一种新机制抗抑郁药：艾司氯胺酮

艾司氯胺酮是一种新型抗抑郁药,经鼻给药,主要的作用机制是可持续阻断N-甲基-D-天冬氨酸(NMDA)受体,阻断真核细胞的延伸因子2 (eEF2)激酶,增加脑源性神经营养性因子(BDNF)的释放及原肌球蛋白受体激酶B (TrkB)的表达,诱导雷帕霉素靶蛋白复合体1 (mTORC1)信号通路及细胞外调节蛋白激酶(ERK)激活,改善神经可塑性和突触的形成。相关临床研究结果均表明艾司氯胺酮治疗难治性抑郁症起效快速,能迅速消除患者的自杀意图,低剂量维持治疗有助于患者病情稳定,不良反应较少。     

艾司氯胺酮在气管镜手术麻醉中的有效性及安全性分析

目的：分析艾司氯胺酮在气管镜手术麻醉中的有效性与安全性。方法：选择医院于2020年10月—2022年8月间收治的140例行气管镜手术麻醉治疗的患者为研究对象,根据患者麻醉方案进行分组,其中对照组患者的麻醉方案为丙泊酚+右美托咪定的联合麻醉方法,观察组患者则接受丙泊酚+艾司氯胺酮联合麻醉,根据两组患者的临床指标总结艾司氯胺酮的临床应用价值。结果：两组患者不同时间段的生命体征数据比较后发现,观察组患者的舒张压、收缩压以及心率等优于对照组(P<0.05);两组患者的不良反应发生率显示,观察组气管镜手术麻醉患者的发生率低于对照组(P<0.05);患者术后VAS评分比较,观察组低于对照组(P<0.05);比较苏醒时间,观察组少于对照组(P<0.05)。结论：在气管镜手术患者麻醉过程中,艾司氯胺酮的麻醉方案安全有效,且具有良好的镇痛效果,有助于缩短苏醒时间。     

艾司氯胺酮联合丙泊酚用于无痛人流手术的有效性和安全性分析

目的 探究无痛人流手术中使用艾司氯胺酮联合丙泊酚的有效性和安全性。方法 选取2022年1月～2022年5月期间行无痛人流手术的320例患者纳入研究,所有患者随机分为艾司氯胺酮(0.3 mg/kg)+丙泊酚组(E₁组)、艾司氯胺酮(0.5 mg/kg)+丙泊酚组(E₂组)、芬太尼(2μg/kg)+丙泊酚组(F组)和丙泊酚组(B组)。观察四组患者心率、血氧饱和度、平均动脉压、丙泊酚用量、舒适度、满意度、MOAA/S、Aldrete评分。结果 对比四组麻醉后(T₁)、结束手术时(T₂)的心率,E₂组>E₁组>F组>B组(P<0.05);对比四组平均动脉压,E₁组2组1组>E₂组>F组>B组(P<0.05)。对比四组丙泊酚用量,E₂     

艾司唑仑治疗失眠症临床疗效及安全性的网状Meta分析

目的 运用网状meta分析探究艾司唑仑、右佐匹克隆、佐匹克隆、米氮平、米氮平联合艾司唑仑在调节失眠症患者匹兹堡睡眠质量指数（PSQI）、睡眠障碍评定量表（SDRS）、睡眠自评量表（SRSS）、阿森斯失眠量表（AIS）、药物不良反应（TESS）的差异。方法 收集截止至2016年11月CNKI、维普、万方、Pubmed数据库中上述药物在治疗失眠症患者的临床试验资料,文章质量评估用Jadad评分,研究结果的分析用Gemtc 14.3、Stata 13、RevMan 5.3软件。结果 纳入13篇研究,Meta分析发现：与艾司唑仑相比,米氮平联合艾司唑仑的PSQI较低[WMD=-6.67,95% CI （-8.38,-4.96）,P<0.000 01];米氮平联合艾司唑仑的AIS较低[WMD=-3.73,95% CI （-4.51,-2.95）,P<0.000 01];佐匹克隆的SDRS较低[WMD=-2.50,95% CI （-3.71,-1.28）,P<0.000 1]。间接网状meta分析显示：SDRS依次为艾司唑仑>右佐匹克隆>佐匹克隆;AIS依次为艾司唑仑>佐匹克隆>米氮平联合艾司唑仑;TESS依次为艾司唑仑>佐匹克隆>右佐匹克隆。结论 艾司唑仑降低失眠患者SDRS、AIS、TESS均不具备明显优势,网状meta分析方法发掘药物疗效与安全性具有一定的参考价值。     

