艾司西酞普兰对比帕罗西汀治疗中国老年抑郁症患者疗效与安全性的系统评价

目的:系统评价艾司西酞普兰对比帕罗西汀治疗中国老年抑郁症患者的疗效与安全性,以为临床治疗提供循证参考。方法:计算机检索中国期刊全文数据库、中文科技期刊数据库、万方数据库、中国生物医学文献数据库,收集艾司西酞普兰(试验组)对比帕罗西汀(对照组)治疗中国老年抑郁症患者的随机对照试验(RCT),对符合纳入标准的临床研究进行资料提取和质量评价后,采用Rev Man 4.2统计软件进行Meta分析。结果:共纳入14项RCT,合计1 148例患者。Meta分析结果显示,试验组患者痊愈率[OR=1.20,95%CI(0.93,1.53),P=0.16]、显效率[OR=1.23,95%CI(0.94,1.61),P=0.12]、头痛发生率[OR=0.81,95%CI(0.40,1.65),P>0.05]、心动过速发生率[OR=0.37,95%CI(0.09,1.52),P>0.05]、失眠发生率[OR=1.26,95%CI(0.33,4.82),P>0.05]、震颤发生率[OR=0.31,95%CI(0.04,2.24),P>0.05]与对照组比较,差异均无统计学意义;试验组患者口干发生率[OR=0.50,95%CI(0.31,0.80),P<0.05]、恶心发生率[OR=0.49,95%CI(0.36,0.66),P<0.05]、出汗发生率[OR=0.31,95%CI(0.15,0.62),P<0.05]、便秘发生率[OR=0.31,95%CI(0.15,0.64),P<0.05]、头晕发生率[OR=0.38,95%CI(0.20,0.72),P<0.05]、厌食发生率[OR=0.45,95%CI(0.21,0.99),P<0.05]均显著低于对照组,差异均有统计学意义。结论:艾司西酞普兰与帕罗西汀治疗中国老年抑郁症患者的疗效相当,但艾司西酞普兰的安全性优于帕罗西汀。但受纳入研究方法学质量和样本量限制,该结论有待更多设计严格、长期随访的大样本RCT加以验证。     

基因多态性对西酞普兰/艾司西酞普兰有效性与安全性影响的Meta分析

目的 评价基因多态性对西酞普兰/艾司西酞普兰有效性与安全性的影响，为临床精准用药提供循证参考。方法 计算机检索PubMed、Embase、the Cochrane Library、中国知网、万方数据、中国生物医学文献服务系统，收集基因多态性与西酞普兰/艾司西酞普兰有效性、安全性相关的临床研究，筛选文献，提取资料并采用纽卡斯尔-渥太华量表评价文献质量后，采用RevMan 5.3软件进行Meta分析。结果 共纳入35篇文献，均为队列研究，共计9 836例患者。Meta分析结果显示，SLC6A4基因5-羟色胺转运体启动子（HTTLPR）LL基因型与西酞普兰/艾司西酞普兰有效率升高[LS/SS vs. LL:OR=0.47,95%CI(0.22,0.98),P=0.05]相关；亚组分析结果显示，携带LL基因的白种人或使用艾司西酞普兰的有效率更高。SLC6A4基因HTTLPR基因型与治愈率[LS/SS vs.LL:OR=0.92,95%CI(0.77,1.10),P>0.05;SS vs. LL/LS:OR=0.73,95%CI(0.45,1.19),P>0.05]无显著相关性。HT...     

艾司西酞普兰与帕罗西汀治疗老年抑郁症的对照研究

目的 探讨艾司西酞普兰与帕罗西汀治疗老年抑郁症的疗效及安全性.方法 80例老年抑郁症患者分为艾司西酞普兰组和帕罗西汀组,每组40例,治疗6周.采用汉密尔顿抑郁量表（HAMD-17）汉密尔顿焦虑量表（HAMA）评定疗效;采用治疗中出现的症状量表（TESS）及实验室检查评定安全性.结果 治疗6周末2组总体疗效差异无统计学意义 （P＞0.05）;治疗1～2周,艾司西酞普兰组显效快.不良反应艾司西酞普兰组发生率较帕罗西汀组显著降低（P＜0.05）.结论 艾司西酞普兰和帕罗西汀治疗抑郁症疗效确切,艾司西酞普兰起效快,不良反应少,耐受性好,可作为老年抑郁症的首选药物.     

