Gamification in eHealth for Chronic Disease Self-Management in Youth: A Systematic Review.

This systematic review primarily aims to provide a summary of the game mechanics implemented in eHealth tools supporting young people's self-management of their chronic diseases. This review secondarily investigates the rationale for implementing game mechanics and the effects of these tools. A systematic search was conducted in Embase, Medline, PsycINFO, and Web of Science, from inception until August 30, 2022. Studies were eligible if focus was on the utilization of gamification in eHealth self-management interventions for young people (age = 10-25 years) with chronic diseases. Primary quantitative, qualitative, and mixed-method studies written in English were included. We identified 34 eHealth tools, of which 20 (59%) were gamified tools and 14 (41%) were serious games. We found that 55 unique game mechanics were implemented. The most commonly used were rewards (50%), score (44%), creative control (41%), and social interaction (32%). In comparison with gamified tools, the number and diversity of game mechanics applied were higher in serious games. For most tools (85%), a general rationale was provided for utilizing gamification, which often was to promote engaging experiences. A rationale for using specific game mechanics was less commonly provided (only for 45% of the game mechanics). The limited availability of experimental research precludes to test the effectiveness of using gamification in eHealth to support self-management in young people with chronic diseases. In this study, we highlight the importance of reporting the rationale for utilizing specific game mechanics in eHealth tools to ensure a proper alignment with evidence-based practice and the need of conducting experimental research. PROSPERO: CRD42021293037.

Integrated care model for patients with functional somatic symptom disorder - a co-produced stakeholder exploration with recommendations for best practice.

BACKGROUND: Functional somatic symptoms (FFS) and bodily distress disorders are highly prevalent across all medical settings. Services for these patients are dispersed across the health care system with minimal conceptual and operational integration, and patients do not currently access therapeutic offers in significant numbers due to a mismatch between their and professionals' understanding of the nature of the symptoms. New service models are urgently needed to address patients' needs and to align with advances in aetiological evidence and diagnostic classification systems to overcome the body-mind dichotomy. METHOD: A panel of clinical experts from different clinical services involved in providing aspects of health care for patients with functional symptoms reviewed the current care provision. This review and the results from a focus group exploration of patients with lived experience of functional symptoms were explored by the multidisciplinary expert group, and the conclusions are summarised as recommendations for best practice. RESULTS: The mapping exercise and multidisciplinary expert consultation revealed five themes for service improvement and pathway development: time/access, communication, barrier-free care, choice and governance. Service users identified four meta-themes for best practice recommendations: focus on healthcare professional communication and listening skills as well as professional attributes and knowledge base to help patients being both believed and understood in order to accept their condition; systemic and care pathway issues such as stronger emphasis on primary care as the first point of contact for patients, resources to reduce the length of the patient journey from initial assessment to diagnosis and treatment. CONCLUSION: We propose a novel, integrated care pathway for patients with 'functional somatic disorder', which delivers care according to and working with patients' explanatory beliefs. The therapeutic model should operate based upon an understanding of the embodied nature of patient's complaints and provide flexible access points to the care pathway.

Diagnosis and Treatment of Generalized Anxiety Disorder in Japan: Psychiatric Specialist Survey.

