sequential trial

序贯试验
  • 文章类型: Journal Article
    背景:超声引导下的针头放置彻底改变了胸椎旁阻滞技术,可应用于胸腔镜手术。
    目的:本研究调查了超声引导单次注射0.3%罗哌卡因作为胸椎旁神经阻滞用于肺癌胸腔镜根治术的中位有效体积(EV50)。
    方法:2018年2月10日至8月13日,共纳入27例接受超声引导下胸椎旁神经单次阻滞并接受胸腔镜肺癌根治术的患者。所有患者均被评为ASA等级I或II。使用超声波作为指导,通过平面内技术,将阻滞针逐渐穿过肋横断韧带到达胸椎旁间隙。在确认没有血液或脑脊液后,注射0.3%盐酸罗哌卡因1-2毫升,以确认针头位置合适,然后给患者服用预定体积的0.3%盐酸罗哌卡因。胸椎旁阻滞注射后每5分钟进行一次针刺的感觉测试,持续30分钟,以确定发生针刺感觉丧失及其阻滞作用的时间段。
    结果:所有患者均完成研究,14例(51.8%)阻断成功。
    结论:0.3%罗哌卡因的EV50为18.46ml(95%CI17.09-19.95ml),EV95为20.89ml。
    BACKGROUND: Ultrasound-guided needle placement has revolutionized the thoracic paravertebral block technique and can be applied in thoracoscopic surgery.
    OBJECTIVE: This study investigated the median effective volume (EV50) of an ultrasound-guided single shot of 0.3% ropivacaine used as a thoracic paravertebral nerve block for the radical thoracoscopic resection of lung cancer.
    METHODS: A total of 27 patients who received a single shot of ultrasound-guided thoracic paravertebral nerve block and underwent radical thoracoscopic resection of lung cancer were enrolled in this study between February 10 and August 13, 2018. All patients were rated as ASA grades I or II. Using ultrasound as a guide, the block needle was gradually pushed through the lateral costotransverse ligaments to the thoracic paravertebral space by the in-plane technique. After confirming the absence of blood or cerebrospinal fluid, 1-2 ml of 0.3% ropivacaine hydrochloride was injected to confirm that the position of the needle was appropriate, and a pre-determined volume of 0.3% ropivacaine hydrochloride was then administered to the patients. Sensory testing by pinprick was performed every 5 minutes for 30 minutes following the thoracic paravertebral block injection to identify the time segments during which the loss of sensation to the pinprick and its blocking effect occurred.
    RESULTS: All patients completed the study and 14 (51.8%) had a successful block.
    CONCLUSIONS: The EV50 of 0.3% ropivacaine was 18.46 ml (95% CI 17.09-19.95 ml) and the EV95 was 20.89 ml.
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  • 文章类型: Journal Article
    涉及多个治疗线的癌症试验大大增加了我们对治疗策略的理解。然而,即使这些研究的主要终点是无进展生存期(PFS),他们的统计分析通常分别关注每一行,或者不考虑重复的事件,因此缺少潜在的相关信息。因此,对治疗策略有效性的评估严重受损.
    我们在ITACa(意大利晚期结直肠癌试验)随机试验中评估了贝伐单抗(B)用于一线或二线治疗转移性结直肠癌(mCRC)的潜在不同效果。ITACa试验包括两组:一线化疗(CT)B,然后是单独的二线CT,而根据KRAS状态,仅一线CT,然后是二线CTB或CTB西妥昔单抗。重复疾病进展的Cox模型,潜在选择偏差采用逆概率审查加权法进行调整。报告了PFS(主要终点)的危险比(HR)[95%置信区间(CI)]。
    B在两条线上的总体效果导致HR=0.80(95%CI0.68-0.95,p=0.008)。评估B在一线和二线的差异效应,与单用CT相比,在一线化疗(CT)中添加B可降低10%的风险(HR=0.90,95%CI0.72~1.12,p=0.340);与单用CT相比,在二线CT中添加B可降低36%的风险(HR=0.64,95%CI0.49~0.84,p=0.0011).
    我们的结果似乎表明,B与二线化疗联合使用时具有PFS优势,这可能有助于改善当前有关最佳序贯治疗策略的国际指南。
    UNASSIGNED: Cancer trials involving multiple treatment lines substantially increase our understanding of therapeutic strategies. However, even when the primary end-point of these studies is progression-free survival (PFS), their statistical analysis usually focuses on each line separately, or does not consider repeated events, thus missing potentially relevant information. Consequently, the evaluation of the effectiveness of treatment strategies is highly impaired.