elobixibat治疗慢性便秘有效性和安全性的Meta分析

目的评价elobixibat治疗慢性便秘的有效性和安全性。方法计算机检索PubMed、 Embase、Clinical Trials Website、 Cochrane Library、中国知网、维普和万方数据库中关于elobixibat治疗慢性便秘的临床随机对照试验(RCT)。采用修改后的Jadad量表对纳入文献进行质量评价,采用RevMan 5.3统计软件进行Meta分析。结果共纳入8项RCT, 1260例患者。Meta分析结果显示,与安慰剂组相比,elobixibat5、 10、 15 mg组每周自发排便频次显著增多(分别为WMD=0.87, 95%CI:0.63～1.11, P <0.000 01;WMD=1.93, 95%CI:0.95～2.92, P=0.000 1; WMD=3.68, 95%CI:3.40～3.97, P <0.000 01),elobixibat 5、10 mg组每周完全自发排便频次显著增多(分别为RR=1.82,95%CI:1.30～2.55,P=0.000 5;RR=1.82,95%CI:1.37～2.43,P <0.000 1)。安全性方面,elobixibat组总不良反应、腹泻、腹痛发生率高于安慰剂组(P <0.05),均为轻中度,患者可耐受。结论现有证据表明elobixibat能显著改善慢性便秘,不良反应可耐受。     

去甲文拉法辛短期治疗重性抑郁障碍的Meta分析

目的系统评价去甲文拉法辛治疗重性抑郁障碍的疗效和安全性。方法计算机检索Medline、Embase、 CENTRAL、 PsycNET、中国生物医学文献数据库、中国知网、维普、万方等数据库,搜索建库至2019年2月去甲文拉法辛治疗重性抑郁障碍的临床随机对照试验(RCT),采用RevMan5.3软件进行Meta分析。结果共纳入13篇RCT文献, 1项研究疗程为12周,其余均为8周,共计6 362例重性抑郁障碍患者。Meta分析结果显示:去甲文拉法辛组HAMD_(17)、 CGI-S、 SDS和MADRS总分减分以及HAMD_(17)有效率和缓解率,均优于安慰剂组,差异有显著意义(MD=-1.82, 95%CI:-2.21～-1.43, P <0.000 01; MD=-0.31, 95%CI:-0.39～-0.23, P <0.000 1; MD=-2.00, 95%CI:-2.55～-1.45, P <0.000 01; MD=-2.81, 95%CI:-3.42～-2.21, P <0.000 01; RR=1.27, 95%CI:1.20～1.34, P <0.000 01; RR=1.30, 95%CI:1.20～1.42, P <0.000 01)。因不良反应退出例数,去甲文拉法辛组明显多于安慰剂组(OR=2.19, 95%CI:1.67～2.86, P <0.000 01);严重不良反应发生率,去甲文拉法辛组与安慰剂组相当(OR=0.96, 95%CI:0.57～1.61, P=0.88);常见不良反应(恶心、口干、头晕、失眠、嗜睡、食欲减退、便秘、疲劳)发生率,去甲文拉法辛组显著高于安慰剂组(P≤0.000 1);头痛和腹泻发生率与安慰剂组相当(P> 0.05)。结论去甲文拉法辛短期治疗重性抑郁障碍的疗效和安全性均较好。     

西酞普兰与阿米替林治疗卒中后抑郁障碍的Meta分析

目的:系统评价西酞普兰与阿米替林治疗卒中后抑郁障碍(PSD)的有效性和安全性。方法:计算机检索Cochrane library、Medline、EMbase、中国生物医学文献数据库(CBM)、中文科技期刊数据库(VIP)、中国期刊全文数据库(CNKI)、万方数字化期刊全文数据库,查找西酞普兰与阿米替林治疗PSD的随机对照试验(RCT),对纳入的RCT进行质量评价,并采用Rev Man5.1软件进行Meta分析。结果:共纳入18项RCT,包括1040例PSD患者。Meta分析结果显示,治疗6周后西酞普兰组的有效率优于阿米替林组[RR=1.10,95%CI(1.02,1.18),P=0.01];治疗8周后2组的有效率比较差异无统计学意义[RR=1.05,95%CI(0.97,1.14),P=0.19];治疗1、2、4、6周后西酞普兰组汉密尔顿抑郁量表评分改善优于阿米替林组;治疗2、4、6、8周后西酞普兰组的治疗副反应量表评分优于阿米替林组。结论:西酞普兰治疗PSD疗效与阿米替林相当,但改善抑郁症状较阿米替林快,安全性优于阿米替林。     

