Innovative Thinking on Endpoint Selection in Clinical Trials

ABSTRACT

In clinical trials, selection of appropriate study endpoints is critical for an accurate and reliable evaluation of safety and effectiveness of a test treatment under investigation. In practice, however, there are usually multiple endpoints available for measurement of disease status and/or therapeutic effect of the test treatment under study. For example, in cancer clinical trials, overall survival, response rate, and/or time to disease progression are usually considered as primary clinical endpoints for evaluation of safety and effectiveness of the test treatment under investigation. Once the study endpoints have been selected, sample size required for achieving a desired power is then determined. It, however, should be noted that different study endpoints may result in different sample sizes. In practice, it is usually not clear which study endpoint can best inform the disease status and measure the treatment effect. Moreover, different study endpoints may not translate one another although they may be highly correlated one another. In this article, we intend to develop an innovative endpoint namely therapeutic index based on a utility function to combine and utilize information collected from all study endpoints. Statistical properties and performances of the proposed therapeutic index are evaluated theoretically. A numerical example concerning a cancer clinical trial is given to illustrate the use of the proposed therapeutic index.     

Utility of Tissue Similarity Maps Based on Relative Cerebral Blood Volume for Grading Gliomas as Validated by Histological Results

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Fundamentals about onset and progressive disease character of type 2 diabetes mellitus

ResearchGate is a world wide web for scientists and researchers to share papers, ask and answer questions, and find collaborators. As one of the more than 15 million members, the author uploads research output and reads and responds to some of the questions raised, which are related to type 2 diabetes. In that way, he noticed a serious gap of knowledge of this disease among medical professionals over recent decades. The main aim of the current study is to remedy this situation through providing a comprehensive review on recent developments in biochemistry and molecular biology, which can be helpful for the scientific understanding of the molecular nature of type 2 diabetes. To fill up the shortcomings in the curricula of medical education, and to familiarize the medical community with a new concept of the onset of type 2 diabetes, items are discussed like: Insulin resistance, glucose effectiveness, insulin sensitivity, cell membranes, membrane flexibility, unsaturation index (UI; number of carbon-carbon double bonds per 100 acyl chains of membrane phospholipids), slow-down principle, effects of temperature acclimation on phospholipid membrane composition, free fatty acids, energy transport, onset of type 2 diabetes, metformin, and exercise. Based on the reviewed data, a new model is presented with proposed steps in the development of type 2 diabetes, a disease arising as a result of a hypothetical hereditary anomaly, which causes hyperthermia in and around the mitochondria. Hyperthermia is counterbalanced by the slow-down principle, which lowers the amount of carbon-carbon double bonds of membrane phospholipid acyl chains. The accompanying reduction in the UI lowers membrane flexibility, promotes a redistribution of the lateral pressure in cell membranes, and thereby reduces the glucose transporter protein pore diameter of the transmembrane glucose transport channel of all Class I GLUT proteins. These events will set up a reduction in transmembrane glucose transport. So, a new blood glucose regulation system, effective in type 2 diabetes and its prediabetic phase, is based on variations in the acyl composition of phospholipids and operates independent of changes in insulin and glucose concentration. UI assessment is currently arising as a promising analytical technology for a membrane flexibility analysis. An increase in mitochondrial heat production plays a pivotal role in the existence of this regulation system.     

糖尿病护理门诊在糖尿病健康教育中的作用探究

目的:研究糖尿病护理门诊在糖尿病健康教育中作用.方法:取78例糖尿病患者,其中39例患者进行常规护理为对照组,39例患者进行糖尿病门诊护理为观察组,对比2组患者护理后自我管理能力和血糖指标.结果:观察组自我管理能力均高于对照组(P<0.05).观察组血糖指标均低于对照组(P<0.05).结论:向糖尿病患者进行健康教育时,糖尿病门诊护理的应用,可以科学创建护理档案,明确随访策略,提升糖尿病的管理水平,使患者具有较强自我管理能力,同时降低其血糖指标.     

Morphological,Functional, and Tissue Characterization of Silent Myocardial Involvement in Patients With Primary Biliary Cholangitis

