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.

Is reduced heart rate variability associated with functional somatic disorders? A cross-sectional population-based study; DanFunD.

OBJECTIVES: It has been hypothesised that functional somatic disorders (FSD) could be initiated by sympathetic predominance in the autonomic nervous system as measured by low heart rate variability (HRV). Earlier studies on the association between HRV and FSD are small case-control studies hampered by selection bias and do not consider the great overlap between the various FSDs. The aim of the present study is to assess any associations between HRV and various FSDs and whether chronic stress confounds such an association. DESIGN: A cross-sectional general population-based study. SETTING: The Danish Study of Functional Somatic Disorders conducted 2013-2015 in 10 municipalities in the western part of Greater Copenhagen, Denmark. PARTICIPANTS: A total of 6891 men and women aged 18-72 years were included in the analyses after exclusion of 602 persons with missing HRV data. Various delimitations of FSD (chronic fatigue, chronic widespread pain, irritable bowel and bodily distress syndrome) were identified by validated questionnaires and diagnostic interviews. HRV parameters in time and frequency domains were calculated from successive beat-to-beat heart rate (HR) data using the 'E-motion' HR monitor device during 7 min of supine rest. Chronic stress was assessed by Cohen's self-perceived stress scale. OUTCOME MEASURES: Logistic regression analyses were used to calculate possible associations between the various delimitations of FSD and HRV adjusting for chronic stress. RESULTS: Persons with FSD had a slightly higher mean HR and lower HRV as measured by time domain parameters, whereas associations with frequency domain parameters were not consistent. Adjusting for chronic stress attenuated associations slightly. CONCLUSION: The study supports a sympathetic predominance in persons with FSD, which could not be entirely explained by chronic stress. However, it is not possible to conclude whether the association is a causal factor to or a consequence of FSD.

Lipid metabolism and functional somatic disorders in the general population. The DanFunD study.

OBJECTIVES: Earlier studies on the association between plasma lipid profiles and functional somatic disorders (FSD) are mainly small case control studies hampered by selection bias and do not consider the great overlap between the various FSDs. The aim of the present study was to investigate the associations between various FSDs and plasma lipid profiles (total cholesterol, HDL cholesterol, non-HDL cholesterol and triglycerides) in a large, unselected population. DESIGN: A cross-sectional general population-based study. SETTING: The Danish Study of Functional Somatic Disorders (DanFunD) conducted in 2011-2015 in 10 municipalities in the western part of greater Copenhagen, Denmark. PARTICIPANTS: A total of 8,608 men and women aged 18-76 years were included in the analyses. Various delimitations of FSD such as chronic fatigue, chronic widespread pain, irritable bowel, and bodily distress syndrome were measured using validated self-administrated questionnaires. Lipid parameters were measured from fasting plasma samples using colorimetric slide methods with Vitros 4600/5600 Ortho Clinical Diagnostics. OUTCOME MEASURES: Logistic regression analyses were used to calculate possible associations between plasma lipids and the various delimitations of FSD. Associations are presented by OR (95% CI) and shown in boxplots. RESULTS: We found a positive association between bodily distress syndrome and triglycerides and non-HDL cholesterol and a negative association with HDL-cholesterol, but no consistent association with total cholesterol. A similar pattern was observed for persons with chronic fatigue, and to some degree for persons with chronic widespread pain, whereas persons with irritable bowel did not show a clear association with the lipid profiles. CONCLUSION: This is the first major study on plasma lipid profiles and FSD indicating an association between some delimitations of FSD and an unfavorable lipid profile. Due to the cross-sectional design, it cannot be determined whether the findings are consequences or determinants of FSD. Further studies-preferable prospective studies-are needed.

Neuroticism, perceived stress, adverse life events and self-efficacy as predictors of the development of functional somatic disorders: longitudinal population-based study (DanFunD).

