Optimizing placebo and minimizing nocebo effects through communication: e-learning and virtual reality training development.

BACKGROUND: The effects of many treatments in healthcare are determined by factors other than the treatment itself. Patients' expectations and the relationship with their healthcare provider can significantly affect treatment outcomes and thereby play a major role in eliciting placebo and nocebo effects. We aim to develop and evaluate an innovative communication training, consisting of an e-learning and virtual reality (VR) training, for healthcare providers across all disciplines, to optimize placebo and minimize nocebo effects through healthcare provider-patient communication. The current paper describes the development, mid-term evaluation, optimization, and final evaluation of the communication training, conducted in The Netherlands. METHODS: The development of both the e-learning and the VR training consisted of four phases: 1) content and technical development, 2) mid-term evaluation by healthcare providers and placebo/communication researchers, 3) optimization of the training, and 4) final evaluation by healthcare providers. To ensure the success, applicability, authenticity, and user-friendliness of the communication training, there was ongoing structural collaboration with healthcare providers as future end users, experts in the field of placebo/communication research, and educational experts in all phases. RESULTS: Placebo/communication researchers and healthcare providers evaluated the e-learning positively (overall 7.9 on 0-10 scale) and the content was perceived as useful, accessible, and interesting. The VR training was assessed with an overall 6.9 (0-10 scale) and was evaluated as user-friendly and a safe method for practicing communication skills. Although there were some concerns regarding the authenticity of the VR training (i.e. to what extent the virtual patient reacts like a real patient), placebo and communication researchers, as well as healthcare providers, recognized the significant potential of the VR training for the future. CONCLUSIONS: We have developed an innovative and user-friendly communication training, consisting of an e-learning and VR training (2D and 3D), that can be used to teach healthcare providers how to optimize placebo effects and minimize nocebo effects through healthcare provider-patient communication. Future studies can work on improved authenticity, translate the training into other languages and cultures, expand with additional VR cases, and measure the expected effects on providers communication skills and subsequently patient outcomes.

System-agnostic prediction of pharmaceutical excipient miscibility via computing-as-a-service and experimental validation.

We applied computing-as-a-service to the unattended system-agnostic miscibility prediction of the pharmaceutical surfactants, Vitamin E TPGS and Tween 80, with Copovidone VA64 polymer at temperature relevant for the pharmaceutical hot melt extrusion process. The computations were performed in lieu of running exhaustive hot melt extrusion experiments to identify surfactant-polymer miscibility limits. The computing scheme involved a massively parallelized architecture for molecular dynamics and free energy perturbation from which binodal, spinodal, and mechanical mixture critical points were detected on molar Gibbs free energy profiles at 180 °C. We established tight agreement between the computed stability (miscibility) limits of 9.0 and 10.0 wt% vs. the experimental 7 and 9 wt% for the Vitamin E TPGS and Tween 80 systems, respectively, and identified different destabilizing mechanisms applicable to each system. This paradigm supports that computational stability prediction may serve as a physically meaningful, resource-efficient, and operationally sensible digital twin to experimental screening tests of pharmaceutical systems. This approach is also relevant to amorphous solid dispersion drug delivery systems, as it can identify critical stability points of active pharmaceutical ingredient/excipient mixtures.

Factors associated with a placebo effect in Parkinson's disease in clinical trials: a meta-analysis.

OBJECTIVES: Outcomes of clinical trials of treatment in patients with Parkinson's disease (PD) may be influenced by placebo effects. The aim of this study was to determine the factors associated with placebo effects in Parkinson's disease (PD) for guidance with design of future clinical trials. METHODS: Factors associated with placebo effects in PD were examined in a meta-analysis using a random effects model with pooling of placebo effects on the Unified Parkinson's Disease Rating Scale part III (UPDRS III) or Movement Disorder Society sponsored revision of UPDRS III (MDS-UPDRS III). The following prespecified variables were included in the analyses: with or without drug at baseline, with or without a placebo run-in phase, with or without motor fluctuation, published year, number of study sites, placebo administration period, age, sex, disease duration, and daily levodopa dose. Publication bias was assessed by visual inspection of funnel plots and adjusted using the trim-and-fill method. RESULTS: Thirty-eight articles with a total of 4828 subjects satisfied the inclusion criteria. There was a significant placebo effect using UPDRS III or MDS-UPDRS III (SMD = - 0.25; 95% CI - 0.35 to - 0.14; p < 0.001, I2 = 92%). Subgroup and/or multivariate meta-regression analyses revealed that placebo effects were associated with advanced PD (p = 0.04), drug exposure at baseline (p < 0.001), placebo administration period (p < 0.001), and disease duration (p < 0.01). CONCLUSIONS: The results of this study are important as guidance in design of future clinical trials in which the influence of placebo effects is minimized.

