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.

The association between common mental disorders and tuberculosis: a case-control study from Guinea-Bissau.

OBJECTIVE: The aim of the study was to explore the association between tuberculosis (TB) and common mental disorders (CMD), in an area with high prevalence of TB. METHODS: We performed a case-control study of TB patients and unmatched healthy controls, from a demographic surveillance site in Guinea-Bissau. Screening for CMD was performed once for controls and at inclusion and follow-up for TB patients. Kessler 10 (K-10) and a brief version of Hopkins Symptom Checklist 25 (SCL-8d) were used as screening instruments. RESULTS: 571 controls were interviewed and 416 interviews were performed for 215 TB cases. Estimated CMD prevalence at the time of diagnosis of TB was 33.6 % (SCL-8d) and 46.2 % (K-10), compared with 6.8 % (SCL-8d) and 6.7 % (K-10) among controls; adjusted OR 7.18 (95 % CI 4.07 to 12.67) and 14.52 (95 % CI 8.15 to 25.84), respectively. No significant difference in CMD prevalence rates was observed between TB patients, after 6 months of treatment, and controls. CONCLUSION: Psychological distress and common mental disorders were more prevalent among TB patients at the time of diagnosis compared with the background population, but after completion of TB treatment no increased prevalence of psychological distress was found.

Large-scale flow field and aerosol particle transport investigations in a classroom using 2D-Shake-The-Box Lagrangian Particle Tracking.

Infections with COVID-19 in enclosed public spaces, where virus-laden aerosol particles can accumulate over time, have significantly contributed to the rapid spread of the virus. It is therefore of great importance to understand the transport and dispersion process of aerosol particles in such spaces, especially against the background of future pandemics. In this work, we present a Lagrangian-Particle-Tracking experiment to assess the mixed convective flow in a classroom with different ventilation strategies. For this purpose, thermal plumes were created by heated dummies, and a collimated LED light-sheet with ∼0.4 m thickness was used for illumination of helium filled soap bubbles (HFSB) acting as passive tracer particles. In this way, the Lagrangian trajectories of the particles were recorded at two approximately 4.2 m × 2.8 m large fields using the novel 2D-Shake-The-Box-Method. As a result, time-resolved trajectories of over 300,000 simultaneously tracked HFSB have been reconstructed, so that both small-scale and large-scale properties of the flow are visualized quantitatively across the entire cross-section of the room. The trajectories show that the thermal plumes create lengthwise circulating vortices, which cannot be destroyed across the entire cross-section of the room by opening or tilting a window. Furthermore, the mixing in the room through the operation of an air purifier is higher compared to opening a window, which suggests that this strategy in combination with its air filtering capability is the most effective strategy to prevent infections.

Experimental study on flow and turbulence characteristics of jet impinging on cylinder using three-dimensional Lagrangian particle tracking velocimetry.

When a round jet impinges on a convex cylindrical surface, complex three-dimensional (3D) flow structures occur, accompanied by the Coanda effect. To characterize the flow and turbulence properties of the general system, ensemble averages of 3D Lagrangian particle tracking velocimetry measurements were taken. The radial bin-averaging method was used in post-processing the tracked particles and corresponding instantaneous velocity vectors to generate appropriate ensemble-averaged statistics. Two impinging angles were selected, and at a fixed Reynolds number, the ensemble-averaged volumetric velocity field and turbulent stress tensor components were measured. The flow and turbulence characteristics of the impinging jet on the cylinder were notably different based on the impinging angle, especially in the downstream region. Surprisingly, the attached wall jet with a half-elliptic shape was abruptly thickened in the wall-normal direction, similar to the axis switching phenomenon observed in elliptic jets in the case of oblique impingement. In the jet-impinging region, the flow spread in all directions with high mean vorticity values. With the development of a 3D curved wall jet, both the Coanda effect and centrifugal force played a significant role in the flow behavior. A notable feature of the self-preserving region was the similarity of mean velocity profiles with scaling by the maximum velocity and the jet half-width for both impinging angle cases. Local isotropy of turbulent normal stresses was observed in this region, supporting the existence of self-preservation in the 3D curved wall jet. The volumetric ensemble-averaged Reynolds stress tensor revealed strong inhomogeneous turbulence in the boundary layer region and the curvature effect on the Reynolds shear stress in the free shear layer.

