Ultrasonic velocity measurements through the calcaneus: Which velocity should be measured?

The assessment of skeletal integrity by the measurement of ultrasonic velocity through the calcaneus has only recently become widely available and is usually made in conjunction with the measurement of broadband ultrasonic attenuation. Using data obtained with a contact ultrasonic bone analyser (CUBA) system, this report examines whether ultrasonic studies of the heel require the measurement of true velocity of sound in the calcaneus (V_bone), or whether heel velocity (V_heel, defined as the mean velocity through bone and soft tissue) or time of flight velocity (V_tof, defined as the mean velocity between the two transducers) are adequate surrogates. The populations selected for study were 15 healthy young women (group 1, mean age 26 years), 231 healthy peri- and postmenopausal women (group 2, mean age 52 years) and 33 osteoporotic women with confirmed vertebral fracture (group 3, mean age 66 years). Precision was studied by performing 10 repeated scans on the subjects in group 1 and duplicate scans on 144 women randomly selected in groups 2 and 3. Precision was expressed as the percentage coefficient of variation (CV). Both precision studies yielded similar results. The precisions (and 5% to 95% ranges) for all groups combined were: V_bone 2.71% (1465–1809 m/s); V_heel, 1.10% (1511–1646 m/s); V_tof, 0.70% (1349–1425 m/s). Although the precision data suggest V_tof should be preferred, when the range of clinical values is taken into account the smaller CV is exactly cancelled by the narrower range. To demonstrate this numerically it is proposed to introduce a new measure of precision, the standardized coefficient of variation (SCV), defined as the percentage CV divided by the percentage ratio of the range over the mean. SCV had a value of 12.7% for V_tof and 12.8% for V_bone and V_heel. For comparison a SCV of 2.2% was estimated for dual X-ray absorptiometry (DXA). Thus the measurement of ultrasonic velocity through the calcaneus compares equally in terms of CV, but not in terms of SCV. A scatter plot of V_bone against V_tof gave a significantly poorer correlation (r=0.828) than that of V_bone against V_heel (r=0.984). This latter correlation can be explained by theoretical studies demonstrating convergence of the two measurements when the velocity through the bone equals that through soft tissue (1540 m/s). Since the measurement of V_heel dispenses with the need to determine soft tissue thickness over the calcaneus, it is the optimum velocity parameter for the CUBA system.     

Inspection by variables as an acceptance criterion in bioanalysis — a proposal

Inspection by variables is proposed as an acceptance criterion for use in bioanalysis. The criteria currently used are deficient either by ignoring the issues of precision (fixed range) and/or accuracy (99% confidence interval), not being able to provide immediate answers (quality charts), or even not being scientifically justified (fixed range). Inspection (sampling) by a variables procedure was originally developed to drive the quality of military supplies (MIL-STD-414) and was consequently incorporated in ISO 3951 as a part of industrial quality control. It is based on the concept of acceptable quality level (AQL), which is the maximum per cent defective (number of results outside of specification per 100 results) that can be considered satisfactory as a process average. It also correlates sample size with batch size. An AQL of 6.5% is proposed as a standard with specification set at ± 20% or ± 15%, which should result in coefficients of variation of approximately 15% and 12%, respectively. This concept has been applied post factum to 14 authentic data sets, thus proving its utility and validity.     

A Unified Approach for Assessing Agreement for Continuous and Categorical Data

Abstract

In simultaneous testing for noninferiority and superiority, Morikawa and Yoshida (Morikawa, T., Yoshida, M. (1995 Morikawa, T. and Yoshida, M. 1995. A useful testing strategy in phase III trials: Combined test of superiority and test of equivalence. J. Biopharmaceutical Statistics, 5: 297–306. [Taylor &; Francis Online] , [Google Scholar]). A useful testing strategy in phase III trails: Combined test of superiority and test of equivalence. J. Biopharmaceutical Statistics 5:297–306) argue that multiplicity adjustment is not necessary by using the closed testing (CT) principle. In fact, using the same argument, no multiplicity adjustment is necessary in simultaneous testing of any number of nested null hypotheses. However, simultaneous testing of many nested null hypotheses is problematic in a confirmatory trial because such simultaneous testing is similar to post-hoc specification of the null hypothesis. Thus, simultaneous testing for noninferiority and superiority may be viewed as an initial step towards exploratory analysis and may be best used cautiously in confirmatory evaluation.     