Assessing the longevity of attribute framing in attenuating the nocebo effect to brand and generic medication.

The perception of taking a generic, relative to brand, medication has been demonstrated to exacerbate the nocebo effect. Conversely, positive attribute framing has been shown to attenuate the nocebo effect. However, little is known about the longevity of positive attribute framing nor how it interacts with generic versus brand treatment cues. Healthy participants (N = 205) were randomised to receive either sham-modafinil capsules with a brand or generic appearance, in conjunction with standard negative side effect framing (brand-negative: N = 42; generic-negative: N = 41) or positive side effect framing (brand-positive: N = 40; generic-positive: N = 40). The remainder were randomised to a no-treatment control (N = 42). Participants were informed that modafinil could enhance alertness and cognitive performance and reduce fatigue. Critically, modafinil was described as having several potential side effects. Treatment-related side effects, alertness, fatigue and cognitive performance were measured at baseline, 30-min post-treatment and 24 h later. Nocebo and placebo effects were observed across modafinil-treated participants relative to control. Positive framing significantly reduced warned side effects for 24 h. Perceived side effect likelihood, severity, and worry mediated the nocebo, but not framing, effect. Results have important implications for the presentation of side effect information, providing a potential route to reduce unwanted negative effects of generic medication.

Statistical learning shapes pain perception and prediction independently of external cues.

The placebo and nocebo effects highlight the importance of expectations in modulating pain perception, but in everyday life we don't need an external source of information to form expectations about pain. The brain can learn to predict pain in a more fundamental way, simply by experiencing fluctuating, non-random streams of noxious inputs, and extracting their temporal regularities. This process is called statistical learning. Here, we address a key open question: does statistical learning modulate pain perception? We asked 27 participants to both rate and predict pain intensity levels in sequences of fluctuating heat pain. Using a computational approach, we show that probabilistic expectations and confidence were used to weigh pain perception and prediction. As such, this study goes beyond well-established conditioning paradigms associating non-pain cues with pain outcomes, and shows that statistical learning itself shapes pain experience. This finding opens a new path of research into the brain mechanisms of pain regulation, with relevance to chronic pain where it may be dysfunctional.

Safety and efficacy of resmetirom in the treatment of patients with non-alcoholic steatohepatitis and liver fibrosis: a systematic review and meta-analysis.

Introduction: Non-alcoholic fatty liver disease (NAFLD), spanning from non-alcoholic steatohepatitis (NASH) to liver fibrosis, poses a global health challenge amid rising obesity and metabolic syndrome rates. Effective pharmacological treatments for NASH and liver fibrosis are limited. Objective: This study systematically reviews and meta-analyzes the safety and efficacy of resmetirom, a selective thyroid hormone receptor-ß agonist, in NASH and liver fibrosis treatment. By analyzing data from clinical trials, we aim to offer evidence-based recommendations for resmetirom's use in managing these conditions and identify avenues for future research. Methods: Electronic databases (PubMed, Scopus, Science Direct, Google Scholar, ClinicalTrials.gov, and Cochrane CENTRAL) were systematically searched, supplemented by manual screening of relevant sources. Only English-language randomized controlled trials were included. Data extraction, risk of bias assessment, pooled analyses, and meta-regression were performed. Results: Three randomized controlled trials involving 2231 participants were analyzed. Resmetirom demonstrated significant reductions in hepatic fat fraction [standardized mean difference (SMD) -4.61, 95% CI -6.77 to -2.44, P < 0.0001], NASH resolution without worsening fibrosis [risk ratio (RR) 2.51, 95% CI 1.74-3.64, P = 0.00001), and liver fibrosis improvement (RR 2.31, 95% CI 1.20-4.44, P = 0.01). Secondary outcomes showed significant improvements in lipid profiles, liver enzymes, and NASH biomarkers with resmetirom treatment. Meta-regression revealed associations between covariates and primary outcomes. Conclusion: Resmetirom exhibits promising efficacy in reducing hepatic fat, improving NASH resolution, and ameliorating liver fibrosis with a favorable safety profile. Further research is warranted to validate findings and optimize therapeutic strategies for NASH and liver fibrosis management.

