Placebo Effect Research Articles

Written Imaginal Exposure for Hoarding Disorder: A Preliminary Pilot Study.

Hoarding disorder (HD) is marked by difficulty discarding possessions. Many refuse treatment or drop out, which may be due to treatment's incorporation of in-home decluttering, which is feared and avoided. Thus, strategies to prepare patients for decluttering/discarding are needed. Imaginal exposure (IE), or imagining one's worst fears about discarding, could be one such strategy. This pilot preliminarily tested a short-duration IE intervention compared with a control intervention. Over 3 days, adults diagnosed with HD (n = 32) were randomly assigned to either write about and imagine their worst fears about discarding (IE condition) or a neutral topic (control writing [CW] condition). The IE condition showed significant improvements in HD symptoms from preintervention to 1-week follow-up, with medium to large effects; however, the CW condition did as well. Comparing change scores between conditions, the IE condition's improvements were not significantly different than the CW condition's. Overall, IE was helpful in improving HD symptoms, but this pilot did not indicate that it was more helpful than CW. This raises important questions about possible demand characteristics, placebo effects, or regression to the mean, and it has implications for the design and methodology of other studies assessing IE's utility.

Comparative Effectiveness of Panchamrut Parpati and Placebo in Management of Grahani W.S.R. to Irritable Bowel Syndrome - Study Protocol for a Single Blind, Randomized Controlled Trial

Abstract: Background: Ayurveda has described several treatment modalities regarding the treatment of Grahani Roga including the usage of herbs and formulations, yoga and lifestyle modifications. On the other hand, systematic data regarding their efficacy relative to placebo are not currently available. The purpose of this study is to compare the efficacy of the Ayurvedic formulation Panchamrut Parpati with a placebo, which contains an inert component called starch, in the treatment of Grahani Roga patients. Methods and design: In a prospective, single- centered, randomized controlled trial,60 patients, between 19 and 60 years, diagnosed with Grahani Roga, presenting with cardinal features of Grahani Roga as presented in Ayurvedic texts, two groups will be randomly assigned. In Group one, the patients will receive Panchamrut Parpati and in Group two, patients will receive Placebo filled with starch. Guidelines regarding Pathya-apathya will be given to both the groups. The course of treatment will last for 28 days for both groups. Outcomes will be evaluated on 14th&28th (During treatment) & 56th day (post-treatment). Result:The primary result will be assessed by checking the grading of the cardinal symptoms of Grahani Roga mentioned in Ayurvedic texts. Secondary outcome will check for improvement in laboratory investigations and quality of life of the patient. Conclusion: This trial compares the efficacy of Panchamrut Parpati with Placebo in the patients of Grahani roga. Panchamrut Parpati is envisioned to improve the symptoms of Grahani Roga, thus proving to be effective in management of patients of Grahani Roga. Trial registration: CTRI/2023/07/055048

Examining the Efficacy of Extended Reality-Enhanced Behavioral Activation for Adults With Major Depressive Disorder: Randomized Controlled Trial.

