Outcomes Associated With Oral Anticoagulants Plus Antiplatelets in Patients With Newly Diagnosed Atrial Fibrillation.

Importance: Patients with nonvalvular atrial fibrillation at risk of stroke should receive oral anticoagulants (OAC). However, approximately 1 in 8 patients in the Global Anticoagulant Registry in the Field (GARFIELD-AF) registry are treated with antiplatelet (AP) drugs in addition to OAC, with or without documented vascular disease or other indications for AP therapy. Objective: To investigate baseline characteristics and outcomes of patients who were prescribed OAC plus AP therapy vs OAC alone. Design, Setting, and Participants: Prospective cohort study of the GARFIELD-AF registry, an international, multicenter, observational study of adults aged 18 years and older with recently diagnosed nonvalvular atrial fibrillation and at least 1 risk factor for stroke enrolled between March 2010 and August 2016. Data were extracted for analysis in October 2017 and analyzed from April 2018 to June 2019. Exposure: Participants received either OAC plus AP or OAC alone. Main Outcomes and Measures: Clinical outcomes were measured over 3 and 12 months. Outcomes were adjusted for 40 covariates, including baseline conditions and medications. Results: A total of 24 436 patients (13 438 [55.0%] male; median [interquartile range] age, 71 [64-78] years) were analyzed. Among eligible patients, those receiving OAC plus AP therapy had a greater prevalence of cardiovascular indications for AP, including acute coronary syndromes (22.0% vs 4.3%), coronary artery disease (39.1% vs 9.8%), and carotid occlusive disease (4.8% vs 2.0%). Over 1 year, patients treated with OAC plus AP had significantly higher incidence rates of stroke (adjusted hazard ratio [aHR], 1.49; 95% CI, 1.01-2.20) and any bleeding event (aHR, 1.41; 95% CI, 1.17-1.70) than those treated with OAC alone. These patients did not show evidence of reduced all-cause mortality (aHR, 1.22; 95% CI, 0.98-1.51). Risk of acute coronary syndrome was not reduced in patients taking OAC plus AP compared with OAC alone (aHR, 1.16; 95% CI, 0.70-1.94). Patients treated with OAC plus AP also had higher rates of all clinical outcomes than those treated with OAC alone over the short term (3 months). Conclusions and Relevance: This study challenges the practice of coprescribing OAC plus AP unless there is a clear indication for adding AP to OAC therapy in newly diagnosed atrial fibrillation

Bivalirudin started during emergency transport for primary PCI.

BACKGROUND: Bivalirudin, as compared with heparin and glycoprotein IIb/IIIa inhibitors, has been shown to reduce rates of bleeding and death in patients undergoing primary percutaneous coronary intervention (PCI). Whether these benefits persist in contemporary practice characterized by prehospital initiation of treatment, optional use of glycoprotein IIb/IIIa inhibitors and novel P2Y12 inhibitors, and radial-artery PCI access use is unknown. METHODS: We randomly assigned 2218 patients with ST-segment elevation myocardial infarction (STEMI) who were being transported for primary PCI to receive either bivalirudin or unfractionated or low-molecular-weight heparin with optional glycoprotein IIb/IIIa inhibitors (control group). The primary outcome at 30 days was a composite of death or major bleeding not associated with coronary-artery bypass grafting (CABG), and the principal secondary outcome was a composite of death, reinfarction, or non-CABG major bleeding. RESULTS: Bivalirudin, as compared with the control intervention, reduced the risk of the primary outcome (5.1% vs. 8.5%; relative risk, 0.60; 95% confidence interval [CI], 0.43 to 0.82; P=0.001) and the principal secondary outcome (6.6% vs. 9.2%; relative risk, 0.72; 95% CI, 0.54 to 0.96; P=0.02). Bivalirudin also reduced the risk of major bleeding (2.6% vs. 6.0%; relative risk, 0.43; 95% CI, 0.28 to 0.66; P<0.001). The risk of acute stent thrombosis was higher with bivalirudin (1.1% vs. 0.2%; relative risk, 6.11; 95% CI, 1.37 to 27.24; P=0.007). There was no significant difference in rates of death (2.9% vs. 3.1%) or reinfarction (1.7% vs. 0.9%). Results were consistent across subgroups of patients. CONCLUSIONS: Bivalirudin, started during transport for primary PCI, improved 30-day clinical outcomes with a reduction in major bleeding but with an increase in acute stent thrombosis. (Funded by the Medicines Company; EUROMAX ClinicalTrials.gov number, NCT01087723.)