The Role of Attention in Placebo and Nocebo Effects.

BACKGROUND: Although some existing models propose that attention may be crucially implicated in placebo/nocebo effects, empirical research on this aspect remains limited and scattered. PURPOSE: This systematic review aims to provide an inclusive overview of studies that have either directly manipulated or assessed attention within the context of placebo and nocebo procedures so to gain a synthetized picture of the role of this variable in placebo/nocebo effects. Importantly, only studies in which attention represented a mechanism or mediator of the placebo/nocebo response, and not a primary outcome, were included. METHODS: A systematic search was conducted across multiple databases, including PubMed, Scopus, PsycINFO, Web of Science, and Embase, to identify peer-reviewed studies. These studies were subjected to methodological evaluation and eligibility criteria for inclusion. RESULTS: We identified and classified 12 studies into three categories based on their focus: (i) those that directly assessed attention, (ii) those that directly manipulated participants' attention, and (iii) those that combined both a direct manipulation and assessment of attention. In all selected studies attention acted as a mechanism or mediator of the placebo/nocebo response, and was not considered a primary outcome of the placebo/nocebo manipulation. CONCLUSIONS: The synthesis of the included studies reveals that the role of attention in placebo and nocebo effects is still a topic of debate, marked by variations in how attention is conceptualized and measured. Results suggest that attention has significant clinical implications, particularly in optimizing therapeutic efficacy by directing patients' focus toward signs of healing and away from indicators of illness or distress. To advance our understanding, future research should explore these attentional mechanisms, in conjunction with neurophysiological correlates.

To date, empirical research on the role of attention in placebo/nocebo effects remains scarce and inconclusive. The aim of this systematic review is to offer an overview of studies that have either directly manipulated or assessed attention as a mechanism or mediator of placebo/nocebo responses. Peer-review studies were subjected to methodological evaluation and eligibility criteria, and 12 studies were selected and classified into 3 categories based on their focus: (i) those that directly assessed attention, (ii) those that directly manipulated participants' attention, and (iii) those that combined both a direct manipulation and assessment of attention. The synthesis of the included studies points to the nuanced methodological approaches to the study of the role of attention in placebo and nocebo effects, marked by variations in how this variable is conceptualized and measured. Overall, results support the idea that placebo/nocebo effects are not always a direct byproduct of expectations, with attention acting as an important factor to consider when exploring this relationship. Particularly, attention plays an important role in optimizing therapeutic efficacy by directing patients' focus toward signs of healing and away from indicators of illness or distress.

Placebo and Nocebo Effects on Sports and Exercise Performance: A Systematic Literature Review Update.

Sports performance could be affected by placebo and nocebo effects. The last literature review on placebo and nocebo effects on sports and exercise performance was published in 2019. In the past five years, several new studies have been published. This review aimed to update the previous synthesis and evaluate the results of new studies focusing on placebo or nocebo interventions in sports and exercise by determining the form and magnitude of their effect. Hence, we searched for empirical studies published from 2019 until the end of May 2024 indexed in PubMed, Medline, Web of Science, EBSCO, and Google Scholar databases. The search yielded 20 eligible studies with control or baseline-control conditions, focusing on nutritional, mechanical, and other mixed ergogenic aids. They yielded small to large placebo effects (Cohen's d) for nutritional (d = 0.86), mechanical (d = 0.38), cream and gel (d = 0.05), and open-label placebo (d = 0.16) interventions. The pooled effect size for placebo effects was moderate to large (d = 0.67), larger than in the earlier review, suggesting that placebo effects can improve motor performance even more than previously reported. However, based on five measures from three studies, the nocebo effects were almost twice as large (d = 1.20). Accordingly, the current findings support and expand the last review in the field by yielding additional support for placebo and nocebo effects in sports and exercise.

