2,970 research outputs found
Clinical and Pharmacological Effects of Apixaban Dose Adjustment in the ARISTOTLE Trial
No full textBACKGROUND In the ARISTOTLE (Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation) trial, patients with atrial fibrillation and >= 2 dose-adjustment criteria (age >= 80 years, weight <= 60 kg, or creatinine >= 1.5 mg/dl [133 mu mol/l]) were randomized to receive apixaban 2.5 mg twice daily or warfarin.
OBJECTIVES The purpose of this study was to describe the effects of apixaban dose adjustment on clinical and pharmacological outcomes.
METHODS Patients receiving the correct dose of study drug were included (n = 18,073). The effect of apixaban 2.5 mg twice daily versus warfarin on population pharmacokinetics, D-dimer, prothrombin fragment 1 + 2 (PF1+2), and clinical outcomes was compared with the standard dose (5 mg twice daily).
RESULTS Patients receiving apixaban 2.5 mg twice daily exhibited lower apixaban exposure (median area under the concentration time curve at a steady state 2,720 ng/ml vs. 3,599 ng/ml; p < 0.0001) than those receiving the standard dose. In patients with >= 2 dose-adjustment criteria, reductions in D-dimers (p interaction = 0.20) and PF1+2 (p interaction = 0.55) were consistent with those observed in the standard-dose population. Patients with >= 2 dose-adjustment criteria (n = 751) were at higher risk for stroke/systemic embolism, major bleeding, and all-cause death than the standard-dose population (0 or 1 dose-adjustment criterion, n = 17,322). The effect of apixaban 2.5 mg twice daily versus warfarin in the >= 2 dose-adjustment criteria population was consistent with the standard dose in the reductions in stroke or systemic embolism (p interaction = 0.26), major bleeding (p interaction = 0.25), and death (p interaction = 0.72).
CONCLUSIONS Apixaban drug concentrations were lower in patients receiving 2.5 mg twice daily compared with 5 mg twice daily. However, the effects of apixaban dose adjustment to 2.5 mg versus warfarin were consistent for coagulation biomarkers and clinical outcomes, providing reassuring data on efficacy and safety. (Apixaban for the Prevention of Stroke in Subjects With Atrial Fibrillation [ARISTOTLE]; NCT00412984)
Apixaban compared with warfarin in patients with atrial fibrillation and previous stroke or transient ischaemic attack : a subgroup analysis of the ARISTOTLE trial
No full textAbstract: Background In the ARISTOTLE trial, the rate of stroke or systemic embolism was reduced by apixaban compared with warfarin in patients with atrial fibrillation (AF). Patients with AF and previous stroke or transient ischaemic attack (TIA) have a high risk of stroke. We therefore aimed to assess the efficacy and safety of apixaban compared with warfarin in prespecified subgroups of patients with and without previous stroke or TIA. Methods Between Dec 19, 2006, and April 2, 2010, patients were enrolled in the ARISTOTLE trial at 1034 clinical sites in 39 countries. 18\u2008201 patients with AF or atrial flutter were randomly assigned to receive apixaban 5 mg twice daily or warfarin (target international normalised ratio 2\ub703\ub70). The median duration of follow-up was 1\ub78 years (IQR 1\ub742\ub73). The primary efficacy outcome was stroke or systemic embolism, analysed by intention to treat. The primary safety outcome was major bleeding in the on-treatment population. All participants, investigators, and sponsors were masked to treatment assignments. In this subgroup analysis, we estimated event rates and used Cox models to compare outcomes in patients with and without previous stroke or TIA. The ARISTOTLE trial is registered with ClinicalTrials.gov, number NTC00412984. Findings Of the trial population, 3436 (19%) had a previous stroke or TIA. In the subgroup of patients with previous stroke or TIA, the rate of stroke or systemic embolism was 2\ub746 per 100 patient-years of follow-up in the apixaban group and 3\ub724 in the warfarin group (hazard ratio [HR] 0\ub776, 95% CI 0\ub756 to 1\ub703); in the subgroup of patients without previous stroke or TIA, the rate of stroke or systemic embolism was 1\ub701 per 100 patient-years of follow-up with apixaban and 1\ub723 with warfarin (HR 0\ub782, 95% CI 0\ub765 to 1\ub703; p for interaction=0\ub771). The absolute reduction in the rate of stroke and systemic embolism with apixaban versus warfarin was 0\ub777 per 100 patient-years of follow-up (95% CI 120\ub708 to 1\ub763) in patients with and 0\ub722 ( 120\ub703 to 0\ub747) in those without previous stroke or TIA. The difference in major bleeding with apixaban compared with warfarin was 1\ub707 per 100 patient-years (95% CI 0\ub7092\ub704) in patients with and 0\ub793 (0\ub7541\ub732) in those without previous stroke or TIA. Interpretation The effects of apixaban versus warfarin were consistent in patients with AF with and without previous stroke or TIA. Owing to the higher risk of these outcomes in patients with previous stroke or TIA, the absolute benefits of apixaban might be greater in this population