Major depressive disorder (MDD) is a global concern with increasing prevalence. While many evidence-based psychotherapies (EBPs) have been identified to treat MDD, there are numerous barriers to patients accessing them. Virtual reality (VR) has been used as a treatment enhancement for a variety of mental health disorders, but few studies have examined its clinical use in treatingMDD. Behavioral activation (BA) is a simple yet effective and established first-lineEBPforMDDthat has the potential to be easily enhanced and adapted withVR technology. A previous report by our group explored the feasibility and acceptability of VR-enhanced BA in a small clinical proof-of-concept pilot. This study examines the clinical efficacy of a more immersive extended reality (XR)-enhanced BA (XR-BA) prototype. This is the first clinical efficacy test of anXR-BA protocol. This study examined whether XR-BA was feasible and efficacious in treatingMDDin an ambulatory telemedicine clinic. A nonblinded between-subject randomized controlled trial comparedXR-BAto traditionalBAdelivered via telehealth.The study used a previously established, brief 3-week, 4-session BA EBPintervention. The experimentalXR-BAparticipantswere directed to use a Meta Quest 2(Reality Labs) VRheadset to engage in simulated pleasant or mastery activities and were compared to a control arm, which used only real-life mastery or pleasant activities as between-session homework. The Patient Health Questionnaire (PHQ)-9 was the primary outcome measure. Independent-sample and paired-sample t tests (2-tailed) were used to determine statistical significance and confirmed using structural equation modeling. Overall, 26 participants with MDD were randomized to receive either XR-BA (n=13, 50%) or traditional BA (n=13, 50%). The mean age of the 26 participants (n=6, 23% male; n=19, 73% female; n=1, 4% nonbinary or third gender) was 50.3 (SD 17.3) years. No adverse events were reported in either group, and no substantial differences in dropout rates or homework completion were observed. XR-BA was found to be statistically noninferior to traditional BA (t18.6=-0.28; P=.78). Both the XR-BA (t9=2.5; P=.04) and traditional BA (t10=2.3; P=.04) arms showed a statistically significant decrease in PHQ-9 and clinical severity from the beginning of session 1 to the beginning of session 4. There was a significant decrease inPHQ-8 to PHQ-9scores between the phone intake and the beginning of session 1 for theXR-BAgroup (t11=2.6;P=.03) but not the traditionalBAgroup (t11=1.4;P=.20). This study confirmed previous findings that XR-BA may be a feasible, non-inferior, and acceptable enhancement to traditional BA. Additionally, there was evidence that supports the potential of XR to enhance expectation or placebo effects. Further research is needed to examine the potential of XR to improve access, outcomes, and barriers to MDD care. ClinicalTrials.gov NCT05525390; https://clinicaltrials.gov/study/NCT05525390.

Non-pharmacological interventions for diabetic peripheral neuropathy: Are we winning the battle?

Despite the advent of relatively reliable modalities of diagnosing diabetic peripheral neuropathy (DPN), such as nerve conduction studies, there is still a knowledge gap about the pathophysiology, and thus limited available interventions for symptom control and curtailing disease progression. The pharmacologic aspect of management is mainly centred on pain control, however, there are several important aspects of DPN such as loss of vibration sense, pressure sense, and proprioception which are associated with risks to lower limb health, which pharmacotherapy does not address. Furthermore, published evidence suggests non-pharmacologic interventions such as glycaemic control through dietary modification and exercise need to be combined with other measures such as psychotherapy, to reach a desired, however modest effect. Acupuncture is emerging as an important treatment modality for several chronic medical conditions including neuropathic and other pain syndromes. In their study published in the World Journal of Diabetes on the potential of acupuncture to reduce DPN symptoms and enhance nerve conduction parameters, Hoerder et al have been able to demonstrate that acupuncture improves sensory function and that this effect is likely sustained two months after treatment cessation. Although previous studies also support these findings, larger multi-center randomized control trials including a sham-controlled arm accounting for a placebo effect are required. Overall, given the satisfactory safety profile and the positive results found in these studies, it is likely that acupuncture may become an important aspect of the repertoire of effective DPN management.

Binaural Beats and Music: A Preliminary Case Report

We recruited subjects who reported feeling stressed and needing a break and were seeking an opportunity to experience relaxation. Inaudible binaural beats (BB) were used to measure the ability of BB to induce relaxation. Measurements included EEG, Menlascan (cardiovascular and ANS) (Menla Technologies, Independence, Missouri), and GDV (Gas Discharge Visualization/Kirlian Photography) (Korotkov et al., 2020). Further, a Big Five Character Assessment was administered, and individual Brief Mood Introspection Scales (BMIS) were collected for each condition. Subjects experienced an improvement in brain function, microcirculation or cardiovascular score, bioenergy, and a calmer brain after adding binaural beats to brown noise or to music plus brown noise, although the Menlascan scores and Big Five character assessment results were less conclusive. BB seems to have profound effects on the physiology of subjects, and since the beats were not audible, these effects could not be attributed to the placebo effect. These results are encouraging in terms of developing musical products incorporating BB to affect human neural rhythms and corollary states of consciousness and warrant further research with more subjects and different frequencies of BB and different music tracks.