中西医结合治疗原发性难治性肾病综合征的meta分析

目的:系统评价中西医结合治疗难治性肾病综合征(Refractory Nephritic Syndrome,RNS)的疗效,为中西医结合治RNS提供科学依据。方法:用循证医学的方法,选用国内外多个权威数据库为资料源,对国内近10年间(2001～2010)正式发表的临床研究文献进行手工检索。按照国际cochrane协作网的系统评价方法,对所纳入的研究进行方法学质量评价,并选取11篇质量良好的随机对照试验(RCT)运用Rev.Man5.0.23软件进行Meta分析。结果:共检索到11个符合纳入标准的RCT,共计922例患者,其中中西医结合组478例,对照组444例。Meta分析显示,在治疗后中西医结合组与对照组的总有效率差异有统计学意义[RR=4.04,95%CI(2.85,5.70),合并效益Z=7.93(P<0.00001)]。结论:中西医结合治疗RNS有助于提高其临床疗效,减少激素或免疫抑制剂不良反应的发生。     

艾司氯胺酮联合苯磺酸瑞马唑仑对ERCP患者影响的meta分析

目的系统评价艾司氯胺酮与苯磺酸瑞马唑仑联合使用对内镜逆行胰胆管造影术(ERCP)患者的影响。方法检索中国知网、维普、万方、PubMed、Web of science、Embase及Cochrance图书馆的数据库, 从建库到2023年3月发表的艾司氯胺酮联合苯磺酸瑞马唑仑用于ERCP的随机对照试验(RCTs)。试验组采用艾司氯胺酮复合苯磺酸瑞马唑仑的麻醉方案, 对照组采用其他静脉麻醉药物联合使用方案。由互不关联的2名研究者根据纳入排除标准对文献进行仔细筛选, 使用Review Manager 5.4软件进行统计分析。结果纳入6项RCTs, 共532例患者。与其他麻醉药物联合使用方案比较, 艾司氯胺酮联合苯磺酸瑞马唑仑组患者发生低血压、呼吸抑制等不良事件的概率更低(RR=0.29, 95%CI 0.17～0.50;RR=0.18, 95%CI 0.08～0.38)。结论采用艾司氯胺酮联合苯磺酸瑞马唑仑能减少患者ERCP中的不良事件发生概率, 是一种更平稳、安全的麻醉方法。     

艾司氯胺酮在剖宫产术后镇痛中应用效果观察

目的 探讨艾司氯胺酮在剖宫产术后镇痛中的效果。方法 选取2020年4月至2021年4月本院收治的76例剖宫产产妇,按随机数字表法分为对照组（38例）和观察组（38例）。对照组给予舒芬太尼+盐酸托烷司琼镇痛,观察组加用艾司氯胺酮镇痛,观察至产妇出院。对比两组疼痛程度、抑郁状况、不良反应。结果 术后2、12、48 h,观察组术口痛、宫缩痛VAS评分低于对照组,差异有统计学意义（P<0.05）;产前,两组汉密尔顿抑郁量表（HAMD）评分相比,差异无统计学意义（P>0.05）;产后3 d,观察组HAMD评分低于对照组,差异有统计学意义（P<0.05）;两组不良反应相当,差异无统计学意义（P>0.05）。结论 艾司氯胺酮在剖宫产术后镇痛中效果确切,能够减轻产妇宫缩痛、手术切口痛,改善抑郁状况,且无严重不良反应,安全可行。     