Randomized Laboratory Study of Single-Dose Cannabis, Dronabinol, and Placebo in Patients With Schizophrenia and Cannabis Use Disorder.

BACKGROUND AND HYPOTHESIS: Up to 43% of people with schizophrenia have a lifetime cannabis use disorder (CUD). Tetrahydrocannabinol (THC) has been shown to exacerbate psychosis in a dose-dependent manner, but little research has assessed its effects on schizophrenia and co-occurring CUD (SCZ-CUD). In this double-dummy, placebo-controlled trial (total n = 130), we hypothesized that a modest dose of THC would worsen cognitive function but not psychosis. STUDY DESIGN: Effects of single-dose oral THC (15 mg dronabinol) or smoked 3.5% THC cigarettes vs placebo in SCZ-CUD or CUD-only on positive and negative symptoms of schizophrenia (only for SCZ-CUD), cognition, and drug experiences assessed several hours after drug administration. SCZ-only and healthy control participants were also assessed. STUDY RESULTS: Drug liking was higher in THC groups vs placebo. Neither smoked THC nor oral dronabinol predicted positive or negative symptom subscale scores 2 and 5 h, respectively, after drug exposure in SCZ-CUD participants. The oral dronabinol SCZ-CUD group, but not smoked THC SCZ-CUD group, performed worse than placebo on verbal learning (B = -9.89; 95% CI: -16.06, -3.18; P = .004) and attention (B = -0.61; 95% CI: -1.00, -0.23; P = .002). Every 10-point increment in serum THC + THCC ng/ml was associated with increased negative symptoms (0.40 points; 95% CI: 0.15, 0.65; P = .001; subscale ranges 7-49) and trends were observed for worse positive symptoms and performance in verbal learning, delayed recall, and working memory. CONCLUSIONS: In people with SCZ-CUD, a modest single dose of oral THC was associated with worse cognitive functioning without symptom exacerbation several hours after administration, and a THC dose-response effect was seen for negative symptoms.

Treatment expectations and clinical outcomes following repetitive transcranial magnetic stimulation for treatment-resistant depression.

BACKGROUND: Patient expectations, including both positive (placebo) and negative (nocebo) effects, influence treatment outcomes, yet their impact on acute repetitive transcranial magnetic stimulation (rTMS) for treatment-resistant depression (TRD) is unclear. METHODS: In this single-center retrospective chart review, 208 TRD patients completed the Stanford Expectation of Treatment Scale (SETS) before starting open-label rTMS treatment. Patients were offered two excitatory rTMS protocols (deep TMS or intermittent theta-burst stimulation), which stimulated the left dorsolateral prefrontal cortex. A minimum of 20 once daily treatments were provided, delivered over 4-6 weeks. Primary outcomes were 1) remission, measured by a post-treatment score of <8 on the Hamilton Depression Rating Scale (HAMD-17), and 2) premature discontinuation. The change in HAMD-17 scores over time was used as a secondary outcome. Physicians were blinded to SETS scores. Logistic and linear regression, adjusting for covariates, assessed SETS and HAMD-17 relationships. RESULTS: Of 208 patients, 177 had baseline and covariate data available. The mean positivity bias score (positive expectancy minus negative expectancy subscale averages) was 0.48 ± 2.21, indicating the cohort was neutral regarding the expectations of their treatment on average. Higher positive expectancy scores were significantly associated with greater odds of remission (OR = 1.90, p = 0.003) and greater reduction in HAMD-17 scores (ß = 1.30, p = 0.005) at the end of acute treatment, after adjusting for covariates. Negative expectancy was not associated with decreased odds of remission (p = 0.2) or treatment discontinuation (p = 0.8). CONCLUSIONS: Higher pre-treatment positive expectations were associated with greater remission rates with open-label rTMS in a naturalistic cohort of patients with TRD.

Efficacy and safety of once-weekly tirzepatide for weight management compared to placebo: An updated systematic review and meta-analysis including the latest SURMOUNT-2 trial.

