)abstract
- Objective Atrial fibrillation (AF) often progresses from paroxysmal or persistent to more sustained forms, but the rate and predictors of AF progression in clinical practice are not well described. Methods Using the Outcomes Registry for Better Informed Treatment of AF, we analysed the incidence and predictors of progression and tested the discrimination and calibration of the HATCH (hypertension, age, TIA/stroke, chronic obstructive pulmonary disease, heart failure) and CHA(2)DS(2)VASc scores for identifying AF progression. Results Among 6235 patients with paroxysmal or persistent AF at baseline, 1479 progressed, during follow-up (median 18 (IQR 12-24) months). These patients were older and had more comorbidities than patients who did not progress (CHADS(2) 2.3 +/- 1.3 vs 2.1 +/- 1.3, p<0.0001). At baseline, patients with AF progression were more often on a rate control as opposed to a rhythm control strategy (66 vs 56%, p<0.0001) and had higher heart rate (72(64-80) vs 68 (60-76) bpm, p<0.0001). The strongest predictors of AF progression were AF on the baseline ECG (OR 2.30, 95% CI 1.95 to 2.73, p<0.0001) and increasing age (OR 1.16, 95% CI1.09 to 1.24, p<0.0001, per 10 increase), while patients with lower heart rate (OR 0.84, 95% CI 0.79 to 0.89, p<0.0001, per 10 decrease <= 80) were less likely to progress. There was no significant interaction between rhythm on baseline ECG and heart rate (p=0.71). The HATCH and CHA(2)DS(2)VASc scores had modest discriminatory power for AF progression (C-indices 0.55 (95% CI 0.53 to 0.58) and 0.55 (95% CI 0.52 to 0.57)). Conclusions Within 1.5 years, almost a quarter of the patients with paroxysmal or persistent AF progress to a more sustained form. Progression is strongly associated with heart rate, and age.
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| 20. |
- Hu, Peter T., et al.
(författare)
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Efficacy and Safety of Apixaban Compared With Warfarin in Patients With Atrial Fibrillation and Peripheral Artery Disease : Insights From the ARISTOTLE Trial
- 2017
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Ingår i: Journal of the American Heart Association. - : WILEY-BLACKWELL. - 2047-9980. ; 6:1
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Tidskriftsartikel (refereegranskat)abstract
- Background- We studied (1) the rates of stroke or systemic embolism and bleeding in patients with atrial fibrillation and peripheral artery disease (PAD) and (2) the efficacy and safety of apixaban versus warfarin in patients with atrial fibrillation with and without PAD. Methods and Results- The Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation (ARISTOTLE) trial randomized 18 201 patients with atrial fibrillation to apixaban or warfarin for stroke/systemic embolism prevention; 884 (4.9%) patients had PAD at baseline. Patients with PAD had higher unadjusted rates of stroke and systemic embolism (hazard ratio [HR] 1.73, 95% CI 1.22-2.45; P=0.002) and major bleeding (HR 1.34, 95% CI 1.00-1.81; P=0.05), but after adjustment, no differences existed in rates of stroke and systemic embolism (HR 1.32, 95% CI 0.93-1.88; P=0.12) and major bleeding (HR 1.03, 95% CI 0.76-1.40; P=0.83) compared with patients without PAD. The risk of stroke or systemic embolism was similar in patients assigned to apixaban and warfarin with PAD (HR 0.63, 95% CI 0.32-1.25) and without PAD (HR 0.80, 95% CI 0.66-0.96; interaction P= 0.52). Patients with PAD did not have a statistically significant reduction in major or clinically relevant nonmajor bleeding with apixaban compared with warfarin (HR 1.05, 95% CI 0.69-1.58), whereas those without PAD had a statistically significant reduction (HR 0.65, 95% CI 0.58-0.73; interaction P=0.03). Conclusions- Patients with PAD in ARISTOTLE had a higher crude risk of stroke or systemic embolism compared with patients without PAD that was not present after adjustment. The benefits of apixaban versus warfarin for stroke and systemic embolism were similar in patients with and without PAD. These findings highlight the need to optimize the treatment of patients with atrial fibrillation and PAD.
