61 research outputs found
Risk of All-Cause Mortality in Alcohol-Dependent Individuals: A Systematic Literature Review and Meta-Analysis.
BACKGROUND: Alcohol dependence (AD) carries a high mortality burden, which may be mitigated by reduced alcohol consumption. We conducted a systematic literature review and meta-analysis investigating the risk of all-cause mortality in alcohol-dependent subjects.
METHODS: MEDLINE, MEDLINE In-Process, Embase and PsycINFO were searched from database conception through 26th June 2014. Eligible studies reported all-cause mortality in both alcohol-dependent subjects and a comparator population of interest. Two individuals independently reviewed studies. Of 4540 records identified, 39 observational studies were included in meta-analyses.
FINDINGS: We identified a significant increase in mortality for alcohol-dependent subjects compared with the general population (27 studies; relative risk [RR] = 3.45; 95% CI [2.96, 4.02]; p < 0.0001). The mortality increase was also significant compared to subjects qualifying for a diagnosis of alcohol abuse or subjects without alcohol use disorders (AUDs). Alcohol-dependent subjects continuing to drink heavily had significantly greater mortality than alcohol-dependent subjects who reduced alcohol intake, even if abstainers were excluded (p < 0.05).
INTERPRETATION: AD was found to significantly increase an individual's risk of all-cause mortality. While abstinence in alcohol-dependent subjects led to greater mortality reduction than non-abstinence, this study suggests that alcohol-dependent subjects can significantly reduce their mortality risk by reducing alcohol consumption
Modelling the consequences of a reduction in alcohol consumption among patients with alcohol dependence based on real-life observational data.
BACKGROUND: Most available pharmacotherapies for alcohol-dependent patients target abstinence; however, reduced alcohol consumption may be a more realistic goal. Using randomized clinical trial (RCT) data, a previous microsimulation model evaluated the clinical relevance of reduced consumption in terms of avoided alcohol-attributable events. Using real-life observational data, the current analysis aimed to adapt the model and confirm previous findings about the clinical relevance of reduced alcohol consumption.
METHODS: Based on the prospective observational CONTROL study, evaluating daily alcohol consumption among alcohol-dependent patients, the model predicted the probability of drinking any alcohol during a given day. Predicted daily alcohol consumption was simulated in a hypothetical sample of 200,000 patients observed over a year. Individual total alcohol consumption (TAC) and number of heavy drinking days (HDD) were derived. Using published risk equations, probabilities of alcohol-attributable adverse health events (e.g., hospitalizations or death) corresponding to simulated consumptions were computed, and aggregated for categories of patients defined by HDDs and TAC (expressed per 100,000 patient-years). Sensitivity analyses tested model robustness.
RESULTS: Shifting from >220 HDDs per year to 120-140 HDDs and shifting from 36,000-39,000 g TAC per year (120-130 g/day) to 15,000-18,000 g TAC per year (50-60 g/day) impacted substantially on the incidence of events (14,588 and 6148 events avoided per 100,000 patient-years, respectively). Results were robust to sensitivity analyses.
CONCLUSIONS: This study corroborates the previous microsimulation modeling approach and, using real-life data, confirms RCT-based findings that reduced alcohol consumption is a relevant objective for consideration in alcohol dependence management to improve public health
The cost-effectiveness and public health benefit of nalmefene added to psychosocial support for the reduction of alcohol consumption in alcohol-dependent patients with high/very high drinking risk levels: a Markov model.
OBJECTIVES: To determine whether nalmefene combined with psychosocial support is cost-effective compared with psychosocial support alone for reducing alcohol consumption in alcohol-dependent patients with high/very high drinking risk levels (DRLs) as defined by the WHO, and to evaluate the public health benefit of reducing harmful alcohol-attributable diseases, injuries and deaths.
DESIGN: Decision modelling using Markov chains compared costs and effects over 5 years.
SETTING: The analysis was from the perspective of the National Health Service (NHS) in England and Wales.
PARTICIPANTS: The model considered the licensed population for nalmefene, specifically adults with both alcohol dependence and high/very high DRLs, who do not require immediate detoxification and who continue to have high/very high DRLs after initial assessment.
DATA SOURCES: We modelled treatment effect using data from three clinical trials for nalmefene (ESENSE 1 (NCT00811720), ESENSE 2 (NCT00812461) and SENSE (NCT00811941)). Baseline characteristics of the model population, treatment resource utilisation and utilities were from these trials. We estimated the number of alcohol-attributable events occurring at different levels of alcohol consumption based on published epidemiological risk-relation studies. Health-related costs were from UK sources.
MAIN OUTCOME MEASURES: We measured incremental cost per quality-adjusted life year (QALY) gained and number of alcohol-attributable harmful events avoided.
RESULTS: Nalmefene in combination with psychosocial support had an incremental cost-effectiveness ratio (ICER) of £5204 per QALY gained, and was therefore cost-effective at the £20,000 per QALY gained decision threshold. Sensitivity analyses showed that the conclusion was robust. Nalmefene plus psychosocial support led to the avoidance of 7179 alcohol-attributable diseases/injuries and 309 deaths per 100,000 patients compared to psychosocial support alone over the course of 5 years.
CONCLUSIONS: Nalmefene can be seen as a cost-effective treatment for alcohol dependence, with substantial public health benefits.
