BackgroundTumor mutation burden (TMB) as a prognostic marker for immunotherapy has shown prognostic value in many cancers. However, there is no systematic investigation on TMB in papillary thyroid carcinoma (PTC).MethodsBased on the somatic mutation data of 487 PTC patients from The Cancer Genome Atlas (TCGA), TMB was calculated, and we classified the samples into high-TMB (H-TMB) and low-TMB (L-TMB) groups. Bioinformatics methods were used to explore the characteristics and potential mechanism of TMB in PTC.ResultsHigh TMB predicts shorter progression-free survival (PFS) (P < 0.001). TMB was positively correlated with age, stage, tumor size, metastasis, the male sex and tall cell PTC. Compared to the L-TMB group, the H-TMB group presented with lower immune cell infiltration, a higher proportion of tumor-promoting immune cells (M0 macrophages, activated dendritic cells and monocytes) and a lower proportion of antitumor immune cells (M1 macrophages, CD8+ T cells and B cells). Additionally, the characteristics displayed by different TMB groups were not driven by critical driver mutations such as BRAF and RAS.ConclusionsPTC patients with high TMB have a worse prognosis. By stratifying PTC patients according to their TMB, advanced PTC patients who are candidates for immunotherapy could be selected. 相似文献
ObjectivesIn many countries, future unrelated medical costs occurring during life-years gained are excluded from economic evaluation, and benefits of unrelated medical care are implicitly included, leading to life-extending interventions being disproportionately favored over quality of life-improving interventions. This article provides a standardized framework for the inclusion of future unrelated medical costs and demonstrates how this framework can be applied in England and Wales.MethodsData sources are combined to construct estimates of per-capita National Health Service spending by age, sex, and time to death, and a framework is developed for adjusting these estimates for costs of related diseases. Using survival curves from 3 empirical examples illustrates how our estimates for unrelated National Health Service spending can be used to include unrelated medical costs in cost-effectiveness analysis and the impact depending on age, life-years gained, and baseline costs of the target group.ResultsOur results show that including future unrelated medical costs is feasible and standardizable. Empirical examples show that this inclusion leads to an increase in the ICER of between 7% and 13%.ConclusionsThis article contributes to the methodology debate over unrelated costs and how to systematically include them in economic evaluation. Results show that it is both important and possible to include future unrelated medical costs. 相似文献
Payers frequently rely on budget impact model (BIM) results to help determine drug coverage policy and its effect on their bottom line. It is unclear whether BIMs typically overestimate or underestimate real-world budget impact.
Objective
We examined how different modeling assumptions influenced the results of 6 BIMs from the Institute for Clinical and Economic Review (ICER).
Study Design
Retrospective analysis of pharmaceutical sales data.
Methods
From ICER reports issued before 2016, we collected estimates of 3 BIM outputs: aggregate therapy cost (ie, cost to treat the patient population with a particular therapy), therapy uptake, and price. We compared these against real-world estimates that we generated using drug sales data. We considered 2 classes of BIM estimates: those forecasting future uptake of new agents, which assumed “unmanaged uptake,” and those describing the contemporaneous market state (ie, estimates of current, managed uptake and budget impact for compounds already on the market).
Results
Differences between ICER's estimates and our own were largest for forecasted studies. Here, ICER's uptake estimates exceeded real-world estimates by factors ranging from 7.4 (sacubitril/valsartan) to 54 (hepatitis C treatments). The “unmanaged uptake” assumption (removed from ICER's approach in 2017) yields large deviations between BIM estimates and real-world consumption. Nevertheless, in some cases, ICER's BIMs that relied on current market estimates also deviated substantially from real-world sales data.
Conclusions
This study highlights challenges with forecasting budget impact. In particular, assumptions about uptake and data source selection can greatly influence the accuracy of results. 相似文献
Objectives: Suicide is best studied by deconstructing the psychological experiences preceding suicidal death. We assessed the characteristics of tedium vitae (feeling tired of life) after first ever stroke in Nigerian survivors.
Methods: Using the Schedule for Clinical Assessment in Neuropsychiatry, tedium vitae was assessed in 130 stroke survivors attending rehabilitation in a large Nigerian university hospital. Global cognitive and executive dysfunctions were evaluated, respectively, using the Mini Mental State Examination and the modi?ed Indiana University Token test. All participants had their index stroke 3 to 24 months before recruitment into the study. We also examined a comparative group of 130 age, gender, and education matched apparently normal persons who were unrelated to the stroke survivors. Associations were explored using univariate and multivariate logistic regression analyses.
Results: Tedium vitae was experienced by 16 (12.3%) stroke survivors compared with 5 (3.9%) in the comparative group (O. R = 3.5, 95% C. I = 1.3–9.9, p = 0.018). Among stroke survivors, those who were retired were more likely to experience tedium vitae (56.2%, p = 0.045). In analyses adjusting for the effect of systemic hypertension, cognitive dysfunction, retirement and marital separation, there was a 3.5-fold increase in the odds of experiencing tedium vitae after surviving a stroke (O. R = 3.5, 95% C. I = 1.1–11.6, p = 0.042).
Conclusions: Tedium vitae is a common suicidal experience after stroke and may be among the earliest perceptible pointer to impending poststroke suicide. It is easy to assess and may be less costly to obtain an adequate sample size in studies aiming to understand the phenomenon of suicide in the stroke population. 相似文献
In this study, we estimated the disease burdens attributable to environmental tobacco smoke (ETS) exposure in Korean adults in 2010 and analyzed the trend of that from 2005 to 2010. We obtained information on the study population from the 2010 Cause of Death Statistic and estimated the ETS-attributable fraction using data from the Korean Community Health Survey and the Korean National Health and Nutrition Examination Survey. The numbers of ETS-attributable deaths in female and male non-smokers were estimated to be 4.1 and 69.6?% of the numbers of deaths attributable to current smoke, respectively. The deaths attributable to ETS were larger in female than in male non-smokers (710 vs. 420). The ETS-attributable deaths increased slightly in 2005–2008 but decreased in 2009–2010. The number of potential years of life lost from ETS was 9077.24?years in 2010. If there were no exposure to ETS in adult non-smokers, we would expect to see 1130 fewer deaths (9.9?% of the deaths from current smoke). The results suggest that ETS poses considerable disease burdens for non-smokers, especially women, in Korea. 相似文献