达格列净应用合理性评价

目的 建立达格列净临床应用合理性评价标准,采用属性层次模型法综合评价达格列净临床应用的合理性。方法以达格列净说明书、中华医学会等发布的相关指南或专家共识为依据,制定达格列净药物利用评价标准。采用属性层次模型对2021年1—9月亳州市人民医院268例应用达格列净的归档病例进行分析评价。结果 达格列净应用主要不合理问题及占比为给药方式(91.0%)、用法用量(69.4%)、用药前评估(60.4%)、用药监护(53.7%)。达格列净应用的合理性评价结果：优秀[90≤病例分值(medicalrecordscore,MRS)<100]16例(6.0%),良好(70≤MRS<90)137例(51.1%),合格(60≤MRS<70)94例(35.1%),不合格(MRS<60)21例(7.8%)。结论 基于属性层次模型的药物利用评价操作简单,结果准确、可信,该方法将评价的多个指标整合,使评价结果更具有直观性,可在药物临床应用评价中推广。     

达格列净安全性的研究进展

目的:了解达格列净安全性的研究进展,为其临床应用提供参考。方法:查阅近年来国内外相关文献,对达格列净的作用机制、不良反应、特殊人群用药、毒理学研究进行归纳、总结。结果:达格列净的不良反应主要有低血糖、泌尿生殖感染、肝损伤、肾损伤、血脂异常等,但发生率较低,无遗传毒性,特殊人群用药尚不完全明确。结论:达格列净上市时间较短,尚需大量长期临床试验证实其不良反应的相关性及在特殊人群中应用的安全性。     

三例达格列净致糖尿病酮症酸中毒的药学监护及文献分析

目的:探讨临床药师在达格列净致糖尿病酮症酸中毒的药物治疗方案制订和药学监护中的作用。方法:临床药师参与3例达格列净致糖尿病酮症酸中毒患者的治疗,结合相关文献,协助医师完善治疗方案,提供用药建议并实施药学服务。结果和结论:达格列净致糖尿病酮症酸中毒的发生与患者胰岛功能差、胰岛素停用或减量等因素相关。临床药师参与临床治疗,制订个体化给药方案,提出药物治疗适应证及合理用药建议,可以促进药物的合理应用,避免糖尿病酮症酸中毒等不良事件的发生。     

达格列净片致正常血糖酮症2例分析

目的提高医务人员对达格列净片导致正常血糖酮症的警惕,为安全使用达格列净片提供参考。方法分析2例由达格列净片导致正常血糖酮症患者的诊疗经过,结合国内外文献分析,探讨达格列净片导致正常血糖酮症的发生情况以及危险因素。结果2例有糖尿病酮症病史的患者分别在使用达格列净片52 d和18 d后出现正常血糖酮症,立即停用达格列净片并予胰岛素治疗,患者酮体转阴。结论应重视达格列净片导致正常血糖酮症的风险,特别是在既往有糖尿病酮症病史患者中的使用风险。     

2021年遂宁市中心医院住院患者应用利伐沙班的合理性分析

目的 调查2021年遂宁市中心医院住院患者临床应用利伐沙班的合理性,为临床合理用药提供参考。方法 回顾性调查分析遂宁市中心医院2021年1月—12月住院患者使用利伐沙班抗凝的病例共2 405份,对其应用的适应症、禁忌症、用法用量、用药时机、用药疗程、药物转换的合理性进行分析。结果 2 405例应用利伐沙班的病历中,适应症不合理306例,存在用药禁忌84例;2 099例具有应用利伐沙班适应症的病历中,用法用量不合理741例,给药时机不合理15例,疗程不合理31例,药物转换不合理104例。结论 遂宁市中心医院住院患者应用利伐沙班主要存在无适应症用药、用法用量不合理等用药现象,应加强宣教。     

2021年天津市第四中心医院阿加曲班药物利用评价标准的建立与应用

目的 建立阿加曲班药物利用评价标准（DUE）,评价阿加曲班的临床应用情况。方法 以阿加曲班药品说明书为基础,参考相关指南和专家共识,并通过与临床专家讨论,建立阿加曲班DUE标准。采用回顾性调查方法,对天津市第四中心医院2021年1月—12月使用阿加曲班的住院患者病例进行合理性评价,评价项目包括适应证、禁忌证、用法用量、溶媒选择、疗程、联合用药、桥接转换和不良反应监测等。结果 共纳入322份病例,其中完全符合评价标准的病例为209份（64.91%）。评价项目符合率较低的项目主要为适应证（87.58%）和用法用量（83.85%）,用法用量不合理主要是特殊人群用药剂量未调整、特殊病理状态患者用药剂量未调整、给药频次不合理。结论 建立的阿加曲班DUE标准具有较强的科学性和实用性,天津市第四中心医院阿加曲班临床应用中尚存在一些问题,应进一步加强干预,以优化阿加曲班的临床应用。     

