7 research outputs found
International longitudinal registry of patients with atrial fibrillation and treated with rivaroxaban: RIVaroxaban Evaluation in Real life setting (RIVER)
Background
Real-world data on non-vitamin K oral anticoagulants (NOACs) are essential in determining whether evidence from randomised controlled clinical trials translate into meaningful clinical benefits for patients in everyday practice. RIVER (RIVaroxaban Evaluation in Real life setting) is an ongoing international, prospective registry of patients with newly diagnosed non-valvular atrial fibrillation (NVAF) and at least one investigator-determined risk factor for stroke who received rivaroxaban as an initial treatment for the prevention of thromboembolic stroke. The aim of this paper is to describe the design of the RIVER registry and baseline characteristics of patients with newly diagnosed NVAF who received rivaroxaban as an initial treatment.
Methods and results
Between January 2014 and June 2017, RIVER investigators recruited 5072 patients at 309 centres in 17 countries. The aim was to enroll consecutive patients at sites where rivaroxaban was already routinely prescribed for stroke prevention. Each patient is being followed up prospectively for a minimum of 2-years. The registry will capture data on the rate and nature of all thromboembolic events (stroke / systemic embolism), bleeding complications, all-cause mortality and other major cardiovascular events as they occur. Data quality is assured through a combination of remote electronic monitoring and onsite monitoring (including source data verification in 10% of cases). Patients were mostly enrolled by cardiologists (n =â3776, 74.6%), by internal medicine specialists 14.2% (n =â718) and by primary care/general practice physicians 8.2% (n =â417). The mean (SD) age of the population was 69.5 (11.0) years, 44.3% were women. Mean (SD) CHADS2 score was 1.9 (1.2) and CHA2DS2-VASc scores was 3.2 (1.6). Almost all patients (98.5%) were prescribed with once daily dose of rivaroxaban, most commonly 20âmg (76.5%) and 15âmg (20.0%) as their initial treatment; 17.9% of patients received concomitant antiplatelet therapy. Most patients enrolled in RIVER met the recommended threshold for AC therapy (86.6% for 2012 ESC Guidelines, and 79.8% of patients according to 2016 ESC Guidelines).
Conclusions
The RIVER prospective registry will expand our knowledge of how rivaroxaban is prescribed in everyday practice and whether evidence from clinical trials can be translated to the broader cross-section of patients in the real world
Fluorescence Probing of Thiol-Functionalized Gold Nanoparticles: Is Alkylthiol Coating of a Nanoparticle as Hydrophobic as Expected?
Understanding the interaction of fluorescent dyes with
monolayer-protected
gold nanoparticles (AuNPs) is of fundamental importance in designing
new fluorescent nanomaterials. Among a variety of molecular sensors
and reporters, fluorescent probes based on a 3-hydroxychromone (3HC)
skeleton appear to be very promising. They exhibit the phenomenon
of dual band emission, resulting from excited-state intramolecular
proton transfer (ESIPT), known to be highly sensitive to a nature
of microenvironment surrounding a fluorophore. In this study, dodecanethiol-protected
gold nanoparticles were synthesized, and, owing to the transmission
electron micrograph imaging, their average diameter was found to be
âŒ1.4 nm. Fluorescence titrations of the 3HC ESIPT probes with
AuNPs in toluene solutions demonstrate significant changes in the
intensity ratio of their normal and tautomeric emission bands, suggesting
that the probe molecules become noncovalently bound to a dodecanethiol
layer of AuNPs. Despite expected fluorescence quenching induced by
close proximity to the metal surface, no fluorescence lifetime decrease
was observed, indicating that a bound-fluorophore is shielded from
a nanoparticle core. Further spectral analysis revealed that the ratiometric
fluorescence changes could be interpreted as a consequence of intermolecular
hydrogen bonding between a probe and residual ethanol molecules, trapped
into the dodecanethiol shell of AuNPs during the synthesis. Evidences
for residual traces of ethanol in the ligand shell of the nanoparticles
were also observed in NMR spectra, suggesting that alkylthiol-coated
gold nanoparticles may not be as hydrophobic as one could expect.
