Placebo Effect

安慰剂效应
  • 文章类型: Editorial
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  • 文章类型: Journal Article
    本文提供了一个包含来自实际研究的编辑数据的表格。该表包含三个好奇心:在没有临床意义的情况下具有统计学意义,窄标准偏差,并且没有安慰剂效应。表中的数据是由经验不足的评估者获得的;解释了经验不足如何损害数据。评估者经验的行动要点,评分员培训,并建议采用评级程序。
    This article presents a table containing redacted data from a real study. The table contains three curiosities: statistical significance in the absence of clinical significance, narrow standard deviations, and the absence of a placebo effect. The data in the table had been obtained by an inexperienced rater; how the inexperience compromised the data is explained. Action points for rater experience, rater training, and rating procedures are suggested.
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  • 文章类型: Journal Article
    背景:安慰剂对此类客观指标的影响,精子质量和不育,以前没有研究过,但是一些研究报告说,安慰剂甚至可能扭曲客观的结果。本研究的目的是评估安慰剂对精子异常和/或不育患者生育能力的影响。
    方法:我们搜索了两个数据库(Scopus和MEDLINE),并确定了安慰剂对照临床试验,重点是精子异常和/或男性不育治疗。主要结果包括精液参数的变化(体积,总计数,精液中的精子浓度,渐进运动,形态(正常细胞)。次要结果包括DNA片段化和妊娠率的变化。
    结果:包括1983年至2022年发表的77篇文章。观察到以下值具有统计学意义的变化:精子总数,平均变化0.16(95%CI0.05,0.26);P=0.004,I2=75.1%;和渐进运动,平均变化0.13(95%CI0.02,0.24);P=0.026,I2=84.9%。相比之下,安慰剂不影响精子浓度,精子体积,精子形态或DNA碎片指数。用Egger测试和漏斗图测量的所有值的发表偏倚都很低。
    结论:目前的荟萃分析表明安慰剂组精子总数和进行性运动性有统计学意义的增加。相比之下,安慰剂不影响精子浓度,精子体积,精子形态和DNA碎片指数。在计划或分析安慰剂对照临床试验时,应考虑这些发现。
    BACKGROUND: Placebo influence on such objective indicators, as sperm quality and infertility, has not been studied previously, but some studies report that placebo may distort even objective outcomes. The aim of current study is to assess the placebo effect on fertility in patients suffering from sperm abnormalities and/or infertility.
    METHODS: We conducted a search of two databases (Scopus and MEDLINE) and identified placebo-controlled clinical trials which focused on sperm abnormalities and/or male infertility treatment. Primary outcomes included changes in semen parameters (volume, total count, sperm concentration in semen, progressive motility, morphology (normal cells)). Secondary outcomes included DNA fragmentation and change in pregnancy rate.
    RESULTS: Seventy-seven articles published from 1983 to 2022 were included. Statistically significant changes were observed for the following values: total sperm count, mean change 0.16 (95% CI 0.05, 0.26); P=0.004, I2=75.1%; and progressive motility, mean change 0.13 (95% CI 0.02, 0.24); P=0.026, I2=84.9%. In contrast, placebo did not affect sperm concentration, sperm volume, sperm morphology or DNA fragmentation index. The publication bias for all the values measured with Egger\'s test and funnel plots was low.
    CONCLUSIONS: The current meta-analysis indicated a statistically significant increase of total sperm count and progressive motility in the placebo group. In contrast, placebo did not affect sperm concentration, sperm volume, sperm morphology and DNA fragmentation index. These findings should be considered while planning or analyzing placebo-controlled clinical trials.
