Étude de faisabilité : l’utilisation de l’imagerie médicale en éducation thérapeutique en radiothérapie

PurposeAssess the feasibility of a randomized controlled trial (RCT) exploring the use of medical imaging as a therapeutic education (TPE) intervention in external radiation therapy.Materials and methodsExperimental feasibility trial of “RCT” type carried out in a single-center, between November 2019 and March 2020, following adult patients treated by thoracic radiotherapy. In addition to the information usually given, the experimental group benefited from an intervention consisting in the visualization of their own medical images using the open-source software “Stone of Orthanc”.ResultsForty-nine patients were recruited with a refusal rate of 8.16% (4/49). 20 patients were withdrawn from the study for health reasons (COVID), 10 for medical reasons. All the remaining 15 participants completed the process. Although not significant, the experimental group showed a median gain in the perception of knowledge compared to the control group (+ 1.9 (1.6 – 2.2)) vs (+ 1.4 (1.4 – 1.8)), as well as a decrease in scores related to anxiety (? 3.0 (?4.5 - (?2.0)) vs ? 1.0 (?5.0 - 0.0)) and emotional distress ((? 5.0 (? 7.5 - (? 3.5)) vs (? 2.0 (? 5.0 - (? 1.0)) A significant reduction (p = 0.043) is observed for the depression score ((? 2.0 (?3.0 - (?1.5)) vs (0.0 (0.0 – 0.0)).ConclusionThis study demonstrates the feasibility of the project, with promising preliminary results. Some adaptations in order to conduct a larger-scale RCT are highlighted.     

不完全契约理论视阈下某跨区域医联体核心医院运行效率评价研究

目的对某跨区域医联体核心医院的运行效率进行评价，以不完全契约理论为分析视角探讨影响因素，为深化医联体建设提供借鉴和参考。方法收集2014年-2021年核心医院相关数据，采用DEA数据分析方法，计算运行效率变化情况。结果核心医院各项投入明显增加，医疗业务产出同步增长，医院运行效率经历了动态波动后持续向好。结论通过构建管理共同体，逐步优化契约，争取医保政策支持，合作共建初见成效。     

Glucose starvation induces resistance to metformin through the elevation of mitochondrial multidrug resistance protein 1

Metformin, a drug for type 2 diabetes mellitus, has shown therapeutic effects for various cancers. However, it had no beneficial effects on the survival rate of human malignant mesothelioma (HMM) patients. The present study was performed to elucidate the underlying mechanism of metformin resistance in HMM cells. Glucose‐starved HMM cells had enhanced resistance to metformin, demonstrated by decreased apoptosis and autophagy and increased cell survival. These cells showed abnormalities in mitochondria, such as decreased ATP synthesis, morphological elongation, altered mitochondrial permeability transition pore and hyperpolarization of mitochondrial membrane potential (MMP). Intriguingly, Mdr1 was significantly upregulated in mitochondria but not in cell membrane. The upregulated mitochondrial Mdr1 was reversed by treatment with carbonyl cyanide m‐chlorophenyl hydrazone, an MMP depolarization inducer. Furthermore, apoptosis and autophagy were increased in multidrug resistance protein 1 knockout HMM cells cultured under glucose starvation with metformin treatment. The data suggest that mitochondrial Mdr1 plays a critical role in the chemoresistance to metformin in HMM cells, which could be a potential target for improving its therapeutic efficacy.     

Marmoset cytochrome P450 2B6, a propofol hydroxylase expressed in liver

1. The common marmoset (Callithrix jacchus) is a useful experimental animal to evaluate the pharmacokinetics of drug candidates. Cytochrome P450 (P450) 2B enzyme in marmoset livers has been identified; however, only limited information on the enzymatic properties and distribution has been available.

2. Marmoset P450 2B6 amino acids showed high sequence identities (>86%) with those of primates including humans and cynomolgus monkeys. Phylogenetic analysis using amino acid sequences indicated that marmoset P450 2B6 was closer to human and cynomolgus monkey P450 2B6 than to P450 2B orthologs of other species, including pigs, dogs, rabbits and rodents.

3. Quantitative polymerase chain reaction analysis using specific primers showed P450 2B6 mRNA predominantly expressed in livers among the five marmoset tissues, similar to those of humans and cynomolgus monkeys.

