Urine cytology: appropriate usage maximizes sensitivity and reduces cost

OBJECTIVE: Urine cytology is costly because of the skilled manpower required for analysis. Inappropriate requests are a significant drain both financially and on the cytopathologist's time. The present study aimed at identifying the extent and cause of this misuse and reduce it. METHODS: An audit of urine cytology usage was undertaken using the hospital results reporting system to identify requests. Patient case notes were then obtained to gain further clinical information. Initially a 2-week period was analysed, following which departmental guidelines for requesting urine cytology were produced and circulated. The audit loop was then closed. RESULTS: Over the initial 2-week period, 117 urine cytology requests were received. Thirty-three per cent were inappropriate, either because they were from patients with benign disease or because of duplication. Following the education programme this number fell to 6%. Expenditure on unnecessary samples thus decreased from pounds 2418 to only pounds 310, giving an annual overall saving of pounds 55,000. CONCLUSION: Significant cost and time savings can be made if urine cytology is sent appropriately. Simple guidelines and staff education are the key to reducing inefficiency. Our findings have implications not just for cytopathology costs but for laboratory and radiology requests in general.     

中国遗传性胰腺炎患者胰蛋白酶原基因多位点杂合突变及其临床特征

用基因产物直接测序法对2个遗传性胰腺炎家系中胰腺炎患者(共有4例成员)的胰蛋白酶原基因(cationic trypsinogen,PRSS1)5个外显子进行测序,并分析其各自的临床特征.在4例胰腺炎患者中均出现了PRSS1基因杂合突变,但两家系PRSS1基因突变的位点不同,且临床表现差异较大,其中家系1出现6例糖尿病患者且发病年龄较家系2明显延迟,平均发病年龄为29岁,分析其PRSS1基因发现3号外显子336位碱基存在G→A杂合性突变,为中性突变,表达的氨基酸从赖氨酸(Lys)→赖氨酸(Lys),同时在同一外显子的361位碱基还存在另一个G→A杂合性突变,造成121位的丙氨酸(Ala)被苏氨酸(Thr)所取代,胰蛋白酶原的空间结构发生改变,其与抑制因子的结合位点消失,"保护失败"而产生有活性的胰蛋白酶,造成胰腺自身的消化.而家系2未发现糖尿病患者,其胰腺炎患者的血清肿瘤标志物不增高,先证者(Ⅲ8)在胰腺炎发病过程中表现为CD4 T/CD8 Tcell和乙肝表面抗体(anti-HBs)随病程进展逐渐降低,而Ⅲ7不表现出此现象,分析其PRSS1基因发现3号外显子361位碱基同样存在G→A(c.361G→A)突变,而且在415位还存在一个杂合性突变点T→A(c.415T→A),其中c.415T→A不存在于Ⅲ7.胰蛋白酶原基因存在多种形式的突变,而且与临床表型相关.     

Designs for phase I clinical trials with multiple courses of subjects at different doses

Summary .   The goal of this article is to provide a new design framework and its corresponding estimation for phase I trials. Existing phase I designs assign each subject to one dose level based on responses from previous subjects. Yet it is possible that subjects with neither toxicity nor efficacy responses can be treated at higher dose levels, and their subsequent responses to higher doses will provide more information. In addition, for some trials, it might be possible to obtain multiple responses (repeated measures) from a subject at different dose levels. In this article, a nonparametric estimation method is developed for such studies. We also explore how the designs of multiple doses per subject can be implemented to improve design efficiency. The gain of efficiency from "single dose per subject" to "multiple doses per subject" is evaluated for several scenarios. Our numerical study shows that using "multiple doses per subject" and the proposed estimation method together increases the efficiency substantially.     

Should the management of radiation therapy for breast cancer be standardized? Results of a survey on current French practices in breast radiotherapy

BackgroundBreast cancer is the most frequent cancer in women in France. Its management has evolved considerably in recent years with a focus on reducing iatrogenic toxicity. The radiotherapy indications are validated in multidisciplinary consultation meetings; however, questions remain outstanding, particularly regarding hypofractionated radiotherapy, partial breast irradiation, and irradiation of the internal mammary chain and axillary lymph node area.Materials and methodsAn online survey was sent to 47 heads of radiotherapy departments in France. The survey consisted of 22 questions concerning indications for irradiation of the supraclavicular, internal mammary and axillary lymph node areas; irradiation techniques and modalities; prescribed doses; and fractionation.ResultsTwenty-four out of 47 centers responded (response rate of 51%). This survey demonstrated a wide variation in the prescribed dose regimen, monoisocentric radiotherapy, and indications of irradiation of the lymph node areas.ConclusionThis survey provides insight into the current radiotherapy practice for breast cancer in France. It shows the need to standardize practices.     

