Pharmacokinetic modeling and simulation of etodolac following single oral administration in dogs

1. Etodolac is a nonsteroidal anti-inflammatory drug with selective cyclooxygenase-2 inhibition to treat pain and inflammation associated with osteoarthritis in humans and dogs. The aim of the study was to investigate the pharmacokinetics of etodolac following single oral administration of 200?mg to 10 healthy beagle dogs.

2. The plasma concentrations of etodolac were detected using liquid chromatography-tandem mass spectrometry. Pharmacokinetic analysis was conducted using the noncompartmental method and modeling approaches.

3. Etodolac was rapidly absorbed (T_max?=?0.85?h, K_a?=?1.49?h^?1) and slowly eliminated (T_1/2?=?39.55?h) following oral administration to the dogs. A two-compartment pharmacokinetic model with first-order absorption and elimination rate constants was successfully explained for the pharmacokinetic aspects of etodolac in dogs. From a Monte Carlo simulation (1000 repetitions), the accumulation index and AUC_τ at steady state were predicted as 1.60 [90% confidence intervals (CI), 1.24–2.81] and 408.18?ng·hr/mL [90% CI, 271.26–590.58?ng·hr/mL], respectively.

4. This study will help to enact a more accurate optimal dosing regimen of etodolac in dogs with osteoarthritis, and may be useful in developing a novel formulation of etodolac for human in the future.

     

Improving Surgical Training

Improving Surgical Training is a programme piloting an innovative, evidence-based approach to training. It was developed in response to the Shape of Training report which reviewed postgraduate training and recommended changes in medical education to meet the demands of the modern NHS. A series of initiatives have been developed to enhance the experience for surgical trainees not only to encourage a more focussed and supported method, but also to improve their job satisfaction. The initiatives have combined a greater emphasis on time for training provided by trainers with allocated time for training with multidisciplinary teamworking and the use of technology enhanced learning with simulation of both technical and non-technical skills. The pilot started in 2018 with core training in general surgery and has been expanded to include vascular surgery, urology and trauma and orthopaedics over the last 2 years. Initial feedback from both trainees, trainers and schools of surgery have identified different challenges to aid implementation. The programme is being very carefully evaluated by an independent company as well as careful oversight by the General Medical Council which are paramount to its success.     

中日友好医院分型股骨头坏死腓骨植入治疗的三维有限元分析

文题释义：股骨头坏死中日友好医院分型的有限元分析：根据李子荣等提出的中日友好医院分型，建立股骨头坏死三维模型，分为 M型(内侧型)、C型(中央型)和 L型(外侧型)，其中 L型包括L1型(次外侧型)、L2型(极外侧型)和 L3型(全头型)。通过对建立的模型进行有限元分析，为该分型的保髋治疗提供了一定力学依据，显示外侧柱的存留是精准预防塌陷的重要因素，为进一步实现个体化治疗提供力学基础。 腓骨支撑坏死股骨头保髋手术：是对于早中期股骨头坏死需要保留股骨头患者进行的一种手术方式。首先需对股骨头进行髓芯减压，清除一定坏死骨，空腔填塞松质骨(髂骨为主)，打压结实后植入腓骨(异体或自体)支撑，给坏死区的提供力学支撑及生物学修复，预防股骨头进一步坏死及塌陷。 背景：研究报道股骨头坏死的保髋疗效与外侧柱存留密切相关，中日友好医院分型是根据三柱结构确立的，对股骨头塌陷的预测准确性高。 目的：建立股骨头坏死中日友好医院分型各分型仿真的三维有限元模型，通过有限元分析各分型腓骨植入的力学变化，探讨外侧柱存留对保髋疗效的意义，为该分型的塌陷精准预测提供基础。 方法：建立正常股骨头、中日友好医院分型(M型、C型、L1型、L2型、L3型)股骨头坏死及其腓骨植入3组11种三维有限元模型，运用ANSYS软件进行有限元分析计算，观察各组模型的最大应力值、最大位移值及股骨头内部载荷传递模式。 结果与结论：①坏死组位移最大，应变最大，且因坏死分型不同而位移不同，位移变化如下：M型相似文献   

General practice pharmacists in England: Integration,mediation and professional dynamics