BACKGROUND: Functional somatic disorder (FSD) is a unifying diagnosis that includes functional somatic syndromes such as irritable bowel, chronic widespread pain (CWP) and chronic fatigue. Several psychological factors are associated with FSD. However, longitudinal population-based studies elucidating the causal relationship are scarce. AIMS: To explore if neuroticism, perceived stress, adverse life events (ALEs) and self-efficacy can predict the development of FSD over a 5-year period. METHOD: A total of 4288 individuals who participated in the DanFunD baseline and 5-year follow-up investigations were included. FSD was established at both baseline and follow-up, with symptom questionnaires and diagnostic interviews. Neuroticism was measured with the short-form NEO Personality Inventory, perceived stress with the Cohen's Perceived Stress Scale, ALEs with the Danish version of the Cumulative Lifetime Adversity Measure and self-efficacy with the General Self-Efficacy Scale. Associations were investigated with multiple logistic regression models. RESULTS: Perceived stress predicted incident FSD, irritable bowel, CWP and chronic fatigue (odds ratios: 1.04-1.17). Neuroticism predicted incident FSD and chronic fatigue (odds ratios: 1.03-1.16). ALEs predicted incident FSD, CWP and chronic fatigue (odds ratios: 1.06-1.18). An increase in perceived stress from baseline to follow-up was associated with incident FSD, irritable bowel, CWP and chronic fatigue (odds ratios: 1.05-1.22). Contrary, an increase in self-efficacy seemed to be a protective factor (odds ratios: 0.89-0.99). CONCLUSIONS: High neuroticism, high perceived stress and a high number of ALEs are risk factors for the development of FSD. Particularly perceived stress seems to be an important contributor to the onset of FSD.

Validity and screening capacity of the FCR-1r for fear of cancer recurrence in long-term colorectal cancer survivors.

PURPOSE: Existing fear of cancer recurrence (FCR) screening measures is being shortened to facilitate clinical use. This study aimed to evaluate the validity and screening capacity of a single-item FCR screening measure (FCR-1r) in long-term colorectal cancer (CRC) survivors with no recurrence and assess whether it performs as well in older as in younger survivors. METHODS: All Danish CRC survivors above 18, diagnosed and treated with curative intent between 2014 and 2018, were located through a national patient registry. A questionnaire including the FCR-1r, which measures FCR on a 0-10 visual analog scale, alongside the validated Fear of Cancer Recurrence Inventory Short Form (FCRI-SF) as a reference standard was distributed between November 2021 and May 2023. Screening capacity and cut-offs were evaluated with a receiver-operating characteristic analysis (ROC) in older (≥ 65 years) compared to younger (< 65 years) CRC survivors. Hypotheses regarding associations with other psychological variables were tested as indicators of convergent and divergent validity. RESULTS: Of the CRC survivors, 2,128/4,483 (47.5%) responded; 1,654 (36.9%) questionnaires were eligible for analyses (median age 76 (range 38-98), 47% female). Of the responders, 85.2% were aged ≥ 65. Ninety-two participants (5.6%) reported FCRI-SF scores ≥ 22 indicating clinically significant FCR. A FCR-1r cut-off ≥ 5/10 had 93.5% sensitivity and 80.4% specificity for detecting clinically significant FCR (AUC = 0.93, 95% CI 0.91-0.94) in the overall sample. The discrimination ability was significantly better in older (AUC = 0.93, 95% CI 0.91-0.95) compared to younger (0.87, 95% (0.82-0.92), p = 0.04) CRC survivors. The FCR-1r demonstrated concurrent validity against the FCRI-SF (r = 0.71, p < 0.0001) and convergent validity against the short-versions of the Symptom Checklist-90-R subscales for anxiety (r = 0.38, p < 0.0001), depression (r = 0.27, p < 0.0001), and emotional distress (r = 0.37, p < 0.0001). The FCR-1r correlated weakly with employment status (r = - 0.09, p < 0.0001) and not with marital status (r = 0.01, p = 0.66) indicating divergent validity. CONCLUSIONS: The FCR-1r is a valid tool for FCR screening in CRC survivors with excellent ability to discriminate between clinical and non-clinical FCR, particularly in older CRC survivors.

Chronic fatigue syndromes: real illnesses that people can recover from.

The 'Oslo Chronic Fatigue Consortium' consists of researchers and clinicians who question the current narrative that chronic fatigue syndromes, including post-covid conditions, are incurable diseases. Instead, we propose an alternative view, based on research, which offers more hope to patients. Whilst we regard the symptoms of these conditions as real, we propose that they are more likely to reflect the brain's response to a range of biological, psychological, and social factors, rather than a specific disease process. Possible causes include persistent activation of the neurobiological stress response, accompanied by associated changes in immunological, hormonal, cognitive and behavioural domains. We further propose that the symptoms are more likely to persist if they are perceived as threatening, and all activities that are perceived to worsen them are avoided. We also question the idea that the best way to cope with the illness is by prolonged rest, social isolation, and sensory deprivation.Instead, we propose that recovery is often possible if patients are helped to adopt a less threatening understanding of their symptoms and are supported in a gradual return to normal activities. Finally, we call for a much more open and constructive dialogue about these conditions. This dialogue should include a wider range of views, including those of patients who have recovered from them.

