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The Prostate May 2022It is a common practice to control efficacy of pharmacological treatment with a placebo group. However, placebo itself may affect subjective and even objective results.... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
It is a common practice to control efficacy of pharmacological treatment with a placebo group. However, placebo itself may affect subjective and even objective results. The purpose of this study was to evaluate the placebo effect on symptoms of CP/CPPS to improve future clinical trials.
METHODS
A search at three databases (Scopus, MEDLINE, and Web of Science) was conducted to identify double-blind placebo-controlled clinical trials on the treatment of CP/CPPS published until April 2021. The primary outcome - National Institutes of Health Chronic Prostatitis Symptom Index (NIH-CPSI) score.
SECONDARY OUTCOMES
Qmax, PVR, IPSS, and prostate volume.
RESULTS
A total of 3502 studies were identified. Placebo arms of 42 articles (5512 patients, median 31 patients) were included in the systematic review. Systematic review identified positive changes in the primary endpoint, meta-analysis of 10 articles found that NIH-CPSI total score results were significantly influenced by placebo, mean difference -4.2 (95% confidence interval [CI]: -6.31, -2.09). Mean difference of NIH-CPSI pain domain was -2.31 (95% CI: -3.4, -1.21), urinary domain -1.12 (95% CI: -1.62, -0.62), quality of life domain -1.67 (95% CI: -2.38, -0.96); p < 0.001 for all. In case of the objective indicator - Qmax, there were three articles included in the meta-analysis. Qmax mean change from baseline was 0.68 (95% CI: -0.85, 2.22, p = 0.38). Systematic review showed no significant changes in pain, measured by VAS or other scores, IPSS and PVR.
CONCLUSIONS
Placebo significantly affected the subjective parameters (NIH-CPSI) and limitedly affected various other measurements of pain (visual analog scale, McGill pain questionnaire). There was no long-term effect on IPSS and objective measurements (Qmax, PVR). This study can be used in further clinical trials to develop general rules of CPPS treatment assessment.
Topics: Chronic Disease; Chronic Pain; Humans; Male; Pelvic Pain; Placebo Effect; Prostatitis; Quality of Life; Randomized Controlled Trials as Topic
PubMed: 35133667
DOI: 10.1002/pros.24311 -
Cognition Sep 2021How people choose between options with differing outcomes (explore-exploit) is a central question to understanding human behaviour. However, the standard explore-exploit...
How people choose between options with differing outcomes (explore-exploit) is a central question to understanding human behaviour. However, the standard explore-exploit paradigm relies on gamified tasks with low-stake outcomes. Consequently, little is known about decision making for biologically-relevant stimuli. Here, we combined placebo and explore-exploit paradigms to examine detection and selection of the most effective treatment in a pain model. During conditioning, where 'optimal' and 'suboptimal' sham-treatments were paired with a reduction in electrical pain stimulation, participants learnt which treatment most successfully reduced pain. Modelling participant responses revealed three important findings. First, participants' choices reflected both directed and random exploration. Second, expectancy modulated pain - indicative of recursive placebo effects. Third, individual differences in terms of expectancy during conditioning predicted placebo effects during a subsequent test phase. These findings reveal directed and random exploration when the outcome is biologically-relevant. Moreover, this research shows how placebo and explore-exploit literatures can be unified.
Topics: Electric Stimulation; Humans; Learning; Pain; Placebo Effect
PubMed: 34023671
DOI: 10.1016/j.cognition.2021.104753 -
Journal of Integrative Medicine Sep 2023The placebo response of sham acupuncture in patients with primary dysmenorrhea is a substantial factor associated with analgesia. However, the magnitude of the placebo... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The placebo response of sham acupuncture in patients with primary dysmenorrhea is a substantial factor associated with analgesia. However, the magnitude of the placebo response is unclear.
OBJECTIVE
This meta-analysis assessed the effects of sham acupuncture in patients with primary dysmenorrhea and the factors contributing to these effects.
SEARCH STRATEGY
PubMed, Embase, Web of Science, and Cochrane CENTRAL databases were searched from inception up to August 20, 2022.
INCLUSION CRITERIA
Randomized controlled trials (RCTs) using sham acupuncture as a control for female patients of reproductive age with primary dysmenorrhea were included.
DATA EXTRACTION AND ANALYSIS
Pain intensity, retrospective symptom scale, and health-related quality of life were outcome measures used in these trials. Placebo response was defined as the change in the outcome of interest from baseline to endpoint. We used standardized mean difference (SMD) to estimate the effect size of the placebo response.
