卫生技术评估在新型噁唑烷酮药物康替唑胺遴选评价中的应用

目的 通过卫生技术评估新型唑烷酮类抗菌药康替唑胺,为医院遴选、临床合理使用新型噁唑烷酮药物提供循证依据。方法 按照药品目录遴选评价管理指南评估细则对国产康替唑胺片进行量化评估,通过检索中国知网、万方、维普、PubMed、Metstr等中外文数据库及相关政府网站获得康替唑胺的适应证、药理作用、指南推荐情况、药品价格等信息,按照药学特性、有效性、安全性、经济性及其他属性量化评价,汇总得分并根据评分划分推荐级别。结果 综合评估结果显示,康替唑胺药学特性18.8分,有效性15分,安全性14.2分,经济性14分,其他属性10分,总得分72分,可推荐进入医疗机构用药目录。结论 康替唑胺作为新品种可以推荐进入医疗机构用药目录,对于临床上利奈唑胺无法治愈的耐甲氧西林金黄色葡萄球菌（MRSA）感染,康替唑胺片有望成为更加安全的抗菌药物选择。     

2016年陕西省基层医疗机构高血压和糖尿病用药分析

目的：分析评价陕西省2016年基层医疗机构高血压和糖尿病药品用药频度和金额等情况。方法：从陕西省药品集中采购平台,调取陕西省基层医疗机构高血压与糖尿病药品2016全年的采购记录,采用用药频度、限定日费用、药品用量/金额排序比等指标进行评价。结果：用药频度最高的高血压药为硝苯地平、螺内酯、吲达帕胺、依那普利、替米沙坦等;用药频度最高的糖尿病药为二甲双胍、格列齐特、格列吡嗪等。这些药品均为一线首选、指南推荐防治高血压或糖尿病的基本药物,其限定日费用均处于中下水平。结论：陕西省基层临床使用最多的高血压和糖尿病药物费用相对不高,均属于广泛使用、价格实惠的基本药物;但是,全省基层医疗机构这两种慢性病的用药量小于实际需求量,说明高血压和糖尿病等慢性病用药管理工作还需进一步加强。     

利格列汀治疗2型糖尿病有效性和安全性的快速评估及其在中国的经济性分析

摘 要 目的：明确利格列汀治疗2型糖尿病的有效性、安全性和经济性,为临床治疗和决策者提供循证依据。方法：按照纳入排除标准,全面检索并筛选卫生技术评估（HTA）报告、系统评价/Meta分析,在质量评价基础上对结果进行综合分析;采用国际多中心随机对照试验的临床数据,基于中国的药品价格与医疗费用,对利格列汀和格列美脲的经济性进行对比分析。结果：快速评估最终纳入HTA报告3篇,系统评价/Meta分析6篇。与安慰剂相比,对于基线平均糖化血红蛋白（HbA1c）水平为7.70%~8.71%、空腹血糖（FPG）水平为7.57 ~ 11.03 mmol·L^-1的患者,利格列汀单药或联合治疗能显著降低HbA1c（-0.62%~-0.76%）和FPG（-1.01 ~-1.12 mmol·L^-1）;同时可提高HbA1c达标率,总体安全性良好。与二甲双胍、格列美脲、伏格列波糖等相比,降糖有效性总体相似,在体重和低血糖等结局指标方面优于磺脲类药物格列美脲,且发生心血管事件的相对危险度更低。经济学分析显示：以医疗卫生系统角度,与格列美脲组相比,利格列汀组每患者年均增量成本为-1 757.32元;以全社会角度分析,每患者年均增量成本为-1 977.70元,可节省更多的医疗费用。结论：利格列汀对2型糖尿病具有良好的血糖控制有效性和安全性,与格列美脲相比,可显著降低低血糖风险、不增加体重且发生心血管事件的相对危险度更低,可为患者节省医疗费用,在中国具有良好的经济性。     

