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.     

Redox active or thiol reactive? Optimization of rapid screens to identify less evident nuisance compounds

Compounds that exhibit assay interference or undesirable mechanisms of bioactivity are routinely encountered in assays at various stages of drug discovery. We observed that assays for the investigation of thiol-reactive and redox-active compounds have not been collected in a comprehensive review. Here, we review these assays and subject them to experimental optimization to improve their reliability. We demonstrate the usefulness of our assay cascade by assaying a library of bioactive compounds, chemical probes, and a set of approved drugs. These high-throughput assays should complement the array of wet-lab and in silico assays during the initial stages of hit discovery campaigns to pursue only hit compounds with tractable mechanisms of action.     

The roles of prostaglandin E2 and D2 in lipopolysaccharide-mediated changes in sleep

When living organisms become sick as a result of a bacterial infection, a suite of brain-mediated responses occur, including fever, anorexia and sleepiness. Systemic administration of lipopolysaccharide (LPS), a common constituent of bacterial cell walls, increases body temperature and non-rapid eye movement (NREM) sleep in animals and induces the production of pro-inflammatory prostaglandins (PGs). PGE₂ is the principal mediator of fever, and both PGE₂ and PGD₂ regulate sleep–wake behavior. The extent to which PGE₂ and PGD₂ are involved in the effect of LPS on NREM sleep remains to be clarified. Therefore, we examined LPS-induced changes in body temperature and NREM sleep in mice with nervous system-specific knockouts (KO) for the PGE₂ receptors type EP₃ or EP₄, in mice with total body KO of microsomal PGE synthase-1 or the PGD₂ receptor type DP, and in mice treated with the cyclooxygenase (COX) inhibitor meloxicam. We observed that LPS-induced NREM sleep was slightly attenuated in mice lacking EP₄ receptors in the nervous system, but was not affected in any of the other KO mice or in mice pretreated with the COX inhibitor. These results suggest that the effect of LPS on NREM sleep is partially dependent on PGs and is likely mediated mainly by other pro-inflammatory substances. In addition, our data show that the main effect of LPS on body temperature is hypothermia in the absence of nervous system EP₃ receptors or in the presence of a COX inhibitor.     

原发性肝癌的彩色多普勒及三维血流能量成像特征及其临床意义

目的:探讨三维血流能量成像(3D-CPA)和彩色多普勒血流成像(CDFI)的临床应用价值。方法:对47例原发性肝癌的病灶进行二维、CDFI及3D-CPA的检查,比较CDFI及3D-CPA显示肿瘤瘤内或瘤周血流多普勒信号丰富程度及血管分布类型,并检测肿瘤的血流参数。结果:3D-CPA显示肿瘤血流分布丰富程度及血管分布类型与CDFI均有显著性差异(均P<0.05),CDFI均可探及肿瘤的搏动性动脉血流,其中,收缩期峰值血流速度(PSV)为43~157cm/s,阻力指数(RI)为0.49~0.82,大于0.65者45例。结论:3D-CPA结合彩色多普勒血流参数的检测可作为临床评价原发性肝癌血供及血管分布的常规检查方法。     

Increase in Power through Multivariate Analyses

Power to detect genetic and environmental influences increases not only with sample size but also with the number of measurements through longitudinal and/or multivariate designs, if those measurements correlate with each other. Power simulations are presented for uni- through quadrivariate cases, with differing genetic and environmental parameters. Even though subject attrition is a problem for most longitudinal studies, the gain in power available may more than make up for this shortcoming in many situations. In terms of planning studies to examine genetic and environmental influences, power calculations should not only consider sample size but number of measurements on particular phenotypes and their intercorrelations.     

The effect of MS-818, a pyrimidine compound,on the regeneration of peripheral nerve fibers of mice after a crush injury

One of the pyrimidine compounds, 2-piperadino-6-methyl-5-oxo-5,6-dihydro(7H)pyrrolo[3,4-d]pyrimidine (MS-818), has neurotropic effects in vitro. Therefore, we studied the effect of MS-818 on the regeneration of the peroneal nerve in C57BL/6J mice after a crush injury. Two test groups, which received a daily intraperitoneal injection of 5 mg/kg or 10 mg/kg MS-818, respectively, were compared with controls, which received daily intraperitoneal injections of physiological saline, over a 14-day period. The maximum foot-width ratio (crushed side/uncrushed side) was obtained on days 1, 8 and 14 after the crush injury, and the various morphometric parameters were evaluated at both 5 and 10 mm distal to the proximal portion of the crush site. The significant effects of MS-818 included a larger maximum foot width (P<0.04) and a greater number of unmyelinated axons per nerve at both levels (P<0.003) in both test groups than in controls. MS-818 had no significant effects on body weight, the increase of total transverse fascicular area after the crush injury, the total number of myelinated fibers with their size distributions, or the number of nuclei of Schwann cells and macrophages. Therefore, we conclude that MS-818 promotes axonal sprouting and elongation after a crush injury in mice.     

复方华蟾胶囊抗小鼠肿中瘤作用的实验研究

目的了解复方华蟾胶囊抗小鼠移植性肿瘤的作用.方法以小鼠肝癌22(H22)、小鼠肉瘤180(S180)为瘤株,应用动物移植性肿瘤的体内试验法对药物进行抗癌药效学试验.结果复方华蟾胶囊灌胃4,2 g/kg@d,连续14 d,对小鼠移植性肝癌实体型生长有明显的抑制作用,抑瘤率分别为38.09%,30.95%.对小鼠移植性S180实体型生长有明显的抑制作用,抑瘤率分别为34.7%,30.08%.复方华蟾胶囊对荷瘤小鼠的胸腺和脾脏重量无影响.结论复方华蟾胶囊在试验条件下有一定抗肿瘤作用.     

银杏竹鼠肌肉成分对小鼠智力、体力的影响

目的：观察银杏竹鼠肌肉成分对小鼠智力体力的影响。方法：小鼠随机分为七组，通过喂饲银杏竹鼠肌肉干粉连续一个月，用小鼠低温游泳存活时间实验，耐缺氧实验及跳台和记忆获得障碍实验分别记录低温游泳存活时间，缺氧存活时间及第一次错误潜伏期和跳台错误次数。结果：各竹肉组小鼠与普通饲料（ＮＳ）组，普肉组，护宝液组比较，均可明显延长小鼠低温游泳存活时间和缺氧存活时间（Ｐ＜０．０５），与洋参丸组相当（Ｐ＞０．０５），竹肉大／超组小鼠跳台错误次数均减少（Ｐ＜０．０５），竹肉超组小鼠第一次错误潜伏期延长（Ｐ＜０．０５），竹肉大组小鼠第一次错误潜伏期有延长趋势，但无统计学意义。结论：口服银杏竹鼠肌肉成分可增强小鼠学习记忆能力，增强小鼠体质，提高小鼠生活质量。这一结果也提示银杏竹鼠肌肉成分很有可能成为极有应用前景和开发前景的保健食品。