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西药联合穴位贴敷中西医结合治疗复治肺结核疗效观察

目的评价西药联合穴位贴敷中西医结合治疗复治肺结核的临床疗效。方法选择本院2017年1月～2018年1月收治的60例复治肺结核患者进行分组研究,全部患者根据治疗方法不同随机分为两组,每组各30例。两组均采取西药进行治疗,采用2HRZE/6HRZ标准化疗方案,实验组同时联合穴位贴敷中西医结合进行治疗,治疗后对比分析两组病灶吸收情况及两组临床症状改善情况。结果实验组病灶恶化9例,其病灶显著吸收率达50.0%,总有效率达70.0%,对照组病灶恶化6例,不变5例,其病灶显著吸收率达33.3%,总有效率达63.3%,两组病灶吸收总有效率组间比较,差异具有显著性(P0.05);实验组的疗效指数治疗6个月后显著高于对照组,组间比较,差异具有显著性(P0.05)。结论西药联合穴位贴敷中西医结合治疗复治肺结核疗效确切,可以显著促进病灶吸收,改善临床症状,安全性好,且还可以扶助人体正气,提高机体免疫力,调节全身状态,以达到治疗目的,是治疗复治肺结核的有效方法之一,值得临床广泛推广和应用。     

临床检验不合格血液标本产生原因及质量改进研究

目的:分析临床检验不合格血液标本的原因为何,研究相应的质量改进方法。方法:本课题自我院检验血液标本样本中抽取140份,其中2018年2月~2019年3月的70份命名成对照组,2019年4月~2020年3月的70份命名成试验组,前一组未进行质量改进,后一组进行质量改进,比较检验结果有何不同。结果:试验组这组的检验标本不合格率要比对照组那组的检验标本不合格率低,数据上是P<0.05的情况,即表明有统计学意义。结论:凝血反应、溶血反应、样本问题、送检失误、抗凝不全等是导致临床检验不合格血液标本的原因所在,实施质量改进可将血液标本质量提高。     

Lower body mass index and higher height are correlated with increased varicocele risk

To evaluate the anthropometric indexes in subjects with varicocele compared to controls and the incidence of varicocele in different body mass index (BMI) groups for the purpose of exploring the association between varicocele and anthropometric indexes. A comprehensive literature search was conducted by using PubMed, MEDLINE, EMBASE databases and Cochrane Library up to February 2019. A systematic review and meta‐analysis was conducted by STATA, and Newcastle–Ottawa Scale was utilised for assessing risk of bias. Ultimately, 13 articles containing seven case–control studies and six cross‐sectional studies with 1,385,630 subjects were involved in our study. Pooled results demonstrated that varicocele patients had a lower BMI (WMD = ?0.77, 95% CI = ?1.03 to ?0.51) and a higher height than nonvaricocele participants, especially in grade 3 varicocele patients. Subgroup analyses showed that normal BMI individuals had a higher risk of varicocele than obese or overweight individuals and a lower risk than underweight individuals. In conclusion, this study indicates that varicocele patients have a lower BMI and a higher height than nonvaricocele participants. Moreover, men with excess bodyweight have a lower incidence of varicocele compared to normal weight or underweight people. That is to say, high BMI and adiposity protect against varicocele and high BMI is associated with a decreased risk of varicocele.     

Association of meibomian gland architecture and body mass index in a pediatric population

PurposeTo determine if meibomian gland architecture in a pediatric population is impacted by body mass index (BMI).MethodsProspective evaluation of 175 eyes of 175 pediatric patients from two clinics. Demographic and clinical information were reviewed. Symptoms of dry eye were assessed with the Standard Patient Evaluation of Eye Dryness (SPEED) questionnaire. Meibography was performed and grading of images was performed by a masked rater using a previously validated 5-point meiboscale (0–4) for gland atrophy and a 3-point score (0–2) for gland tortuosity.Results175 eyes of 175 participants aged 4–17 years (11.6 ± 3.7 years) were imaged. The mean meiboscore was 0.82 ± 0.94 (range 0–4) and the mean gland tortuosity score was 0.53 ± 0.70 (range 0–2). Ninety-six patients (56%) showed evidence of gland atrophy (meiboscore greater than 0) and the majority of patients (n=50, 29%) had a gland tortuosity score of 1. The mean BMI was 20.5 ± 4.86 kg/m² with 39.4% of patients (n = 69) above the 85th percentile. BMI percentile was not found to be a significant predictor of a meiboscore greater than 0 (odds ratio (OR) 1.004 95% confidence interval (CI) (0.99–1.10, p = 0.41). However, BMI percentile was found to be a significant predictor of gland tortuosity score (OR 1.01 95% CI (1.00–1.02), p = 0.02). Patients with BMI percentiles between 41 and 60 were 3.79 times more likely to have a gland tortuosity score of greater than 0 than patients with BMI percentiles between 0 and 20 (OR 3.789 CI (1.17–12.24)). No significant associations were found between age, race, or sex and meiboscore or tortuosity. There was a trend towards reduction in lipid layer thickness with increasing BMI percentile (p = 0.028, r² = 0.04).ConclusionIn this pediatric population, there was an association between meibomian gland tortuosity and higher percentiles of BMI. Future studies are needed to elucidate the pathogenesis of meibomian gland tortuosity and atrophy in pediatric patients.