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- Furtado, R. H. M., et al.
(författare)
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Caffeinated Beverage Intake, Dyspnea With Ticagrelor, and Cardiovascular Outcomes: Insights From the PEGASUS-TIMI 54 Trial
- 2020
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Ingår i: Journal of the American Heart Association. - : Ovid Technologies (Wolters Kluwer Health). - 2047-9980. ; 9:10
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: A proposed cause of dyspnea induced by ticagrelor is an increase in adenosine blood levels. Because caffeine is an adenosine antagonist, it can potentially improve drug tolerability with regard to dyspnea. Furthermore, association between caffeine and cardiovascular events is of clinical interest. METHODS AND RESULTS: This prespecified analysis used data from the PEGASUS TIMI 54 (Prevention of Cardiovascular Events in Patients With Prior Heart Attack Using Ticagrelor Compared to Placebo on a Background of Aspirin-Thrombolysis in Myocardial Infarction 54) trial, which randomized 21 162 patients with prior myocardial infarction to ticagrelor 60 mg or 90 mg or matching placebo (twice daily). Baseline caffeine intake in cups per week was prospectively collected for 9694 patients. Outcomes of interest included dyspnea, major adverse cardiovascular events (ie, the composite of cardiovascular death, myocardial infarction, or stroke), and arrhythmias. Dyspnea analyses considered the pooled ticagrelor group, whereas cardiovascular outcome analyses included patients from the 3 randomized arms. After adjustment, caffeine intake, compared with no intake, was not associated with lower rates of dyspnea in patients taking ticagrelor (adjusted hazard ratio (HR), 0.91; 95% CI, 0.76-1.10; P= 0.34). There was no excess risk with caffeine for major adverse cardiovascular events (adjusted HR, 0.78; 95% CI, 0.63-0.98; P=0.031), sudden cardiac death (adjusted HR, 0.98; 95% CI, 0.57-1.70; P=0.95), or atrial fibrillation (adjusted odds ratio, 1.07; 95% CI, 0.56-2.04; P=0.84). CONCLUSIONS: In patients taking ticagrelor for secondary prevention after myocardial infarction, caffeine intake at baseline was not associated with lower rates of dyspnea compared with no intake. Otherwise, caffeine appeared to be safe in this population, with no apparent increase in atherothrombotic events or clinically significant arrhythmias.
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| 5. |
- Bonaca, M. P., et al.
(författare)
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Reduction in subtypes and sizes of myocardial infarction with ticagrelor in PEGASUS-TIMI 54
- 2018
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Ingår i: Journal of the American Heart Association. - 2047-9980. ; 7:22
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Tidskriftsartikel (refereegranskat)abstract
- Background-—Ticagrelor reduced cardiovascular death, myocardial infarction (MI), or stroke in patients with prior MI in PEGASUSTIMI 54 (Prevention of Cardiovascular Events [eg, Death From Heart or Vascular Disease, Heart Attack, or Stroke] in Patients With Prior Heart Attack Using Ticagrelor Compared to Placebo on a Background of Aspirin). MI can occur in diverse settings and with varying severity; therefore, understanding the types and sizes of MI events prevented is of clinical importance. Methods and Results-—MIs were adjudicated by a blinded clinical events committee and categorized by subtype and fold elevation of peak cardiac troponin over the upper limit of normal. A total of 1042 MIs occurred in 898 of the 21 162 randomized patients over a median follow-up of 33 months. The majority of the MIs (76%) were spontaneous (Type 1), with demand MI (Type 2) and stent thrombosis (Type 4b) accounting for 13% and 9%, respectively; sudden death (Type 3), percutaneous coronary intervention–related (Type 4a) and coronary artery bypass graft–related (Type 5) each accounted for <1%. Half of MIs (520, 50%) had a peak troponin ≥10x upper limit of normal and 21% of MIs (220) had a peak troponin ≥1009 upper limit of normal. A total of 21% (224) were ST-segment–elevation MI STEMI. Overall ticagrelor reduced MI (4.47% versus 5.25%, hazard ratio 0.83, 95% confidence interval 0.72–0.95, P=0.0055). The benefit was consistent among the subtypes, including a 31% reduction in MIs with a peak troponin ≥1009 upper limit of normal (hazard ratio 0.69, 95% confidence interval 0.53–0.92, P=0.0096) and a 40% reduction in ST-segment elevation MI (hazard ratio 0.60, 95% confidence interval 0.46–0.78, P=0.0002). Conclusions-—In stable outpatients with prior MI, the majority of recurrent MIs are spontaneous and associated with a high biomarker elevation. Ticagrelor reduces the MI consistently among subtypes and sizes including large MIs and ST-segment elevation MI. Clinical Trial Registration-URL: https://www.clinicaltrials.gov. Unique identifier: NCT01225562. © 2018 The Authors.