297例重组人促红素及铁剂治疗血液透析肾性贫血的合理性评价

摘 要 目的：调查分析血液透析肾性贫血治疗药物的使用情况,建立点评标准,为临床合理用药提供参考。方法：利用信息化系统抽取西安中心区院2014年6月～2016年6月诊断为血液透析肾性贫血的患者共297例。根据临床指南、专家共识及药品说明书建立点评标准,评价分析治疗药物重组人促红素及铁剂的用药合理性。结果：重组人促红素用药不合理率为29.29%(87/297),主要表现为该用药而未用;铁剂用药不合理率为56.23%(167/297),主要表现为未检测铁蛋白含量而给予补铁。结论：血液透析肾性贫血药物治疗不合理现象普遍存在,需加强其合理用药的监管力度,保障患者用药安全。     

临床药师干预对促进粒细胞集落刺激因子临床合理应用的实践与探讨

目的 评价临床药师干预对合理应用粒细胞集落刺激因子（G-CSF）的促进效果,为G-CSF的临床合理应用提供参考。方法 随机抽取2019年1月—2020年2月我院临床药师干预前后的肿瘤化疗患者各50例,收集G-CSF用药相关信息,并根据评价标准进行合理性评价分析。结果 共收集100例患者的380次化疗情况,G-CSF应用不合理主要表现为预防使用、用药时机、血常规监测以及用药疗程不合理。临床药师干预后,G-CSF使用率及不合理使用率均明显降低（P<0.05）;一、二级预防使用G-CSF不合理率显著降低,用药时机、血常规监测等不合理情况均得到明显改善（P<0.05）;用药疗程不合理率有一定程度的降低,但差异无统计学意义（P>0.05）。结论 临床药师的干预规范了G-CSF的临床应用,保障了患者的用药安全。     

2017-2018年广州市红十字会医院利伐沙班片的使用合理性分析

目的 评价广州市红十字会医院利伐沙班片临床应用的合理性,提升临床合理用药水平。方法 收集广州市红十字会医院2017-2018年应用利伐沙班片的住院患者病历共358份,对利伐沙班片临床应用的适应症、用法用量、用药时机、疗程、禁忌症进行系统的回顾性调查分析。结果 利伐沙班主要应用于非瓣膜性房颤、外周动脉疾病、深静脉血栓、静脉血栓栓塞高危患者和骨科大手术患者。利伐沙班片用药不合理共174例（48.6%）,其中用法用量不合理140例（42.42%）、超适应症用药28例（7.82%）、用药时机不合理7例（20.59%）、用药疗程不合理11例（32.35%）和存在用药禁忌5例（1.4%）。结论 目前利伐沙班片在临床应用中仍存在一些不合理现象,应积极开展利伐沙班片的临床药学服务,促进其合理使用。     

雷公藤多苷联合达格列净治疗糖尿病肾病的疗效分析

目的 探讨雷公藤多苷联合达格列净治疗糖尿病肾病的临床疗效。方法 将2020年1月—2021年6月本院确诊的2型糖尿病肾病患者120例,按照随机数表法分为对照组及观察组,每组患者60例。两组均进行常规治疗,在此基础上对照组给予达格列净治疗,观察组给予雷公藤多苷联合达格列净治疗。比较两组的临床治疗效果,包括治疗前后的肾功能指标、代谢指标,同时记录治疗过程中出现的不良反应。结果 治疗效果方面,观察组的血肌酐、24小时尿蛋白定量均较对照组下降,血白蛋白较对照组升高,肾功能指标差异具有统计学意义（P＜0.05）;两组的空腹血糖、糖化血红蛋白、血尿酸水平均较治疗前明显下降,但组间无统计学差异（P＞0.05）。不良反应方面,观察组和对照组治疗后低血糖、肝功损害等相关不良反应发生率分别为8.33%和6.67%,但差异无统计学意义（P＞0.05）。结论 在糖尿病肾病的治疗中,雷公藤多苷联合达格列净可有效降低患者血肌酐和尿蛋白水平,升高血清白蛋白,进而改善患者的肾脏预后,同时不良反应无明显增加,整体临床效果较理想。     

Synthesis,Cytotoxicity and Antileishmanial Activity of Some N-(2-(indol-3-yl)ethyl)-7-chloroquinolin-4-amines

We report herein the condensation of 4,7-dichloroquinoline (1) with tryptamine (2) and D-tryptophan methyl ester (3) . Hydrolysis of the methyl ester adduct (5) yielded the free acid (6) . The compounds were evaluated in vitro for activity against four different species of Leishmania promastigote forms and for cytotoxic activity against Kb and Vero cells. Compound (5) showed good activity against the Leishmania species tested, while all three compounds displayed moderate activity in both Kb and Vero cells.     