Second-generation distal attachment cuff for adenoma detection in screening colonoscopy: a randomized multicenter study.

BACKGROUND AND AIMS: Randomized studies have demonstrated that a distal attachment cap with rubber side arms, the Endocuff Vision (ECV; Olympus America, Center Valley, Pa, USA), increased colonoscopic adenoma detection rate (ADR) in various mixed patient collectives. This is the first study to evaluate its use in a primary colonoscopic screening program. METHODS: Patients over age 55 years undergoing screening colonoscopy in 9 German private offices in Berlin and Hamburg were randomized to either the study group using ECV or the control group using high-definition colonoscopies (standard of care). The main outcome parameter was ADR, whereas secondary outcomes were detection rates of all adenomas per colonoscopy (APCs), of adenoma subgroups, and of hyperplastic polyps. RESULTS: Of 1416 patients (mean age, 61.1 years; 51.8% women), with a median of 41 examinations per examiner (n = 23; interquartile range, 12-81), 700 were examined with ECV and 716 without. Adjusting for the effects of the colonoscopies, ADR was 39.5% (95% confidence interval [CI], 32.6%-46.3%) in the ECV group versus 32.2% (95% CI, 25.9%-38.6%) in the control group, which resulted in an increase of 7.2% (95% CI, 2.3%-12.2%; P = .004). The increase in ADR was mainly because of small polyps, with adjusted ADRs for adenomas <10 mm of 33.3% (95% CI, 26.5%-40.2%) for study patients versus 24.0% (95% CI, 18.2%-29.8%) for control patients (P < .001). APC was also significantly increased (.57 ECV vs .51 control subjects, P = .045). CONCLUSIONS: A distal attachment cap with side arms significantly increased the ADR in patients undergoing primary colonoscopic screening. Because of the correlation of ADR and interval cancer, its use should be encouraged, especially in this setting. (Clinical trial registration number: NCT03442738.).

Aetiological Understanding of Fibromyalgia, Irritable Bowel Syndrome, Chronic Fatigue Syndrome and Classificatory Analogues: A Systematic Umbrella Review.

Background: This umbrella review systematically assesses the variety and relative dominance of current aetiological views within the scientific literature for the three most investigated symptom-defined functional somatic syndromes (FSS) and their classificatory analogues within psychiatry and psychology. Method: An umbrella review of narrative and systematic reviews with and without meta-analyses based on a search of electronic databases (PubMed, Web of Science, Embase, PsychINFO) was conducted. Eligible reviews were published in English, focused on research of any kind of aetiological factors in adults diagnosed with fibromyalgia syndrome (FMS), irritable bowel syndrome (IBS), chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME), and somatic symptom disorder (SSD)/somatoform disorder (SFD). Results: We included 452 reviews (132 systematic reviews including meta-analyses, 133 systematic reviews, 197 narrative reviews), of which 132 (29%) focused on two or more of the investigated health conditions simultaneously. Across diagnoses, biological factors were addressed in 90% (k = 405), psychological in 33% (k = 150), social in 12% (k = 54), and healthcare factors in 5% (k = 23) of the reviews. The methodological quality of the included systematic reviews (k = 255) was low (low/critically low: 41% [k = 104]; moderate: 49% [k = 126]; high quality: 10% [k = 25]). The high-quality systematic reviews suggest that deficient conditioned pain modulation, genetic factors, changes in the immune, endocrinological, gastrointestinal, cardiovascular, and nervous system, and psychosocial factors such as sexual abuse and pain catastrophizing increase the risk for FSS. Conclusion: Only very few systematic reviews have used comprehensive, biopsychosocial disease models to guide the selection of aetiological factors in FSS research. Future research should strive for higher scientific standards and broaden its perspective on these health conditions.

Fully discrete approximation schemes for rate-independent crack evolution.

Over the past two decades, several distinct solution concepts for rate-independent evolutionary systems driven by non-convex energies have been suggested in an attempt to model properly jump discontinuities in time. Much attention has been paid in this context to the modelling of crack propagation. This paper studies two fully discrete (in time and space) approximation schemes for the rate-independent evolution of a single crack in a two-dimensional linear elastic material. The crack path is assumed to be known in advance, and the evolution of the crack tip along it relies on the Griffith theory. On the time-discrete level, the first scheme is based on local minimization, whereas the second scheme is a regularized version of the first one. The crucial feature of the schemes is their adaptive time-stepping nature, with finer time steps at those points where the evolution of the crack tip might develop a discontinuity. The set of discretization parameters includes the mesh size, crack increment, locality parameter and regularization parameter. In both cases, we explore the interplay between the discretization parameters and derive sufficient conditions on them ensuring the convergence of discrete interpolants to parametrized balanced viscosity solutions of the continuous model. To illustrate the performance of the approximation schemes, we support our theoretical analysis with numerical simulations. This article is part of the theme issue 'Non-smooth variational problems and applications'.