TRIAL REGISTRATION NUMBERS: This cost-effectiveness analysis was developed based on data from three randomised clinical trials: ESENSE 1 (NCT00811720), ESENSE 2 (NCT00812461) and SENSE (NCT00811941)
Antimatter from the cosmological baryogenesis and the anisotropies and polarization of the CMB radiation
We discuss the hypotheses that cosmological baryon asymmetry and entropy were
produced in the early Universe by phase transition of the scalar fields in the
framework of spontaneous baryogenesis scenario. We show that annihilation of
the matter-antimatter clouds during the cosmological hydrogen recombination
could distort of the CMB anisotropies and polarization by delay of the
recombination. After recombination the annihilation of the antibaryonic clouds
(ABC) and baryonic matter can produce peak-like reionization at the high
redshifts before formation of quasars and early galaxy formation. We discuss
the constraints on the parameters of spontaneous baryogenesis scenario by the
recent WMAP CMB anisotropy and polarization data and on possible manifestation
of the antimatter clouds in the upcoming PLANCK data.Comment: PRD in press with minor change
Elastic scattering and breakup of 17^F at 10 MeV/nucleon
Angular distributions of fluorine and oxygen produced from 170 MeV 17^F
incident on 208^Pb were measured. The elastic scattering data are in good
agreement with optical model calculations using a double-folding potential and
parameters similar to those obtained from 16^O+208^Pb. A large yield of oxygen
was observed near \theta_lab=36 deg. It is reproduced fairly well by a
calculation of the (17^F,16^O) breakup, which is dominated by one-proton
stripping reactions. The discrepancy between our previous coincidence
measurement and theoretical predictions was resolved by including core
absorption in the present calculation.Comment: 9 pages, 5 figure
On the variation of the gauge couplings during inflation
It is shown that the evolution of the (Abelian) gauge coupling during an
inflationary phase of de Sitter type drives the growth of the two-point
function of the magnetic inhomogeneities. After examining the constraints on
the variation of the gauge coupling arising in a standard model of inflationary
and post-inflationary evolution, magnetohydrodynamical equations are
generalized to the case of time evolving gauge coupling. It is argued that
large scale magnetic fields can be copiously generated. Other possible
implications of the model are outlined.Comment: 5 pages in RevTex style, one figur
EBAG9-silencing exerts an immune checkpoint function without aggravating adverse effects
Chimeric antigen receptor (CAR) T cells have revolutionized treatment of B-cell malignancies. However, enhancing the efficacy of engineered T cells without compromising their safety is warranted. The estrogen receptor-binding fragment-associated antigen 9 (EBAG9) inhibits release of cytolytic enzymes from cytotoxic T lymphocytes. Here, we examined the potency of EBAG9-silencing for the improvement of adoptive T cell therapy. Micro-RNA-mediated EBAG9 downregulation in transplanted CTLs from immunized mice improved their cytolytic competence in a tumor model. In tolerant female recipient mice that received organ transplants, a minor histocompatibility antigen was turned into a rejection antigen by Ebag9 deletion, indicating an immune checkpoint function for EBAG9. Considerably less EBAG9-silenced human CAR T cells were needed for tumor growth control in a xenotransplantation model. Transcriptome profiling did not reveal additional risks regarding genotoxicity or aberrant differentiation. A single-step retrovirus transduction process links CAR or TCR expression with miRNA-mediated EBAG9 downregulation. Despite higher cytolytic efficacy, release of cytokines associated with cytokine release syndrome remains unaffected. Collectively, EBAG9-silencing enhances effector capacity of TCR- and CAR-engineered T cells, results in improved tumor eradication, facilitates efficient manufacturing, and decreases the therapeutic dose
First-order cosmological phase transitions in the radiation dominated era
We consider first-order phase transitions of the Universe in the
radiation-dominated era. We argue that in general the velocity of interfaces is
non-relativistic due to the interaction with the plasma and the release of
latent heat. We study the general evolution of such slow phase transitions,
which comprise essentially a short reheating stage and a longer phase
equilibrium stage. We perform a completely analytical description of both
stages. Some rough approximations are needed for the first stage, due to the
non-trivial relations between the quantities that determine the variation of
temperature with time. The second stage, instead, is considerably simplified by
the fact that it develops at a constant temperature, close to the critical one.
Indeed, in this case the equations can be solved exactly, including
back-reaction on the expansion of the Universe. This treatment also applies to
phase transitions mediated by impurities. We also investigate the relations
between the different parameters that govern the characteristics of the phase
transition and its cosmological consequences, and discuss the dependence of
these parameters with the particle content of the theory.Comment: 38 pages, 3 figures; v2: Minor changes, references added; v3: several
typos correcte
Magnetogenesis and the dynamics of internal dimensions
The dynamical evolution of internal space-like dimensions breaks the
invariance of the Maxwell's equations under Weyl rescaling of the (conformally
flat) four-dimensional metric. Depending upon the number and upon the dynamics
of internal dimensions large scale magnetic fields can be created. The
requirements coming from magnetogenesis together with the other cosmological
constraints are examined under the assumption that the internal dimensions
either grow or shrink (in conformal time) prior to a radiation dominated epoch.
If the internal dimensions are growing the magnitude of the generated magnetic
fields can seed the galactic dynamo mechanism.Comment: 27 in RevTex style, four figure
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