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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.

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.

Multiple chemical sensitivity (MCS) is characterized by widespread symptoms attributed to exposure to airborne chemicals. MCS is categorized as a functional somatic syndrome (FSS), and MCS cases often meet the criteria for other types of FSS, e.g. fibromyalgia. The primary aim was to characterize MCS regarding symptom triggers, symptoms, lifestyle and describe demographics, socioeconomics and lifestyle factors associated with MCS. A secondary aim was to examine the implication of FSS comorbidity. Data were derived from a random sample of the Danish adult population enrolled in the Danish Study of Functional Disorders (DanFunD; n = 9,656). Questionnaire data comprised information used to delimit MCS and four additional types of FSS, as well as data on demographics, socioeconomics and lifestyle. MCS cases (n = 188) was stratified into subgroups; MCS only (n = 109) and MCS with comorbid FSS (n = 73). Information regarding FSS comorbidities were missing for six MCS cases. MCS subgroups and controls without FSS comorbidities (n = 7,791) were compared by means of logistic regression analyses, adjusted for age and sex. MCS was associated with female sex, not being in occupation and low social status, but not with age or education. MCS cases reported normal dietary intake and smoking habits and lower alcohol consumption. Additional associations were found between MCS and low rate of cohabitation, sedentarism, daily physically limitations, and poor quality of sleep. However, subgroup analysis revealed that these findings were primarily associated with MCS with comorbid FSS. MCS was associated with lower socioeconomic status, physically inactivity and poor quality of sleep. Subgroup analysis revealed that several associations was explained by FSS comorbidity, i.e. MCS cases with no comorbid FSS showed normal rate of cohabitation and did not report physical limitations or difficulties sleeping. Overall, our findings emphasise the importance of screening MCS cases for FSS comorbidity both in epidemiological and clinical settings.

IntroductionStudies investigating the economic burden of functional somatic disorder (FSD) in general populations are lacking. The current study incorporated data from a randomly sampled general population to examine healthcare use and costs in FSD using comprehensive national register data.MethodsThe study included 9656 adults from the DanFunD general population cohort study. FSD was identified via self-reported questionnaires and verified by diagnostic interviews conducted by a physician. Data on healthcare were sourced from the comprehensive Danish central registries in the period 10 years before and 4 years after DanFunD inclusion. Healthcare use was investigated with Poisson and Zero-inflated Poisson regression models. Healthcare costs were investigated with linear regression models. Analyses comprised sex- and age-adjusted regression models with non-parametric bootstrap resampling (10 000 repetitions).ResultsIndividuals with FSD used more healthcare facilities and it costed more compared with individuals without FSD. For example, the incidence rate ratio of having used healthcare services for participants with interview-diagnosed severe FSD was 1.62 (95% CI 1.37 to 1.94) in the 10-year period before DanFunD inclusion, and the annual healthcare costs were 1038 € (339 € to 1846 €) higher. Individuals with FSD also had a higher use of healthcare than individuals with other severe physical disease, but in most cases, no differences were found for costs.ConclusionsFSD carries a significant economic burden on society due to increased healthcare use and costs compared with individuals without FSD, and for most, also for individuals with other severe physical disease.Trial registration numberNCT05811663.

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.

Antiarrhythmic drugs prolong the atrial action potential and refractory period, and thereby prevent recurrent atrial fibrillation after cardioversion. The atrial action potential normalises after 2–4 weeks of sinus rhythm, suggesting that antiarrhythmic drugs might not be needed beyond that period. Therefore, we investigated whether short-term antiarrhythmic drug treatment after cardioversion is non-inferior to long-term treatment. We enrolled patients in a prospective, randomised, open-label, blinded endpoint assessment trial between May 4, 2007, and March 12, 2010, at 44 centres in Germany. Eligible patients were adults with persistent atrial fibrillation undergoing planned cardioversion. After successful cardioversion, patients were randomly assigned in permuted blocks of six per centre to: no antiarrhythmic drug treatment (control); treatment with flecainide (200–300 mg per day) for 4 weeks (short-term treatment); or flecainide for 6 months (long-term treatment). The primary endpoint was time to persistent atrial fibrillation or death. Patients and clinicians were unmasked to group assignment and treatment. The primary outcome was assessed in a core laboratory, members of which were masked to treatment group. Patients were monitored for 6 months by daily telemetric electrocardiograph (ECG) and centrally adjudicated Holter ECG recordings whenever atrial fibrillation was noted in two consecutive ECGs. Analyses were per protocol. This trial is registered, number ISRCTN62728742. After assay sensitivity was established with 4-week follow-up data from 242 patients showing that flecainide was superior to no treatment (Kaplan-Meier survival 70·2%vs 52·5%; p=0·0160), the trial continued to compare short-term versus long-term treatment. The primary outcome occurred in 120 (46%) of 261 patients receiving short-term treatment and in 103 (39%) of 263 patients receiving long-term treatment (event-free survival 48·4% [95% CI 41·9–55·0] vs 56·4% [49·1–63·6]; Kaplan-Meier estimate of difference 7·9% [–1·9 to 17·7]; p=0·2081 for non-inferiority; margin prespecified at 12%). In a post-hoc landmark analysis of patients who had not reached the primary endpoint in the first month, long-term treatment was superior to short-term treatment (Kaplan-Meier estimate of difference 14·3% [5·1–23·6]; hazard ratio 0·31 [0·18–0·56]; p=0·0001). Short-term antiarrhythmic drug treatment after cardioversion is less effective than is long-term treatment, but can prevent most recurrences of atrial fibrillation. The German Federal Ministry of Education and Research, Deutsche Forschungsgemeinschaft, 3M Medica, and MEDA Pharmaceuticals.

