A Direct Approach to Simultaneous Tests of Superiority and Noninferiority with Multiple Endpoints

Simultaneous tests of superiority and non-inferiority hypotheses on multiple endpoints are often performed in clinical trials to demonstrate that a new treatment is superior over a control on at least one endpoint and non-inferior on the remaining endpoints. Existing methods tackle this problem by testing the superiority and non-inferiority hypotheses separately and control the Type I error rate each at $\alpha$ level. In this paper we propose a unified approach to testing the superiority and non-inferiority hypotheses simultaneously. The proposed approach is based on the UI-IU test and the least favorable configurations of the combined superiority and non-inferiority hypotheses, which leads to the solution of an adjusted significance level $\alpha'$ for marginal tests that controls the overall Type I error rate at pre-defined $\alpha$. Simulations show that the proposed approach maintains a higher power than existing methods in the settings under investigation. Since the adjusted significance level $\alpha'$ is obtained by controlling the Type I error rate at $\alpha$, one can easily construct the exact $(1 - \alpha)\%$ simultaneous confidence intervals for treatment effects on all endpoints. The proposed approach is illustrated with two real examples

Efficacy of EGFR-TKI therapy in patients with brain metastases from non-small-cell lung cancer: A metaanalysis

Purpose: This meta-analysis aimed to systematically evaluate the efficacy of tyrosine kinase inhibitors of epidermal growth factor receptor (EGFR-TKIs) for patients with brain metastases (BM) from nonsmall- cell lung cancer (NSCLC), and to compare this treatment modality to chemotherapy or radiotherapy.Methods: PubMed, EMBASE (OvidSP), the Cochrane Central Register of Controlled Trials (CENTRAL), Web of Science and ASCO Annual Meeting Abstracts were searched. Controlled clinical studies that compared the efficacy of EGFR-TKIs with chemotherapy or radiotherapy for NSCLC patients with BM were included in the analysis. Efficacy indicators included overall survival (OS), local progression-free survival (LPFS) and objective response rate (ORR).Results: The final sample consisted of 24,637 NSCLC patients with BM from 11 clinical studies. In primary efficacy analysis, it was found that EGFR-TKIs were significantly superior to chemotherapy or radiotherapy in terms of ORR (odds ratio (OR) = 2.10, p = 0.035), OS (hazard ratio (HR) = 0.78, p = 0.011) and LPFS (HR = 0.60, p < 0.001).Conclusion: Among the patients with BM from NSCLC, EGFR-TKIs exhibit a therapeutic advantage over chemotherapy or radiotherapy, which is reflected in the elevation of ORR and improvement in OS and LPFS.Keywords: Brain metastasis, Non-small-cell lung cancer (NSCLC), Protein kinase Inhibitors, Epidermal growth factor, Meta-analysi

Incidence and Survival Analysis of Gastrointestinal Stromal Tumors in Shanghai: A Population-Based Study from 2001 to 2010

Objectives. A population-based study was undertaken to investigate the epidemiological features of gastrointestinal stromal tumors (GISTs) in Shanghai, especially the incidence and the preliminary exploration of survival. Methods. A total of 1923 patients with GISTs diagnosed from 2001 to 2010 in Shanghai were reviewed. The annual incidence and overall survival of GISTs were calculated; Cox proportional hazards’ regression was used to analyze several prognostic factors. Results. The average crude incidence of GISTs was 2.11 per 100,000 between 2004 and 2008, and the age-standardized incidence was 1.28 per 100,000. The incidence increased gradually from 2004 to 2008. In addition, 57% of cases had GIST in the stomach and 33% in the intestine. The 5-year overall survival of GISTs was 86.98%. The Cox regression analysis showed older age (≥65 yr versus <40 yr, HR = 5.085; (40, 65) yr versus <40 yr, HR = 1.975), male gender (HR = 1.474), and tumor locations (intestinal versus stomach, HR = 1.609) were predictors of its mortality. Conclusion. GISTs, mainly occurring in the stomach, are more common in elderly population, with an increasing incidence from 2004 to 2008. Older age, male gender, and tumor locations are risk factors for its mortality

Tumor suppressor genes are frequently methylated in lymph node metastases of breast cancers

<p>Abstract</p> <p>Introduction</p> <p>Metastasis represents a major adverse step in the progression of breast carcinoma. Lymph node invasion is the most relevant prognostic factor; however little is known on the molecular events associated with lymph node metastasis process. This study is to investigate the status and role of methylation in lymph node metastatic tumors.</p> <p>Materials and methods</p> <p>Bisulfite pyrosequencing is used to screen 6 putative tumor suppressor genes (<it>HIN-1, RASSF1A, RIL, CDH13, RARβ2 </it>and E-cadherin) in 38 pairs of primary breast tumors and lymph node metastases.</p> <p>Results</p> <p>We found that <it>HIN-1, CDH13, RIL, RASSF1A </it>and <it>RARβ2 </it>were frequently methylated both in primary and metastatic tissues (range: 55.3%~89.5%). E-cadherin was not frequently methylated in either setting (range: 18.4%~23.7%). The methylation status of <it>HIN-1, CDH13, RIL</it>, and <it>RARβ2 </it>in lymph nodes metastasis were correlated with that in primary tumors. The Pearson correlation values ranged from 0.624 to 0.472 (<it>p </it>values < 0.01 to 0.001). Interestingly, we observed an association between <it>HIN-1 </it>methylation and hormone status in metastatic lymph nodes. Hypermethylation of <it>HIN-1 </it>in metastasis lymph nodes was significantly associated with expression of ER (odds ratio, 1.070; P = 0.024) and with PR (odds ratio, 1.046; P = 0.026).</p> <p>Conclusions</p> <p>This study suggests that hypermethylation of tumor suppressor genes is extended from primary to metastatic tumors during tumor progression.</p