利格列汀联合二甲双胍治疗2型糖尿病的临床疗效观察

目的分析利格列汀与二甲双胍联合方案在2型糖尿病治疗中的有效性。方法回顾性比较我院应用联合药物治疗的97例2型糖尿病患者(即观察组,利格列汀+二甲双胍治疗)和单独应用二甲双胍治疗(即对照组)的94例2型糖尿病患者在空腹血糖、餐后血糖(即2h PG)、糖化血红蛋白(HbA1c)、药物不良反应等方面的差异性。结果规范治疗12周之后,两组患者的空腹血糖、2h PG、HbA1c均有明显改善,组内治疗前后数据具有显著差异(P<0.05);治疗后,观察组各项指标的改善效果均优于对照组,组间比较,P<0.05,具有显著性差异;组间不良反应相近(P>0.05)。结论利格列汀联合二甲双胍具有良好的降糖作用,且药物不良反应少,是2型糖尿病安全有效的治疗方案。     

2015—2017年天津医科大学代谢病医院住院药房口服降糖药使用情况分析

目的 分析2015-2017年天津医科大学代谢病医院住院药房口服降糖药的使用情况,为内分泌临床用药提供参考。方法 对2015-2017年天津医科大学代谢病医院住院药房口服降糖药的用量、销售金额、用药频度（DDDs）、日均费用（DDC））和排序比（B/A）等进行统计分析。结果 2015-2017,口服降糖药的销售金额和药品的总销售金额都有明显下降。α-糖苷酶抑制剂类药物的销售金额始终保持在首位;双胍类和磺脲类药物的销售金额、构成比和排序呈持续上升趋势,噻唑烷二酮类药物和DDP-4抑制剂类药物的构成比则处于下降趋势。阿卡波糖的销售金额和构成比分别在2015、2017年居于首位,2016年伏格列波糖的销售金额跃升为第1位。二甲双胍和伏格列波糖的DDDs连续3年排在前两位。DDC最高的是阿卡波糖;最低的是二甲双胍。2015-2017年,大部分药品的B/A值均接近于1.00,阿卡波糖的B/A值在0.50以下,而二甲双胍的B/A值在2.00以上。结论 天津医科大学代谢病医院住院药房口服降糖药的使用基本合理,符合糖尿病防治指南中的推荐,双胍类或α-葡萄糖苷酶抑制剂类为临床首选药品;受惠于新的药品价格政策,患者的用药经济负担得到减轻。     

ＵＰＬＣ/ＭＳ/ＭＳ检测好康舒胶囊中非法添加降糖类化学药物

摘 要 目的：对好康舒胶囊进行添加降糖类化学药物进行检测。方法: 采用超高效液相色谱 串联质谱（UPLC-MS/MS）法,ACQUITY BEH C₁₈柱（50 mm×2.1 mm,1.7 μm）;以甲醇和0.01 mol·L^-1的乙酸铵溶液进行梯度洗脱。通过分子离子峰、二级质谱的碎片离子信息及多反应监测（MRM）模式下色谱峰的保留时间等信息,对本品中是否含盐酸二甲双胍等11种化学降糖药物的检出情况进行判定。 结果: 对11种化学降糖药物检测分析,好康舒胶囊中检出盐酸苯乙双胍及格列苯脲二种化学降糖药物。结论:好康舒胶囊中非法添加了盐酸苯乙双胍和格列苯脲化学降糖药物。     

2018年天津中医药大学第一附属医院口服降糖药的使用情况分析

目的 分析2018年天津中医药大学第一附属医院口服降糖药物的使用情况,为促进临床合理用药提供依据。方法 应用限定日剂量（DDD）法对2018年天津中医药大学第一附属医院口服降糖药物的种类、销量、销售金额、用药频度（DDDs）、日均费用（DDC）和排序比（B/A）进行统计。结果 α-糖苷酶抑制剂类药物的销售金额占所有口服降糖药的49.84%,排名第1位。双胍类药物的年销售总量居第1位。盐酸二甲双胍片、格列美脲片（2 mg）、阿卡波糖片（进口）、格列喹酮片、伏格列波糖片为DDDs排名前5的药品。阿卡波糖片的DDC明显高于其他降糖药。双胍类药物的B/A均高于1.00,伏格列波糖片、格列齐特缓释片、盐酸吡格列酮分散片、磷酸西格列汀片的B/A均为1.00,餐时血糖调节剂的B/A均低于1.00。结论 天津中医药大学第一附属医院口服降糖药物的应用基本合理,仍需进一步降低患者的经济负担,促进临床合理用药。     