RESULTS
Thirteen RCTs were included. The pooled placebo response size for pain intensity was the largest (SMD = -0.99; 95% confidence interval [CI], -1.31 to -0.68), followed by the retrospective symptom scale (Total frequency rating score: SMD = -0.20; 95% CI, -0.80 to -0.39. Average severity score: SMD = -0.35; 95% CI, -0.90 to -0.20) and physical component of SF-36 (SMD = 0.27; 95% CI, -0.17 to 0.72). Studies using blunt-tip needles, single-center trials, studies with a low risk of bias, studies in which patients had a longer disease course, studies in which clinicians had < 5 years of experience, and trials conducted outside Asia were more likely to have a lower placebo response.
CONCLUSION
Strong placebo response and some relative factors were found in patients with primary dysmenorrhea. PROSPERO registration number: CRD42022304215. Please cite this article as: Sun CY, Xiong ZY, Sun CY, Ma PH, Liu XY, Sun CY, Xin ZY, Liu BY, Liu CZ, Yan SY. Placebo response of sham acupuncture in patients with primary dysmenorrhea: A meta-analysis. J Integr Med. 2023; 21(5): 455-463.
Topics: Female; Humans; Dysmenorrhea; Acupuncture Therapy; Pain Management; Needles; Placebo Effect
PubMed: 37620224
DOI: 10.1016/j.joim.2023.08.005 -
Nutrients May 2024This study aimed to analyse the placebo effect associated with a high dose of caffeine (9 mg/kg) on heart rate and its variability and on strength tests. (Randomized Controlled Trial)
Randomized Controlled Trial
UNLABELLED
This study aimed to analyse the placebo effect associated with a high dose of caffeine (9 mg/kg) on heart rate and its variability and on strength tests.
METHODS
18 participants experienced in strength training (19.7 ± 2.3 years; 72.2 ± 15.0 kg; 169.6 ± 9.0 cm) performed two days of trials (caffeine-informed/placebo-ingested (placebo) and non-ingested (control)). Firstly, heart rate and its variability were measured while participants lay down for 15 min. After that, bench press and squat tests were performed at 3 different loads (50%, 75% and 90% of 1RM). Perception of performance, effort and side effects were also evaluated.
RESULTS
no differences were found in the vast majority of strength variables analysed. Resting heart rate decreased in the placebo trial (60.39 ± 10.18 bpm control vs. 57.56 ± 9.50 bpm placebo, = 0.040), and mean RR increased (1020.1 ± 172.9 ms control vs. 1071.5 ± 185.7 ms placebo, = 0.032). Heart rate variability and perception of performance and effort were similar between conditions ( > 0.05 in all cases). Side effects such as activeness and nervousness were reported while consuming the placebo.
CONCLUSIONS
the placebo effect did not modify performance in the majority of the strength test variables, HRV and perception of performance and effort. However, resting heart rate was reduced, mean RR increased, and some side effects appeared in the placebo trial.
Topics: Humans; Caffeine; Heart Rate; Young Adult; Male; Placebo Effect; Female; Adult; Physical Functional Performance; Adolescent; Muscle Strength; Resistance Training
PubMed: 38794643
DOI: 10.3390/nu16101405 -
International Forum of Allergy &... Mar 2024The placebo effect observed in clinical trials evaluating medical treatments for chronic rhinosinusitis (CRS) is not well understood. This systematic review and... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The placebo effect observed in clinical trials evaluating medical treatments for chronic rhinosinusitis (CRS) is not well understood. This systematic review and meta-analysis sought to characterize the placebo effect present within CRS outcomes.
METHODS
A systematic review of PubMed, Scopus, and Cumulated Index in Nursing and Allied Health Nursing (CINAHL) was performed. Randomized controlled trials (RCTs) evaluating medical treatments for CRS versus placebo were included. We assessed patient-reported (sino-nasal outcome test 22 [SNOT-22], nasal obstruction, sense of smell, nasal obstruction visual analogue score [VAS], sense of smell VAS, anterior rhinorrhea, and postnasal drip) and objective (Lund-Mackay Computed tomography (CT) score, peak nasal inspiratory flow [PNIF], nasal polyp scores, 40-item Smell Identification Test, serum IgE, and blood eosinophil levels) outcomes.
RESULTS
Twenty-one RCTs were included, comprising 1437 patients (mean age 49.2 years). Biologics were the most common treatment investigated (n = 9). Eleven studies administered background steroids along with placebo. Following placebo administration, multiple patient-reported outcomes significantly decreased, including SNOT-22 (mean difference -9.49, 95% confidence interval [CI] [-11.26, -7.73]), nasal obstruction (-0.33 [-0.54, -0.13]), sense of smell (-0.22 [-0.33, -0.11]), nasal obstruction VAS (-2.47 [-2.87, -2.06]), and loss of smell VAS (-2.31 [-4.14, -0.47]) scores. For objective measures, significant changes occurred in Lund-Mackay CT score (-0.82, [-1.48, -0.16]) and PNIF (4.70, [4.76, 24.64]) with placebo. Placebo arms had the greatest impact when no background medications were used.