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| 21. |
- Hylek, Elaine M., et al.
(författare)
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Major Bleeding in Patients With Atrial Fibrillation Receiving Apixaban or Warfarin
- 2014
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Ingår i: Journal of the American College of Cardiology. - : Elsevier BV. - 0735-1097 .- 1558-3597. ; 63:20, s. 2141-2147
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Tidskriftsartikel (refereegranskat)abstract
- Objectives This study sought to characterize major bleeding on the basis of the components of the major bleeding definition, to explore major bleeding by location, to define 30-day mortality after a major bleeding event, and to identify factors associated with major bleeding. Background Apixaban was shown to reduce the risk of major hemorrhage among patients with atrial fibrillation in the ARISTOTLE (Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation) trial. Methods All patients who received at least 1 dose of a study drug were included. Major bleeding was defined according to the criteria of the International Society on Thrombosis and Haemostasis. Factors associated with major hemorrhage were identified using a multivariable Cox model. Results The on-treatment safety population included 18,140 patients. The rate of major hemorrhage among patients in the apixaban group was 2.13% per year compared with 3.09% per year in the warfarin group (hazard ratio [HR] 0.69, 95% confidence interval [CI]: 0.60 to 0.80; p < 0.001). Compared with warfarin, major extracranial hemorrhage associated with apixaban led to reduced hospitalization, medical or surgical intervention, transfusion, or change in antithrombotic therapy. Major hemorrhage followed by mortality within 30 days occurred half as often in apixaban treated patients than in those receiving warfarin (HR 0.50, 95% CI: 0.33 to 0.74; p < 0.001). Older age, prior hemorrhage, prior stroke or transient ischemic attack, diabetes, lower creatinine clearance, decreased hematocrit, aspirin therapy, and nonsteroidal anti-inflammatory drugs were independently associated with an increased risk. Conclusions Apixaban, compared with warfarin, was associated with fewer intracranial hemorrhages, less adverse consequences following extracranial hemorrhage, and a 50% reduction in fatal consequences at 30 days in cases of major hemorrhage. (c) 2014 by the American College of Cardiology Foundation
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| 22. |
- Kharrazi, Sogol, 1980-, et al.
(författare)
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A review of more than a decade of research and field tests on longer vehicle combinations in Sweden that supported road approval
- 2024
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Ingår i: Technology Convergence 2023. - : International Forum for Heavy Vehicle Transport & Technology; The International Society for Weigh-In-Motion.
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- For more than a decade, Longer Vehicle Combinations (LVCs) have been tested in Sweden on roads and test tracks and studied in simulations. Based on the outcomes of this research, the government in Sweden has decided to open part of the road network for LVCs with a length up to 34.5 m. Necessary regulatory framework should be in place before this change can be applied. Thus, the LVCs are not expected on the roads before winter 2023-2024. This article reviews outcomes of the extensive research which has been performed on High Capacity Transport (HCT) to support introduction of LVCs in Sweden. Summary of studies on various aspects of HCT, such as regulation, safety, maneuverability, electrification, and emissions, are presented.
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| 23. |
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| 24. |
- Kumsars, Indulis, et al.
(författare)
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Randomised comparison of provisional side branch stenting versus a two-stent strategy for treatment of true coronary bifurcation lesions involving a large side branch : the Nordic-Baltic Bifurcation Study IV
- 2020
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Ingår i: Open heart. - : BMJ Publishing Group Ltd. - 2053-3624. ; 7:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: It is still uncertain whether coronary bifurcations with lesions involving a large side branch (SB) should be treated by stenting the main vessel and provisional stenting of the SB (simple) or by routine two-stent techniques (complex). We aimed to compare clinical outcome after treatment of lesions in large bifurcations by simple or complex stent implantation.Methods: The study was a randomised, superiority trial. Enrolment required a SB >= 2.75 mm, >= 50% diameter stenosis in both vessels, and allowed SB lesion length up to 15 mm. The primary endpoint was a composite of cardiac death, non-procedural myocardial infarction and target lesion revascularisation at 6 months. Two-year clinical follow-up was included in this primary reporting due to lower than expected event rates.Results: A total of 450 patients were assigned to simple stenting (n = 221) or complex stenting (n=229) in 14 Nordic and Baltic centres. Two-year follow-up was available in 218 (98.6%) and 228 (99.5%) patients, respectively. The primary endpoint of major adverse cardiac events (MACE) at 6 months was 5.5% vs 2.2% (risk differences 3.2%, 95% CI -0.2 to 6.8, p=0.07) and at 2 years 12.9% vs 8.4% (HR 0.63, 95% CI 0.35 to 1.13, p = 0.12) after simple versus complex treatment. In the subgroup treated by newer generation drug-eluting stents, MACE was 12.0% vs 5.6% (HR 0.45, 95% CI 0.17 to 1.17, p = 0.10) after simple versus complex treatment.Conclusion: In the treatment of bifurcation lesions involving a large SB with ostial stenosis, routine two-stent techniques did not improve outcome significantly compared with treatment by the simpler main vessel stenting technique after 2 years.
