Modeling HCV cure after an ultra-short duration of therapy with direct acting agents

AbstractWe have developed a model for theH2OandOHevolution in a comet outburst, assuming that together with the gas, a distribution of icy grains is ejected. With an initial mass of icy grains of 108kg released, theH2OandOHproductions are increased up to a factor two, and the growth curves change drastically in the first two days. The model is applied to eruptions detected in theOHradio monitorings and fits well with the slow variations in the flux. On the other hand, several events of short duration appear, consisting of a sudden rise ofOHflux, followed by a sudden decay on the second day. These apparent short bursts are frequently found as precursors of a more durable eruption. We suggest that both of them are part of a unique eruption, and that the sudden decay is due to collisions that de-excite theOHmaser, when it reaches the Cometopause region located at 1.35 × 105kmfrom the nucleus.

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Safety and efficacy of direct acting oral anticoagulants and vitamin K antagonists in nonvalvular atrial fibrillation – a network meta-analysis of real-world data

VASA ◽

10.1024/0301-1526/a000746 ◽

2019 ◽

Vol 48 (2) ◽

pp. 134-147 ◽

Cited By ~ 8

Author(s):

Mirko Hirschl ◽

Michael Kundi

Keyword(s):

Real World ◽

Meta Analysis ◽

Vitamin K Antagonists ◽

Oral Anticoagulants ◽

Efficacy And Safety ◽

Nonvalvular Atrial Fibrillation ◽

Real World Data ◽

Hazard Ratios ◽

Direct Acting ◽

Event Rates

Abstract. Background: In randomized controlled trials (RCTs) direct acting oral anticoagulants (DOACs) showed a superior risk-benefit profile in comparison to vitamin K antagonists (VKAs) for patients with nonvalvular atrial fibrillation. Patients enrolled in such studies do not necessarily reflect the whole target population treated in real-world practice. Materials and methods: By a systematic literature search, 88 studies including 3,351,628 patients providing over 2.9 million patient-years of follow-up were identified. Hazard ratios and event-rates for the main efficacy and safety outcomes were extracted and the results for DOACs and VKAs combined by network meta-analysis. In addition, meta-regression was performed to identify factors responsible for heterogeneity across studies. Results: For stroke and systemic embolism as well as for major bleeding and intracranial bleeding real-world studies gave virtually the same result as RCTs with higher efficacy and lower major bleeding risk (for dabigatran and apixaban) and lower risk of intracranial bleeding (all DOACs) compared to VKAs. Results for gastrointestinal bleeding were consistently better for DOACs and hazard ratios of myocardial infarction were significantly lower in real-world for dabigatran and apixaban compared to RCTs. By a ranking analysis we found that apixaban is the safest anticoagulant drug, while rivaroxaban closely followed by dabigatran are the most efficacious. Risk of bias and heterogeneity was assessed and had little impact on the overall results. Analysis of effect modification could guide the clinical decision as no single DOAC was superior/inferior to the others under all conditions. Conclusions: DOACs were at least as efficacious as VKAs. In terms of safety endpoints, DOACs performed better under real-world conditions than in RCTs. The current real-world data showed that differences in efficacy and safety, despite generally low event rates, exist between DOACs. Knowledge about these differences in performance can contribute to a more personalized medicine.

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