Interdisciplinary intervention (GAIN) for adults with post-concussion symptoms: a study protocol for a stepped-wedge cluster randomised trial.

BACKGROUND: Persistent post-concussion symptoms (PCS) are associated with prolonged disability, reduced health-related quality of life and reduced workability. At present, no strong evidence for treatments for people with persistent PCS exists. Our research group developed a novel intervention, "Get going After concussIoN (GAIN)", that incorporates multiple evidence-based strategies including prescribed exercise, cognitive behavioural therapy, and gradual return to activity advice. In a previous randomised trial, GAIN provided in a hospital setting was effective in reducing symptoms in 15-30-year-olds with PCS 2-6 months post-injury. In the current study, we describe the protocol for a trial designed to test the effectiveness of GAIN in a larger municipality setting. Additionally, we test the intervention within a broader age group and evaluate a broader range of outcomes. The primary hypothesis is that participants allocated to enhanced usual care plus GAIN report a higher reduction in PCS 3 months post-intervention compared to participants allocated to enhanced usual care only. METHODS: The study is a stepped-wedge cluster-randomised trial with five clusters. The 8-week interdisciplinary GAIN program will be rolled out to clusters in 3-month intervals. Power calculation yield at least 180 participants to be enrolled. Primary outcome is mean change in PCS measured by the Rivermead Post-Concussion Symptoms Questionnaire from enrolment to 3 months after end of treatment. Secondary outcomes include participation in and satisfaction with everyday activities, labour market attachment and other behavioural measures. Self-reported outcomes are measured at baseline, by end of treatment and at 3, 6, and 18 months after end of treatment. Registry-based outcomes are measured up to 36 months after concussion. DISCUSSION: The trial will provide important information concerning the effectiveness of the GAIN intervention in a municipality setting. Furthermore, it will provide knowledge of possible barriers and facilitators that may be relevant for future implementation of GAIN in different settings. TRIAL REGISTRATION: The current GAIN trial is registered in ClinicalTrials.gov (study identifier: NCT04798885 ) on 20 October 2020.

Are study populations in trials of antidepressants and psychotherapy comparable? A retrospective case study of two parallel running trials for multi- organ functional somatic disorder.

This study retrospectively compares two previous parallel running, randomized, controlled trials of pharmacotherapy (imipramine) and psychotherapy (acceptance and commitment therapy) for multi-organ functional somatic disorder (FSD). Differences in demographics, psychiatric comorbidity, illness severity, and illness duration associated with eligibility for the two trials and patients' willingness to participate are explored using linear or binary regression models. 418 patients with multi-organ FSD was included. We found that 377 (95%) were eligible for psychotherapy and 257 patients (61%) for pharmacotherapy. Patients eligible for pharmacotherapy were less severely impaired, less often received disability pension, reported shorter illness duration and experienced less psychological distress than patients eligible for psychotherapy. Whilst exclusion criteria for both trials differed markedly, it was not possible to clearly identify patient or illness characteristics associated with patients' willingness to participate. The study showed that trial-specific exclusion criteria led to the selection of less complex and less severely impaired patients in the pharmacological trial in this sample of multi-organ FSD. Our findings have important implications for the interpretation and comparability of RCT results of different treatments in multi-organ FSD and may point to some common flaws in study design and interpretation of pharmacological vs. psychotherapeutic intervention trials in psychiatry.

Characterization of persistent post-traumatic headache and management strategies in adolescents and young adults following mild traumatic brain injury.