Purpose: Generalized anxiety disorder (GAD) is a suboptimally managed chronic recurring psychiatric condition with a lifetime prevalence of 2.6% in Japan. We assessed the current status of GAD management in Japan. Patients and Methods: This was an observational, cross-sectional study conducted through an anonymous web-based survey in Japan from December 12-16, 2022. Psychiatrists and psychosomatic medicine physicians who agreed to participate and saw ≥10 outpatients in the previous month were eligible. Survey questionnaire comprised 37 single/multiple choice, numerical entry, or open-ended questions in Japanese. Results: Among 509 participants (493 psychiatrists and 16 psychosomatic medicine physicians), 96.9% were aware of GAD. On average, 12.4 outpatients and 1.0 inpatient were diagnosed with GAD per physician per month. Of 433 physicians having patients diagnosed with GAD, 46.9% used operational diagnostic tools; among these, DSM-5 diagnostic criteria were used by 81.5% physicians. The majority (54.7%) of participants did not use a self-administered rating scale; depression scales were used more than anxiety scales. Among these 433 physicians, 96.8% used selective serotonin reuptake inhibitors for GAD management, and 79.2% used it as the first choice; of 431 physicians who prescribed drug therapy, 54.3% gave antidepressant monotherapy as first choice. The most frequent symptom in patients diagnosed with GAD was excessive anxiety/worry (96.5%); depression was the most commonly reported comorbidity (84.3%) as per physicians aware of GAD (N=508). Conclusion: This study illustrates that although GAD awareness is high among Japanese psychiatric specialists, GAD is not frequently diagnosed using operational diagnostic approaches. Due to a lack of Japanese guidelines for GAD diagnosis and treatment, diverse international guidelines are followed, with similar treatment paradigms as that of depression. This may not be an optimal approach given cultural/geographical differences. These findings highlight the need for uniform diagnosis and treatment recommendations for GAD management in Japan. Clinical Trial Registration: UMIN-CTR: UMIN000049572.

Insights into discrepancies in professional identities and role models in undergraduate medical education in the context of affective burden.

Introduction: International evidence strongly suggests that medical students are at high risk of mental health problems. This distress, which can be mediated by a variety of individual, interpersonal and contextual factors within the curriculum, can be mitigated by effective coping strategies and interventions. Central to this discourse is the recognition that the challenges of professional identity formation can contribute significantly to medical students' distress. The focus of our study is therefore to examine discrepancies in professional identities and role models in undergraduate medical education in relation to affective burden. Methods: Medical students at different stages of university education and high school graduates intending to study medicine were surveyed in a cross-sectional study. The study employed Osgood and Hofstätter's polarity profile to evaluate the self-image of participants, the image of an ideal and real physician, and their correlation with depression (PHQ-9) and anxiety (GAD-7). Results: Out of the 1535 students recruited, 1169 (76.2%) participated in the study. Students rated their self-image as somewhere between a more critical real image of physicians and a more positive ideal image. Medical students at all training levels consistently rated the ideal image as remaining constant. Significant correlations were found between the professional role models of medical students and affective symptoms, particularly for the discrepancy between the ideal image of a physician and their self-image. Furthermore, 17% and nearly 15% reported significant symptoms of depression and anxiety, respectively. Discussion: Our study adds to the growing body of knowledge on professional identity formation in medicine and socialisation in the medical environment. The study highlights the importance of discrepancies between self-image and ideal image in the experience of depressive and anxiety symptoms. Primary prevention-oriented approaches should incorporate these findings to promote reflective competence in relation to professional role models and strengthen the resilience of upcoming physicians in medical training.

Biosemiotic medicines: Symbolic formulations for placebo enhancements.

The healing response is a complex and multiform procedure that involves many physical and symbolic interactions and synchronizations. In the clinical research model, certain factors are abstracted during which contextual elements, such as placebo responses and communicative factors, are excluded to reveal the pieces of evidence that are necessary for the mass production of clinical materials and methods. On the other side, clinical practice is a singular and chaotic communicative action in which we should include contextual and discursive factors for prompting proper biological as well as behavioral responses. Placebo responses, personal history and attitudes, and clinical relationships and communication are some of the contextual and individual factors that can be changed effectively if we can communicate with the symbolic and reflective matrices of clinical practice. In this article, the author introduces a biosemiotic formula for healing responses that include symbolic and reflective factors of healing response aligned with the related biological procedures. Not only are psychological interventions beneficial in mental health problems and symptom control but they could also be used as co-treatments to reinforce placebo responses and improve illness behavior and treatment narratives.

Efficacy of patient education and duloxetine, alone and in combination, for patients with multisystem functional somatic disorder: Study protocol for the EDULOX trial.