Lecanemab Questions.

The recently published results of the 18-month randomized controlled trial of lecanemab, reporting the efficacy of the drug in slowing the progression of early Alzheimer disease, quickly led to approval by the FDA and widespread acceptance of lecanemab treatment. However, there are a number of matters that deserve further consideration. The success of blinding was not assessed, even as infusion reactions and the cerebral pathology underlying amyloid-related imaging abnormalities could have signaled to many participants that they were on drug, potentially exerting a potent placebo effect. The value of the outcome to participants is not defined in the absolute terms necessary for clinical decision-making, and the difference attributable to lecanemab was between 18% and 46% of estimates of the minimal clinically important difference on the Clinical Dementia Rating Scale Sum of Boxes. The attenuation of change on the Alzheimer's Disease Assessment Scale-Cognitive 14 achieved by lecanemab at 18 months was 50% of that achieved by donepezil at 6 months. Lecanemab treatment imposes a high treatment burden. The fact that the burden commences at the initiation of lecanemab treatment, whereas the benefit accrues years later requires us to take into account value discounting over time, which would significantly reduce the benefit/burden ratio. Finally, treatment with monoclonal antibodies to cerebral amyloid has consistently been associated with progressive cerebral atrophy. At the least, these issues should be raised in treatment discussions with patients. They also suggest a need to very seriously reconsider how we evaluate clinical trial results preparatory to translating them into clinical practice. Some suggestions are provided.

Placebo Effects Are Small on Average in the 7.5% CO2 Inhalational Model of Generalised Anxiety.

Anxiety disorders are highly prevalent and socio-economically costly. Novel pharmacological treatments for these disorders are needed as many patients do not respond to current agents or experience unwanted side-effects. However, a barrier to treatment development is the variable and large placebo response rate seen in trials of novel anxiolytics. Despite this, the mechanisms that drive placebo responses in anxiety disorders have been little investigated, possibly due to low availability of convenient experimental paradigms. We aimed to develop and test a novel protocol for inducing placebo anxiolysis in the 7.5% CO2 inhalational model of generalised anxiety in healthy volunteers. Following a baseline 20-minute CO2 challenge, 32 healthy volunteers were administered a placebo intranasal spray labelled as either the anxiolytic 'lorazepam' or 'saline'. Following this, participants surreptitiously underwent a 20-minute inhalation of normal air. Post-conditioning, a second dose of the placebo was administered, after which participants completed another CO2 challenge. Participants administered sham 'lorazepam' reported significant positive expectations of reduced anxiety (p = 0.001) but there was no group-level placebo effect on anxiety following CO2 challenge post-conditioning (p's > 0.350). Surprisingly, we found many participants exhibited unexpected worsening of anxiety, despite positive expectations. Contrary to our hypothesis, our novel paradigm did not induce a placebo response, on average. It is possible that effects of 7.5% CO2 inhalation on prefrontal cortex function, or behaviour in line with a Bayesian predictive coding framework, attenuated the effect of expectations on subsequent placebo response. Future studies are needed to explore these possibilities.

The rationality of explanation or human capacity? Understanding the impact of explainable artificial intelligence on human-AI trust and decision performance

Artificial intelligence models can process massive amounts of data and surpass human experts in predictions. However, the lack of trust in algorithms sealed in the “black box” is one of the most challenging barriers to taking advantage of AI in human decision-making. Improving algorithm transparency by presenting explanations is one of the most common approaches to curing this. Explainable artificial intelligence (XAI) has been a recent research focus, but most concentrate on explainable algorithm development rather than human factors. Thus, the objective of this study is twofold: (1) to explore whether or not XAI can improve human performance and trust in AI in the competitive tasks of sales prediction, and (2) to reveal the different impact routines XAI on individuals with different task-related capacities. Based on a quasi-experimental study, our results indicate that XAI can improve human decision accuracy in the scenario of sales prediction in cross-border e-commerce. XAI cannot improve self-report trust to AI but can improve behavioral trust. We also found the placebo effect of explanation for relatively low task-related capacity.