Characteristics of persistent post-traumatic headache (PTH) in young individuals are poorly known leading to diagnostic problems and diverse management. We aimed to describe headache phenotypes and self-reported management strategies in young individuals with PTH following mild traumatic brain injury (mTBI). A comprehensive structured questionnaire was used to evaluate headache phenotypes/characteristics and management strategies to relieve headache in 107, 15-30-year-old individuals with PTH. Around 4 months post-injury, migraine-like headache in combination with tension-type like headache (40%) was the most commonly encountered headache phenotype followed by migraine-like headache (36%). Around 50% reported aura-like symptoms before/during the headache attack. Medication-overuse headache was diagnosed in 10%. Stress, sleep disturbances, and bright lights were the most common trigger factors. More than 80% reported that their headache was worsened by work-related activity and alleviated by rest/lying down. Simple analgesics were commonly used (88%) whereas prophylactic drugs were rarely used (5%). Bedrest and physiotherapy were also commonly used as management strategies by 56% and 34% of the participants, respectively. In conclusion, most young individuals with PTH after mTBI presented with combined migraine-like and tension-type-like headache followed by migraine-like headache, only. Preventive headache medication was rarely used, while simple analgesics and bedrest were commonly used for short-term headache relief.

Three different approaches to delimitation of functional somatic disorders: DanFunD.

OBJECTIVE: The Danish Study of Functional Disorders (DanFunD) approaches functional somatic disorders (FSD) with three delimitations: Five functional somatic syndromes (FSS), Bodily Distress Syndrome (BDS), and eight data-driven symptom profiles (SP). This paper presents each delimitation and discusses optimal approaches for further original research into FSD epidemiology. METHODS: A total of 9656 adults from the general Danish population participated in this cross-sectional study. Case assignment of the three FSD delimitations was based on self-reported symptom questionnaires. Overlap of FSS, BDS, and SP and their association with poor self-perceived health were calculated as descriptive statistics and shown with Venn diagrams. Difference in self-perceived health between participants with severe FSD were compared with participants with no FSD and calculated as risk ratios with generalized linear models with binomial family and log link. RESULTS: We found pronounced overlaps between any FSS, BDS, and the SP with multiple symptoms as well as for multi-organ BDS and the SP with all symptoms. Symptoms and syndromes related to clusters of musculoskeletal and general symptoms contributed particularly to poor health as did multi-organ BDS and categories of SP with multiple symptoms. CONCLUSION: Each of the three delimitations has its strengths and weaknesses, and with this study, we offer a contribution to a more valid delimitation of FSD. Future research within DanFunD and other epidemiological studies may benefit from using more than just one delimitation for capturing the diverse nature of the FSD.

A Phase Ib/II Study of Pepinemab in Combination with Avelumab in Advanced Non-Small Cell Lung Cancer.

PURPOSE: The CLASSICAL-Lung clinical trial tested the combination of pepinemab, an IgG4 humanized mAb targeting semaphorin 4D, with the PD-L1 inhibitor avelumab to assess the effects of coupling increased T-cell infiltration and reversal of immune suppression via pepinemab with sustained T-cell activation via checkpoint inhibition. PATIENTS AND METHODS: This phase Ib/II, single-arm study was designed to evaluate the safety, tolerability, and efficacy of pepinemab in combination with avelumab in 62 patients with advanced non-small cell lung cancer (NSCLC), including immunotherapy-naïve (ION) patients and patients whose tumors progressed following anti-PD-1/L1 monotherapy (IOF). The main objectives were to evaluate safety/tolerability, establish a recommended phase 2 dose (RP2D), obtain a preliminary evaluation of antitumor activity, and investigate candidate biomarker activity. RESULTS: The combination was well tolerated with no major safety signals identified. Pepinemab, 10 mg/kg with avelumab, 10 mg/kg, every 2 weeks, was selected as the RP2D. Among 21 evaluable ION patients, 5 patients experienced partial responses (PR), 4 patients evidenced clinical benefit ≥1 year, and the disease control rate (DCR) was 81%. Notably, overall response rate with the combination therapy was higher than previously reported for single-agent avelumab in the PD-L1-negative/low population. Among 29 evaluable IOF patients, the combination resulted in a DCR of 59%, including 2 PR and 7 patients with durable clinical benefit of ≥23 weeks. Biomarker analysis of biopsies demonstrated increased CD8 T-cell density correlating with RECIST response criteria. CONCLUSIONS: The combination of pepinemab with avelumab was well tolerated in NSCLC and showed signs of antitumor activity in immunotherapy-resistant and PD-L1-negative/low tumors.

Group-based Acceptance and Commitment Therapy (AHEAD) for adolescents with multiple functional somatic syndromes: A randomised trial.

