The nocebo effect, negative treatment outcomes arising from patient expectations, therapeutic context, or clinician communication, plays a possibly significant yet often underestimated role in psychotherapy. Drawing on recent empirical and theoretical contributions, possible mechanisms how nocebo effects occur and can be attenuated in psychotherapeutic practice are discussed. Nocebo effects may arise from therapist communication, previous treatment failures, adverse therapeutic dynamics, poorly managed expectations, social influences outside the therapy, or context factors elements such as waiting lists. Strategies for mitigating such effects include, for example, empathic engagement, expectation management, and reconditioning of previous negative treatment experiences in clinical settings.

The nocebo effect, negative treatment outcomes arising from patient expectations, therapeutic context, or clinician communication, plays a possibly significant yet often under-estimated role in psychotherapy. Drawing on recent empirical and theoretical contributions, possible mechanisms how nocebo effects occur and can be attenuated in psychotherapeutic practice are discussed. Nocebo effects may arise from therapist communication, previous treatment failures, adverse therapeutic dynamics, poorly managed expectations, social influences outside the therapy, or context-factor elements such as waiting lists. Strategies for mitigating such effects include, for example, empathic engagement, expectation management, and reconditioning of previous negative treatment experiences in clinical settings.

Background Placebo and nocebo effects significantly influence health outcomes, yet healthcare professionals receive limited training and guidance on their mechanisms and clinical application, creating a gap in education and practical understanding. Conducted within the European PANACEA Consortium, this study evaluated healthcare professionals’ knowledge, attitudes, and practices regarding placebo and nocebo effects, and assessed their needs in further education. Methods An online cross-sectional survey among a European multi-country convenience sample of healthcare professionals collected data assessing participants’ knowledge, perceptions, and experiences regarding placebo and nocebo effects; their application and ethical considerations in clinical practice; and investigated educational needs and interest in further training. Quantitative data were analyzed using descriptive statistics, and thematic analysis was applied to the free-text responses. Results Amongst 807 participants, 71.7% reported taking advantage of placebo effects in their practice, and over half of participants (55.8%) observing nocebo effects. Participants reported feeling somewhat confident (53.3%) in harnessing placebo effects with 47.5% feeling confident in preventing nocebo effects. The majority of respondents had not received formal training on placebo and nocebo effects, with most expressing an interest in further training in areas such as healthcare education, emphasizing communication skills to enhance placebo effects, and knowledge to recognize and reduce nocebo effects. Conclusions There is a significant need for more comprehensive training on placebo and nocebo effects, particularly in early health professional education. These findings informed the development of educational resources and best practice recommendations developed as part of the outcomes from the PANACEA Consortium, improving the understanding and application of these effects among healthcare professionals across Europe.

Summary Background: Vaccinations often elicit significant distress in school-aged children, which can impact pain perception and future medical experiences. This study examined the effects of three stages of a video-based magic intervention on self-reported distress and pain in children receiving HPV vaccinations. Methods: This cluster-randomized controlled trial randomized 412 children (aged 9–11 years) who received their first HPV vaccination at five mass-vaccination sites in The Netherlands. Based on vaccination date and time, children were assigned to one of four groups: 1. watching a magic trick video during the vaccination, 2. watching the trick with revelation of the secret, 3. watching the trick with revelation of the secret, followed by a brief post-vaccination video-training, and 4. a regular care control. Children completed questionnaires before (T0) and after (T1) the first vaccination in April 2024, and before the second vaccination six months later (T2) in September/October 2024. The primary outcome of child-reported distress was assessed at T0, T1, and T2 using the Facial Image Scale (FIS) and the short form of the State-Trait Anxiety Inventory (STAI-6). The study was preregistered on OSF (https://doi.org/10.17605/OSF.IO/5ASM9, registered April 4, 2024). Findings: All randomized participants were analyzed according to the intention-to-treat principle. Children in the combined magic-intervention groups (groups 1–3) reported less distress and lower pain after the first vaccination compared to the control group (group 4; distress: p < 0.0001, partial η2 = 0.11; pain: p = 0.0039, η2 = 0.02, 95% CI [0.002–0.058]). The most extensive magic intervention (group 3) showed the largest distress reduction as compared to all other groups (p < 0.0001). No significant differences in distress were observed preceding the second vaccination, indicating a lack of sustained effects. Interpretation: The video-based magic intervention reduced distress and pain immediately following the vaccination, with the largest effect found for the most elaborate intervention group involving active engagement. These findings suggest a promising, easily implementable intervention to improve children’s vaccination experiences during mass vaccinations. Funding: LUMC Foundation (non-profit).

