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Thomas Meinertz Dantoft,1 Jeanette Frost Ebstrup,1 Allan Linneberg,1–3 Sine Skovbjerg,1 Anja Lykke Madsen,1 Jesper Mehlsen,4 Louise Brinth,4 Lene Falgaard Eplov,5 Tina Wisbech Carstensen,6,7 Andreas Schroder,6,7 Per Klausen Fink,6,7 Erik Lykke Mortensen,8 Torben Hansen,9 Oluf Pedersen,9 Torben Jørgensen1,10,11 1Research Centre for Prevention and Health, The Capital Region of Denmark, Glostrup, 2Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, 3Department of Clinical Experimental Research, Rigshospitalet, Glostrup, 4Coordinating Research Centre, Bispebjerg and Frederiksberg Hospital, Frederiksberg, 5Mental Health Centre Copenhagen, Research Unit, Mental Health Services, Capital Region of Denmark, Copenhagen, 6The Research Clinic for Functional Disorders and Psychosomatics, Aarhus University Hospital, 7Faculty of Health Sciences, University of Aarhus, Aarhus, 8Department of Public Health and Center for Healthy Aging, 9Novo Nordisk Foundation Center for Basic Metabolic Research, 10Department of Public Health, Faculty of Health and Medical Sciences, University of Copenhagen, 11Faculty of Medicine, Aalborg University, Aalborg, Denmark Abstract: 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. Keywords: functional somatic syndromes, medically unexplained symptoms, epidemiology, longitudinal cohort study, pathophysiology, risk factors

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.

Objective: To describe the use of prescription drugs and their association with patient characteristics in patients with multiple functional somatic syndromes (FSS) focusing on drugs generally recommended and not recommended in FSS treatment., Method: Using data from a national prescription registry, we describe the drug use during a two-year period for 239 trial participants. Using regression models, we analyse the associations of patient characteristics with the patterns of use of antidepressants, anticonvulsants, opioids and sedatives., Results: The use of prescription drugs was highly heterogeneous. Antidepressants were used at least temporarily by 34% (88/239), anticonvulsants by 7% (16/239), opioids by 26% (61/239) and sedatives by 20% (47/239) of the patients. Severe impairment due to multiple FSS was associated with use of opioids or sedatives (OR 6.49 (95% CI 2.68-15.68; p < 0.001)) but also with use of antidepressants or anticonvulsants (OR 3.42 (95% CI 1.35-8.65; p = 0.009)). Poor self-reported physical health, additional physical comorbidities and low socioeconomic status were associated with use of opioids or sedatives only., Conclusion: Antidepressants and anticonvulsants were modestly used. Opioids and sedatives were especially used by the severely affected patients. Balancing treatment expectations and enhancing patients' understanding of FSS may direct treatments towards more generally recommended drugs., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: Functional somatic syndromes, including chronic fatigue syndrome or irritable bowel syndrome, often co-exist. Treatment guidelines supported by high quality evidence exist for most functional somatic syndromes, but are lacking for multiple comorbid functional somatic syndromes. We aimed to assess the effect of the tricyclic antidepressant, imipramine, in patients with multiple functional somatic syndromes defined by the criteria for multiorgan bodily distress syndrome, a unifying diagnosis that encompasses most functional somatic syndromes and somatoform disorders., Methods: In this single-centre, double-blind, randomised trial done in a Danish university hospital setting, participants were patients consecutively referred (age 20-50 years) fulfilling criteria for multiorgan bodily distress syndrome with no concurrent comorbid depression or anxiety disorder. Participants were randomly assigned (1:1) to receive either 10 weeks of low-dose imipramine or placebo (oral daily doses of 25-75 mg). The hospital pharmacy handled randomisation (computer-generated) and masking, providing sequentially numbered packs of study drug that were given serially to the participants. All others involved were masked to allocation. Primary outcome was patient-rated overall health improvement on a 5-point clinical global improvement scale. Improvement was defined as patients responding "better" or "much better" as opposed to "unchanged" and "worse" or "much worse" when rating their overall health status after 10 weeks of minimum 25 mg study drug. Analyses included patients who received at least one dose of study drug. This study is registered with ClinicalTrials.gov, number NCT01518634., Findings: Between Jan 30, 2012, and Nov 24, 2014, 138 patients were randomly assigned; 70 to receive imipramine and 68 to receive placebo. The study was completed on May 1, 2015. 125 patients received at least one dose of study drug: 65 received imipramine and 60 received placebo. Treatment was terminated prematurely for eight (12%) patients receiving imipramine and seven (12%) patients receiving placebo. Data were missing for two (3%) patients receiving imipramine and three (5%) patients receiving placebo. Of the 120 patients (96%) who provided primary outcome data, 33 (53%) receiving imipramine reported their overall health status as "better" or "much better" compared with 14 patients (25%) receiving placebo. The improvement after imipramine was significantly greater than after placebo (odds ratio 3·3 [95% CI 1·6-6·8]; p=0·001). Number needed to treat was 3·6 (95% CI 2·3-8·9). Analysis of the worst-case scenario for patients with missing outcome did not change the interpretation of the results. 32 patients (49%) receiving imipramine and 10 patients (17%) receiving placebo had at least one adverse event of moderate intensity (p=0·0001); eight patients (12%) receiving imipramine and three patients (5%) receiving placebo had at least one adverse event of severe intensity (p=0·1496). One patient (1%) receiving placebo experienced a serious adverse event (a subdural haematoma sustained after an accident). Adverse events caused dropout in four patients (6%) receiving imipramine and three patients (5%) receiving placebo., Interpretation: Imipramine treatment compared with placebo significantly improved overall health in patients with multiple functional somatic syndromes when both treatments were supported by regular contacts with clinicians. Adverse events were more common in the imipramine group, but only rarely led to discontinuation of treatment., Funding: The Danish Foundation, Trygfonden., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

