Nocebo Research Articles

Socially Acquired Nocebo Effects Generalize but Are Not Attenuated by Choice.

Socially observing a negative treatment-related experience has been shown to modulate our own experience with the same intervention, leading to worsened health outcomes. However, whether this social learning generalizes to similar but distinct interventions has not been explored nor what manipulations can reduce these effects. To determine whether socially acquired nocebo effects can be generated by observing a negative experience with a similar, but distinct intervention, and whether choice can reduce these effects. Across three experiments, a community sample of healthy adults (N = 336) either watched a confederate report cybersickness to the same Virtual Reality (VR) activity they were assigned to (Social Modeling: Consistent); a similar, but different VR activity (Social Modeling: Inconsistent); or did not view the confederate (No Social Modeling). Participants were either given choice over the VR (Choice) or assigned by the experimenter (No Choice). Across the experiments, there was significantly greater cybersickness in both Social Modeling groups relative to No Social Modeling, while the two Social Modeling groups did not differ. There was no significant effect of Choice or a Choice by Social Modeling interaction. Social Modeling elicited greater anxiety and expectancies for cybersickness. Furthermore, these mechanisms mediated the association between social modeling and cybersickness. Socially acquired side-effects were demonstrated to generalize to similar, but distinct interventions, highlighting the diffuse and robust effect social modeling can have on our experiences. However, choice did not attenuate the experience of cybersickness, highlighting the need for alternative methods to counteract the effect of social modeling.

Race and Utilization of Dental Care

Racial discrimination in healthcare has been associated with suboptimal utilisation of dental services which may be linked to inequity in healthcare. Discriminatory behaviour of a healthcare professional could lead to a nocebo effect and a decrease in the oral health related quality of life. Colonialism could be to blame for historically segregating various races according to skin colour, language barriers, religion and socioeconomic status. But continual of such behaviour in the modern era has led to dehumanisation, where the ideal treatment plan may not even be informed to the patient, because the healthcare professional(s) assume that the patient may not / may not be able to avail such services, which results in doubtful obtainment of consent. Also, the lack of dentists belonging to discriminated races also contributes to non-attendance and/or non-availability of dental services for vulnerable patients. Cultural differences among the races, with regards to the importance of dental preventive care, oral hygiene maintenance and individual’s dependence on family heads for consent, could result in lack of compliance from patients despite correct advice from dentists. In conclusion, intercultural and international education are necessary components of a dental curriculum. Healthcare professionals need to be trained in remote and international areas in order to imbibe empathy and be respectful towards other races.

Placebo analgesia and nocebo hyperalgesia in patients with Alzheimer disease and healthy participants.

The role of placebo analgesia and nocebo hyperalgesia in patients with Alzheimer disease (AD) is largely unknown, with only few studies in the area. Therefore, this study aims to investigate to which extent placebo analgesia and nocebo hyperalgesia effects are present in patients experiencing mild-to-moderate AD. Twenty-one patients with AD (test population) and 26 healthy participants (HP; design validation) were exposed to thermal pain stimulation on 3 test days: Lidocaine condition (open/hidden lidocaine administration), capsaicin condition (open/hidden capsaicin administration), and natural history (no treatment), in a randomized, within-subject design. Open lidocaine and open capsaicin were accompanied by verbal suggestions for pain relief and pain increase, respectively. Expected pain and actual pain intensity were measured on a numerical rating scale (0-10). Placebo and nocebo effects were calculated as pain differences in open-hidden lidocaine and capsaicin, respectively, controlled for no treatment. Healthy participants obtained a placebo effect ( P = 0.01) and a trend for a nocebo effect ( P = 0.07). Patients with AD did not obtain a placebo effect ( P = 0.44) nor a significant nocebo effect ( P = 0.86). Healthy participants expected lower and higher pain with open vs hidden lidocaine and capsaicin, respectively ( P < 0.001). The same expectation effects were seen in patients with AD (open vs hidden lidocaine, P = 0.008; open vs hidden capsaicin, P < 0.001). With a well-controlled experimental setting, this study suggests that patients with AD may not experience placebo analgesia effects. Nocebo hyperalgesia effects in patients with AD needs further research. These findings may have implications for the conduction of clinical trials and the treatment of patients with AD in clinical practice.

