UNASSIGNED: Chronic back pain (CBP) is a leading cause of disability. Placebo treatments often provide as much pain relief as bona fide treatments, such as steroid injections. Open-label (honestly prescribed) placebos (OLPs) may relieve CBP without deception, but OLP mechanisms remain poorly understood.
UNASSIGNED: To investigate the long-term efficacy and neurobiological mechanisms of OLP for CBP.
UNASSIGNED: A randomized clinical trial of CBP with longitudinal functional magnetic resonance imaging (MRI) comparing OLP with usual care, with 1-year follow-up, was conducted in a university research setting and a community orthopedic clinic. Participants were individuals aged 21 to 70 years with CBP. The trial was conducted from November 2017 to August 2018, with 1-year follow-up completed by November 2019. Data analysis was performed from April 2020 to May 2024. The primary analysis was conducted on an intention-to-treat sample.
UNASSIGNED: Participants randomized to OLP received a 1-time subcutaneous lumbar saline injection presented as placebo accompanied by information about the power of placebo to relieve pain, alongside their ongoing care. Usual care participants continued their ongoing care.
UNASSIGNED: The primary outcome was pain intensity (0-10, with 0 indicating no pain and 10 the most intense) at 1 month posttreatment. Secondary outcomes included pain interference, depression, anxiety, anger, and sleep quality. Functional MRI was performed before and after treatment during evoked and spontaneous back pain.
UNASSIGNED: A total of 101 adults (52 [51.4%] females; mean [SD] age, 40.4 [15.4] years) with moderate severity CBP (mean [SD], 4.10 [1.25] intensity; duration, 9.7 [8.5] years) were enrolled. Compared with usual care, OLP reduced CBP intensity posttreatment (relative reduction, 0.61; Hedges g = 0.45; 95% CI, -0.89 to 0.04; P = .02). Through 1-year follow-up, pain relief did not persist, although significant benefits were observed for depression, anger, anxiety, and sleep disruption (Hedges g = 0.3-0.5; all P < .03). Brain responses to evoked back pain for OLP vs usual care increased in rostral anterior cingulate and ventromedial prefrontal cortex and decreased in somatomotor cortices and thalamus. During spontaneous pain, functional connectivity analyses identified OLP vs usual care increases in ventromedial prefrontal cortex connectivity to the rostral ventral medulla, a pain-modulatory brainstem nucleus. No adverse effects of treatment were reported by participants.
UNASSIGNED: In this randomized clinical trial of OLP vs usual care, a single nondeceptive placebo injection reduced CBP intensity for 1 month posttreatment and provided benefits lasting for at least 1 year posttreatment. Brain mechanisms of OLP in a clinical population overlap with those of deceptive placebos in healthy volunteers, including engagement of prefrontal-brainstem pain modulatory pathways.
UNASSIGNED: ClinicalTrials.gov Identifier: NCT03294148.

UNASSIGNED: Use of placebo in oncology randomized controlled trials (RCT) is ethically controversial. Placebo may introduce bias, as toxicity profiles of treatment arms can inadvertently unblind subjects and investigators. We investigated the use of placebo in urologic oncology RCTs, hypothesizing that most placebo-controlled trials are effectively unblinded, either explicitly with open-label design or implicitly due to large differences in adverse events (AE) or oncologic outcomes.
UNASSIGNED: Urologic oncology RCTs utilizing placebo were identified via ClinicalTrials.gov. Interventional prostate, bladder/urothelial, and renal cancer trials from 2014 to 2024 were included. Subject incompletion, all-cause mortality, AE rates, and serious AE (SAE) rates were identified and compared between placebo and active arms using χ2 and Fisher\'s exact tests.
UNASSIGNED: Sixty studies met inclusion criteria and included 66 placebo arms with 12,918 subjects and 81 active arms with 16,098 subjects. There was no significant difference in incompletion rates between placebo and active arms. Subjects enrolled in active arms reported statistically significant higher SAE and AE rates compared to those in placebo arms across the majority of physiological domains, including 18/24 domains for SAEs and 13/24 for AEs. This relationship persisted in sensitivity analyses where unblinded trials were excluded.
UNASSIGNED: In urologic oncology placebo-controlled RCTs, active arms are associated with significantly higher rates of AEs and SAEs compared with placebo arms. These findings indicate a strong possibility that true blinding is not possible in oncology RCTs, even with optimal study design, and serve to better inform future clinical trial design and implementation challenges in employing placebo control.