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  • 文章类型: Case Reports
    我们报告了一个新的病例,在间歇性theta爆发刺激的临床试验(NCT02927236)期间发生的持续性震颤[iTBS,一种用于可卡因使用障碍的重复磁经颅磁刺激(rTMS)]。尽管参与者表现出异常强烈的临床反应,随后的脱盲显示他们接受了假iTBS.这个案例强调了rTMS试验中强大的功能性神经安慰剂反应的潜力,和功能障碍可能是安慰剂反应的标志。此外,我们注意到一些假rTMS系统产生的弱电场可能会引起临床相关效应。
    We report a case of a new-onset, persistent tremor that developed during a clinical trial (NCT02927236) of intermittent theta burst stimulation [iTBS, a form of repetitive magnetic transcranial magnetic stimulation (rTMS)] for cocaine use disorder. Although the participant exhibited an exceptionally strong clinical response, subsequent unblinding revealed that they received sham iTBS. This case highlights the potential for strong functional neurological placebo responses in rTMS trials, and functional disorders might be a marker of a placebo response. Additionally, we note the possibility that the weak e-fields produced by some sham rTMS systems may induce clinically relevant effects.
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  • 文章类型: Journal Article
    疼痛的药物治疗通常不会超过安慰剂,并且需要更好地了解安慰剂机制以改善治疗开发和临床实践。在一项具有预注册分析的大规模功能磁共振成像研究(N=392)中,我们测试了安慰剂镇痛治疗是否能调节伤害性过程,以及其效果是否从条件性疼痛模式推广到非条件性疼痛模式。安慰剂治疗在条件性热痛中引起强烈的镇痛作用,这种疼痛一般为非条件性机械性疼痛。然而,安慰剂并没有降低与伤害性疼痛相关的大脑功能磁共振成像活性,包括神经疼痛信号(NPS)和脊髓丘脑通路区域,在贝叶斯因子分析中强烈支持零效应。此外,令人惊讶的是,安慰剂在非条件性机械性疼痛的一些脊髓丘脑区域增加了活动。相比之下,安慰剂降低了与更高水平的疼痛相关的神经标记的活性,与刺激强度无关的疼痛信号(SIPS),以及与动机和价值相关的大脑区域的活动受到影响,在两种疼痛模式中。行为镇痛的个体差异与两种方式的神经变化有关。我们的结果表明,认知和情感过程主要驱动安慰剂镇痛,并显示了神经标记物用于将治疗对伤害感受的影响与对评估过程的影响分开的潜力。
    Drug treatments for pain often do not outperform placebo, and a better understanding of placebo mechanisms is needed to improve treatment development and clinical practice. In a large-scale fMRI study (N = 392) with pre-registered analyses, we tested whether placebo analgesic treatment modulates nociceptive processes, and whether its effects generalize from conditioned to unconditioned pain modalities. Placebo treatment caused robust analgesia in conditioned thermal pain that generalized to unconditioned mechanical pain. However, placebo did not decrease pain-related fMRI activity in brain measures linked to nociceptive pain, including the Neurologic Pain Signature (NPS) and spinothalamic pathway regions, with strong support for null effects in Bayes Factor analyses. In addition, surprisingly, placebo increased activity in some spinothalamic regions for unconditioned mechanical pain. In contrast, placebo reduced activity in a neuromarker associated with higher-level contributions to pain, the Stimulus Intensity Independent Pain Signature (SIIPS), and affected activity in brain regions related to motivation and value, in both pain modalities. Individual differences in behavioral analgesia were correlated with neural changes in both modalities. Our results indicate that cognitive and affective processes primarily drive placebo analgesia, and show the potential of neuromarkers for separating treatment influences on nociception from influences on evaluative processes.