Anomalies in the review process and interpretation of the evidence in the NICE guideline for chronic fatigue syndrome and myalgic encephalomyelitis.

Chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) is a disabling long-term condition of unknown cause. The National Institute for Health and Care Excellence (NICE) published a guideline in 2021 that highlighted the seriousness of the condition, but also recommended that graded exercise therapy (GET) should not be used and cognitive-behavioural therapy should only be used to manage symptoms and reduce distress, not to aid recovery. This U-turn in recommendations from the previous 2007 guideline is controversial.We suggest that the controversy stems from anomalies in both processing and interpretation of the evidence by the NICE committee. The committee: (1) created a new definition of CFS/ME, which 'downgraded' the certainty of trial evidence; (2) omitted data from standard trial end points used to assess efficacy; (3) discounted trial data when assessing treatment harm in favour of lower quality surveys and qualitative studies; (4) minimised the importance of fatigue as an outcome; (5) did not use accepted practices to synthesise trial evidence adequately using GRADE (Grading of Recommendations, Assessment, Development and Evaluations trial evidence); (6) interpreted GET as mandating fixed increments of change when trials defined it as collaborative, negotiated and symptom dependent; (7) deviated from NICE recommendations of rehabilitation for related conditions, such as chronic primary pain and (8) recommended an energy management approach in the absence of supportive research evidence.We conclude that the dissonance between this and the previous guideline was the result of deviating from usual scientific standards of the NICE process. The consequences of this are that patients may be denied helpful treatments and therefore risk persistent ill health and disability.

High Perceived Stress and Low Self-Efficacy are Associated with Functional Somatic Disorders: The DanFunD Study.

Objective: Several psychological factors have been proposed to be associated with functional somatic disorders (FSD) including functional somatic syndromes, such as irritable bowel, chronic widespread pain, and chronic fatigue. However, large randomly selected population-based studies of this association are sparse. This study aimed to investigate the association between FSD and perceived stress and self-efficacy, respectively, and to investigate if FSD differed from severe physical diseases on these aspects. Methods: This cross-sectional study included a random sample of the adult Danish population (n = 9656). FSD were established using self-reported questionnaires and diagnostic interviews. Perceived stress was measured with Cohen's Perceived Stress Scale and self-efficacy with the General Self-Efficacy Scale. Data were analysed with generalized linear models and linear regression models. Results: FSD were associated with higher perceived stress and lower self-efficacy, especially for the multi-organ and the general symptoms/fatigue FSD types and for chronic fatigue. However, controlling for the personality trait neuroticism altered the associations with self-efficacy so it became insignificant. The analysis did not support an important interaction between perceived stress and self-efficacy on the likelihood of having FSD. Individuals with FSD presented levels of perceived stress that were not equal, ie higher, to those in individuals with severe physical diseases. Conclusion: FSD were positively associated with perceived stress and negatively associated with self-efficacy. Our study may point to stress being part of the symptomatology of FSD. This underlines the severity of having FSD and stresses the relevance of the resilience theory in the understanding of the condition.

Internet-delivered treatment for patients suffering from severe functional somatic disorders: Protocol for a randomized controlled trial.

Background: Functional somatic disorders (FSDs) with symptoms from multiple organs, i.e., multi-system type, are common in the general population and may lead to disability and reduced quality of life. Evidence for efficient treatment programs has been established, however, there is a need for making treatments accessible to a larger group of patients. Internet-delivered therapy has become prevalent and has proven as effective as face-to-face therapy, while providing a flexible and easily accessible treatment alternative. The aim of the current study is to compare the efficacy of the therapist-assisted internet-delivered treatment program One step at a time (OneStep) with the internet-delivered self-help program Get started (GetStarted). Methods: A total of 166 participants aged 18-60 years diagnosed with multi-system FSD will be assessed and randomized to either 1) OneStep: a 14-week program consisting of 11 treatment modules based on principles from cognitive behavioural therapy or 2) GetStarted consisting of 1 module on psychoeducation. The primary outcome is physical health, assessed by a Short Form Health Survey (SF-36) aggregate score of the subscales vitality, physical functioning, and bodily pain 3 months after end-of-treatment and self-reported improvement assessed by the Clinical Global Improvement Scale. Secondary outcomes include symptom load, depression, anxiety, and illness worry. Process measures include emotional distress, illness perception, illness behaviour, and symptom interference. Conclusions: This study is the first study to test an internet-delivered treatment program for FSD, multi-system type and has the potential to show the importance of making evidence-based internet-delivered treatment for FSD more accessible.