Lung disease and PKCs

The lung offers a rich opportunity for development of therapeutic strategies focused on isozymes of protein kinase C (PKCs). PKCs are important in many cellular responses in the lung, and existing therapies for pulmonary disorders are inadequate. The lung poses unique challenges as it interfaces with air and blood, contains a pulmonary and systemic circulation, and consists of many cell types. Key structures are bronchial and pulmonary vessels, branching airways, and distal air sacs defined by alveolar walls containing capillaries and interstitial space. The cellular composition of each vessel, airway, and alveolar wall is heterogeneous. Injurious environmental stimuli signal through PKCs and cause a variety of disorders. Edema formation and pulmonary hypertension (PHTN) result from derangements in endothelial, smooth muscle (SM), and/or adventitial fibroblast cell phenotype. Asthma, chronic obstructive pulmonary disease (COPD), and lung cancer are characterized by distinctive pathological changes in airway epithelial, SM, and mucous-generating cells. Acute and chronic pneumonitis and fibrosis occur in the alveolar space and interstitium with type 2 pneumocytes and interstitial fibroblasts/myofibroblasts playing a prominent role. At each site, inflammatory, immune, and vascular progenitor cells contribute to the injury and repair process. Many strategies have been used to investigate PKCs in lung injury. Isolated organ preparations and whole animal studies are powerful approaches especially when genetically engineered mice are used. More analysis of PKC isozymes in normal and diseased human lung tissue and cells is needed to complement this work. Since opposing or counter-regulatory effects of selected PKCs in the same cell or tissue have been found, it may be desirable to target more than one PKC isozyme and potentially in different directions. Because multiple signaling pathways contribute to the key cellular responses important in lung biology, therapeutic strategies targeting PKCs may be more effective if combined with inhibitors of other pathways for additive or synergistic effect. Mechanisms that regulate PKC activity, including phosphorylation and interaction with isozyme-specific binding proteins, are also potential therapeutic targets. Key isotypes of PKC involved in lung pathophysiology are summarized and current and evolving therapeutic approaches to target them are identified.     

Gender-related symptoms and correlates of alcohol dependence among men and women with a lifetime diagnosis of alcohol use disorders

This study explored gender-related symptoms and correlates of alcohol dependence in a crosssectional study of 150 men and 150 women with a lifetime diagnosis of alcohol use disorders (AUD). Participants were recruited in equal numbers from treatment settings, correctional centres and the general community. Standardized measures were used to determine participants' use of substances, history of psychiatric disorders and psychosocial stress, their sensation seeking and family history of substance use and mental health disorders. Multivariate analyses were used to detect patterns of variables associated with gender and the lifetime severity of AUD. Men had a longer history of severe AUD than women. Women had similar levels of alcohol dependence and medical and psychological sequelae as men, despite 6 fewer years of AUD. More women than men had a history of severe psychosocial stress, severe dependence on other substances and antecedent mental health problems, especially mood and anxiety disorders. There were differences in family history of alcohol-related problems approximating same-gender aggregation. The severity of a lifetime AUD was predicted by its earlier age at onset and the occurrence of other disorders, especially anxiety, among both men and women. The limitations in the generalizability of these findings due to sample idiosyncrasies are discussed.     

Biochemical and molecular characterisation of cubozoan protein toxins

Class Cubozoa includes several species of box jellyfish that are harmful to humans. The venoms of box jellyfish are stored and discharged by nematocysts and contain a variety of bioactive proteins that are cytolytic, cytotoxic, inflammatory or lethal. Although cubozoan venoms generally share similar biological activities, the diverse range and severity of effects caused by different species indicate that their venoms vary in protein composition, activity and potency. To date, few individual venom proteins have been thoroughly characterised, however, accumulating evidence suggests that cubozoan jellyfish produce at least one group of homologous bioactive proteins that are labile, basic, haemolytic and similar in molecular mass (42-46 kDa). The novel box jellyfish toxins are also potentially lethal and the cause of cutaneous pain, inflammation and necrosis, similar to that observed in envenomed humans. Secondary structure analysis and remote protein homology predictions suggest that the box jellyfish toxins may act as α-pore-forming toxins. However, more research is required to elucidate their structures and investigate their mechanism(s) of action. The biological, biochemical and molecular characteristics of cubozoan venoms and their bioactive protein components are reviewed, with particular focus on cubozoan cytolysins and the newly emerging family of box jellyfish toxins.     

Dose tolerability of chronically inhaled voriconazole solution in rodents

Invasive pulmonary aspergillosis (IPA) is a fungal disease of the lung associated with high mortality rates in immunosuppressed patients despite treatment. Targeted drug delivery of aqueous voriconazole solutions has been shown in previous studies to produce high tissue and plasma drug concentrations as well as improved survival in a murine model of IPA. In the present study, rats were exposed to 20 min nebulizations of normal saline (control group) or aerosolized aqueous solutions of voriconazole at 15.625 mg (low dose group) or 31.25 mg (high dose group). Peak voriconazole concentrations in rat lung tissue and plasma after 3 days of twice daily dosing in the high dose group were 0.85 ± 0.63 μg/g wet lung weight and 0.58 ± 0.30 μg/mL, with low dose group lung and plasma concentrations of 0.38 ± 0.01 μg/g wet lung weight and 0.09 ± 0.06 μg/mL, respectively. Trough plasma concentrations were low but demonstrated some drug accumulation over 21 days of inhaled voriconazole administered twice daily. Following multiple inhaled doses, statistically significant but clinically irrelevant abnormalities in laboratory values were observed. Histopathology also revealed an increase in the number of alveolar macrophages but without inflammation or ulceration of the airway, interstitial changes, or edema. Inhaled voriconazole was well tolerated in a rat model of drug inhalation.