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  • 文章类型: Journal Article
    运动表现可能受到安慰剂和nocebo效应的影响。关于安慰剂和nocebo对运动和运动表现的影响的最后一篇文献综述于2019年发表。在过去的五年里,一些新的研究已经发表。这篇综述旨在更新以前的综合研究,并通过确定安慰剂或nocebo干预运动和运动的形式和程度来评估新研究的结果。因此,我们搜索了从2019年到2024年5月底在PubMed中索引的实证研究,Medline,WebofScience,EBSCO,和谷歌学者数据库。搜索产生了20个合格的对照或基线控制条件的研究,专注于营养,机械,和其他混合的致麦剂。他们对营养(d=0.86)产生了小到大的安慰剂效应(Cohen'sd),机械(d=0.38),奶油和凝胶(d=0.05),和开放标签安慰剂(d=0.16)干预措施。安慰剂效应的合并效应大小为中等至较大(d=0.67),比以前的审查要大,这表明安慰剂效应可以改善运动表现甚至比以前报道的更多。然而,根据三项研究的五项措施,nocebo效应几乎是其两倍(d=1.20)。因此,目前的研究结果支持并扩大了该领域的最新审查,为运动和锻炼中的安慰剂和nocebo效应提供了额外的支持。
    Sports performance could be affected by placebo and nocebo effects. The last literature review on placebo and nocebo effects on sports and exercise performance was published in 2019. In the past five years, several new studies have been published. This review aimed to update the previous synthesis and evaluate the results of new studies focusing on placebo or nocebo interventions in sports and exercise by determining the form and magnitude of their effect. Hence, we searched for empirical studies published from 2019 until the end of May 2024 indexed in PubMed, Medline, Web of Science, EBSCO, and Google Scholar databases. The search yielded 20 eligible studies with control or baseline-control conditions, focusing on nutritional, mechanical, and other mixed ergogenic aids. They yielded small to large placebo effects (Cohen\'s d) for nutritional (d = 0.86), mechanical (d = 0.38), cream and gel (d = 0.05), and open-label placebo (d = 0.16) interventions. The pooled effect size for placebo effects was moderate to large (d = 0.67), larger than in the earlier review, suggesting that placebo effects can improve motor performance even more than previously reported. However, based on five measures from three studies, the nocebo effects were almost twice as large (d = 1.20). Accordingly, the current findings support and expand the last review in the field by yielding additional support for placebo and nocebo effects in sports and exercise.
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  • 文章类型: Letter
    在安慰剂对照随机临床试验中,坚持安慰剂通常被认为对感兴趣的主要结果没有影响:当使用无偏见的方法时,调查人员希望估计无效。因此,在这些情况下,评估坚持安慰剂的效果已被提出并推广为检测偏倚的策略,例如,来自无法测量的混淆。这种策略可以被视为一种阴性对照暴露的应用,我们称之为安慰剂依从性阴性对照暴露。这里,我们正式陈述了它的定义假设,并讨论了单世界干预图对它们进行推理的独特优势。
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  • 文章类型: Journal Article
    采用通用的感觉,相对于品牌,药物已被证明会加剧nocebo效应。相反,正属性框架已被证明可以减弱nocebo效应。然而,人们对积极属性框架的寿命以及它如何与通用和品牌治疗线索相互作用知之甚少。健康参与者(N=205)被随机分配接受具有品牌或通用外观的假莫达非尼胶囊,与标准负面副作用框架(品牌阴性:N=42;通用阴性:N=41)或正面副作用框架(品牌阳性:N=40;通用阳性:N=40)。其余的被随机分配到无治疗对照(N=42)。参与者被告知,莫达非尼可以提高警觉性和认知能力,减轻疲劳。严重的,莫达非尼被描述为具有几种潜在的副作用。治疗相关的副作用,机敏,在基线测量疲劳和认知表现,治疗后30分钟和24小时后。相对于对照组,在莫达非尼治疗的参与者中观察到了Nocebo和安慰剂效应。积极的框架显着减少了24小时的警告副作用。感知到的副作用可能性,严重程度,担心调解了nocebo,但不是框架,效果。结果对副作用信息的呈现有重要意义,提供一个潜在的途径,以减少不必要的负面影响的仿制药。
    The perception of taking a generic, relative to brand, medication has been demonstrated to exacerbate the nocebo effect. Conversely, positive attribute framing has been shown to attenuate the nocebo effect. However, little is known about the longevity of positive attribute framing nor how it interacts with generic versus brand treatment cues. Healthy participants (N = 205) were randomised to receive either sham-modafinil capsules with a brand or generic appearance, in conjunction with standard negative side effect framing (brand-negative: N = 42; generic-negative: N = 41) or positive side effect framing (brand-positive: N = 40; generic-positive: N = 40). The remainder were randomised to a no-treatment control (N = 42). Participants were informed that modafinil could enhance alertness and cognitive performance and reduce fatigue. Critically, modafinil was described as having several potential side effects. Treatment-related side effects, alertness, fatigue and cognitive performance were measured at baseline, 30-min post-treatment and 24 h later. Nocebo and placebo effects were observed across modafinil-treated participants relative to control. Positive framing significantly reduced warned side effects for 24 h. Perceived side effect likelihood, severity, and worry mediated the nocebo, but not framing, effect. Results have important implications for the presentation of side effect information, providing a potential route to reduce unwanted negative effects of generic medication.
