内、外科临床药师工作实践类型对比分析

目的对比临床药师在内、外科工作特点的异同,为临床药师更深入地开展工作指明方向。方法回顾该院2013年1-6月临床药师的工作记录,并进行分类汇总分析。结果临床药师解决案例数为449例(内科293例,外科156例),内科工作主要为用药咨询、患者用药教育;外科主要工作为不合理用药干预、调整用药等。结论临床药师需要加强专科药学知识;根据不同类型科室明显不同的工作内容,把握专科服务方向。     

肾内科临床药师在药物整合服务中的实践探索

目的通过临床药师在肾内科对药物整合(medication reconciliation)的实践,探讨临床药师在药物整合中的重要作用。方法对2014年1月18日-2月18日入院的20名患者进行药物整合,主要通过询问患者近1年内的用药情况,对比入院医嘱和药师询问结果,分析存在差异的原因。结果药品数量与入院医嘱不相符率占60%,药品产地不同占55%,药师问诊的准确率更高。结论临床药师在药物整合中起到重要的作用,通过加强医生和患者对药物整合的重视,以及加强医院系统网络建设等措施可以更好地帮助医务工作者实行药物整合服务,减少用药差错的产生。     

临床药师参与1例特发性肺纤维化治疗的药学实践

目的：评价药师参与特发性肺纤维化治疗的药学实践及对治疗效果的改善情况。方法：药师与医师密切配合,参考《热病》和相关文献及指南,根据患者病情变化和治疗效果及时调整药物治疗方案,密切观察疗效。结果：患者病情较前好转。结论：临床药师参与药物治疗全过程,将药学理论与临床实践有机结合,减少不良反应,促进合理用药。     

Non‐clinical safety evaluation of single and repeated intramuscular administrations of MAGE‐A3 Cancer Immunotherapeutic in rabbits and cynomolgus monkeys

The MAGE‐A3 recombinant protein combined with AS15 immunostimulant (MAGE‐A3 Cancer Immunotherapeutic) is under development by GlaxoSmithKline for the treatment of lung cancer and melanoma. We performed non‐clinical safety studies evaluating potential local and systemic toxic effects induced by MAGE‐A3 Cancer Immunotherapeutic in rabbits (study 1) and cynomolgus monkeys (study 2). Animals were allocated to two groups to receive a single (rabbits) or 25 repeated (every 2 weeks) injections (monkeys) of MAGE‐A3 Cancer Immunotherapeutic (treatment groups) or saline (control groups). All rabbits were sacrificed 3 days post‐injection and monkeys 3 days following last injection (3/5 per gender per group) or after a 3‐month treatment‐free period (2/5 per gender per group). Local and systemic reactions and MAGE‐A3‐specific immune responses (monkeys) were assessed. Macroscopic and microscopic (for rabbits, injection site only) post‐mortem examinations were performed on all animals. No systemic toxicity or unscheduled mortalities were recorded. Single (rabbits) and repeated (monkeys; up to four times at the same site) injections were well tolerated. Following five to seven repeated injections, limb circumferences increased up to 26% (5 h post‐injection), but returned to normal after 1–8 days. Three days after the last injection, enlargements of iliac, popliteal, axillary and inguinal lymph nodes, and increased incidence or severity of mononuclear inflammatory cell infiltrates was observed in injected muscles of treated monkeys. No treatment‐related macroscopic findings were recorded after the treatment‐free period. MAGE‐A3‐specific antibody and T‐cell responses were raised in all treated monkeys, confirming test item exposure. Single or repeated intramuscular injections of MAGE‐A3 Cancer Immunotherapeutic were well tolerated in rabbits and monkeys. Copyright © 2014 GlaxoSmithKline Vaccines. Journal of Applied Toxicology published by John Wiley & Sons, Ltd.     

Physiologically based pharmacokinetics model predicts the lack of inhibition by repaglinide on the metabolism of pioglitazone

Purpose: Repaglinide and pioglitazone are both CYP2C8 and CYP3A4 substrates. This study was to determine whether repaglinide has an inhibitory effect on the metabolism of pioglitazone in vitro, in silico and in vivo. Method: In vitro, the effect of repaglinide on the metabolism of pioglitazone was assessed in pooled human liver microsomes. In silico, an IVIVE‐PBPK linked model was built with Simcyp®. Then, a randomized, 2‐phase cross‐over clinical study was conducted in 12 healthy volunteers. Results: Repaglinide showed a strong inhibitory effect on the metabolism of pioglitazone in vitro (K_i = 0.0757 µm ), [I]/K_i > 0.1. The Simcyp® prediction ratios of AUC and C_max between the two treatment groups were both about 1.01. The pharmacokinetics of pioglitazone in clinical trials showed no significant difference between these two treatment groups (p > 0.05). Conclusion: Repaglinide has no significant inhibitory effect on the metabolism of pioglitazone in vivo, which is inconsistent with the in vitro results. The lack of an inhibitory effect was partly due to extensive plasma protein binding and to the high in vivo clearance of repaglinide, for the concentration of repaglinide in vivo was far smaller than in vitro. Copyright © 2015 John Wiley & Sons, Ltd.     

