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American Journal of Otolaryngology 2024Meniere's Disease is a condition known for its recurrent vertigo, fluctuating sensorineural hearing loss, aural fullness, and tinnitus. Previous studies have... (Meta-Analysis)
Meta-Analysis
PURPOSE
Meniere's Disease is a condition known for its recurrent vertigo, fluctuating sensorineural hearing loss, aural fullness, and tinnitus. Previous studies have demonstrated significant influence of placebo treatments. Our objective was to quantify the magnitude of the placebo effect in randomized controlled trials for Meniere's Disease.
MATERIALS AND METHODS
A systematic review was performed by searching PubMed, SCOPUS, CINAHL, and Cochrane databases from inception through September 27, 2022. Data extraction, quality rating, and risk of bias assessment were performed by two independent reviewers. A meta-analysis of mean differences with 95 % confidence interval, weighted summary proportions, and proportion differences were calculated using random and fixed effects models.
RESULTS
A total of 15 studies (N = 892) were included in the review. Significant improvement was seen in the functional level scores of the pooled placebo groups, with a mean difference of -0.6 points, (95%CI: -1.2 to -0.1). There was no difference in pure tone audiometry, speech discrimination score, or vertigo frequency at 1 and 3 months for the placebo group. Patient-reported vertigo episodes were improved in 52.5 % (95%CI: 39.2 to 65.5) of the placebo group and was significantly less than the pooled experimental group (90.1 %, 95%CI: 39.2 to 65.5, p < 0.001).
CONCLUSIONS
The placebo effect in Meniere's Disease trials is associated with some symptomatic improvement in subjective outcomes, such as patient reported vertigo episodes. However, the clinical significance is questionable across other outcomes measures, especially when analyzing objective data. The extent and strength of the placebo effect continues to be a hurdle in the search for better treatment options.
Topics: Humans; Meniere Disease; Placebo Effect; Randomized Controlled Trials as Topic; Vertigo; Tinnitus
PubMed: 38101129
DOI: 10.1016/j.amjoto.2023.104178 -
The Journal of Medicine and Philosophy Apr 2024The placebo effect is now generally defined widely as an individual's response to the psychosocial context of a clinical treatment, as distinct from the treatment's...
The placebo effect is now generally defined widely as an individual's response to the psychosocial context of a clinical treatment, as distinct from the treatment's characteristic physiological effects. Some researchers, however, argue that such a wide definition leads to confusion and misleading implications. In response, they propose a narrow definition restricted to the therapeutic effects of deliberate placebo treatments. Within the framework of modern medicine, such a scope currently leaves one viable placebo treatment paradigm: the non-deceptive and non-concealed administration of "placebo pills" or open-label placebo (OLP) treatment. In this paper, I consider how the placebo effect occurs in OLP. I argue that a traditional, belief-based account of OLP is paradoxical. Instead, I propose an account based on the non-doxastic attitude of pretence, understood within a fictionalist framework.
Topics: Humans; Placebo Effect
PubMed: 38530636
DOI: 10.1093/jmp/jhae008 -
Inflammatory Bowel Diseases Apr 2024Precise estimates of placebo response rates help efficient clinical trial design. In this systematic review and meta-analysis, we assessed contemporary placebo... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Precise estimates of placebo response rates help efficient clinical trial design. In this systematic review and meta-analysis, we assessed contemporary placebo endoscopic and histological response rates in Crohn's disease (CD) clinical trials.
METHODS
MEDLINE, EMBASE, and Cochrane CENTRAL were searched from inception to April 2022 to identify placebo-controlled studies of pharmacological interventions for CD. Endoscopic response, remission, and mucosal healing rates for participants assigned to placebo in induction and maintenance studies were pooled using a random-effects model. Point estimates and associated 95% confidence intervals (CIs) were calculated.