艾司西酞普兰治疗儿童青少年抑郁症的临床研究

目的观察艾司西酞普兰治疗儿童青少年抑郁症的临床疗效及安全性。方法对50例儿童青少年抑郁症患者给予艾司西酞普兰治疗4周。于治疗前及治疗后1、2、4周末采用汉密尔顿抑郁量表（HAMD）及汉密尔顿焦虑量表（HAMA）评定疗效,采用副反应量表（TESS）评定不良反应。结果入组患者于治疗第1周末起,汉密尔顿抑郁量表和汉密尔顿焦虑量表总分均较治疗前显著下降（P〈0.01）,并随治疗时间的延长而持续下降;治疗4周末艾司西酞普兰治疗抑郁的有效率达86.0%。不良反应主要为消化系统症状,多于治疗初期出现,无需特殊处理即可逐渐自行缓解。结论艾司西酞普兰临床治疗儿童青少年抑郁症安全有效。     

艾司西酞普兰与帕罗西汀治疗老年抑郁症对照研究

目的评价艾司西酞普兰与帕罗西汀治疗老年抑郁症的临床疗效及安全性。方法将64例老年抑郁症患者随机分为艾司西酞普兰组32例,帕罗西汀组32例,观察6周。于治疗前和治疗1周、2周、4周、6周末采用汉密顿抑郁量表（HAMD）评定疗效,副反应量表（TESS）评定不良反应。结果艾司西酞普兰组显效率78.1%,帕罗西汀组75%,两组比较差异无显著性（P〉0.05）;治疗第2周末艾司西酞普兰组汉密顿抑郁量表评分（HAMD）显著低于帕罗西汀组（P〈0.05）。1周、4周、6周末两组评分比较差异无显著性（P〉0.05）;艾司西酞普兰组不良反应发生率40.6%,帕罗西汀组43.8%,两组比较差异无显著性（P〉0.05）。结论艾司西酞普兰与帕罗西汀治疗老年抑郁症具有同等疗效,但艾司西酞普兰起效较帕罗西汀快。     

艾司西酞普兰与米氮平用于治疗老年抑郁症疗效与安全性的Meta分析

摘 要 目的：系统评价艾司西酞普兰与米氮平对老年抑郁症的疗效与安全性。方法：计算机检索PubMed、Embase、Cochrane Library（2017年第1期）、SinoMed、CNKI、WanFang Data和VIP数据库,搜集有关艾司西酞普兰与米氮平治疗老年抑郁症的随机对照试验（RCTs）,检索时限均为建库至2018年1月。由两名研究者独立筛选文献、提取资料并评价偏倚风险后,采用RevMan 5.3 软件进行Meta分析。结果：共纳入5个RCTs,合计294例患者。Meta分析结果显示,①治疗6周后艾司西酞普兰组与米氮平组患者总有效率的差异无统计学意义[OR=0.94,95%CI（0.43,2.06）,P=0.87];治疗1,2,4,6周时,艾司西酞普兰组与米氮平组汉密尔顿抑郁量表（HAMD）评分的差异均无统计学意义（P＞0.05）;②艾司西酞普兰在嗜睡、头痛/头昏、体重变化等药品不良反应的发生率均低于米氮平组,差异均有统计学意义[体重变化：RR=0.36,95%CI（0.14,0.95）, P=0.04;嗜睡：RR=0.16,95%CI（0.06,0.44）,P=0.000 3;头痛/头昏：RR=0.47,95%CI（0.24,0.91）,P=0.02],两组其余药品不良反应发生率的差异无统计学意义（P＞0.05）。结论：艾司西酞普兰与米氮平治疗老年抑郁症的疗效相当。在常见的药品不良反应中,米氮平易引起嗜睡、体重变化及头痛/头昏。受纳入研究数量和质量的限制,上述结论尚待更多高质量研究予以验证。     

艾司西酞普兰与氟西汀治疗抑郁症疗效观察

目的：探讨艾司西酞普兰与氟西汀治疗抑郁症的疗效和安全性。方法：将110例抑郁症患者随机分为艾司西酞普兰组与氟西汀组,治疗6周,用汉密尔顿抑郁量表（HAMD）和治疗中出现的症状量表（TESS）评定疗效和不良反应。结果：艾司西酞普兰组与氟西汀组总体疗效相当,艾司西酞普兰起效快,不良反应较轻。结论：艾司西酞普兰治疗抑郁症既有效又安全。     

Role of glutathione in reduction of arsenate and of gamma-glutamyltranspeptidase in disposition of arsenite in rats