Motivational communication skills to improve motivation and adherence in cardiovascular disease prevention: A narrative review.

Lifestyle optimization is one of the most essential components of cardiovascular disease prevention. Motivational counseling provided by health care professionals could promote lifestyle modification. The purpose of the review is to identify possible evidence-based psychological principles that may be applicable to motivational counseling in the prevention of cardiovascular disease. These motivational communication skills promote behavioral change, improved motivation and adherence to cardiovascular disease prevention. A personal collection of the relevant publications. The review identified and summarized the previous evidence of implementation intentions, mental contrasting, placebo effect and nocebo effects and identity-based regulations in behavior change interventions and proposed their potential application in cardiovascular disease prevention. However, it is challenging to provide real support in sustainable CVD-risk reduction and encourage patients to implement lifestyle changes, while avoiding being unnecessarily judgmental, disrespectful of autonomy, or engaging patients in burdensome efforts that have little or no effect on the long run. Motivational communication skills have a great potential for effectuating sustainable lifestyle changes that reduce CVD-related risks, but it is also surrounded by ethical issues that should be appropriately addressed in practice. It is key to realize that motivational communication is nothing like an algorithm that is likely to bring about sustainable lifestyle change, but a battery of interventions that requires specific expertise and long term joint efforts of patients and their team of caregivers.

Diet associations in endometriosis: a critical narrative assessment with special reference to gluten.

Endometriosis is characterized by the presence of endometrium-like tissue outside the uterus. The etiology remains largely unknown. Despite adequate treatment, patients can still experience symptoms or side effects resulting in therapy incompliance and in self-management strategies such as dietary measures is increasing. A gluten free diet is thought to be contributory in reducing endometriosis-related pain, thereby optimizing quality of life. However, data is conflicting and currently provides no evidence for causality. This narrative review aims to put the effect of dietary self-management strategies on endometriosis in a balanced perspective, especially the effect of gluten and a gluten free diet. Several studies have found a strong overlap in symptoms, metabolic and immune responses associated with endometriosis and those associated with celiac disease, ulcerative colitis, Crohn's disease, irritable bowel syndrome and non-celiac wheat sensitivity. However, it remains unclear whether these diseases and/or disorders are causal to an increased risk of endometriosis. Some studies have found a positive effect on the risk of endometriosis, endometriosis-related symptoms and quality of life (QoL) when women either avoided certain nutrients or foods, or applied a specific nutrient supplementation. This includes the avoidance of red meat, an increasing intake of foods rich in anti-oxidants, omega-3, micronutrients and dietary fibers (e.g., fruit, vegetables) and the appliance of a gluten free diet. However, data from the available studies were generally graded of low quality and it was noted that placebo and/or nocebo effects influenced the reported positive effects. In addition, such effects were no longer seen when adjusting for confounders such as overweight, when a translation was made from in vitro to in vivo, or when the nutrients were not supplemented as isolated sources but as part of a mixed daily diet. Finally, some studies showed that long-term adherence to a gluten free diet is often associated with an impaired diet quality and nutrient intake, leading to negative health outcomes and reduced QoL. Concluding, scientific evidence on the efficacy of dietary interventions on well-defined clinical endpoints of endometriosis is lacking and recommending a gluten free diet to women solely diagnosed with endometriosis should therefore not be advised.

The Nocebo Effect.

Adverse nocebo responses can cause harm to patients and interfere with treatment adherence and effects in both clinic practice and clinical trials. Nocebo responses refer to negative outcomes to active medical treatments in clinical trials or practice that cannot be explained by the treatment's pharmacologic effects. Negative expectancies and nocebo effects are less known than placebo responses. Nocebo effects can be triggered by verbal suggestions, prior negative experiences, observation of others experiencing negative outcomes, and other contextual and environmental factors. As research advances over the years, mechanistic knowledge is accumulating on the neurobiological mechanisms of nocebo effects. This review summarizes studies on different facets of nocebo effects and responses and discusses clinical implications, ethical considerations,and future directions.