NB09方案治疗高危和极高危神经母细胞瘤近期疗效观察

目的评价中国儿童神经母细胞瘤协作组09方案(NB09方案)治疗高危和极高危神经母细胞瘤的初步疗效。方法回顾性分析2009年1月—2013年1月天津医科大学肿瘤医院收治的高危和极高危神经母细胞瘤患儿的临床及随访资料。38例患儿纳入分析,其中男27例,女11例。高危组7例,极高危组31例。诊断时月龄19~160个月(中位就诊月龄36.5个月)。高危组:术前新辅助化疗A、B方案交替4~6周期后评估、手术。极高危组手术前后化疗,然后自体干细胞移植,瘤床放疗,停化疗后维甲酸治疗同高危组。结果治疗结束时CR 25例,PR 5例,SD 3例,PD 5例,其中死亡2例,治疗总有效率(CR+PR+SD)86.8%。至随访结束,全组无瘤生存15例,带瘤生存9例,死于肿瘤复发7例,死于进展7例,生存期6~52个月(中位生存期25.5个月),其1、2、3年总生存率(OS)分别为91.7%、64.5%和57.3%。Kaplan-Meier生存曲线和Log-rank检验提示高危组与极高危组之间生存率差异无统计学意义(P=0.56)。结论 NB09方案治疗高危和极高危神经母细胞瘤的近期疗效初步肯定,值得进一步临床验证。     

Pharmacokinetic–pharmacodynamic modelling in anaesthesia

Anaesthesiologists adjust drug dosing, administration system and kind of drug to the characteristics of the patient. They then observe the expected response and adjust dosing to the specific requirements according to the difference between observed response, expected response and the context of the surgery and the patient.The approach above can be achieved because on one hand quantification technology has made significant advances allowing the anaesthesiologist to measure almost any effect by using noninvasive, continuous measuring systems. On the other the knowledge on the relations between dosing, concentration, biophase dynamics and effect as well as detection of variability sources has been achieved as being the benchmark specialty for pharmacokinetic–pharmacodynamic (PKPD) modelling.The aim of the review is to revisit the most common PKPD models applied in the field of anaesthesia (i.e. effect compartmental, turnover, drug–receptor binding and drug interaction models) through representative examples. The effect compartmental model has been widely used in this field and there are multiple applications and examples. The use of turnover models has been limited mainly to describe respiratory effects. Similarly, cases in which the dissociation process of the drug–receptor complex is slow compared with other processes relevant to the time course of the anaesthetic effect are not frequent in anaesthesia, where in addition to a rapid onset, a fast offset of the response is required. With respect to the characterization of PD drug interactions different response surface models are discussed. Relevant applications that have changed the way modern anaesthesia is practiced are also provided.     

Clinical trials in children

Safety and efficacy data on many medicines used in children are surprisingly scarce. As a result children are sometimes given ineffective medicines or medicines with unknown harmful side effects. Better and more relevant clinical trials in children are needed to increase our knowledge of the effects of medicines and to prevent the delayed or non-use of beneficial therapies. Clinical trials provide reliable evidence of treatment effects by rigorous controlled testing of interventions on human subjects. Paediatric trials are more challenging to conduct than trials in adults because of the paucity of funding, uniqueness of children and particular ethical concerns. Although current regulations and initiatives are improving the scope, quantity and quality of trials in children, there are still deficiencies that need to be addressed to accelerate radically equitable access to evidence-based therapies in children.     

人感染H7N9禽流感26例临床特征与病毒基因分析研究

目的探讨人感染H7N9禽流感病毒患者的流行病学和临床特征,以及病毒分子生物学特征。方法收集湖南省2013、2014年确诊的26例人感染H7N9禽流感病毒患者的资料,对人和禽分离的H7N9病毒进行鉴定和测序分析。结果26例患者中,发热和咳嗽是最常见的起病症状,所有患者均存在肺炎;20例(76.92%)出现急性呼吸窘迫综合征(ARDS),25例(96.15%)初诊时白细胞下降或正常,发病至开始进行抗病毒治疗的平均时间为10 d。10例死亡,病死率达38.46%。患者分离的H7N9病毒株测序分析表明,发生了H7基因Gln226Leu和Gly186Val替换,PB2基因Asp701Asn突变。结论急性呼吸系统损害是人感染H7N9禽流感的主要临床表现,活禽暴露是人感染H7N9禽流感的重要危险因素,H7N9禽流感病毒基因发生了部分位点的适应性突变,更容易从禽类向人跨种传播引起人类严重疾病,需加强病原学监测。     

224例不明原因发热患者病因分析

目的了解某院不明原因发热(FUO)患者病因,及其明确诊断的方法,为临床诊断和治疗FUO提供参考。方法应用血清学、细菌学、分子生物学、骨髓穿刺、组织活检,以及诊断性治疗等方法,对该院2008年1月—2014年7月收治的FUO住院患者进行临床诊断,回顾性分析224例FUO患者病因和最终诊断。结果最终明确病因者189例,占84.38%;未明确者35例,占15.62%。其中感染性疾病、结缔组织病、恶性肿瘤、其他类疾病分别占50.45%、18.75%、9.82%、5.36%。在感染性疾病中,细菌为主要病原体,其次为病毒;结缔组织病以系统性红斑狼疮和结节性多动脉炎为主;恶性肿瘤以血液系统肿瘤为主,而淋巴瘤最常见。189例确诊患者采用病原学检查者占30.16%,病理学检查者占24.34%,其他方法(综合分析)占20.11%。结论感染性疾病、结缔组织病、肿瘤为FUO的主要病因。