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  • 文章类型: Letter
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  • 文章类型: Journal Article
    目的:治疗帕金森病(PD)患者的临床试验结果可能受安慰剂效应的影响。这项研究的目的是确定与帕金森病(PD)安慰剂效应相关的因素,以指导未来临床试验的设计。
    方法:在一项荟萃分析中,使用随机效应模型对帕金森病患者中与安慰剂效应相关的因素进行了研究,该模型汇集了统一帕金森病评定量表第三部分(UPDRSIII)或运动障碍协会赞助的UPDRSIII修订版(MDS-UPDRSIII)的安慰剂效应。分析中包括以下预先指定的变量:基线有或没有药物,有或没有安慰剂磨合期,有或没有电机波动,发表年,研究地点的数量,安慰剂给药期间,年龄,性别,疾病持续时间,和每日左旋多巴剂量。通过目视检查漏斗图评估出版偏差,并使用修剪和填充方法进行调整。
    结果:38篇,共4828名受试者符合纳入标准。使用UPDRSIII或MDS-UPDRSIII有显著的安慰剂效应(SMD=-0.25;95%CI-0.35至-0.14;p<0.001,I2=92%)。亚组和/或多变量荟萃回归分析显示,安慰剂效应与晚期PD相关(p=0.04),基线时的药物暴露(p<0.001),安慰剂给药期(p<0.001),和病程(p<0.01)。
    结论:这项研究的结果对于未来临床试验的设计具有重要的指导意义,在这些临床试验中,安慰剂效应的影响将被最小化。
    OBJECTIVE: Outcomes of clinical trials of treatment in patients with Parkinson\'s disease (PD) may be influenced by placebo effects. The aim of this study was to determine the factors associated with placebo effects in Parkinson\'s disease (PD) for guidance with design of future clinical trials.
    METHODS: Factors associated with placebo effects in PD were examined in a meta-analysis using a random effects model with pooling of placebo effects on the Unified Parkinson\'s Disease Rating Scale part III (UPDRS III) or Movement Disorder Society sponsored revision of UPDRS III (MDS-UPDRS III). The following prespecified variables were included in the analyses: with or without drug at baseline, with or without a placebo run-in phase, with or without motor fluctuation, published year, number of study sites, placebo administration period, age, sex, disease duration, and daily levodopa dose. Publication bias was assessed by visual inspection of funnel plots and adjusted using the trim-and-fill method.
    RESULTS: Thirty-eight articles with a total of 4828 subjects satisfied the inclusion criteria. There was a significant placebo effect using UPDRS III or MDS-UPDRS III (SMD = - 0.25; 95% CI - 0.35 to - 0.14; p < 0.001, I2 = 92%). Subgroup and/or multivariate meta-regression analyses revealed that placebo effects were associated with advanced PD (p = 0.04), drug exposure at baseline (p < 0.001), placebo administration period (p < 0.001), and disease duration (p < 0.01).
    CONCLUSIONS: The results of this study are important as guidance in design of future clinical trials in which the influence of placebo effects is minimized.
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