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Now is an exciting era of development in immunotherapy checkpoint inhibitors and their effect on the treatment of NPC. While the general prognosis of R/M disease is poor, immunotherapy offers some promise in a malignancy associated with EBV and characterized by a peritumoural immune infiltrate. Our study aims to review past and on-going clinical trials of monoclonal antibody therapies against the checkpoint inhibitors (e.g. PD1 and CTLA-4), in R/M NPC. All randomized and nonrandomized controlled trials involving immune checkpoint inhibitor interventions for treatment of NPC were included in the study. We utilized a validated “risk of bias” tool to assess study quality. Four separate Phase I–II trials report the potential of PD1 inhibitor treatment for patients with NPC. Within the observed groups, camrelizumab combined with chemotherapy achieved an objective response in 91% of patients as first-line treatment for metastatic NPC (PFS 68% at 1-year) but this was associated with a high rate of grade >3 adverse events (87%; CTCAE version 4.03). The remaining three studies focused on recurrent NPC disease in patients who had received at least one line of prior chemotherapy. Within this group, camrelizumab monotherapy achieved an objective response in 34% of patients (PFS 27% at 1-year; range across all three studies 20.5–34%). No NPC trial has yet reported on specific outcomes for non-PD1 checkpoint inhibitors but 11 on-going studies include alternative targets (e.g. PD-L1/CTLA-4) as combination or monotherapy treatments. In considering checkpoint immunotherapies for NPC, initial results show promise for anti-PD1 interventions. Further phase I–III trials are in progress to clarify clinical outcomes, fully determine safety profiles, and optimize drug combinations and administration schedules.  相似文献   
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Objective:The purpose of this study was to provide an updated profile of gambling and problem gambling in Canada and to examine how the rates and pattern of participation compare to 2002.Method:An assessment of gambling and problem gambling was included in the 2018 Canadian Community Health Survey and administered to 24,982 individuals aged 15 and older. The present analyses selected for adults (18+).Results:A total of 66.2% of people reported engaging in some type of gambling in 2018, primarily lottery and/or raffle tickets, the only type in which the majority of Canadians participate. There are some significant interprovincial differences, with perhaps the most important one being the higher rate of electronic gambling machine (EGM) participation in Manitoba and Saskatchewan. The overall pattern of gambling in 2018 is very similar to 2002, although participation is generally much lower in 2018, particularly for EGMs and bingo. Only 0.6% of the population were identified as problem gamblers in 2018, with an additional 2.7% being at-risk gamblers. There is no significant interprovincial variation in problem gambling rates. The interprovincial pattern of problem gambling in 2018 is also very similar to what was found in 2002 with the main difference being a 45% decrease in the overall prevalence of problem gambling.Conclusions:Gambling and problem gambling have both decreased in Canada from 2002 to 2018 although the provincial patterns are quite similar between the 2 time periods. Several mechanisms have likely collectively contributed to these declines. Decreases have also been reported in several other Western countries in recent years and have occurred despite the expansion of legal gambling opportunities, suggesting a degree of inoculation or adaptation in large parts of the population.  相似文献   
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