氨溴索伍用抗菌药物顺序与抗菌疗效的文献分析

摘 要本文综述了氨溴索药动学、药效学特点以及氨溴索与抗菌药物相互作用的文献,对氨溴索与抗菌药物的使用顺序进行了分析探讨。氨溴索与抗菌药物联合使用可提高抗菌药物在肺泡灌洗液(BALF)中的浓度;氨溴索对病原菌生物膜（BF）具有抑制和破坏作用,且氨溴索对BF的作用具有剂量依赖性,大剂量氨溴索安全性良好。临床上先应用氨溴索,再使用抗菌药物,可有利于提高抗菌药物在肺组织中的浓度,有利于抗菌药物进入病原菌BF内部,从而增强抗菌效果。针对氨溴索药品说明书,建议进一步修改和完善：①在药品说明书相关项下明确氨溴索与抗菌药物的用药顺序;②在说明书中增加氨溴索在不同适应症下的用药剂量;③明确大剂量氨溴索临床使用的安全性和有效性。     

Celecoxib is a substrate of CYP2D6: Impact on celecoxib metabolism in individuals with CYP2C9*3 variants

Celecoxib was characterized as a substrate of human cytochrome P450 (CYP) 2D6 in vitro. In recombinant CYP2D6, celecoxib hydroxylation showed atypical substrate inhibition kinetics with apparent K_m, K_i, and V_max of 67.2 μM, 12.6 μM, and 1.33 μM/min, respectively. In human liver microsomes (HLMs), a concentration-dependent inhibition of celecoxib hydroxylation by quinidine was observed after CYP2C9 and CYP3A4 were inhibited. In individual HLMs with variable CYP2D6 activities, a significant correlation was observed between celecoxib hydroxylation and CYP2D6-selective dextromethorphan O-demethylation when CYP2C9 and CYP3A4 activities were suppressed (r = 0.97, P < 0.0001). Molecular modeling showed two predominant docking modes of celecoxib with CYP2D6, resulting in either a substrate or an inhibitor. A second allosteric binding antechamber, which stabilized the inhibition mode, was revealed. Modeling results were consistent with the observed substrate inhibition kinetics. Using HLMs from individual donors, the relative contribution of CYP2D6 to celecoxib metabolism was found to be highly variable and dependent on CYP2C9 genotypes, ranging from no contribution in extensive metabolizers with CYP2C9*1*1 genotype to approximately 30% in slow metabolizers with allelic variants CYP2C9*1*3 and CYP2C9*3*3. These results demonstrate that celecoxib may become a potential victim of CYP2D6-associated drug-drug interactions, particularly in individuals with reduced CYP2C9 activity.     

早期亲子互动常用观察法评估量表研究进展

为儿童早期提供高质量的养育照护是保障儿童充分实现其未来潜能的重要因素,早期亲子互动作为养育照护的一个重要指标正在得到愈来愈多的关注。通过观察亲子互动,可以对亲子互动质量进行客观评价,以期发现其中存在的养育优缺点并予以科学指导。目前,国际上已有数十种用于探究亲子互动质量的观察法评估工具。其中,最常用且信效度较好的三种评估工具分别是:情绪水平量表(EAS)、亲子互动量表(PCI Scales)、儿童-养育者关系指数(CARE-Index)。本综述将系统介绍上述三种量表的框架背景、信效度及应用进展,以便为相关科研人员和临床医生选择合适的亲子互动评估量表提供参考。     

Nurses’ elicitation of patient error as a practice in training end‐stage renal patients in automated home peritoneal dialysis

As part of a reorganisation of the delivery of health care in Denmark therapies for chronic medical conditions are moved out of hospitals and disease‐specific patient education programmes instituted to train patients to assume responsibility for treating their disease at home, that is, perform tasks and functions traditionally done by healthcare professionals. Drawing on video‐recordings (90:25h) from a programme for self‐management of end‐stage renal disease through automated home peritoneal dialysis, the study employs conversation analysis to examine nurses’ instructional practices for providing patients with the necessary knowledge, skill and competences. Showing training to rely on an error‐based monitoring strategy, the study demonstrates that rather than solely waiting for random errors to emerge, nurses on occasion steer patients towards specific errors to bring about particular instructional opportunities. Surprising given the seriousness of the therapy, this elicitation of error is shown to reflect a deliberate instructional choice; nurses promote select errors to impart patients with an understanding of the procedural logic behind the therapy and medical technology. The study argues that training patients for chronic disease self‐management and providing them with a proficiency level, normally associated with certified professionals, necessitates pushing patients beyond what is strictly accurate and exposing them to medically delicate events.     