AIM: Tirzepatide, a newly developed dual glucose-dependent insulinotropic peptide (GIP) and glucagon-like peptide-1 (GLP-1) receptor agonist, has received approval for treating type 2 diabetes (T2D) and is currently being studied for its potential in long-term weight control. We aim to explore the safety and efficacy of once-weekly subcutaneous tirzepatide for weight loss in T2D or obese patients. METHODS: A comprehensive search was performed on various databases including PubMed, Embase, Cochrane Library, Web of Science, and ClinicalTrials.gov from inception up to April 29, 2024, to identify randomized controlled trials (RCTs) that assessed the efficacy of once-weekly tirzepatide compared to a placebo in adults with or without T2D. The mean difference (MD) and risk ratio (RR) were calculated for continuous and dichotomous outcomes, respectively. The risk of bias was evaluated using the RoB-2 tool (Cochrane), while the statistical analysis was conducted utilizing RevMan 5.4.1 software. RESULTS: Seven RCTs comprising 4795 individuals ranging from 12 to 72 weeks were identified. Compared to the placebo group, tirzepatide at doses of 5, 10, and 15 mg demonstrated significant dose-dependent weight loss. The mean difference (MD) in the percentage change in body weight (BW) was -8.07% (95% CI -11.01, -5.13; p < 0.00001), -10.79% (95% CI -13.86, -7.71; p < 0.00001), and -11.83% (95% CI -14.52, -9.14; p < 0.00001), respectively. Additionally, the MD in the absolute change in BW was -7.5 kg (95% CI -10.9, -4.1; p < 0.0001), -11.0 kg (95% CI -16.9, -5.2; p = 0.0002), and -11.5 kg (95% CI -16.2, -6.7; p < 0.00001), for the 5, 10, and 15 mg doses, respectively. All three doses of tirzepatide also significantly reduced body mass index and waist circumference. Furthermore, it led to a greater percentage of patients experiencing weight loss exceeding 5, 10, 15, 20, and 25%. Moreover, tirzepatide showed great success in reducing blood pressure, blood sugar levels, and lipid profiles. In terms of safety, gastrointestinal side effects were the most frequently reported adverse events in all three doses of tirzepatide groups, which were generally mild-to-moderate and transient. CONCLUSION: Tirzepatide treatment could lead to remarkable and sustained weight loss that is well-tolerated and safe, representing a novel and valuable therapeutic strategy for long-term weight management.

Placebo effects of repetitive transcranial magnetic stimulation on negative symptoms and cognition in patients with schizophrenia spectrum disorders: a systematic review and meta-analysis.

Background: Negative symptoms and cognitive impairments are highly frequent in schizophrenia spectrum disorders (SSD), associated with adverse functional outcomes and quality of life. Repetitive transcranial magnetic stimulation (rTMS) has been considered a promising therapeutic option in SSD. However, placebo effects of rTMS on these symptoms remained unclear. Objective: To investigate placebo effects of rTMS on alleviating negative symptoms and cognitive impairment in patients with SSD and to explore potential moderators. Methods: We systematically searched five electronic databases up to 15 July 2023. Randomized, double-blind, sham-controlled trials investigating effects of rTMS on negative symptoms or cognition in patients with SSD were included. The pooled placebo effect sizes, represented by Hedges' g, were estimated using the random-effects model. Potential moderators were explored through subgroup analysis and meta-regression. Results: Forty-four randomized controlled trials with 961 patients (mean age 37.53 years; 28.1% female) in the sham group were included. Significant low-to-moderate pooled placebo effect sizes were observed for negative symptoms (g=0.44, p<0.001), memory (g=0.31, p=0.010), executive function (g=0.35, p<0.001), working memory (g=0.26, p=0.004), and processing speed (g=0.36, p=0.004). Subgroup analysis indicated that placebo effects were affected by sham stimulation methods, rTMS targeting approaches, and stimulation frequency. Conclusions: Placebo effects of rTMS on negative symptoms and cognition in patients with SSD are significant in a small-to-moderate magnitude, which might be mediated by rTMS parameters. Our findings will provide new insights for practitioners to further optimize and establish standardized rTMS protocols for future RCTs tackling cardinal symptoms in SSD. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/, identifier CRD42023390138.