To elucidate structural features of dodecanethiol-stabilized gold
nanoparticles at the supramolecular level, a molecular dynamics (MD)
model of AuNP was developed. The model was based on the all-atom CHARMM27
force field parameters and parametrized according to available experimental
data of the synthesized AuNPs. Our MD simulations show that in bulk
toluene the 3HC probe molecule becomes weakly bound to a dodecanethiol
monolayer, so that a fluorophore favors residence in an outer shell
of AuNP. In addition, MD simulations of transfer of AuNP from bulk
ethanol to toluene demonstrate that a small population of ethanol
molecules are able to penetrate deeply into the dodecanethiol layer
and may indeed be trapped into the ligand shell of alkylthiol-functionalized
gold nanoparticles. The results of our fluorescence experiments and
molecular dynamics simulation suggest that 3-hydroxychromones can
be used as a noncovalent fluorescent labeling agent for alkylthiol-stabilized
noble metal nanoparticles
Fluorescence Probing of Thiol-Functionalized Gold Nanoparticles: Is Alkylthiol Coating of a Nanoparticle as Hydrophobic as Expected?
Understanding the interaction of fluorescent dyes with
monolayer-protected
gold nanoparticles (AuNPs) is of fundamental importance in designing
new fluorescent nanomaterials. Among a variety of molecular sensors
and reporters, fluorescent probes based on a 3-hydroxychromone (3HC)
skeleton appear to be very promising. They exhibit the phenomenon
of dual band emission, resulting from excited-state intramolecular
proton transfer (ESIPT), known to be highly sensitive to a nature
of microenvironment surrounding a fluorophore. In this study, dodecanethiol-protected
gold nanoparticles were synthesized, and, owing to the transmission
electron micrograph imaging, their average diameter was found to be
âŒ1.4 nm. Fluorescence titrations of the 3HC ESIPT probes with
AuNPs in toluene solutions demonstrate significant changes in the
intensity ratio of their normal and tautomeric emission bands, suggesting
that the probe molecules become noncovalently bound to a dodecanethiol
layer of AuNPs. Despite expected fluorescence quenching induced by
close proximity to the metal surface, no fluorescence lifetime decrease
was observed, indicating that a bound-fluorophore is shielded from
a nanoparticle core. Further spectral analysis revealed that the ratiometric
fluorescence changes could be interpreted as a consequence of intermolecular
hydrogen bonding between a probe and residual ethanol molecules, trapped
into the dodecanethiol shell of AuNPs during the synthesis. Evidences
for residual traces of ethanol in the ligand shell of the nanoparticles
were also observed in NMR spectra, suggesting that alkylthiol-coated
gold nanoparticles may not be as hydrophobic as one could expect.
To elucidate structural features of dodecanethiol-stabilized gold
nanoparticles at the supramolecular level, a molecular dynamics (MD)
model of AuNP was developed. The model was based on the all-atom CHARMM27
force field parameters and parametrized according to available experimental
data of the synthesized AuNPs. Our MD simulations show that in bulk
toluene the 3HC probe molecule becomes weakly bound to a dodecanethiol
monolayer, so that a fluorophore favors residence in an outer shell
of AuNP. In addition, MD simulations of transfer of AuNP from bulk
ethanol to toluene demonstrate that a small population of ethanol
molecules are able to penetrate deeply into the dodecanethiol layer
and may indeed be trapped into the ligand shell of alkylthiol-functionalized
gold nanoparticles. The results of our fluorescence experiments and
molecular dynamics simulation suggest that 3-hydroxychromones can
be used as a noncovalent fluorescent labeling agent for alkylthiol-stabilized
noble metal nanoparticles