Acute effects of MitoQ on vascular endothelial function are influenced by cardiorespiratory fitness and baseline FMD in middle-aged and older adults.

A key mechanism promoting vascular endothelial dysfunction is mitochondrial-derived reactive oxygen species (mtROS). Aerobic exercise preserves endothelial function in preclinical models by lowering mtROS. However, the effects of mtROS on endothelial function in exercising and non-exercising adults is limited. In a double-blind, randomized, placebo-controlled crossover study design 23 (10M/13 F, age 62.1 ± 11.5 years) middle-aged and older (MA/O, ≥45 years) adults were divided into two groups: exercisers (EX, n=11) and non-exercisers (NEX, n=12). All participants had endothelial function (brachial artery flow-mediated dilatation, FMDBA) measured before and ∼1h after mitoquinone mesylate (MitoQ) (single dose, 80mg) and placebo supplementation. A two-way repeated measures ANOVA was used to determine the effects of MitoQ and placebo on FMDBA. Pearson correlations assessed the association between the change in FMDBA with MitoQ and baseline FMDBA and cardiorespiratory fitness (CRF). Compared with placebo, MitoQ increased FMDBA in NEX by + 2.1% (MitoQ pre: 4.9 ± 0.4 vs. post: 7.0 ± 0.4 %, P=0.004, interaction) but not in EX (P=0.695, interaction). MitoQ also increased endothelial function in adults with a FMDBA <6% (P < 0.0001, interaction) but not >6% (P=0.855, interaction). Baseline FMDBA and CRF were correlated (r=0.44, P=0.037), whereas the change in FMDBA with MitoQ was inversely correlated with CRF (r=-0.66, P < 0.001) and baseline FMDBA (r=-0.73, P < 0.0001). The relationship between the change in FMDBA and baseline FMDBA remained correlated after adjusting for CRF (r=-0.55, P=0.007). These data demonstrate that MitoQ acutely improves FMDBA in NEX and EX adults who have a baseline FMDBA <6%. KEY POINTS: A key age-related change contributing to increased cardiovascular disease (CVD) risk is vascular endothelial dysfunction due to increased mitochondrial-derived reactive oxygen species (mtROS). Aerobic exercise preserves endothelial function via suppression of mtROS in preclinical models but the evidence in humans is limited. In the present study, a single dose of the mitochondria-targeted antioxidant, mitoquinone mesylate (MitoQ), increases endothelial function in non-exercisers with lower cardiorespiratory fitness (CRF) but not in exercisers with higher CRF. The acute effects of MitoQ on endothelial function in middle-aged and older adults (MA/O) are influenced by baseline endothelial function independent of CRF. These data provide initial evidence that the acute MitoQ-enhancing effects on endothelial function in MA/O adults are influenced, in part, via CRF and baseline endothelial function.

Short-term clinical and manometric outcomes of percutaneous tibial nerve stimulation for faecal incontinence: a large single-centre series