Preliminary pharmacokinetic study of ibuprofen enantiomers after administration of a new oral formulation (ibuprofen arginine) to healthy male volunteers

The pharmacokinetics of ibuprofen enantiomers were investigated in a crossover study in which seven healthy male volunteers received single oral doses of 800 mg racemic ibuprofen as a soluble granular formulation (sachet) containing L-arginine (designated trade name: Spedifen®), 400 mg (-)R-ibuprofen arginine or 400 mg (+)S-ibuprofen arginine. Plasma levels of both enantiomers were monitored up to 480 minutes after drug intake using an enantioselective analytical method (HPLC with ultraviolet detection) with a quantitation limit of 0.25 mg/l. Substantial inter-subject variability in the evaluated pharmacokinetic parameters was observed in the present study. After (+)S-ibuprofen arginine, the following mean pharmacokinetic parameters ±SD were calculated for (+)S-ibuprofen: t_max 28.6 ± 28.4 min; C_max 36.2 ± 7.7 mg/l; AUC 86.4 ± 14.9 mg · h/l; t½ 105.2 ± 20.4 min. After (-)R-ibuprofen arginine, the following mean pharmacokinetic parameters were calculated for (+)S-ibuprofen and (-)R-ibuprofen, respectively: t_max 90.0 ± 17.3 and 50.5 ± 20.5 min; C_max 9.7 ± 3.0 and 35.3 ± 5.0 mg/l; AUC 47.0 ± 17.2 and 104.7 ± 27.7 mg · h/l; t_½ 148.1 ± 63.6 and 97.7 ± 23.3 min. After racemic ibuprofen arginine, the following mean pharmacokinetic parameters were calculated for (+)S- and (-)R-ibuprofen, respectively: t_max 30.7 ± 29.1 and 22.9 ± 29.8 min.; C_max 29.9 ± 5.6 and 25.6 ± 4.4 mg/l; AUC 105.1 ± 23.0 and 65.3 ± 15.0 mg · h/l; t_½ 136.6 ± 20.7 and 128.6 ± 45.0 min. T_max values of S(+)- and (-)R-ibuprofen after a single dose of 400 mg of each enantiomer did not differ significantly from the corresponding parameters obtained after a single dose of 800 mg of racemic ibuprofen arginine, indicating that the absorption rate of (-)R- and (+)S-ibuprofen is not different when the two enantiomers are administered alone or as a racemic compound. An average of 49.3 ± 9.0% of a dose of the (-)R-ibuprofen arginine was bioinverted into its antipode during the study period (480 minutes post-dosing). The percent bioinversion during the first 30 minutes after (-)R-ibuprofen arginine intake averaged 8.1 ± 3.9%. The mean AUC of (+)S-ibuprofen calculated after 800 mg racemic ibuprofen arginine (105.1 ± 23.0 mg · h/l) was lower than the mean AUC value obtained by summing the AUCs of (+)S-ibuprofen after administration of 400 mg (+)S-ibuprofen arginine and 400 mg (-)R-ibuprofen arginine (133.4 ± 26.6 mg · h/l). In conclusion, the administration of Spedifen® resulted in very rapid absorption of the (+)S-isomer (eutomer) with t_max values much lower than those observed for this isomer when conventional oral solid formulations such as capsules or tablets of racemic ibuprofen are administered. This characteristic is particularly favourable in those conditions in which a very rapid analgesic effect is required. Chirality 9:297–302, 1997. © 1997 Wiley-Liss, Inc.     

组学时代下机器学习方法在临床决策支持中的应用

随着组学技术的不断发展,对于不同层次和类型的生物数据的获取方法日益成熟。在疾病诊治过程中会产生大量数据,通过机器学习等人工智能方法解析复杂、多维、多尺度的疾病大数据,构建临床决策支持工具,辅助医生寻找快速且有效的疾病诊疗方案是非常必要的。在此过程中,机器学习等人工智能方法的选择显得尤为重要。基于此,本文首先从类型和算法角度对临床决策支持领域中常用的机器学习等方法进行简要综述,分别介绍了支持向量机、逻辑回归、聚类算法、Bagging、随机森林和深度学习,对机器学习等方法在临床决策支持中的应用做了相应总结和分类,并对它们的优势和不足分别进行讨论和阐述,为临床决策支持中机器学习等人工智能方法的选择提供有效参考。     

血液透析滤过治疗维持性血液透析患者顽固性高血压的临床观察

目的分析血液透析滤过治疗维持性血液透析患者顽固性高血压的临床效果。方法选取2015年1月~2017年2月我院收治的维持性血液透析顽固性高血压患者46例,随机分为对照组与研究组,每组23例。对照组行常规血液透析治疗,研究组采用血液透析滤过方式,观察比较两组患者治疗前后的血压、血浆RA水平及AngII水平变化情况。结果治疗后,研究组的收缩压与舒张压均明显低于对照组(P0.05),血浆RA、AngII水平亦明显低于对照组(P0.05)。结论血液透析滤过治疗维持性血液透析患者顽固性高血压的效果显著,值得临床推广应用。