Clinical practice guidelines for therapeutic drug monitoring of arbekacin: A consensus review of the Japanese Society of Chemotherapy and the Japanese Society of Therapeutic Drug Monitoring

Arbekacin (ABK) was approved and widely used in Japan for treatment of patients infected with MRSA, and TDM was introduced in clinical practice. The Japanese Society of Chemotherapy and the Japanese Society of Therapeutic Drug Monitoring decided to develop a clinical practice guidelines for TDM of ABK for the following reasons. First, although the daily dose of 150–200 mg was approved in Japan, recent PK-PD studies revealed that higher serum concentration is required to achieve better clinical efficacy and several findings concerning the usefulness of higher dosage regimen have obtained recently. Second, although maximal concentrations that obtained immediately after the end of administration (C_max) was generally adopted, the serum concentration at 1 h after initiation of administration [peak serum concentration (C_peak)] proved to be more suitable as an efficacy indicator of aminoglycosides. Lastly, as ABK is approved only in Japan, no international practice guideline for TDM has not been available in ABK to date. This guideline evaluated the scientific data associated with serum ABK monitoring and provided recommendations based on the available evidence. Potential limitations of this guideline, however, include the findings that few prospective clinical trials of TDM of ABK are available in the treatment of MRSA infections and that most of the published literature describes observational studies.     

Determination of Voriconazole Serum Concentration by Bioassay,a Valid Method for Therapeutic Drug Monitoring for Clinical Laboratories

We describe here a simple, fast, and reliable bioassay method for therapeutic drug monitoring of voriconazole. Fifty-eight clinical and external quality control samples were evaluated with this microbiological assay, and results were compared with those obtained with a previously validated chromatographic method. A good correlation between both assays was observed. This particular microbiological method was demonstrated to be simple and offers enough precision and accuracy to perform voriconazole therapeutic drug monitoring in laboratories without specialized equipment.     

脑卒中水中运动治疗中国循证临床实践指南(2019版)

脑卒中是我国康复医学从业者日常工作中接触最多的疾病之一,具有发病率高、致残率高、死亡率高、复发率高等特点[1-3]。世界范围内,脑卒中是造成长期残疾的首要原因,无论是缺血性脑卒中还是出血性脑卒中,均可能造成运动、感觉、吞咽、言语、认知等功能障碍,给患者、家庭及社会造成巨大的负担[4-6]。目前,以“卒中单元”为主要形式的多学科跨专业综合治疗模式是脑卒中康复的主体,其中,物理治疗是脑卒中康复的重要组成部分[5,7]。近年来,一种较新的物理治疗形式——水中运动治疗(aquatic therapeutic exercise),逐渐受到重视并推广普及[8-10]。     

Methadone Overdose and Cardiac Arrhythmia Potential: Findings From a Review of the Evidence for an American Pain Society and College on Problems of Drug Dependence Clinical Practice Guideline

The number of deaths associated with methadone use increased dramatically in parallel with marked increases in its use, particularly for treatment of chronic pain. To develop a clinical guideline on methadone prescribing to reduce potential harms, the American Pain Society commissioned a review of various aspects related to methadone safety. This article summarizes evidence related to unintentional overdose due to methadone and harms related to cardiac arrhythmia potential. We searched Ovid MEDLINE, the Cochrane Library, and PsycINFO databases through January 2014 for studies assessing harms associated with methadone use; we judged 70 studies to be relevant and to meet inclusion criteria. The majority of studies on overdose and cardiac arrhythmia risk are observational and provide weak evidence on which to base clinical guidelines. In patients prescribed methadone for treatment of opioid dependence, data suggest that mortality benefits related to reduction in illicit drug use outweigh harms. Despite epidemiologic data showing marked increases in the numbers of methadone-related deaths that have been primarily attributed to increased use of methadone for chronic pain, evidence on methadone and mortality risk in this population has been somewhat contradictory. There is some evidence that recent initiation of methadone, psychiatric admissions, and concomitant use of benzodiazepines are associated with a higher risk for overdose. Evidence on cardiac risks is primarily limited to case reports of torsades de pointes, primarily in patients on high doses of methadone, and to studies showing an association between methadone use and prolongation of QTc intervals. Research is needed to understand the effectiveness of dosing methods, electrocardiogram monitoring, and other risk mitigation strategies in patients prescribed methadone.PerspectiveThis systematic review synthesizes the evidence related to methadone use and risk for overdose and cardiac arrhythmia. Findings regarding the association between methadone use and QTc interval prolongation and risk factors for methadone-associated overdose suggest potential targets for risk mitigation strategies, though research is needed to determine the effectiveness of such strategies at reducing adverse outcomes.     

