Quantification of the placebo response in ulcerative colitis
Abstract
BACKGROUND & AIMS: There is consistently a measurable benefit noted among placebo users in treatment trials of ulcerative colitis (UC). The aim of this study was to define the placebo response in active UC and identify study features that influence the placebo response. METHODS: MEDLINE database was searched for placebo-controlled treatment studies of active UC. Data extraction was performed by two reviewers, and one separate investigator reviewed all trials and data extraction before data tabulation. Placebo remission and benefit rates were determined for clinical, endoscopic, and histological outcomes. Synthesis analysis on the weighted proportions from the different studies explored the placebo response as it related to eight study variables. RESULTS: Thirty-eight of 44 studies identified were included in the analysis. The clinical remission rate was 9.1% (confidence interval [CI], 6.6- 11.6) and the benefit rate was 26.7% (CI, 24.1-29.2). Similar rates were observed endoscopically and histologically. The number of study visits (< or =3 vs. >3) modified placebo response as assessed by clinical benefit (P = 0.05), endoscopic remission (P = 0.02), and histological remission (P = 0.04). Other study variables were not significant placebo response modifiers. CONCLUSIONS: In trials of active UC, the placebo remission rate is approximately 10% and the placebo benefit rate is approximately 30%. These rates are consistent regardless of assessment end point. The placebo response is greater in trials with more frequent study visits (more than three). (Gastroenterology 1997 Jun;112(6):1854-8)
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Repetitive transcranial magnetic stimulation in treatment-seeking subjects with cocaine use disorder: A randomized, double-blind, sham-controlled trial
2022, Progress in Neuro-Psychopharmacology and Biological PsychiatryCocaine use disorder (CUD) is a chronic and relapsing brain disorder with no approved treatments. Repetitive transcranial magnetic stimulation (rTMS) has shown promising results in open label and single-blind studies, reducing cocaine craving and consumption. Although, large randomized, double-blind, controlled trials are still missing.
This multi-center, randomized, double-blind, sham-controlled study was designed to evaluate the safety and efficacy of multiple sessions of active rTMS compared to sham stimulation in patients with CUD.
rTMS (15 Hz, 2 daily sessions for 5 days/week,for a total of 20 stimulation sessions) was delivered over the left DLPFC for two weeks of continuous treatment followed by 12 weeks of maintenance (1 day/week, twice a day), in a double-blind, randomized sham-controlled design. Our primary outcomes included self-reported cue-induced craving and cocaine consumption, as measured by percentage of negative urine tests. Our secondary outcomes included: 1) changes in depressive symptoms; 2) changes in cocaine withdrawal symptoms; and 3) changes in self-reported days of cocaine use.
Forty-two outpatients with CUD were enrolled in the active rTMS group and 38 patients in the sham group. We observed a significant decrease in self-reported cue-induced cocaine craving and consumption in both the active rTMS and sham, whereas no main effect of treatment was found. However, the active rTMS group showed greater changes in depressive symptoms. The improvement on depressive symptomatology was particularly marked among patients receiving a total number of rTMS sessions greater than 40 and those reporting more severe depressive symptoms at baseline.
A significant improvement of CUD symptoms during active rTMS treatment was observed. However, we did not observe significant differences in cocaine craving and consumption between treatment groups, highlighting the complexity of factors contributing to CUD maintenance. A significant improvement in depressive symptoms was observed in favour of the active group.
Clinical trial registration details:clinicaltrials.govidentifierNCT03333460
Radiofrequency Ablation Is Associated with Decreased Neoplastic Progression in Patients with Barrett's Esophagus and Confirmed Low-Grade Dysplasia
2015, GastroenterologyBarrett's esophagus (BE) with low-grade dysplasia (LGD) can progress to high-grade dysplasia (HGD) and esophageal adenocarcinoma (EAC). Radiofrequency ablation (RFA) has been shown to be an effective treatment for LGD in clinical trials, but its effectiveness in clinical practice is unclear. We compared the rate of progression of LGD after RFA with endoscopic surveillance alone in routine clinical practice.
We performed a retrospective study of patients who either underwent RFA (n = 45) or surveillance endoscopy (n = 125) for LGD, confirmed by at least 1 expert pathologist, from October 1992 through December 2013 at 3 medical centers in the United States. Cox regression analysis was used to assess the association between progression and RFA.
Data were collected over median follow-up periods of 889 days (interquartile range, 264−1623 days) after RFA and 848 days (interquartile range, 322−2355 days) after surveillance endoscopy (P = .32). The annual rates of progression to HGD or EAC were 6.6% in the surveillance group and 0.77% in the RFA group. The risk of progression to HGD or EAC was significantly lower among patients who underwent RFA than those who underwent surveillance (adjusted hazard ratio = 0.06; 95% confidence interval: 0.008−0.48).
Among patients with BE and confirmed LGD, rates of progression to a combined end point of HGD and EAC were lower among those treated with RFA than among untreated patients. Although selection bias cannot be excluded, these findings provide additional evidence for the use of endoscopic ablation therapy for LGD.