Discourse on formation of investigators’ competencies
No full textOne of the most important aims of law enforcement agencies is crime investigation and
prevention. Consequently, one of the main activities of the law enforcement agencies, especially in the
pre-trial investigation sphere, is to optimise the organisation of the pre-trial investigation in order to
save the experienced skilled and competent specialists. The author of this research offers a new
approach and analyses the qualification and competence of the pre-trial investigation subjects not only
in terms of personnel management, but all elements of the model of pre-trial investigation to make
pre-trial investigation organisation more effective. It should be noted that the content of an
investigators‘ qualification or levels of competence are still not determined or strictly regulated and
this is the reason for many discussions in this area. These discussions surround what qualification and level of competence the investigators should have in pre-trial investigation, what general and special
competencies they should acquire and how the content of the competencies should be determined. In the present article the author analyses the investigators‘ qualification and competence as a
presumption that it is an essential aspect of an effective pre-trial investigation. Analysing this question
the author compares other subjects such as the regulation of qualifications and levels of competence of
the prosecutors and pre-trial investigation judges. The author also identifies the problem of how to
define an investigators qualification and level of competence making recommendations to create a
Description of Investigators Competencies. Qualification requirements should be determined in this
legal act and general, occupational and special competencies should be identified with the content also
being determined within this framework. Formation of the Description of Investigators‘ Competencies
should determine not only the content of the investigators‘ required level of competence but also this
process should be consistent with the assessment and career development of investigators‘ including
the process of gaining the investigators‘ qualification. The aim of this research is to identify the problems associated with defining an investigators‘
qualification and levels of competence and to propose recommendations on how this could be
achieved. The subject of this research is limited to only looking at investigators‘ qualification and
level of competence. The author is using a qualitative method for this research based upon the contents of documents.
The author will analysis eight legal acts related to the qualification and competence of pre-trial
investigation and fifty different investigators‘ job descriptions.Straipsnyje nagrinėjama ikiteisminio tyrimo pareigūnų (tyrėjų) kvalifikacija ir kompetencija kaip viena iš veiksmingo ikiteisminio tyrimo organizavimo prielaidų. Analizuojant tyrėjų kvalifikacijos ir kompetencijos turinį ir jo reglamentavimą, lyginama kitų ikiteisminio tyrimo subjektų – prokurorų ir ikiteisminio tyrimo teisėjų – kvalifikacijos ir kompetencijos turinio reglamentavimo ypatumai, identifikuojamos tyrėjų kvalifikacijos ir kompetencijos apibrėžties problemos ir pateikiami sprendimo būdai – siūlomas ikiteisminio tyrimo pareigūnų (tyrėjų) kompetencijų aprašas, kuriame būtų tiksliai nustatyti tyrėjų kvalifikaciniai reikalavimai, identifikuotos bendrosios, profesinės ir specialiosios kompetencijos ir apibrėžtas šių kompetencijų turinys. Ikiteisminio tyrimo pareigūnų kompetencijų aprašo suformavimas sudarytų galimybę ne tik aiškiai apibrėžti tyrėjo kompetencijos turinį, bet ir šį procesą nuosekliai susieti su tyrėjo veiklos vertinimu, karjera ir kvalifikacijos tobulinimu. Straipsnį sudaro įvadas ir dvi dalys. Pirmoje dalyje nagrinėjama tyrėjo kvalifikacijos apibrėžties problematika, gretinama ikiteisminio tyrimo pareigūno, prokuroro ir teisėjo kvalifikacijos apibrėžtys. Šioje dalyje siūloma tiksliai nustatyti ir apibrėžti tyrėjo kvalifikacinius reikalavimus. Antrojoje dalyje analizuojama tyrėjo kompetencijos turinys. Nagrinėjant prokurorų, teisėjų kompetencijos turinį ir jo reglamentavimo ypatumus, siūloma sudaryti tyrėjo kompetencijų aprašą, kuriame būtų tiksliai apibrėžtas tyrėjo kompetencijos turinys
Sepsis-driven temporal variability in cytokine secretion and heart rate is potentiated by withdrawing vagal innervation: Evidence of higher order neuroimmunological communication via the cholinergic anti-inflammatory pathway in the ovine fetus near term
