腰椎间盘突出症规范化非手术治疗模式下的个性化方案

腰椎间盘突出症是坐骨神经痛的常见病因,病因与临床表现复杂多变,各种非手术治疗疗效满意且被多国推荐使用,其有效性与优势取决于如何被有效运用。在规范化的治疗方案指导下,根据具体患者的疾病特点,制定出既有原则性,又有针对性的个性化治疗方案,具有非常重要的临床意义。     

EGFR靶向药物个体化治疗转移性结直肠癌的研究进展

靶向表皮生长因子受体(epidermal growth factor receptor,EGFR)单抗目前已成为晚期结直肠癌治疗的一个突破,对此类药物相关基因的研究也开创了结直肠癌个体化治疗的先河。EGFR信号转导系统中EGFR基因、配体以及下游的KRAS,BRAF和PIK3CA基因一直都是研究的热点。本文就EGFR靶向药物疗效相关预测因子的研究现状做一综述。     

连续性静脉-静脉血液滤过患者血清中利奈唑胺的浓度监测

目的:对连续性静脉-静脉血液滤过(continuous venovenous hemofiltration,CVVH)治疗的危重患者进行利奈唑胺血药浓度监测,为临床个体化治疗提供依据。方法:建立高效液相色谱法(以左氧氟沙星为内标),测定患者血清中利奈唑胺谷浓度。结果:利奈唑胺在0.31～20.00μg.mL-1内线性关系良好(r=0.999 5),定量限为0.31μg.mL-1。5例危重患者在治疗期间监测23次的利奈唑胺谷浓度变化明显,变化范围为1.53～17.10μg.mL-1。有2例患者谷浓度变化较大(相差近5倍)。结论:高效液相色谱法简单、快速、准确、灵敏、重复性好,可用于临床利奈唑胺的血药浓度监测。进行连续性静脉-静脉血液滤过治疗的患者,应用利奈唑胺时血药浓度变化较大,需要通过治疗药物监测的方法制定个体化给药方案。     

Atopic dermatitis - from new pathophysiologic insights to individualized therapy

Recently, important novel insights into the complex pathophysiology of atopic dermatitis (AD) have been gained. However, in most cases the therapy of AD is limited to base line therapy with emollients combined with symptomatic, rather general immunosuppressive treatment approaches of the flare-ups. Latest research findings together with experiences from daily clinical practice, which support the concept that a combination of general disease features together with specific trigger factors in the individual patients drive the disease, might be helpful for a subclassification of patients with AD based on the most relevant pathophysiologic modifications. Subclassification of patients with AD seems indispensable to introduce rationale-based, individualized treatment approaches of AD, which target specific modified pathways. In this review, we provide an overview about a selection of pathophysiologic pathways, which hold promise to represent targets of such therapeutic approaches in the near future.     

2011年美国FDA批准新药简析

2011年美国食品药品监督管理局(FDA)共批准30个新药。简要介绍其中的重点品种,并就新药研发的现状与趋势进行分析。在2011年FDA批准上市的新药中,有11个为首创一类新药,其中50余年来首次上市的系统性红斑狼疮治疗药物贝利单抗、30余年来首次获准上市的霍奇金淋巴瘤靶向治疗药物本图希单抗-维度汀、慢性丙型肝炎治疗药物特拉普韦和波塞普韦、肿瘤免疫治疗药物依普利单抗、基于基因学检测的肿瘤个体化治疗药物克唑替尼和维拉芬尼等药物作用独特或市场前景广阔,颇受关注。     

An Improved Methodology for Individualized Performance Prediction of Sleep-Deprived Individuals with the Two-Process Model