维格列汀治疗2型糖尿病的卫生技术评估

摘 要 目的：明确维格列汀临床使用的获益与风险,为临床治疗和决策者提供循证依据。方法：系统检索PubMed、 EMbase、The Cochrane Library、CNKI等数据库。由2位评价者根据纳入与排除标准独立筛选文献、提取资料和评价质量后,对结果进行定性和定量分析。结果：共纳入2篇卫生技术评估（HTA）报告、10篇Meta分析、67篇随机对照研究（RCT）、1篇观察性研究和8篇经济学研究。维格列汀与安慰剂、伏格列波糖相比可显著降低糖化血红蛋白（HbA1c）水平,与二甲双胍、磺脲类等阳性对照药比较HbA1c降低水平的差异无统计学意义;与西格列汀相比可显著降低空腹血糖（FPG）水平。维格列汀不增加低血糖风险,与磺脲类相比显著降低低血糖风险;不增加心力衰竭、心脑血管事件、胰腺炎等不良事件风险。与磺脲类、噻唑烷二酮类药物相比,维格列汀联合二甲双胍可延长患者的质量调整生命年(QALY)并具有良好的成本 效果比。结论：维格列汀治疗2型糖尿病具有良好的有效性、安全性和经济性,建议纳入医保药品目录。     

2019—2021年某中医院门诊口服降糖药使用情况分析

目的 了解某中医院门诊2019—2021年口服降糖药的使用情况和变化趋势,为临床合理用药提供参考。方法 回顾性统计分析漳州市中医院门诊2019—2021年在用口服降糖药物的品种、销售数量、销售金额、用药频度(DDDs)、限定日费用(DDC)、用药金额排序与DDDs排序的比值(B/A)等情况。结果 2019—2021年医院部分口服降糖药物因实施带量采购政策,阿卡波糖、二甲双胍、格列美脲的年销售金额下降明显,其他药品的销售金额呈逐年增长趋势;DDDs排序前4位的药品依次为二甲双胍、瑞格列奈、阿卡波糖、西格列汀;实施带量采购政策的药品DDC有不同幅度的下降,其余药品DDC保持不变;B/A在0.25～13.00之间。结论 医院口服降糖药物品种齐全,二甲双胍、瑞格列奈、阿卡波糖、西格列汀为门诊最常用品种,临床使用基本合理,符合糖尿病防治指南中的推荐。     

利格列汀联合二甲双胍治疗糖尿病的临床疗效研究

目的:探讨糖尿病患者采用二甲双胍联合利格列汀治疗的临床疗效。方法:将2017年6月~2018年6月治疗糖尿病的86例患者随机分为两组,A组采用格列齐特联合二甲双胍治疗,B组采用二甲双胍联合利格列汀治疗,比较两组的治疗效果。结果:两组患者治疗前HbAlc、2hPG、FPG水平比较差异不明显(P>0.05);B组患者治疗后以上血糖指标明显低于A组,治疗总有效率明显高于A组,对比差异有统计学意义(P<0.05)。结论:糖尿病患者采用利格列汀联合二甲双胍治疗,能有效降低患者的血糖水平,提高其治疗效果,适合在临床上应用。     

Efficacy of gut lavage,hemodialysis, and hemoperfusion in the therapy of paraquat or diquat intoxication

