德谷胰岛素在中国2型糖尿病起始胰岛素治疗中的短期成本-效用分析

目的:评价德谷胰岛素和甘精胰岛素(100 u·mL~(-1))在接受基础胰岛素起始治疗的中国2型糖尿病患者中的短期成本-效用。方法:应用短期成本-效用DOSE模型,基于中国基础胰岛素临床观察性登记研究中患者低血糖发生率以及公开发表的数据,对比德谷胰岛素和甘精胰岛素短期(1年)的健康结果和经济成本差异。结果:与甘精胰岛素相比,德谷胰岛素治疗使每人每年增加0.02质量调整生命年(quality adjusted life year,QALY),直接医疗成本总费用每人每年节省984.36元、治疗药费节省812.12元、严重低血糖治疗费用降低87.52元、自我血糖监测费用降低84.64元。敏感性分析进一步验证了结果的稳健性。结论:在中国2型糖尿病起始胰岛素治疗中,与甘精胰岛素相比,德谷胰岛素是成本更低、效用更高的优势方案。     

新型超长效胰岛素类似物——德谷胰岛素

糖尿病病人的胰岛素治疗往往是长期的。胰岛素所致的低血糖、体重增加、肿瘤风险是选择胰岛素治疗方案时需要考虑的问题。德谷胰岛素作为基础胰岛素,是最新型的一种超长效胰岛素类似物,它以平稳缓慢释放、维持作用时间长、吸收变异性小、低血糖发生率低、用药灵活、有利于控制高血糖和降低夜间低血糖的发生等独特优势,为糖尿病病人的胰岛素治疗提供了一种新选择。     

德谷胰岛素与甘精胰岛素对于2型糖尿病患者临床疗效及安全性的比较

目的 比较德谷胰岛素和甘精胰岛素对于2型糖尿病患者的临床疗效及安全性的差异。方法 选取就诊于石家庄市人民医院血糖控制不佳的2型糖尿病患者80例,随机分为2组(徳谷组和甘精组),每组40例,分别给予相应胰岛素治疗。前2周通过动态血糖仪监测,后续每周随访1次,共观察12周。检测指标包括空腹及餐后2 h血糖、HbA1c、胰岛素剂量以及反映血糖变异性的多个指标。结果 共有75例患者完成随访,其中徳谷组39例,甘精组36例,2组人群年龄、BMI、血糖和HbA1c等基线资料差异无统计学意义。徳谷组的FPG-SD和FPG-CV低于甘精组(P<0.001),但2组间的TIR、MBG、SD、MAGE、LAGE和MODD等指标无明显差异。随访结束时,徳谷组的FPG和胰岛素剂量均低于甘精组(P<0.05),而2组的HbA1c和HbA1c下降幅度大致相同。无论是低血糖还是夜间低血糖,徳谷组的发生风险均低于甘精组(P<0.05)。结论 德谷胰岛素具有不劣于甘精胰岛素的临床疗效,同时血糖变异性较小,低血糖风险更低,具有更高的安全性。     

德谷胰岛素联合达格列净对老年2型糖尿病患者的疗效及安全性评估

目的 评估德谷胰岛素联合达格列净对于老年2型糖尿病患者的降糖效果及其安全性。方法 于石家庄市人民医院选取血糖控制不佳的老年2型糖尿病患者90例，随机分为对照组、甘精组和徳谷组，每组30例。对照组给予达格列净治疗，甘精组和徳谷组分别给予达格列净联合相应胰岛素治疗。每2周随访1次，共观察12周，随访时记录受试者的FPG和胰岛素使用剂量。于试验开始和结束时抽血检测患者血糖、胰岛素、HbA1c和血脂等指标。结果 随访结束时，甘精组和徳谷组的FPG和HbA1c水平低于对照组(P<0.05),甘精组和德谷组的HbA1c水平比较，差异无统计学意义(P>0.05),但徳谷组FPG水平、胰岛素用量低于甘精组(P<0.05)。3组研究对象在治疗后的体重、FPG和HbA1c水平均低于各自的基线状态，差异有统计学意义(P<0.05)。随访过程中，徳谷组受试者发生低血糖的风险低于甘精组(P<0.05)。结论 德谷胰岛素联合达格列净治疗老年2型糖尿病患者疗效显著，安全性较高，值得临床推广。     

德谷门冬双胰岛素的临床研究进展

德谷门冬双胰岛素是由新一代超长效基础胰岛素类似物（德谷胰岛素）联合餐时胰岛素类似物（门冬胰岛素）组成的新型胰岛素类似物复方制剂,可以每天使用一或两次,同时提供基础和餐时胰岛素需求,与目前的胰岛素制剂相比具有较低的低血糖风险。综述了德谷门冬双胰岛素与预混胰岛素、基础餐时胰岛素及基础胰岛素方案比较的临床研究进展,为临床上更好地应用提供参考。     