分子靶向药物治疗难治性甲状腺癌的疗效及安全性的meta分析

目的　对分子靶向药物治疗难治性甲状腺癌的疗效及安全性进行meta分析,为临床应用提供有价值的循证医学证据。方法　检索PubMed、Embase、the Cochrane Library、Web of Science、中国知网、万方数据知识服务平台以及中国生物医学文献服务系统从建库到2022年4月13日关于甲状腺癌分子靶向治疗的文献,筛选文献提取数据,评价纳入研究的偏倚风险,采用RevMan5.4软件进行meta分析。结果　共纳入8项研究,试验组（分子靶向药物）样本量为1 201例,对照组（安慰剂）样本量为748例。meta分析结果显示,相比于安慰剂,分子靶向药物有更佳的客观缓解率（objective response rate,ORR）（RR=14.19,95%CI 4.12～48.93,P<0.000 1）以及疾病控制率（disease control rate,DCR）（RR=1.40,95%CI 1.20～1.63,P<0.000 1）,并且明显提高了难治性甲状腺癌患者的无进展生存期（progression-free survival,PFS）（HR=0.35,95%CI 0.25～0.51,P<0.000 01）。试验组≥3级不良事件（adverse events,AEs）发生率高于对照组（RR=3.85,95%CI 2.90～7.10,P<0.000 1）,主要为腹泻、高血压、疲劳、手足综合征、食欲下降以及体质量下降。结论　分子靶向药物具有良好的疗效,并且通过调整剂量和给予支持治疗可使大部分AEs得以控制。因此,分子靶向药物可成为治疗难治性甲状腺癌新的选择。                         

艾司氯胺酮在气管镜手术麻醉中的应用研究

目的 观察气管镜手术麻醉中应用艾司氯胺酮的麻醉效果研究.方法 临床选择2019年9月至2021年1月在本院接受诊治的气管镜手术患者210例,根据随机数字表法分组,分为观察组(n=105)、对照组(n=105),观察组予以艾司氯胺酮与丙泊酚联合麻醉,对照组予以右美托咪定与丙泊酚联合麻醉,监测两组在麻醉诱导前(T1)、手术...     

度洛西汀治疗老年抑郁症与广泛性焦虑障碍有效性及安全性meta分析

目的:系统评价度洛西汀与安慰剂比较治疗老年抑郁症及广泛性焦虑障碍的疗效及安全性。方法:计算机检索PubMed、CochraneLibrary、EMbase、中国期刊全文数据库、中文科技期刊全文数据库、万方数字化期刊全文数据库,检索日期截至2016年11月。纳入度洛西汀与安慰剂比较治疗老年抑郁症及广泛性焦虑障碍的随机对照试验,按照Cochrane Handbook 5.1.0的质量评价标准评价纳入研究的质量后,采用Rev Man5.3软件进行meta分析。结果:共纳入6个研究,4篇研究针对老年抑郁症患者,2篇研究针对老年广泛性焦虑障碍患者。Meta分析结果显示:(1)治疗后度洛西汀组与安慰剂组的HAM-D治疗前后变化差值差异有统计学意义(SMD=-0.39,95%CI:-0.65~-0.12);HAM-A治疗前后变化差值差异亦有统计学意义(SMD=-0.54,95%CI:-0.76~-0.33);治疗后两组抑郁及焦虑痊愈率差异也有统计学意义。(2)治疗结束度洛西汀组与安慰剂组在总退出率、因不良反应退出率及严重不良反应发生率上差异无统计学意义;而在恶心、疲倦、便秘、口干、腹泻、嗜睡、出汗等不良反应发生率上两组差异有统计学意义,度洛西汀组发生率更高。(3)治疗后度洛西汀组与安慰剂组生活质量量表评分变化差值差异有统计学意义,度洛西汀能提高患者生活质量。结论:度洛西汀能提高老年抑郁症及广泛性焦虑障碍患者的临床治愈率,降低抑郁及焦虑量表评分,提高患者的生活质量,但增加恶心、疲倦、便秘、口干、腹泻、嗜睡、出汗等不良反应发生。     

Relationship Between Dissociation and Antidepressant Effects of Esketamine Nasal Spray in Patients With Treatment-Resistant Depression