Association between infections and functional somatic disorders: a cross-sectional population-based cohort study.

OBJECTIVES: It has been suggested that infections can trigger functional somatic disorders (FSD). However, current evidence is limited by inconsistent findings in smaller studies conducted in clinical settings within selected populations and short follow-up times. We aimed to test the hypothesis that former infections are associated with FSD using data from nationwide registries and a large population-based cohort study, the Danish Study of Functional Disorders study. DESIGN: FSD cases were identified in a cross-sectional population-based cohort and linked retrospectively to former hospital contacts with infections identified in the Danish National Patient Registry. The associations between FSD and former infections within 17 years were analysed using logistic regressions to calculate ORs and 95% CIs adjusted for age, sex and subjective social status. SETTING: A population-based cohort in Denmark examined between 2011 and 2015. PARTICIPANTS: A total of 9656 men and women aged 18-76 years. MAIN OUTCOME MEASURES: FSD measured by various delimitations, including bodily distress syndrome (BDS), irritable bowel (IB), chronic fatigue (CF), chronic widespread pain (CWP), and multiple chemical sensitivity (MCS). RESULTS: Overall, infections were associated with increased risk of all delimitations of FSD. The associations were more pronounced for multisystemic FSD. The number of prior infections increased the risk in a dose-response manner (p<0.0001). Bacterial but not viral infections were significantly associated with BDS (OR 1.69 (95% CI 1.46 to 1.96)), IB (OR 1.41 (95% CI 1.06 to 1.88)), CWP (OR 1.47 (95% CI 1.13 to 1.90)) and CF (OR 1.62 (95% CI 1.34 to 1.96)), but not MCS. CONCLUSION: Former infections leading to hospital contacts were associated with a higher risk of having FSD. These associations were more pronounced for bacterial than viral infections, and more infections increased the risk in a dose-response manner. These results tend to support the idea that severe infections could play a role in FSD.

Neuroticism and adverse life events are important determinants in functional somatic disorders: the DanFunD study.

Several psychological factors have been proposed to be associated with functional somatic disorders (FSD). However, large population-based studies investigating the importance of both personality and adverse life events (ALE) are sparse. This study aimed to investigate the association between FSD and neuroticism and the accumulated number of ALE, respectively. This cross-sectional study included a random sample of the adult Danish population (N = 7493). FSD were established by means of self-reported questionnaires and diagnostic interviews. Neuroticism was measured with the Danish version of the short-form NEO Personality Inventory. ALE were measured with the Danish version of the Cumulative Lifetime Adversity Measure. Strong positive associations were found between neuroticism and FSD, and ALE and questionnaire-based FSD. For interview-based FSD, strong positive associations were found for FSD, multi-organ type, and for the subtype of the general symptoms. The level of self-efficacy did not modify these associations, and no moderating effect of neuroticism and ALE in combination on the probability of having FSD was found. FSD were strongly associated with both neuroticism and the accumulated number of ALE, and these associations were not modified by self-efficacy. In combination, neuroticism and ALE did not have a moderating effect on the probability of having FSD.

Examine the public health impacts of functional somatic disorders using the DanFunD study.

Background: Persistent physical symptoms (e.g. pain, fatigue) are prevalent in the population and some persons may develop a functional somatic disorder (FSD). We still need to explore the limits between general bodily sensations and FSD, and great controversies exist as regard delimitation, occurrence, risk factors, prognosis, and costs of FSD in the general population. This is mainly due to the lack of focused, sufficient powered, population-based epidemiological studies. Material and Methods: The DanFunD study is the largest focused population-based study on FSD and has the potential to answer these crucial questions regarding the FSD disorders. DanFunD has its origin in the Copenhagen area of Denmark and was initiated in 2009 by an interdisciplinary team of researchers including basic scientists, clinical researchers, epidemiologists, and public health researchers. A population-based cohort of nearly 10,000 people have filled in detailed questionnaires, gone through a thorough health examination, and a biobank is established. The cohort was re-examined after five years. Results:The prevalence of FSD in the Danish population is about 10-15% and is twice as common in women as in men. Persons with FSD report impaired daily activities and low self-perceived health, which qualifies FSD as a major public health problem. The research plan to unravel the risk factors for FSD employs a bio-psycho-social approach according to a detailed plan. Preliminary results are presented, and work is in progress. Likewise, plans for assessing prognosis and health care costs are provided. Conclusion: We invite researchers in the field to collaborate on this unique data material.