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| 25. |
- Laine, Veronika N., et al.
(författare)
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Whole-genome Analysis Reveals Contrasting Relationships Among Nuclear and Mitochondrial Genomes Between Three Sympatric Bat Species
- 2023
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Ingår i: Genome Biology and Evolution. - : Oxford University Press (OUP). - 1759-6653. ; 15:1
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Tidskriftsartikel (refereegranskat)abstract
- Understanding mechanisms involved in speciation can be challenging, especially when hybridization or introgression blurs species boundaries. In bats, resolving relationships of some closely related groups has proved difficult due subtle interspecific variation both in morphometrics and molecular data sets. The endemic South American Histiotus bats, currently considered a subgenus of Eptesicus, harbor unresolved phylogenetic relationships and of those is a trio consisting of two closely related species: Eptesicus (Histiotus) macrotus and Eptesicus (Histiotus) montanus, and their relationship with a third, Eptesicus (Histiotus) magellanicus. The three sympatric species bear marked resemblance to each other, but can be differentiated morphologically. Furthermore, previous studies have been unable to differentiate the species from each other at a molecular level. In order to disentangle the phylogenetic relationships of these species, we examined the differentiation patterns and evolutionary history of the three Eptesicus (H.) species at the whole-genome level. The nuclear DNA statistics between the species suggest strong gene flow and recent hybridization between E. (H.) montanus and E. (H.) macrotus, whereas E. (H.) magellanicus shows a higher degree of isolation. In contrast, mitochondrial DNA shows a closer relationship between E. (H.) magellanicus and E. (H.) montanus. Opposing patterns in mtDNA and nuclear markers are often due to differences in dispersal, and here it could be both as a result of isolation in refugia during the last glacial maximum and female philopatry and male-biased dispersal. In conclusion, this study shows the importance of both the nuclear and mitochondrial DNA in resolving phylogenetic relationships and species histories.
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| 26. |
- Lopes, Renato D., et al.
(författare)
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Digoxin and Mortality in Patients With Atrial Fibrillation
- 2018
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Ingår i: Journal of the American College of Cardiology. - : ELSEVIER SCIENCE INC. - 0735-1097 .- 1558-3597. ; 71:10, s. 1063-1074
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Digoxin is widely used in patients with atrial fibrillation (AF). OBJECTIVES The goal of this paper was to explore whether digoxin use was independently associated with increased mortality in patients with AF and if the association was modified by heart failure and/or serum digoxin concentration.METHODS: The association between digoxin use and mortality was assessed in 17,897 patients by using a propensity score-adjusted analysis and in new digoxin users during the trial versus propensity score-matched control participants. The authors investigated the independent association between serum digoxin concentration and mortality after multivariable adjustment.RESULTS: At baseline, 5,824 (32.5%) patients were receiving digoxin. Baseline digoxin use was not associated with an increased risk of death (adjusted hazard ratio [HR]: 1.09; 95% confidence interval [CI]: 0.96 to 1.23; p = 0.19). However, patients with a serum digoxin concentration $ 1.2 ng/ml had a 56% increased hazard of mortality (adjusted HR: 1.56; 95% CI: 1.20 to 2.04) compared with those not on digoxin. When analyzed as a continuous variable, serum digoxin concentration was associated with a 19% higher adjusted hazard of death for each 0.5-ng/ml increase (p = 0.0010); these results were similar for patients with and without heart failure. Compared with propensity score-matched control participants, the risk of death (adjusted HR: 1.78; 95% CI: 1.37 to 2.31) and sudden death (adjusted HR: 2.14; 95% CI: 1.11 to 4.12) was significantly higher in new digoxin users.CONCLUSIONS: In patients with AF taking digoxin, the risk of death was independently related to serum digoxin concentration and was highest in patients with concentrations $ 1.2 ng/ml. Initiating digoxin was independently associated with higher mortality in patients with AF, regardless of heart failure.