德谷胰岛素与甘精胰岛素U100治疗2型糖尿病的疗效与安全性评价

目的对比分析德谷胰岛素和甘精胰岛素U100用于治疗2型糖尿病的疗效和安全性。方法本研究为回顾性队列研究, 研究对象为2018年9月至2021年12月于山东省13家三级综合医院住院治疗的2型糖尿病患者。根据使用的基础胰岛素种类, 将患者分为德谷胰岛素组和甘精胰岛素U100组。收集2组患者的一般资料和实验室检查结果, 比较2组患者的空腹血糖水平、低血糖发生率;选择2组中血糖监测数据完整的患者, 分析其血糖波动情况。结果本研究共纳入1 152例患者, 德谷胰岛素组552例, 甘精胰岛素U100组600例, 2组患者基本情况差异无统计学意义(均P>0.05)。2组患者治疗后空腹血糖水平均低于治疗前, 差异有统计学意义[10.2(8.8, 12.5)mmol/L比7.5(6.6, 8.7)mmol/L, Z=-19.443, P<0.001;10.0(8.6, 11.7)mmol/L比7.8(6.6, 9.0)mmol/L, Z=-15.449, P<0.001], 但2组治疗后空腹血糖水平差异无统计学意义(Z=-1.427,P>0.05)。德谷胰岛素组患者的低血糖发生率...     

德谷门冬双胰岛素对比甘精胰岛素联合门冬胰岛素治疗基础胰岛素控制不佳的2型糖尿病患者的短期成本-效果分析

摘要：目的:评价基础胰岛素控制不佳的2型糖尿病患者使用德谷门冬双胰岛素,对比甘精胰岛素联合门冬胰岛素治疗的短期成本-效果。方法:使用短期成本效果DACE模型计算德谷门冬双胰岛素和甘精胰岛素联合门冬胰岛素治疗基础胰岛素控制不佳的2型糖尿病患者2年的健康产出和卫生成本,并进行成本-效果分析。研究基于卫生体系角度,成本包括降糖治疗成本及相关的低血糖治疗、自我血糖监测(SMBG)等直接医疗成本,效果数据来自已发表的NCT02906917试验和其他文献,采用质量调整生命年(QALYs)表示。并采用单因素敏感性分析和概率敏感性分析评价结果的稳定性。结果:与甘精胰岛素联合门冬胰岛素治疗方案相比,德谷门冬双胰岛素治疗可使患者多获得0.028 8 QALYs(1.461 7 vs.1.432 9),并节约直接医疗成本19 748元(22 722 vs.42 470),费用节约主要来自降糖治疗费用的节约,其中胰岛素、SMBG及针头费用分别节约11 863元、5 388元、2 230元。敏感性分析显示结果稳定可靠。结论:对于基础胰岛素控制不佳的2型糖尿病患者,与甘精胰岛素联合门冬胰岛素的治疗方案相比,使用德谷门冬双胰岛素可改善患者健康产出并节约成本,更具有药物经济学优势。     

德谷胰岛素及其复方制剂在2型糖尿病中的临床研究现状及进展

2型糖尿病是我国临床上最常见的糖尿病类型,易引起患者多饮、多食、多尿,同时消瘦或者短期内体重减轻,导致患者时常感到乏力、疲劳,对其日常生活和工作造成严重的影响。目前,2型糖尿病的治疗常选用综合治疗的方式,通过降血糖以及根据患者个体并发症情况进行降血压、调节血脂、抗血小板、控制体重的增减以及改善生活方式等方式治疗,从而平稳的控制血糖水平,提高生活质量。2型糖尿病的病因以及发病机制较为复杂,而深入了解2型糖尿病的病理学理论,在一定程度上可有效帮助患者降低血糖水平,减轻身心上的痛苦,同时促进临床上对于2型糖尿病的治疗和研究。德谷胰岛素是一种通过修饰人胰岛素分子结构而得到的新一代可溶性超长效基础胰岛素类似物,具有持久、平稳、长期简化血糖的功效,常被用于2型糖尿病患者的治疗。德谷胰岛素-利拉鲁肽复方制剂（IDegLira）以及德谷门冬双胰岛素（DegludecPlus）是德谷胰岛素的复方制剂,具有较高的安全性以及有效性,能够平稳降低血糖水平,并且降糖风险相对较小,受到临床上糖尿病医生以及患者的青睐,同时也为糖尿病患者的治疗提供一种新的选择。至今为止已有多项临床研究证实IDegLira以及Degl...     

德谷胰岛素和甘精胰岛素在中国北方1型糖尿病患者中血糖控制方面的差异性研究

目的 比较德谷胰岛素(IDeg)与甘精胰岛素(IGlar)在中国北方1型糖尿病患者中血糖变异性(GV)的差异.方法 采用开放标签、随机、双向交叉研究,16例接受餐时加基础胰岛素治疗的中国北方1型糖尿病患者随机(1:1)分到2个治疗序列(A:基础胰岛素为IDeg-IGlar,B:基础胰岛素为IGlar-IDeg),在为期...     

地特胰岛素:基础胰岛素的理想选择

胰岛素是治疗糖尿病的有效药物,但胰岛素治疗在降糖的同时还会带来低血糖和体重增加等不良反应。地特胰岛素独特的分子结构和作用机制使其吸收时间减缓,同时延缓了胰岛素分子从循环血液向外周靶器官的扩散和分布,从而使其作用时间持久,并接近生理性基础胰岛素分泌,减少血糖波动。地特胰岛素对于1型糖尿病和2型糖尿病患者,均有效降低空腹血糖和HbA1c水平,且低血糖风险小,治疗引起的体重增加少。     

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.     

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.     

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.     

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.