BackgroundFaecal incontinence (FI) is common, with a significant impact on quality of life. Percutaneous tibial nerve stimulation (PTNS) is a therapy for FI; however, its role has recently been questioned. Here we report the short-term clinical and manometric outcomes in a large tertiary centre.MethodsA retrospective review of a prospective PTNS database was performed, extracting patient-reported FI outcome measures including bowel diary, the St Marks’s Incontinence Score (SMIS) and Manchester Health Questionnaire (MHQ). Successful treatment was > 50% improvement in symptoms, whilst a partial response was 25–50% improvement. High-resolution anorectal manometry (HRAM) results before and after PTNS were recorded.ResultsData were available from 135 patients [119 (88%) females; median age: 60 years (range: 27–82years)]. Overall, patients reported a reduction in urge FI (2.5–1) and passive FI episodes (2–1.5; p < 0.05) alongside a reduction in SMIS (16.5–14) and MHQ (517.5–460.0; p < 0.001). Some 76 (56%) patients reported success, whilst a further 20 (15%) reported a partial response. There were statistically significant reductions in rectal balloon thresholds and an increase in incremental squeeze pressure; however, these changes were independent of treatment success.ConclusionPatients report PTNS improves FI symptoms in the short term. Despite this improvement, changes in HRAM parameters were independent of this success. HRAM may be unable to measure the clinical effect of PTNS, or there remains the possibility of a placebo effect. Further work is required to define the role of PTNS in the treatment of FI.

The Effect of Singular Nonverbal Behaviours of Experimenters on Pain Reports.

Studies suggest facial expressions of caregivers may be important in placebo effects; however, this has not been systematically tested. This experiment investigated the effects of caregivers' singular positive nonverbal behaviours (NBs) on pain reports. Fifty-one males and 53 females (total of 104) participants were randomized to four groups that were displayed positive facial expressions, tone of voice, body movement, or neutral NBs of videotaped experimenters. Subjective reports of pain, stress, arousal, and cardiac activity were obtained in a pre-test, a conditioning phase, and at a post-test. Four minutes of heat pain was induced in each test, and a placebo cream was administered before the conditioning and post-test in all groups. There were no differences between the NB groups in the reduced pain. Males had larger reduction in pain in the post-test, and females had lower arousal than the opposite sex. During the conditioning, females had larger reduction in pain ie, unconditioned pain response (UPR). In females, the UPR predicted the reinforced expectation ie, increase in expectations from conditioning to post-test, and fear of minor pain negatively predicted both the UPR and reinforced expectation. Singular NBs of caregiver were weak to enhance placebo effects. Females had lower pain during conditioning, and the UPR amplitude in females was associated with positive expectations. Moreover, for females, fear of minor pain weakened the UPR and expectations of cream. No NB of caregivers is more effective in reducing pain. Caregivers' NBs are less effective when displayed individually. Males and females may be different in underlying mechanisms of placebo effects.

Body mass index and cardiorenal outcomes in the EMPEROR-Preserved trial: Principal findings and meta-analysis with the DELIVER trial.

Both low and high body mass index (BMI) are associated with poor heart failure outcomes. Whether BMI modifies benefits of sodium-glucose cotransporter 2 inhibitors (SGLT2i) in heart failure with preserved ejection fraction (HFpEF) requires further investigation. Using EMPEROR-Preserved data, the effects of empagliflozin versus placebo on the risks for the primary outcome (hospitalization for heart failure [HHF] or cardiovascular [CV] death), change in estimated glomerular filtration rate (eGFR) slopes, change in Kansas City Cardiomyopathy Questionnaire clinical summary score (KCCQ-CSS), and secondary outcomes across baseline BMI categories (<25 kg/m2, 25 to <30 kg/m2, 30 to <35 kg/m2, 35 to <40 kg/m2 and ≥40 kg/m2) were examined, and a meta-analysis conducted with DELIVER. Forty-five percent had a BMI of ≥30 kg/m2. For the primary outcome, there was a consistent treatment effect of empagliflozin versus placebo across the BMI categories with no formal interaction (p trend = 0.19) by BMI categories. There was also no difference in the effects on secondary outcomes including total HHF (p trend = 0.19), CV death (p trend = 0.20), or eGFR slope with slower declines with empagliflozin regardless of BMI (range 1.12-1.71 ml/min/1.73 m2 relative to placebo, p trend = 0.85 for interaction), though there was no overall impact on the composite renal endpoint. The difference in weight change between empagliflozin and placebo was -0.59, -1.48, -1.54, -0.87, and - 2.67 kg in the lowest to highest BMI categories (p trend = 0.016 for interaction). A meta-analysis of data from EMPEROR-Preserved and DELIVER showed a consistent effect of SGLT2i versus placebo across BMI categories for the outcome of HHF or CV death. There was a trend toward greater absolute KCCQ-CSS benefit at 32 weeks with empagliflozin at higher BMIs (p = 0.08). Empagliflozin treatment resulted in broadly consistent cardiac effects across the range of BMI in patients with HFpEF. SGLT2i treatment yields benefit in patients with HFpEF regardless of baseline BMI.