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| 27. |
- Lopes, Renato D., et al.
(författare)
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Intracranial hemorrhage in patients with atrial fibrillation receiving anticoagulation therapy
- 2017
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Ingår i: Blood. - : AMER SOC HEMATOLOGY. - 0006-4971 .- 1528-0020. ; 129:22, s. 2980-2987
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Tidskriftsartikel (refereegranskat)abstract
- We investigated the frequency and characteristics of intracranial hemorrhage (ICH), the factors associated with the risk of ICH, and outcomes post-ICH overall and by randomized treatment. We identified patients with ICH from the overall trial population enrolled in the Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation trial who received >= 1 dose of the study drug (n = 18 140). ICH was adjudicated by a central committee. Cox regression models were used to identify factors associated with ICH. ICH occurred in 174 patients; most ICH events were spontaneous (71.7%) versus traumatic (28.3%). Apixaban resulted in significantly less ICH (0.33% per year), regardless of type and location, than warfarin (0.80% per year). Independent factors associated with increased risk of ICH were enrollment in Asia or Latin America, older age, prior stroke/transient ischemic attack, and aspirin use at baseline. Among warfarin-treated patients, the median (25th, 75th percentiles) time from most recent international normalized ratio (INR) to ICH was 13 days (6, 21 days). Median INR prior to ICH was 2.6 (2.1, 3.0); 78.5% of patients had a pre-ICH INR <3.0. After ICH, the modified Rankin scale score at discharge was >= 4 in 55.7% of patients, and the overall mortality rate at 30 days was 43.3% with no difference between apixaban- and warfarin-treated patients. ICH occurred at a rate of 0.80% per year with warfarin regardless of INR control and at a rate of 0.33% per year with apixaban and was associated with high short-termmorbidity and mortality. This highlights the clinical relevance of reducing ICH by using apixaban rather than warfarin and avoiding concomitant aspirin, especially in patients of older age. This trial was registered at www.clinicaltrials.gov as #NCT00412984.
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| 28. |
- McCarthy, Randy J., et al.
(författare)
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Registered Replication Report on Srull and Wyer (1979)
- 2018
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Ingår i: Advances in Methods and Practices in Psychological Science. - : SAGE Publications Inc. - 2515-2459 .- 2515-2467. ; 1:3, s. 321-336
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Tidskriftsartikel (refereegranskat)abstract
- Srull and Wyer (1979) demonstrated that exposing participants to more hostility-related stimuli caused them subsequently to interpret ambiguous behaviors as more hostile. In their Experiment 1, participants descrambled sets of words to form sentences. In one condition, 80% of the descrambled sentences described hostile behaviors, and in another condition, 20% described hostile behaviors. Following the descrambling task, all participants read a vignette about a man named Donald who behaved in an ambiguously hostile manner and then rated him on a set of personality traits. Next, participants rated the hostility of various ambiguously hostile behaviors (all ratings on scales from 0 to 10). Participants who descrambled mostly hostile sentences rated Donald and the ambiguous behaviors as approximately 3 scale points more hostile than did those who descrambled mostly neutral sentences. This Registered Replication Report describes the results of 26 independent replications (N = 7,373 in the total sample; k = 22 labs and N = 5,610 in the primary analyses) of Srull and Wyer?s Experiment 1, each of which followed a preregistered and vetted protocol. A random-effects meta-analysis showed that the protagonist was seen as 0.08 scale points more hostile when participants were primed with 80% hostile sentences than when they were primed with 20% hostile sentences (95% confidence interval, CI = [0.004, 0.16]). The ambiguously hostile behaviors were seen as 0.08 points less hostile when participants were primed with 80% hostile sentences than when they were primed with 20% hostile sentences (95% CI = [?0.18, 0.01]). Although the confidence interval for one outcome excluded zero and the observed effect was in the predicted direction, these results suggest that the currently used methods do not produce an assimilative priming effect that is practically and routinely detectable.