The effect of nocebo explanation and empathy on side-effect expectations of medication use following a fictional GP consultation

ABSTRACT The simple act of informing patients about side-effects increases the likelihood they will experience them (i.e. the nocebo effect). Explaining this psychological phenomenon could help to reduce side-effect experience, however, it is yet to be explored if this can be applied to clinical settings where new medication is prescribed. In addition, the degree to which a health-care provider empathetically communicates this to patients may have an impact. To investigate this, we carried out 2 × 2 factorial trial to assess the effect of nocebo explanation and empathy (plus their interaction) on side-effect expectations following a fictional GP consultation prescribing a new medication. Overall, 208 participants were randomised to watch one of the four fictive GP consultations and play the role of the patient. In all videos, participants received information about the reason for the consultation, the recommendation of a new fictive medicine, how to take it, benefits and side-effects. The videos differed in whether the GP provided an explanation of the nocebo effect (yes/no) and whether they communicated in an empathetic style (yes/no). After watching the video, participants were asked about their side-effect expectations and rated the quality of the GP’s communication. Two-way ANOVAs revealed no main effect of nocebo explanation on expectation of side-effects warned or not warned about in the consultation. However, there was a main effect of empathy, with participants watching the empathetic consultations having significantly lower expectations of non-warned-about side-effects. There was no significant interaction. Findings suggest that explaining the nocebo effect and GP empathy did little to allay expectations of side-effects that were specifically mentioned in the consultation. However, GP empathy had an effect by helping to reduce additional side-effect expectations participants still had. Future work should extend these findings to real GP consultations where the full dimensions of empathy can be explored.

A new experimental rat model of nocebo-related nausea involving double mechanisms of observational learning and conditioning.

The nocebo effect, such as nausea and vomiting, is one of the major reasons patients discontinue therapy. The underlying mechanisms remain unknown due to a lack of reliable experimental models. The goal of this study was to develop a new animal model of nocebo-related nausea by combining observational learning and Pavlovian conditioning paradigms. Male Sprague-Dawley rats with nitroglycerin-induced migraine were given 0.9% saline (a placebo) or LiCl (a nausea inducer) following headache relief, according to different paradigms. Both strategies provoked nocebo nausea responses, with the conditioning paradigm having a greater induction impact. The superposition of two mechanisms led to a further increase in nausea responses. A preliminary investigation of the underlying mechanism revealed clearly raised peripheral and central cholecystokinin (CCK) levels, as well as specific changes in the 5-hydroxytryptamine and cannabinoid systems. Brain networks related to emotion, cognition, and visceral sense expressed higher c-Fos-positive neurons, including the anterior cingulate cortex (ACC), insula, basolateral amygdala (BLA), thalamic paraventricular nucleus (PVT), hypothalamic paraventricular nucleus (PVN), nucleus tractus solitarius (NTS), periaqueductal gray (PAG), and dorsal raphe nucleus-dorsal part (DRD). We also found that nausea expectances in the model could last for at least 12 days. The present study provides a useful experimental model of nocebo nausea that might be used to develop potential molecular pathways and therapeutic strategies for nocebo.

Placebo and nocebo responses in painful diabetic neuropathy: systematic review and meta-analysis.

This preregistered (CRD42021223379) systematic review and meta-analysis aimed to characterize the placebo and nocebo responses in placebo-controlled randomized clinical trials (RCTs) on painful diabetic neuropathy (PDN), updating the previous literature by a decade. Four databases were searched for PDN trials published in the past 20 years, testing oral medications, adopting a parallel-group design. Magnitude of placebo or nocebo responses, Cochrane risk of bias, heterogeneity, and moderators were evaluated. Searches identified 21 studies (2425 placebo-treated patients). The overall mean pooled placebo response was -1.54 change in the pain intensity from baseline [95% confidence interval (CI): -1.52, -1.56, I2 = 72], with a moderate effect size (Cohen d = 0.72). The pooled placebo 50% response rate was 25% [95% CI: 22, 29, I2 = 50%]. The overall percentage of patients with adverse events (AEs) in the placebo arms was 53.3% [95% CI: 50.9, 55.7], with 5.1% [95% CI: 4.2, 6] of patients dropping out due to AEs. The year of study initiation was the only significant moderator of placebo response (regression coefficient = -0.06, [95% CI: -0.10, -0.02, P = 0.007]). More recent RCTs tended to be longer, bigger, and to include older patients (N = 21, rs = 0.455, P = 0.038, rs = 0.600, P = 0.004, rs = 0.472, P = 0.031, respectively). Our findings confirm the magnitude of placebo and nocebo responses, identify the year of study initiation as the only significant moderator of placebo response, draw attention to contextual factors such as confidence in PDN treatments, patients' previous negative experiences, intervention duration, and information provided to patients before enrollment.