Translating knowledge on placebo and nocebo effects into clinical practice.

Positive and negative treatment expectations are powerful modulators of health and treatment outcomes. A substantial part of treatment success is due to contextual factors modulating patient's expectations towards a treatment. Consequently, treatment expectations should be a target of therapeutic interventions themselves. This article highlights the neurobiological underpinnings of treatment expectations as well as strategies to modulate contextual factors to optimize treatment outcomes in daily clinical settings. This clinical update aligns with the 2022 IASP Global Year Translating Pain Knowledge into Practice and selectively reviews the best available evidence and practice. The effects of treatment expectations, also known as placebo and nocebo effects, are observed in various clinical conditions and physiological systems. However, most of our knowledge comes from the field of pain, where expectation effects substantially contribute to overall analgesic treatment outcomes. Experimental placebo analgesia paradigms provide the best illustration of how analgesic effects can be attributed not only to a pharmacological or specific treatment, but instead are the result of the expectation towards the treatment. The impact of expectations on treatment outcome is highly variable between individuals, and the identification of factors predicting an individual's response has proven to be challenging. Further research is required to provide personalized treatment strategies for the daily clinical practice. Patient's previous experiences and expectations are powerful modulators of treatment efficacy, tolerability, and adherence. By providing a comprehensive overview of recent advances in this field, this review offers valuable insights for clinicians and researchers seeking to improve patient-clinician interaction.

Alirocumab and cardiovascular outcomes according to sex and lipoprotein(a) after acute coronary syndrome: ODYSSEY OUTCOMES

BackgroundThe ODYSSEY OUTCOMES trial (NCT01663402) compared the effects of the proprotein convertase subtilisin/kexin type 9 inhibitor alirocumab with placebo on major adverse cardiovascular events (MACE) in patients with recent acute coronary syndrome (ACS). ObjectiveWe assessed efficacy and safety of alirocumab versus placebo according to sex and lipoprotein(a) level. MethodsThis prespecified analysis compared the effects of alirocumab versus placebo on lipoproteins, MACE (coronary heart disease death, non-fatal myocardial infarction, fatal/non-fatal ischemic stroke, unstable angina requiring hospitalization), death, total cardiovascular events, and adverse events in 4762 women and 14,162 men followed for a median of 2.8 years. In post-hoc analysis, we evaluated total cardiovascular events according to sex, baseline lipoprotein(a), and treatment. ResultsWomen were older, had higher baseline LDL-C levels (89.6 vs 85.3 mg/dL) and lipoprotein(a) (28.0 vs 19.3 mg/dL) and had more co-morbidities than men. At 4 months, alirocumab lowered LDL-C by 49.4 mg/dL in women and 54.0 mg/dL in men and lipoprotein(a) by 9.7 and 8.1 mg/dL, respectively (both p<0.0001). Alirocumab reduced MACE, death, and total cardiovascular events similarly in both sexes. In the placebo group, lipoprotein(a) was a risk factor for total cardiovascular events in women and men. In both sexes, reduction of total cardiovascular events was greater at higher baseline lipoprotein(a), but this effect was more evident in women than men (pinteraction=0.08). Medication adherence and adverse event rates were similar in both sexes. ConclusionsAlirocumab improves cardiovascular outcomes after ACS irrespective of sex. SummaryAfter recent ACS, addition of alirocumab to GDMT improves outcomes consistently in women and men. Reduction of total cardiovascular events was greater at higher baseline Lp(a).