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| 29. |
- Melloni, Chiara, et al.
(författare)
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Efficacy and Safety of Apixaban Versus Warfarin in Patients with Atrial Fibrillation and a History of Cancer : Insights from the ARISTOTLE Trial.
- 2017
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Ingår i: American Journal of Medicine. - : Elsevier BV. - 0002-9343 .- 1555-7162. ; 130:12, s. 1440-1448.e1
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Cancer is associated with a prothrombotic state and increases the risk of thrombotic events in patients with atrial fibrillation. We described the clinical characteristics and outcomes and assessed the safety and efficacy of apixaban versus warfarin in patients with atrial fibrillation and cancer in the Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation (ARISTOTLE) trial.METHODS: The association between cancer and clinical outcomes was assessed using Cox regression models. At baseline, 1236 patients (6.8%) had a history of cancer; 12.7% had active cancer, and 87.3% had remote cancer.RESULTS: There were no significant associations between history of cancer and stroke/systemic embolism, major bleeding, or death. The effect of apixaban versus warfarin for the prevention of stroke/systemic embolism was consistent among patients with a history of cancer (event/100 patient-years = 1.4 vs 1.2; hazard ratio [HR], 1.09; 95% confidence interval [CI], 0.53-2.26) and no cancer (1.3 vs 1.6; HR, 0.77; 95% CI, 0.64-0.93) (P interaction = .37). The safety and efficacy of apixaban versus warfarin were preserved among patients with and without active cancer. Apixaban was associated with a greater benefit for the composite of stroke/systemic embolism, myocardial infarction, and death in active cancer (HR, 0.30; 95% CI, 0.11-0.83) versus without cancer (HR, 0.86; 95% CI, 0.78-0.95), but not in remote cancer (HR, 1.46; 95% CI, 1.01-2.10) (interaction P = .0028).CONCLUSIONS: Cancer was not associated with a higher risk of stroke. The superior efficacy and safety of apixaban versus warfarin were consistent in patients with and without cancer. Our positive findings regarding apixaban use in patients with atrial fibrillation and cancer are exploratory and promising, but warrant further evaluation.
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| 30. |
- Rao, Meena P, et al.
(författare)
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Blood Pressure Control and Risk of Stroke or Systemic Embolism in Patients With Atrial Fibrillation : Results From the Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation (ARISTOTLE) Trial
- 2015
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Ingår i: Journal of the American Heart Association. - 2047-9980. ; 4:12
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Patients with atrial fibrillation (AF) and hypertension are at high risk for stroke. Previous studies have shown elevated risk of stroke in patients with AF who have a history of hypertension (regardless of blood pressure [BP] control) and in patients with elevated BP. We assessed the association of hypertension and BP control on clinical outcomes.METHODS AND RESULTS: In ARISTOTLE (n=18 201), BP was evaluated as history of hypertension requiring treatment and elevated BP (systolic ≥140 and/or diastolic ≥90 mm Hg) at study entry and any point during the trial. Hazard ratios (HRs) were derived from Cox proportional hazards models including BP as a time-dependent covariate. A total of 15 916 (87.5%) patients had a history of hypertension requiring treatment. In patients with elevated BP measurement at any point during the trial, the rate of stroke or systemic embolism was significantly higher (HR, 1.53; 95% confidence interval [CI], 1.25-1.86), as was hemorrhagic stroke (HR 1.85; 95% CI, 1.26-2.72) and ischemic stroke (HR, 1.50; 95% CI, 1.18-1.90). Rates of major bleeding were lower in patients with a history of hypertension (HR, 0.80; 95% CI, 0.66-0.98) and nonsignificantly lower in patients with elevated BP at study entry (HR, 0.89; 95% CI, 0.77-1.03). The benefit of apixaban versus warfarin on preventing stroke or systemic embolism was consistent among patients with and without a history of hypertension (P interaction=0.27), BP control at baseline (P interaction=0.43), and BP control during the trial (P interaction=0.97).CONCLUSIONS: High BP measurement at any point during the trial was independently associated with a substantially higher risk of stroke or systemic embolism. These results strongly support efforts to treat elevated BP as an important strategy to optimally lower risk of stroke in patients with AF.CLINICAL TRIAL REGISTRATION: URL: https://ClinicalTrials.gov/. Unique identifier: NCT00412984.
