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61.
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63.
W. L. Woolverton 《Psychopharmacology》1995,120(3):296-302
Rhesus monkeys (n=5) were prepared with chronic IV catheters and trained to lever press under a PR schedule of drug injection. The schedule
consisted of five components, each made up of four trials (i.e., 20 trials total). Each trial within a component had the same
response requirement. The response requirement in the first component was 120/trial and doubled in successive components to
a maximum of 1920 in the fifth. A trial ended with an injection or the expiration of a 12-min limited hold (LH). The inter-trial
interval (ITI) was 15 or 30 min. Following an injection or expiration of the LH, all stimulus lights were extinguished and
responding had no consequence for the remainder of the trial. A session ended when either all 20 injections were self-administered
or the response requirement was not met within the LH for two consecutive trials. The number of injections/session and responses/session
increased with dose for cocaine (0.012–0.1 mg/kg per injection) and procaine (0.12–2.0 mg/kg per injection) at both ITI values.
At the 15-min ITI, responding decreased again at higher doses in some monkeys with cocaine and in all monkeys with procaine.
At maximum, cocaine maintained significantly more injections and responses/session when the ITI was 30 min than when it was
15 min. In contrast, the increase in ITI did not increase the maximum maintained by procaine. Cocaine was approximately 10-fold
more potent than procaine and maintained at maximum significantly more injections and responses than procaine when the ITI
was 30 min but not when the ITI was 15 min. These results are consistent with previous studies demonstrating that cocaine
is a more efficacious positive reinforcer than procaine. Moreover, they extend recent findings suggesting that number of injections/session
provides a measure of PR performance that is amenable to statistical analysis and may, therefore, be useful in establishing
reliable differences among drugs in terms of relative reinforcing efficacy. Reliable quantification of between-drug differences
in reinforcing efficacy can enhance not only estimates of relative abuse liability but also pharmacological analysis of central
mechanisms mediating reinforcing effects. 相似文献
64.
S D Walter 《Annals of oncology》2003,14(8):1190-1192
BACKGROUND: The case-control design can be used to evaluate the benefit of cancer screening programmes. MATERIALS AND METHODS: This paper outlines the main methodological features of the case-control design in this context, and indicates some potential biases. It also reviews the existing case-control literature on mammographic screening. RESULTS: Case-control studies consistently indicate a reduction of approximately 50% in breast cancer mortality associated with mammography. This result indicates greater benefit than shown in randomised trials; however, one should recognise that trials indicate effectiveness whereas case-control studies indicate efficacy. The two types of evidence are broadly compatible when one allows for screening non-compliance and contamination in the randomised trials. CONCLUSIONS: The case-control evidence supports and is consistent with the findings of randomised trials of mammography. Effectiveness estimates from trials indicate the benefit of screening to the population as a whole, and are pertinent to the public policy debate as to the value of offering screening. In contrast, case-control studies indicate benefit to actual screening participants. As such, case-control estimates of efficacy are appropriate for individual decision-making by women about their use of mammography when it is potentially available to them. 相似文献
65.
Bayesian decision theoretic approaches (BDTAs) have been widely studied in the literature as tools for designing and conducting phase II clinical trials. However, full Bayesian approaches that consider multiple endpoints are lacking. Since the monitoring of toxicity is a major goal of phase II trials, we propose an adaptive group sequential design using a BDTA, which characterizes efficacy and toxicity as correlated bivariate binary endpoints. We allow trade‐off between the two endpoints. Interim evaluations are conducted group sequentially, but the number of interim looks and the size of each group are chosen adaptively based on current observations. We utilize a loss function consisting of two components: the loss associated with accruing, treating, and monitoring patients, and the loss associated with making incorrect decisions. The performance of our Bayesian modeling, and the operating characteristics of decision rules under a wide range of loss function parameters are evaluated using seven scenarios in a simulation study. Our method is illustrated in the context of a single‐arm phase II trial of bevacizumab, gemcitabine, and oxaliplatin in patients with metastatic pancreatic adenocarcinoma. Copyright © 2009 John Wiley & Sons, Ltd. 相似文献
66.