Methadone Safety: A Clinical Practice Guideline From the American Pain Society and College on Problems of Drug Dependence,in Collaboration With the Heart Rhythm Society

Methadone is used for the treatment of opioid addiction and for treatment of chronic pain. The safety of methadone has been called into question by data indicating a large increase in the number of methadone-associated overdose deaths in recent years that has occurred in parallel with a dramatic rise in the use of methadone for chronic pain. The American Pain Society and the College on Problems of Drug Dependence, in collaboration with the Heart Rhythm Society, commissioned an interdisciplinary expert panel to develop a clinical practice guideline on safer prescribing of methadone for treatment of opioid addiction and chronic pain. As part of the guideline development process, the American Pain Society commissioned a systematic review of various aspects related to safety of methadone. After a review of the available evidence, the expert panel concluded that measures can be taken to promote safer use of methadone. Specific recommendations include the need to educate and counsel patients on methadone safety, use of electrocardiography to identify persons at greater risk for methadone-associated arrhythmia, use of alternative opioids in patients at high risk of complications related to corrected electrocardiographic QTc interval prolongation, careful dose initiation and titration of methadone, and diligent monitoring and follow-up. Although these guidelines are based on a systematic review, the panel identified numerous research gaps, most recommendations were based on low-quality evidence, and no recommendations were based on high-quality evidence.PerspectiveThis guideline, based on a systematic review of the evidence on methadone safety, provides recommendations developed by a multidisciplinary expert panel. Safe use of methadone requires clinical skills and knowledge in use of methadone to mitigate potential risks, including serious risks related to risk of overdose and cardiac arrhythmias.     

Research Gaps on Methadone Harms and Comparative Harms: Findings From a Review of the Evidence for an American Pain Society and College on Problems of Drug Dependence Clinical Practice Guideline

Methadone-associated overdose deaths have dramatically increased. In order to inform an evidence-based clinical practice guideline to improve safety of methadone prescribing, the American Pain Society commissioned a systematic review on various aspects related to methadone safety. We searched Ovid MEDLINE, Cochrane Library, and PsycINFO databases through July 2012 to identify studies that addressed 1 or more of 17 Key Questions related to methadone safety; an update search was performed in 2014 for new studies related to methadone-related overdose and risks related to cardiac arrhythmias. A total of 168 studies met inclusion criteria for the review. The purpose of this article is to highlight critical research gaps in the literature related to methadone safety. These include lack of evidence on risk factors associated with methadone-overdose deaths and adverse events, limited evidence to evaluate the comparative mortality of methadone versus other opioids, insufficient evidence to fully understand the harms associated with methadone use during pregnancy, and insufficient evidence to determine effects of risk mitigation strategies such as electrocardiogram monitoring, strategies for managing patients with prolonged QTc intervals on screening, urine drug testing, alternative dosing regimens for initiation and titration of therapy, and timing of follow-up. Therefore, most guideline recommendations are based on weak evidence. More research is needed to guide safe methadone prescribing practices and decrease the adverse events associated with methadone.PerspectiveThis article summarizes critical research gaps in the literature related to methadone safety, based on a systematic review commissioned by the American Pain Society. Critical research gaps were identified in a number of areas, highlighting the need for additional research to guide safer prescribing and risk mitigation strategies.     

ICU经口气管插管口腔护理实践指引的制订及临床应用

目的制订ICU经口气管插管口腔护理实践指引(以下简称"指引"),探讨其应用效果。方法通过查阅病历资料、访谈医护人员及检索文献等方法,归纳分析经口气管插管口腔护理实践中的常见问题,并依据文献指南、医院内感染制度及临床实践需求制订"指引"。2014年1-10月,便利抽取浙江大学医学院附属第一医院综合ICU两个护理单元的127例经口气管插管患者为研究对象,其中单号楼层为对照组,采用常规口腔护理方法;双号楼层为观察组,在对照组基础上应用"指引"进行口腔护理。比较两组患者第1、3、5天当日首次口腔护理前的Beck口腔评分(Beck oral assessment scale,BOAS)及呼吸机相关性肺炎(ventilator-associated pneumonia,VAP)的发生率。结果观察组患者第3、5天当日首次口腔护理前的BOAS评分及VAP的发生率均低于对照组,差异均有统计学意义(均P0.05)。结论经口气管插管口腔护理实践指引有较好的临床指导作用,值得推广应用。     

医院药物不良反应监察工作模式的研究与临床实践

药物不良反应(ADR)监察是医院药学监护工作中的一项重要内容。目前国内医院集中监察ADR仅限于人工或计算机网络技术对于不良反应报告表的搜集、统计，对于病人发生ADR后的详细用药情况、药物对原患疾病的影响、ADR的治疗等缺乏系统的药学监护。如何充分发挥临床药师的作用，更好地开展这项工作，目前国内尚无固定成熟的模式。我院在开展这项工作的实践中，逐步摸索出ADR监察与临床药学监护为一体的工作模式，收到了较好的效果。现总结体会如下。     