Estimation of the Risk Difference Under a Noncompliance Randomized Clinical Trial with Missing Outcomes

In a randomized clinical trial (RCT), we often come across the situations in which there are patients who do not comply with their assigned treatments or whose outcomes are missing due to their refusal or loss to follow-up. Because noncompliance and missing outcomes do not generally occur completely at random, analyzing data as treated or excluding patients with missing outcomes from our analysis can produce a biased estimate of a treatment effect. In this paper, we consider estimation of the risk difference (RD) in the presence of both noncompliance and missing outcomes under a RCT. On the basis of a constant risk additive model proposed elsewhere, we derive the maximum likelihood estimator (MLE) and develop three asymptotic interval estimators in closed form for the RD when we have outcome missing at random. We apply Monte Carlo simulation to evaluate and compare the performance of these estimators in a variety of situations. We note that all interval estimators developed here can perform well with respect to the coverage probability in all the situations considered here. We find that the interval estimator using tanh  ? 1 (x) transformation is generally more precise than the other two estimators with respect to the average length. Finally, we use the data taken from a randomized trial studying the association between flu vaccine and the risk of flu-related hospitalization to illustrate the practical use of these interval estimators.     

Profiling Cancer Gene Mutations in Clinical Formalin‐Fixed,Paraffin‐Embedded Colorectal Tumor Specimens Using Targeted Next‐Generation Sequencing

Purpose.

The success of precision oncology relies on accurate and sensitive molecular profiling. The Ion AmpliSeq Cancer Panel, a targeted enrichment method for next-generation sequencing (NGS) using the Ion Torrent platform, provides a fast, easy, and cost-effective sequencing workflow for detecting genomic “hotspot” regions that are frequently mutated in human cancer genes. Most recently, the U.K. has launched the AmpliSeq sequencing test in its National Health Service. This study aimed to evaluate the clinical application of the AmpliSeq methodology.

Methods.

We used 10 ng of genomic DNA from formalin-fixed, paraffin-embedded human colorectal cancer (CRC) tumor specimens to sequence 46 cancer genes using the AmpliSeq platform. In a validation study, we developed an orthogonal NGS-based resequencing approach (SimpliSeq) to assess the AmpliSeq variant calls.

Results.

Validated mutational analyses revealed that AmpliSeq was effective in profiling gene mutations, and that the method correctly pinpointed “true-positive” gene mutations with variant frequency >5% and demonstrated high-level molecular heterogeneity in CRC. However, AmpliSeq enrichment and NGS also produced several recurrent “false-positive” calls in clinically druggable oncogenes such as PIK3CA.

Conclusion.

AmpliSeq provided highly sensitive and quantitative mutation detection for most of the genes on its cancer panel using limited DNA quantities from formalin-fixed, paraffin-embedded samples. For those genes with recurrent “false-positive” variant calls, caution should be used in data interpretation, and orthogonal verification of mutations is recommended for clinical decision making.     

三种抗环瓜丝氨酸抗体检测试剂性能评价及临床应用

目的评价3种抗环瓜丝氨酸(CCP)抗体检测试剂盒的分析性能,并比较临床应用。方法收集93例类风湿性关节炎(RA)患者、118例非RA疾病(自身免疫性疾病82例、骨关节炎36例)患者以及20名表面健康人群的血清样本,评价罗氏、欧蒙、富纯3种抗CCP抗体试剂的分析性能,比较不同试剂间的相关性,评估各自的初步临床应用价值。结果 3种试剂检测精密度差异无统计学意义,批内、天间变异系数(CV)均<10%。罗氏和欧蒙2种试剂在检测范围内呈线性,富纯试剂的真实线性范围为25.0～1 027.9 RU/mL。3种试剂检测结果相关性较好,罗氏与欧蒙、富纯试剂的相关系数(r)分别为0.90、0.87,欧蒙、富纯试剂的相关系数(r)为0.97。根据厂商提供的Cut-off值,诊断灵敏度可达83.9%～86.0%,特异性为92.0%～97.1%。罗氏、欧蒙、富纯检测试剂的受试者工作特征(ROC)曲线下面积(AUC)分别为0.91、0.92和0.89,比较任意2种检测试剂的AUC,差异均无统计学意义(Z值分别为0.27、0.89、0.63,P均>0.05)。结论总体来说,不同方法抗CCP抗体检测试剂的检测结果之间具有一定的可比性,临床应用的诊断特性差异不明显,但标准化仍存在问题。     

加强精准防治 推动山丘型地区消除血吸虫病进程

我国山丘型流行区主要分布于四川和云南2省。通过60余年的积极防控,山丘型流行区血吸虫病防治工作取得了显著成效。近年来,四川、云南2省抓住农村农业发展新机遇,积极落实以传染源控制为主的综合防治策略,有效利用现代信息技术手段,创新防治模式,构建敏感、高效的监测体系,积极应对消除进程中面临的诸多挑战,有力推动了我国山丘型流行区血吸虫病消除工作进程。     

牙颌模型测量的三维进展

随着计算机技术的发展,三维扫描技术在临床诊断中已得到广泛应用,并且在治疗方面也具有显著的指导意义。由于该三维立体重建和测量方法有非介入性、直观逼真等特点,在牙颌模型测量和分析的临床和科研中有着广泛的研究价值和应用前景,为口腔领域的诊断和治疗提供了重要依据。在此回顾总结了三维扫描技术的优缺点,并对其今后的研究方向进行了展望。