4. Marmoset P450 2B6 heterologously expressed in Escherichia coli membranes oxidized 7-ethoxycoumarin, pentoxyresorufin, propofol and testosterone, at roughly similar rates to those of humans and/or cynomolgus monkeys. A high capacity of marmoset P450 2B6 with propofol 4-hydroxylation (at low ionic strength conditions) with a low K_m value was relatively comparable to that for marmoset livers.

5. These results collectively indicated a high propofol 4-hydroxylation activity of P450 2B6 expressed in marmoset livers.

     

Current state of biologic pharmacovigilance in the European Union: improvements are needed

Introduction: Pharmacovigilance is essential to monitoring the safety profiles of authorized medicines. Compared with small-molecule drugs, biological drugs are more complex, more susceptible to structural variability due to manufacturing processes, and have the potential to induce immune-related reactions, underscoring the importance of safety monitoring for these products. Although highly similar to reference products, biosimilars are not expected to be structurally identical. For these reasons, proper reporting of potential adverse drug reactions (ADRs) using distinguishable names and batch numbers is essential for accurate tracing of all biological drugs. To address the need for robust pharmacovigilance, the European Parliament and Council of the European Union provided legislation regarding pharmacovigilance of biologics in 2010.

Areas covered: This narrative review examines the current state of pharmacovigilance for biologics in the European Union (EU) and discusses relevant information on pharmacovigilance of biosimilars, the current EU pharmacovigilance system, and areas that could be improved.

Expert opinion: Although steps have been taken to improve pharmacovigilance of biologics in the EU, several enhancements can still be made, including additional training for healthcare professionals on ADR reporting, the use of 2D barcodes that enhance traceability, and an open discussion of potentially missed opportunities in the pharmacovigilance of biosimilars.     

2017年安徽省某三甲医院细菌耐药性监测

目的 了解铜陵市人民医院2017年临床分离细菌对抗菌药物的耐药状况。方法 对2017年1-12月临床分离菌采用纸片扩散法(KB)进行药敏试验，按CLSI 2017年版标准判读药敏试验结果，采用WHONET 5.6软件进行数据分析。结果 临床分离细菌共3436株，其中革兰阳性菌719株，占20.9%；革兰阴性菌2717株，占79.1%。耐甲氧西林金黄色葡萄球菌(MRSA)和耐甲氧西林凝固酶阴性葡萄球菌(MRCNS)的检出率分别为23.8%和72.3%，耐甲氧西林株对β-内酰胺类抗生素和其他测试抗菌药物的耐药率显著高于甲氧西林敏感株，未发现对万古霉素和替考拉宁耐药的葡萄球菌。粪肠球菌对青霉素、氨苄西林和呋喃妥因的耐药率较低，屎肠球菌对氯霉素的耐药率较低，5.3%屎肠球菌对万古霉素耐药。大肠埃希菌、克雷伯菌属(肺炎克雷伯菌和产酸克雷伯菌)和奇异变形菌中ESBLs的检出率分别为41.4%、50.7%和19.4%。肠杆菌科细菌中克雷伯菌属和沙雷菌属对碳青霉烯类抗生素耐药率较高，分别为37.5%和36.0%，其他菌属的耐药率低于3%。鲍曼不动杆菌对亚胺培南和美罗培南的耐药率分别80.3%和79.1%；铜绿假单胞菌对亚胺培南和美罗培南的耐药率分别为29.7%和28.4%。肺炎克雷伯菌、鲍曼不动杆菌和铜绿假单胞菌中广泛耐药株的检出率分别为31.3%(171/546)、0.6%(3/508)和0.7%(3/416)。结论 本院革兰阴性菌呈增多趋势，尤其广泛耐药的肺炎克雷伯菌应引起高度关注，做好细菌耐药性监测，加强临床抗菌药物的合理使用和医院感染控制。     

大承气汤加减治疗脑病医案3则

通过病案举例,介绍大承气汤在中医脑病治疗中的使用技巧,说明大承气汤可以运用于出血性中风头痛、癫痫、失眠等多种脑病的治疗,疗效显著。大承气汤具有通腑泄热、祛邪外出的作用。对于六经辨证属阳明腑实证者,无论病种,皆可用大承气汤加味化裁。