CONCLUSIONS
Placebo treatments have a statistically and potentially clinically significant effect on patient-reported and some objective CRS outcomes. Further investigation is required to fully understand placebo effect, which could improve assessment of RCTs and impact patient care.
Topics: Humans; Middle Aged; Nasal Obstruction; Rhinosinusitis; Rhinitis; Nasal Polyps; Sinusitis; Chronic Disease; Placebo Effect; Randomized Controlled Trials as Topic
PubMed: 37985206
DOI: 10.1002/alr.23302 -
The Journal of Pain Dec 2019Placebo analgesia is a robust phenomenon readily observed in both experimental and clinical settings. While researchers have begun to unpack its psychobiological... (Randomized Controlled Trial)
Randomized Controlled Trial
Placebo analgesia is a robust phenomenon readily observed in both experimental and clinical settings. While researchers have begun to unpack its psychobiological mechanisms, important questions remain regarding how we can capitalize on the placebo effect to improve clinical pain outcomes. The current study tested whether providing individuals with instrumental control-that is, control over if and when they administer a treatment-is capable of enhancing placebo analgesia. Using an established electrocutaneous pain design, 87 healthy volunteers either received placebo conditioning with instrumental control over treatment administration, standard passive placebo conditioning without any control over treatment administration, or were allocated to natural history control group with no conditioning and were later tested at equivalent shock intensity with and without placebo applied. Both placebo groups demonstrated initial placebo analgesia. Importantly, however, those provided with instrumental control demonstrated significantly larger and longer lasting placebo analgesia as well as reduced anticipatory autonomic arousal than those receiving standard passive placebo conditioning. This suggests that providing instrumental control over treatment administration can facilitate placebo analgesia by enhancing its magnitude and durability. As such, providing instrumental control over treatment administration may be a cheap and ethical method of using the placebo effect to improve clinical pain outcomes. PERSPECTIVE: Placebo research typically involves passive designs where individuals have no control over treatment administration. We present novel data demonstrating that providing control over treatment administration substantially enhances both the magnitude and duration of placebo analgesia. As such, where possible, providing control may improve clinical pain outcomes via the placebo effect.
Topics: Adult; Analgesia, Patient-Controlled; Female; Humans; Male; Motivation; Placebo Effect; Transcutaneous Electric Nerve Stimulation; Young Adult
PubMed: 31150780
DOI: 10.1016/j.jpain.2019.05.013 -
Journal of the American Academy of... Jul 2021The Neurofeedback Collaborative Group made substantial efforts in assessing clinical effects of neurofeedback (NF) as a promising nonpharmacological treatment option for...
The Neurofeedback Collaborative Group made substantial efforts in assessing clinical effects of neurofeedback (NF) as a promising nonpharmacological treatment option for attention-deficit/hyperactivity disorder (ADHD). In a double-blind, placebo-controlled randomized clinical trial (RCT), they evaluated the specific effects of a standard NF protocol (theta/beta ratio [TBR] training) compared to a placebo-like control group. Similar to pharmacological studies, the placebo-like intervention can be considered as a gold standard, as it allows evaluation of specific effects of NF training.
Topics: Attention Deficit Disorder with Hyperactivity; Double-Blind Method; Humans; Neurofeedback; Placebo Effect
PubMed: 34048885
DOI: 10.1016/j.jaac.2021.05.008 -
British Journal of Anaesthesia Aug 2019Over the past decade, the mechanisms underlying placebo effects have begun to be identified. At the same time, the placebo response appears to have increased in... (Review)
Review
Over the past decade, the mechanisms underlying placebo effects have begun to be identified. At the same time, the placebo response appears to have increased in pharmacological trials and marked placebo effects are found in neurostimulation and surgical trials, thereby posing the question whether non-pharmacological interventions should be placebo-controlled to a greater extent. In this narrative review we discuss how the knowledge of placebo mechanisms may help to improve placebo control in pharmacological and non-pharmacological trials. We review the psychological, neurobiological, and genetic mechanisms underlying placebo analgesia and outline the current problems and potential solutions to the challenges with placebo control in trials on pharmacological, neurostimulation, and surgical interventions. We particularly focus on how patients' perception of the therapeutic intervention, and their expectations towards treatment efficacy may help develop more precise placebo controls and blinding procedures and account for the contribution of placebo factors to the efficacy of active treatments. Finally, we discuss how systematic investigations into placebo mechanisms across various pain conditions and types of treatment are needed in order to 'personalise' the placebo control to the specific pathophysiology and interventions, which may ultimately lead to identification of more effective treatment for pain patients. In conclusion this review shows that it is important to understand how patients' perception and expectations influence the efficacy of active and placebo treatments in order to improve the test of new treatments. Importantly, this applies not only to assessment of drug efficacy but also to non-pharmacological trials on surgeries and stimulation procedures.