BACKGROUND: Multisystem functional somatic disorder is characterized by specific patterns of persistent physical symptoms with a complex biopsychosocial etiology. The disorder can lead to disability and personal suffering. Current treatment options require specialized settings, therefore patients often wait a long time to receive specific treatment. Patient education is considered important in most treatment programs, but has only been investigated sparsely as a stand-alone treatment. Pharmacological treatment is limited to tricyclic antidepressants in low doses with no antidepressant properties. Duloxetine has been found effective in single organ functional disorders. As a treatment for multisystem functional somatic disorder, duloxetine could reduce symptoms and treat comorbid anxiety and depression. It may furthermore enhance the effect of patient education through a hypothesized effect on cognitive functioning. The purpose of the EDULOX trial is to study psycho-EDUcation and duLOXetine alone and in combination. METHODS: This is a nested study design. The parent trial "EDULOX1" (n = 424) will compare a patient education program with enhanced usual care in an open-labelled, randomized controlled trial. In addition to this, eligible participants will furthermore receive either duloxetine or active placebo in the nested, double-blinded, randomized controlled trial, "EDULOX2" (n = 212). Patient and clinician reported outcomes will be collected through questionnaires. CONCLUSION: The EDULOX trial may establish evidence for treatments applicable for the majority of patients with multisystem functional somatic disorder. If effective, duloxetine would be a more tolerable pharmacological treatment option that can target comorbid depression and anxiety, and potentially boost the effect of patient education. Trial registration number The study is registered at www. CLINICALTRIALS: gov (NCT06232473) and the internal list of research projects at the Region of Central Denmark (Case number 1-16-02-305-23). Approval from the Danish Medical Research Ethics Committees (Case number: 2212291) and the Danish Medicines Agency was obtained under EudraCT Number: 2022-002780-30 and Sponsor's Protocol Code Number: 9515.

A Single-Session Process-Based Cognitive-Behavioral Intervention Combined with Multimodal Rehabilitation Treatment for Chronic Pain Associated with Emotional Disorders.

BACKGROUND AND OBJECTIVES: Defined by chronic pain, rheumatic diseases are often co-occurring with anxiety and depression. Among the available psychological interventions, cognitive-behavioral therapies have an already-proven efficiency in these cases. However, the need to adjust their structure became ubiquitous during the post-pandemic period. Hence, the objective of this study was to investigate the impact of a single-session, process-based cognitive-behavioral intervention for patients with rheumatic conditions within an in-patient setting. MATERIALS AND METHODS: A total of 31 participants (mean age 58.9 years) completed the single-session intervention. Assessments were conducted prior to the intervention, post-intervention and after one month. RESULTS: Pearson's correlations, paired samples T tests and a covariance analysis based on the Linear Mixed Model were performed for exploring the relations between baseline variables and evaluating the impact of the SSI intervention. Immediately after the intervention, a significant reduction in cognitive fusion (p = 0.001, d = 1.78), experiential avoidance (p = 0.001, d = 1.4) and dysfunctional behavioral processes was observed. At the one-month evaluation, participants reported decreased pain (p = 0.001, d = 1.11), anxiety (p = 0.004, d = 0.55) and depression (p = 0.001, d = 0.72). CONCLUSIONS: The single-session, process-based approach represents a promising intervention in healthcare contexts, as an integrative part of a multimodal rehabilitation treatment in patients with rheumatic conditions.

Current State of Consultation-Liaison Psychiatry in China and Future Directions.

This article provides an overview of the history and current status of consultation-liaison psychiatry (CLP) in China and its development within the Chinese Society of Psychosomatic Medicine. Over the past decade, various CLP practice models have been developed to meet the diverse needs of different regions in China. Notably, the Chinese Multidisciplinary Integrated Centers of Psychosomatic Medicine have been established as regional hubs throughout the country. Additionally, this article delves into the role of Chinese traditional medicine in the practice of CLP in China. Finally, several projects involving CLP-based multidisciplinary collaboration are highlighted. We hope this article offers a bird's-eye view of CLP in China and opens a window for future collaboration with CLP initiatives in other countries.