Transcript of The Dory Derby Accident

This story is an excerpt from a longer interview that was collected as part of the Launching through the Surf: The Dory Fleet of Pacific City project. In this story, Don Grotjohn recounts an accident that occurred during a Dory Derby competition

Gastrointestinal symptoms in low-dose aspirin users: a comparison between plain and buffered aspirin

Contains fulltext : 127588.pdf (publisher's version ) (Open Access)BACKGROUND: Aspirin is associated with gastrointestinal side effects such as gastric ulcers, gastric bleeding and dyspepsia. High-dose effervescent calcium carbasalate (ECC), a buffered formulation of aspirin, is associated with reduced gastric toxicity compared with plain aspirin in healthy volunteers, but at lower cardiovascular doses no beneficial effects were observed. AIM: To compare the prevalence of self-reported gastrointestinal symptoms between low-dose plain aspirin and ECC. METHODS: A total of 51,869 questionnaires were sent to a representative sample of the Dutch adult general population in December 2008. Questions about demographics, gastrointestinal symptoms in general and specific symptoms, comorbidity, and medication use including bioequivalent doses of ECC (100 mg) and plain aspirin (80 mg) were stated. We investigated the prevalence of self-reported gastrointestinal symptoms on ECC compared with plain aspirin using univariate and multivariate logistic regression analyses. RESULTS: A total of 16,715 questionnaires (32 %) were returned and eligible for analysis. Of these, 911 (5 %) respondents reported the use of plain aspirin, 633 (4 %) ECC and 15,171 reported using neither form of aspirin (91 %). The prevalence of self-reported gastrointestinal symptoms in general was higher in respondents using ECC (27.5 %) compared with plain aspirin (26.3 %), but did not differ significantly with either univariate (OR 1.06, 95 %CI 0.84-1.33), or multivariate analysis (aOR 1.08, 95 %CI 0.83-1.41). Also, none of the specific types of symptoms differed between the two aspirin formulations. CONCLUSIONS: In this large cohort representative of the general Dutch population, low-dose ECC is not associated with a reduction in self-reported gastrointestinal symptoms compared with plain aspirin

Efficient Response Simulation Strategies for Jacket-based Offshore Wind Turbines - An integrated approach combining model reduction and nonlinear irregular wave theory

The offshore wind industry has been growing exponentially over the last two decades, thereby establishing itself as one of the most promising alternative energy sources. Technological developments are required to reach ambitious cost reduction targets, set to decrease the industry s dependency on governmental support. One way to cut costs is by the implementation of a more accurate hydrodynamic model, resulting in less uncertainty and consequently in a more efficient foundation design. Two key trends are identified in the development of new offshore wind parks. Firstly, the turbine size increases and secondly, the parks are being built further offshore. Both trends cause the jacket to become increasing popular with respect to the monopile foundation. Considering the modeling of the foundation, the geometrical complexity of the jacket makes the design more computationally expensive than for a monopile. The challenge is to keep the model to manageable proportions while incorporating sufficient accuracy, both in wave and structural modeling. The goal of this thesis is therefore to develop an integrated calculation strategy to accurately and efficiently determine the fatigue loads on a jacket-based offshore wind turbine. To this end, a nonlinear irregular wave model is implemented and the Morison equation is used to translate wave kinematics to nodal forces in the jacket model. Furthermore, different model reduction techniques are considered to determine the optimal calculation strategy of the response to the hydrodynamic loading. The nonlinear wave model is compared to the linear model in terms of response of the jacket for a case study of a site in the German Bight. It is found that the nonlinear model induces 1% to 6% stress increase in the jacket members, depending on the location of the specific member. The stress increase is most pronounced in the splash zone. When considering the amount of kinetic energy triggered by both models, it is demonstrated that the nonlinear model can have a significant contribution to the dynamic response of the jacket. A sensitivity study shows that the eigenfrequencies and damping of the structure play an important role in the response, both in absolute as well as in relative (nonlinear vs. linear) terms. In the quest for an optimal reduced model three types of models are considered: Guyan, Craig-Bampton (CB) and Augmented Craig-Bampton (ACB). The models are compared in terms of their spectral and spatial convergence with respect to the full model. It is found that the fixed interface vibration modes significantly improve the spectral convergence of the reduced model. To also ensure a high spatial convergence the addition of Modal Truncation Augmentation vectors (MTAs) proves to be essential. Models containing these load case specific modes yield a very small error in terms of potential energy (max. 0.08%), compared to the full model. By clustering the load cases it was found that even a single reduced model containing generic MTAs produces only a small error (max. 1%). To be able to accurately describe the combined wave-wind loading it is recommended to include both fixed interface vibration modes and MTAs. The reduced model approach reveals its added value when considering the computational times: an averaged size reduced model (± 400 DoF) performs the dynamic simulation nearly ten times faster than the full model (± 1300 DoF). The calculation time of the nonlinear wave model (Tc = 200 s) causes an increase with respect to the linear model (Tc = 110 s) for the wave load generation. However, in the light of the complete analysis, including the dynamic simulation (Tc = 30 min) using a reduced model, the gain in accuracy outweighs the relatively small increase in computational time. Summarizing, the nonlinear irregular wave model is successfully implemented and the difference in terms of dynamic response is quantified with respect to the linear model. A model reduction strategy is developed which provides an optimal composition of the reduction basis, in terms of accuracy and computational efficiency. These two tools together provide an efficient, integrated calculation strategy for the dynamic fatigue load analysis of a jacket-based OWT subjected to nonlinear irregular wave loading, thereby fulfilling the thesis objective