HPV vaccination offers protection against ~70% of cervical cancers, however, serious concerns have been raised about the possible side effects from HPV vaccination. Studies have found no increased risk of neurologic disease, autoimmune disorder, thromboembolic disease, postural orthostatic tachycardia syndrome, or complex regional pain syndrome in HPV-vaccinated persons compared to unvaccinated persons. Affected individuals should undergo a proper clinical examination to ensure a correct diagnosis and treatment, because symptoms might arise due to a somatic, psychiatric or functional disorder.

A high number of somatic symptoms have been associated with poor health status and increased health care use. Previous studies focused on number of symptoms without considering the specific symptoms. The aim of the study was to investigate 1) the prevalence of 19 somatic symptoms, 2) the associations between the symptoms, and 3) the associations between the somatic symptoms, self-perceived health and limitations due to physical health accounting for the co-occurrence of symptoms. Information on 19 somatic symptoms, self-perceived health and limitations due to physical health was achieved from a population-based questionnaire survey of 36,163 randomly selected adults in the Capital Region of Denmark in 2006/07. Chain graph models were used to transparently identify and describe the associations between symptoms, self-perceived health and limitations due to physical health. In total, 94.9% of the respondents were bothered by one or more of the 19 somatic symptoms. The symptoms were associated in a complex structure. Still, recognisable patterns were identified within organ systems/body parts. When accounting for symptom co-occurrence; dizziness, pain in legs, respiratory distress and tiredness were all strongly directly associated with both of the outcomes (γ>0.30). Chest pain was strongly associated with self-perceived health, and other musculoskeletal symptoms and urinary retention were strongly associated with limitations due to physical health. Other symptoms were either moderate or not statistically associated with the health status outcomes. Opposite, almost all the symptoms were strongly associated with the two outcomes when not accounting for symptom co-occurrence. In conclusion, we found that somatic symptoms were frequent and associated in a complex structure. The associations between symptoms and health status measures differed between the symptoms and depended on the co-occurrence of symptoms. This indicates an importance of considering both the specific symptoms and symptom co-occurrence in further symptom research instead of merely counting symptoms.

