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psed without irAE development. Although the monthly incidence of irAEs decreased over time on therapy, patients can still develop delayed irAEs beyond ICI discontinuation, and thus, continuous vigilant monitoring is warranted. © Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.BACKGROUND Malignant pleural mesothelioma (MPM) is a highly lethal malignancy in need for new treatment options. Although immunotherapies have been shown to boost a tumor-specific immune response, not all patients respond and prognostic biomarkers are scarce. In this study, we determined the peripheral blood T cell receptor β (TCRβ) chain repertoire of nine MPM patients before and 5 weeks after the start of dendritic cell (DC)-based immunotherapy. MATERIALS AND METHODS We separately profiled PD1+ and PD1-CD4+ and CD8+ T cells, as well as Tregs and analyzed 70 000 TCRβ sequences per patient. RESULTS Strikingly, limited TCRβ repertoire diversity and high average clone sizes in total CD3+ T cells before the start of immunotherapy were associated with a better clinical response. To explore the differences in TCRβ repertoire prior-DC-therapy and post-DC-therapy, for each patient the TCRβ clones present in the total CD3+ T cell fractions were classified into five categories, based on therapy-associated frequency chiling in sorted T cell subsets could serve as predictive biomarker for the selection of MPM patients that benefit from immunotherapy. TRIAL REGISTRATION NUMBER NCT02395679. © Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.BACKGROUND Lymphocyte activating 3 (LAG3, LAG-3, CD223) is a promising target for immune checkpoint inhibition in clear cell renal cell carcinoma (KIRC). The aim of this study was to investigate the epigenetic regulation of LAG3 in KIRC by methylation. METHODS We correlated quantitative LAG3 methylation levels with transcriptional activity, immune cell infiltration, and overall survival in a cohort of n=533 patients with KIRC and n=160 normal adjacent tissue (NAT) samples obtained from The Cancer Genome Atlas (TCGA). Furthermore, we analyzed LAG3 methylation in peripheral blood mononuclear cells (PBMCs) and KIRC cell lines. We validated correlations between LAG3 expression, immune cell infiltrates, survival, and methylation in an independent KIRC cohort (University Hospital Bonn (UHB) cohort, n=118) by means of immunohistochemistry and quantitative methylation-specific PCR. RESULTS We found differential methylation profiles among PBMCs, NAT, KIRC cell lines, and KIRC tumor tissue. Methylation strongly correlayer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.INTRODUCTION In Taiwan, national tobacco use surveys show that e-cigarette use has increased since 2014 among youth, while, at the same time, conventional cigarette smoking has continuously decreased. The purpose of this study is to examine whether the increased popularity of e-cigarettes has undermined this favourable declining trend for cigarette smoking. METHODS We examined conventional cigarette and e-cigarette prevalence among male high school students (aged 16-18 years) and adults from 2004 to 2017, using data from cross-sectional nationally representative surveys. Applying interrupted time series analysis, we assessed whether there was a change in trend in 2014, when e-cigarette use started to gain popularity from long-term trends in prior years (2004-2013). RESULTS E-cigarette use prevalence increased from 2.5% in 2014 to 6.4% in 2017 among male high school students but was negligible among male adults, declining from 1.4% in 2015 to 0.8% in 2017. The annual relative decline in the cigarette smoking rate after e-cigarettes started to gain popularity was greater (-10%) than the long-term trend (-2%) among high school students. Among adults, the change in trend over time after e-cigarettes started to gain popularity was not significant (ie, not significantly different from 0). CONCLUSIONS The increased popularity of e-cigarettes since 2014 is associated with a greater decline in youth smoking, compared with previous years. On the contrary, e-cigarette use has remained very low among Taiwanese male adults and no additional impact on the conventional smoking trend is found. © Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.BACKGROUND Some opportunities to routinely capture and improve respectful maternity care (RMC) during facility-based childbirth include quality improvement (QI) initiatives, community-based monitoring efforts through community score cards (CSC), and performance-based financing (PBF) initiatives. But there is limited guidance on which types of RMC indicators are best suited for inclusion in these initiatives. We sought to provide practical evidence-based recommendations on indicators that may be used for routine measurement of RMC in programs. METHODS We used a rapid review approach, which included (1) reviewing existing documents and publications to extract RMC indicators and identify which have or can be used in facility-based QI, CSCs, and PBF schemes; (2) surveying RMC and maternal health experts to rank indicators, and (3) analyzing survey data to select the most recommended indicators. RESULTS We identified 49 indicators spanning several domains of RMC and mistreatment including dignified/nondignified caf care as a means of reducing maternal and neonatal morbidity and mortality. © Afulani et al.BACKGROUND A home-based record (HBR) is a health document kept by the patient or their caregivers, rather than by the health care facility. HBRs are used in 163 countries, but they have not been implemented universally or consistently. Effective implementation maximizes both health impacts and cost-effectiveness. We sought to examine this research-to-practice gap and delineate the facilitators and barriers to the effective implementation and use of maternal and child health HBRs especially in low- and middle-income countries (LMICs). METHODS Using a framework analysis approach, we created a framework of implementation categories in advance using subject expert inputs. We collected information through 2 streams. First, we screened 69 gray literature documents, of which 18 were included for analysis. Second, we conducted semi-structured interviews with 12 key informants, each of whom had extensive experience with HBR implementation. find more We abstracted the relevant data from the documents and interviews into an analytic matrix.
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