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| 6. |
- Davies, Thomas G., et al.
(författare)
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Open data and digital morphology.
- 2017
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Ingår i: Proceedings of the Royal Society of London. Biological Sciences. - : The Royal Society. - 0962-8452 .- 1471-2954. ; 284:1852, s. 1-10
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Tidskriftsartikel (refereegranskat)abstract
- Over the past two decades, the development of methods for visualizing and analysing specimens digitally, in three and even four dimensions, has transformed the study of living and fossil organisms. However, the initial promise that the widespread application of such methods would facilitate access to the underlying digital data has not been fully achieved. The underlying datasets for many published studies are not readily or freely available, introducing a barrier to verification and reproducibility, and the reuse of data. There is no current agreement or policy on the amount and type of data that should be made available alongside studies that use, and in some cases are wholly reliant on, digital morphology. Here, we propose a set of recommendations for minimum standards and additional best practice for three-dimensional digital data publication, and review the issues around data storage, management and accessibility.
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| 8. |
- Ganguly, Koustav, et al.
(författare)
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Computational modeling of lung deposition of inhaled particles in chronic obstructive pulmonary disease (COPD) patients : identification of gaps in knowledge and data
- 2019
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Ingår i: Critical reviews in toxicology. - : TAYLOR & FRANCIS LTD. - 1040-8444 .- 1547-6898. ; 49:2, s. 160-173
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Forskningsöversikt (refereegranskat)abstract
- Computational modeling together with experimental data are essential to assess the risk for particulate matter mediated lung toxicity and to predict the efficacy, safety and fate of aerosolized drug molecules used in inhalation therapy. In silico models are widely used to understand the deposition, distribution, and clearance of inhaled particles and aerosols in the human lung. Exacerbations of chronic obstructive pulmonary disease (COPD) have been reported due to increased particulate matter related air pollution episodes. Considering the profound functional, anatomical and structural changes occurring in COPD lungs, the relevance of the existing in silico models for mimicking diseased lungs warrants reevaluation. Currently available computational modeling tools were developed for the healthy adult (male) lung. Here, we analyze the major alterations occurring in the airway structure, anatomy and pulmonary function in the COPD lung, as compared to the healthy lung. We also scrutinize the various physiological and particle characteristics that influence particle deposition, distribution and clearance in the lung. The aim of this review is to evaluate the availability of the fundamental knowledge and data required for modeling particle deposition in a COPD lung departing from the existing healthy lung models. The extent to which COPD pathophysiology may affect aerosol deposition depends on the relative contribution of several factors such as altered lung structure and function, bronchoconstriction, emphysema, loss of elastic recoil, altered breathing pattern and altered liquid volumes that warrant consideration while developing physiologically relevant in silico models.
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| 10. |
- Johanson, Per, 1963, et al.
(författare)
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A dynamic model forecasting myocardial infarct size before, during, and after reperfusion therapy: an ASSENT-2 ECG/VCG substudy
- 2005
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Ingår i: Eur Heart J. - : Oxford University Press (OUP). - 0195-668X. ; 26:17, s. 1726-33
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Tidskriftsartikel (refereegranskat)abstract
- AIMS: Serial forecasts of final myocardial infarct (MI) size during fibrinolytic treatment (Rx) of ST-elevation MI would allow the identification of high-risk patients with a predicted major loss of viable myocardium, at a point when treatment may still be modified. We investigated a model for such forecasting, using time and the ECG. METHODS AND RESULTS: We collected 234 patients with ST-elevation MI, without signs of previous MI, bundle branch block, or hypertrophy. MI size was determined by the Selvester score and was "forecasted" at: admission with patients stratified by delay time and an ECG acuteness score into three groups (EARLY, DISCORDANT, and LATE); 90 min after Rx by > or =70% ST-recovery or not and occurrence of "reperfusion peaks"; 4 h after Rx by ST re-elevations. EARLY patients had smaller final infarct sizes than LATE (9.4 vs. 20%, P=0.01). EARLY patients with > or =70% ST-recovery without a reperfusion peak had smaller infarct sizes than those with (3.1 vs. 12.5%, P=0.001). EARLY patients without ST re-elevations had smaller infarct sizes (1.5%) than those with some (9%) or many re-elevations (12%), P<0.001. CONCLUSION: Final infarct size can be forecasted using delay time and serial ECGs. Serially updated forecasts seem especially important when both clock-time and initial ECG- signs indicate earliness.
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