No full textFetal brain-gut communication is disrupted during sepsis and associated with a higher degree of intestinal inflammation: Implications for non-evasive monitoring
No full textInternet technologies relevant to private investigators’ working practices
No full textMuch has been written and discussed especially in the various US media and in legislative organs, about how the Internet is used illegally (hacking, stalking for instance), but hardly if any research has been done as to how the investigative industry employs the new medium to its benefit. The author described in this thesis how private investigators (PIs) execute their profession these days using the facilities the Internet avail them in contrast to the time before the dawn of the Internet. This contrast is also investigated in an international context, an important part of the thesis, drawn from the author's 32 years of international business experience and that of PIs worldwide. The availability of the various online facilities in different countries are compared. To better understand the new medium, and its facilities a short outline of the Internet’s history, it’s set up in general and for the use of PIs in particular is supplied. PIs also face limitations in their daily work, limitations originating from online, legal, educational, financial and international causes. The new medium not only helps PIs in their investigative, but also in their office work. Finally PIs' wishes for new tools to facilitate their daily investigative work and their outlook as to where the new medium will head are also discussed
A signature of fetal systemic inflammatory response in the temporal pattern of heart rate variability measures
No full textManaging atrial fibrillation in the global community: The European perspective.
No full textAtrial fibrillation is a common, global problem, with great personal, economic and social burdens. As populations age it increases in prevalence and becomes another condition that requires careful chronic management to ensure its effects are minimised. Assessment of the risk of stroke using well established risk prediction models is being aided by modern computerised databases and the choice
of drugs to prevent strokes is ever expanding to try and improve the major cause of morbidity in AF. In addition, newer drugs for controlling rhythm are available and guidelines are constantly changing to reflect this. As well as medications, modern techniques of electrophysiology are becoming more widely embraced worldwide to provide more targeted treatment for the underlying pathophysiology. In this review we consider these factors to concisely describe how AF can be successfully managed
Apixaban versus warfarin in patients with atrial fibrillation
No full textAbstract: Background Vitamin K antagonists are highly effective in preventing stroke in patients with atrial fibrillation but have several limitations. Apixaban is a novel oral direct factor Xa inhibitor that has been shown to reduce the risk of stroke in a similar population in comparison with aspirin. Methods In this randomized, double-blind trial, we compared apixaban (at a dose of 5 mg twice daily) with warfarin (target international normalized ratio, 2.0 to 3.0) in 18,201 patients with atrial fibrillation and at least one additional risk factor for stroke. The primary outcome was ischemic or hemorrhagic stroke or systemic embolism. The trial was designed to test for noninferiority, with key secondary objectives of testing for superiority with respect to the primary outcome and to the rates of major bleeding and death from any cause. Results The median duration of follow-up was 1.8 years. The rate of the primary outcome was 1.27% per year in the apixaban group, as compared with 1.60% per year in the warfarin group (hazard ratio with apixaban, 0.79; 95% confidence interval [CI], 0.66 to 0.95; P<0.001 for noninferiority; P=0.01 for superiority). The rate of major bleeding was 2.13% per year in the apixaban group, as compared with 3.09% per year in the warfarin group (hazard ratio, 0.69; 95% CI, 0.60 to 0.80; P<0.001), and the rates of death from any cause were 3.52% and 3.94%, respectively (hazard ratio, 0.89; 95% CI, 0.80 to 0.99; P=0.047). The rate of hemorrhagic stroke was 0.24% per year in the apixaban group, as compared with 0.47% per year in the warfarin group (hazard ratio, 0.51; 95% CI, 0.35 to 0.75; P<0.001), and the rate of ischemic or uncertain type of stroke was 0.97% per year in the apixaban group and 1.05% per year in the warfarin group (hazard ratio, 0.92; 95% CI, 0.74 to 1.13; P=0.42). Conclusions In patients with atrial fibrillation, apixaban was superior to warfarin in preventing stroke or systemic embolism, caused less bleeding, and resulted in lower mortality. (Funded by Bristol-Myers Squibb and Pfizer; ARISTOTLE ClinicalTrials.gov number, NCT00412984.
- …