Nocebo response intensity and influencing factors in the randomized clinical trials of functional dyspepsia: A systematic review and meta-analysis.

In this study we aimed to evaluate the nocebo response rate in patients with functional dyspepsia (FD) and to explore its influencing factors. A literature search of the EMBASE, PubMed, and Cochrane Library databases was conducted for all articles published up to March 2021. Randomized, parallel-designed, placebo-controlled trials on pharmacological interventions for patients with FD were included. A meta-analysis that utilized random effects to analyze the incidence of adverse events (AEs) among participants who were given placebo was conducted, and the correlation between trial characteristics and the magnitude of the nocebo response rate was analyzed. Altogether, 27 studies including 1866 paitents were deemed eligible and included in the analysis. The total nocebo response rate was 26% (95% confidence interval [CI] 18%-33%). The most frequently reported AEs included nasopharyngitis (9%), constipation (6%), headache (5%), and diarrhea (3%). There were significant differences in nocebo response rates among studies conducted in different country or region, treatment duration, types of medication, sponsorship and different versions of theRome criteria used for FD diagnosis. While number of centers engaged in the study, types of FD diagnosis and dosing frequency were not significantly associated with the nocebo response rate. Patients with FD exhibit notable nocebo response strength in clinical trials. The researchers should adopt a more careful approach when analyzing the relationships between AEs and interventions in such trials.

Effects of a video-based positive side-effect information framing: An online experiment.

Despite the public health value of vaccines, vaccination uptake rates are stagnating. Expected adverse events following immunization are a major source of concern and play a role in the emergence of vaccine hesitancy. Since nocebo mechanisms are involved in the perception of adverse reactions, positive side-effect communication is warranted. The aim of the present study was to compile a comprehensive communication strategy that minimizes expectations of nocebo effects while respecting the informed consent procedure. In a randomized 2 × 2 between-subject design, 652 participants received information about COVID-19 or influenza vaccination using either standard side-effect messaging or messaging enriched with proven elements of expectation-optimizing framing. A physician presented information online via video. Moderation analyses were conducted to examine effects among particular subpopulations. Expected adverse event ratings following an imagined immunization, cost-benefit ratios of the vaccination, and future vaccination intentions were assessed. Information content ratings were equally high in each group. Positive framing significantly decreased adverse event expectations in the COVID-19 information group and raised the cost-benefit ratio in the influenza condition, indicating higher benefits than cost expectations. Moderation analysis revealed that the framed side-effect communication lowered the expected COVID-19 vaccination uptake willingness in individuals with strong anti-vaccination attitudes. Facing the ongoing coronavirus mass vaccinations, positive information frames have a small but significant impact on vaccination concerns while upholding informed consent. Although intervention trials are still pending, this approach could help decrease vaccine hesitancy by reducing fearful expectations. However, it seems that it should not be used without considering vaccination attitudes. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

A Systematic Literature Review of Gaps and Challenges in Value Assessment of Biosimilars: An ISPOR Special Interest Group Report