Background: Evidence for treatment of adolescents with multiple functional somatic syndromes (FSS) is sparse. This study examined the efficacy of 'Acceptance and Commitment Therapy for Health in Adolescents' (AHEAD), a generic group-based treatment for adolescents with co-occurrence of multiple FSS. Methods: A randomized trial was conducted at a specialized university hospital clinic. Adolescents (15-19 years) with multiple FSS of at least 1 year's duration were randomly assigned to AHEAD or enhanced usual care (EUC). AHEAD consisted of nine modules (i.e., 27 h) and one follow-up meeting. Primary outcome was physical health (SF-36). Various secondary outcomes and treatment targets were included (e.g., symptom severity, symptom impact, and illness perception). A linear mixed-effects model was used for analysis. Trial-registration: ClinicalTrials.gov NCT02346071. Results: Ninety-one patients were included. At 12 months, no significant difference in physical health was identified between groups (mean adjusted difference 1.2 [95% CI -1.6 to 4.0], p = .404). However, different developments over time were seen with an interaction effect between intervention arm and time (χ2(5) = 14.1, p = .0148). AHEAD patients (n = 44) reported a clinically relevant improvement at end of treatment and at 8 and 12 months, while EUC patients (n = 47) displayed a clinically relevant improvement at 12 months. Furthermore, AHEAD patients showed a faster improvement on symptom severity, symptom impact and illness perception. EUC patients received more psychological treatment outside the trial (p ≤ .001) than AHEAD patients. Treatment satisfaction with AHEAD was high in contrast to EUC. Conclusions: Compared with EUC, AHEAD had no additional advantage on the improvement of physical health at the primary endpoint of 12 months. However, a faster improvement of physical health was seen in AHEAD and considerably more psychological treatment was received outside the trial in EUC with clinically meaningful improvements in both groups. The results underpin the importance of an organised and systematic treatment offer for the most severely affected youth.

Microstructural changes in the brain after long-term post-concussion symptoms: A randomized trial.

A recent randomized controlled trial in young patients with long-term post-concussion symptoms showed that a novel behavioral intervention "Get going After concussIoN" is superior to enhanced usual care in terms of symptom reduction. It is unknown whether these interventional effects are associated with microstructural brain changes. The aim of this study was to examine whether diffusion-weighted MRI indices, which are sensitive to the interactions between cellular structures and water molecules' Brownian motion, respond differently to the interventions of the above-mentioned trial and whether such differences correlate with the improvement of post-concussion symptoms. Twenty-three patients from the intervention group (mean age 22.8, 18 females) and 19 patients from the control group (enhanced usual care) (mean age 23.9, 14 females) were enrolled. The primary outcome measure was the mean kurtosis tensor, which is sensitive to the microscopic complexity of brain tissue. The mean kurtosis tensor was significantly increased in the intervention group (p = 0.003) in the corpus callosum but not in the thalamus (p = 0.78) and the hippocampus (p = 0.34). An increase in mean kurtosis tensor in the corpus callosum tended to be associated with a reduction in symptoms, but this association did not reach significance (p = 0.059). Changes in diffusion tensor imaging metrics did not differ between intervention groups and were not associated with symptoms. The current study found different diffusion-weighted MRI responses from the microscopic cellular structures of the corpus callosum between patients receiving a novel behavioral intervention and patients receiving enhanced usual care. Correlations with improvement of post-concussion symptoms were not evident.

The BDS checklist as measure of illness severity: a cross-sectional cohort study in the Danish general population, primary care and specialised setting.