RESULTS
In total, 16 studies (11 induction, 3 maintenance, 2 induction and maintenance) that randomized 1646 participants to placebo were eligible. For induction trials, the pooled placebo endoscopic response, endoscopic remission, and mucosal healing rates in participants assigned to placebo were 13% (95% CI, 10-16; I2 = 14.1%; P = .14), 6% (95% CI, 3-11; I2 = 74.7%; P < .001), and 6% (95% CI, 4-9; I2 = 26.9%; P = .29), respectively. The pooled endoscopic remission rate in patients who were bio-naïve was 10% (95% CI, 4-23) compared with only 4% (95% CI, 3-7) in bio-experienced patients. For maintenance trials, the pooled endoscopic response, remission, and mucosal healing rates were 7% (95% CI, 1-31; I2 = 78.2%; P = .004), 11% (95% CI, 4-27; I2 = 70.8%; P = .06), and 7% (95% CI, 3-15; I2 = 29.7; P = .23), respectively. Only 3 trials assessed histological outcomes.
CONCLUSIONS
Endoscopic placebo rates vary according to trial phase and prior biologic exposure. These contemporary data will serve to inform CD trial design, sample size calculation, and end point selection for future trials.
Topics: Humans; Crohn Disease; Endoscopy; Remission Induction; Placebo Effect; Randomized Controlled Trials as Topic
PubMed: 37002875
DOI: 10.1093/ibd/izad052 -
The Journal of Nutrition Nov 2023Despite compositional alterations in gastrointestinal microbiota being purported to underpin some of the therapeutic effects of ginger, the effect of a standardized... (Randomized Controlled Trial)
Randomized Controlled Trial
Effect of Ginger Root Powder on Gastrointestinal Bacteria Composition, Gastrointestinal Symptoms, Mental Health, Fatigue, and Quality of Life: A Double-Blind Placebo-Controlled Trial.
BACKGROUND
Despite compositional alterations in gastrointestinal microbiota being purported to underpin some of the therapeutic effects of ginger, the effect of a standardized ginger supplement on gut microbiota has not been tested in humans.
OBJECTIVES
To determine the effect of a standardized ginger (Zingiber officinale) root powder, compared to placebo, on gastrointestinal bacteria and associated outcomes in healthy adults.
METHODS
A randomized double-blind placebo-controlled trial allocated participants aged 18 to 30 y to ginger or microcrystalline cellulose (MCC) placebo. The intervention comprised 1.2 g/d of ginger (4 capsules per day totaling 84 mg/d of active gingerols/shogaols) for 14 d following a 1-wk run-in period. Primary outcomes were gastrointestinal community composition, alpha and beta diversity, and differential abundance, measured using 16S rRNA gene sequencing of fecal samples. Secondary outcomes were gastrointestinal symptoms, bowel function, depression, anxiety, stress, fatigue, quality of life, and adverse events.
RESULTS
Fifty-one participants were enrolled and analyzed (71% female; mean age 25 ± 3 y; ginger: n = 29, placebo: n = 22). There was a greater increase in relative abundance of phylum, Actinobacteria, observed following ginger supplementation compared to placebo (U: 145.0; z: -2.1; P = 0.033). Ginger was associated with a greater abundance of the genera Parabacteroides, Bacillus, Ruminococcaceae incertae sedis, unclassified Bacilli, families Defluviitaleaceae, Morganellaceae, and Bacillaceae as well as lower abundance of the genus Blautia and family Sphingomonadaceae (P < 0.05). An improvement in indigestion symptoms was observed with ginger supplementation (U: 196.0; z: -2.4; P = 0.015). No differences between ginger and placebo groups were found for alpha and beta diversity or other secondary outcomes. No moderate or severe adverse events were reported.
CONCLUSIONS
Supplementation with ginger root powder was safe and altered aspects of gastrointestinal bacteria composition; however, it did not change alpha- or beta diversity, bowel function, gastrointestinal symptoms, mood, or quality of life in healthy adults. These results provide further understanding regarding the mechanisms of action of ginger supplementation. This trial was registered in the Australia New Zealand Clinical Trials Registry as ACTRN12620000302954p and the Therapeutic Goods Administration as CT-2020-CTN-00380-1.
