Development and User Experiences of a Biopsychosocial Interprofessional Online Course on Persistent Somatic Symptoms.

Background: Communication between healthcare providers and patients with persistent somatic symptoms (PSS) is frequently hampered by mutual misunderstanding and dissatisfaction. Methods: We developed an online, interprofessional course to teach healthcare providers the knowledge, skills, and attitude they need to diagnose and treat PSS in a patient-centered manner based on the biopsychosocial model. The course consisted of six modules of 45-60 min. Each module contained different types of assignments, based on six cases: videos, discussion boards, reading assignments, polls, and quizzes. For this study, we included (1) medical residents, following the course as part of their residency training, and (2) healthcare providers (general practitioners, medical specialists, physiotherapists, nurses, and psychologists), following the course as continuing vocational training. Throughout the course, participants were asked to fill out online surveys, enquiring about their learning gains and satisfaction with the course. Results: The biopsychosocial approach was integrated across the modules and teached health care workers about recent insights on biological, psychological and social aspects of PSS. In total, 801 participants with a wide variety in clinical experience started the course; the largest groups of professionals were general practitioners (N = 400), physiotherapists (N = 124) and mental healthcare workers (N = 53). At the start of the course, 22% of the participants rated their level of knowledge on PSS as adequate. At the end of the course, 359 participants completed the evaluation questionnaires. Of this group, 81% rated their level of knowledge on PSS as adequate and 86% felt that following the course increased their competencies in communicating with patients with PSS (N = 359). On a scale from 1 to 10, participants gave the course a mean grade of 7.8 points. Accordingly, 85% stated that they would recommend the course to a colleague. Conclusion: Our course developed in a co-design process involving multiple stakeholders can be implemented, is being used, and is positively evaluated by professionals across a variety of health care settings.

Exploring temporal relationships among worrying, anxiety, and somatic symptoms.

OBJECTIVES: The role of anxiety symptoms in the development of functional somatic symptoms (FSS) is unknown. Somatic symptoms may be triggered by or give rise to anxiety symptoms. This study aimed to 1) explore interrelationships among within-day worrying, feeling anxious, and somatic symptoms, and 2) investigate the association between these interrelationships and overall level of FSS. METHODS: This study included 767 participants (83% females, mean age 39 years), who were recruited through an online crowdsourcing study in the Dutch general population. Somatic, and anxiety symptoms were reported thrice daily (6-h intervals) for 30 days using electronic diaries. FSS were assessed at baseline (PHQ-15). Temporal relationships among worrying, feeling anxious, and somatic symptoms were modeled using a multilevel vector autoregressive model. RESULTS: We observed large heterogeneity in the within-person interrelationships among worrying, feeling anxious and somatic symptoms. Averaged over participants, higher-than-usual somatic symptoms were associated with increases in levels of worrying six hours later (B = 0.017, 95% CI [0.006, 0.027]). At the between-person level, FSS levels predicted the persistence of feeling anxious (B = 0.230 95% CI [0.105, 0.350]) and the carry-over of worrying to feeling anxious over six-hours (B = 0.159, 95% CI [0.031, 0.283]). CONCLUSIONS: In contrast to what we expected, higher levels of somatic symptoms over multiple weeks were associated with the persistence and carry-over of within-day anxiety-related symptoms. One within-person association between psychological and somatic symptoms during the day was observed, suggesting that, over a time span of 6-h, anxiety symptoms relate to somatic symptoms only in a minority of people from the general population.

The importance of contextual aspects in the care for patients with functional somatic symptoms.

Functional somatic symptoms refer to physical symptoms that cannot be (bio) medically explained. The pattern or clustering of such symptoms may lead to functional syndromes like chronic fatigue syndrome, fibromyalgia, irritable bowel syndrome, among many others. Since the underlying pathophysiology remains unknown, several explanatory models have been proposed, nearly all including social and psychological parameters. These models have stimulated effectiveness studies of several psychological and psychopharmacological therapies. While the evidence for their effectiveness is steadily growing, effect-sizes are at most moderate and many patients do not benefit. We hypothesize that the context in which interventions for functional somatic symptoms are delivered substantially influences their effectiveness. Although this hypothesis is in line with explanatory models of functional somatic symptoms, to our knowledge, studies primarily focusing on the influence of contextual aspects on treatment outcome are scarce. Contextual research in the field of somatic symptoms has (irrespective whether these symptoms can be medically explained or not), however, just begun and already yielded some valuable results. These findings can be organized according to Duranti's and Goodwin's theoretical approach to context in order to substantiate our hypothesis. Based on this approach, we categorized empirical findings in three contextual aspects, i.e. 1) the setting, 2) the behavioural environment, and 3) the language environment. Collectively, some support is found for the fact that early identification of patients with functional somatic symptoms, starting treatment as soon as possible, having a neat appearance and an organized office interior, a warm and friendly nonverbal approach and a language use without defensiveness are contextual parameters which enhance the assessment by the patient of the physician's competence to help. Nonetheless, in vivo studies addressing the most aspects, i.e. nonverbal behaviour and language, are needed for better understanding of these contextual aspect. Moreover, future research should address to what extent optimizing contextual aspects improve care for functional somatic symptoms.