Physician resilience and perceived quality of care among medical doctors with training in psychosomatic medicine during the COVID-19 pandemic: a quantitative and qualitative analysis.

BACKGROUND: At an individual level, physician resilience protects against burnout and against its known negative effects on individual physicians, patient safety, and quality of care. However, it remains uncertain whether physician resilience also correlates with maintaining a high level of healthcare quality during crises such as a pandemic. This study aimed to investigate whether higher resilience among physicians, who had received training in resilience-related competences in the past, would be associated with higher quality of care delivered during the COVID-19 pandemic. METHODS: This study enrolled physicians working in family medicine, psychiatry, internal medicine, and other medical specialties, who had obtained at least one of three consecutive diplomas in psychosomatic medicine in the past. Participants completed a quantitative and qualitative anonymous online survey. Resilience was measured using the Connor-Davidson Resilience Scale, and healthcare quality was assessed through single-item quality indicators, including perceived quality of care, professional autonomy, adequate time for patient care, and job satisfaction. RESULTS: The study included 229 physicians (70 males/159 females) with additional training in psychosomatic medicine, working in family medicine (42.5%), psychiatry (28.1%), internal medicine (7.0%), or other medical specialties (22.4%). Participants represented four intensity levels of training background (level 1 to level 4: 9.2%, 32.3%, 46.3%, and 12.2% of participants). Training background in psychosomatic medicine was positively associated with resilience (B = 0.08, SE = 0.04, p <.05). Resilience and training background independently predicted perceived quality of care, even after controlling for variables such as own health concerns, involvement in the treatment of COVID-19 patients, financial strain, percentage of working hours spent on patient care, age, and gender (resilience: B = 0.33, SE = 0.12, p <.01; training background: B = 0.17, SE = 0.07, p <.05). Both resilience and training background predicted job satisfaction (resilience: B = 0.42, SE = 0.12, p <.001; training background: B = 0.18, SE = 0.07, p <.05), while resilience alone predicted professional autonomy (B = 0.27, SE = 0.12, p <.05). In response to an open question about their resources, resilient physicians more frequently reported applying conscious resilient skills/emotion regulation (p <.05) and personal coping strategies (p <.01) compared to less resilient medical doctors. CONCLUSION: Physician resilience appears to play a significant role in the perceived quality of patient care, professional autonomy, and job satisfaction during healthcare crises.

Somatic disease burden and depression risk in late life: a community-based study.

AIMS: Co-occurring somatic diseases exhibit complex clinical profiles, which can differentially impact the development of late-life depression. Within a community-based cohort, we aimed to explore the association between somatic disease burden, both in terms of the number of diseases and their patterns, and the incidence of depression in older people. METHODS: We analysed longitudinal data of depression- and dementia-free individuals aged 60+ years from the population-based Swedish National Study on Aging and Care in Kungsholmen. Depression diagnoses were clinically ascertained following the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition Text Revision over a 15-year follow-up. Somatic disease burden was assessed at baseline through a comprehensive list of chronic diseases obtained by combining information from clinical examinations, medication reviews and national registers and operationalized as (i) disease count and (ii) patterns of co-occurring diseases from latent class analysis. The association of somatic disease burden with depression incidence was investigated using Cox models, accounting for sociodemographic, lifestyle and clinical factors. RESULTS: The analytical sample comprised 2904 people (mean age, 73.2 [standard deviation (SD), 10.5]; female, 63.1%). Over the follow-up (mean length, 9.6 years [SD, 4 years]), 225 depression cases were detected. Each additional disease was associated with the occurrence of any depression in a dose-response manner (hazard ratio [HR], 1.16; 95% confidence interval [CI]: 1.08, 1.24). As for disease patterns, individuals presenting with sensory/anaemia (HR, 1.91; 95% CI: 1.03, 3.53), thyroid/musculoskeletal (HR, 1.90; 95% CI: 1.06, 3.39) and cardiometabolic (HR, 2.77; 95% CI: 1.40, 5.46) patterns exhibited with higher depression hazards, compared to those without 2+ diseases (multimorbidity). In the subsample of multimorbid individuals (85%), only the cardiometabolic pattern remained associated with a higher depression hazard compared to the unspecific pattern (HR, 1.71; 95% CI: 1.02, 2.84). CONCLUSIONS: Both number and patterns of co-occurring somatic diseases are associated with an increased risk of late-life depression. Mental health should be closely monitored among older adults with high somatic burden, especially if affected by cardiometabolic multimorbidity.