OBJECTIVES: Guidelines advocate goal setting for promoting lifestyle changes in cardiovascular disease (CVD) patients. This study investigates 1) preferences in health and life goal domains in CVD patients, 2) the impact of linking life goals to health goals on intention-to-change-lifestyle and explores 3) socio-demographic and health-related variables influencing intention-to-change-lifestyle. DESIGN: Online experimental study. METHODS: Patients (N = 629, mean age 66.6; 39% female) were randomized to health-goal-group (HG) or life-and-health-goal-group (LHG). HG set a health goal, and LHG first established a life goal and then set a supporting health goal. Directly after goal setting, the primary outcome, intention-to-change-lifestyle, was measured and analysed using logistic regression (high: 9-10 vs. lower: ≤8.5), as were the secondary outcomes. RESULTS: Exercise goals were most frequently selected in LHG (66.0%) and HG (66.9%). Preference for selecting stress management was significantly higher in LHG (17.3%) than HG (9.3%), χ2(1) = 8.85, p = .003; OR = 2.05, 95%CI [1.27-3.30]. The direct effect of goal-setting condition on intention-to-change-lifestyle was non-significant (OR = .98, 95%CI [.71-1.34], p = .88). In exploratory analyses, lower- and medium-educated patients showed significantly higher intention when life and health goals were linked (OR = 2.55, 95%CI [1.03-6.27], p = .04, and OR = 2.47, 95%CI [1.15-5.30], p = .02, respectively). Perceived meaning in life was positively associated with intention. CONCLUSIONS: No main effect of goal-setting condition on intention-to-change-lifestyle was found. Linking life goals to health goals increased preference for stress management and, in exploratory analyses, was associated with higher intention-to-change-lifestyle among lower- and medium-educated patients. Findings emphasize the relevance of personalized, value-based goal setting within cardiac rehabilitation.

Background
The overwhelming evidence of nocebo effects adversely affecting the experience of physical symptoms, such as pain, puts emphasis on the study of possible strategies to reduce nocebo effects. Counterconditioning, during which a previously conditioned effect is reversed, has been shown to be a possible promising strategy in a previous study in an open-label design, in which people were informed about the use of inert treatments and the counterconditioning procedure. However, it is unclear whether open-label counterconditioning is as effective as closed-label procedures in comparison to extinction.

Methods
In a randomised controlled trial, we investigated in 66 healthy female participants whether conditioned nocebo effects on pressure pain can be reduced via open-label counterconditioning, closed-label counterconditioning, or extinction.

Results
A significant reduction of nocebo effects was found after open-label counterconditioning (d = 1.13), closed-label counterconditioning (d = 0.69), and extinction (d = 0.66). Open-label counterconditioning was more effective than extinction (d = 0.85), reversed the nocebo effect, and also resulted in a placebo effect. Closed-label counterconditioning was more effective than extinction (d = 0.45) in the sensitivity analyses of nocebo responders only. Finally, larger placebo expectancies predicted a higher response to the open- and closed-label counterconditioning procedures, but not extinction.

Conclusions
These results show that particularly open-label counterconditioning is an effective method to modulate nocebo effects on pressure pain. This provides promise in designing non-deceptive learning-based treatments to reduce nocebo effects in diverse patient groups, including chronic pain disorders.

Significance Statement
Few studies have investigated the efficacy open-label counterconditioning to reduce nocebo effects or have compared it to deceptive reduction strategies. The current study demonstrates that open-label counterconditioning is as effective as more deceptive nocebo-reducing strategies and may thus be a promising new method for reducing nocebo effects in a non-deceptive and ethical manner. Results can be helpful while designing learning-based treatments to reduce nocebo effects in patients with, for example, chronic pain disorders.