Topics: Adult; Humans; Female; Young Adult; Male; Zingiber officinale; Powders; Quality of Life; Mental Health; RNA, Ribosomal, 16S; Fatigue; Double-Blind Method
PubMed: 37690779
DOI: 10.1016/j.tjnut.2023.09.002 -
Japanese Journal of Ophthalmology Sep 2023Having previously demonstrated the efficacy of 0.01% atropine eye drops for inhibiting progression of childhood myopia, we conducted additional analyses to assess... (Randomized Controlled Trial)
Randomized Controlled Trial
PURPOSE
Having previously demonstrated the efficacy of 0.01% atropine eye drops for inhibiting progression of childhood myopia, we conducted additional analyses to assess post-treatment changes in myopia progression.
STUDY DESIGN
Analysis of follow-up data from a previously reported randomized controlled trial METHODS: A mixed-effects model was used to compare intergroup changes in spherical equivalent (SE) and axial length (AL) at 1 month and 12 months after discontinuation of 2-year treatment with atropine or placebo in 167 school-age children.
RESULTS
Follow-up measurements were available for 149 participants at 1 month after discontinuation of treatment and for 51 participants at 12 months after discontinuation. At 1 month post-treatment, differences between the atropine and placebo groups in least squares (LS) mean changes in SE and AL, respectively, from 24 months were -0.06 diopters (D) (95% CI: -0.21, 0.08; P = .39) and 0.02 mm (95% CI: -0.05, 0.08; P = .60). At 12 months post-treatment, intergroup differences (atropine vs placebo) in LS mean changes in SE and AL, respectively, were -0.13 D (95% CI: -0.35, 0.10; P = .26) and -0.02 mm (95% CI: -0.12, 0.09; P = .75). LS mean changes in SE and AL from treatment discontinuation did not differ between the groups at 1 or 12 months post-treatment.
CONCLUSION
Axial elongation was significantly less in the atropine group than in the placebo group. The suppression effect obtained at 2 years was maintained after 12 months. The absence of intergroup differences in myopia progression since treatment cessation suggests that myopic rebound did not occur.
Topics: Humans; Child; Atropine; Ophthalmic Solutions; East Asian People; Disease Progression; Myopia; Refraction, Ocular; Axial Length, Eye
PubMed: 37548816
DOI: 10.1007/s10384-023-01012-8 -
Optometry and Vision Science : Official... Aug 2023Low-dose atropine is one of the leading treatments of myopia progression in children. However, the effect of low-dose atropine on binocular vision measurements has not... (Randomized Controlled Trial)
Randomized Controlled Trial
SIGNIFICANCE
Low-dose atropine is one of the leading treatments of myopia progression in children. However, the effect of low-dose atropine on binocular vision measurements has not been thoroughly studied.
PURPOSE
This study aimed to determine the effect of 0.01, 0.03, and 0.05% atropine on visual acuity, pupil size, binocular vision, and accommodation in children aged 6 to 17 years.
METHODS
Forty-six children (28 girls and 18 boys) were randomized into four groups: placebo (n = 10) and 0.01% (n = 13), 0.03% (n = 11), and 0.05% (n = 12) atropine. One drop of atropine or placebo was administered into each eye once. The following measurements were collected before applying the eye drops and 30 minutes, 60 minutes, and 24 hours after application of eye drops: habitual visual acuity at distance and near, pupil size, dissociated phoria at distance and near, negative and positive fusional vergence, near point convergence, near point convergence stamina and fragility, accommodative lag, and amplitude of accommodation. Repeated-measures analysis of variance was used, and P < .05 was considered statistically significant.
RESULTS
Differences in pupil diameters under photopic and scotopic conditions were statistically significant when comparing all three atropine groups with placebo over time ( P < .001). Pupil size in both the 0.03 and 0.05% atropine groups was enlarged from baseline at the 30-minute, 60-minute, and 24-hour time points ( P < .05) in both photopic and scotopic conditions. Pupil size in the 0.01% atropine group had minimal change, and only the scotopic 60-minute time point was statistically significant ( P = .02). All three concentrations of atropine eye drops have no significant effect on accommodation, binocular vision measurements, or visual acuity compared with the control group.
CONCLUSIONS
Pupil size was significantly enlarged by 0.03 and 0.05% atropine in both photopic and scotopic conditions. Low-dose atropine eye drops have no significant effect on accommodation, binocular vision measurements, or visual acuity compared with control.
