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

Clinical characteristics and patient-reported outcomes in patients with inadequately controlled rheumatoid arthritis despite ongoing treatment

Background Despite the wide array of treatments available for rheumatoid arthritis (RA), some patients continue to report unmet clinical needs. We investigated the extent of inadequate disease control in patients with RA. Methods Data were drawn from the Adelphi 2014 RA Disease-Specific Program in France, Germany, Italy, Spain and the UK. Rheumatologists provided patient demographics, comorbidities, satisfaction with RA control and other clinical details. Patients reported their level of satisfaction and completed the EuroQoL 5-Dimensions Health Questionnaire and Work Productivity and Activity Impairment Questionnaire. Patients had been on their current therapy 653 months and had 28-joint disease activity scores (DAS28) reported. Adequately controlled (DAS28 643.2) and inadequately controlled (DAS28 >3.2) patient cohorts were compared using univariate tests. Results Of 1147 patients, 74% were women, the mean age was 52 years and the mean time since RA diagnosis was 7 years. Twenty-seven percent of patients had inadequately controlled RA, whereas 73% had adequately controlled RA. Inadequately controlled patients were more affected clinically versus adequately controlled patients; 69% vs 13% had moderate/severe RA, the current level of pain was 4.6 vs 2.3, and 67% vs 41% experienced flares, respectively (all p<0.0001). Inadequately controlled patients had higher rates of depression (16% vs 5%; p<0.0001), worse health state, greater work and activity impairment, and lower satisfaction rates among the patients and their physicians than the adequately controlled cohort. Conclusion RA was insufficiently controlled in over a quarter of patients despite their current therapy and this had a negative impact on the patients

Factors influencing the use of biologic therapy and adoption of treat-to-target recommendations in current european rheumatology practice

Objective: The aim of this study was to identify factors that influence treatment adjustments and adoption of a treat-to-target (T2T) strategy in patients with rheumatoid arthritis (RA) in European practices. Methods: Cross-sectional data were drawn from the Adelphi 2014 RA Disease Specific Programme. Treatment patterns and clinical characteristics were investigated in patients treated with biologic disease-modifying antirheumatic drugs (bDMARDs) vs non-bDMARDs. For the T2T analysis, patients were subdivided into two subsets (RA diagnosis <2 or 652 years) and compared according to the approach used (no target = no T2T approach; pragmatic = target different from remission; and aspirational = target set as remission). Results: Data from 2,536 patients were analyzed (mean age: 52.76 years and mean time since RA diagnosis: 6.05 years). Of the 1,438 patients eligible to receive bDMARDs, 55% did not receive them. Initiation of bDMARDs in a bDMARD-na\uefve patient was prompted by worsening of the disease. In the RA diagnosis <2 years subset, a T2T approach was not adopted in 58% of the patients, whereas 8% and 34% adopted a pragmatic and aspirational approach, respectively. In the RA diagnosis 652 years subset, 45%, 19%, and 36% of the patients adopted a no target, pragmatic, and aspirational approach, respectively. Physician satisfaction with RA control was lower in the RA diagnosis <2 years subset than in the RA diagnosis 652 years subset (65% vs 77% satisfied, respectively; P<0.0001). Conclusion: This analysis shows that the use of bDMARDs remains suboptimal and that a T2T strategy is not universally adopted

Cholinergic system and the thalamus in dementia with Lewy bodies, Alzheimer's disease and schizophrenia A neurochemical study

SIGLEAvailable from British Library Document Supply Centre-DSC:DXN016902 / BLDSC - British Library Document Supply CentreGBUnited Kingdo

Systematic review and network meta-analysis of combination and monotherapy treatments in disease-modifying antirheumatic drug-experienced patients with rheumatoid arthritis: analysis of American College of Rheumatology criteria scores 20, 50, and 70

Michelle E Orme,1 Katherine S MacGilchrist,2 Stephen Mitchell,2 Dean Spurden,3 Alex Bird31Icera Consulting, Swindon, Wiltshire, UK; 2Systematic Review Department, Abacus International, Bicester, Oxfordshire, UK; 3Pfizer UK Limited, Tadworth, Surrey, UKBackground: Biologic disease-modifying antirheumatic drugs (bDMARDs) extend the treatment choices for rheumatoid arthritis patients with suboptimal response or intolerance to conventional DMARDs. The objective of this systematic review and meta-analysis was to compare the relative efficacy of EU-licensed bDMARD combination therapy or monotherapy for patients intolerant of or contraindicated to continued methotrexate.Methods: Comprehensive, structured literature searches were conducted in Medline, Embase, and the Cochrane Library, as well as hand-searching of conference proceedings and reference lists. Phase II or III randomized controlled trials reporting American College of Rheumatology (ACR) criteria scores of 20, 50, and 70 between 12 and 30 weeks' follow-up and enrolling adult patients meeting ACR classification criteria for rheumatoid arthritis previously treated with and with an inadequate response to conventional DMARDs were eligible. To estimate the relative efficacy of treatments whilst preserving the randomized comparisons within each trial, a Bayesian network meta-analysis was conducted in WinBUGS using fixed and random-effects, logit-link models fitted to the binomial ACR 20/50/70 trial data.Results: The systematic review identified 10,625 citations, and after a review of 2450 full-text papers, there were 29 and 14 eligible studies for the combination and monotherapy meta-analyses, respectively. In the combination analysis, all licensed bDMARD combinations had significantly higher odds of ACR 20/50/70 compared to DMARDs alone, except for the rituximab comparison, which did not reach significance for the ACR 70 outcome (based on the 95% credible interval). The etanercept combination was significantly better than the tumor necrosis factor-α inhibitors adalimumab and infliximab in improving ACR 20/50/70 outcomes, with no significant differences between the etanercept combination and certolizumab pegol or tocilizumab. Licensed-dose etanercept, adalimumab, and tocilizumab monotherapy were significantly better than placebo in improving ACR 20/50/70 outcomes. Sensitivity analysis indicated that including studies outside the target population could affect the results.Conclusion: Licensed bDMARDs are efficacious in patients with an inadequate response to conventional therapy, but tumor necrosis factor-α inhibitor combination therapies are not equally effective.Keywords: bDMARD, rheumatoid arthritis, etanercept, systematic review, network meta-analysis, comparative effectivenes

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

Expression of the alpha3 nicotinic receptor subunit mRNA in aging and Alzheimer's disease

Changes in the number of high-affinity nicotine binding sites have been widely reported in specific regions of the human brain during aging and in degenerative neurological diseases associated with aging, such as Alzheimer's disease. Nicotinic receptors are highly diverse and a description of the molecular subtypes affected in such conditions has not been achieved to date. To investigate the status of the alpha3 subunit-containing subtypes in such conditions, we assessed by in situ hybridisation the alpha3 mRNA density in the hippocampus, entorhinal cortex and thalamus of Alzheimer's patients and age-matched controls. No significant difference in the expression of the alpha3 mRNA, either qualitative or quantitative, was found between Alzheimer's individuals and controls in any of the analysed areas. This result suggests that the nicotine binding changes occurring in these areas in Alzheimer's patients are not correlated to a variation of the alpha3 mRNA in the same regions. Nevertheless, a negative correlation between the alpha3 mRNA density and the age was observed in the entorhinal cortex of both the Alzheimer's and the normal subjects, suggesting a potentially extensive decay of the alpha3-expressing neurons or loss of alpha3-containing receptors in intact neurons of the entorhinal cortex in the late elderly