Objectives: eHealth interventions favor those with higher socio-economic positions (SEPs). This can widen disparities, as people with lower SEPs may lack resources and face digital or financial barriers, making tailored solutions necessary. This study evaluates professionals' perceptions of the Inclusive eHealth Guide (IeG) regarding its content. The aim was to ensure it meets the needs of professionals and the targeted lower SEP demographic, thereby enhancing the effectiveness of eHealth interventions.

Methods: This mixed-method study used qualitative research through semi-structured interviews and the think-aloud method with 13 professionals involved in eight different eHealth lifestyle interventions using the eHealth guide. Quantitative feedback was obtained through a survey with evaluative multiple-choice questions. Participants evaluated the IeG at various stages. They identified positive aspects and points for improvement, and provided recommendations for the guide's content and structure.

Results: Participants valued the IeG's practicality and comprehensiveness, noting its usefulness in developing accessible eHealth solutions for populations with lower SEP. They suggested improving content clarity, expanding informational depth, and refining the guide's structure.

Conclusions: The IeG has potential as a valuable tool for professionals developing eHealth interventions for lower SEP populations. Continuous refinement is crucial to ensure the guide remains relevant and effective, contributing to reducing health disparities.

Importance: General practitioners (GPs) sometimes initiate a treatment despite not expecting it to improve patients' symptoms by any physiological mechanism. These essentially placebo treatments are ethically controversial, and their frequency is unclear. They involve risks for patients, but to estimate these, more data are needed. Objective: To develop a more precise overview of the rate at which GPs prescribe essentially placebo treatments. Design, Setting, and Participants: This cross-sectional survey study included currently practicing GPs from 20 European countries and Israel who responded to online questionnaires. The online questionnaires were taken between December 12, 2019, and August 4, 2021, and analyzed on April 28, 2022. Respondents were contacted by national representatives, either through personal networks (convenience sampling) or an existing database (volunteer sampling). Main Outcomes and Measures: The main outcome was the rate of essentially placebo prescriptions, given as the rate per week and the proportion of consultations. Secondary outcomes were the associations between this rate and GP background characteristics (gender, age, education about placebos, years of experience, patients seen, and working hours per week). Results: A total of 952 practicing GPs responded (453 of 745 [61%] female; mean [SD] age of 48.02 [11.95] years), and 669 answered all questions. Overall, 689 of 818 respondents (84%) indicated they had prescribed an essentially placebo treatment at least once. Overall, the median (IQR) rate of essentially placebo prescriptions was 0.5 (0.1 to 2.0) per week or 0.67% (0.06% to 2.50%) of consultations. The prescription rate was higher in men (β = 1.94 [95% CI, 0.58 to 3.29]; P = .005), those with more work experience (β = 0.12 [95% CI, 0.06 to 0.18]; P < .001), and those who work fewer hours per week (β = -0.08 [95% CI, -0.13 to -0.03]; P = .001). Conclusions and Relevance: In this survey study of GPs across 21 countries, essentially placebo prescriptions featured in a small minority of consultations, but they nevertheless occurred regularly for most GPs. Rates varied only slightly by GP background characteristics. This suggests that essentially placebo prescriptions were common at a population level, which poses risks for the patient-GP relationship and creates medical risks for patients. Future research should further investigate the decision-making process behind these prescriptions and their effects on patients.