Topics: Male; Female; Humans; Child; Atropine; Vision, Binocular; Visual Acuity; Accommodation, Ocular; Ophthalmic Solutions
PubMed: 37278695
DOI: 10.1097/OPX.0000000000002031 -
NeuroImage Dec 2023Literature suggests that attention is a critical cognitive process for pain perception and modulation and may play an important role in placebo and nocebo effects. Here,... (Randomized Controlled Trial)
Randomized Controlled Trial
Modulation effects of repeated transcranial direct current stimulation on the dorsal attention and frontal parietal networks and its association with placebo and nocebo effects.
Literature suggests that attention is a critical cognitive process for pain perception and modulation and may play an important role in placebo and nocebo effects. Here, we investigated how repeated transcranial direct current stimulation (tDCS) applied at the dorsolateral prefrontal cortex (DLPFC) for three consecutive days can modulate the brain functional connectivity (FC) of two networks involved in cognitive control: the frontoparietal network (FPN) and dorsal attention network (DAN), and its association with placebo and nocebo effects. 81 healthy subjects were randomized to three groups: anodal, cathodal, and sham tDCS. Resting state fMRI scans were acquired pre- and post- tDCS on the first and third day of tDCS. An Independent Component Analysis (ICA) was performed to identify the FPN and DAN. ANCOVA was applied for group analysis. Compared to sham tDCS, 1) both cathodal and anodal tDCS increased the FC between the DAN and right parietal operculum; cathodal tDCS also increased the FC between the DAN and right postcentral gyrus; 2) anodal tDCS led to an increased FC between the FPN and right parietal operculum, while cathodal tDCS was associated with increased FC between the FPN and left superior parietal lobule/precuneus; 3) the FC increase between the DAN and right parietal operculum was significantly correlated to the placebo analgesia effect in the cathodal group. Our findings suggest that both repeated cathodal and anodal tDCS could modulate the FC of two important cognitive brain networks (DAN and FPN), which may modulate placebo / nocebo effects.
Topics: Humans; Transcranial Direct Current Stimulation; Nocebo Effect; Prefrontal Cortex; Brain; Pain
PubMed: 37939891
DOI: 10.1016/j.neuroimage.2023.120433 -
Food & Function Jul 2023Energy drinks take advantage of caffeine's effects on wakefulness and performance; however, excessive intake has a negative effect on sleep. Green tea is consumed...
Energy drinks take advantage of caffeine's effects on wakefulness and performance; however, excessive intake has a negative effect on sleep. Green tea is consumed worldwide and has both a stimulating effect from caffeine and a calming or relaxing effect from theanine. Theanine reduces the excitotoxicity of caffeine. This study evaluated whether theanine improves the sleep quality worsened by caffeine in healthy young women. Sleep latency, sleep time, wake after sleep onset (WASO) time, and the number of WASOs were measured. A crossover study was performed using four treatment groups: theanine (50 mg), caffeine (30 mg), combined theanine and caffeine (TC), and placebo. The sleep stage was determined using electroencephalograms, and cerebral blood flow was measured using near-infrared spectroscopy. The caffeine group showed a significant increase in the WASO time compared with the placebo group; no difference was observed between the theanine or TC group and the placebo group. There were no differences in the sleep-onset latency or number of WASOs between the theanine, caffeine, or TC groups and the placebo group. In combination with theanine, only the caffeine-induced increase in the WASO time was suppressed. Our results suggest that theanine can reduce caffeine's effects on sleep quality.
Topics: Humans; Female; Caffeine; Wakefulness; Sleep Quality; Cross-Over Studies; Double-Blind Method
PubMed: 37458751
DOI: 10.1039/d3fo01247f -
Neuromodulation : Journal of the... Dec 2023The magnitude of the placebo response depends on both the modality used as the "placebo" and the intervention with which it is compared, both of which can complicate the...
BACKGROUND
The magnitude of the placebo response depends on both the modality used as the "placebo" and the intervention with which it is compared, both of which can complicate the interpretation of randomized controlled trials (RCTs) for depression in late life. Given that neurostimulation and pharmacotherapy are among the most common interventions studied for late-life depression, comparing the relative placebo responses in studies of these interventions can aid interpretation of relative effect sizes.
