Background Nicotine replacement therapy (NRT) aims to temporarily replace much of the nicotine from cigarettes to reduce motivation to smoke and nicotine withdrawal symptoms, thus easing the transition from cigarette smoking to complete abstinence. Objectives To determine the e ectiveness and safety of nicotine replacement therapy (NRT), including gum, transdermal patch, intranasal spray and inhaled and oral preparations, for achieving long-term smoking cessation, compared to placebo or 'no NRT' interventions. Search methods We searched the Cochrane Tobacco Addiction Group trials register for papers mentioning 'NRT' or any type of nicotine replacement therapy in the title, abstract or keywords. Date of most recent search is July 2017. Selection criteria Randomized trials in people motivated to quit which compared NRT to placebo or to no treatment. We excluded trials that did not report cessation rates, and those with follow-up of less than six months. We recorded adverse events from included and excluded studies that compared NRT with placebo. Studies comparing di erent types, durations, and doses of NRT, and studies comparing NRT to other pharmacotherapies, are covered in separate reviews. Data collection and analysis Screening, data extraction and 'Risk of bias' assessment followed standard Cochrane methods. The main outcome measure was abstinence from smoking a er at least six months of follow-up. We used the most rigorous definition of abstinence for each trial, and biochemically validated rates if available. We calculated the risk ratio (RR) for each study. Where appropriate, we performed meta-analysis using a Mantel-Haenszel fixed-e ect model. Main results We identified 136 studies; 133 with 64,640 participants contributed to the primary comparison between any type of NRT and a placebo or non-NRT control group. The majority of studies were conducted in adults and had similar numbers of men and women. People enrolled in the studies typically smoked at least 15 cigarettes a day at the start of the studies. We judged the evidence to be of high quality; we judged most studies to be at high or unclear risk of bias but restricting the analysis to only those studies at low risk of bias did not significantly alter the result. The RR of abstinence for any form of NRT relative to control was 1.55 (95% confidence interval (CI) 1.49 to 1.61). The pooled RRs for each type were 1.

Di erent doses, durations and modes of delivery of nicotine replacement therapy for smoking cessation.

Patients with PsA who are female and have metabolic syndrome-related co-morbidities have lower TNFi persistence. Although persistence was lower in patients who had switched to a second TNFi, a substantial proportion of these cases responded, advocating switching to a second TNFi as a valid therapeutic strategy.

Organic solar cells (OSCs) have great potential to completely change the development trend of entire industries and become the next generation of commercial solar cells. Compared with polymer solar cells, the nonfullerene all‐small‐molecule organic solar cells (NF‐ASM OSCs) system has the advantages of easy purification, no batch effect, etc. Moreover, their power conversion efficiency (PCE) exceeds the commercialization threshold of 10%. Recently, the diversity of small‐molecule materials and the steady increase in PCE values suggest a bright future for NF‐ASM OSCs. Herein, small‐molecule donor and acceptor materials that have been developed in recent years to produce higher device efficiency are introduced.

Background Immune checkpoint blockers (ICBs) activate CD8+ T cells, eliciting both anti-cancer activity and immune-related adverse events (irAEs). The relationship of irAEs with baseline parameters and clinical outcome is unclear. Methods Retrospective evaluation of irAEs on survival was performed across primary (N = 144) and secondary (N = 211) independent cohorts of patients with metastatic melanoma receiving single agent (pembrolizumab/nivolumab—sICB) or combination (nivolumab and ipilimumab—cICB) checkpoint blockade. RNA from pre-treatment and post-treatment CD8+ T cells was sequenced and differential gene expression according to irAE development assessed. Results 58.3% of patients developed early irAEs and this was associated with longer progression-free (PFS) and overall survival (OS) across both cohorts (log-rank test, OS: P < 0.0001). Median survival for patients without irAEs was 16.6 months (95% CI: 10.9–33.4) versus not-reached (P = 2.8 × 10−6). Pre-treatment monocyte and neutrophil counts, but not BMI, were additional predictors of clinical outcome. Differential expression of numerous gene pathway members was observed in CD8+ T cells according to irAE development, and patients not developing irAEs demonstrating upregulated CXCR1 pre- and post-treatment. Conclusions Early irAE development post-ICB is associated with favourable survival in MM. Development of irAEs is coupled to expression of numerous gene pathways, suggesting irAE development in-part reflects baseline immune activation.