Background: Remote patient management (RPM) using smartphone-enabled health monitoring devices (SHMDs) can be an effective, value-added part of cardiovascular care. However, cardiac patients’ adherence to RPM is variable. Personas are fictional representations of users with common behaviors, needs, and motivation and can thereby help guide tailoring of interventions to be meaningful and possibly more effective. Personas can be used to understand the needs of the patient group and guide tailoring toward more personalized and effective eHealth intervention. Objective: The aim of this study was to develop data-driven personas for patients with myocardial infarction (MI) based on both quantitative and qualitative results. Methods: This study used a mixed methods design involving (1) database analysis of patients with MI (N=261) SHMD usage data (blood pressure [BP], weight, step count) over the course of a one-year care track and (2) semistructured interviews with patients with MI (N=16) currently using SHMDs. Overall, 12-month adherence rates were calculated based on the number of weeks patients performed the prescribed home measurements with the SHMDs. Results: A cluster analysis was conducted on the self-monitoring data resulting in four distinctive usage patterns labeled as stiff starting (low adherent in first 6 weeks: 13%, 34/261 of users), temporary persisting (decreasing adherence: 24%, 62/261), loyally persisting (continuously adherent: 26%, 68/261), and negligent quitting (nonadherent: 37%, 97/261). Health outcomes (BP, step count, and weight) were analyzed based on these patterns. More adherent usage patterns show better controlled BP when compared to less adherent usage patterns, suggesting that adherence is associated with health outcomes. Patient experiences regarding adherence or nonadherence to the RPM relating to the four distinctive usage patterns were uncovered by means of semistructured interviews, providing insight into adherence factors most relevant for each of the clusters. Thus, 4 distinct personas were developed by data collection (database analysis and semistructured interviews), persona segmentation, and persona creation, named Tamara, Sam, Peter, and Kim. Conclusions: This study identified 4 personas regarding adherence experiences and usage patterns of patients within an RPM care track. Adherent usage patterns were characterized by improved BP and step count. These personas can guide future tailoring of eHealth interventions to maximize patient adherence.

Background
To improve lifestyle guidance within cardiac rehabilitation (CR), a comprehensive understanding of the motivation and lifestyle-supporting needs of patients with cardiovascular disease (CVD) is required.

Objectives
This study's purpose is to evaluate patients’ lifestyle and their motivation, self-efficacy and social support for change when starting CR.

Methods
1782 CVD patients (69 % male, mean age 62 years) from 7 Dutch outpatient CR centers participated between 2020 and 2022. Modifiable risk factors were assessed with a survey and interviews by healthcare professionals during CR intake.

Results
Most patients exhibited an elevated risk in 3–4 domains. Elevated risks were most prominent in domains of (1) waist circumference and BMI (2) physical exercise (3) healthy foods intake and (4) sleep duration. Most patients chose to focus on increasing physical exercise, but about 20 % also wanted to focus on a healthy diet and/or decrease stress levels. Generally, motivation, self-efficacy and social support to reach new lifestyle goals were high. However, patients with an unfavorable risk profile had lower motivation and self-efficacy to work on lifestyle changes, while patients with lower social support had a higher chance to quit the program prematurely.

Conclusions
Our results underscore the need to begin CR with a comprehensive lifestyle assessment and highlight the importance of offering lifestyle interventions tailored to patients’ specific modifiable risk factors and lifestyle-supporting needs, targeting multiple lifestyle domains. Expanding the current scope of CR programs to address diverse patient needs and strengthening support may enhance motivation and adherence and lead to significant long-term benefits for cardiovascular health.

Objectives: Placebo effects can relieve acute and chronic pain in both research and clinical treatments by learning mechanisms. However, the application of placebo-based treatment strategies in routine medical care is questioned. The current study investigated the opinions of patients with fibromyalgia and healthy controls regarding learning of placebo effects and their practical applications. Method: An online survey asked 158 age- and sex-matched adult patients and controls (79 per group) to rate the perceived influence of various placebo learning mechanisms on pain relief, and the acceptability and perceived effectiveness of placebo-based strategies (open-label, closed-label, dose-extending, and treatment-enhancing strategies). Respondents' knowledge about placebo effects was obtained through a 7-item quiz. Results: The groups did not differ in the perceived influence of placebo learning mechanisms on pain relief (p = 0.217). Controls considered closed-label and treatment-enhancing strategies more acceptable than patients (p = 0.003 and p < 0.001), whereas controls perceived all strategies more effective. In both groups, closed-label strategies were significantly less acceptable than any other strategy (p-values < 0.001), and treatment-enhancing or dose-extending strategies were most acceptable. Higher acceptability was predicted by higher perceived effectiveness ratings (p < 0.001). Also, increased placebo knowledge was related to higher acceptability (p = 0.03) and perceived effectiveness (p < 0.001). Discussion: This survey suggests that both the medical history of patients and knowledge about placebo effects affect the acceptability and perceived effectiveness of placebo-based strategies. Furthermore, strategies that are transparent, assumed effective, or combined with existing medical treatments are deemed most acceptable. Keeping these factors in mind is essential for the clinical implementation of placebo-based strategies in routine medical care.

