A case of sudden cardiac death due to mitochondrial disease

A 25-year-old, emaciated man without medical treatment was found to have died suddenly at home by his mother. At autopsy, there were no injuries to his body, but significant circulatory insufficiency was observed. Electron microscopy revealed abnormal mitochondria in cells of the cardiac conduction system. The conduction system was filled with mitochondrial size abnormalities and mitochondrial cristae abnormalities. No notable abnormal findings were observed in other organs. Genetic examination of the blood revealed the mitochondrial pathogenetic variant m.3243A>G. Epileptic seizures, diabetic ketoacidosis, and hyperosmolar hyperglycemic state were unlikely to be the cause of sudden death. The cause of death was diagnosed as arrhythmia possibly induced by the failure of the cardiac conduction system due to mitochondrial disease. This is a rare case of sudden death caused by an accumulation of abnormal mitochondria in the cardiac conduction system.     

A Proposal for an Alternative Approach to Particle Size Method Development During Early-Stage Small Molecule Pharmaceutical Development

Particle size analysis in the pharmaceutical industry has long been a source of debate regarding how best to define measurement accuracy; the degree to which the result of a measurement or calculation conforms to the true value. Defining a “true” value for the size of a particle can be challenging as the output of its measurement will differ because of variations in measurement approaches, instrumental differences and calculation methods. Consequently, for “real” particles, a universal “true” value does not exist and accuracy is therefore not a definable characteristic. Accordingly, precision is then a measure of the ability to reproducibly achieve a measurement of unknown relevance.This article proposes, in place of accuracy, a means to define the “appropriateness” of a measurement in line with the critical quality attributes (CQA) of the material being characterized. The decision as to whether the measurement is correct should involve a link to the CQA; that is, correlation should be demonstrated, without which the measured particle size cannot be defined as a critical material attribute.Correspondingly, methods should also be able to provide sufficient precision to demonstrate discrimination relating to variation in the CQA. The benefits and challenges of this approach are discussed.     

P-Values and Power in Orthopedic Research: Myths and Reality

The results of statistical tests in orthopedic studies are typically reported using P-values. If a P-value is smaller than the pre-determined level of significance (eg, < .05), the null hypothesis is rejected in support of the alternative. This automaticity in interpreting statistical results without consideration of the power of the study has been denounced over the years by statisticians, since it can potentially lead to misinterpretation of the study conclusions. In this paper, we review fundamental misconceptions and misinterpretations of P-values and power, along with their connection with confidence intervals, and we provide guidelines to orthopedic researchers for evaluating and reporting study results. We provide real-world orthopedic examples to illustrate the main concepts. Please visit the following https://youtu.be/bdPU4luYmF0 for videos that explain the highlights of the paper in practical terms.     

Sample size re-estimation for clinical trials with longitudinal negative binomial counts including time trends

In some diseases, such as multiple sclerosis, lesion counts obtained from magnetic resonance imaging (MRI) are used as markers of disease progression. This leads to longitudinal, and typically overdispersed, count data outcomes in clinical trials. Models for such data invariably include a number of nuisance parameters, which can be difficult to specify at the planning stage, leading to considerable uncertainty in sample size specification. Consequently, blinded sample size re-estimation procedures are used, allowing for an adjustment of the sample size within an ongoing trial by estimating relevant nuisance parameters at an interim point, without compromising trial integrity. To date, the methods available for re-estimation have required an assumption that the mean count is time-constant within patients. We propose a new modeling approach that maintains the advantages of established procedures but allows for general underlying and treatment-specific time trends in the mean response. A simulation study is conducted to assess the effectiveness of blinded sample size re-estimation methods over fixed designs. Sample sizes attained through blinded sample size re-estimation procedures are shown to maintain the desired study power without inflating the Type I error rate and the procedure is demonstrated on MRI data from a recent study in multiple sclerosis.     

Tumour volume distribution can yield information on tumour growth and tumour control

BackgroundIt is shown that tumour volume distributions can yield information on two aspects of cancer research: tumour induction and tumour control.Materials and methodsFrom the hypothesis that the intrinsic distribution of breast cancer volumes follows an exponential distribution, firstly the probability density function of tumour growth time was deduced via a mathematical transformation of the probability density functions of tumour volumes. In a second step, the distribution of tumour volumes was used to model the variation of the clonogenic cell number between patients in order to determine tumour control probabilities for radiotherapy patients.ResultsDistribution of lag times, i.e. the time from the appearance of the first fully malignant cell until a clinically observable cancer, can be used to deduce the probability of tumour induction as a function of patient age. The integration of the volume variation with a Poisson-TCP model results in a logistic function which explains population-averaged survival data of radiotherapy patients.ConclusionsThe inclusion of tumour volume distributions into the TCP formalism enables a direct link to be deduced between a cohort TCP model (logistic) and a TCP model for individual patients (Poisson). The TCP model can be applied to non-uniform tumour dose distributions.     

艾烟的作用与安全性评价＊

艾灸作为中医学最古老的疗法之一，作用多样，应用广泛，疗效显著。随着科技的发展，人们对灸法的认识逐渐深入，其中艾烟的相关研究也硕果累累，其安全性广受关注。通过对艾烟作用和安全性评价研究中取得的成果进行归纳分析，以期为艾灸临床安全应用提供指导。     

抑郁症康复技能训练程式在基层医院推广应用的价值研究

背景　抑郁症的康复技能训练是一种很好的辅助治疗方法，本课题通过引进成熟的抑郁症康复技术，使基层医务人员熟练掌握，为辖区内广大抑郁症患者开展康复训练，以期提高抑郁症患者的疗效，降低自杀风险。目的　探讨抑郁症康复技能训练程式在基层医院推广应用的价值。方法　选取门头沟区龙泉医院2018年1-9月门诊就诊的65例抑郁症患者为研究对象。入选患者全部接受康复训练，分别于训练前和训练结束3个月后采用汉密尔顿抑郁量表（HAMD）、社会功能缺陷筛选量表（SDSS）、服药依从性、自杀风险评估量表（nurses' global assessment of suicide risk，NGASR）和自杀风险问卷对患者进行评估。结果　共61例患者完成研究，与训练前比较，训练结束3个月后患者HAMD、SDSS评分明显降低，服药依从性除自行停药外均明显提高，自杀风险明显降低，差异有统计学意义（P<0.05）。结论　抑郁症康复训练程式能有效提高患者服药依从性，改善抑郁症状，减少自杀观念，在基层医院有推广价值。     

个体化糖尿病教育对初次使用胰岛素的2型糖尿病患者的疗效评价

目的探讨针对初次应用胰岛素治疗的2型糖尿病患者开展个体化糖尿病教育的临床价值。方法对照组患者开展常规的糖尿病健康教育,观察组则在该基础上开展个体化糖尿病教育。结果两组健康教育前SDSCA-6依从性量表各维度评分较低;健康教育后观察组SDSCA-6依从性量表各维度评分均高于对照组(P<0.05);两组健康教育FPG、2 hPG、HbAlc前较高(P>0.05);健康教育后观察组FPG、2 hPG、HbAlc低于对照组(P<0.05)。结论对于首次应用胰岛素治疗的2型糖尿病患者进行个体化的糖尿病教育可以有效提升其依从性,并更好的控制血糖水平。