BackgroundA number of key publications in recent years have advocated a more integrated vision of UK primary care involving increased multi-professional communication and understanding. This has resulted in a marked change in the roles being undertaken by pharmacists. Community pharmacists have traditionally provided a medicine supply function and treated minor ailments in addition to delivering a suite of locally commissioned services; however these functions have not necessarily been part of a programme of care involving the other clinicians associated with the patient. An integrated model of care would see much closer working between pharmacy and general practice but also with pharmacists not only working with, but in the practice, in an enhanced patient-facing role, trained as independent prescribers. This has implications for the dynamics amongst professionals in this environment.ObjectivesThis exploratory multiple case study attempts to explore these changing dynamics across ten GP surgeries throughout the South-East of England.MethodsSemi-structured, in-depth interviews were conducted with one nurse, one pharmacist and one physician from each clinic, and survey data was collected from 38 patients who had appointments with a pharmacist.ResultsThe data suggested that the pharmacists who had enhanced roles perceived some uncertainty about their professional role and identity, which resulted in instability and insecurity and that this uncertainty led to both professional and interprofessional tension with their primary care colleagues. The survey data revealed that n = 35 (92%) patients stated they were ‘very satisfied’ or ‘satisfied’ with their appointment. And n = 37 (97%) were ‘very comfortable’ or ‘comfortable’ discussing their medications with the pharmacist. In addition, 36 patients (95%) reported that they strongly agreed or agreed with the clinical recommendations made by the pharmacist.ConclusionsThese findings are discussed in relation to role expansion and professional/interprofessional relations before key practical suggestions are offered.     

The scope of computerized simulation in competency-based maxillofacial training: a systematic review

Oral and maxillofacial surgery (OMS) teaching is set to undergo a paradigm shift towards competency-based training. With increasing focus on resident skill development and patient safety, computerized simulators are likely to play a more mainstream role in OMS training. A systematic review of the available literature was conducted, in accordance with the PRISMA guidelines, to highlight the scope of computerized simulation in OMS teaching. A PubMed search was performed by two independent reviewers, and 35 articles published in English between 2010 and 2021 that reported the use of computerized simulation for teaching maxillofacial procedures were included in the analysis. Eight articles on minor oral surgery, seven on orthognathic surgery, five on maxillofacial trauma, five on cleft lip and palate surgery, three articles each on nerve block techniques, endoscopic procedures, and reconstructive surgery, and one article on fibre-optic intubation reported the use of computerized simulation that can be applied to OMS training. Ten randomized controlled trials were identified in the search. However there was marked heterogeneity among the studies. Simulator training for skill acquisition mentored by an expert OMS educator could offer holistic resident training; however more studies that test common themes of resident training such as knowledge acquisition and skill development are necessary.     

替考拉宁在中国成人患者中的群体药动学研究

目的建立中国成年患者的替考拉宁(teicoplanin,TEC)群体药动学(population pharmacokinetics,PPK)模型,考察TEC药动学参数的影响因素。方法前瞻性收集139例革兰阳性球菌感染患者静脉注射TEC后的222份常规监测血药浓度和相关信息,采用一级消除的一室模型进行数据拟合,并应用非线性混合效应模型(nonlinear mixed effect model,NONMEM)程序建立PPK模型。采用Bootstrap、正态预测分布误差法(normalized predictive distribution error,NPDE)进行最终模型评价。利用蒙特卡洛模拟法对给药方案进行优化。结果确定了肌酐清除率(creatinine clearance,CLcr)、白蛋白(albumin,ALB)为影响TEC清除率的主要因素。最终模型为:CL(L·h^-1)=1.24×(CLcr/77)0.564×31/ALB;V(L)=69.2。验证表明,模型稳定、有效,且有较好的预测效能。对于不同ALB和CLcr的多数患者起始负荷剂量400 mg/q12h,iv,3次,维持剂量400~800 mg·d^-1的给药方案可达有效治疗谷浓度。严重感染者需调整负荷剂量至800 mg/q12h,iv,3次,维持剂量400~800 mg·d^-1的给药方案来确保血药浓度达到15 mg·L^-1以上。结论本实验报道了CLcr、ALB对TEC清除率有显著影响,所建模型对TEC在中国成人患者中实现个体化给药具有重要应用价值。