Objectives:
Although the multifactorial nature of chronic pain is well established, research has predominantly examined isolated variables or singular pathways that may contribute to this condition. We use a complex systems perspective to examine the interplay of psychological factors in the context of chronic pain.

Methods:
We analyzed 2 cross-sectional data sets (N=935 and 1366) collected at a pain clinic and rehabilitation center in Belgium from individuals primarily with musculoskeletal pain. These included self-reported data on pain-related fear and avoidance beliefs, depression and anxiety symptoms, pain intensity, and disability. We used Gaussian Graphical Models to examine conditional associations between these variables, their relative importance (having more/stronger relationships), and how they are moderated by pain-related fear and pain intensity.

Results:
Our analyses revealed highly interrelated networks, with several unique, positive associations between the included factors. Depressive symptoms and pain intensity were most strongly related to pain disability. Fear-avoidance beliefs featured less prominently than previous studies looking at this concept in isolation have suggested. Apart from differences in 2 associations between samples, and 2 moderation effects of pain intensity in 1 sample, the network structure was similar across the 2 samples.

Discussion:
Overall, our results show that psychological factors related to disability have intricate interrelations, highlighting the complexity of chronic pain and the need to study its many components in relation to each other. The consistency across the 2 samples provides encouraging evidence that the results reflect a stable pattern within this complex system.

Expectancies and avoidance behavior are key factors influencing pain perception and its maintenance, but few empirical studies have investigated their relationship. Thus, two separate studies with a two-fold primary aim were conducted. The first part of the primary aim was to investigate whether negative expectancies lead to hyperalgesia. The second part of the primary aim was to investigate whether negative expectancies lead to more costly pain avoidance. The studies included a total of 116 and 98 participants respectively. In both studies, participants were randomly assigned to either the experimental or the control group. Pain expectancies were induced verbally and via conditioning, and avoidance was measured through a novel pain avoidance task in which participants could choose between avoiding a more painful stimulus by playing a difficult game or enduring a more painful stimulus by playing an easy game. In Study 2, adjustments were made to the conditioning procedure and the novel pain avoidance task based on the results of Study 1. Both studies demonstrated that negative expectancies led to hyperalgesia, indicating that the negative expectancy paradigm produces robust effects. However, negative expectancies did not lead to more pain avoidance suggesting that other factors may be at play in avoiding more pain. Further studies are needed to fully unravel the interplay between expectancies and avoidance in pain.

Perspective
This article found that negative expectancies can lead to hyperalgesia but not necessarily to more pain avoidance behavior in individuals without chronic pain. Findings from this article support the ample studies indicating that expectancies provide a strong target for pain treatment.

Complex eHealth interventions - featuring multiple components within dynamic systems - are used for healthcare improvement. Public-private partnerships (PPPs), combining resources, expertise, and technology, are crucial in this context. Yet, integrating these interventions into practice remains challenging. This study identifies barriers and facilitators affecting implementation of the BENEFIT programme, a complex eHealth intervention targeting cardiovascular disease patients, by PPP within practice. A qualitative study design was employed. Ten key stakeholders from four cardiac rehabilitation (CR) sites, who were all PPP partners involved in developing and implementing the BENEFIT programme, were interviewed semistructured. Transcripts were analysed using Consolidated Framework for Implementation Research. Facilitators included programme adaptability, communication and planning within teams, digital healthcare needs, dedicated PPP leadership, PPP meeting structure and PPP's ability to quickly modify the implementation strategy. Barriers involved specific PPP challenges (frequently changing roles, unclear roles and responsibilities and limited staffing), workplace disruptions, poor information technology (IT) integration, and ambiguous implementation goals amongst CR sites. This case study highlights challenges in implementing complex eHealth interventions by PPPs within practice. The findings underscore the need for a comprehensive implementation approach considering specific PPP dynamics, including combined expertise and resources, transparent role definition, sufficient staffing, clear goal communication and adaptable strategies for sustainable implementation.