OBJECTIVE: The bodily distress syndrome (BDS) checklist has proven to be useful in the diagnostic categorisation and as screening tool for functional somatic disorders (FSD). This study aims to investigate whether the BDS checklist total sum score (0-100) can be used as a measure of physical symptom burden and FSD illness severity. DESIGN: Cross-sectional. SETTING: Danish general population, primary care and specialised clinical setting. PARTICIPANTS: A general population cohort (n=9656), a primary care cohort (n=2480) and a cohort of patients with multiorgan BDS from specialised clinical setting (n=492). OUTCOME MEASURES: All data were self-reported. Physical symptoms were measured with the 25-item BDS checklist. Overall self-perceived health was measured with one item from the 36-item Short-Form Health Survey (SF-36). Physical functioning was measured with an aggregate score of four items from the SF-36/SF-12 scales 'physical functioning', 'bodily pain' and 'vitality'. Emotional distress was measured with the mental distress subscale (SCL-8) from the Danish version of the Hopkins Symptom Checklist-90. Illness worry was measured with the six-item Whiteley Index. RESULTS: For all cohorts, bifactor models established that despite some multidimensionality the total sum score of the BDS checklist adequately reflected physical symptom burden and illness severity. The BDS checklist had acceptable convergent validity with measures of overall health (r=0.25-0.58), physical functioning (r=0.22-0.58), emotional distress (r=0.47-0.62) and illness worry (r=0.36-0.55). Acceptability was good with a low number of missing responses to items (<3%). Internal consistency was high (α ≥0.879). BDS score means varied and reflected symptom burden across cohorts (13.03-46.15). We provide normative data for the Danish general population. CONCLUSIONS: The BDS checklist total sum score can be used as a measure of symptom burden and FSD illness severity across settings. These findings establish the usefulness of the BDS checklist in clinics and in research, both as a diagnostic screening tool and as an instrument to assess illness severity.

Feasibility of group-based acceptance and commitment therapy for adolescents (AHEAD) with multiple functional somatic syndromes: a pilot study.

BACKGROUND: Recurrent and impairing functional somatic syndromes (FSS) are common in adolescents. Despite a high need for care, empirically supported treatments are lacking for youth. The aim of this uncontrolled pilot study was to assess feasibility and treatment potential of a new intervention with group-based Acceptance and Commitment Therapy (ACT) in a generic treatment approach for adolescents with multiple FSS. METHODS: Twenty-one patients received 'ACT for Health in Adolescents' (AHEAD) (30 h), specifically developed for adolescents (aged 15-19 years) with moderate to severe FSS. Close relatives attended an information meeting to facilitate support of the patients throughout treatment. Treatment satisfaction was evaluated by means of self-report and relatives' impressions. Self-reported physical health at 3 months follow-up (FU) after end of treatment was the primary outcome whereas secondary outcomes included symptom burden, limitation due to symptoms, illness worry, emotional distress and physical and emotional symptoms. Treatment targets were assessed by measures on illness behaviour, illness perception and psychological inflexibility. RESULTS: Nineteen patients (90.5%) completed the treatment with a high overall attendance rate of 93%. All would recommend the treatment to a friend with similar problems. Close relatives rated it valuable to participate in an information meeting. Patients' physical health improved significantly from assessment to FU with a clinically relevant mean change of 8.9 points (95% CI [5.4; 12.4]; SRM 0.91 [0.26;1.57]). Improvement was also seen on all secondary outcome measures, from assessment to FU. Maladaptive illness behaviours and perceptions as well as psychological inflexibility showed a significant decline from assessment to FU. CONCLUSION: AHEAD was feasible and potentially efficacious and warrants testing in a larger clinical trial. TRIAL REGISTRATION: Clinical Trials gov NCT04464447 , registration date July 9th, 2020. Retrospectively registered.

Irritable bowel, chronic widespread pain, chronic fatigue and related syndromes are prevalent and highly overlapping in the general population: DanFunD.

Prevalence of functional somatic syndromes (FSS) in the general population varies with observed overlap between syndromes. However, studies including a range of FSS are sparse. We investigated prevalence and characteristics of various FSS and the unifying diagnostic construct bodily distress syndrome (BDS), and identified mutual overlap of the FSS and their overlap with BDS. We included a stratified subsample of 1590 adults from a randomly selected Danish general population sample (n = 7493). Telephonic diagnostic interviews performed by three trained physicians were used to identify individuals with FSS and BDS. Prevalence of overall FSS was 9.3%; 3.8% for irritable bowel, 2.2% for chronic widespread pain, 6.1% for chronic fatigue, 1.5% for whiplash associated disorders, and 0.9% for multiple chemical sensitivity. Prevalence of BDS was 10.7% where 2.0% had the multi-organ type. FSS were highly overlapping with low likelihood of having a "pure" type. Diagnostic agreement of FSS and BDS was 92.0%. Multi-syndromatic FSS and multi-organ BDS were associated with female sex, poor health, physical limitations, and comorbidity. FSS are highly prevalent and overlapping, and multi-syndromatic cases are most affected. BDS captured the majority of FSS and may improve clinical management, making the distinction between multi- and mono-syndromatic patients easier.