Pulsed arterial spin labeling perfusion imaging at 3 T: estimating the number of subjects required in common designs of clinical trials

Pulsed arterial spin labeling (PASL) is an increasingly common technique for noninvasively measuring cerebral blood flow (CBF) and has previously been shown to have good repeatability. It is likely to find a place in clinical trials and in particular the investigation of pharmaceutical agents active in the central nervous system. We aimed to estimate the sample sizes necessary to detect regional changes in CBF in common types of clinical trial design including (a) between groups, (b) a two-period crossover and (3) within-session single dosing. Whole brain CBF data were acquired at 3 T in two independent groups of healthy volunteers at rest; one of the groups underwent a repeat scan. Using these data, we were able to estimate between-groups, between-session and within-session variability along with regional mean estimates of CBF. We assessed the number of PASL tag-control image pairs that was needed to provide stable regional estimates of CBF and variability of regional CBF across groups. Forty tag-control image pairs, which take approximately 3 min to acquire using a single inversion label delay time, were adequate for providing stable CBF estimates at the group level. Power calculations based on the variance estimates of regional CBF measurements suggest that comparatively small cohorts are adequate. For example, detecting a 15% change in CBF, depending on the region of interest, requires from 7-15 subjects per group in a crossover design, 6-10 subjects in a within-session design and 20-41 subjects in a between-groups design. Such sample sizes make feasible the use of such CBF measurements in clinical trials of drugs.     

Scheduling the hospital-wide flow of elective patients

In this paper, we address the problem of planning the patient flow in hospitals subject to scarce medical resources with the objective of maximizing the contribution margin. We assume that we can classify a large enough percentage of elective patients according to their diagnosis-related group (DRG) and clinical pathway. The clinical pathway defines the procedures (such as different types of diagnostic activities and surgery) as well as the sequence in which they have to be applied to the patient. The decision is then on which day each procedure of each patient’s clinical pathway should be done, taking into account the sequence of procedures as well as scarce clinical resources, such that the contribution margin of all patients is maximized. We develop two mixed-integer programs (MIP) for this problem which are embedded in a static and a rolling horizon planning approach. Computational results on real-world data show that employing the MIPs leads to a significant improvement of the contribution margin compared to the contribution margin obtained by employing the planning approach currently practiced. Furthermore, we show that the time between admission and surgery is significantly reduced by applying our models.     

美能针配合化疗治疗妇科肿瘤的临床观察

目的观察美能注射液联合化疗治疗恶性肿瘤的疗效和毒副反应。方法将患者分为美能联合化疗组（治疗组）和单纯化疗组（对照组）进行疗效和毒副反应比较，统计方法以卡方检验。结果治疗组有效率58．3％（35／60），对照组有效率40．0％（24／60），两组比较有显著差异（P〈0．05）。治疗组无肝功能损害，消化道反应占30．0％（18／60）程度轻，对照组肝功能损害占38.3％（23／60），消化道反应占43．3％（26／60）程度重。结论美能注射液联合化疗治疗恶性肿瘤，提高了疗效，预防药物性肝损害的发生，并减轻恶心、呕吐、乏力、食欲下降等其它消化道毒副反应的程度，提高患者的生存质量，值得推广。     

Recent advances in clinical microdialysis

Clinical microdialysis (MD) is a minimally invasive sampling technique that offers selective in-vivo measurement of free, active drug or biomolecule concentrations in human tissues and organs. From a regulatory perspective, MD can thus be seen as a suitable scientific tool that meets regulatory requirements for the study of tissue distribution or bioequivalence during drug development. From a clinical perspective, the use of MD in different applications has shown the potential to rationalize drug-dosing regimens and to influence clinical decision-making, although validation and correlation of MD-derived results with clinical response are required to promote routine clinical use of the technique. From an analytical perspective, highly sensitive analytical systems have increasingly become available for MD-sample analysis, and these have further improved the quality and the power of MD-derived information. Given the constant development in recent years, MD data might become an important part of new drug submissions and clinical treatment algorithms, and might positively influence patient benefit in the future.     