Efficacy and safety of transcranial magnetic stimulation in the acute treatment of major depression: a multisite randomized controlled trial. 总被引:6,自引:0,他引:6
John P O'Reardon H Brent Solvason Philip G Janicak Shirlene Sampson Keith E Isenberg Ziad Nahas William M McDonald David Avery Paul B Fitzgerald Colleen Loo Mark A Demitrack Mark S George Harold A Sackeim 《Neuropsychopharmacology》2007,62(11):1208-1216
BACKGROUND: We tested whether transcranial magnetic stimulation (TMS) over the left dorsolateral prefrontal cortex (DLPFC) is effective and safe in the acute treatment of major depression. METHODS: In a double-blind, multisite study, 301 medication-free patients with major depression who had not benefited from prior treatment were randomized to active (n = 155) or sham TMS (n = 146) conditions. Sessions were conducted five times per week with TMS at 10 pulses/sec, 120% of motor threshold, 3000 pulses/session, for 4-6 weeks. Primary outcome was the symptom score change as assessed at week 4 with the Montgomery-Asberg Depression Rating Scale (MADRS). Secondary outcomes included changes on the 17- and 24-item Hamilton Depression Rating Scale (HAMD) and response and remission rates with the MADRS and HAMD. RESULTS: Active TMS was significantly superior to sham TMS on the MADRS at week 4 (with a post hoc correction for inequality in symptom severity between groups at baseline), as well as on the HAMD17 and HAMD24 scales at weeks 4 and 6. Response rates were significantly higher with active TMS on all three scales at weeks 4 and 6. Remission rates were approximately twofold higher with active TMS at week 6 and significant on the MADRS and HAMD24 scales (but not the HAMD17 scale). Active TMS was well tolerated with a low dropout rate for adverse events (4.5%) that were generally mild and limited to transient scalp discomfort or pain. CONCLUSIONS: Transcranial magnetic stimulation was effective in treating major depression with minimal side effects reported. It offers clinicians a novel alternative for the treatment of this disorder. 相似文献
67.
68.
精神分裂症患者氯氮平使用现况调查 总被引:2,自引:0,他引:2
目的:了解精神分裂症患者氯氮平的使用现状。方法:按一定的抽样比例,抽取10个省市46家专科医院或综合医院精神科,于2002年4月22日至24日,采用自制问卷对4779例门诊和住院精神分裂症患者进行氯氮平使用情况调查。结果:39.0%(1863/4779)的患者使用氯氮平治疗,平均剂量为(216±133)mg/d;其中41.2%的患者为联合用药,合并使用抗胆碱能药物者为19.2%。与未使用氯氮平的患者比较,使用氯氮平的患者病程较长、家庭收入较低;男性及住院患者更多使用氯氮平,氯氮平治疗者疗效指数低于非氯氮平治疗者。患者的性别、就诊部门、家庭收入和是否首次住院以及抑郁和攻击症状为是否使用氯氮平治疗的影响因素。结论:精神分裂症患者氯氮平使用率为39.0%,其中41.2%为联合用药。是否使用氯氮平治疗与患者的经济状况和临床特征等因素有关。 相似文献
69.
目的:从现代药理学角度阐述何首乌"补肝肾、益精血、强筋骨"功效.方法:通过查阅中国期刊全文数据库(CNKI)、维普全文数据库(VIP)等,分析1989~2007年期间与何首乌功效与药理相关文献,归纳汇总何首乌的中药功效及现代药理学研究,探讨两者间的相关性.结果:[1]何首乌药理作用与其性味归经功效有相合之处.何首乌性温味苦涩,温能补肝,苦能补肾,收敛精气.与功效相关的药理作用主要有:"久服延年不老"与延缓衰老;"入血分,消痰毒"与调节血脂;"止心痛,益血气"与抗心肌缺血;"调气血,泻肝风"与抗动脉粥样硬化;"专入肾,益精髓"与提高学习记忆;"补肝肾,入肝肾脾经"与增强免疫等.[2]与何乌"乌须发"功效相关的药理研究有待于进一步深入.[3]生何首乌、制何首乌功效不同,药理研究应根据其功能主治加以辨别.结论:何首乌现代药理研究与其性味归经功效有一定的相吻之处,这为合理阐述何首乌的中药药性理论提供依据,并为何首乌进一步的药理研究与临床应用提供参考. 相似文献
70.
提高中医临床疗效的科学学检讨(连载三) 总被引:1,自引:0,他引:1
李致重 《河南中医学院学报》2003,18(6):5-7
中医学的生命力在于临床疗效 ,社会对于中医学的需要也在于临床疗效。提高中医临床疗效的科学学研究 ,要以中医基础理论为依据 ,以理、法、方、药一脉相承的辨证论治为前提。造成中医临床疗效下降的问题在于“三个脱节” ,即中医学与自身文化基础脱节 ,中医临床与辨证论治脱节 ,中药与中医临床脱节。中医学正处于行将消亡的边缘 ,也处在新的突破的前夜。实事求是地进行科学、历史的反思 ,中医学完全有可能走出百年困惑 ,得到振兴和发展。 相似文献