BackgroundIn this post-hoc analysis, data from 2 positive, pivotal, phase 3 trials of esketamine nasal spray (ESK) in treatment-resistant depression (TRD)—short-term study (TRANSFORM-2) and maintenance study (SUSTAIN-1)—were analyzed to evaluate the relationship between dissociation and antidepressant effects of ESK.MethodsAnalysis by responder status, correlation analysis, and mediation analysis were performed to assess the relationships between peak Clinician Administered Dissociative States Scale (CADSS) scores after first (day 1) and last (day 25) ESK dose and change in Montgomery-Åsberg Depression Rating Scale (MADRS) total scores at the first (day 2) and last assessments (day 28) in TRANSFORM-2 and peak CADSS after first maintenance ESK dose and time to relapse in SUSTAIN-1 (only for mediation analysis).ResultsIn TRANSFORM-2, the percentage of responders (>50% reduction in MADRS) at day 2 and day 28 did not significantly differ between patients who did vs did not manifest significant dissociation (peak CADSS scores >4 or ≤4, respectively) following the first ESK dose. Spearman correlation coefficients between dissociation and depression improvement were nonsignificant and close to zero. CADSS scores did not significantly mediate the reduction in MADRS at day 2 or 28 in TRANSFORM-2 or the time to depression relapse in SUSTAIN-1. The mean difference in MADRS between ESK and active-control arms persisted beyond day 2 without significant change across time, although the mean peak CADSS scores significantly decreased across consecutive doses and fewer patients experienced significant dissociation after the last ESK dose compared with the first.ConclusionWithin the dose range tested, the dissociative and antidepressant effects of ESK were not significantly correlated.Trial registration{"type":"clinical-trial","attrs":{"text":"NCT02417064","term_id":"NCT02417064"}}NCT02417064 (TRANSFORM-1); {"type":"clinical-trial","attrs":{"text":"NCT02418585","term_id":"NCT02418585"}}NCT02418585(TRANSFORM-2); {"type":"clinical-trial","attrs":{"text":"NCT02493868","term_id":"NCT02493868"}}NCT02493868 (SUSTAIN-1)     

Effects of Mu-Opiate Receptor Gene Polymorphism rs1799971 (A118G) on the Antidepressant and Dissociation Responses in Esketamine Nasal Spray Clinical Trials

BackgroundAt ketamine and esketamine doses at which antidepressant doses are achieved, these agents are relatively selective, noncompetitive, N-methyl-D-aspartate receptor antagonists. However, at substantially higher doses, ketamine has shown mu-opioid receptor (MOR–gene symbol: OPRM1) agonist effects. Preliminary clinical studies showed conflicting results on whether naltrexone, a MOR antagonist, blocks the antidepressant action of ketamine. We examined drug-induced or endogenous MOR involvement in the antidepressant and dissociative responses to esketamine by assessing the effects of a functional single nucleotide polymorphism rs1799971 (A118G) of OPRM1, which is known to alter MOR agonist-mediated responses.MethodsParticipants with treatment-resistant depression from 2 phase III, double-blind, controlled trials of esketamine (or placebo) nasal spray plus an oral antidepressant were genotyped for rs1799971. Participants received the experimental agents twice weekly for 4 weeks. Antidepressant responses were rated using the change in Montgomery–Åsberg Depression Rating Scale (MADRS) score on days 2 and 28 post-dose initiation, and dissociative side effects were assessed using the Clinician-Administered Dissociative-States Scale at 40 minutes post-dose on days 1 and 25.ResultsIn the esketamine + antidepressant arm, no significant genotype effect of single nucleotide polymorphism rs1799971 (A118G) on MADRS score reductions was detected on either day 2 or 28. By contrast, in the antidepressant + placebo arm, there was a significant genotype effect on MADRS score reductions on day 2 and a nonsignificant trend on day 28 towards an improvement in depression symptoms in G-allele carriers. No significant genotype effects on dissociative responses were detected.ConclusionsVariation in rs1799971 (A118G) did not affect the antidepressant response to esketamine + antidepressant. Antidepressant response to antidepressant + placebo was increased in G-allele carriers, compatible with previous reports that release of endorphins/enkephalins may play a role in mediating placebo effect.Trial Registration{"type":"clinical-trial","attrs":{"text":"NCT02417064","term_id":"NCT02417064"}}NCT02417064 and {"type":"clinical-trial","attrs":{"text":"NCT02418585","term_id":"NCT02418585"}}NCT02418585; www.clinicaltrials.gov     