Arsenate (AsV), the environmentally prevalent form of arsenic, is converted sequentially in the body to arsenite (AsIII), monomethylarsonic acid (MMAsV), monomethylarsonous acid (MMAsIII), and dimethylarsinic acid (DMAsV) and some trimethylated metabolites. Although the biliary excretion of arsenic in rats is known to be glutathione (GSH)-dependent, involving transport of arsenic-GSH conjugates, the role of GSH in the reduction of AsV to the more toxic AsIII in vivo has not been defined. Therefore, we studied how the fate of AsV is influenced by buthionine sulfoximine (BSO), which depletes GSH in tissues. Control and BSO-treated rats were given AsV (50 micromol/kg, i.v.) and arsenic metabolites in bile, urine, blood and tissues were analysed by HPLC-HG-AFS. BSO increased retention of AsV in blood and tissues and decreased appearance of AsIII in blood, bile (by 96%) and urine (by 63%). The biliary excretion of MMAsIII was also nearly abolished, the appearance of MMAsIII and MMAsV in the blood was delayed and the renal concentrations of these monomethylated arsenicals were decreased by BSO. Interestingly, appearance of DMAsV in blood and urine remained unchanged and the concentrations of this metabolite in the kidneys and muscle were even increased in response to BSO. To test the role of gamma-glutamyltranspeptidase (GGT) in arsenic disposition, the effect of the of the GGT inhibitor acivicin was investigated in rats injected with AsIII (50 micromol/kg, i.v.). Acivicin lowered the hepatic and renal GGT activities and increased the biliary as well as urinary excretion of GSH, but failed to alter the disposition (i.e. blood and tissue concentrations, biliary and urinary excretion) of AsIII and its metabolites. In conclusion, shortage of GSH decreases not only the hepatobiliary transport of arsenic, but also reduction of AsV and the formation of monomethylated arsenic, while not hindering the production of dimethylated arsenic. While GSH plays an important role in the disposition and toxicity of arsenic, GGT, which hydrolyses GSH and GSH conjugates, apparently does not influence the fate of the GSH-reactive trivalent arsenicals in rats.     

微透析取样技术在中药体内分析中的应用研究进展

本文综述了微透析取样技术在中药体内分析中的应用,介绍微透析取样技术的原理、组成、探针类型、特点,重点阐述了微透析取样技术在测定脑、血液、皮肤等组织器官中中药有效成分浓度的应用实例。表明微透析取样技术在中药药效研究中具有广阔的前景。     

应用PASS系统分析我院2010年住院医嘱

目的:了解我院2010年住院患者的合理用药情况,探讨如何利用合理用药监测系统( PASS)提高合理用药水平.方法:利用PASS对我院2010年15 966例住院患者的1 184 997条用药医嘱进行监测,以黑色警示医嘱为依据,收集不合理用药信息,并对监测结果进行统计、分析.结果:不合理用药医嘱50 261条,发生率为4.24％.绝对禁止黑色医嘱5441条,主要为药物相互作用(66.54％)、注射液体外配伍(17.86％)、用法用量(15.46％)、儿童警告(1.14％).结论:应用PASS系统能有效监测医嘱中的不合理用药情况,有利于提高临床合理用药水平,但PASS系统尚存在局限性,有待进一步完善.     

Changes in levels of dependency and predictors of mortality in elderly people in institutional care in Dunedin

The 1983 study of dependency of subjects in institutional care in Dunedin was repeated two years later. A significant increase in levels of dependency in residential homes, particularly in the Religious and Welfare sector was found. In 1983 there were 29 high dependency residents and 73 medium dependency residents in residential homes. In 1985 these numbers had increased to 55 and 86 respectively. There was no change in the number of low dependency residents. In 1983, 6 high dependency residents had been admitted to residential home care in the year prior to the study. In 1985 the number of high dependency residents recently admitted had increased to 23. There had also been a significant increase in the dependency of patients in Religious and Welfare continuing care hospitals. Of the 933 subjects in institutional care in 1983 who were able to be followed, 354 (37.9%) died in the following 2 years. Mortality rate was higher for those in hospital care (48.1%) than for those in residential home care (29.6%). Mortality rates were higher in more dependent subjects and this was evident for each measure of dependency.     

应用PASS系统对我院2008年住院医嘱的分析

目的监测分析2008年我院住院患者用药情况。方法将PASS系统嵌入医生工作站、临床药学工作站等子系统,构建合理用药计算机网络系统,对住院医嘱进行及时监测,将监测结果向医生反馈,并对其进行统计、分析。结果2008年共监测医嘱3 620 241条,不合理医嘱908条,占0.02%。不合理医嘱中,配伍禁忌(381条)占41.96%,用法用量(381条)占41.96%,药物相互作用(108条)占11.89%,儿童用药(38条)占4.19%。经与医生沟通后,更改不合理医嘱856条,占94.27%。结论PASS系统可有效监测医嘱中的不合理用药,通过与医生交流,大大减少药物不良事件的发生,值得临床推广应用,也为临床药师开展工作带来了极大的便利。但PASS系统尚存在局限性,有待进一步完善。     