The Danish study of Functional Disorders (DanFunD) cohort was initiated to outline the epidemiology of functional somatic syndromes (FSS) and is the first larger coordinated epidemiological study focusing exclusively on FSS. FSS are prevalent in all medical settings and can be defined as syndromes that, after appropriate medical assessment, cannot be explained in terms of a conventional medical or surgical disease. FSS are frequent and the clinical importance varies from vague symptoms to extreme disability. No well-described medical explanations exist for FSS, and how to delimit FSS remains a controversial topic. The specific aims with the cohort were to test delimitations of FSS, estimate prevalence and incidence rates, identify risk factors, delimitate the pathogenic pathways, and explore the consequences of FSS. The study population comprises a random sample of 9,656 men and women aged 18-76 years from the general population examined from 2011 to 2015. The survey comprises screening questionnaires for five types of FSS, ie, fibromyalgia, whiplash-associated disorder, multiple chemical sensitivity, irritable bowel syndrome, and chronic fatigue syndrome, and for the unifying diagnostic category of bodily distress syndrome. Additional data included a telephone-based diagnostic interview assessment for FSS, questionnaires on physical and mental health, personality traits, lifestyle, use of health care services and social factors, and a physical examination with measures of cardiorespiratory and morphological fitness, metabolic fitness, neck mobility, heart rate variability, and pain sensitivity. A biobank including serum, plasma, urine, DNA, and microbiome has been established, and central registry data from both responders and nonresponders are similarly available on morbidity, mortality, reimbursement of medicine, heath care use, and social factors. A complete 5-year follow-up is scheduled to take place from year 2017 to 2020, and further reexaminations will be planned. Several projects using the DanFunD data are ongoing, and findings will be published in the coming years.

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. A cross-sectional general population-based study. The Danish Study of Functional Somatic Disorders (DanFunD) conducted in 2011-2015 in 10 municipalities in the western part of greater Copenhagen, Denmark. 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. 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. 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. 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.

Recruitment and activation of polymorphonuclear neutrophils (PMNs) reflects a primary immunological response to invading pathogens and has also emerged as a hallmark of vascular inflammation. One of the principal enzymes released upon PMN activation is myeloperoxidase (MPO), a heme protein that not only generates cytotoxic oxidants but also impacts deleteriously on nitric oxide-dependent signaling cascades within the vasculature. Because MPO also associates with the membrane of PMN, we evaluated whether MPO could also function as an autocrine modulator of PMN activation. The extent of PMN membrane-associated MPO was elevated in patients with acute inflammatory vascular disease compared with healthy individuals. Isolated PMNs bound free MPO by a CD11b/CD18 integrin-dependent mechanism. PMNs exposed to MPO were characterized by increased tyrosine phosphorylation and p38 mitogen-activated protein kinase activation. Also, nuclear translocation of NFκB in PMN was enhanced after incubation with MPO, as was surface expression of CD11b. Binding of PMN to MPO-coated fibronectin surfaces amplified PMN degranulation, as evidenced by increased release of MPO and elastase. MPO also augmented PMN-dependent superoxide ( O2 · -) production, which was prevented by anti-CD11b antibodies, but not MPO inhibitors. Collectively, these results reveal that binding of MPO to CD11b/CD18 integrins stimulates PMN signaling pathways to induce PMN activation in a mechanism independent of MPO catalytic activity. These cytokine-like properties of MPO thus represent an additional dimension of the proinflammatory actions of MPO in vascular disease.

ObjectiveThe 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.DesignCross-sectional.SettingDanish general population, primary care and specialised clinical setting.ParticipantsA 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 measuresAll 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.ResultsFor 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.ConclusionsThe 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.