Clinical and in vitro investigations were carried out to test the efficacy of gut lavage, hemodialysis, and hemoperfusion in the treatment of poisoning with paraquat or diquat. In a patient suffering from diquat intoxication 130 times more diquat was removed by gut lavage 30 h after ingestion than was removed by complete aspiration of the gastric contents.Determination of in vitro clearances for paraquat and diquat by hemodialysis showed that, at serum concentrations of 1–2 ppm, such as are frequently encountered in poisoning in man, toxicologically relevant quantities of herbicide cannot be removed from the body. At a concentration of 20 ppm, on the other hand, hemodialysis proved to be effective, the clearance being 70 ml/min at a blood flow rate of 100 ml/min. The efficacy of hemoperfusion with coated activated charcoal was on the whole better. Especially at concentrations around 1–2 ppm, the clearance values for hemoperfusion were some 5–7 times higher than those for hemodialysis.In a patient suffering from paraquat poisoning, both hemodialysis as well as hemoperfusion were carried out. The in vitro results could be confirmed: At serum concentrations of paraquat less than 1 ppm no clearance could be obtained by hemodialysis while by hemoperfusion with activated charcoal quite high clearance values were measured and the serum level dropped down to zero.

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Zusammenfassung Klinische Untersuchungen und Laboratoriumsversuche wurden durchgeführt, um die Wirksamkeit von Darmspülung, Hämodialyse und Hämoperfusion bei Paraquat- und Deiquat-Vergiftungen zu prüfen.Bei einem Patienten wurde 30 Std nach Deiquat-Aufnahme durch Darmspülung 130mal mehr Deiquat entfernt als durch vollständige Aspiration des Mageninhaltes. In vitro-Versuche ergaben, daß bei Blutserumkonzentrationen von 1–2 ppm, die bei Vergiftungen oft gemessen werden, durch Hämodialyse keine toxikologisch relevanten Paraquat- oder Deiquat-Mengen entfernt werden können. Dagegen erwies sich die Hämodialyse bei 20 ppm und einer Blutumlaufgeschwindigkeit von 100 ml/min mit einer Clearance von 70 ml/min als wirksam. Die Hämoperfusion mit beschicheter Aktivkohle war in diesen Versuchen aber eindeutig überlegen, denn insbesondere bei Konzentrationen um 1–2 ppm waren die Clearance-Werte 5–7mal höher als bei der Hämodialyse.Die in vitro-Ergebnisse wurden bei einem Patienten mit einer Paraquat-Vergiftung bestätigt: Bei Konzentrationen unter 1 ppm war die Hämodialyse wirkungslos, während durch Hämoperfusion relativ hohe Clearance-Werte erreicht wurden, so daß der Serumspiegel rasch unter die Nachweisgrenze abfiel.

     

In vitro studies on sterically stabilized liposomes (SL) as enzyme carriers in organophosphorus (OP) antagonism

This study describes a new approach for organophosphorous (OP) antidotal treatment by encapsulating an OP hydrolyzing enzyme, OPA anhydrolase (OPAA), within sterically stabilized liposomes. The recombinant OPAA enzyme was derived from Alteromonas strain JD6. It has broad substrate specificity to a wide range of OP compounds: DFP and the nerve agents, soman and sarin. Liposomes encapsulating OPAA (SL)* were made by mechanical dispersion method. Hydrolysis of DFP by (SL)* was measured by following an increase of fluoride ion concentration using a fluoride ion selective electrode. OPAA entrapped in the carrier liposomes rapidly hydrolyze DFP, with the rate of DFP hydrolysis directly proportional to the amount of (SL)* added to the solution. Liposomal carriers containing no enzyme did not hydrolyze DFP. The reaction was linear and the rate of hydrolysis was first order in the substrate. This enzyme carrier system serves as a biodegradable protective environment for the recombinant OP-metabolizing enzyme, OPAA, resulting in prolongation of enzymatic concentration in the body. These studies suggest that the protection of OP intoxication can be strikingly enhanced by adding OPAA encapsulated within (SL)* to pralidoxime and atropine.     