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| 31. |
- Santangelo, James S., et al.
(författare)
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Global urban environmental change drives adaptation in white clover
- 2022
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 375
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Tidskriftsartikel (refereegranskat)abstract
- Urbanization transforms environments in ways that alter biological evolution. We examined whether urban environmental change drives parallel evolution by sampling 110,019 white clover plants from 6169 populations in 160 cities globally. Plants were assayed for a Mendelian antiherbivore defense that also affects tolerance to abiotic stressors. Urban-rural gradients were associated with the evolution of clines in defense in 47% of cities throughout the world. Variation in the strength of clines was explained by environmental changes in drought stress and vegetation cover that varied among cities. Sequencing 2074 genomes from 26 cities revealed that the evolution of urban-rural dines was best explained by adaptive evolution, but the degree of parallel adaptation varied among cities. Our results demonstrate that urbanization leads to adaptation at a global scale.
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| 32. |
- Sormunen, Piia, et al.
(författare)
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Capturing stakeholder values : Stakeholder values, stakeholder preferences and requirements for the life cycle design process
- 2009
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- The objective of Task 2.3 was to create a framework for capturing the values of different stakeholders over the life cycle of a building. The framework should work as a method for capturing goals and preferences of all stakeholders and add value to the client and constructor as well as to the society and citizens. Another goal was to create a list of value groups, values, requirements and parameters to serve as a checklist for value mapping in a design project. The framework acts as an incentive for model-based working to enable evaluation of design performance and open collaboration between all stakeholders. It presents a process during which the needs and preferences that add value to society/citizens, clients/users, and the construction sector over the life cycle of a building are captured. These stakeholder values for a facility and process are translated into requirements and attributes for the specific business case to give a clear set of design targets for the life cycle design process. In the purposes of this task, briefing is proposed as the main procedure for identifying and capturing stakeholder values. Briefing is the process in which the client’s needs, wishes and ambitions are identified, expressed and clarified in the building process. The briefing process is an integral part of the design process. It is iterative and moves from the general to the particular. Strategic briefing deals with the business case, stakeholders and project goals. Operational briefing concerns functional requirements derived from the strategic briefing. Technical briefing specifies in technical terms the consequences of the functional requirements. The briefing methods and its tools must support a top-down systems approach. The Concurrent Design Method, originally a space-born design methodology developed and used by the European Space Agency (ESA), is chosen to support the briefing process of the framework. This method ensures collaborative work where the various stakeholders interact and influence each other’s values and proposals when in sessions concurrently working on the same IT-based platform. The design work is done in collocated sessions with all stakeholders involved and present, creating an integrated design and enabling good communication and exchange of information between team members. The concurrent design method was applied by the task group in three one-day workshops with the Swedish Post head office in Stockholm as the case building. The sessions resulted in a list of all the value groups, values, requirements and parameters that were exchanged, discussed and added during the sessions. From this list, an exemplary list of value groups, values, requirements and parameters was created. This set of generalized values can be recommended to serve as a checklist for value mapping in further projects. The work in the concurrent design sessions is based on assumptions in the briefs and the results of the sessions are fed back into the briefs and can even affect the initial goals. The method was found to be very supportive for the briefing process. Because the method is iterative, it can successively contribute to a mutual, better understanding of the total project. The task group can therefore recommend it for application as a tool for briefing support. To test the created framework two studies were made: one to proof that the framework efficiently captures the stakeholder values and one to to demonstrate the detection of contradictory goals and values. The results of these studies are presented in Part 2 of this report. The work done in T2.3 is the first part of the global life cycle process, which goes from the capture of the client’s values to the evaluation of the performance of the project. The results of Task 2.3 will be further used in InPro Task 2.4 “Life Cycle Design Processes” and Task 1.3 “Key Performance Indicators”. Lists of requirements and parameters were delivered for the different life cycle processes (LCD) of InPro Task 2.4: energy performance, facility management & maintenance, enviReport – Capturing Stakeholder Values, Values, Preferences and Requirements ■ May 2009 5/45 ronmental performance & materials, cost management and project planning. These lists were placed in quality gates of different life cycle processes in order to verify and evaluate the implementation of the stakeholder values. Task 1.3 will use proposed parameters as performance indicators. The goal of the Deliverable D10 (An Evaluation Framework for Early Design based on Key Performance Indicators) is to detail the method to highlight the Key Performance Indicators, i.e. to classify and prioritise the more relevant parameters, in order to evaluate the performance of the design and of the building, and in order to compare the client’s expected requirements with the real life cycle processes. These KPI give common and reliable hypothesis, with which each actor can carry out its design, and which help taking decision with an accurate quality level to reach.
