Systematic Review of Medicine-Related Problems in Adult Patients with Atrial Fibrillation on Direct Oral Anticoagulants

New oral anticoagulant agents continue to emerge on the market and their safety requires assessment to provide evidence of their suitability for clinical use. There-fore, we searched standard databases to summarize the English language literature on medicine-related problems (MRPs) of direct oral anticoagulants DOACs (dabigtran, rivaroxban, apixban, and edoxban) in the treatment of adults with atri-al fibrillation. Electronic databases including Medline, Embase, International Pharmaceutical Abstract (IPA), Scopus, CINAHL, the Web of Science and Cochrane were searched from 2008 through 2016 for original articles. Studies pub-lished in English reporting MRPs of DOACs in adult patients with AF were in-cluded. Seventeen studies were identified using standardized protocols, and two reviewers serially abstracted data from each article. Most articles were inconclusive on major safety end points including major bleeding. Data on major safety end points were combined with efficacy. Most studies inconsistently reported adverse drug reactions and not adverse events or medication error, and no definitions were consistent across studies. Some harmful drug effects were not assessed in studies and may have been overlooked. Little evidence is provided on MRPs of DOACs in patients with AF and, therefore, further studies are needed to establish the safety of DOACs in real-life clinical practice

Stabilization of pulses by competing instability mechanisms

Abstract The (cubic) Ginzburg-Landau equation has various unstable solitary pulse solutions, which have, however, been observed in systems with two competing instability mechanisms. In such systems, the Ginzburg- Landau equation is coupled to a diffusion equation. In previous work, it has been shown by an Evans function approach that the effect of the slow diffusion can indeed stabilize a pulse when the diffusive mode is (weakly) damped, and when higher-order nonlinearities are taken into account. In the current work the more natural case where the diffusion equation has a neutrally stable mode at kc = 0 is studied by means of asymptotic expansions. The neutrally stable mode introduces pulses that decay algebraically rather than exponentially, which is essential for the Evans function approach. Key words Ginzburg-Landau, asymptotic expansions, pulse solution, stabilization

Stabilization by slow diffusion in a real Ginzburg-Landau system

The Ginzburg-Landau equation is essential for understanding the dynamics of patterns in a wide variety of physical contexts. It governs the evolution of small amplitude instabilities near criticality. It is well known that the (cubic) Ginzburg-Landau equation has various unstable solitary pulse solutions. However, such localized patterns have been observed in systems in which there are two competing instability mechanisms. In such systems, the evolution of instabilities is described by a Ginzburg-Landau equation coupled to a diffusion equation. In this article we study the influence of this additional diffusion equation on the pulse solutions of the Ginzburg-Landau equation in light of recently developed insights into the effects of slow diffusion on the stability of pulses. Therefore, we consider the limit case of slow diffusion, i.e., the situation in which the additional diffusion equation acts on a long spatial scale. We show that the solitary pulse solution of the Ginzburg-Landau equation persists under this coupling. We use the Evans function method to analyze the effect of the slow diffusion and to show that it acts as a control mechanism that influences the (in)stability of the pulse. We establish that this control mechanism can indeed stabilize a pulse when higher order nonlinearities are taken into account

Algebraically decaying pulses in a Ginzburg-Landau system with a neutrally stable mode

In this paper, we study the existence and stability of pulse solutions in a system with interacting instability mechanisms, that is described by a Ginzburg-Landau equation for an A-mode, coupled to a diffusion equation for a B-mode. Our main question is whether this coupling may stabilize solutions of the Ginzburg-Landau equation that are unstable when the interactions with the neutrally stable B-mode are not included in the model. The spatially homogeneous B-mode is supposed to be neutrally stable. This implies that the pulse solutions cannot decay exponentially, bul must decay with an algebraic rate as x - infty. As a consequence, the methods that exist in the literature by which the stability of pulses in singularly perturbed reaction-diffusion systems can be studied, need to be extended. This results in an 'algebraic NLEP approactV, that is expected to be relevant beyond the setting of this paper. As in the case of a (weakly) stable B-mode [7], we establish by the application of this approach, that the B-mode indeed introduces a mechanism that may stabilize pulses that are unstable when the interactions with the B-mode are not taken into accoun