Aquatic Insects and Trace Metals: Bioavailability,Bioaccumulation, and Toxicity

Abstract

The uptake of metals from food and water sources by insects is thought to be additive. For a given metal, the proportions taken up from water and food will depend both on the bioavailable concentration of the metal associated with each source and the mechanism and rate by which the metal enters the insect. Attempts to correlate insect trace metal concentrations with the trophic level of insects should be made with a knowledge of the feeding relationships of the individual taxa concerned. Pathways for the uptake of essential metals, such as copper and zinc, exist at the cellular level, and other nonessential metals, such as cadmium, also appear to enter via these routes. Within cells, trace metals can be bound to proteins or stored in granules. The internal distribution of metals among body tissues is very heterogeneous, and distribution patterns tend to be both metal and taxon specific. Trace metals associated with insects can be both bound on the surface of their chitinous exoskeleton and incorporated into body tissues. The quantities of trace meals accumulated by an individual reflect the net balance between the rate of metal influx from both dissolved and particulate sources and the rate of metal efflux from the organism. The toxicity of metals has been demonstrated at all levels of biological organization: cell, tissue, individual, population, and community. Much of the literature pertaining to the toxic effects of metals on aquatic insects is based on laboratory observations and, as such, it is difficult to extrapolate the data to insects in nature. The few experimental studies in nature suggest that trace metal contaminants can affect both the distribution and the abundance of aquatic insects. Insects have a largely unexploited potential as biomonitors of metal contamination in nature. A better understanding of the physico-chemical and biological mechanisms mediating trace metal bioavailability and exchange will facilitate the development of general predictive models relating trace metal concentrations in insects to those in their environment. Such models will facilitate the use of insects as contaminant biomonitors.     

Pharmacological treatment of COVID-19: an opinion paper

The precocity and efficacy of the vaccines developed so far against COVID-19 has been the most significant and saving advance against the pandemic. The development of vaccines has not prevented, during the whole period of the pandemic, the constant search for therapeutic medicines, both among existing drugs with different indications and in the development of new drugs. The Scientific Committee of the COVID-19 of the Illustrious College of Physicians of Madrid wanted to offer an early, simplified and critical approach to these new drugs, to new developments in immunotherapy and to what has been learned from the immune response modulators already known and which have proven effective against the virus, in order to help understand the current situation.     

Steroidal sapogenin contents in some domestic plants

In order to find out the values of the steroid resources for the future use. the compositions and contents of steroidal sapogenins from 13 domestic plants have been investigated. As a result,Dioscorea nipponica, D. quinqueloba andSmilax china were found to have large amount of diosgenin. And pennogenin inTrillium kamtschaticum andParis verticillata, yuccagenin inAllium fistulosum, hecogenin inAgave americana and neochlorogenin inSolanum nigum were appeared to be major steroidal sapogenins.     

Alzheimer’s disease – current trends in basic and clinical research. Highlights from the 16th ECNP

Advances in the molecular biological knowledge of neuronal nicotinic acetylcholine receptors (nAChRs) have led to a growing interest by the pharmaceutical industry in the development of novel compounds that selectively modulate nAChR function. The ability of (-)-nicotine, an activator of nAChRs, to enhance attentional aspects of cognition in animals and humans, to exert neuroprotective and anxiolytic-like effects, and presumably to mediate the negative correlation between smoking and Alzheimer's (and Parkinson's) Disease, has focused interest on the potential therapeutic utility of modulators of nAChR function for treatment of some of the deficits associated with these progressive, neurodegenerative conditions. Numerous compounds are known which activate nAChRs and which might serve as lead compounds toward the development of such agents. The pharmacologic diversity of neuronal nAChR subtypes suggests the possibility of developing selective compounds which would have more favourable side-effect profiles than existing agents. This broader class of agents, collectively called cholinergic channel modulators (ChCMs), is anticipated to encompass compounds which would have more favourable side-effect profiles than existing agents, which generally exhibit low selectivity. This selectivity may be achieved by preferentially activating some subtypes of nAChRs (i.e., Cholinergic Channel Activators, ChCAs) or inhibiting the function of other subtypes (Cholinergic Channel Inhibitors, ChCIs). An overview of the biology of nAChRs and the rationale for the use of ChCMs for the treatment of dementia related to neurodegenerative diseases are presented, followed by a discussion of lead compounds and compounds under consideration for clinical evaluation.