Background: Medically Unexplained Symptoms (MUS) are frequently encountered in general practice. However, little is known whether MUS affects labor market participation. We investigated the prospective association between MUS at baseline and risk of long-term sickness absence (LTSA), unemployment, and disability pensioning in a 5-year-follow-up study., Methods: In the Danish Work Environment Cohort Study 2005, 8187 randomly selected employees from the Danish general population answered a questionnaire on work and health. Responses were linked with national registers on prescribed medication and hospital treatment. Participants were classified with MUS if they: a) had reported three or more symptoms during the last month, and b) did not have a chronic condition, neither in the self-reported nor the register data. We assessed LTSA, unemployment, and disability pensioning by linking our data with National registers of social transfer payments., Results: Of the 8187 participants, 272 (3.3%) were categorized with MUS. Compared to healthy participants, participants with MUS had an increased risk of LTSA (Rate ratio (RR) = 1.76, 95% CI = 1.28-2.42), and of unemployment (RR = 1.48, 95% CI = 1.02-2.15) during follow-up. MUS participants also showed an elevated RR with regard to risk of disability pensioning, however this association was not statistically significant (RR = 2.06, 95% CI = 0.77-5.52)., Conclusion: MUS seem to have a negative effect on labor market participation defined by LTSA and unemployment, whereas it is more uncertain whether MUS affects risk of disability pensioning.

Objectives: We examined whether primary care patients were more likely to perceive a current health problem as 'physical illness only' as opposed to entailing psychological difficulties if they had a comorbid somatoform disorder compared to patients who had (a) both comorbid somatoform disorder and anxiety/depression or (b) comorbid anxiety and/or depression, and a reference group of (c) patients with well-defined physical disease. We examined whether attributions predicted future health expenditures., Methods: A total of 1209 of 1785 patients completed questions on patient-perceived illness. The physicians diagnosed the current health problem. A stratified subsample was interviewed using the Schedules for Clinical Assessment in Neuropsychiatry. Health expenditure was obtained from registers for a 2-year period., Results: The belief that the current health problem was only physical was endorsed by 86% of patients presenting physical disease, 58% of patients with somatoform disorders, 29% of patients with both somatoform disorders and anxiety/depression and 24% of patients with anxiety or depressive disorders (χ2=269.2, df=3, P<.0001). In a multiple regression model, a 'physical illness only' perception predicted lower health expenditures [β = -0.31, 95% confidence interval (-0.55; -0.07), P=.013]., Conclusions: The prevalent assumption that physical symptom attributions are a central aspect in somatoform disorders is not supported by the current study., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Objectives: To examine (1) whether the patients' perceptions of their symptoms immediately after the accident and at 3-month follow-up predict working ability and neck pain at 12-month follow-up and (2) the possible changes in patients' illness perceptions during the follow-up period., Materials and Methods: A total of 740 consecutive patients exposed to acute whiplash trauma consulting emergency units and general practitioners in 4 Danish counties from 2001 to 2003. The patients completed questionnaires at baseline, 3-, and 12-month follow-up. Illness perceptions were measured using a condensed version of the Illness Perception Questionnaire and a 1-item question concerning return to work expectation. Neck pain was measured using an 11-point box scale, and working ability was measured by self-report at 12-month follow-up. Multiple logistic regression analyses were applied controlling for possible confounders., Results: Patients with pessimistic illness perceptions at baseline and 3-month follow-up were more likely to experience neck pain and affected working ability at 12 months compared with patients with optimistic illness perceptions. Negative return-to-work expectation predicted affected working ability at 12 months. Furthermore, patients with high neck pain intensity or affected working ability report more changes in their illness perceptions during follow-up than patients with low neck pain intensity or unaffected working ability., Discussion: The findings are in line with the common-sense model of illness and previous research demonstrating that patient's expectations for recovery and illness perceptions might influence the course after whiplash injury. Illness perceptions and expectations may provide a useful starting point for future interventions and be targeted in the prevention of chronicity.