    UNASSIGNED: We evaluated the potentially different effect of bevacizumab (B) administered for the first- or second-line treatment of metastatic colorectal cancer (mCRC) in the ITACa (Italian Trial in Advanced Colorectal Cancer) randomized trial. The ITACa trial consisted of two arms: first-line chemotherapy (CT)+B followed by second-line CT alone versus first-line CT alone followed by second-line CT+B or CT+B+cetuximab according to KRAS status. Cox models for repeated disease progression were performed, and potential selection bias was adjusted using the inverse probability of censoring weighting method. Hazard ratios (HR) [95% confidence interval (CI)] for PFS (primary endpoint) were reported.
    UNASSIGNED: The overall effect of B across the two lines resulted in a HR = 0.80 (95% CI 0.68-0.95, p = 0.008). Evaluating the differential effect of B in first- and second-line, the addition of B to first-line chemotherapy (CT) produced a 10% risk reduction (HR = 0.90, 95% CI 0.72-1.12, p = 0.340) versus CT alone; B added to second-line CT produced a 36% risk reduction (HR = 0.64, 95% CI 0.49-0.84, p = 0.0011) versus CT alone.
    UNASSIGNED: Our results seem to suggest that B confers a PFS advantage when administered in combination with second-line chemotherapy, which could help to improve current international guidelines on optimal sequential treatment strategies.
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  • 文章类型: Journal Article
    目的:提高临床医生和流行病学家的认识,即单患者(n-of-1)试验可能有助于为慢性病患者提供个性化治疗决策。
    方法:我们回顾了关于单患者试验方法和应用的临床和统计文献,然后批判性地评估了进一步方法学发展的需求。
    结果:现有文献报道在108项针对不同临床条件的研究中应用了2,154项单患者试验;最近的各种评论主张在临床决策中更广泛地应用此类试验。最近几项初步可接受性研究的初步证据表明,单患者试验有可能被患者和临床医生广泛接受,作为提高治疗精度的有效方式。贝叶斯和自适应统计方法有望提高单患者试验的信息产量,同时减轻参与者的负担。但没有广泛使用。可以通过进一步开发和应用适应性试验设计方法来增强单患者试验的个性化应用,停止规则,网络荟萃分析,冲洗方法,以及将试验结果传达给患者和临床医生的方法。
    结论:单患者试验可能会成为方法学器械的重要组成部分,用于比较有效性研究和以患者为中心的结果研究。通过允许直接估计个体治疗效果,它们可以促进精细分级的个性化护理,提高治疗精度,改善患者预后,并降低成本。
    OBJECTIVE: To raise awareness among clinicians and epidemiologists that single-patient (n-of-1) trials are potentially useful for informing personalized treatment decisions for patients with chronic conditions.
    METHODS: We reviewed the clinical and statistical literature on methods and applications of single-patient trials and then critically evaluated the needs for further methodological developments.
    RESULTS: Existing literature reports application of 2,154 single-patient trials in 108 studies for diverse clinical conditions; various recent commentaries advocate for wider application of such trials in clinical decision making. Preliminary evidence from several recent pilot acceptability studies suggests that single-patient trials have the potential for widespread acceptance by patients and clinicians as an effective modality for increasing the therapeutic precision. Bayesian and adaptive statistical methods hold promise for increasing the informational yield of single-patient trials while reducing participant burden, but are not widely used. Personalized applications of single-patient trials can be enhanced through further development and application of methodologies on adaptive trial design, stopping rules, network meta-analysis, washout methods, and methods for communicating trial findings to patients and clinicians.
    CONCLUSIONS: Single-patient trials may be poised to emerge as an important part of the methodological armamentarium for comparative effectiveness research and patient-centered outcomes research. By permitting direct estimation of individual treatment effects, they can facilitate finely graded individualized care, enhance therapeutic precision, improve patient outcomes, and reduce costs.
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  • 文章类型: Journal Article
    Individuals with major depressive disorder (MDD) show alterations in the cognitive control function of conflict processing. We examined the influence of these deficits on behavioral and event-related potential (ERP) indices of conflict adaptation, a cognitive control process wherein previous-trial congruency modulates current-trial performance, in 55 individuals with MDD and 55 matched controls. ERPs were calculated while participants completed a modified flanker task. There were nonsignificant between-groups differences in response time, error rate, and N2 indices of conflict adaptation. Higher depressive symptom scores were associated with smaller mean N2 conflict adaptation scores for individuals with MDD and when collapsed across groups. Results were consistent when comorbidity and medications were analyzed. These findings suggest N2 conflict adaptation is associated with depressive symptoms rather than clinical diagnosis alone.
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