Role of desacetylation in the detoxification of cephalothin in renal cells in culture

The toxicity of three cephalosporin antibiotics to rabbit kidney cells in culture was compared to their known nephrotoxic potential in vivo (cephaloridine greater than cefazolin greater than cephalothin). While cephalothin is considered to be a relatively nonnephrotoxic cephalosporin when administered to many species including humans and rabbits, in several in vitro systems involving rabbit renal tissue, cephalothin was comparatively more toxic than anticipated based on in vivo data. Cephalothin is extensively desacetylated in rabbits to a less microbiologically active metabolite, desacetylcephalothin. When a microsomal S9 fraction from rabbit kidney was added to the in vitro assay in cultured rabbit renal cells, cephalothin was desacetylated and its toxicity to kidney cells was reduced. The addition of S9 in vitro provided a toxicity ranking of the cephalosporins that correlated with their known in vivo nephrotoxic potentials (cephaloridine greater than cefazolin greater than cephalothin). The in vitro detoxification of cephalothin by S9 was blocked by the coadministration of the esterase inhibitor, aminocarb. Desacetylcephalothin was relatively nontoxic to rabbit renal tissue in vitro. These results suggest that the desacetylation of cephalothin in vivo represents a previously unrecognized mechanism of detoxification of this cephalosporin antibiotic. Furthermore, this mechanism of detoxification may be applicable to other acetylated cephalosporins.     

2009年某院住院患者抗真菌药用药调查

目的:分析讨论某院抗真菌药使用的合理性,为临床安全有效地使用抗真菌药提供参考。方法:回顾性统计分析某院2009年住院患者抗真菌药用药信息。结果:2009年某院住院患者抗真菌药DDDs排名前3名分别为:氟康唑、制霉菌素和伊曲康唑;使用金额排名前3名分别为:氟康唑、米卡芬净及卡泊芬净;更换一种抗真菌药进行治疗的患者数为176人,在全部患者中占13.4%。结论:应进一步强化用药指征的意识,提高标本送检率,同时改善某些抗真菌用药不合理更换的现象,以避免耐药性发生,从而更好更长远地体现抗真菌药的治疗价值。     

Kinetics of in vitro metabolism of methoxyphenamine in rats

1. Methoxyphenamine (MP) was metabolized in vitro by rat liver preparations to O-desmethylmethoxyphenamine (O-desmethyl-MP), N-desmethylmethoxyphenamine (N-desmethyl-MP) and 5-hydroxymethoxyphenamine (5-hydroxy-MP). These metabolic pathways were inhibited by SKF 525-A and carbon monoxide, which indicates that these reactions were mediated at least partly by an NADPH-dependent cytochrome P-450 system. 2. Strain differences in the metabolism of this drug in vitro were observed in female Lewis and Dark Agouti (DA) rats, which are proposed models for human debrisoquine phenotypes. Methoxyphenamine O-demethylase and 5-hydroxylase activity in DA rats were lower than those in Lewis rats. 3. The metabolic transformation of methoxyphenamine in vitro to O-desmethyl-MP was inhibited competitively by debrisoquine and sparteine. This indicates that the cytochrome P-450 isoenzyme mediating the metabolism of MP to O-desmethyl-MP is similar to that mediating metabolism of debrisoquine and sparteine. However, no inhibition was observed with methenytoin.     

Comparison of in vitro cell models in predicting in vivo brain entry of drugs

Although several in vitro models have been reported to predict the ability of drug candidates to cross the blood-brain barrier, their real in vivo relevance has rarely been evaluated. The present study demonstrates the in vivo relevance of simple unidirectional permeability coefficient (P(app)) determined in three in vitro cell models (BBMEC, Caco-2 and MDCKII-MDR1) for nine model drugs (alprenolol, atenolol, metoprolol, pindolol, entacapone, tolcapone, baclofen, midazolam and ondansetron) by using dual probe microdialysis in the rat brain and blood as an in vivo measure. There was a clear correlation between the P(app) and the unbound brain/blood ratios determined by in vivo microdialysis (BBMEC r=0.99, Caco-2 r=0.91 and MDCKII-MDR1 r=0.85). Despite of the substantial differences in the absolute in vitro P(app) values and regardless of the method used (side-by-side vs. filter insert system), the capability of the in vitro models to rank order drugs was similar. By this approach, thus, the additional value offered by the true endothelial cell model (BBMEC) remains obscure. The present results also highlight the need of both in vitro as well as in vivo methods in characterization of blood-brain barrier passage of new drug candidates.