1,354 research outputs found
A re-examination of the BEST Trial using composite outcomes, including emergency department visits
Objectives:
The influence of choice of endpoint on trial size, duration, and interpretation of results was examined in patients with heart failure who were enrolled in BEST (Beta-blocker Evaluation of Survival Trial).
Background:
The choice of endpoints in heart failure trials has evolved over the past 3 decades.
Methods:
In the BEST trial, we used Cox regression analysis to examine the effect of bucindolol on the current standard composite of cardiovascular death or heart failure hospitalization (CVD/HFH) compared with the original primary mortality endpoint and the expanded composite that included emergency department (ED) visits. We also undertook an analysis of recurrent events primarily using the Lin, Wei, Ying, and Yang model.
Results:
Overall, 448 (33%) patients on placebo and 411 (30%) patients on bucindolol died (hazard ratio [HR]: 0.90; 95% confidence interval [CI]: 0.78 to 1.02; p = 0.11). A total of 730 (54%) patients experienced CVD/HFH on placebo and 624 (46%) on bucindolol (HR: 0.80; 95% CI: 0.72 to 0.89; p < 0.001). Adding ED visits increased these numbers to 768 (57%) and 668 (49%), respectively (HR: 0.81; 95% CI: 0.73 to 0.90; p < 0.001). A total of 568 (42%) patients on placebo experienced HFH compared with 476 (35%) patients on bucindolol (HR: 0.78; 95% CI: 0.69 to 0.89; p < 0.001), with a total of 1,333 and 1,124 admissions, respectively. With the same statistical assumptions, using the composite endpoint instead of all-cause mortality would have reduced the trial size by 40% and follow-up duration by 69%. The rate ratio for recurrent events (CVD/HFH) was 0.83 (95% CI: 0.73 to 0.94; p = 0.003).
Conclusions:
Choice of endpoint has major implications for trial size and duration, as well as interpretation of results. The value of broader composite endpoints and inclusion of recurrent events needs further investigation. (Beta Blocker Evaluation in Survival Trial [BEST]; NCT00000560
Simplifying the mosaic description of DNA sequences
By using the Jensen-Shannon divergence, genomic DNA can be divided into
compositionally distinct domains through a standard recursive segmentation
procedure. Each domain, while significantly different from its neighbours, may
however share compositional similarity with one or more distant
(non--neighbouring) domains. We thus obtain a coarse--grained description of
the given DNA string in terms of a smaller set of distinct domain labels. This
yields a minimal domain description of a given DNA sequence, significantly
reducing its organizational complexity. This procedure gives a new means of
evaluating genomic complexity as one examines organisms ranging from bacteria
to human. The mosaic organization of DNA sequences could have originated from
the insertion of fragments of one genome (the parasite) inside another (the
host), and we present numerical experiments that are suggestive of this
scenario.Comment: 16 pages, 1 figure, Accepted for publication in Phys. Rev.
Cosmological models with linearly varying deceleration parameter
We propose a new law for the deceleration parameter that varies linearly with
time and covers Berman's law where it is constant. Our law not only allows one
to generalize many exact solutions that were obtained assuming constant
deceleration parameter, but also gives a better fit with data (from SNIa, BAO
and CMB), particularly concerning the late time behavior of the universe.
According to our law only the spatially closed and flat universes are allowed;
in both cases the cosmological fluid we obtain exhibits quintom like behavior
and the universe ends with a big-rip. This is a result consistent with recent
cosmological observations.Comment: 12 pages, 7 figures; some typo corrections; to appear in
International Journal of Theoretical Physic
A Comparison of the LVDP and {\Lambda}CDM Cosmological Models
We compare the cosmological kinematics obtained via our law of linearly
varying deceleration parameter (LVDP) with the kinematics obtained in the
{\Lambda}CDM model. We show that the LVDP model is almost indistinguishable
from the {\Lambda}CDM model up to the near future of our universe as far as the
current observations are concerned, though their predictions differ
tremendously into the far future.Comment: 6 pages, 5 figures, 1 table, matches the version to be published in
International Journal of Theoretical Physic
Modeling water waves beyond perturbations
In this chapter, we illustrate the advantage of variational principles for
modeling water waves from an elementary practical viewpoint. The method is
based on a `relaxed' variational principle, i.e., on a Lagrangian involving as
many variables as possible, and imposing some suitable subordinate constraints.
This approach allows the construction of approximations without necessarily
relying on a small parameter. This is illustrated via simple examples, namely
the Serre equations in shallow water, a generalization of the Klein-Gordon
equation in deep water and how to unify these equations in arbitrary depth. The
chapter ends with a discussion and caution on how this approach should be used
in practice.Comment: 15 pages, 1 figure, 39 references. This document is a contributed
chapter to an upcoming volume to be published by Springer in Lecture Notes in
Physics Series. Other author's papers can be downloaded at
http://www.denys-dutykh.com
Longitudinal metabolic and gut bacterial profiling of pregnant women with previous bariatric surgery
Objective Due to the global increase in obesity rates and success of bariatric surgery in weight reduction, an increasing number of women now present pregnant with a previous bariatric procedure. This study investigates the extent of bariatric-associated metabolic and gut microbial alterations during pregnancy and their impact on fetal development.