Social Learning of Placebo Effects in Pain: A Critical Review of the Literature and a Proposed Revised Model.

Relatively recently, in 2009, experimental studies were undertaken to determine the role of social observational learning in forming hypoalgesic, analgesic and hyperalgesic responses to a placebo. The research findings obtained in studies published before 2018 were integrated and formed the basis of the theoretical model of social learning of placebo effects in pain proposed by Bajcar and Babel. This model considered the involvement of different types of modeling (ie, behavioral modeling, symbolic modeling, and verbal modeling) in shaping placebo hypoalgesia/analgesia and nocebo hyperalgesia. The model assumed that pain expectancies might be involved in observationally induced placebo effects in pain and that the effectiveness of observational learning in shaping placebo effects could be moderated by the observer's dispositions, especially empathy. Based on the latest research data, we propose a modified and significantly extended version of this model. The revised model includes the involvement of particular types of modeling in placebo effects and their role in shaping conscious pain-related expectancies. It explains the role of dispositional empathy in shaping observationally induced placebo effects. Notably, the extended version of the model considers the contribution of the characteristics of the observed person to the magnitude of placebo effects induced by social learning. PERSPECTIVE: The paper proposes a comprehensive theoretical approach to explaining the role of observational learning in shaping placebo effects in pain. The proposed model emphasizes the potential of this form of learning in shaping placebo responses and indicates factors that can modify the effectiveness of observational learning.

The Roles of Endogenous Opioids in Placebo and Nocebo Effects: From Pain to Performance to Prozac.

Placebo and nocebo effects have been well documented for nearly two centuries. However, research has only relatively recently begun to explicate the neurobiological underpinnings of these phenomena. Similarly, research on the broader social implications of placebo/nocebo effects, especially within healthcare delivery settings, is in a nascent stage. Biological and psychosocial outcomes of placebo/nocebo effects are of equal relevance. A common pathway for such outcomes is the endogenous opioid system. This chapter describes the history of placebo/nocebo in medicine; delineates the current state of the literature related to placebo/nocebo in relation to pain modulation; summarizes research findings related to human performance in sports and exercise; discusses the implications of placebo/nocebo effects among diverse patient populations; and describes placebo/nocebo influences in research related to psychopharmacology, including the relevance of endogenous opioids to new lines of research on antidepressant pharmacotherapies.

A study on acute expectation effects on affective state and intention after a brief full-body workout in a student sample.

Brief exercise bouts can have positive effects on the affective state, which in turn could affect the intention for future exercise. Such benefits may be enhanced by manipulating expectations. The aim of this study was to examine whether the affective state after physical activity or the intention for future exercise can be influenced by manipulating expectations. Furthermore, the relationship between affect and intention was investigated. In an online experiment, 121 persons completed either a 10-minute workout (PA), a workout after manipulation of expectations (PA + EM), or a control intervention (CG) after randomized group allocation. Data on affective state, expectations, and intention were collected before and after the intervention using questionnaires. After intervention, PA groups showed significantly more positive values than CG in several affective parameters, in other affective parameters, only PA + EM differed from CG. Affect was positively associated with intention alongside outcome expectations. No difference was found in intention. Although no significant effects of expectation manipulation on affective state or intention were found, latent effects cannot be ruled out. Further exploration of the importance of word choice in describing physical activity in the context of interventions to increase physical activity is necessary. Here, affect should be considered.

Assessing a potential therapeutic effect of cannabidiol for lower back pain, requires appropriately designed studies.

We read with interest the article by Kulesza et al. about a narrative review on the question of whether cannabidiol is really effective in treating lower back pain [1]. After a literature search using suitable search terms and application of inclusion and exclusion criteria, the authors included 10 studies in the analysis [1]. One of the articles included was an editorial and four papers were reviews [1]. Cannabidiol has been found to be ineffective in treating lower back pain and further studies are needed to answer the question of interest. The review is impressive, but several points require discussion.

The impact of patients' pre-treatment expectations on immunosuppressive treatment outcomes in myasthenia gravis: A pilot correlational study.