Shared demographics and comorbidities in different functional motor disorders.

INTRODUCTION: Functional motor disorders are often delineated according to the dominant motor symptom. In a large cohort, we aimed to find if there were differences in demographics, mode of onset, pain, fatigue, depression and anxiety and levels of physical functioning, quality of life and social adjustment between patients with different dominant motor symptoms. METHODS: Baseline data from the Self-Help and Education on the Internet for Functional Motor Disorders Trial was used. Patients were divided into dominant motor symptom groups based on the diagnosis of the referring neurologist. Data on the above topics were collected by means of an online questionnaire and compared between groups using parametric and nonparametric statistics. RESULTS: In 160 patients a dominant motor symptom could be determined, 31 had tremor, 45 myoclonus, 23 dystonia, 30 paresis, 31 gait disorder. No statistical differences between groups were detected for demographics, mode of onset and severity of pain, fatigue, depression and anxiety. Physical functioning was worse in the gait disorder group (median 20, IQR 25) compared to tremor (50 (55), p = 0.002) and myoclonus (50 (52), p = 0.001). Work and social adjustment was less impaired in the myoclonus group (median 20, IQR 18) compared to gait disorder (median 30, IQR18, p < 0.001) and paresis (28, IQR 10, p = 0.001). Self-report showed large overlap in motor symptoms. CONCLUSION: No differences were detected between groups of functional motor symptoms, regarding demographics, mode of onset, depression, anxiety, pain and fatigue. The large overlap in symptoms contributes to the hypothesis of shared underlying mechanisms of functional motor disorders.

Identification of inflammatory markers suitable for non-invasive, repeated measurement studies in biobehavioral research: A feasibility study.

INTRODUCTION: Studying the role of the immune system in the interaction between mental and physical health is challenging. To study individuals with an intensive, longitudinal study design that requires repetitive sampling in their daily life, non-invasive sampling techniques are a necessity. Urine can be collected in a non-invasive way, but this may be demanding for participants and little is known about fluctuation of inflammatory markers in urine over time. The aim of this study was to investigate the feasibility of non-invasive sampling, and to explore intra-individual differences in inflammatory markers in urine. MATERIALS & METHODS: Ten healthy individuals collected 24-hour urine for 63 consecutive days. In a pilot analysis, 39 inflammatory markers were examined for detectability in urine, stability over time and under storage conditions, and daily fluctuations. Multiplex analyses were used to quantify levels of eight selected markers: C-reactive protein (CRP), Fractalkine, Interleukin-1 receptor-antagonist (IL-1RA), interferon-α (IFNα), interferon-γ (IFNγ), Interferon gamma-induced protein 10 (IP10), Macrophage inflammatory protein-1ß (MIP-1ß), and Vascular Endothelial Growth Factor (VEGF). Cross-correlations were calculated between the overnight and 24-hour samples were calculated, to examine whether 24-hour urine could be replaced by the overnight portion for better feasibility. We examined intra- and interindividual differences in the levels of inflammatory markers in urine and the fluctuations thereof. RESULTS: This study showed that levels of selected inflammatory markers can be detected in urine. Cross-correlation analyses showed that correlations between levels of inflammatory markers in the night portion and the 24-hour urine sample varied widely between individuals. In addition, analyses of time series revealed striking inter- and intra-individual variation in levels of inflammatory markers and their fluctuations. CONCLUSION: We show that the assessment of urinary inflammatory markers is feasible in an intensive day-to-day study in healthy individuals. However, 24-hour urine cannot be replaced by an overnight portion to alleviate the protocol burden. Levels of inflammatory markers show substantial variation between and within persons.

Individual variation in temporal relationships between exposure to radiofrequency electromagnetic fields and non-specific physical symptoms: A new approach in studying 'electrosensitivity'.