Effect of liraglutide on thigh muscle fat and muscle composition in adults with overweight or obesity: Results from a randomized clinical trial.

Excess muscle fat is observed in obesity and associated with greater burden of cardiovascular risk factors and higher risk of mortality. Liraglutide reduces total body weight and visceral fat but its effect on muscle fat and adverse muscle composition is unknown. This is a pre-specified secondary analysis of a randomized, double-blind, placebo-controlled trial that examined the effects of liraglutide plus a lifestyle intervention on visceral adipose tissue and ectopic fat among adults without diabetes with body mass index ≥30kg/m2 or ≥27kg/m2 and metabolic syndrome. Participants were randomly assigned to a once-daily subcutaneous injection of liraglutide (target dose 3.0mg) or matching placebo for 40weeks. Body fat distribution and muscle composition was assessed by magnetic resonance imaging at baseline and 40-week follow-up. Muscle composition was described by the combination of thigh muscle fat and muscle volume. Treatment difference (95% confidence intervals [CI]) was calculated by least-square means adjusted for baseline thigh muscle fat. The association between changes in thigh muscle fat and changes in body weight were assessed using Spearman correlation coefficients. The effect of liraglutide versus placebo on adverse muscle composition, denoted by high thigh muscle fat and low thigh muscle volume, was explored. Among the 128 participants with follow-up imaging (92.2% women, 36.7% Black), median muscle fat at baseline was 7.8%. The mean percent change in thigh muscle fat over median follow-up of 36weeks was -2.87% among participants randomized to liraglutide (n=73) and 0.05% in the placebo group (absolute change: -0.23% vs. 0.01%). The estimated treatment difference adjusted for baseline thigh muscle fat was -0.24% (95% CI, -0.41 to -0.06, P-value 0.009). Longitudinal change in thigh muscle fat was significantly associated with change in body weight in the placebo group but not the liraglutide group. The proportion of participants with adverse muscle composition decreased from 11.0% to 8.2% over follow-up with liraglutide, but there was no change with placebo. In a cohort of predominantly women with overweight or obesity in the absence of diabetes, once-daily subcutaneous liraglutide was associated with a reduction in thigh muscle fat and adverse muscle composition compared with placebo. The contribution of muscle fat improvement to the cardiometabolic benefits of liraglutide requires further study.

A Placebo - a strategy to improve physical fitness of normal adolescents: a randomized control trial

Background: The capacity of the placebo effect to affect a range of physiological and psychological characteristics, including strength, endurance, and pain perception. Its use for teenage physical fitness, however, is still largely unknown. Objective: To determine the effects of placebo drink administration on physical fitness among normal-weight adolescents compared to plain water. Methods: This randomized control trial with n=60 adolescents aged 10-19 years, of both genders and normal weight was conducted at Shifa Tameer-e-Millat University, Islamabad from May 2021 to August 2021. Randomization was performed using the envelope method dividing the sample into an experimental group who were given a placebo drink (water + red food colour) and a control group who were given water. Tools used for data collection included the Physical Activity of Leisure Motivation Scale for motivation level determination, the Physical Activity Questionnaire, and four fitness tests including 20 m running, a broad jump, a reach test, and a reduced cooper test. Results: Post-intervention results revealed a significant difference in means for experimental and control groups for reduced Cooper test (P=0.003), pulse rate (p=0.033), and exertion level (p&lt;0.001). post- intervention palms score revealed significantly better results in the experimental group for mastery (p=0.004) physical (p=0.008) and psychological levels (p&lt;0.001). the results also indicate that the experimental group showed a more significant mean difference regarding the affiliation subscale with (p&lt;0.001) and total PALMS score (p&lt;0.001). Conclusion: Administered placebo drink boosts physical performance by increasing motivational levels and decreasing the exertion of normal-weight adolescents. Keywords: Adolescent; exercise; health; heart rate; placebo; physical fitness; water. IRCT # 20211052405138N1

