托莫西汀治疗儿童注意缺陷多动障碍的疗效与安全性的系统评价

目的:系统评价托莫西汀治疗儿童注意缺陷多动障碍(ADHD)的疗性与安全性。方法:计算机检索Cochrane library、Medline、EMbase、中国生物医学文献数据库,查找托莫西汀治疗儿童ADHD的随机对照试验(RCT),采用Rev Man 5.1统计软件进行Meta分析。结果:共纳入17项RCT,包括2 548例患儿。Meta分析结果显示,治疗后托莫西汀组的注意缺陷/多动评定量表(ADHD-RS)总分值[MD=-7.53,95%CI(-9.56,-5.51),P<0.01]、ADHD-RS多动/冲动分量表分值[MD=-4.15,95%CI(-5.25,-3.06),P<0.01]、ADHD-RS注意缺陷分量表分值[MD=-3.80,95%C(I-5.08,-2.51),P<0.01]及临床总体印象-总体严重度量表(CGI-S)分值[MD=-0.74,95%C(I-1.23,-0.26),P<0.01]改善均显著优于对照组,两组比较差异有统计学意义;两组患儿治疗过程中脱落失访例数比较,差异无统计学意义[RR=1.00,95%C(I0.85,1.18),P=0.99];托莫西汀组患儿比对照组更容易发生恶心、呕吐、食欲减退、腹痛、头痛、头晕、倦怠、易激惹、疲劳、体质量下降等不良反应(P<0.05)。结论:托莫西汀治疗儿童ADHD具有良好的疗效,可显著改善儿童ADHD的多动/冲动以及注意缺陷,其耐受性与对照组无显著性差异,但应注意其不良反应。     

盐酸托莫西汀治疗注意缺陷多动障碍的Meta分析

目的:采用Meta分析方法对盐酸托莫西汀治疗注意缺陷多动障碍的疗效及安全性进行评价。方法:查询Medline,EmBase,SCI,Elsevier,CBMdisc等数据库,收集盐酸托莫西汀治疗注意缺陷多动障碍的临床试验文献,提取疗效指标及安全性数据,采用Review Manager 4.2软件进行统计计算。结果:检索到年龄<18岁的儿童及青少年的随机双盲安慰剂对照临床研究文献14篇,均为国外文献(Jadad评分≥4分);样本含量1 995例;药物剂量0.5~1.8 mg.kg-1.d-1。在忽略药物剂量的条件下,盐酸托莫西汀与安慰剂相比,儿童及青少年的ADHD-RS评分和CGI-S评分平均减分值分别为[WMD-7.26(-8.28,-6.24)]和[WMD-0.62(-0.75,-0.48)](P<0.01)。试验中出现的不良反应有食欲下降[RR:4.46(2.89,6.89)]、恶心[RR:2.97(2.00,4.41)]、呕吐[RR:2.14(1.42,3.21)]及体重改变[WMD-1.88(-2.23,-1.52)]。结论:盐酸托莫西汀在改善注意缺陷多动障碍患者的核心症状方面疗效显著,耐受性良好。     

托莫西汀治疗注意缺陷多动障碍的疗效和药物经济学研究进展

目的:关注托莫西汀治疗注意缺陷多动障碍(ADHD)的临床疗效及药物经济学评价的研究进展。方法:查阅近年来国内外相关文献,介绍ADHD的治疗方案,对托莫西汀治疗ADHD的临床疗效和药物经济学研究进展进行归纳和总结。结果:多项多中心、双盲随机临床试验显示托莫西汀疗效较好,且具有良好的耐受性和安全性。较少的药物经济学研究显示托莫西汀治疗ADHD更经济。结论:托莫西汀的临床疗效和经济性在总体上具有优势,但还需进一步研究。     