BACKGROUND: Everyday exposure to radiofrequency electromagnetic fields (RF-EMF) emitted from wireless devices such as mobile phones and base stations, radio and television transmitters is ubiquitous. Some people attribute non-specific physical symptoms (NSPS) such as headache and fatigue to exposure to RF-EMF. Most previous laboratory studies or studies that analyzed populations at a group level did not find evidence of an association between RF-EMF exposure and NSPS. OBJECTIVES: We explored the association between exposure to RF-EMF in daily life and the occurrence of NSPS in individual self-declared electrohypersensitive persons using body worn exposimeters and electronic diaries. METHODS: We selected seven individuals who attributed their NSPS to RF-EMF exposure. The level of and variability in personal RF-EMF exposure and NSPS were determined during a three-week period. Data were analyzed using time series analysis in which exposure as measured and recorded in the diary was correlated with NSPS. RESULTS: We found statistically significant correlations between perceived and actual exposure to wireless internet (WiFi - rate of change and number of peaks above threshold) and base stations for mobile telecommunications (GSM + UMTS downlink, rate of change) and NSPS scores in four of the seven participants. In two persons a higher EMF exposure was associated with higher symptom scores, and in two other persons it was associated with lower scores. Remarkably, we found no significant correlations between NSPS and time-weighted average power density, the most commonly used exposure metric. CONCLUSIONS: RF-EMF exposure was associated either positively or negatively with NSPS in some but not all of the selected self-declared electrohypersensitive persons.

Fatigue, not self-rated motor symptom severity, affects quality of life in functional motor disorders.

While fatigue is found to be an impairing symptom in functional motor disorders (FMD) in clinical practice, scientific evidence is lacking. We investigated fatigue severity and subtypes in FMD compared to organic neurological disease. Furthermore, the role of fatigue within FMD and its impact on quality of life and self-rated health were investigated. Data from 181 patients participating in the self-help on the internet for functional motor disorders, randomised Trial were included. Data from 217 neurological controls with neuromuscular disorders (NMD) originated from a historical cohort. Fatigue was measured using the checklist individual strength (CIS). Motor symptom severity, depression and anxiety were correlated to fatigue. For multivariable regression analyses, physical functioning and pain were additionally taken into account. Severe fatigue was, respectively, present in 78 and 53% of FMD and NMD patients (p < 0.001). FMD patients scored higher than NMD patients on all fatigue subdomains (p < 0.001). In the FMD group, fatigue subdomains were correlated to depression, anxiety and partly to motor symptom severity. Quality of life was negatively associated with fatigue [OR 0.93 (0.90-0.96), p < 0.001] and depression [OR 0.87 (0.81-0.93), p < 0.001], but not self-rated motor symptom severity. Self-rated health was negatively associated with fatigue [OR 0.92 (0.88-0.96), p < 0.001] and pain [OR 0.98 (0.97-0.99), p < 0.001]. Fatigue was found to be a prevalent problem in FMD, more so than in organic neurological disease. It significantly affected quality of life and self-rated health, while other factors such as motor symptom severity did not. Fatigue should be taken into account in clinical practice and treatment trials.

Assessment of Somatization and Medically Unexplained Symptoms in Later Life.

The assessment of medically unexplained symptoms and "somatic symptom disorders" in older adults is challenging due to somatic multimorbidity, which threatens the validity of somatization questionnaires. In a systematic review study, the Patient Health Questionnaire-15 (PHQ-15) and the somatization subscale of the Symptom Checklist 90-item version (SCL-90 SOM) are recommended out of 40 questionnaires for usage in large-scale studies. While both scales measure physical symptoms which in younger persons often refer to unexplained symptoms, in older persons, these symptoms may originate from somatic diseases. Using empirical data, we show that PHQ-15 and SCL-90 SOM among older patients correlate with proxies of somatization as with somatic disease burden. Updating the previous systematic review, revealed six additional questionnaires. Cross-validation studies are needed as none of 46 identified scales met the criteria of suitability for an older population. Nonetheless, specific recommendations can be made for studying older persons, namely the SCL-90 SOM and PHQ-15 for population-based studies, the Freiburg Complaint List and somatization subscale of the Brief Symptom Inventory 53-item version for studies in primary care, and finally the Schedule for Evaluating Persistent Symptoms and Somatic Symptom Experiences Questionnaire for monitoring treatment studies.

[The prognosis of medically unexplained symptoms]. / De prognose van somatisch onvoldoende verklaarde lichamelijke klachten.