ObjectivesThis study aims to provide an overview of the gaps and challenges in the value assessment of biosimilars and to identify potential approaches to address them. MethodsA multidisciplinary, international team of biosimilar experts identified gaps and challenges. A systematic review was conducted of the peer-reviewed literature in PubMed, EMBASE, Web of Science Core Collection, EBSCOhost Business Source Complete; and of the gray literature. Preliminary results were presented at ISPOR conferences and this article benefited from 2 review rounds among ISPOR Biosimilar Special Interest Group members. ResultsGiven that a biosimilar is highly similar to its reference biologic, health technology assessment agencies should accept the comparability exercise approved by regulatory authorities and, thus, conduct a price comparison when biosimilar reimbursement is requested for the same indication as the reference biologic. If the reference biologic is not reimbursed or is not the standard of care, a full economic evaluation of the biosimilar versus a relevant comparator needs to be conducted. To date, little consideration has been given to specific challenges, such as how biosimilar value assessment can account for the nocebo effect, potential differences between biologic-naive and biologic-experienced patients, the availability of intravenous and subcutaneous administration forms or different administration devices for the same active compound, value-added services, and the contribution of biosimilars for generating health gain at the population level. ConclusionsThere is a need to gather further insights in the methodology of value assessment for biosimilars, and health technology assessment agencies need to develop more elaborate guidance on biosimilar value assessment in specific circumstances.

Electrophysiological markers for anticipatory processing of nocebo-augmented pain.

Nocebo effects on pain are widely thought to be driven by negative expectations. This suggests that anticipatory processing, or some other form of top-down cognitive activity prior to the experience of pain, takes place to form sensory-augmenting expectations. However, little is known about the neural markers of anticipatory processing for nocebo effects. In this event-related potential study on healthy participants (n = 42), we tested whether anticipatory processing for classically conditioned nocebo-augmented pain differed from pain without nocebo augmentation using stimulus preceding negativity (SPN), and Granger Causality (GC). SPN is a slow-wave ERP component thought to measure top-down processing, and GC is a multivariate time series analysis used to measure functional connectivity between brain regions. Fear of pain was assessed with the Fear of Pain Questionnaire-III and tested for correlation with SPN and GC metrics. We found evidence that both anticipatory processing measured with SPN and functional connectivity from frontal to temporoparietal brain regions measured with GC were increased for nocebo pain stimuli relative to control pain stimuli. Other GC node pairs did not yield significant effects, and a lag in the timing of nocebo pain stimuli limited interpretation of the results. No correlations with trait fear of pain measured after the conditioning procedure were detected, indicating that while differences in neural activity could be detected between the anticipation of nocebo and control pain trials, they likely were not related to fear. These results highlight the role that top-down processes play in augmenting sensory perception based on negative expectations before sensation occurs.

Clinical efficacy and nocebo effect following non-medical biosimilar switch in patients with inflammatory bowel disease: A prospective observational study

BackgroundWe aimed to evaluate clinical efficacy, biomarker activity, therapeutic drug monitoring (TDM), adverse events (AEs), and nocebo effect in inflammatory bowel disease (IBD) patients who underwent non-medical biosimilar switching. MethodsA prospective observational study of consecutive IBD patients who underwent biosimilar switch. Disease activity, biomarkers, TDM, and AEs, including the nocebo effect were captured 8 weeks before switch, at the time of switch (baseline),12 and 24 weeks after the switch. Results210 patients were included [81.4% had Crohn's disease (CD), the median age at inclusion: 42 years (IQR 29–61)]. There was no significant difference in the rates of clinical remission at week 8 before switch, baseline, week12, and 24 after switch: 89.0%,93.4%,86.3%,and 90.8%,p = 0.129. The biomarker remission rates were not significantly different; CRP:81.3%,74.7%,81.2%,73.0%,p = 0.343; fecal calprotectin: 78.3%,74.5%,71.7%,76.3%,p = 0.829. The rates of maintaining therapeutic levels (84.7%,83.9%,83.0%,85.3%,p = 0.597) and prevalence of positive anti-drug antibodies remained unchanged. Drug persistence at 12 week of switch was 97.1%, regardless of disease phenotype and originator. The nocebo effect was observed in 13.3%. The discontinuation rate was 4.8%. ConclusionDespite a significant number of early nocebo complaints within the first 6 months after the biosimilar switch, no significant changes were found in clinical efficacy, biomarkers, therapeutic drug level, or anti-drug antibodies.

How familiar are German dermatologists with placebo and nocebo effects and to what extent are these targeted in clinical practice: A survey within the dermatological community.