Objective: To investigate the frequency of and factors linked to medical consultation for functional somatic symptoms (FSS) among 5- to 7-year-old children., Methods: We assessed 1327 children from the Copenhagen Child Cohort 2000 for FSS at ages 5 to 7 years. Register data on past health care use in general practice were compared between children with and those without parent-reported medical consultation for FSS at the age of 5 to 7 years: respective consulters (n = 96) and nonconsulters (n = 211) and children without FSS (n = 1019). Degree of parental worries about the child's symptoms and parent-reported symptom characteristics and associated impacts were compared between consulters and nonconsulters., Results: Among 308 children with FSS, 31.1% were consulters. Being a consulter was significantly associated with multisymptomatic presentation, parental worries about the symptoms, symptom impact, and a higher past health care use in general practice. Multiple logistic regression analysis controlled for gender, comorbid physical disease, and symptom severity revealed that the number of face-to-face contacts in general practice during the child's first 4 years of life predicted being an consulter for FSS at 5 to 7 years (odds ratio 1.03, 95% confidence interval 1.00-1.06; odds ratio interpreted per unit change in number of contacts)., Conclusions: This study adds to our understanding of health care use for FSS in childhood by highlighting the influence of parents' early consultation patterns with their child and the influence of parental perceptions of their child's health and FSS-related impact on pediatric health care use for FSS. Management of health care use in children with FSS should address these aspects.

Patients with acute whiplash trauma were followed to examine if pre-collision pain and psychological distress were associated with reduced work capability and neck pain at 12 month follow-up. Pre-collision unspecified pain was associated with reduced work capability, and neck pain and pre-collision psychological distress was associated with neck pain. In conclusion unspecified pain (as opposed to specified pain) and high accumulation of pre-collision psychological distress (as opposed to a single psychological disorder) before the collision was associated with poor recovery at follow-up.

The narrow ICD-10 and DSM-IV definition of hypochondriasis makes it a rarely used diagnosis. Based on a latent class analysis of the symptoms exhibited by 701 patients (ages 18-65) in general practice, a new and more valid hypochondriasis diagnosis was defined in this study. The main symptom is "obsessive rumination about illnesses", and the patient must also have at least one of five other symptoms. The prevalence was 9.5 for both genders. There was a good agreement between the diagnoses made during the psychiatric interview and the physicians' assessments.

Patients with unexplained physical symptoms are very common in primary care. Some patients attribute these symptoms to physical disease (somatizing patients). Somatization can be a symptom of psychiatric disorder, which is found in 1/4 to 1/3 of the patients in a primary care setting. This form of somatization makes diagnosing difficult and is the main reason why psychiatric disorders are underdiagnosed. Simple techniques for diagnosing and treating somatizing patients are available to general practitioners. However, to improve diagnostic sensitivity and treatment, further teaching and development in primary care settings are necessary.

Consultation-liaison psychiatry (C-L psychiatry) was founded in the USA in the 1930's as a clinical pendant of Psychosomatic medicine. By support and grants provided from the NIMH (National Institute for Mental Health) during the 1970's and 1980's, C-L psychiatry has now become an integrated part of the health care system in the USA. C-L psychiatric services are now being established in some European countries also. The aim of this review has thus been to introduce the C-L psychiatry sub-specialty to a Danish audience.

The purpose of the study was to describe the physical complaints and symptoms of persistently somatizing patients. Individuals in the general population (age 17-49 years) with at least ten general admissions during an eight-year period were studied. Persistent somatizers (i.e. patients with more than six medically unexplained general admissions) were compared with patients whose admissions could be ascribed to well-defined somatic disorders. Somatizers were characterized by multiple symptoms from many organ systems, and their physical complaints simulated most types of somatic disorders. Although some symptoms were more common than others, none were infrequent, so neither "classic" conversion symptoms nor pain symptoms were found to be especially characteristic of the persistent somatizer. These findings question the use of a predefined symptom checklist in the diagnostic criteria for somatizing disorder. One fifth of the persistent somatizers had been admitted at least once for factitious illness, but apart from the fact that they had more symptoms and admissions, they did not differ from the other persistent somatizers.

Existing expert systems have a high percentage agreement with experts in a particular field in many situations. However, in many ways their overall behavior is not like that of a human expert. These areas include the inability to give flexible, functional explanations of their reasoning processes, and the failure to degrade gracefully when dealing with problems at the periphery of their knowledge. These two important shortcomings can be improved when the right knowledge is available to the system. This paper presents an expert system design, called the integrated diagnostic model (IDM), that integrates two sources of knowledge, a shallow, reasoning-oriented, experiential knowledge base and a deep, functionally oriented, physical knowledge base. To demonstrate the IDM's usefulness in the problem area of diagnosis and repair, an implementation in the mechanical domain is described.