112 research outputs found
FIRST-DOSE SUCCESS OF PDE5 INHIBITORS
Summary First-dose success of phosphodiesterase type 5 (PDE5) inhibitors may be adversely affected in patients with comorbidities. This article reports first-dose success rates for vardenafil 10 mg in men with erectile dysfunction (ED) and associated comorbidities who participated in the challenge phase of the Reliability – Vardenafil for Erectile Dysfunction I study. This study involved an open-label, single-dose, 1-week challenge period where patients who achieved SEP-2 (penetration) success were randomised to vardenafil 10 mg or placebo for 12 weeks in a double-blind manner. The first-dose success rates for SEP-2 and SEP-3 (maintenance of erection to completion of intercourse) were stratified according to comorbidities. Safety was assessed using adverse events (AEs). Of 600 men who received a single 10 mg dose of vardenafil, 32% had hypertension, 16% had diabetes and 19% had dyslipidaemia. Vardenafil demonstrated overall effectiveness, including first-dose SEP-2 and SEP-3 success rates in patients with and without specific comorbidities. Initial overall success rates for SEP-2 and SEP-3 during the challenge phase were 87% and 74% respectively. First-dose SEP-2 and SEP-3 success rates were 84% and 66% in men with hypertension (n = 191); 84% and 72% in men with dyslipidaemia (n = 116); and 75% and 58% in men with diabetes (n = 95). Vardenafil was well tolerated and most AEs, including the most frequently reported flushing (3.5%), were mild to moderate in intensity. Vardenafil 10 mg is generally well tolerated and efficacious, providing first-dose success with a consistently high rate of reliability of penetration and maintenance of erection in men with ED and associated comorbidities
On the Structure of Lie Pseudo-Groups
We compare and contrast two approaches to the structure theory for Lie pseudo-groups, the first due to Cartan, and the second due to the first two authors. We argue that the latter approach offers certain advantages from both a theoretical and practical standpoint
Difference schemes with point symmetries and their numerical tests
Symmetry preserving difference schemes approximating second and third order
ordinary differential equations are presented. They have the same three or
four-dimensional symmetry groups as the original differential equations. The
new difference schemes are tested as numerical methods. The obtained numerical
solutions are shown to be much more accurate than those obtained by standard
methods without an increase in cost. For an example involving a solution with a
singularity in the integration region the symmetry preserving scheme, contrary
to standard ones, provides solutions valid beyond the singular point.Comment: 26 pages 7 figure
Differences in the rate of lymph node invasion in men with clinically localized prostate cancer might be related to the continent of origin
OBJECTIVETo test whether the rate of lymph node invasion (LNI) differs between patients treated with radical prostatectomy (RP) at a European or a North American centre.PATIENTS AND METHODSIn all, 1385 men had RP with bilateral lymphadenectomy for clinically localized prostate cancer (587 from Dallas, Texas and 798 from Milan, Italy). Univariate and multivariate analyses focused on the association between the continent of origin and the rate of LNI, after controlling for prostate‐specific antigen (PSA) level, clinical stage, biopsy Gleason sum and the number of examined and removed lymph nodes.RESULTSEuropean men had higher PSA levels (9.1 vs 7.8 ng/mL), a higher proportion of palpable cancers (44.5 vs 32.8%), more nodes removed (mean 14.9 vs 7.8) and a higher rate of LNI (9.0% vs 1.2%; all differences P < 0.001). In multivariate analyses that controlled for PSA level and clinical variables, European men had an 8.9‐fold higher risk of LNI (P < 0.001) than their counterparts from the USA. Among preoperative variables, the continent of origin was the third most informative predictor of LNI (67.5%), after biopsy Gleason sum (74.3%) and the number of examined lymph nodes (71.0%), and improved the ability to predict LNI by 4.7%.CONCLUSIONMen treated at a European centre had a 7.3–8.9‐fold higher rate of LNI, despite adjusting for all clinical and pathological variables. It remains to be shown what predisposes European men to a higher rate of LNI
Multiscale expansions of difference equations in the small lattice spacing regime, and a vicinity and integrability test. I
We propose an algorithmic procedure i) to study the ``distance'' between an
integrable PDE and any discretization of it, in the small lattice spacing
epsilon regime, and, at the same time, ii) to test the (asymptotic)
integrability properties of such discretization. This method should provide, in
particular, useful and concrete informations on how good is any numerical
scheme used to integrate a given integrable PDE. The procedure, illustrated on
a fairly general 10-parameter family of discretizations of the nonlinear
Schroedinger equation, consists of the following three steps: i) the
construction of the continuous multiscale expansion of a generic solution of
the discrete system at all orders in epsilon, following the Degasperis -
Manakov - Santini procedure; ii) the application, to such expansion, of the
Degasperis - Procesi (DP) integrability test, to test the asymptotic
integrability properties of the discrete system and its ``distance'' from its
continuous limit; iii) the use of the main output of the DP test to construct
infinitely many approximate symmetries and constants of motion of the discrete
system, through novel and simple formulas.Comment: 34 pages, no figur
Energy landscape of relaxed amorphous silicon
We analyze the structure of the energy landscape of a well-relaxed 1000-atom
model of amorphous silicon using the activation-relaxation technique (ART
nouveau). Generating more than 40,000 events starting from a single minimum, we
find that activated mechanisms are local in nature, that they are distributed
uniformly throughout the model and that the activation energy is limited by the
cost of breaking one bond, independently of the complexity of the mechanism.