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| 33. |
- Verschuere, Bruno, et al.
(författare)
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Registered Replication Report on Mazar, Amir, and Ariely (2008)
- 2018
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Ingår i: Advances in Methods and Practices in Psychological Science. - : SAGE Publications. - 2515-2459 .- 2515-2467. ; 1:3, s. 299-317
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Tidskriftsartikel (refereegranskat)abstract
- The self-concept maintenance theory holds that many people will cheat in order to maximize self-profit, but only to the extent that they can do so while maintaining a positive self-concept. Mazar, Amir, and Ariely (2008, Experiment 1) gave participants an opportunity and incentive to cheat on a problem-solving task. Prior to that task, participants either recalled the Ten Commandments (a moral reminder) or recalled 10 books they had read in high school (a neutral task). Results were consistent with the self-concept maintenance theory. When given the opportunity to cheat, participants given the moral-reminder priming task reported solving 1.45 fewer matrices than did those given a neutral prime (Cohen’s d = 0.48); moral reminders reduced cheating. Mazar et al.’s article is among the most cited in deception research, but their Experiment 1 has not been replicated directly. This Registered Replication Report describes the aggregated result of 25 direct replications (total N = 5,786), all of which followed the same preregistered protocol. In the primary meta-analysis (19 replications, total n = 4,674), participants who were given an opportunity to cheat reported solving 0.11 more matrices if they were given a moral reminder than if they were given a neutral reminder (95% confidence interval = [−0.09, 0.31]). This small effect was numerically in the opposite direction of the effect observed in the original study (Cohen’s d = −0.04).
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| 34. |
- Vesterinen, Eero J, et al.
(författare)
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What you need is what you eat? Prey selection by the bat Myotis daubentonii.
- 2016
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Ingår i: Molecular Ecology. - : Wiley. - 0962-1083 .- 1365-294X. ; 25, s. 1581-1594
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Tidskriftsartikel (refereegranskat)abstract
- Optimal foraging theory predicts that predators are selective when faced with abundant prey, but become less picky when prey gets sparse. Insectivorous bats in temperate regions are faced with the challenge of building up fat reserves vital for hibernation during a period of decreasing arthropod abundances. According to optimal foraging theory, pre-hibernating bats should adopt a less selective feeding behavior - yet empirical studies have revealed many apparently generalized species to be composed of specialist individuals. Targeting the diet of the bat Myotis daubentonii, we used a combination of molecular techniques to test for seasonal changes in prey selectivity and individual-level variation in prey preferences. DNA metabarcoding was used to characterise both the prey contents of bat droppings and the insect community available as prey. To test for dietary differences among M. daubentonii individuals, we used ten microsatellite loci to assign droppings to individual bats. The comparison between consumed and available prey revealed a preference for certain prey items regardless of availability. Non-biting midges (Chironomidae) remained the most highly consumed prey at all times, despite a significant increase in the availability of black-flies (Simuliidae) towards the end of the season. The bats sampled showed no evidence of individual specialization in dietary preferences. Overall, our approach offers little support for optimal foraging theory. Thus, it shows how novel combinations of genetic markers can be used to test general theory, targeting patterns at both the level of prey communities and individual predators. This article is protected by copyright. All rights reserved.