Design A parallel metabonomic (molecular phenotyping based on proton nuclear magnetic resonance spectroscopy) and gut bacterial (16S ribosomal RNA gene amplicon sequencing) profiling approach was used to determine maternal longitudinal phenotypes associated with malabsorptive/mixed (n=25) or restrictive (n=16) procedures, compared with women with similar early pregnancy body mass index but without bariatric surgery (n=70). Metabolic profiles of offspring at birth were also analysed.
Results Previous malabsorptive, but not restrictive, procedures induced significant changes in maternal metabolic pathways involving branched-chain and aromatic amino acids with decreased circulation of leucine, isoleucine and isobutyrate, increased excretion of microbial-associated metabolites of protein putrefaction (phenylacetlyglutamine, p-cresol sulfate, indoxyl sulfate and p-hydroxyphenylacetate), and a shift in the gut microbiota. The urinary concentration of phenylacetylglutamine was significantly elevated in malabsorptive patients relative to controls (p=0.001) and was also elevated in urine of neonates born from these mothers (p=0.021). Furthermore, the maternal metabolic changes induced by malabsorptive surgery were associated with reduced maternal insulin resistance and fetal/birth weight.
Conclusion Metabolism is altered in pregnant women with a previous malabsorptive bariatric surgery. These alterations may be beneficial for maternal outcomes, but the effect of elevated levels of phenolic and indolic compounds on fetal and infant health should be investigated further
Earthquake Forecast via Neutrino Tomography
We discuss the possibility of forecasting earthquakes by means of
(anti)neutrino tomography. Antineutrinos emitted from reactors are used as a
probe. As the antineutrinos traverse through a region prone to earthquakes,
observable variations in the matter effect on the antineutrino oscillation
would provide a tomography of the vicinity of the region. In this preliminary
work, we adopt a simplified model for the geometrical profile and matter
density in a fault zone. We calculate the survival probability of electron
antineutrinos for cases without and with an anomalous accumulation of electrons
which can be considered as a clear signal of the coming earthquake, at the
geological region with a fault zone, and find that the variation may reach as
much as 3% for emitted from a reactor. The case for a beam
from a neutrino factory is also investigated, and it is noted that, because of
the typically high energy associated with such neutrinos, the oscillation
length is too large and the resultant variation is not practically observable.
Our conclusion is that with the present reactor facilities and detection
techniques, it is still a difficult task to make an earthquake forecast using
such a scheme, though it seems to be possible from a theoretical point of view
while ignoring some uncertainties. However, with the development of the
geology, especially the knowledge about the fault zone, and with the
improvement of the detection techniques, etc., there is hope that a medium-term
earthquake forecast would be feasible.Comment: 6 pages, 4 figures, 1 tabl
Dynamics near the Surface Reconstruction of W(100)
Using Brownian molecular dynamics simulation, we study the surface dynamics
near the reconstruction transition of W(100) via a model Hamiltonian. Results
for the softening and broadening of the surface phonon spectrum near the
transition are compared with previous calculations and with He atom scattering
data. From the critical behavior of the central peak in the dynamical structure
factor, we also estimate the exponent of the power law anomaly for adatom
diffusion near the transition temperature.Comment: 8 pages, 8 figures, to appear in Phys. Rev.
Contemporary characteristics and outcomes in chagasic heart failure compared with other nonischemic and ischemic cardiomyopathy
Background: Chagas’ disease is an important cause of cardiomyopathy in Latin America. We aimed to compare clinical characteristics and outcomes in patients with heart failure (HF) with reduced ejection fraction caused by Chagas’ disease, with other etiologies, in the era of modern HF therapies.
Methods and Results: This study included 2552 Latin American patients randomized in the PARADIGM-HF (Prospective Comparison of ARNI With ACEI to Determine Impact on Global Mortality and Morbidity in Heart Failure) and ATMOSPHERE (Aliskiren Trial to Minimize Outcomes in Patients With Heart Failure) trials. The investigator-reported etiology was categorized as Chagasic, other nonischemic, or ischemic cardiomyopathy. The outcomes of interest included the composite of cardiovascular death or HF hospitalization and its components and death from any cause. Unadjusted and adjusted Cox proportional hazards models were performed to compare outcomes by pathogenesis. There were 195 patients with Chagasic HF with reduced ejection fraction, 1300 with other nonischemic cardiomyopathy, and 1057 with ischemic cardiomyopathy. Compared with other etiologies, Chagasic patients were more often female, younger, and had lower prevalence of hypertension, diabetes mellitus, and renal impairment (but had higher prevalence of stroke and pacemaker implantation) and had worse health-related quality of life. The rates of the composite outcome were 17.2, 12.5, and 11.4 per 100 person-years for Chagasic, other nonischemic, and ischemic patients, respectively—adjusted hazard ratio for Chagasic versus other nonischemic: 1.49 (95% confidence interval, 1.15–1.94; P=0.003) and Chagasic versus ischemic: 1.55 (1.18–2.04; P=0.002). The rates of all-cause mortality were also higher.
Conclusions: Despite younger age, less comorbidity, and comprehensive use of conventional HF therapies, patients with Chagasic HF with reduced ejection fraction continue to have worse quality of life and higher hospitalization and mortality rates compared with other etiologies.
Clinical Trial Registration: PARADIGM-HF: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01035255; ATMOSPHERE: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00853658
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