小儿湿疹局部用中药新药临床试验设计与评价技术指南

《儿科常见疾病中药新药临床试验设计与评价技术指南》是中华中医药学会儿科分会临床评价学组制定的、指导儿科中药Ⅱ期、Ⅲ期临床试验和上市后有效性再评价方案设计的、具有病种特色的系列临床评价技术指南,旨在推动儿科中药临床试验设计与评价水平的提高,并为临床提供安全有效的儿童用药。采用世界卫生组织(WHO)推荐的“共识会议法”和美国国立卫生研究院(NIH)发展共识方案(GPP)有关原则,国内全部18 个国家药物临床试验机构中医儿科专业的临床儿科专家以及国内相关临床评价专家参加了急性上呼吸道感染、急性支气管炎、支气管哮喘、反复呼吸道感染、厌食、轮状病毒性肠炎、注意缺陷-多动障碍、抽动障碍、遗尿症、手足口病、湿疹11 个儿科常见病种指南的起草或多次提出修改建议,历经3 年反复完善,最终形成共识,并由中华中医药学会儿科分会于2013 年10 月发布。本指南从研究背景、研究目标、总体设计、诊断标准、受试者的选择、给药方案、安全性评价、有效性评价、试验流程、数据管理与统计分析、质量保证、相关伦理学要求、试验结束后的医疗措施、资料保存等方面阐述了小儿湿疹中药新药临床试验的设计与评价技术要点,期望能为申办者与研究者在临床试验方案设计中提供指导。     

口服降糖药物在妊娠糖尿病治疗中的临床应用及对控制血糖水平的作用分析

目的妊娠糖尿病74例患者,治疗统计,讨论口服降糖药物的效果。方法2019年5—9月搜集患者库妊娠糖尿病患者并选出74例分两组(随机数表法),对照组皮下注射胰岛素,观察组在上述基础上口服二甲双胍。比较两组血糖、母婴结局。结果病情对比血糖,两组治疗前FPG、2 hPG、NPG水平差异无统计学意义(P>0.05);观察组治疗后FPG、2 hPG、NPG水平相对于对照组均较低,差异有统计学意义(P<0.05);效果对比母婴结局,观察组不良妊娠结局发生率相对于对照组较低(5.41%vs 21.62%),差异有统计学意义(P<0.05);观察组产妇Barthel指数、新生儿出生时、出生5 min时Apgar评分相对于对照组均较高,差异有统计学意义(P<0.05)。结论口服降糖药物二甲双胍可改善妊娠糖尿病患者血糖控制情况,降低血糖水平,改善妊娠结局。     

Nanocrystals for enhancement of oral bioavailability of poorly water-soluble drugs

Nanocrystals, a carrier-free colloidal delivery system in nano-sized range, is an interesting approach for poorly soluble drugs. Nanocrystals provide special features including enhancement of saturation solubility, dissolution velocity and adhesiveness to surface/cell membranes. Several strategies are applied for nanocrystals production including precipitation, milling, high pressure homogenization and combination methods such as NanoEdge™, SmartCrystal and Precipitation-lyophilization-homogenization (PLH) technology. For oral administration, many publications reported useful advantages of nanocrystals to improve in vivo performances i.e. pharmacokinetics, pharmacodynamics, safety and targeted delivery which were discussed in this review. Additionally, transformation of nanocrystals to final formulations and future trends of nanocrystals were also described.     

2型糖尿病老年患者降糖药物使用合理性分析

目的探讨2型糖尿病老年患者降糖药物临床使用的合理性。方法选取2019年3月—2020年3月期间的640例2型糖尿病老年患者作为研究对象。回顾性分析患者的临床资料,统计所有患者的降糖药物使用情况、用药频度、用药合理性、安全性。结果2型糖尿病老年患者的常用降糖药物,根据用药频度,分别为阿卡波糖、二甲双胍、瑞格列奈、格列美脲、格列齐特、格列吡嗪。640份处方中,合理598份,合理率93.44%;不合理42份,不合理率6.56%;不合理处方中,药物用法不合理23份3.59%,书写不规范10份1.56%、用药剂量不合理5份0.78%、药物数量不合理3份0.47%、药物联用不合理1份0.16%。640例2型糖尿病老年患者中,不良反应包括胃肠道反应85例13.28%、低血糖55例8.59%,便秘50例7.81%,头晕乏力23例3.59%,贫血3例0.47%,乳酸性酸中毒1例0.16%。结论2型糖尿病老年患者降糖药物的临床用药合理性较好,但存在药物用法不合理、处方书写不规范、用药剂量不合理等问题,需针对性地预防,提高临床用药合理性、安全性。     