[Transdisciplinary treatment of functional movement disorders: integration instead of dissociation]. / Die transdisziplinäre Behandlung funktioneller Bewegungsstörungen: Integration statt Dissoziation.

Successful treatment of patients with functional motor disorders is integrative in several ways: the primary treatment goal is the (re)integration of sensorimotor, cognitive and social functioning. The prerequisites for this are an integrated biopsychosocial model of everyone involved as well as close transdisciplinary cooperation. Instead of a simple addition of treatment components, all care providers and patients act in concert.

The Role of Female Physicians in Psychosomatic Medicine: Opportunities and Challenges.

Background: Female physicians are in some cases preferred by patients due to their sex-related characteristics such as softness and empathy. Psychosomatic medicine presents a compelling working environment due to its holistic approach. Methods: This brief review synthesizes the challenges encountered by female physicians in psychosomatic medicine and outlines potential strategies for overcoming these barriers. Results: The presence of female role models may constitute a crucial advancement in this process. There exists a pressing demand for specialized clinical and scientific programs in psychosomatic medicine at both national and international levels. Such programs, offered by universities and ministries, as well as comprehensive training initiatives, are indispensable in fostering the next generation of females in psychosomatics. Leading journals can lend their support by publishing special issues dedicated to female physicians. Conclusion: Strengthening female physicians throughout all positions in psychosomatic medicine can contribute ultimately to the improvement of patient care.

Integrated Care Models for Older Adults with Depression and Physical Comorbidity: A Scoping Review.

Objective: Multimorbidity is a growing challenge in the care for older people with mental illness. To address both physical and mental illnesses, integrated care management is required. The purpose of this scoping review is to identify core components of integrated care models for older adults with depression and physical comorbidity, and map reported outcomes and implementation strategies. Methods: PubMed, EMBASE, CINAHL and Cochrane Library were searched independently by two reviewers for studies concerning integrated care interventions for older adults with depression and physical comorbidity. We used the SELFIE framework to map core components of integrated care models. Clinical and organisational outcomes were mapped. Results: Thirty-eight studies describing thirteen care models were included. In all care models, a multidisciplinary team was involved. The following core components were mainly described: continuity, person-centredness, tailored holistic assessment, pro-activeness, treatment interaction, individualized care planning, and coordination tailored to complexity of care needs. Twenty-seven different outcomes were evaluated, with more attention given to clinical than to organisational outcomes. Conclusion: The core components that comprise integrated care models are diverse. Future studies should focus more on implementation aspects of the intervention and describe financial parts, e.g., the cost of the intervention for the healthcare user, more transparently.

[Henry Head (1861-1940) and his importance for neurology]. / Henry Head (1861­1940) und seine Bedeutung für die Neurologie.