INTRODUCTION/AIMS: The impact of treatment expectations on active treatment outcomes has not been specifically investigated in neuromuscular disorders. We thus explored in myasthenia gravis (MG) the contribution of patients' pre-treatment expectations combined with an immunosuppressant drug on treatment outcomes. METHODS: This pilot correlational study involved 17 patients with generalized MG, scheduled to start immunosuppressant azathioprine. At baseline, a healthcare professional administered: (i) the Stanford Expectations of Treatment Scale; (ii) a structured checklist paper form asking patients which side-effects they expected to develop after starting azathioprine, coupled with a standardized framing of statements. Quantitative Myasthenia Gravis (QMG) score and daily dose of concomitant drugs were assessed by neurologists as clinical outcomes. Clinical outcomes and side-effects were re-assessed at 3 and 6 months, and clinical outcomes were monitored at 18 months. RESULTS: Clinically significant improvement in the QMG scores was achieved at 3 or 6 months. The level of state anxiety appeared to act as moderator of pre-treatment negative expectations (strong, positive, indicative correlation, rs = .733, p = .001). The latter were, in turn, associated with the fulfillment of side-effects that patients expected to develop with the new treatment (moderate, positive, indicative correlation, rs = .699, p = .002). No significant correlation emerged between positive and negative expectations. DISCUSSION: Our findings show a very quick clinical response and also suggest that patients' expectations and anxiety contributed to treatment outcomes, highlighting the importance of promoting safety messages and education strategies around newly introduced treatments. Future goals include evaluating a larger cohort that includes a matched control group.

Interventions to reduce adult state anxiety, dental trait anxiety, and dental phobia: A systematic review and meta-analyses of randomized controlled trials.

This review evaluates randomized controlled trials (RCTs) intervening on adult state anxiety (fear and emotional distress during dental treatment), chronic dental (trait) anxiety or dental phobia (disproportionately high trait anxiety; meeting diagnostic criteria for specific phobia). Seven online databases were systematically searched. 173 RCTs met inclusion criteria, of which 67 qualified for 14 pooled analyses. To alleviate state anxiety during oral surgery, moderate-certainty evidence supports employing hypnosis (SMD=-0.31, 95 %CI[-0.56,-0.05]), and low-certainty evidence supports prescribing benzodiazepines (SMD=-0.43, [-0.74,-0.12]). Evidence for reducing state anxiety is inconclusive regarding psychotherapy, and does not support virtual reality exposure therapy (VRET), virtual reality distraction, music, aromatherapy, video information and acupuncture. To reduce trait anxiety, moderate-certainty evidence supports using Cognitive Behavioral Therapy (CBT; SMD=-0.65, [-1.06, -0.24]). Regarding dental phobia, evidence with low-to-moderate certainty supports employing psychotherapy (SMD=-0.48, [-0.72,-0.24]), and CBT specifically (SMD=-0.43, [-0.68,-0.17]), but not VRET. These results show that dental anxieties are manageable and treatable. Clinicians should ensure that interventions match their purpose-managing acute emotions during treatment, or alleviating chronic anxiety and avoidance tendencies. Existing research gaps underscore the necessity for future trials to minimize bias and follow CONSORT reporting guidelines.

Heal Me!-Investigating the "Red Potion" Concept and Its Influence on Gamers' Cardiovascular Endurance.

The "red potion," inspired by video games, emulates the health point replenishment mechanism for injured game characters. Conversely, red ginger, known for its potential tonic properties in enhancing cardiovascular endurance, poses challenges in acquisition within specific regions. Several previous studies have highlighted the existence of an inseparable link when gamers are engaged in real-world activities, even without actively playing the game in the virtual world. This suggests the potential for the "red potion" concept to enhance the well-being of gamers in reality. A statistical ANOVA experiment involved 90 participants, all avid gamers, categorized into three groups: basic, placebo, and experimental. The basic group (BG) received a red-colored beverage without red ginger infusion or the 'red potion' concept. In contrast, the placebo group (PG) received a similar beverage described as a "red potion" but without red ginger. Lastly, the experimental group (EG) received a red ginger-infused beverage without the "red potion" concept. Despite receiving different treatments, all beverages were presented in the same red color. Participants underwent the "beep test" to assess their baseline stamina. The results revealed that both PG and EG exhibited comparable cardiovascular endurance, affirming the potential of the "red potion" concept to positively influence gamers.