The overall shape of the activation-energy-barrier distribution is also
insensitive to the exact details of the configuration, indicating that
well-relaxed configurations see essentially the same environment. These results
underscore the localized nature of relaxation in this material.Comment: 8 pages, 12 figure
The Jacobi last multiplier for difference equations
We present a discretization of the Jacobi last multiplier, with some
applications to the computation of solutions of difference equations.Comment: 9 page
Continuous Symmetries of Difference Equations
Lie group theory was originally created more than 100 years ago as a tool for
solving ordinary and partial differential equations. In this article we review
the results of a much more recent program: the use of Lie groups to study
difference equations. We show that the mismatch between continuous symmetries
and discrete equations can be resolved in at least two manners. One is to use
generalized symmetries acting on solutions of difference equations, but leaving
the lattice invariant. The other is to restrict to point symmetries, but to
allow them to also transform the lattice.Comment: Review articl
Lagrangian Curves in a 4-dimensional affine symplectic space
Lagrangian curves in R4 entertain intriguing relationships with second order deformation of plane curves under the special affine group and null curves in a 3-dimensional Lorentzian space form. We provide a natural affine symplectic frame for Lagrangian curves. It allows us to classify La- grangrian curves with constant symplectic curvatures, to construct a class of Lagrangian tori in R4 and determine Lagrangian geodesic
Faecal pharmacokinetics of orally administered vancomycin in patients with suspected Clostridium difficile infection
<p>Abstract</p> <p>Background</p> <p>Oral vancomycin (125 mg qid) is recommended as treatment of severe <it>Clostridium difficile </it>infection (CDI). Higher doses (250 or 500 mg qid) are sometimes recommended for patients with very severe CDI, without supporting clinical evidence. We wished to determine to what extent faecal levels of vancomycin vary according to diarrhoea severity and dosage, and whether it is rational to administer high-dose vancomycin to selected patients.</p> <p>Methods</p> <p>We recruited hospitalized adults suspected to have CDI for whom oral vancomycin (125, 250 or 500 mg qid) had been initiated. Faeces were collected up to 3 times/day and levels were measured with the AxSYM fluorescence polarization immunoassay.</p> <p>Results</p> <p>Fifteen patients (9 with confirmed CDI) were treated with oral vancomycin. Patients with ≥4 stools daily presented lower faecal vancomycin levels than those with a lower frequency. Higher doses of oral vancomycin (250 mg or 500 mg qid) led to consistently higher faecal levels (> 2000 mg/L), which were 3 orders of magnitude higher than the MIC<sub>90 </sub>of vancomycin against <it>C. difficile</it>. One patient receiving 125 mg qid had levels below 50 mg/L during the first day of treatment.</p> <p>Conclusions</p> <p>Faecal levels of vancomycin are proportional to the dosage administered and, even in patients with increased stool frequency, much higher than the MIC<sub>90</sub>. Patients given the standard 125 mg qid dosage might have low faecal levels during the first day of treatment. A loading dose of 250 mg or 500 mg qid during the first 24-48 hours followed by the standard dosage should be evaluated in larger studies, since it might be less disruptive to the colonic flora and save unnecessary costs.</p
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