Nowadays, Henry Head is best known for his Head zones. The concept was understood very differently by Head in comparison to what current medical books falsely describe them to be. In reality, there is no direct relationship between one particular skin zone and one single organ. It is certain that the drawings considered depictions of the Head zones in today's medical textbooks were actually not created by Head. From a neurological point of view, Head is important for two reasons: his self-experiment in 1909 to damage one of his own peripheral nerves followed by regeneration was heroic. It has helped generations of neurologists to have a better understanding of the pathophysiology of peripheral nerve damage and thus make a better assessment of the prognosis of such injuries. Head's second contribution pertains to the radicular organization at the level of the spinal cord. The pathophysiology of herpes zoster radiculitis enabled him to develop the concept of the dermatomes on the basis of preliminary work around 1900. Henry Head's contribution was the systematic compilation of the existing publications of the time and amendment of his own cases. As he was the most important neurologist at that time, at least in the English speaking world, and was well connected with people in the German neurology community, it was probably easy for him to make his dermatome maps well known. In retrospect, Head was less successful in neuropsychology with holistic concepts for higher cognitive functions which were in vogue during his lifetime. His late work on aphasia is now considered refuted. Head's criticism of the strict localization was well in syncronization with the zeitgeist of the early twentieth century. Establishing the fact that Broca's aphasia and Wernicke's aphasia are not easily diagnostically distinguishable from each other was more an achievement of subsequent generations of neurologists and neuropsychologists as well as technical advances.

Sociodemographic and hospital characteristics for patients with severe functional disorder receiving specialized treatment at hospital. A regional register-based cross-sectional study from Denmark.

OBJECTIVE: 10% of all adult Danish citizen has a functional disorder (FD). This study aimed to describe how patients referred to specialized treatment (CFD; Clinic for Functional Disorders) differentiate from those not referred to specialized treatment in terms of sex, comorbidty, different types of hospital contacts and affiliation to labour market 12 and 60 months prior discharged from the hospital with a FD-diagnosis between 2019 and 2021. METHODS: The study was a register-based cross-sectional study of patients discharged with a FD in North Denmark Region between 2019 and 2021 (study period). Patients between 18 and 65 years of age with FD were identified in the regional patient administrative system. RESULTS: A total of 6831 patients were discharged from the hospital with a FD, of which 160 were referred to CFD. Patients with FD were more likely to be referred to CFD, if they were female, had reduced or no affiliation to the labour market or most hospital contacts were as outpatient. Moreover, an increase in hospital contacts as outpatient and a reduction in affiliation to labour market over time increased the chance of being treated at CFD. CONCLUSION: Patients referred to CFD differed from patients not referred to CFD. Patients referred to CFD were to a lesser extent affiliated to the labour market but had more often hospital contacts as outpatient prior to being discharged with FD. In addition, patients referred to CFD increased their contacts to the hospital as outpatient more than those not referred during the preceding 5 years from discharge with FD.

Renal failure following insulin purging in atypical anorexia nervosa and type 1 diabetes mellitus.

Objective: Anorexia nervosa (AN) and atypical anorexia nervosa (AAN) are severe and complex eating disorders that can be prevalent among individuals with type 1 diabetes mellitus (T1DM). Insulin purging, characterized by the intentional underuse / omission of insulin to control weight, is under-recognized in medicine and is a purging strategy of patients with AN or AAN and comorbid T1DM. Often, this can lead to renal failure, necessitating a (pancreas-) kidney transplantation. This article presents a comprehensive overview of the interplay between AN/AAN and T1DM and summarizes the evidence in literature. Methods: A narrative review is presented on basis of a detailed case study of a 32-year-old female with end-stage renal failure seeking (pancreas-) kidney transplantation displaying etiology, diagnosis, comorbidities, complications, and treatment of AN and AAN with emphasis on those patients with T1DM. Results: Insulin purging in patients with AN/AAN and coexisting T1DM can exacerbate T1DM complications, including accelerating the onset of end-stage renal failure. A multidisciplinary approach including nutrition treatment and psychotherapeutic techniques was considered necessary for treatment, focusing on psychosomatic in-patient care before and after organ transplantation. Conclusion: Insulin purging in patients with AAN and T1DM poses severe health risks, including accelerated renal complications. For those considering transplantation, insulin purging has explicitly to be diagnosed and a holistic treatment addressing both the renal condition and psychosomatic symptoms/disorders is crucial for successful post-transplant outcomes.

Corrigendum: Validation of the neuroconnective endophenotype questionnaire (NEQ): a new clinical tool for medicine and psychiatry resulting from the contribution of Ehlers-Danlos syndrome.