Every medical treatment inevitably comprises not only physiological, but also psychological components, reflected by placebo and nocebo effects, which significantly affect treatment outcome. However, the extent of knowledge on the mechanisms steering placebo and nocebo effects in the dermatological community in Germany is currently unclear. To assess the state of knowledge about placebo and nocebo effects in the German dermatological community, to evaluate whether this knowledge is already being used in clinical practice, and to investigate whether German dermatologists are interested in learning more about the topic. German Dermatologists, the majority working in their own practice, were asked to fill in an online survey addressing the knowledge about placebo and nocebo effects and the feasibility of special techniques to enhance placebo and minimize nocebo effects within the clinical routine. N = 154 complete (79%) or partial (21%) responses to the survey were recorded in the online database and included in the analysis. All participants reported to know what the placebo effect is and 59.7% (74/124) indicated that they already had experience with prescribing or recommending a treatment without active substances. In contrast, only 62.0% (80/129) stated to know what the nocebo effect is. Participants showed a rather superficial knowledge regarding placebo and nocebo mechanisms. The majority of participants (76.7%, 99/129) expressed their willingness to be further educated about the underlying mechanisms mediating placebo and nocebo effects and the possible application in clinical practice. The current survey offers a so far unique insight into the state of knowledge of German dermatologists on placebo and nocebo effects. The results indicate a need for education about this topic. Encouragingly, however, German dermatologists considered communication strategies to maximize placebo and reduce nocebo effects and expressed motivation to be trained to implement these strategies in everyday clinical practice.

The Biology of Placebo and Nocebo Effects on Experimental and Chronic Pain: State of the Art.

(1) Background: In recent years, placebo and nocebo effects have been extensively documented in different medical conditions, including pain. The scientific literature has provided strong evidence of how the psychosocial context accompanying the treatment administration can influence the therapeutic outcome positively (placebo effects) or negatively (nocebo effects). (2) Methods: This state-of-the-art paper aims to provide an updated overview of placebo and nocebo effects on pain. (3) Results: The most common study designs, the psychological mechanisms, and neurobiological/genetic determinants of these phenomena are discussed, focusing on the differences between positive and negative context effects on pain in experimental settings on healthy volunteers and in clinical settings on chronic pain patients. Finally, the last section describes the implications for clinical and research practice to maximize the medical and scientific routine and correctly interpret the results of research studies on placebo and nocebo effects. (4) Conclusions: While studies on healthy participants seem consistent and provide a clear picture of how the brain reacts to the context, there are no unique results of the occurrence and magnitude of placebo and nocebo effects in chronic pain patients, mainly due to the heterogeneity of pain. This opens up the need for future studies on the topic.

A Narrative Review of Placebo and Nocebo Effects on Itch

A Narrative Review of Placebo and Nocebo Effects on Itch

Statin intolerance-Statin tolerance

Statins are the first-line treatment for reducing low-density lipoprotein (LDL) cholesterol levels, because the evidence regarding safety, tolerability, and reduction of cardiovascular morbidity and mortality is very good. For combination treatment several options are available. Nevertheless, LDL cholesterol values are often not sufficiently lowered. One reason is intolerance of the lipid-lowering medications. In addition to the study situation regarding statin tolerability, possible approaches to overcome intolerability are also shown. In randomized trials adverse effects due to statin treatment are as rare as in the placebo groups. In clinical practice patients more frequently report complaints, particularly muscular symptoms. One important reason for intolerability is the nocebo effect. Complaints during treatment can lead to the fact that statins are not taken or are taken in insufficient doses. As a result, the LDL cholesterol level is insufficiently lowered with unfavorable effects on the incidence of cardiovascular events. Therefore, it is important to establish atolerable treatment together with the patient on an individual basis. Information about the facts is one important aspect. In addition, apositively guided communication with the patient helps to reduce the nocebo effect. Most adverse effects that patients attribute to statins are not caused by statins. This shows that other reasons are frequent and should be the focus of medical care. In this article international recommendations and personal experiences of aspecialized lipid outpatient clinic are described.

Impact of statin withdrawal on perceived and objective muscle function.