盐酸托莫西汀对注意缺陷多动障碍伴对立违抗患者治疗效果的荟萃分析

目的分析评价盐酸托莫西汀对注意缺陷多动障碍(ADHD)伴对立违抗障碍(ODD)患者的治疗效果。方法检索Medline、PubMed、中国生物医学文献数据库等数据库中发表的相关研究,选择符合标准的随机对照试验(RCT),并提取相关数据。采用Cochhrane协作网RevMan4.2软件进行Meta分析。结果有3项RCT试验共437例患者纳入研究中,其中托莫西汀治疗组291例,安慰剂治疗组146例。托莫西汀治疗后父母评定量表第4版(ADHDRS-Ⅳ)总分变化值明显高于安慰剂治疗组(WMD=-8.12,95%CI:-11.52~-4.73,P<0.01),临床总体印象-总体严重度量表(CGI-ADHD-S)分降低值明显高于安慰剂组,Conner′s简式父母评定量表修订版(CPRS-R:S)多动症症状评分变化值明显高于安慰剂组(WMD=-5.75,95%CI:-8.24~-3.27,P<0.01);托莫西汀治疗组CPRS-R:S(ODD症状)评分变化值较安慰剂治疗组高(WMD=-1.65,95%CI:-2.89~-0.41,P<0.01)。结论盐酸托莫西汀可有效改善ADHD伴ODD患者的ADHD症状,并对ODD症状具有较好的疗效。     

牛磺酸与盐酸托莫西汀联用对儿童注意缺陷多动障碍模型大鼠的影响

目的 评价牛磺酸与盐酸托莫西汀联合用药对儿童注意缺陷多动障碍(ADHD)模型大鼠的多动行为及智力发育的影响.方法 选择幼年期自发性高血压大鼠作为ADHD模型,通过开场实验、Y迷宫实验、生化指标检测研究ADHD大鼠的动物行为学.结果 ADHD大鼠进入旷场实验箱中央区的次数明显高于正常对照组.与模型组比较,牛磺酸与盐酸托莫...     

哌甲酯及托莫西汀对注意缺陷多动障碍儿童HPA轴功能的影响

目的:通过研究哌甲酯(MPH)及托莫西汀(ATX)治疗前后注意缺陷多动障碍(ADHD)儿童下丘脑-垂体-肾上腺(HPA)轴的功能状态,探讨HPA轴在ADHD中的作用.方法:采用前瞻、双盲、随机对照研究方法,根据美国<精神病诊断与统计手册>(第4版)(DSM-IV)ADHD诊断和分型标准确诊111例6～14岁ADHD男童...     

哌甲酯与托莫西汀治疗中国儿童和青少年注意缺陷多动障碍的安全性评价

目的评价哌甲酯与托莫西汀治疗中国儿童和青少年注意力缺陷多动障碍的安全性。方法检索关于中国儿童和青少年使用哌甲酯与托莫西汀治疗注意力缺陷多动障碍的安全性研究文献包括随机对照研究(RCT)研究、半随机临床对照试验研究(CCT)研究、病例报告以及上市后药物不良反应监测。按纳入和排除标准筛选文献,评价文献质量,提取资料。RCT文献采用RevMan 5.3软件进行Meta分析,余文献采用描述性分析,采用世界卫生组织-乌普萨拉监测中心(WHO-UMC)评价体系评价病例报告中不良反应与哌甲酯或托莫西汀的关联性。结果检出符合纳入标准的RCT文献9篇,病例报告2篇,未检索到哌甲酯或托莫西汀上市后不良反应监测报告。(1)RCT文献结果:托莫西汀组整体不良反应发生率低于哌甲酯组(P=0.003)。(2)病例报告分析结果:1例服用托莫西汀出现口周皮炎;1例服用哌甲酯出现视物模糊、头颈歪斜。(3)上市后不良反应监测结果:未检索到中国哌甲酯或托莫西汀的不良反应监测数据。结论中国青少年儿童口服托莫西汀的整体不良反应发生率低于哌甲酯,而嗜睡不良反应发生率托莫西汀组高于哌甲酯组,其余不良反应发生率未见明显差异。     