Studies with adults and school children have shown that placebos can enhance motivation and performance in physical activities. This study aimed to investigate whether similar effects are present in kindergarten-aged children. A total of 101 children (58 girls, 43 boys) aged 3 to 6 years were randomly assigned to one of two groups that either received a deceptive placebo (DP: \"magic potion\") or a nondeceptive placebo (NDP: \"water\") to enhance physical abilities. Each child completed three tasks (sprinting; balancing: standing on a balance board; strength: using a handheld dynamometer) both with and without the placebo. The variables assessed included task performance, enjoyment, and expected and perceived placebo efficacy (measured with nonverbal pictorial rating scales). Results showed that both the DP and NDP increased speed. For strength, balance, and task enjoyment (which was very high), no placebo-induced changes were observed. Expected efficacy was higher for the DP; perceived efficacy did not differ between DP and NDP. In conclusion, reported outcome expectations indicated that kindergarten-aged children were already able to differentiate between the two types of placebos which exhibited positive effects concerning running performance. This encourages further research on using nondeceptive placebos to enhance physical activity, which is crucial for children\'s overall health.

暂无摘要。

This single-centre substudy of a double-blind, randomized, placebo-controlled trial aimed to determine the effect of 96 weeks of rosuvastatin on pulse wave velocity (PWV) in men (n = 55, 54 years) with HIV at moderate cardiovascular risk (Framingham risk score 10-15%). PWV increased in both rosuvastatin [0.54 m/s standard error of difference (SED) 0.26] and placebo [0.50 m/s (SED 0.26), P = 0.896] arms, leading to no difference in PWV at week 96 [rosuvastatin 9.40 m/s (SE 0.31); placebo 9.21 m/s (SE0.31), P = 0.676].

Objectives: Prevalence of irregular menstrual cycle ranges from 81.7% to 96.3%. Recent research suggested that homeopathy is one of the most popular choices for women with various gynecological disorders. This trial was aimed at differentiating individualized homeopathic medicinal products (IHMPs) from identical-looking placebos in the treatment of menstrual irregularities in early reproductive women. Design: Double-blind, randomized (1:1), two parallel arms, placebo-controlled trial. Setting: D. N. De Homoeopathic Medical College & Hospital, Kolkata, West Bengal, India. Subjects: Ninety-two females with menstrual irregularities. Interventions: Group verum (n = 46; IHMPs plus concomitant care) versus group control (n = 46; placebos plus concomitant care). Outcome Measures: Primary-The proportion of early reproductive females in whom menstrual irregularities can be corrected for consecutive three cycles; Secondary-Menstrual Distress Questionnaire (MDQ) total score; all of them were measured at baseline and every month, up to 4 months. Results: Intention-to-treat sample (n = 92) was analyzed. Group differences were examined by chi-squared tests with categorical outcomes, two-way repeated measure analysis of variance accounting for the time-effect interactions, and unpaired t-tests comparing the mean estimates obtained individually every month. The level of significance was set at p < 0.05 two-tailed. After 4 months of intervention, the group difference in the primary outcome was nonsignificant statistically-IHMPs: 22/46 v/s placebo: 24/46, chi-square (Yates corrected) = 0.043, p = 0.835. The improvement observed in the MDQ total score (F1,90 = 0.054, p = 0.816) and subscales scores were higher in the IHMPs group than in placebos, however statistically nonsignificant in most of the occasions, except for the behavioral change subscale (F1,90 = 0.029, p < 0.001). Pulsatilla nigricans was the most frequently prescribed medicine. Kent\'s Repertory and Zandvoort\'s Complete Repertory were the most frequently used repertories. No harm or serious adverse events were reported from either group. Conclusions: The analysis failed to demonstrate clearly that IHMPs were effective beyond placebos in all but one of the outcomes. More appropriate outcome measures may be sought for future trials. Clinical Trial Registration Number: CTRI/2022/04/041659.

