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

Aligned copper nanorod arrays for highly efficient generation of intense ultra-broadband THz pulses

We demonstrate an intense broadband terahertz (THz) source based on the interaction of relativistic-intensity femtosecond lasers with aligned copper nanorod array targets. For copper nanorod targets with a length of 5 μm, a maximum 13.8 times enhancement in the THz pulse energy (in ≤20 THz spectral range) is measured as compared to that with a thick plane copper target under the same laser conditions. A further increase in the nanorod length leads to a decrease in the THz pulse energy at medium frequencies (≤20 THz) and increase of the electromagnetic pulse energy in the high-frequency range (from 20–200 THz). For the latter, we measure a maximum energy enhancement of 28 times for the nanorod targets with a length of 60 μm. Particle-in-cell simulations reveal that THz pulses are mostly generated by coherent transition radiation of laser produced hot electrons, which are efficiently enhanced with the use of nanorod targets. Good agreement is found between the simulation and experimental results

Economic burden associated with alcohol dependence in a German primary care sample : a bottom-up study

BACKGROUND: A considerable economic burden has been repeatedly associated with alcohol dependence (AD) - mostly calculated using aggregate data and alcohol-attributable fractions (top-down approach). However, this approach is limited by a number of assumptions, which are hard to test. Thus, cost estimates should ideally be validated with studies using individual data to estimate the same costs (bottom-up approach). However, bottom-up studies on the economic burden associated with AD are lacking. Our study aimed to fill this gap using the bottom-up approach to examine costs for AD, and also stratified the results by the following subgroups: sex, age, diagnostic approach and severity of AD, as relevant variations could be expected by these factors. METHODS: SAMPLE: 1356 primary health care patients, representative for two German regions. AD was diagnosed by a standardized instrument and treating physicians. Individual costs were calculated by combining resource use and productivity data representing a period of six months prior to the time of interview, with unit costs derived from the literature or official statistics. The economic burden associated with AD was determined via excess costs by comparing utilization of various health care resources and impaired productivity between people with and without AD, controlling for relevant confounders. Additional analyses for several AD characteristics were performed. RESULTS: Mean costs among alcohol dependent patients were 50 % higher compared to the remaining patients, resulting in 1836 € excess costs per alcohol dependent patient in 6 months. More than half of these excess costs incurred through increased productivity loss among alcohol dependent patients. Treatment for alcohol problems represents only 6 % of these costs. The economic burden associated with AD incurred mainly among males and among 30 to 49 year old patients. Both diagnostic approaches were significantly related to the economic burden, while costs increased with alcohol use disorder severity but not with other AD severity indicators. CONCLUSIONS: Our study confirms previous studies using top-down approaches to estimate the economic burden associated with AD. Further, we highlight the need for efforts aimed at preventing adverse outcomes for health and occupational situation associated with alcohol dependence based on factors associated with particularly high economic burden

DSIF and RNA Polymerase II CTD Phosphorylation Coordinate the Recruitment of Rpd3S to Actively Transcribed Genes

Histone deacetylase Rpd3 is part of two distinct complexes: the large (Rpd3L) and small (Rpd3S) complexes. While Rpd3L targets specific promoters for gene repression, Rpd3S is recruited to ORFs to deacetylate histones in the wake of RNA polymerase II, to prevent cryptic initiation within genes. Methylation of histone H3 at lysine 36 by the Set2 methyltransferase is thought to mediate the recruitment of Rpd3S. Here, we confirm by ChIP–Chip that Rpd3S binds active ORFs. Surprisingly, however, Rpd3S is not recruited to all active genes, and its recruitment is Set2-independent. However, Rpd3S complexes recruited in the absence of H3K36 methylation appear to be inactive. Finally, we present evidence implicating the yeast DSIF complex (Spt4/5) and RNA polymerase II phosphorylation by Kin28 and Ctk1 in the recruitment of Rpd3S to active genes. Taken together, our data support a model where Set2-dependent histone H3 methylation is required for the activation of Rpd3S following its recruitment to the RNA polymerase II C-terminal domain