托莫西汀治疗儿童注意缺陷多动障碍疗效观察

目的:探讨托莫西汀(ATX)对门诊符合DSM-IV诊断标准的注意缺陷多动障碍(ADHD)患儿的有效性及安全性。方法:采用开放性研究方法,对温州市第七人民医院儿童青少年心理门诊诊断为ADHD的患儿共48例口服托莫西汀0.8 mg/(kg·d)治疗8周,采用ADHDRS-IV-Parent:Inv、CGI-ADHD-S、Conners多动指数量表进行临床疗效评定,采用TESS量表对药物不良反应进行临床监测。结果:ADHDRS-IV-Parent:Inv总体有效率77.08%(37/48);治疗前CGI-ADHD-S(5.19±0.71)分、Conners多动总分(26.2±3.1)分、行为总分(39.1±5.2)分,治疗8周后CGI-ADHD-S(2.98±0.89)分、Conners多动总分(12.3±2.9)分、行为总分(18.2±4.6)分,治疗前后比较差异均有统计学意义(P<0.01);其主要的不良反应为食欲下降、上腹痛、恶心呕吐、头晕、心悸等。结论:ATX对ADHD患儿的注意缺陷、多动、冲动症状均有较好的疗效,而且安全性好。     

托莫西汀联合脑电生物反馈治疗儿童注意缺陷多动障碍疗效观察

目的：研究托莫西汀联合脑电生物反馈治疗儿童注意缺陷多动障碍（ADHD）的疗效。方法：对46例ADHD惠儿给予托莫西汀与脑电生物反馈治疗4个月,于治疗前后详细记录患儿注意力商数与反应控制商数中视觉、听觉商数以及进行Conners儿童行为量表父母问卷并进行评估。结果：与治疗前比较,观察组注意力商数与反应控制商数中视觉、听觉商数较治疗前明显升高,差异有统计学意义（P〈0．05）;Conners量表评分较治疗前均明显下降,差异有统计学意义（P〈0．05）。与对照组比较,治疗后注意力商数与反应控制商数中视觉、听觉商数差异均无统计学意义（P〉0．05）;治疗后Conners量表评分在多动指数、学习问题、冲动一多动、品行问题等4个方面差异均无统计学意义（P〉0．05）,而在心身障碍、焦虑两个方面评分明显下降,差异有统计学意义（P〈0．05）。结论：托莫西汀联合脑电生物反馈治疗ADHD可以更好的改善患儿的注意缺陷、多动和冲动等核心症状。     

托莫西汀联合感觉统合训练治疗注意缺陷多动障碍患儿效果及对TCD参数、动态肌电图的影响

目的:探讨托莫西汀联合感觉统合训练治疗注意缺陷多动障碍(ADHD)患儿效果及对经颅多普勒超声检查(TCD)参数、动态肌电图的影响。方法:按随机数字表法将2021年9月至2022年9月我院收治的60例ADHD患儿分为两组，各30例。对照组采用托莫西汀治疗，研究组在对照组基础上加用感觉统合训练治疗，对比两组临床疗效、TCD参数[大脑基底动脉(BA)、左侧中动脉(MCA-L)、左侧前动脉(ACA-L)、左侧后动脉(PCA-L)]、儿童感觉统合能力发展评定量表评分、中文版注意缺陷多动障碍评定量表-父母版(SNAP-IV)评分和不良反应。结果:研究组治疗后总有效率高于对照组(P<0.05);两组治疗后BA对比，无统计学差异(P>0.05);研究组治疗后MCA-L、ACA-L、PCA-L高于对照组(P<0.05);研究组治疗后儿童感觉统合能力发展评定量表评分高于对照组(P<0.05);研究组治疗后SNAP-IV评分低于对照组(P<0.05);两组治疗期间均无严重不良反应发生。结论:托莫西汀联合感觉统合训练可有效提升ADHD患儿的注意力和感觉统合能力，促进大脑动脉局部灌...     

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.