86例渗出性结核性胸膜炎的临床分析

目的：总结结核性胸膜炎的临床特点，并探讨治疗方法．方法：对1998—01-2003—12住院，并资料完整的86例结核性胸膜炎采用回顾性分析．结果：86例中青壮年占大多数（77．9％），老年患病率较高（16．28％），大多数具有典型的结核中毒症状．在积极抗结核治疗的同时采用不限量缓慢抽液及胸腔内注药治疗。治愈48例（占55．81％），胸膜增厚38例（占44．19％），其预后与诊治的时机有密切关系．结论：掌握结核性胸膜炎的临床特点，早期诊断，合理治疗，可取得较好疗效．     

神经营养素的生物学作用及临床应用前景

神经营养素是一类神经营养因子，目前已被用于神经萎缩、神经变性、外伤修复等疾病的治疗中．它的研究极大地推动了神经生物学和细胞生物学的发展，本文拟就神经营养素的生物学作用及临床应用前景作一简要的介绍．     

Analysis of patient self-assessment visual analogue scales

The present paper describes an example of practical analysis of data from an application of visual analogue scales. Potentially useful and simple methods for analysing visual analogue scales are described for effective handling of complex data when the desire is to compare two or more groups of patients. Visual analogue scales were used to assess subjective tolerability in the International Prospective Primary Prevention Study in Hypertension, a large scale clinical trial. The methods are illustrated on the IPPPSH data.     

Sensitivity and significance of disease outcome measures in inflammatory bowel disease

In inflammatory bowel disease (IBD), proxy measures of clinical outcome are often collected into summary indices of qualitative self-rated disease markers, clinical observations, and quantitative biochemical analyses. In Crohn's disease (CD), a frequently used index is the Crohn's disease activity index (DCAI). This index consists of six qualitative variables and two quantitative variables. The aim of this presentation is to illustrate the use of this index to calculate its range, to estimate errors in the index, its sensitivity, and the number of significant steps in the index. The measure of sensitivity of the summary index was analyzed for the signal-to-noise ratio (SNR), the reference change value (RCV) and the confidence interval (CI). If identical errors were assumed in patient self-rated health and clinically judged disease manifestations, such as tumours and fistulas, the majority of the variance of the index was caused by the self-rated experience of health, the number of days over which the individual variable was rated, and the prognostic multiplier of each variable.The range of the index has no upper limit, but can be estimated to 403 units, of which patient self-rating of well-being account for up to one-third of the summary index maximal score range. The median signal noise measure of index sensitivity was 18 SDs. The two disease classification limits of 150 units for moderate disease and 450 for severe disease on average cover an interval of limit ±41.5 units vs. ±60.5 units. In judgments on change in clinical outcome the RCV interval of steps of 121 units are valid. Conclusion: Both variance and range of the CDAI summary score are primarily decided by the self-rated experience of well-being. Variables on disease signs have a minor impact on the index. Rating of the two important outcome parameters: Self-experienced health and medical outcome would favourably be given in two individual scores.Presented at the 10th Conference Quality in the Spotlight, March 2005, Antwerp, Belgium.     

Determination of neopterin, kynurenine, tryptophan and creatinine in human serum by high throuput HPLC

A new HPLC method for simultaneous determination of neopterin, creatinine, kynurenine and tryptophan in human serum was developed and validated. Monolithic stationary phase's technology (two monolithic columns RP-18e were connected with guard monolithic cartridge 4.6 mm × 50 mm + 3.0 mm × 100 mm and 4.6 × 10 mm) and special auto sampler for micro titration plates (samples are storage in dark cooled place protected against evaporation) were combined with easy sample preparation step. As mobile phase 15 mmol/L phosphate buffer at pH 4.50 was used. Neopterin and tryptophan were detected using fluorescent detection and kynurenine and creatinine were detected by diode-array detection. This method may be suitable for large sequences of samples in clinical research and routine practice.     

On the use of double cross-validation for the combination of proteomic mass spectral data for enhanced diagnosis and prediction

We consider a proteomic mass spectrometry case-control study for the calibration of a diagnostic rule for the detection of early-stage breast cancer. For each patient, a pair of two distinct mass spectra is recorded, each of which is derived from a different prior fractionation procedure on the available patient serum. We propose a procedure for combining the distinct spectral expressions from patients for the calibration of a diagnostic discriminant rule. This is achieved by first calibrating two distinct prediction rules separately, each on only one of the two available spectral data sources. A double cross-validatory approach is used to summarize the available spectral data using the two classifiers to posterior class probabilities, on which a combined predictor can be calibrated.