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| 35. |
- Wallentin, Lars, et al.
(författare)
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Efficacy and safety of apixaban compared with warfarin at different levels of predicted international normalized ratio control for stroke prevention in atrial fibrillation
- 2013
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Ingår i: Circulation. - 0009-7322 .- 1524-4539. ; 127:22, s. 2166-2176
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundIn the Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation (ARISTOTLE) trial, apixaban compared with warfarin reduced stroke and systemic embolism, major bleeding, and mortality. We evaluated treatment effects in relation to 2 predictions of time in therapeutic range (TTR).Methods and ResultsThe trial randomized 18 201 patients with atrial fibrillation to apixaban 5 mg twice daily or warfarin for at least 12 months. For each patient, a center average TTR was estimated with the use of a linear mixed model on the basis of the real TTRs in its warfarin-treated patients, with a fixed effect for country and random effect for center. For each patient, an individual TTR was also predicted with the use of a linear mixed effects model including patient characteristics as well. Median center average TTR was 66% (interquartile limits, 61% and 71%). Rates of stroke or systemic embolism, major bleeding, and mortality were consistently lower with apixaban than with warfarin across center average TTR and individual TTR quartiles. In the lowest and highest center average TTR quartiles, hazard ratios for stroke or systemic embolism were 0.73 (95% confidence interval [CI], 0.53–1.00) and 0.88 (95% CI, 0.57–1.35) (Pinteraction=0.078), for mortality were 0.91 (95% CI, 0.74–1.13) and 0.91 (95% CI, 0.71–1.16) (Pinteraction=0.34), and for major bleeding were 0.50 (95% CI, 0.36–0.70) and 0.75 (95% CI, 0.58–0.97) (Pinteraction=0.095), respectively. Similar results were seen for quartiles of individual TTR.ConclusionsThe benefits of apixaban compared with warfarin for stroke or systemic embolism, bleeding, and mortality appear similar across the range of centers’ and patients’ predicted quality of international normalized ratio control.Clinical Trial RegistrationURL: http://www.clinicaltrials.gov. Unique identifier: NCT00412984.
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| 36. |
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| 37. |
- Westenbrink, B. Daan, et al.
(författare)
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Anemia is associated with bleeding and mortality, but not stroke, in patients with atrial fibrillation : Insights from the Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation (ARISTOTLE) trial
- 2017
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Ingår i: American Heart Journal. - : MOSBY-ELSEVIER. - 0002-8703 .- 1097-6744. ; 185, s. 140-149
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Tidskriftsartikel (refereegranskat)abstract
- Background Patients with atrial fibrillation (AF) are prone to cardiovascular events and anticoagulation-related bleeding complications. We hypothesized that patients with anemia are at increased risk for these outcomes. Methods We performed a post hoc analysis of the ARISTOTLE trial, which included >18,000 patients with AF randomized to warfarin (target international normalized ratio, 2.0-3.0) or apixaban 5 mg twice daily. Multivariable Cox regression analysis was used to determine if anemia (defined as hemoglobin <13.0 in men and <12.0 g/dL in women) was associated with future stroke, major bleeding, or mortality. Results Anemia was present at baseline in 12.6% of the ARISTOTLE population. Patients with anemia were older, had higher mean CHADS2 and HAS-BLED scores, and were more likely to have experienced previous bleeding events. Anemia was associated with major bleeding (adjusted hazard ratio [HR], 1.92; 95% CI, 1.62-2.28; P < .0001) and all-cause mortality (adjusted HR, 1.68; 95% CI, 1.46-1.93; P <. 0001) but not stroke or systemic embolism (adjusted HR, 0.92; 95% CI, 0.70-1.21). The benefits of apixaban compared with warfarin on the rates of stroke, mortality, and bleeding events were consistent in patients with and without anemia. Conclusions Chronic anemia is associated with a higher incidence of bleeding complications and mortality, but not of stroke, in anticoagulated patients with AF. Apixaban is an attractive anticoagulant for stroke prevention in patients with AF with or without anemia.
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