[This corrects the article DOI: 10.3389/fmed.2023.1039223.].

Osteopathic Manipulative Medicine and Its Role in Psychiatry.

This paper reviews the current literature to examine what elements of osteopathic medicine can be used in psychiatry. The aim of this study was to use the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines to conduct a systematic review of studies describing the efficacy of osteopathic manipulative medicine (OMM) in treating psychiatric problems directly and indirectly. The authors searched the databases PubMed, PsycINFO, and CINAHL (Cumulative Index to Nursing and Allied Health Literature), reviewing peer-reviewed articles from 1980 to April 2023. The literature demonstrates that OMM has a positive effect on psychiatric symptoms indirectly when treating certain medical conditions, such as chronic pain, fibromyalgia, and irritable bowel syndrome; however, there are many limitations on these studies, and further research is required prior to making firm recommendations. The evidence is lacking for osteopathic manual medicine being used directly to treat psychiatric conditions. This review demonstrates that in some populations, such as individuals with chronic pain, fibromyalgia, and irritable bowel syndrome, OMM could be considered by an osteopathic psychiatrist as an adjunct treatment. More research should be conducted in this area due to the many limitations in the available studies but current research suggests that the use of OMM by osteopathic psychiatrists could be beneficial for some patient populations.

Patients with depression symptoms are more likely to experience improvements of internet-based cognitive behavioral therapy: a secondary analysis of effect modifiers in patients with non-cardiac chest pain in a randomized controlled trial.

BACKGROUND: Non-cardiac chest pain is common and associated with increased anxiety and reduced health-related quality of life. Randomized controlled trials on psychological interventions for patients with non-cardiac chest pain have reported mixed results. Patients with non-cardiac chest pain are a heterogeneous group. Identifying sub-groups that could potentially benefit more (or less) from an intervention would be valuable knowledge. We have conducted a randomized controlled trial where internet-based cognitive behavioural therapy (iCBT) had effect on reducing cardiac anxiety and increasing health-related quality of life at 12-month follow-up. The aim of the present study was to explore potential effect modifiers of iCBT in patients with non-cardiac chest pain on cardiac anxiety and/or health related quality of life at 12-month follow-up. METHODS: We analysed data from our randomized, controlled trial where 161 patients with non-cardiac chest pain were included and randomized to either iCBT or a treatment as usual (control). Cardiac anxiety measured by the Cardiac Anxiety Questionnaire and health-related quality of life measured by the EuroQol Visual Analog Scale at 12 month follow-up were the primary outcomes. Four potential baseline characteristics where identified as potential effect modifiers by a theory-based approach: (1) depression measured by the Patient Health Questionnaire; (2) anxiety measured by the Body Sensations Questionnaire; (3) prior healthcare contacts measured by a self-developed question; and (4) chest pain frequency measured by a self-developed question. Each potential effect modifier was analysed in a linear regression model where cardiac anxiety and EQ-VAS scores at 12-month follow-up, separately, were used as dependent variables. The potential differential treatment effect for each effect modifier was assessed by the interaction term: effect modifier x treatment group. RESULTS: Depression symptoms at baseline predicted a differential treatment effect at 12-month follow-up on health-related quality of life in favor of the iCBT group (regression coefficient of the interaction term: -1.85 (CI -3.28 to -0.41), p = 0.01), but not on cardiac anxiety at 12-month follow-up. Fear of bodily symptoms, chest pain frequency and prior health care contacts at baseline did not predict a treatment effect on either health-related quality of life or cardiac anxiety. CONCLUSIONS: Depression symptoms at baseline predicted a positive treatment effect of iCBT on health-related quality of life in patients suffering from non-cardiac chest pain. This indicates that it is important to identify patients with non-cardiac chest pain and co-occurring depression symptoms given that they are particularly likely to benefit from iCBT. TRIAL REGISTRATION: ClinicalTrials.gov NCT03096925 .