Efficacy of pharmacotherapies for short-term smoking abstinance: A systematic review and meta-analysis

Background: Smoking cessation has important immediate health benefits. The comparative shorttermeffectiveness of smoking cessation interventions is not well known. We aimed to determinethe relative effectiveness of nicotine replacement therapy (NRT), bupropion and varenicline at 4weeks post-target quit date. Methods: We searched 10 electronic medical databases (inception to October 2008). Weselected randomized clinical trials [RCTs] evaluating interventions for our primary outcome ofabstinence from smoking at at-least 4 weeks post-target quit date, with biochemical confirmation.We conducted random-effects odds ratio (OR) meta-analysis and meta-regression. We comparedtreatment effects across interventions using head-to-head trials and calculated indirectcomparisons. Results: We combined a total of 101 trials evaluating delivery of NRT versus inert controls atapproximately 4 weeks post-target quit date (total n = 31,321). The pooled overall OR is OR 2.05(95% Confidence Interval [CI], 1.89-2.23, P =< 0.0001). We pooled data from 31 bupropion trialscontributing a total n of 11,118 participants and found a pooled OR of 2.25 (95% CI, 1.94-2.62, P=< 0.0001). We evaluated 9 varenicline trials compared to placebo. Our pooled estimate forcessation at 4 weeks post-target quit date found a pooled OR of 3.16 (95% CI, 2.55-3.91, P =<0.0001). Two trials evaluated head to head comparisons of varenicline and bupropion and found apooled estimate of OR 1.86 (95% CI, 1.49-2.33, P =< 0.0001 at 4 weeks post-target quit date.Indirect comparisons were: NRT and bupropion, OR, 1.09, 95% CI, 0.93-1.31, P = 0.28; vareniclineand NRT, OR 1.56, 95% CI, 1.23-1.96, P = 0.0002; and, varenicline and bupropion, OR 1.40, 95%CI, 1.08-1.85, P = 0.01. Conclusion: Pharmacotherapeutic interventions are effective for increasing smoking abstinencerates in the short-term

Long-Term Drug Survival of TNF Inhibitor Therapy in RA Patients: A Systematic Review of European National Drug Registers

Objective. The present systematic review of RA registry data was undertaken to analyse the time on treatment of licensed TNF inhibitors in patients with RA in Europe. Methods. English language European registry studies comparing TNF inhibitors were searched using MEDLINE, Embase, Cochrane, and WHO: ICTRP up to 16 April 2012 and proceedings of three selected conferences held between 2010 and 2012. Pooled analysis was performed to determine drug survival rates for each TNF inhibitor. Results. Sixteen studies met the inclusion criteria, of which 11 studies assessed biologic-naive patients and five studies included a mixed population of biologic-naive and biologic pretreated patients. The overall effectiveness of TNF inhibitors diminished with time, leading to decreased drug survival rates. Pooled drug survival rates after 60 months follow-up were 37% (infliximab), 48% (adalimumab), and 52% (etanercept). Further, in an observational study, when TNF inhibitors were used in combination with methotrexate, a longer drug survival was observed compared to TNF inhibitors alone. Conclusion. The findings of this systematic review indicated numerically lower drug discontinuation rates with etanercept than adalimumab, whereas infliximab had the highest rate. Further research is needed to understand the underlying mechanisms of treatment discontinuation with TNF inhibitors

Efficacy of pharmacotherapies for short-term smoking abstinance: A systematic review and meta-analysis

Abstract Background Smoking cessation has important immediate health benefits. The comparative short-term effectiveness of smoking cessation interventions is not well known. We aimed to determine the relative effectiveness of nicotine replacement therapy (NRT), bupropion and varenicline at 4 weeks post-target quit date. Methods We searched 10 electronic medical databases (inception to October 2008). We selected randomized clinical trials [RCTs] evaluating interventions for our primary outcome of abstinence from smoking at at-least 4 weeks post-target quit date, with biochemical confirmation. We conducted random-effects odds ratio (OR) meta-analysis and meta-regression. We compared treatment effects across interventions using head-to-head trials and calculated indirect comparisons. Results We combined a total of 101 trials evaluating delivery of NRT versus inert controls at approximately 4 weeks post-target quit date (total n = 31,321). The pooled overall OR is OR 2.05 (95% Confidence Interval [CI], 1.89-2.23, P = Conclusion Pharmacotherapeutic interventions are effective for increasing smoking abstinence rates in the short-term.</p

Near-complete adaptation of the PRiMA knockout to the lack of central acetylcholinesterase

Acetylcholinesterase (AChE) rapidly hydrolyzes acetylcholine. At the neuromuscular junction, AChE is mainly anchored in the extracellular matrix by the collagen Q, whereas in the brain, AChE is tethered by the proline-rich membrane anchor (PRiMA). The AChE-deficient mice, in which AChE has been deleted from all tissues, have severe handicaps. Surprisingly, PRiMA KO mice in which AChE is mostly eliminated from the brain show very few deficits. We now report that most of the changes observed in the brain of AChE-deficient mice, and in particular the high levels of ambient extracellular acetylcholine and the massive decrease of muscarinic receptors, are also observed in the brain of PRiMA KO. However, the two groups of mutants differ in their responses to AChE inhibitors. Since PRiMA-KO mice and AChE-deficient mice have similar low AChE concentrations in the brain but differ in the AChE content of the peripheral nervous system, these results suggest that peripheral nervous system AChE is a major target of AChE inhibitors, and that its absence in AChE- deficient mice is the main cause of the slow development and vulnerability of these mice. At the level of the brain, the adaptation to the absence of AChE is nearly complete.</p