Background: Financial incentives are a promising tool to help people increase their physical activity, but they are expensive to provide. Deposit contracts are a type of financial incentive in which participants pledge their own money. However, low uptake is a crucial obstacle to the large-scale implementation of deposit contracts. Therefore, we investigated whether (1) matching the deposit 1:1 (doubling what is deposited) and (2) allowing for customizable deposit amounts increased the uptake and short term effectiveness of a deposit contract for physical activity. Methods: In this randomized controlled trial, 137 healthy students (age M = 21.6 years) downloaded a smartphone app that provided them with a tailored step goal and then randomized them to one of four experimental conditions. The deposit contract required either a €10 fixed deposit or a customizable deposit with any amount between €1 and €20 upfront. Furthermore, the deposit was either not matched or 1:1 matched (doubled) with a reward provided by the experiment. During 20 intervention days, daily feedback on goal progress and incentive earnings was provided by the app. We investigated effects on the uptake (measured as agreeing to participate and paying the deposit) and effectiveness of behavioral adoption (measured as participant days goal achieved). Findings: Overall, the uptake of deposit contracts was 83.2%, and participants (n = 113) achieved 14.9 out of 20 daily step goals. A binary logistic regression showed that uptake odds were 4.08 times higher when a deposit was matched (p = .010) compared to when it was not matched. Furthermore, uptake odds were 3.53 times higher when a deposit was customizable (p = .022) compared to when it was fixed. Two-way ANCOVA showed that matching (p = .752) and customization (p = .143) did not impact intervention effectiveness. However, we did find a marginally significant interaction effect of deposit matching X deposit customization (p = .063, ηp2 = 0.032). Customization decreased effectiveness when deposits were not matched (p = .033, ηp2 = 0.089), but had no effect when deposits were matched (p = .776, ηp2 = 0.001). Conclusions: We provide the first experimental evidence that both matching and customization increase the uptake of a deposit contract for physical activity. We recommend considering both matching and customization to overcome lack of uptake, with a preference for customization since matching a deposit imposes significant additional costs. However, since we found indications that customizable deposits might reduce effectiveness (when the deposits are not matched), we urge for more research on the effectiveness of customizable deposit contracts. Finally, future research should investigate which participant characteristics are predictive of deposit contract uptake and effectiveness. Pre-registration: OSF Registries, https://osf.io/cgq48.

Stroke is a highly disabling condition, for which music therapy is regularly used in rehabilitation. One possible mechanism for the effects of music therapy is the motivational aspect of music, for example regarding treatment adherence based on improved mood. In this study, changes in motivation related to Neurologic Music Therapy (NMT) techniques during rehabilitation in the subacute phase after stroke will be investigated. Using a randomised within-subjects cross-over design, the effects of two NMT techniques and related motivational indices will be investigated. Data will be collected at three timepoints: baseline (TP1), after being randomised into groups and receiving NMT or standard care (TP2), and then at a third time point after the cross-over and having received both conditions (TP3). This design allows to counteract order effects, time effects due to spontaneous and/or nonlinear recovery, as well as single-subject comparisons in a relatively heterogeneous sample. Twenty adult participants who have experienced a supratentorial ischaemic or haemorrhagic stroke and are experiencing upper-limb impairments and/or cognitive deficits will be included. Behavioural measures of motor function, cognition, and quality of life will be collected, along with self-reported indices of overall motivation. The study outcomes will have implications for the understanding of the underlying mechanisms of music therapy in stroke recovery, more specifically regarding the relevance of motivational states in neurorehabilitation.

