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.     

提升“湘九味”品牌价值 高质量发展湖南中药材产业

湖南省历经8年聚力打造“湘九味”中药材品牌，已逐渐形成品牌品种引领的产业链发展模式。为达成湖南省中药材产业链千亿发展目标，梳理了“湘九味”品牌培育历程，厘清并阐释了相关概念，分析了产业发展现状及问题，研判了大健康应用背景下未来的中药材产业的发展趋势，并提出相关发展建议。     

中药复方配伍的研究方法及其进展

中药复方是由2味或2味以上中药遵循中医理论组合而成的方剂。多味中药在合适的剂量配比之下,协同发挥作用,实现中医的整体调节治疗。研究中药复方的配伍对推动中药现代化发展、新药开发以及临床应用有着重要意义。近年来,研究者们在传统的"七情和合"与"君臣佐使"的基础上,运用新技术和新方法对中药复方的成分、药效活性和药代动力学性质等进行了研究,从不同角度探讨了中药复方配伍的科学内涵。同时,多种数理方法和模型的建立、网络药理学和数据挖掘方法的发展与应用,也对中药复方配伍研究提供了很大帮助。研究方法的发展虽促进了中药复方配伍的科学研究,但还需进一步建立适合中药复方配伍复杂关系的研究方法,以阐明中药复方及其成分/组分配伍的内在规律,进而构建新的现代中药复方,这也是目前中药复方配伍研究的重点任务。     

可吸收明胶海绵棒在椎弓根内止血的应用

[目的]观察评价可吸收明胶海绵棒在椎弓根置钉过程中的止血效果。[方法]2017年10月~2018年6月,48例胸腰椎骨折即将行后路手术的患者纳入本研究,采用随机数字表法分为明胶海绵组和骨蜡组。明胶海绵组共23例,置钉过程中应用明胶海绵棒填塞至椎弓根孔道止血;骨蜡组共25例,在透视定位时应用骨蜡封闭椎弓根孔道。记录置钉情况;记录术中出血量、自体血回输量、置钉过程中的出血量、输血量;检测术前和术后5 d RBC、HB和HCT。[结果]两组在置钉总数、伤椎置钉数、伤椎位置各椎置钉数量的差异均无统计学意义(P>0.05)。术后两组各出现1例小腿肌间静脉血栓,抗凝治疗后于复查时消失。术后两组均无明胶海绵或骨蜡导致的不良反应。两组在术中出血量、术中自体血回收量、输血量的差异无统计学意义(P>0.05),但明胶海绵组上述指标均小于骨蜡组。每钉置入过程中明胶海绵组的出血量显著少于骨蜡组,差异有统计学意义(P<0.05)。两组术后5 d的RBC、HB和HCT均较术前显著减少,两时间点间差异均有统计学意义(P<0.05)。术前两组在RBC、HB和HCT的差异均无统计学意义(P>0.05),术后5 d两组在RBC、HB和HCT的差异亦均无统计学意义(P>0.05)。[结论]应用明胶海绵棒填塞椎弓根孔道止血可显著减少安置椎弓根螺钉过程中的出血,是一种简单、安全、有效的脊柱外科术中止血方法。