Statin-associated muscle symptoms (SAMS) are frequently reported. Nevertheless, few data on objective measures of muscle function are available. Recent data suggesting an important nocebo effect with statin use could confound such effects. The objective was to assess if subjective and objective measures of muscle function improve after drug withdrawal in SAMS reporters. Patients (59 men, 33 women, 50.3±9.6 yrs.) in primary cardiovascular prevention composed three cohorts: statin users with (SAMS, n = 61) or without symptoms (No SAMS, n = 15), and controls (n = 16) (registered at clinicaltrials.gov, NCT01493648). Force (F), endurance (E) and power (P) of the leg extensors (ext) and flexors (fle) and handgrip strength (Fhg) were measured using isokinetic and handheld dynamometers, respectively. A 10-point visual analogue scale (VAS) was used to self-assess SAMS intensity. Measures were taken before and after two months of withdrawal. Following withdrawal, repeated-measures analyses show improvements for the entire cohort in Eext, Efle, Ffle, Pext and Pfle (range +7.2 to +13.3%, all p≤0.02). Post-hoc analyses show these changes to occur notably in SAMS (+8.8 to +16.6%), concurrent with a decrease in subjective perception of effects in SAMS (VAS, from 5.09 to 1.85). Fhg was also improved in SAMS (+4.0 to +6.2%) when compared to No SAMS (-1.7 to -4.2%) (all p = 0.02). Whether suffering from "true" SAMS or nocebo, those who reported SAMS had modest but relevant improvements in muscle function concurrent with a decrease in subjective symptoms intensity after drug withdrawal. Greater attention by clinicians to muscle function in frail statin users appears warranted. This study is registered in clinicaltrials.gov (NCT01493648).

The Effect of Positive Therapeutic Communication on Pain (POPAIN) and Anxiety During Arterial Blood Gas Standardized Procedures in the Emergency Department Compared to Traditional Communication: Protocol for a Monocentric Randomized Controlled Trial.

In the emergency department (ED), medical procedures, such as arterial blood gas (ABG) testing, can cause pain and high stress levels. However, ABG testing is a routine procedure assessing the severity of the patient's condition. To reduce the pain of ABG, several methods have been investigated without significant difference in pain perception. Communication, a key element of care, has shown a significant effect on pain perception. A positive communication strategy, including positive, kind, or reassuring words, can reduce pain perception, while negative words can raise this perception, causing discomfort, known as the "nocebo effect." Although some studies have compared the impact of verbal attitudes, particularly in anesthesia and mainly with staff already trained in hypnosis, to the best of our knowledge, none have investigated the effect of communication in the emergency setting, where patients may be more suggestible to the words used. In this study, we will investigate the effect of positive therapeutic communication on pain, anxiety, discomfort, and global satisfaction in patients requiring ABG compared to nocebo and neutral communication. A single-center, double-blind randomized controlled trial (RCT) with 3 parallel arms will be conducted with 249 patients requiring ABG during their ED visit. Patients will be randomly assigned to 1 of 3 groups before receiving ABG: positive communication group, negative communication (nocebo) group, or neutral communication (neutral) group. The communication and the words used by the physicians during hygiene preparation, artery location, and puncture will be imposed in each group. The study will be proposed to each patient corresponding to the inclusion criteria. The physicians will not be trained in hypnosis or in positive therapeutic communication. The procedure will be recorded with audio recorders to test its quality. Intention-to-treat analysis will be performed. The primary endpoint is the onset of pain. The secondary outcomes are patient comfort, patient anxiety, and global satisfaction of the patient with the communication strategy used. On average, 2000 ABG procedures are performed each year in the EDs of hospitals. In this study, 249 patients are expected to be included. With a projected positive response rate of 80%, we intend to include 25 (10%) patients per month. The inclusion period began in April 2023 and will run until July 2024. We hope to publish the results of the study during the fall of 2024. To the best of our knowledge, this study is the first RCT assessing the use of positive communication on pain and anxiety in patients undergoing the ABG procedure in the ED. A reduction in pain, discomfort, and anxiety is expected when using positive communication. If the results are positive, this could be useful to the medical community and encourage clinicians to monitor their communication during care. ClinicalTrials.gov NCT05434169; https://clinicaltrials.gov/ct2/show/NCT05434169. PRR1-10.2196/42043.