Spicing up the Treatment of Mild to Moderate Ulcerative Colitis
2015, Clinical Gastroenterology and HepatologyPlacebo response rate in clinical trials of fistulizing Crohn's disease: Systematic Review and Meta-analysis
2014, Clinical Gastroenterology and HepatologyIt is important to determine the magnitude and identify modifiers of the rate of response to placebo in clinical trials of fistulizing Crohn’s disease (CD), to understand disease progression, and to calculate sample size. We conducted a systematic review and meta-analysis of rates of response to placebo in trials of patients with fistulizing CD.
We searched MEDLINE, EMBASE, EMBASE CLASSIC, and the Cochrane central register of controlled trials for randomized controlled trials (RCTs) comparing pharmacologic agents with placebo in adults with fistulizing CD. We identified studies that reported complete fistula closure, partial closure, or response. Data were extracted as intention-to-treat analyses and pooled by using a random-effects model. Proportions of patients who received placebo and had complete or partial fistula(e) closure were calculated, with 95% confidence intervals (CIs). The effects of trial characteristics on the magnitude of response to placebo were examined.
Thirteen RCTs were eligible for our analysis; these included 579 patients assigned to placebo groups. The pooled rate of response to placebo, among all RCTs, for complete fistula closure was 15.6% (95% CI, 10.9%–20.9%), with significant heterogeneity (I2 = 62.5%, P = .001). The pooled rate of response to placebo for partial fistula closure or response in 9 trials, comprising 423 patients, was 18.3% (95% CI, 14.8%–22.1%). Rates of response to placebo were significantly lower in trials with shorter durations of therapy and shorter intervals to assessment of fistula closure. Neither exposure to the pharmacologic agent during the induction phase of the same (or related) RCT nor concomitant medications had any effect.
In a meta-analysis of rate of response to placebo in patients with fistulizing CD, we found that fistulae closed in almost 1/6 patients given placebo in RCTs of pharmacologic agents. Future research should identify characteristics of patients that predict response to placebo.
The placebo effect and homeopathy
2014, Revista Medica de HomeopatiaComo otras formas de medicina, incluyendo la medicina complementaria y alternativa, la homeopatía provoca expectativas de los pacientes. La relación médicopaciente, el tratamiento personal y amplio, y la falta de efectos adversos, constituyen elementos para crear expectativas positivas. Otros elementos pueden asociarse a las expectativas negativas.
Realizamos una revisión sistemática de la bibliografía sobre los efectos placebo y nocebo en la acupuntura y la homeopatía, utilizando Medline.
Se revisaron los hallazgos sobre los mecanismos psicofisiológicos y neuromediadores. Los estudios de dichos efectos revelan el modo en que pueden medirse las expectativas y el condicionamiento inconsciente mediante métodos de escáner y electroencefalografía. Ello deriva en efectos terapéuticos significativos y no específicos que pueden confundir la evaluación del tratamiento de los efectos terapéuticos específicos, dificultando la selección del simillimum.
Se abordan las orientaciones de la investigación futura sobre los efectos terapéuticos no específicos de la homeopatía, para mejorar la práctica y la investigación clínicas.
Like other forms of medicine, including complementary and alternative medicine, homeopathy elicits expectations in patients. The physician–patient relationship, personal and comprehensive treatment and lack of adverse effects are elements in creating positive expectations. Other elements may be associated with negative expectations.
We conducted a systematic literature review on placebo and nocebo effects in acupuncture and homeopathy using Medline.
Findings on the psychophysiological and neuromediating mechanisms of the placebo-nocebo phenomenon are reviewed. Studies of these effects reveal how expectations and unconscious conditioning can be measured by imaging and electroencephalography methods. They result in signifi t, non-specifi therapeutic effects, which may confuse the evaluation of the specifi therapeutic effects treatment, hampering selection of the simillimum.
Directions for future research on non-specifi therapeutic effects of homeopathy to improve clinical practice and clinical research are discussed.
What are the Best Placebo Interventions for the Treatment of Pain?
2013, Placebo and Pain: From Bench to BedsideMore invasive and impressive therapeutic rituals are generally believed to be more powerful interventions than less impressive ones. This chapter reviews and discusses evidence from randomized clinical trials and meta-analyses for such a differential effectiveness of placebo interventions. Evidence from clinical research that different types of placebo are regularly associated with different magnitudes of placebo effect is limited. However, one area where hints from a variety of sources are accumulating is sham acupuncture in the treatment of pain. Furthermore, there is preliminary evidence that sham surgery and ambiguous evidence that sham injections are associated with enhanced placebo effects on pain. Among the factors that may account for a greater effectiveness of such treatment procedures are the lively perceptual context of the procedures themselves, the attention and enhanced emotional support by healthcare providers, and the increased expectation and motivation of patients. A differential effectiveness of placebo control procedures in clinical trials would have important implications for clinical research.