OBJECTIVE: To assess the efficacy and safety of Sanjie Analgesic Capsule (SAC) in Chinese patients with endometriosis-associated pain.
METHODS: This was a multicenter, randomized, double-blind, placebo-controlled trial conducted at 15 centers between November 2013 and July 2017 in China. Eligible 323 patients with endometriosis were randomized at a 3:1 ratio to the SAC group (241 cases) and placebo group (82 cases) by stratified block randomization. Patients in the SAC or placebo groups were given SAC or placebo 1.6 g 3 times per day, orally, respectively since the first day of menstruation for 3 consecutive menstrual cycles. The primary endpoint was clinical response to dysmenorrhea evaluated using a 10-point Visual Analogue Scale at 3 and 6 months. The secondary endpoint was the pain score evaluated by VAS (chronic pelvic pain, defecation pain, and dyspareunia) at 3 and 6 months, and the pain recurrence rate at 6 months. Adverse events (AEs) were recorded during the study.
RESULTS: A total of 241 women were included in the SAC group, and 82 were in the placebo group. Among these women, 217 (90.0%) and 71 (86.6%) completed the intervention, respectively. At 3 months, overall response rate (ORR) was significantly higher in women administered SAC (80.1%) compared with those who received a placebo (30.5%, P<0.01). Six months after treatment, the ORR for dysmenorrhea was 62.7% in the SAC group and 31.7% in the placebo group (P<0.01). Chronic pelvic pain and defecation pain were significantly improved by SAC compared with placebo (both P<0.05). The incidence rates of total AEs events in the SAC and placebo groups were 6.6% and 9.8%, respectively, and no significant difference was shown between the two groups (P=0.339).
CONCLUSIONS: SAC is well-tolerated and may improve dysmenorrhea in women with endometriosis-associated pain. (Trial registration: ClinicalTrials.gov, No. NCT02031523).