伴心房颤动的老老年高血压患者降压药服药依从性不良影响因素分析

目的探讨伴心房颤动(房颤)的老老年高血压患者降压药服药依从性不良的影响因素。方法连续入选2018年10月至2019年2月期间在阜外医院就诊的合并房颤的老老年高血压患者共110例。通过电子病历系统收集患者一般情况及临床资料,应用量表评估患者焦虑、抑郁、认知功能状态、社会支持度以及降压药服药依从性。根据依从性的不同将患者分为依从性良好组与依从性不良组。比较两组患者一般情况及临床资料,行Logistic回归分析明确依从性不良预测因素。结果107例患者完成问卷,41.1%的患者服用降压药依从性不良。多因素Logistic分析提示,抑郁、认知功能损害为依从性不良的预测因素[优势比(oddsratio,OR)=4.16,95%置信区间(confidenceinterval,CI)1.39~12.44,P<0.05;0R=4.26,95%CI 1.39~12.98,P<0.05],焦虑、开展服药自我提醒以及社会支持评分>35分是依从性良好的预测因索(OR=0.23,95%CI 0.08~0.69,P<0.01;0R=0.17,95%CI 0.04~0.62,P<0.01;OR=0.16,95%CI 0.06~0.45,P<0.01)。结论伴房颤的老老年高血压患者降压药服药依从性总体不良。抑郁和认知功能损害为依从性不良的预测因素,焦虑和开展服药自我提醒以及社会支持评分>35分是依从性良好的预测因素。     

Developing a Conversation Aid to Support Shared Decision Making: Reflections on Designing Anticoagulation Choice

Patient-centered care requires that treatments respond to the problematic situation of each patient in a manner that makes intellectual, emotional, and practical sense, an achievement that requires shared decision making (SDM). To implement SDM in practice, tools—sometimes called conversation aids or decision aids—are prepared by collating, curating, and presenting high-quality, comprehensive, and up-to-date evidence. Yet, the literature offers limited guidance for how to make evidence support SDM. Herein, we describe our approach and the challenges encountered during the development of Anticoagulation Choice, a conversation aid to help patients with atrial fibrillation and their clinicians jointly consider the risk of thromboembolic stroke and decide whether and how to respond to this risk with anticoagulation.     

Norovirus antivirals: Where are we now?

Human noroviruses inflict a significant health burden on society and are responsible for approximately 699 million infections and over 200 000 estimated deaths worldwide each year. Yet despite significant research efforts, approved vaccines or antivirals to combat this pathogen are still lacking. Safe and effective antivirals are not available, particularly for chronically infected immunocompromised individuals, and for prophylactic applications to protect high-risk and vulnerable populations in outbreak settings. Since the discovery of human norovirus in 1972, the lack of a cell culture system has hindered biological research and antiviral studies for many years. Recent breakthroughs in culturing human norovirus have been encouraging, however, further development and optimization of these novel methodologies are required to facilitate more robust replication levels, that will enable reliable serological and replication studies, as well as advances in antiviral development. In the last few years, considerable progress has been made toward the development of norovirus antivirals, inviting an updated review. This review focuses on potential therapeutics that have been reported since 2010, which were examined across at least two model systems used for studying human norovirus or its enzymes. In addition, we have placed emphasis on antiviral compounds with a defined chemical structure. We include a comprehensive outline of direct-acting antivirals and offer a discussion of host-modulating compounds, a rapidly expanding and promising area of antiviral research.     

Inhibitory effects of aspirin and indometacin on the growth of Helicobacter pylori in vitro

OBJECTIVE: The interactions between non‐steroidal anti‐inflammatory drugs and Helicobacter pylori have not been sufficiently documented to date. The aim of this study was to investigate the possible effects of aspirin and indometacin on the growth of H. pylori and to determine the effects of aspirin on the susceptibility of H. pylori to some antimicrobials. METHODS: Kinetic studies were performed by inoculating strains of H. pylori in brucella broth with different concentrations of aspirin and indometacin. Growth of bacteria in the broth was assessed spectrophotometrically and by viable colony counts after incubation for 24 and 48 h. Bacterial morphology was determined by Gram stain under light microscopy. The minimal inhibitory concentration (MIC) of aspirin and indometacin was determined by the standard agar dilution method. The MIC of amoxicillin, clarithromycin and metronidazole was measured in the presence and absence of aspirin by the E‐test method. RESULTS: Kinetic studies revealed that aspirin and indometacin inhibited the growth of H. pylori in a dose‐dependent manner. The bactericidal activity of these agents was expressed by cell lysis. Aspirin at 400 µg/mL produced an almost 2‐log decrease in the number of CFU/mL at 48 h. Similar inhibitory effects were obtained when 100 µg/mL indometacin was tested. The MIC at which 90% of H. pylori was inhibited was 512 µg/mL and 128 µg/mL for aspirin and indometacin, respectively. Increased susceptibility of H. pylori to amoxicillin, clarithromycin and metro­nidazole was found in the presence of aspirin. CONCLUSIONS: Aspirin and indometacin could significantly inhibit the growth of H. pylori when incubated in brucella broth in vitro. A subinhibitory concentration of aspirin enhanced the susceptibility of H. pylori to some antimicrobial agents.