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.     

Impact of sampling rate on statistical significance for single subject fMRI connectivity analysis

A typical time series in functional magnetic resonance imaging (fMRI) exhibits autocorrelation, that is, the samples of the time series are dependent. In addition, temporal filtering, one of the crucial steps in preprocessing of functional magnetic resonance images, induces its own autocorrelation. While performing connectivity analysis in fMRI, the impact of the autocorrelation is largely ignored. Recently, autocorrelation has been addressed by variance correction approaches, which are sensitive to the sampling rate. In this article, we aim to investigate the impact of the sampling rate on the variance correction approaches. Toward this end, we first derived a generalized expression for the variance of the sample Pearson correlation coefficient (SPCC) in terms of the sampling rate and the filter cutoff frequency, in addition to the autocorrelation and cross‐covariance functions of the time series. Through simulations, we illustrated the importance of the variance correction for a fixed sampling rate. Using the real resting state fMRI data sets, we demonstrated that the data sets with higher sampling rates were more prone to false positives, in agreement with the existing empirical reports. We further demonstrated with single subject results that for the data sets with higher sampling rates, the variance correction strategy restored the integrity of true connectivity.     

存样食物在追查食物中毒源头中的作用

[目的]针对食物中毒事件追查源头的困难局面,探索1种新的食物中毒追查方法。[方法]通过分析各种常见类型食物中毒的潜伏期,结合各种实际情况,探讨存样食物保存的时间和方法。[结果]存样食物至少要保存24h。[结论]这种存样待检方法有其先进性,但仍存在不少问题,需进一步改进。     

新生儿出生信息样本分析

目的:了解和探讨新生儿出生信息的分布态势及规律。方法:对本院2006年1~6月间所有新生儿出生信息进行样本分析。结果:半年间分娩的新生儿共1075例,其中死亡19例,双胞胎15例,以1028例单胎活产新生儿的出生体重、胎龄及产妇年龄作为研究样本进行分析,统计数据与传统意义上的正常胎龄和新生儿体重基本相符,胎龄、体重均值均有所提高。结论:孕产妇的健康状况和新生儿的体质均有所改善,随胎龄的增加,新生儿出生体重亦随之增加,并且,目前新生儿的整体统计体重要大于现有的临床指标,因此,应对现有的临床指标进行适当调整,重新确定低出生体重儿和巨大儿的临床指标。     

尿液自动分析、尿沉渣及尿常规镜检对尿中有形成份的对比分析

目的：观察尿常规、尿自动分析仪和尿沉渣对100例尿中有形成份检测的敏感性。方法：100例病人的尿标本分别进行干化学分析，尿沉渣镜检和尿常规镜检，根据检查结果与临床诊断作对比，了解其诊断的符合率。结果：三种方法红细胞，白细胞，管型检测均有差异（P＜0．05），其中：干化学法和尿沉渣镜检法对RBC的检出率明显高于常规法（P＜0．001），而干化学法与尿沉渣镜检法对RBC的检出无显著性差异（P＞0．05），尿沉渣镜检对WBC的检出率高于常规镜检及干化学法（P＜0．05），而常规镜检对WBC的检出率与干化学法无显著性差异（P＞0．05），尿沉渣镜检和尿常规镜检对管型的检出有显著性差异（P＜0．05），以尿沉渣的检出率为高，结论：尿沉渣检镜是三种方法中对尿有形成份检出最好的一种方法。     

Sialic acid concentrations in the urine of men with and without renal stones

Summary It has been suggested that urinary sialidase may play a role in the formation of renal stones. The present study was therefore undertaken to compare spectrophotometrically the different types of sialic acid concentrations and sialidase activities in fresh first morning urine specimens of men (21–65 years) with (13) and without (9) calcium oxalate renal stones. Although the free urinary sialic acid concentrations of the two groups of men were statistically about the same (P=0.0614), the total (P=0.003) and bound (P=0.0012) urinary sialic acid concentrations differed significantly. Both the total and bound sialic acid concentrations were lower in the urine specimens of the stone patients than in their healthy counterparts. This decrease in urinary sialic acid concentrations was firstly thought to be the result of elevated breakdown enzymes of sialic acid, which would favour the production of pyruvate. However, spectrophotometric determinations of the endogenous pyruvate concentrations of the two types of urine specimens did not differ significantly (P=0.0708). Secondly, the decrease in total urinary total sialic acid concentration of stone patients, could be attributed to less sialic acid synthesis or less renal excretion. Therefore, the same experiments were repeated using serum of 13 patients and 9 healthy men. Conversely, the total (P=0.4425) and bound (P=0.2850) serum sialic acid concentrations were found to be similar in the two types of subjects. However, the free serum sialic acid concentration of stone patients was significantly lower than in the healthy subjects (P=0.0062). This phenomenon is also reflected in the average ratio for serum free: bound sialic acid in healthy and stone patients, 1:7.9 and 1:18.7 respectively (P=0.0009). The lower free serum sialic acid concentration may lead to lower renal excretions of sialic acid. This may explain the decrease in total urinary sialic acid concentration in stone patients. The lower bound urinary sialic acid concentrations in patients was also reflected in the urinary free: bound sialic acid ratio for healthy (1:2.3) and stone patients (1:1.3). The difference between these two groups of men was highly significant (P=0.0001). This phenomenon might be explained by the urinary sialidase activities, which was spectrophotometrically determined at 334 nm at 37°C of 11 patients with stones and 17 healthy men. The ages of both groups of men were the same (P=0.326). An increase in urinary sialidase activity was observed with the stone patients (P=0.00001) when compared to specimens of healthy men. This might explain the decrease in urinary bound sialic acid concentration of the stone group. It seems from these results that the urinary concentration of sialic acid and the activity of urinary sialidase, may play a role in the pathogenesis of the multifactorial disease, urolithiasis.     

Effects of different doses of alkaline citrate on urine composition and crystallization of calcium oxalate

Summary Prophylactic treatment with alkaline citrate in patients with recurrent calcium oxalate (CaOx) stone disease results in reduced CaOx supersaturation and increased urinary citrate. The effects of a single evening dose were compared with those of two and three daily doses in six recurrent CaOx stone formers with hypercalciuria, hypocitraturia or raised calcium/citrate quotients. While on a standardized hospital diet the patients were given 7.5 g (28 mmol) of sodium potassium citrate (URALYT-U) in one, two, and three doses. Fractional urine collections during 24 hours were analyzed for pH, composition, and crystallization risk (CR). All dosage regimens had favourable effects on urinary calcium, citrate, calcium/citrate quotients, and CaOx-CR. The most sustained effect was recorded with three divided doses. Single evening doses resulted in the most pronounced effects between 22.00–06.00 h, thereby counteracting the increased risk of CaOx crystallization during that period. In terms of 24 h urine composition the best effect was recorded with alkaline citrate administered three times daily, but because of the favourable response by a single evening dose between 22.00–06.00 h the assumption was made that this dosage regimen might be sufficient to reduce the risk of CaOx crystallization and stone formation. However, the validity of such an assumption can only be established by long-term clinical studies.