美国退伍军人事务部/国防部成人脑卒中康复治疗管理临床实践指南(执行简写版)

背景专家委员会制定的卒中康复指南应用于退伍军人健康管理部门及国防部卫生保健系统。方法根据以前发表的指南，委员会利用美国预防服务特别工作组制定的标准。评价了截至到2002年发表的文献。指南根据临床随机化实验、非对照性研究等证据提出建议（如缺乏确定的数据则根据专家组的建议）。结果 Ⅰ级水平的建议包括：在多学科康复环境中或卒中单元中传递卒中治疗，通过NIHSS对卒中患者进行评价，早期启动康复治疗，对吞咽困难患者进行吞咽功能筛查，积极进行二级预防，预防深静脉血栓等。推荐应用标准化的评价上具制定适合每个患者的全面的治疗计划。强烈建议进行抗抑郁及情感波动方面的治疗。语言治疗师应评价患者的交流及认知障碍。并在需要时提供治疗。患者、家属及护理者是康复小组的重要成员，应当介入康复的全部疗程。这些建议在以下网站可查询：http：／／stroke．ahajournals．org／cgi／content／full／36／9／e100。并附有每项建议的全文证据表。结论这些建议应平等地应用于所有临床环境中的所有卒中康复患者，而不是仅针对联邦医疗系统的临床问题或资源。     

Pharmacokinetic Modeling and Optimal Sampling Strategies for Therapeutic Drug Monitoring of Rifampin in Patients with Tuberculosis

Rifampin, together with isoniazid, has been the backbone of the current first-line treatment of tuberculosis (TB). The ratio of the area under the concentration-time curve from 0 to 24 h (AUC_0–24) to the MIC is the best predictive pharmacokinetic-pharmacodynamic parameter for determinations of efficacy. The objective of this study was to develop an optimal sampling procedure based on population pharmacokinetics to predict AUC_0–24 values. Patients received rifampin orally once daily as part of their anti-TB treatment. A one-compartmental pharmacokinetic population model with first-order absorption and lag time was developed using observed rifampin plasma concentrations from 55 patients. The population pharmacokinetic model was developed using an iterative two-stage Bayesian procedure and was cross-validated. Optimal sampling strategies were calculated using Monte Carlo simulation (n = 1,000). The geometric mean AUC_0–24 value was 41.5 (range, 13.5 to 117) mg · h/liter. The median time to maximum concentration of drug in serum (T_max) was 2.2 h, ranging from 0.4 to 5.7 h. This wide range indicates that obtaining a concentration level at 2 h (C₂) would not capture the peak concentration in a large proportion of the population. Optimal sampling using concentrations at 1, 3, and 8 h postdosing was considered clinically suitable with an r² value of 0.96, a root mean squared error value of 13.2%, and a prediction bias value of −0.4%. This study showed that the rifampin AUC_0–24 in TB patients can be predicted with acceptable accuracy and precision using the developed population pharmacokinetic model with optimal sampling at time points 1, 3, and 8 h.     

Dried Blood Spot Analysis for Therapeutic Drug Monitoring of Linezolid in Patients with Multidrug-Resistant Tuberculosis

Linezolid is a promising antimicrobial agent for the treatment of multidrug-resistant tuberculosis (MDR-TB), but its use is limited by toxicity. Therapeutic drug monitoring (TDM) may help to minimize toxicity while adequate drug exposure is maintained. Conventional plasma sampling and monitoring might be hindered in many parts of the world by logistical problems that may be solved by dried blood spot (DBS) sampling. The aim of this study was to develop and validate a novel method for TDM of linezolid in MDR-TB patients using DBS sampling. Plasma, venous DBS, and capillary DBS specimens were obtained simultaneously from eight patients receiving linezolid. A DBS sampling method was developed and clinically validated by comparing DBS with plasma results using Passing-Bablok regression and Bland-Altman analysis. This study showed that DBS analysis was reproducible and robust. Accuracy and between- and within-day precision values from three validations presented as bias and coefficient of variation (CV) were less than 17.2% for the lower limit of quantification and less than 7.8% for other levels. The method showed a high recovery of approximately 95% and a low matrix effect of less than 8.7%. DBS specimens were stable at 37°C for 2 months and at 50°C for 1 week. The ratio of the concentration of linezolid in DBS samples to that in plasma was 1.2 (95% confidence interval [CI], 1.12 to 1.27). Linezolid exposure calculated from concentrations DBS samples and plasma showed good agreement. In conclusion, DBS analysis of linezolid is a promising tool to optimize linezolid treatment in MDR-TB patients. An easy sampling procedure and high sample stability may facilitate TDM, even in underdeveloped countries with limited resources and where conventional plasma sampling is not feasible.