Giving the green light : analysis of transition management within the Dutch energy transition

Investing in renewable energy sources (RES) is one pivotal way to ensure future energy sustainability that also mitigates climate change. The EU has committed to increase the share of renewable energy (RE), and has tasked member states with targets. The Netherlands has now issued the ‘Energy Agreement for Sustainable Growth’ to attain a share of 14% RE by 2020. Coincidentally the theoretical knowledge of transition management (TM) has been part of Dutch policy making since 2001. This thesis sets about analysing how TM has been incorporated in this policy to appraise its probable efficacy in meeting the objective. First the transition typology is assessed. Then, through using the analytical framework of TM as lens, the Energy Agreement is scrutinised. The policy’s strategic, tactical, and operational levels are discerned, as well as their respective objectives, actions and instruments. Co-evolution is furthermore examined. The study finds the energy transition to follow a targeted typology with much governmental interference and an integral approach. Overall, the Energy Agreement follows the theoretical ideas of TM to a large extent, where there is a multi-level and multi-actor approach. Nevertheless, there are some parts within the Energy Agreement that are worrisome and can prove detrimental to its own success. For example, co-evolution is hampered because the strategic level is locked due to supranational influence. The analysis also demonstrates a dominance of incumbent regime actors, as well as a strong focus on cost-effectiveness that hampers innovation and niche chances which are much needed for a longer-term energy transition. The findings also point towards drawbacks of TM in itself where too much faith is fostered in the dominant regime and government. As a result, enhanced niche participation and inclusion is warranted to ensure the regime is fundamentally challenged. Furthermore, parameters are needed for directed incrementalism to allow more time for niches to ripen. Finally, this study illustrates the need to add an external, supranational level to be incorporated in the analytical framework of TM to facilitate co-evolution

GARFIELD-AF model for prediction of stroke and major bleeding in atrial fibrillation: a Danish nationwide validation study.

OBJECTIVES: To externally validate the accuracy of the Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF) model against existing risk scores for stroke and major bleeding risk in patients with non-valvular AF in a population-based cohort. DESIGN: Retrospective cohort study. SETTING: Danish nationwide registries. PARTICIPANTS: 90 693 patients with newly diagnosed non-valvular AF were included between 2010 and 2016, with follow-up censored at 1 year. PRIMARY AND SECONDARY OUTCOME MEASURES: External validation was performed using discrimination and calibration plots. C-statistics were compared with CHA2DS2VASc score for ischaemic stroke/systemic embolism (SE) and HAS-BLED score for major bleeding/haemorrhagic stroke outcomes. RESULTS: Of the 90 693 included, 51 180 patients received oral anticoagulants (OAC). Overall median age (Q1, Q3) were 75 (66-83) years and 48 486 (53.5%) were male. At 1-year follow-up, a total of 2094 (2.3%) strokes/SE, 2642 (2.9%) major bleedings and 10 915 (12.0%) deaths occurred. The GARFIELD-AF model was well calibrated with the predicted risk for stroke/SE and major bleeding. The discriminatory value of GARFIELD-AF risk model was superior to CHA2DS2VASc for predicting stroke in the overall cohort (C-index: 0.71, 95% CI: 0.70 to 0.72 vs C-index: 0.67, 95% CI: 0.66 to 0.68, p<0.001) as well as in low-risk patients (C-index: 0.64, 95% CI: 0.59 to 0.69 vs C-index: 0.57, 95% CI: 0.53 to 0.61, p=0.007). The GARFIELD-AF model was comparable to HAS-BLED in predicting the risk of major bleeding in patients on OAC therapy (C-index: 0.64, 95% CI: 0.63 to 0.66 vs C-index: 0.64, 95% CI: 0.63 to 0.65, p=0.60). CONCLUSION: In a nationwide Danish cohort with non-valvular AF, the GARFIELD-AF model adequately predicted the risk of ischaemic stroke/SE and major bleeding. Our external validation confirms that the GARFIELD-AF model was superior to CHA2DS2VASc in predicting stroke/SE and comparable with HAS-BLED for predicting major bleeding