Purpose of reviewPsoriatic arthritis (PsA) is a chronic inflammatory spondyloarthritis that can cause progressive joint damage and irreversible disability. Advances in modern therapies, now mean a target of remission is an achievable goal in PsA. There is strong and consistent evidence that a treat-to-target (T2T) approach to PsA management results in better patient outcomes; however, the practicalities of incorporating this strategy into routine clinical practice remain a challenge. The heterogeneous nature of this condition and the need for validated outcome measures have to-date hampered consensus on a definition of remission. This review aims to summarise the current T2T research landscape in PsA and highlight potential roles for biomarkers and imaging advances in revolutionising the T2T concept.Recent findingsThere is a growing body of evidence to support the implementation of a T2T strategy, using a pre-defined target in PsA management, with significant benefits in disease outcome, physical function and quality of life.SummaryWhilst remission is the ultimately goal for PsA patients and their clinicians, further comparative studies of different treatment targets are needed to establish a widely acceptable definition of remission.

Treatment with immune checkpoint blockade (ICB) frequently triggers immune-related adverse events (irAEs), causing considerable morbidity. In 214 patients receiving ICB for melanoma, we observed increased severe irAE risk in minor allele carriers of rs16906115, intronic to IL7. We found that rs16906115 forms a B cell-specific expression quantitative trait locus (eQTL) to IL7 in patients. Patients carrying the risk allele demonstrate increased pre-treatment B cell IL7 expression, which independently associates with irAE risk, divergent immunoglobulin expression and more B cell receptor mutations. Consistent with the role of IL-7 in T cell development, risk allele carriers have distinct ICB-induced CD8+ T cell subset responses, skewing of T cell clonality and greater proportional repertoire occupancy by large clones. Finally, analysis of TCGA data suggests that risk allele carriers independently have improved melanoma survival. These observations highlight key roles for B cells and IL-7 in both ICB response and toxicity and clinical outcomes in melanoma.

The introduction of biologic disease modifying anti-rheumatic drugs (bMDARDs) have revolutionised the treatment of psoriatic arthritis (PsA). This, combined with a 'treat-to-target' approach, means that achieving remission is increasingly possible. In patients with well-controlled PsA, there is little consensus on whether bDMARDs should be continued, tapered or discontinued altogether. Tapering or discontinuation of bDMARDs could offer significant financial savings and minimise patient burden and unwanted drug-related side effects. However, there is a risk of loss of remission. This primary focus of this paper is to review the current evidence on bDMARD tapering and discontinuation in PsA. We explore the criteria employed by studies to define patients eligible for bDMARD tapering or discontinuation and the process by which this occurs. We also review the outcomes of bDMARD tapering and discontinuation, the predictors, and the likelihood of restoring remission following relapse. To date, bDMARD tapering seems to be feasible and safe in patients with PsA who are in remission or with low disease activity. Lower disease activity and increased duration on tumour necrosis factor inhibitors (TNFi) increases the likelihood of successful bDMARD tapering. In contrast, discontinuing bDMARDs appears to carry a substantial risk of loss of remission. Those with higher disease activity at time of TNFi discontinuation, current smokers, male sex, increased skin involvement, and synovial hypertrophy seen on ultrasound prior to discontinuation are at greater risk of losing remission post bDMARD discontinuation. In those who lose remission, reinstating the standard dose of bDMARD appears to be effective in restoring remission. Key points •In patients with well-controlled psoriatic arthritis on biologics, there is little consensus on whether they should continue on the same dose, taper the dose or discontinue the biologic altogether.• Current evidence is based on small retrospective observational studies, and suggests that biologic tapering is preferable to discontinuation, which carries a substantial risk of loss of remission.• There is a need for high-quality randomised controlled trials to substantiate current evidence in order to guide clinical decision making. If safe and feasible, tapering or discontinuation can result in substantial financial savings and also minimise treatment burden and drug-related side effects for patients.