鲑鱼降钙素喷鼻剂的人体生物等效性研究

目的:研究国产和进口鲑鱼降钙素鼻喷剂的生物等效性。方法:采用双周期自身随机交叉设计。用放射免疫法(RIA)测定22例健康志愿者喷鼻给药后的血药浓度。结果:国产制剂及进口鼻喷剂实测平均血药峰浓度C_(max)分别为(64.72±9.68)ng·L~(-1)和(65.61±8.46)ng·L~(-1);实测平均达峰时间t_(max)分别为(0.27±0.05)h和(0.27±0.05)h;国产制剂及进口制剂t_(1/2)(ke)分别为(0.68±0.23)h和(0.69±0.24)h;血药浓度-时间曲线下面积AUC_(0-8)h平均值分别为(61.70±15.53)ng·L~(-1)·h和(64.89±15.12)ng·L~(-1)·h;以进口制剂为参比制剂,试验制剂鲑鱼降钙素鼻喷剂的相对生物利用度为(95.95±15.21)%。结论:国产与进口鲑鱼降钙素鼻喷剂生物等效。     

鲑降钙素鼻喷雾剂的研制

制备了用于治疗骨质疏松症的鲑降钙素鼻喷雾剂，采用正交试验法，以加速实验后产品的含量为指标对处方进行优化，以HPLC法测定含量。结果显示制剂的稳定性达到实验设计要求。2－8℃贮存稳定性好。     

艾司氯胺酮联合右美托咪定用于小儿纤支镜检查安全性研究

目的:探讨右美托咪定联合艾司氯胺酮是否能够安全用于儿童纤维支气管镜(纤支镜)的检查;如果加用舒芬太尼,是否能够减少艾司氯胺酮的用量,降低不良反应发生率。方法:选取我院拟择期行纤支镜检查的患儿40例,按随机数表法分为E组和S组各20例。E组采用“右美托咪定1μg/kg+艾司氯胺酮1 mg/kg”麻醉方案,S组采用“右美托咪定1μg/kg+艾司氯胺酮1 mg/kg+舒芬太尼0.1μg/kg”麻醉方案。比较两组患儿基础(T₀)、诱导后(T₁)、纤支镜通过声门(T₂)、纤支镜通过隆突(T₃)、检查完成10 min(T₄)5个时间点的心率(HR)、平均动脉压(MAP)、血氧饱和度(SpO₂)水平和不良反应。结果:E组T₂、T₃的HR水平高于T₁(P均<0.05),T₀～T₄的MAP、SpO₂水平变化差异均无统计学意义(P均>...     

Atypical Antipsychotic Augmentation for Treatment-Resistant Depression: A Systematic Review and Network Meta-Analysis

Background:

Previous meta-analyses of atypical antipsychotics for depression were limited by few trials with direct comparisons between two treatments. We performed a network meta-analysis, which integrates direct and indirect evidence from randomized controlled trials (RCTs), to investigate the comparative efficacy and tolerability of adjunctive atypical antipsychotics for treatment-resistant depression (TRD).

Methods:

Systematic searches resulted in 18 RCTs (total n = 4422) of seven different types and different dosages of atypical antipsychotics and a placebo that were included in the review.

Results:

All standard-dose atypical antipsychotics were significantly more efficacious than placebo in the efficacy (standardized mean differences [SMDs] ranged from -0.27 to -0.43). There were no significant differences between these drugs. Low-dose atypical antipsychotics were not significantly more efficacious than the placebo. In terms of tolerability, all standard-dose atypical antipsychotics, apart from risperidone, had significantly more side-effect discontinuations than placebo (odds ratios [ORs] ranged from 2.72 to 6.40). In terms of acceptability, only quetiapine (mean 250–350mg daily) had significantly more all-cause discontinuation than placebo (OR = 1.89). In terms of quality of life/functioning, standard-dose risperidone and standard-dose aripiprazole were more beneficial than placebo (SMD = -0.38; SMD = -0.26, respectively), and standard-dose risperidone was superior to quetiapine (mean 250–350mg daily).

Conclusions:

All standard-dose atypical antipsychotics for the adjunctive treatment of TRD are efficacious in reducing depressive symptoms. Risperidone and aripiprazole also showed benefits in improving the quality of life of patients. Atypical antipsychotics should be prescribed with caution due to abundant evidence of side effects.     