Normative values of short-term heart rate variability in a cross-sectional study of a Danish population. The DanFunD study.

AIMS: The autonomic nervous system includes parasympathetic and sympathetic components that monitor and regulate most of the bodily functions and play a central role in the physiology and homeostasis of the human body. Heart rate variability is a non-invasive tool for quantification of rhythmic fluctuations in heart rate that reflects the function of the autonomic nervous system. The study aims to describe the heart rate variability distribution in the general population, stratified in sex and age groups, which is currently insufficiently described. METHODS: A cross-sectional population-based study recruited participants in 10 municipalities in the western part of the greater Copenhagen area in Denmark, including 6891 men and women aged 18-72 years (participation rate was 29.5%). Short-term heart rate variability measures were obtained and related to age and gender. RESULTS: Both time and frequency domain measures showed a huge variation in the different sex and age groups. Women had a higher median heart rate than men, and the association with age was U-shaped. Measures indicating a predominance of the parasympathetic component in relation to the sympathetic component were more frequent in women and younger age groups. CONCLUSIONS: Both sex and age influence the heart rate variability in this adult Danish population. Therefore, our age- and sex-related reference values of heart rate variability in the time and frequency domain should be used in further epidemiological and clinical research.

[Facts and myths about chronic fatigue syndrome].

Contrary to its precursor, the new NICE guidelines for myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) caution against graded exercise therapy for the severely ill, and cognitive behavioural therapy is only recommended for treating consequence of ME/CFS and not the condition itself. Instead, energy management is recommended. The recommendations are based on dismissing most current evidence from studies not using new diagnostic criteria introduced by NICE or not including patient viewpoints. As argued in this review, instead of a scientific approach, the committee attaches importance to a consensus-driven approach among a biased group of specialists and patients; many associated to the ME action community.

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.

Conditioned pain modulation and pain sensitivity in functional somatic disorders: The DanFunD study.

BACKGROUND: Disrupted pain regulation has been proposed as a component in functional somatic disorders (FSD). The objective of this study was to examine a general population sample, encompassing three delimitations of FSD while assessing pain sensitivity and conditioning pain modulation (CPM). METHODS: Pressure pain thresholds (PPTs) at the tibialis and trapezius muscles were recorded at baseline. During cold pressor stimulation of the hand, the tibialis PPTs were re-assessed and the difference from baseline measures defined the CPM effect. Participants (n = 2,198, 53% females) were randomly selected from the adult Danish population. FSD was established by self-reported symptom questionnaires. RESULTS: With a few exceptions, only weak associations were seen between PPTs and CPM in cases with FSD (p > .1). A high PPT was associated with lower odds of having multi-organ bodily distress syndrome (ORPPT trapezius : 0.66, 95% CI: 0.49-0.88, p = .005), with the symptom profile characterized by all symptoms (ORPPT trapezius : 0.72, 95% CI: 0.58-0.90, p = .003 and ORPPT tibialis : 0.75, 95% CI: 0.62-0.91, p = .004), and with multiple chemical sensitivity (ORPPT trapezius : 0.81, 95% CI: 0.67-0.97, p = .022). High CPM was associated with high odds of having irritable bowel (ORCPM relative : 1.22, 95% CI: 1.04-1.43, p = .013 and ORCPM absolute  = 2.66, 95% CI: 1.07-6.45, p = .033). CONCLUSION: However, only PPT measured over the trapezius muscle were still significant after correction for multiple testing for the symptom profile characterized by all symptoms. Findings from this study do not support altered pain regulation in questionnaire-based FSD which is in contrast with the existing presumption. Further epidemiological studies in this field are needed. SIGNIFICANCE: Disrupted pain regulation as measured by abnormal pain thresholds has been hypothesized as a central mechanism in Functional Somatic Disorders (FSD). The hypothesis has been raised in clinical setting where patients presented subjective and objective features of hypersensitivity. The present population-based study does not support this notion. This points to the importance of further studies into the underlying pathophysiology mechanisms of FSD.

The impact of the Covid-19 pandemic on mental and physical health in Denmark - a longitudinal population-based study before and during the first wave.