- The condition where someone has physical symptoms for a number of weeks for which no clear somatic cause can be found, is known as medically unexplained symptoms (MUS).- In this article we give an overview of current insights into the prognosis of MUS.- Extensive somatic testing in patients diagnosed with MUS by a physician, rarely results in a somatic diagnosis.- In approximately half of these patients, MUS disappear spontaneously within one year.- Symptom-related characteristics - such as experiencing multiple physical symptoms simultaneously-, and psychological characteristics - such as unhelpful thoughts - are predictors of an unfavourable prognosis for MUS.- Close monitoring of patients with MUS enables timely interventions, and may help to prevent MUS following an unfavourable course. Existing guidelines may help in choosing treatment and tailoring it to the individual patient.

Childhood life events, immune activation and the development of mood and anxiety disorders: the TRAILS study.

The experience of childhood life events is associated with higher vulnerability to develop psychiatric disorders. One of the pathways suggested to lead to this vulnerability is activation of the immune system. The aim of this study is to find out whether the association between childhood life events and the development of mood and anxiety disorders is predicted by the activation of the immune system. This study was performed in TRAILS, a large prospective population cohort, from which a subgroup was selected (N=1084, 54.3% female, mean age 19.0 (s.d., 0.6)). Childhood life events before age 16 were assessed using questionnaires at age 12, 14, 16 and 19. Immune activation was assessed at age 16 by elevated high-sensitive C-reactive protein (hsCRP) and by levels of immunoglobulin G antibodies against the herpes viruses herpes simplex virus 1, cytomegalovirus and Epstein-Barr virus. At age 19, the presence of mood and anxiety disorders was determined using the World Health Organization Composite International Diagnostic Interview Version 3.0. Regression analyses were used to study the association between life events, the inflammatory markers and mental health. We found that childhood life events score was associated with risk of mood disorders (B=0.269, P<0.001) and anxiety disorders (B=0.129, P<0.001). Childhood life events score was marginally associated with elevated hsCRP (B=0.076, P=0.006), but not with the antibody levels. This was especially due to separation trauma (P=0.015) and sexual abuse (P=0.019). Associations lost significance after correcting for lifestyle factors such as body mass index and substance abuse (P=0.042). None of the inflammatory markers were associated with development of anxiety disorders or mood disorders. In conclusion, the life event scores predicted the development of anxiety disorders and mood disorders at age 19. Life event scores were associated with elevated hsCRP, which was partly explained by lifestyle factors. Elevated hsCRP was not associated with the development of psychiatric disorders at age 19.

Functional outcomes of child and adolescent mental disorders. Current disorder most important but psychiatric history matters as well.

BACKGROUND: Various sources indicate that mental disorders are the leading contributor to the burden of disease among youth. An important determinant of functioning is current mental health status. This study investigated whether psychiatric history has additional predictive power when predicting individual differences in functional outcomes. METHOD: We used data from the Dutch TRAILS study in which 1778 youths were followed from pre-adolescence into young adulthood (retention 80%). Of those, 1584 youths were successfully interviewed, at age 19, using the World Health Organization Composite International Diagnostic Interview (CIDI 3.0) to assess current and past CIDI-DSM-IV mental disorders. Four outcome domains were assessed at the same time: economic (e.g. academic achievement, social benefits, financial difficulties), social (early motherhood, interpersonal conflicts, antisocial behavior), psychological (e.g. suicidality, subjective well-being, loneliness), and health behavior (e.g. smoking, problematic alcohol, cannabis use). RESULTS: Out of the 19 outcomes, 14 were predicted by both current and past disorders, three only by past disorders (receiving social benefits, psychiatric hospitalization, adolescent motherhood), and two only by current disorder (absenteeism, obesity). Which type of disorders was most important depended on the outcome. Adjusted for current disorder, past internalizing disorders predicted in particular psychological outcomes while externalizing disorders predicted in particular health behavior outcomes. Economic and social outcomes were predicted by a history of co-morbidity of internalizing and externalizing disorder. The risk of problematic cannabis use and alcohol consumption dropped with a history of internalizing disorder. CONCLUSION: To understand current functioning, it is necessary to examine both current and past psychiatric status.

The network structure of major depressive disorder, generalized anxiety disorder and somatic symptomatology.