Co‐production in community mental health services: blurred boundaries or a game of pretend?

The concept of co‐production suggests a collaborative production of public welfare services, across boundaries of participant categories, for example professionals, service users, peer‐workers and volunteers. While co‐production has been embraced in most European countries, the way in which it is translated into everyday practice remains understudied. Drawing on ethnographic data from Danish community mental health services, we attempt to fill this gap by critically investigating how participants interact in an organisational set‐up with blurred boundaries between participant categories. In particular, we clarify under what circumstances the blurred boundaries emerge as believable. Theoretically, we combine Lamont and Molnár's (2002) distinction between symbolic boundaries and social boundaries with Goffman's (1974) microanalysis of “principles of convincingness”. The article presents three findings: (1) co‐production is employed as a symbolic resource for blurring social boundaries; (2) the believability of blurred boundaries is worked up through participants’ access to resources of validation, knowledge and authority; and (3) incongruence between symbolic and social boundaries institutionalises practices where participants merely act ‘as if’ boundaries are blurred. Clarification of the principles of convincingness contributes to a general discussion of how co‐production frames the everyday negotiation of symbolic and social boundaries in public welfare services.     

红酒多酚对细胞色素P4503A4介导的硝苯地平代谢的影响

目的体外研究红酒多酚成分对细胞色素P4503A4(CYP3A4)介导的硝苯地平代谢的影响。方法将红酒多酚、人肝微粒体及探针底物睾酮孵育后,用高效液相色谱法测定代谢产物6β-羟基睾酮的生成量,用来考察红酒多酚对CYP3A4抑制的浓度依赖性。将不同浓度红酒多酚、人肝微粒体与硝苯地平孵育,测定硝苯地平的减少率并计算IC₅₀值。在不同浓度硝苯地平存在下,绘制米氏曲线,得到红酒多酚存在时硝苯地平的代谢清除率CL_红酒(K_m-红酒/V_max-红酒),对比空白组,考察红酒多酚对硝苯地平代谢的影响。结果红酒多酚对CYP3A4存在明显的浓度依赖抑制效应(IC₅₀=18.29%)。在以硝苯地平为底物时,IC₅₀为25.04%。红酒多酚对硝苯地平的代谢清除率CL_红酒为14μL·min^-1·mg^-1,显著低于空白组(640μL·min^-1·mg^-1)。结论红酒多酚可通过抑制CYP3A4的活性,减少其对硝苯地平的代谢,具有诱导食物-药物不良反应的风险。     

肾移植术后免疫抑制药方案调整与患者教育的病例分析

目的探讨临床药师在肾移植术后免疫抑制药方案调整中的作用。方法临床药师参与1例肾移植术后免疫抑制药方案调整的过程,通过血药浓度监测、药物基因组学检测不断调整免疫抑制药他克莫司的给药剂量以及利用药物相互作用,使血药浓度达标。结果与结论临床药师通过参与整个治疗过程,利用治疗药物浓度监测、基因检测等在个体化用药中的作用和优势,提高治疗的疗效,避免药物不良反应的发生。     

临床试验尿液成瘾药物筛查探讨

尿液成瘾药物筛查是目前药物Ⅰ期临床试验和生物等效性试验纳入健康受试者的关键操作之一,也是保证受试者的安全、试验结果准确可靠的必要措施之一。虽然《化学药物临床药代动力学研究技术指导原则》等指南提出临床试验需要筛查成瘾药物,但都未明确指出尿液成瘾药物筛查的品种以及在临床试验中的意义。本文根据北京大学第一医院药物Ⅰ期临床试验研究室近几年开展的项目中尿液成瘾药物筛查品种以及筛查结果,分析与探讨尿液滥用药物筛查在临床试验中的必要性及重要意义。     

长链非编码RNA与微小RNA相互作用对调控疾病的研究进展

非编码RNA(ncRNA)与基因调控密切相关,ncRNA主要包括微小RNA(miRNA)和长链非编码RNA(lncRNA)。lncRNA与miRNA之间存在着相互调控关系,两者间的相互作用参与了众多疾病的发生发展。本文主要综述其在癌症、心血管疾病、免疫系统和神经系统疾病中的作用及其作用机制。