Validity of in Vitro Tests on Aqueous Spray Pumps as Surrogates for Nasal Deposition

Purpose. To determine whether deposition pattern is related to in vitromeasurements of droplet size, plume geometry, and spray pattern between two different nasal spray pumps believed to have different performance characteristics. Methods. Ten healthy volunteers inhaled radiolabeled saline from two different spray pumps (pump A and pump B). Deposition pattern was quantified from lateral views of the nose by gamma scintigraphy, expressed as the ratio of anterior to posterior (I:O) and superior to inferior (U:L) deposition. Droplet size was determined by Malvern Mastersizer S. Spray patterns were determined at 2.5 and 5 cm from the tip of the spray nozzle. Two-dimensional images of the emitted plume were captured by high-speed still photography. Results. There were no significant differences in I:O or U:L ratios for pump A compared to pump B, indicating no significant differences in deposition pattern. The volume diameters, D_v10 and D_v50, were not statistically different for pump A compared to pump B. There was a significant difference in D_v90 between pump A and pump B, (86.9 ± 5.8 m and 77.4 ± 2.4 m, respectively; P < 0.001). The ratio of the longest to shortest diameter for the spray pattern with pump A was 1.26 ± 0.06 at 2.5 cm and 1.44 ± 0.08 at 5 cm. The ratio for pump B was 1.13 ± 0.03 at 2.5 cm and 1.19 ± 0.05 at 5 cm. Ratios at both heights were statistically different for pump A compared to pump B (P < 0.00002 and P < 0.000001, respectively) Plume geometry analysis indicated statistical differences in both the width (17.0 ± 0.97 vs. 18.5 ± 0.56 cm, respectively; p<0.001) and the maximum length of the plumes (46.0 ± 1.83 vs. 53.1 ± 4.88 cm, respectively; p < .002). The differences in velocity of the plume and spray angle between the two pumps were not statistically different. Conclusions. Certain in vitrotests detected performance differences between the two pumps. However, these differences did not translate into different deposition patterns in vivo.     

生理性海水鼻喷剂治疗儿童鼻窦炎疗效观察

目的:探讨生理性海水鼻喷剂治疗小儿鼻窦炎的临床疗效。方法:将临床确诊的鼻窦炎患儿120例随机分为观察组和对照组各60例,对照组使用抗生素、黏液促排剂以及鼻渊通窍颗粒治疗,观察组在对照组治疗基础上配合使用生理性海水鼻喷剂治疗,两组均连续治疗6周,期间停用其他一切可影响鼻通气的药物。结果:治疗后观察组总有效率为93.33%,高于对照组的78.33%(P<0.05);VAS 总分、Lund-Kennedy 总分均低于对照组(P均<0.05)。结论:生理性海水鼻喷剂配合常规药物治疗可有效提高儿童鼻窦炎的疗效,减少不良反应的发生。     

缩宫素鼻喷雾剂对排乳的影响

目的:探讨缩宫素鼻喷雾剂对排乳的影响.方法:按对照研究的方法,将60例晚期妊娠正常分娩的初产妇按入院先后分为实验组和对照组,每组各30例.实验组使用缩宫素鼻喷雾剂,对照组使用安慰剂.比较2组总乳汁量、吸空时间及乳腺管通畅度的差别,判断缩宫素鼻喷雾剂对排乳的影响.结果:实验组乳腺管通畅率60%,乳汁量较对照组增多,2组比...     

布地奈德鼻喷雾剂和地氯雷他定片联合治疗过敏性鼻炎

目的探讨布地奈德喷雾剂和地氯雷他定片联合应用治疗过敏性鼻炎的疗效。方法 150例确诊为过敏性鼻炎的患者分为3组,分别给予布地奈德鼻喷雾剂和地氯雷他定片(联合组)50例,布地奈德喷雾剂(单药A组)50例,地氯雷他定片(单药B组),观察2周,并对治疗前后的症状和体征记分比较。结果联合组的近期疗效总有效率达96%,单药A组为75%,单药B组为68%,联合组效果明显优于单药A组和单药B组,无明显的不良反应。结论布地奈德鼻喷雾剂和地氯雷他定片联合治疗过敏性鼻炎安全有效。