Association between socioeconomic status and obesity in a Chinese adult population

BACKGROUND: Existing studies which regarding to the association between individual socioeconomic status (SES) and obesity are still scarce in developing countries. The major aim of this study is to estimate such association in an adult population which was drawn from an economically prosperous province of China. METHODS: Study population was determined by multilevel randomized sampling. Education and income were chosen as indicators of individual SES, general obesity and abdominal obesity were measured by body mass index (BMI) and waist circumference (WC). Descriptive statistical methods were used to depict overall and factor-specific distributions of general and abdominal obesity among 16,013 respondents. Two-step logistic regression models were fitted on gender basis. RESULTS: The age-and-sex adjusted rates of general overweight, general obesity, abdominal overweight and abdominal obesity in study population were 28.9% (95%CI: 27.9%-29.9%), 7.5% (95%CI: 7.0%-8.1%), 32.2% (95%CI: 31.2%-33.3%) and 12.3% (95%CI: 11.6%-13.1%), respectively. Based on model fitting results, a significant inverse association between education and obesity only existed in women, while in men, income rather than education was positively related to obesity. CONCLUSIONS: The atypical SES-obesity relationship we found reflected the on-going social economy transformation in affluent regions of China. High-income men and poorly-educated women were at higher risk of obesity in Zhejiang province, thus merit intense focuses

Ozone and Daily Mortality in Shanghai, China

BACKGROUND: Controversy remains regarding the relationship between ambient ozone and mortality worldwide. In mainland China, the largest developing country, there has been no prior study investigating the acute effect of O(3) on death risk. Given the changes in types of air pollution from conventional coal combustion to the mixed coal combustion/motor vehicle emissions in China’s large cities, it is worthwhile to investigate the acute effect of O(3) on mortality outcomes in the country. OBJECTIVES: We conducted a time-series study to investigate the relation between O(3) and daily mortality in Shanghai using 4 years of daily data (2001–2004). METHODS: We used the generalized additive model with penalized splines to analyze mortality, O(3) pollution, and covariate data in warm and cold seasons. We considered daily counts of all-cause mortality and several cause-specific subcategories (respiratory and cardiovascular). We also examined these associations among several subpopulations based on age and sex. RESULTS: O(3) was significantly associated with total and cardiovascular mortality in the cold season but not in the warm season. In the whole-year analysis, an increase of 10 μg/m(3) of 2-day average (lag01) O(3) corresponds to 0.45% [95% confidence interval (CI), 0.16–0.73%], 0.53% (95% CI, 0.10–0.96%), and 0.35% (95% CI, −0.40 to 1.09%) increase of total nonaccidental, cardiovascular, and respiratory mortality, respectively. In the cold season, the estimates increased to 1.38% (95% CI, 0.68–2.07%), 1.53% (95% CI, 0.54–2.52%), and 0.95% (95% CI, −0.71 to 2.60%), respectively. In the warm season, we did not observe significant associations for both total and cause-specific mortality. The results were generally insensitive to model specifications such as lag structure of O(3) concentrations and degree of freedom for time trend. Multipollutant models indicate that the effect of O(3) was not confounded by particulate matter ≤ 10 μm in diameter (PM(10)) or by sulfur dioxide; however, after adding nitrogen dioxide into the model, the association of O(3) with total and cardiovascular mortality became statistically insignificant. CONCLUSIONS: O(3) pollution has stronger health effects in the cold than in the warm season in Shanghai. Our analyses also strengthen the rationale for further limiting levels of O(3) pollution in outdoor air in the city

Material Removal Mechanism and Force Model of Nanofluid Minimum Quantity Lubrication Grinding

Numerous researchers have developed theoretical and experimental approaches to force prediction in surface grinding under dry conditions. Nevertheless, the combined effect of material removal and plastic stacking on grinding force model has not been investigated. In addition, predominant lubricating conditions, such as flood, minimum quantity lubrication (MQL), and nanofluid minimum quantity lubrication (NMQL), have not been considered in existing force models. In this study, material removal mechanism under different lubricating conditions was researched. An improved theoretical force model that considers material removal and plastic stacking mechanisms was presented. Grain states, including cutting and ploughing, are determined by cutting efficiency (β). The influence of lubricating conditions was also considered in the proposed force model. Simulation was performed to obtain the cutting depth (a g) of each “dynamic active grain.” Parameter β was introduced to represent the plastic stacking rate and determine the force algorithms of each grain. The aggregate force was derived through the synthesis of each single-grain force. Finally, pilot experiments were conducted to test the theoretical model. Findings show that the model’s predictions were consistent with the experimental results, with average errors of 4.19% and 4.31% for the normal and tangential force components, respectively