Efficacy of a stannous fluoride dentifrice for relieving dentinal hypersensitivity in Chinese population: an 8-week randomized clinical trial

ObjectivesTo compare the effectiveness of using a 0.454% stannous fluoride-containing dentifrice twice daily in relieving dentinal hypersensitivity (DH) in a Chinese population.Materials and methodsThis was a single-centre, randomized, controlled, examiner-blind, three-treatment-arm, parallel-group study in participants with clinically diagnosed DH. Subjects who met inclusion criteria (n = 197) were randomly allocated into 3 groups: test group (n = 66)—using a 0.454% stannous fluoride-containing dentifrice twice daily; positive control group (n = 64)—using a 5.0% calcium sodium phosphosilicate-containing dentifrice twice daily; negative control group (n = 67)—using a 1150 ppm of NaF dentifrice twice daily. Status of DH was assessed at week 4 and week 8 by the same independent examiner. Changes from baseline in Schiff sensitivity score, tactile threshold and Dentine Hypersensitivity Experience Questionnaire (DHEQ) score were analysed using analysis of covariance models. The DHEQ evaluated subject-perceived oral health-related quality of life (OHRQoL).ResultsStatistically significant improvements in mean Schiff scores (p < 0.0001 for all products at Weeks 4 and 8), tactile threshold (p < 0.0001 for test and negative control at Weeks 4 and 8: Week 4 p = 0.0040 and Week 8 p < 0.0001 for positive control) and all DHEQ scores (p < 0.01 for all groups) were observed. No statistically significant differences were observed in the adjusted mean between all dentifrices at both timepoints, potentially driven by a placebo effect. Forty-two treatment-emergent adverse events (TEAEs) were reported (n = 32 subjects), with 2 serious AEs (n = 1) in the test group. TEAEs were not considered treatment-related.ConclusionsAll groups demonstrated statistically significant improvements in Schiff score, tactile threshold and OHRQoL. However, due to a possible placebo effect in the negative control, there were no statistically significant differences between the dentifrices.Clinical relevanceThis study adds to the growing research exploring why the placebo effect is a common phenomenon in DH studies.Trial registration: ClinicalTrials.gov Identifier: NCT04950465.

Profiling the colonic mucosal response to fecal microbiota transplantation identifies a role for GBP5 in colitis in humans and mice

Host molecular responses to fecal microbiota transplantation (FMT) in ulcerative colitis are not well understood. Here, we profile the human colonic mucosal transcriptome prior to and following FMT or placebo to identify molecules regulated during disease remission. FMT alters the transcriptome above the effect of placebo (n = 75 vs 3 genes, q < 0.05), including modulation of structural, metabolic and inflammatory pathways. This response is attributed to responders with no consistency observed in non-responders. Regulated pathways in responders include tight junctions, calcium signalling and xenobiotic metabolism. Genes significantly regulated longitudinally in responders post-FMT could discriminate them from responders and non-responders at baseline and non-responders post-FMT, with GBP5 and IRF4 downregulation being associated with remission. Female mice with a deletion of GBP5 are more resistant to developing colitis than their wild-type littermates, showing higher colonic IRF4 phosphorylation. The colonic mucosal response discriminates UC remission following FMT, with GBP5 playing a detrimental role in colitis.

The Social Epistemology of Clinical Placebos.

Many extant theories of placebo focus on their causal structure wherein placebo effects are those that originate from select features of the therapy (e.g., client expectations or "incidental" features like size and shape). Although such accounts can distinguish placebos from standard medical treatments, they cannot distinguish placebos from everyday occurrences, for example, when positive feedback improves our performance on a task. Providing a social-epistemological account of a treatment context can rule out such occurrences, and furthermore reveal a new way to distinguish clinical placebos from standard medical treatments.

Stress and placebo effects: Two sides of the same coin

Stress and placebo effects: Two sides of the same coin