We present a method based on the two-process model of sleep regulation for developing individualized biomathematical models that predict performance impairment for individuals subjected to total sleep loss. This new method advances our previous work in two important ways. First, it enables model customization to start as soon as the first performance measurement from an individual becomes available. This was achieved by optimally combining the performance information obtained from the individual''s performance measurements with a priori performance information using a Bayesian framework, while retaining the strategy of transforming the nonlinear optimization problem of finding the optimal estimates of the two-process model parameters into a series of linear optimization problems. Second, by taking advantage of the linear representation of the two-process model, this new method enables the analytical computation of statistically based measures of reliability for the model predictions in the form of prediction intervals.Two distinct data sets were used to evaluate the proposed method.Results using simulated data with superimposed white Gaussian noise showed that the new method yielded 50% to 90% improvement in parameter-estimate accuracy over the previous method. Moreover, the accuracy of the analytically computed prediction intervals was validated through Monte Carlo simulations. Results for subjects representing three sleep-loss phenotypes who participated in a laboratory study (82 h of total sleep loss) indicated that the proposed method yielded individualized predictions that were up to 43% more accurate than group-average prediction models and, on average, 10% more accurate than individualized predictions based on our previous method.

Citation:

Rajaraman S; Gribok AV; Wesensten NJ; Balkin TJ; Reifman J. An improved methodology for individualized performance prediction of sleep-deprived individuals with the two-process model.     

代谢组学研究在肿瘤药效学和耐药研究中的进展

随着核磁共振和质谱等检测手段,以及计算机分析技术的不断进步,代谢组学在肿瘤中的研究越来越广泛,特别是在肿瘤药物疗效判断、毒性作用以及耐药预测上有着重要作用,对临床个体化药物治疗起到指导作用。文章对此进行综述。     

基于药物基因组学的质子泵抑制剂个体化精准治疗分析

目的:探讨CYP2C19基因型对质子泵抑制剂(proton pump inhibitor,PPI)个体化治疗的影响,为临床个体化精准用药提供有益参考。方法:查阅国内外权威指南及最新研究等相关文献,就CYP2C19基因多态性对PPI代谢与治疗的影响及基于药物基因组学的剂量建议进行综述与分析。结果:CYP2C19基因多态性与PPI抑酸治疗效果、安全性具有相关性,在临床治疗中根据患者(尤其是特殊群体)CYP2C19表型进行PPI个体化治疗有助于提升疗效与安全性。结论:基于药物基因组学的PPI个体化应用或可为临床治疗提供新的思路,进一步促进临床用药的合理性与精细化。     

Individualized estimates of second cancer risks after contemporary radiation therapy for Hodgkin lymphoma

BACKGROUND: Estimates of radiation-related second cancer risk among Hodgkin lymphoma survivors are largely based on radiation therapy (RT) fields and doses no longer in use, and these estimates do not account for differences in normal tissue dose among individual patients. This study gives individualized estimates for the risks of lung and female breast cancer expected with contemporary involved-field RT and low-dose (20 Gy) RT for mediastinal Hodgkin lymphoma. METHODS: Three RT plans were constructed for 37 consecutive patients with mediastinal Hodgkin lymphoma: 35 Gy mantle RT, 35 Gy involved-field RT (IFRT), and 20 Gy IFRT. For each of the 111 RT plans, individual-level dosimetry data were incorporated into a cell initiation/inactivation/proliferation model to estimate the excess relative risk (ERR) and cumulative incidence of radiation-induced second cancer. RESULTS: ERR estimates were compatible with results of epidemiological studies. Compared with 35 Gy mantle radiation therapy, 35 Gy IFRT was predicted to reduce the 20-year ERRs of breast and lung cancer by 63% and 21%, respectively, primarily because of lower normal tissue doses with the omission of axillary RT. Low-dose (20 Gy) IFRT was associated with a 77% and 57% decrease in these ERRs. Patient-specific differences in normal tissue dose with IFRT led to 11-fold and 3.6-fold variations among individual's estimates of breast and lung cancer ERR, respectively. CONCLUSIONS: Contemporary IFRT is predicted to substantially reduce risk of secondary breast and lung cancer compared with mantle RT, with considerable variation in risk among individuals. Individualized prospective risk estimates could facilitate patient-specific counseling and the development of more effective RT techniques.