BACKGROUND: In the continuation of the first wave of the Covid-19 outbreak in Denmark, unprecedented restrictions with great impact on the citizen's everyday life were implemented. The objectives of this study were to investigate the influence of the Covid-19 pandemic on mental and physical health in the Danish population during the spring 2020 first wave outbreak and lockdown. METHODS: A sample from the adult Danish population (n = 2190) were included. Self-reported measures of illness worry (Whiteley-6-R), emotional distress (SCL-90), and physical symptom load (SLC-90) were obtained before and during the first wave of the pandemic and compared with Wilcoxon signed-rank tests. Impact of covariates on physical and mental health was evaluated with ordinal regression analyses. Results from a tailored questionnaire regarding the Covid-19 pandemic were presented to explore the direct impact of the pandemic. RESULTS: We only found minor increases in illness worry, emotional distress and physical symptom load (0-1 points difference, p ≤ 0.007) during the Covid-19 pandemic compared to before the pandemic. Sex, age, education, and physical disease were not associated with illness worry, emotional distress, or physical symptom load. Overall, the participants were trustful in the authorities' recommendations and felt that they managed the pandemic and the restrictions to a great extent despite that some expected great/major future consequences of the pandemic. CONCLUSIONS: This study suggested that the first wave of the Covid-19 pandemic only had minor impact on mental and physical health in the Danish general population. Future studies should address the impact of the second wave of the pandemic and the renewed implementation of the concomitant restrictions.

Psychometric Evaluation of the Whiteley Index-8 in Chinese Outpatients in General Hospitals.

Background: Excessive and persistent health anxiety is a common and disabling but often unrecognized illness. Therefore, screening patients for health anxiety is recommended in primary care. The aim of the present study was to examine the psychometric properties of an updated version of the eight-item Whiteley Index (WI-8) among outpatients in general hospitals in China. Methods: The presented data were derived from a multicenter cross-sectional study. The Chinese version of the WI-8 was administered to a total of 696 outpatients. Cronbach's alpha was used to evaluate the internal consistency of the scale. The validity of the scale was evaluated based on factor analysis and correlation analyses. To assess the discriminant ability, receiver operating characteristic (ROC) analysis was conducted. Results: Cronbach's alpha was 0.937, and it decreased (0.925) after deleting the new 8th item. Factor analysis extracted one factor accounting for 69.2% of the variance. Moderate correlations were found (0.414-0.662) between the WI-8 and General Anxiety Disorder (GAD-7), Patient Health Questionnaire-9 (PHQ-9), Patient Health Questionnaire-15 (PHQ-15) and Somatic Symptom Disorder B-criteria (SSD-12). The ROC curve indicated excellent discriminatory ability to discriminate among patients with health anxiety (AUC = 0.822). Conclusions: The new WI-8 version is a reliable and valid tool to screen for health anxiety in general hospital patients. We recommend the WI-8 as a useful screening tool for health anxiety.

Use of register- and survey-based measures of anxiety in a population-based Danish cohort.

OBJECTIVE: We explored the comparability of anxiety measures from register- and survey-based data including analyses of prevalence and associations with selected psychiatric and somatic diseases. METHODS: We measured anxiety using Danish registers (hospital diagnosis and anxiolytic drug prescriptions), self-reports, symptom checklist (SCL) scores, and a clinical interview in 7493 adults with mean age 52 (SD 13.3) years who participated in a health survey between 2012 and 2015. We estimated the prevalence of anxiety, agreement between different measures and performed quantitative bias analysis. RESULTS: The lifetime prevalence of hospital diagnosed anxiety, anxiolytic drug prescriptions, and self-reported anxiety were 4.4%, 6.2%, and 5.1%, respectively, after adjusting for selective participation. The agreement between the different anxiety measures was low. Thus, 25% with an anxiety diagnosis and 20% with anxiolytic drug prescriptions also had a high SCL score. Anxiolytic drugs were the only measure significantly associated with higher odds of heart disease. Hospital diagnosis and self-reported anxiety were associated with depression with odds ratio (OR) above 15, whereas anxiolytic drug prescriptions were less strongly associated (OR = 2.2(95% confidence interval: 1.26-3.91)). The risk estimates attenuated considerably when correcting for measurement error, whereas the ORs became slightly higher when the selective participation in the survey was accounted for. CONCLUSION: Anxiety diagnosed in hospitals and self-reported anxiety showed low level of agreement but provide comparable results regarding frequency measures and associations with disease outcomes.