Topics: Analgesia; Humans; Pain; Placebo Effect; Placebos; Treatment Outcome
PubMed: 30915982
DOI: 10.1016/j.bja.2019.01.040 -
Annals of Palliative Medicine Jan 2020Acupuncture is a common alternative therapy for clinical treatment of insomnia. As the underlying mechanism is yet unclear, its efficacy is often considered as placebo... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Acupuncture is a common alternative therapy for clinical treatment of insomnia. As the underlying mechanism is yet unclear, its efficacy is often considered as placebo effect. To clarify whether acupuncture treatment of insomnia is only due to its placebo effect, a systematic review and a meta-analysis were designed based on the comparison between acupuncture and sham acupuncture.
METHODS
Four English (PubMed, Embase, Web of Science, and The Cochrane Library) and three Chinese (CNKI, VIP, and Wanfang) databases were searched, and the validity of the eligible studies was critically appraised. Thirteen eligible randomized controlled trials of moderate-to-high quality that employed polysomnography (PSG), actigraphy, or self-assessment sleep quality tools were included in the present study. A meta-analysis was conducted using a random-effects model with the Pittsburgh Sleep Quality Index (PSQI) as the primary outcome measure (911 adult patients, 13 trials) for trials investigating the effects of acupuncture as compared to the sham acupuncture. Then, a subgroup analysis was performed to detect the sources of heterogeneity, identify the selection of sham acupuncture methods and different crowd characteristics, and explore its contributions to the total score change of PSQI.
RESULTS
Compared to the sham groups, acupuncture significantly decreased the PSQI score (P<0.0001). A subgroup analysis showed that the selection of sham acupuncture methods did not affect the results of PSQI. A subgroup of two trials with a total of 141 participants with major depressive disorder did not show any significant reductions in total PSQI scores (P=0.11). In addition, a significant difference was detected in the change of Insomnia Severity Index (ISI) scores (362 adult patients, 4 trials) between acupuncture and sham acupuncture (P<0.0001). The PSG and actigraphy data from acupuncture and the sham did not reveal any significant differences in the sleep structure changes.
CONCLUSIONS
Acupuncture treatment of insomnia is efficacious, not because of its placebo effect. For the selection of sham acupuncture, both methods performed similarly in a clinical setting. Moreover, insomnia patients with major depression disorder were not recommended to use only acupuncture treatment.
Topics: Acupuncture Therapy; Humans; Placebo Effect; Randomized Controlled Trials as Topic; Sleep Initiation and Maintenance Disorders
PubMed: 32005059
DOI: 10.21037/apm.2019.11.15 -
Sleep Medicine Jun 2023New drug treatments are under development in obstructive sleep apnea (OSA). The placebo effect is well recognized in various conditions, but its relevance in OSA is... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
New drug treatments are under development in obstructive sleep apnea (OSA). The placebo effect is well recognized in various conditions, but its relevance in OSA is debated. In the current study we determined the influence of a placebo effect in studies of drug therapy in OSA.
METHODS
A systematic review and meta-analysis (PROSPERO CRD42021229410) with searches in MEDLINE, Scopus, Web of Science and Cochrane CENTRAL from inception to 2021-01-19. Inclusion criteria were (i) RCTs of adults with OSA, (ii) drug intervention with placebo baseline and follow-up sleep study (iii) outcomes: apnea hypopnea index (AHI), mean oxygen saturation (mSaO), oxygen desaturation index (ODI) and/or Epworth Sleepiness Scale (ESS). Risk-of-bias was assessed with Cochrane RoB 2.
RESULTS
7436 articles were identified and 29 studies included (n = 413). Studies were generally small (median n = 14), with 78% men, baseline AHI range 9-74 events/h and treatment duration range 1-120 days. Meta-analyses were conducted for main outcomes. Mean change of the primary outcome, AHI, was -0.84 (95% CI -2.98 to 1.30); mSaO and ODI estimations were also non-significant. ESS showed a trend towards a reduction of -1 unit. Subgroup analysis did not show significant differences. Risk-of-bias assessment indicated mostly low risk but studies were small with wide confidence intervals.
CONCLUSIONS
In this meta-analysis we did not identify systematic placebo effects on the AHI, ODI or mSaO while ESS score showed a trend for a small reduction. These results have an impact on the design and interpretation of drug trials in OSA.
Topics: Humans; Oxygen; Placebo Effect; Sleep Apnea, Obstructive; Sleepiness
PubMed: 37023489
DOI: 10.1016/j.sleep.2023.03.019