Search

Aim The goal of this systematic review was to identify moderators of naltrexone efficacy in the treatment of alcohol dependence. Methods We searched Pubmed, CINHAL, Embase, PsycINFO and the Cochrane Library from 1990 to April 2012 and reference lists of pertinent review articles, which yielded 622 trial, pooled analysis and review articles. Using pre-established eligibility criteria, two reviewers independently determined whether abstracts contained evidence of demographic or biological characteristics, i.e. moderators, influencing naltrexone response in alcohol dependence. We assessed each publication for risk of bias and evaluated the strength of the body of evidence for each moderator. Results Twenty-eight publications (on 20 studies) met criteria for data synthesis. These included 26 publications from 12 randomized, placebo-controlled trials, three non-randomized, non-placebo studies and one randomized, non-placebo study. In addition, there were two publications from pooled analyses of four randomized, placebo-controlled trials. Family history of alcohol problems and the Asn40 Asp polymorphism of the μ-opioid receptor gene showed a positive association with efficacy in four of five and three of five studies, respectively. Other moderators reported to be associated with efficacy included male sex (two of five studies), pre-treatment drinking (two of two studies) and high craving (two of five studies). However, the overall risk of bias in the published literature is high. Conclusions The identification of naltrexone-responsive alcohol-dependent patients is still in development. Studies to date point to two potential moderators-family history and presence of the OPRM1 Asn40 Asp polymorphism-as having the strongest evidence. However, the data to date is still insufficient to recommend that any moderator be used in determining clinical treatment. [ABSTRACT FROM AUTHOR]

Aims To illustrate the impact of different proportions of injecting drug users (IDUs) sharing high dead-space syringes (HDSS) or low dead-space syringes (LDSS) on the probability of human immunodeficiency virus (HIV) transmission; and thus the impact on injection-related HIV prevalence and incidence. Design A stochastic mathematical model was used to evaluate the impact of HDSS use in high- and low-risk IDU populations. Model parameters were obtained from peer-reviewed publications. Analytical solutions of a simplified deterministic model were obtained to explain the effect of HDSS on HIV endemic states. Findings Simulation analysis shows that the HIV epidemic could be sustained even when a small percentage of sharing (10%) involved HDSS. The effect is much stronger in high-risk compared with low-risk populations. Steady state HIV prevalence increases with the proportion of HDSS, and for high- and low-risk populations reaches around 80% and 20%, respectively. For low-risk populations, the use of LDSS could result in the virtual elimination of HIV. These results are dependent upon an evidence-supported assumption of a significant difference in HIV transmission risk associated with HDSS versus LDSS. Conclusions Our models suggest that injection-related HIV epidemics may not occur when most (e.g. 95% or more) IDUs use LDSS. While these results are based on indirect risk measures and a number of simplifying assumptions, the effect of blood retained in high dead-space syringes on HIV prevalence seems to be very strong, even using relatively conservative assumptions. The findings have potential implications for needle exchange programs and the types of syringes produced and distributed world-wide. [ABSTRACT FROM AUTHOR]