MATERIALS AND METHODS
We analyzed data from two RCTs of adults aged ≥60 years in an episode of treatment-resistant major depression, one comparing aripiprazole and matching placebo pills and the other comparing deep repetitive transcranial magnetic stimulation (rTMS) and sham rTMS. In both RCTs, depression was assessed using the 17-item Hamilton Depression Rating Scale (HDRS-17). The primary comparison occurred after four weeks using analysis of covariance (ANCOVA) of HDRS-17 scores in participants who received placebo pills or sham rTMS. Relevant covariates included years of education, duration of depressive episode, and baseline HDRS-17 score.
RESULTS
Accounting for covariates, there was a larger reduction of HDRS-17 after four weeks in the sham rTMS group (estimated marginal mean ± SE: -5.90 ± 1.45; 95% CI: [-8.82, 2.98]) than in the placebo pills group (-1.07 ± 1.45; [-3.98, 1.85]). There were no significant differences between these groups in the binary outcome analysis of response and remission rates at four weeks or any outcome at trial end point comparison.
CONCLUSIONS
Sham rTMS may have a larger placebo response than placebo pills early in the treatment of older adults with treatment-resistant depression. Differential placebo responses should be considered in both the interpretation and design of RCTs.
Topics: Humans; Aged; Depression; Depressive Disorder, Major; Transcranial Magnetic Stimulation; Placebo Effect; Treatment Outcome; Double-Blind Method
PubMed: 35088720
DOI: 10.1016/j.neurom.2021.10.019 -
Journal of Applied Physiology... Aug 2023We tested the hypothesis that ingestion of cocoa flavanols would improve cognition during acute hypoxia equivalent to 5,500 m altitude (partial pressure of end-tidal... (Randomized Controlled Trial)
Randomized Controlled Trial
We tested the hypothesis that ingestion of cocoa flavanols would improve cognition during acute hypoxia equivalent to 5,500 m altitude (partial pressure of end-tidal oxygen = 45 mmHg). Using placebo-controlled double-blind trials, 12 participants ingested 15 mg·kg of cocoa flavanols 90 min before completing cognitive tasks during normoxia and either poikilocapnic or isocapnic hypoxia (partial pressure of end-tidal carbon dioxide uncontrolled or maintained at the baseline value, respectively). Cerebral oxygenation was measured using functional near-infrared spectroscopy. Overall cognition was impaired by poikilocapnic hypoxia (main effect of hypoxia, = 0.008). Cocoa flavanols improved a measure of overall cognitive performance by 4% compared with placebo (effect of flavanols, = 0.033) during hypoxia, indicating a change in performance from "low average" to "average." The hypoxia-induced decrease in cerebral oxygenation was two-fold greater with placebo than with cocoa flavanols (effect of flavanols, = 0.005). Subjective fatigue was increased by 900% with placebo compared with flavanols during poikilocapnic hypoxia (effect of flavanols, = 0.004). Overall cognition was impaired by isocapnic hypoxia (effect of hypoxia, = 0.001) but was not improved by cocoa flavanols (mean improvement = 1%; effect of flavanols, = 0.72). Reaction time was impaired by 8% with flavanols during normoxia and further impaired by 11% during isocapnic hypoxia (effect of flavanols, = 0.01). Our findings are the first to show that flavanol-mediated improvements in cognition and mood during normoxia persist during severe oxygen deprivation, conferring a neuroprotective effect. We show for the first time that cocoa flavanols exert a neuroprotective effect during severe hypoxia. Following acute cocoa flavanol ingestion, we observed improvements in cognition, cerebral oxygenation, and subjective fatigue during normoxia and severe poikilocapnic hypoxia. Cocoa flavanols did not improve cognition during severe isocapnic hypoxia, suggesting a possible interaction with carbon dioxide.
Topics: Humans; Cacao; Carbon Dioxide; Cognition; Hypoxia; Mental Fatigue; Neuroprotective Agents; Oxygen; Polyphenols; Double-Blind Method
PubMed: 37471213
DOI: 10.1152/japplphysiol.00219.2023