Transcutaneous electrical nerve stimulation (TENS) is a non-pharmacological treatment that works by delivering electrical currents via electrodes attached to the skin at the site of pain. It can be an alternative to pharmacological treatments. The mechanism of action of TENS for pain relief is related to the inhibition of the transmission of painful stimuli, release of endogenous opioids, and reduced muscle ischaemia of the uterus. Although it has been used for primary dysmenorrhoea ((PD); period pain or menstrual cramps), evidence of the efficacy and safety of high-frequency TENS, low-frequency TENS, or other treatments for PD is limited.
To evaluate the effectiveness and safety of transcutaneous electrical nerve stimulation (TENS) in comparison with placebo, no treatment, and other treatments for primary dysmenorrhoea (PD).
We searched the Gynaecology and Fertility Group\'s Specialized Register of controlled trials, CENTRAL, MEDLINE, Embase, PsycINFO, AMED, CINAHL, and the Korean and Chinese language databases up to 9 April 2024. We also searched for ongoing trials in trials registries and the reference lists of relevant studies for additional trials. Language restrictions were not applied.
We included randomized controlled trials (RCTs) that included women (aged 12 to 49 years) with PD. Included trials compared low-frequency TENS or high-frequency TENS with other TENS, placebo, or other treatment.
Four review authors screened the trials, extracted the data according to the protocol, assessed the risk of bias using RoB 2, and assessed the certainty of evidence for all review comparisons and primary outcomes (i.e. pain relief and adverse effects) using the GRADE approach.
This review replaces the current review, published in 2009. We included 20 RCTs involving 585 randomized women with high-frequency TENS, low-frequency TENS, placebo or no treatment, or other treatment. We included five comparisons: high-frequency TENS versus placebo or no treatment, low-frequency TENS versus placebo or no treatment, high-frequency TENS versus low-frequency TENS, high-frequency TENS versus other treatments, and low-frequency TENS versus other treatments. High-frequency TENS versus placebo or no treatment High-frequency TENS may reduce pain compared with placebo or no treatment (mean difference (MD) -1.39, 95% confidence interval (CI) -2.51 to -0.28; 10 RCTs, 345 women; low-certainty evidence; I2 = 88%). Two out of three RCTs reported no adverse effects and hence we were unable to estimate the effect of high-frequency TENS on adverse effects. Low-frequency TENS versus placebo or no treatment Low-frequency TENS may reduce pain compared with placebo or no treatment (MD -2.04, 95% CI -2.95 to -1.14; 3 RCTs, 645 women; low-certainty evidence; I2 = 0%). No trials reported adverse effects for this comparison. High-frequency TENS versus low-frequency TENS It is uncertain whether high-frequency TENS had an effect on pain relief compared with low-frequency TENS (MD 0.89, 95% CI -0.19 to 1.96; 3 RCTs, 54 women; low-certainty evidence; I2 = 0%). One trial contributed data on adverse effects but no adverse events occurred. High-frequency TENS versus other treatments It is uncertain whether high-frequency TENS had an effect on pain relief compared to acupressure (MD -0.66, 95% CI -1.72 to 0.40; 1 RCT, 18 women; very low-certainty evidence), acetaminophen (paracetamol) (MD -0.98, 95% CI -3.30 to 1.34; 1 RCT, 20 women; very low-certainty evidence), and interferential current therapy (MD -0.03, 95% CI -1.04 to 0.98; 2 RCTs, 62 women; low-certainty evidence; I2 = 0%). The occurrence of adverse effects may not differ significantly between high-frequency TENS and NSAIDs (OR 12.06, 95% CI 0.26 to 570.62; 2 RCTs, 88 women; low-certainty evidence; I2 = 78%). Low-frequency TENS versus other treatments It is uncertain whether low-frequency TENS had an effect on pain relief compared with acetaminophen (MD -1.48, 95% CI -3.61 to 0.65; 1 RCT, 20 women; very low-certainty evidence). No trials reported adverse effects for this comparison.
High-frequency TENS and low-frequency TENS may reduce pain compared with placebo or no treatment. We downgraded the certainty of the evidence because of the risk of bias. Future RCTs should focus more on secondary outcomes of this review (e.g. requirement for additional analgesics, limitation of daily activities, or health-related quality of life) and should be designed to ensure a low risk of bias.

暂无摘要。

OBJECTIVE: This study aims to investigate the underexplored prevalence of placebo-reported immune-related adverse events (irAEs) in immune checkpoint inhibitor (ICI) trials.
METHODS: We searched public databases for randomized clinical trials (RCTs) involving ICI versus placebo treatments in patients with malignancies. Study characteristics and irAEs occurrences were extracted for meta-analyses using a random-effects model.
RESULTS: Proportions of patients reported to experience any grade and grade 3 to 5 placebo irAEs; the risk ratio (RR) of reporting \'false\' irAEs in the experiment arm (defined as \'false-irAE ratio\', calculated by dividing the proportion of patients documented with irAEs in the placebo arm by that in the experimental arm).
RESULTS: 47 RCTs with 30,119 patients were analyzed. The pooled proportion of patients reported to experience any grade and grade 3 to 5 irAEs among placebo participants was 22.85 % (17.33 %-29.50 %) and 3.40 % (2.35 %-4.63 %), respectively. The pooled proportion of placebo-treated patients who experienced serious irAEs was 0.67 % (0.03 %-1.91 %). Treatment discontinuation and death due to placebo irAEs occurred in 0.69 % (<0.01 %-1.30 %) and 0.12 % (<0.01 %-0.40 %) of patients, respectively. The false-irAE ratio for any grade and grade 3 to 5 irAEs were 0.49 and 0.28. The false-irAE ratio was significantly higher in RCTs with control arms of placebo plus non-immunotherapy than in those with placebo alone (any grade: 0.57 vs. 0.32, P < 0.001; grade 3 to 5: 0.36 vs. 0.12, P = 0.009).
CONCLUSIONS: Our analyses of placebo-treated participants in ICI RCTs document the common occurrence of placebo irAEs. These findings are important for interpreting irAE profiles, avoiding inappropriate therapeutic interventions.