Negative expectations can increase pain sensitivity, leading to nocebo hyperalgesia. However, the physiological and psychological factors that predispose individuals to this phenomenon are still not well understood. The present study examined whether stress induced by a social stressor affects nocebo hyperalgesia, and whether this effect is mediated by self-reported and physiological stress responses. We recruited 52 healthy participants (15 men) who were randomly assigned to either the Trier Social Stress Test (TSST) or a control condition (a friendly version of the TSST). Nocebo hyperalgesia was induced using negative suggestions combined with a validated pain conditioning paradigm. We assessed self-reported (anxiety and stress) and physiological (cortisol, alpha-amylase, heart rate, and skin conductance) responses to stress. Both groups exhibited significant nocebo hyperalgesia. The stress group showed higher levels of anxiety, self-reported stress, and cortisol levels compared to the control group while no significant differences were found in other physiological markers. The stress and control groups did not differ in the magnitude of nocebo hyperalgesia, but anxiety levels partially mediated the effects of the stress test on nocebo hyperalgesia. Our findings suggest that an external social stressor does not directly affect nocebo hyperalgesia, but that increased anxiety due to the stressor enhances its magnitude. Thus, it may be worthwhile to investigate whether reducing stress-related anxiety in clinical settings would help alleviate nocebo effects.

Somatic symptoms like pain, itch, and fatigue, can negatively affect daily functioning. In the acute phase, these somatic symptoms are adaptive as they push the body to protect itself from potential bodily threat. However, when these symptoms turn chronic, they may instead cause disability. Pain, itch, and fatigue have been shown to share mechanisms that maintain them towards chronicity and they commonly occur in various medical conditions. For example, pain and fatigue are common co-occurring symptoms in patients with multiple sclerosis, cancer, chronic low back pain, fibromyalgia, and functional neurological disorders (e.g., Eccles and Davies, 2021; Maggio et al., 2020; Mense and Schiltenwolf, 2010; Petersen et al., 2020) and symptoms of itch, pain, and fatigue are often reported in patients with chronic skin diseases and other chronic conditions, such as some forms of cancer or kidney disease (e.g., Verhoeven et al., 2007). Additionally, each of these symptoms have a high prevalence rate (Dahlhamer et al., 2018, Lim et al., 2020, Weisshaar, 2016) and share the same evolutionary function; to protect the body from disease and harm (Boullosa and Nakamura, 2013, Cevikbas and Lerner, 2020, Walters and Williams, 2019). Furthermore, chronic pain, itch, and fatigue cause similar burden to those that experience them. These chronic symptoms can also limit productivity and interfere with daily activities which have been shown to lower quality of life (Cole et al., 2021, Gerbershagen et al., 2002, Van Heck and de Vries, 2002). Moreover, the stigma that may be associated with these symptoms could also contribute to low quality of life (Froehlich et al., 2022, Perugino et al., 2022, Warlich et al., 2015). [...]

eHealth lifestyle interventions without human support (self-help interventions) are generally less effective, as they suffer from lower adherence levels. To solve this, we investigated whether (1) using a text-based conversational agent (TCA) and applying human cues contribute to a working alliance with the TCA, and whether (2) adding human cues and establishing a positive working alliance increase intervention adherence. Participants (N = 121) followed a TCA-supported app-based physical activity intervention. We manipulated two types of human cues: visual (ie, message appearance) and relational (ie, message content). We employed a 2 (visual cues: yes, no) x 2 (relational cues: yes, no) between-subjects design, resulting in four experimental groups: (1) visual and relational cues, (2) visual cues only, (3) relational cues only, or (4) no human cues. We measured the working alliance with the Working Alliance Inventory Short Revised form and intervention adherence as the number of days participants responded to the TCA's messages. Contrary to expectations, the working alliance was unaffected by using human cues. Working alliance was positively related to adherence (t(78) = 3.606, p = .001). Furthermore, groups who received visual cues showed lower adherence levels compared to those who received relational cues only or no cues (U = 1140.5, z = −3.520, p < .001). We replicated the finding that establishing a working alliance contributes to intervention adherence, independently of the use of human cues in a TCA. However, we were unable to show that adding human cues impacted the working alliance and increased adherence. The results indicate that adding visual cues to a TCA may even negatively affect adherence, possibly because it may create confusion concerning the true nature of the coach, which may prompt unrealistic expectations.