BACKGROUND: Major depressive disorder (MDD) and generalized anxiety disorder (GAD) often co-occur with somatic symptomatology. Little is known about the contributions of individual symptoms to this association and more insight into their relationships could help to identify symptoms that are central in the processes behind the co-occurrence. This study explores associations between individual MDD/GAD symptoms and somatic symptoms by using the network approach. METHOD: MDD/GAD symptoms were assessed in 2704 participants (mean age 41.7 years, 66.1% female) from the Netherlands Study of Depression and Anxiety using the Inventory of Depressive Symptomatology. Somatic symptoms were assessed with the somatization scale of the Four-Dimensional Symptom Questionnaire. The technique eLasso was used to estimate the network of MDD/GAD and somatic symptoms. RESULTS: The network structure showed numerous associations between MDD/GAD and somatic symptoms. In general, neurovegetative and cognitive/affective MDD/GAD symptoms showed a similar strength of connections to the somatic domain. However, associations varied substantially across individual symptoms. MDD/GAD symptoms with many and strong associations to the somatic domain included anxiety and fatigue, whereas hypersomnia and insomnia showed no connections to somatic symptoms. Among somatic symptoms, excessive perspiration and pressure/tight feeling in chest were associated with the MDD/GAD domain, while muscle pain and tingling in fingers showed only a few weak associations. CONCLUSIONS: Individual symptoms show differential associations in the co-occurrence of MDD/GAD with somatic symptomatology. Strongly interconnected symptoms are important in furthering our understanding of the interaction between the symptom domains, and may be valuable targets for future research and treatment.

The relationship between 63days of 24-h urinary free cortisol and hair cortisol levels in 10 healthy individuals.

BACKGROUND: Interest in measuring cortisol in scalp hair is increasing because of its assumed ability to provide a historical timeline of previous systemic levels of cortisol. Yet, it remains uncertain how well hair cortisol represents the total systemic secretion of cortisol over time. METHODS: Ten healthy individuals collected 24-h urine samples for 63 consecutive days and provided a hair sample at the end of the study period. 24-h urinary creatinine levels in every urine sample were determined to assess completeness of the samples. Cortisol levels in 24-h urine samples and in hair were measured with liquid chromatography tandem mass spectrometry. The correlations between urinary cortisol and hair cortisol were calculated using Kendall's tau. RESULTS: We found a nonsignificant moderate correlation between average urinary cortisol secretion and average hair cortisol concentration rт=0.422, p=0.089. CONCLUSIONS: Hair cortisol concentration correlates low to moderately with 24-h urinary cortisol concentration over a period of 63days.

A systematic review and meta-analysis of the percentage of revised diagnoses in functional somatic symptoms.

BACKGROUND: Functional somatic symptoms (FSS) are bodily complaints of unclear etiology, which are (currently) not fully explained by well-recognized somatic pathology. Doctors are often hesitant to diagnose FSS, due to the risk to miss a somatic disease. The purpose of this study is to review available literature on the percentage of patients diagnosed with FSS reported to have an underlying somatic disease that explains their symptoms previously labeled as FSS. METHODS: We performed a systematic search of Medline, Embase and PsycINFO databases and reference lists of selected articles. We included studies published between January 1980 and July 2014 without language restrictions. Studies that measured the percentage of underlying somatic diseases after a diagnostic evaluation or naturalistic follow-up period in adult patients initially diagnosed with FSS were included. As primary outcome measure the weighted percentage of revised diagnoses was calculated using meta-analyses. RESULTS: Six diagnostic evaluation studies (total N=1804 patients) and 16 follow-up studies (total N=2440 patients) were included. The percentage of revised diagnosis in patients initially diagnosed with FSS was 8.8% (95% CI 1.0 to 22.2, p=0.007) in diagnostic evaluation studies and 0.5% (95% CI 0.01 to 1.5, p=0.03) in follow-up studies. Partially or possibly related diagnoses were rarely found. No specific somatic diagnosis seemed to be missed systematically. CONCLUSIONS: The percentage of underlying somatic diseases in patients previously diagnosed with FSS is relatively small but unneglectable.

The association of air pollution and depressed mood in 70,928 individuals from four European cohorts.

BACKGROUND: Exposure to ambient air pollution may be associated with impaired mental health, including depression. However, evidence originates mainly from animal studies and epidemiological studies in specific subgroups. We investigated the association between air pollution and depressed mood in four European general population cohorts. METHODS: Data were obtained from LifeLines (the Netherlands), KORA (Germany), HUNT (Norway), and FINRISK (Finland). Residential exposure to particles (PM2.5, PM2.5absorbance, PM10) and nitrogen dioxide (NO2) was estimated using land use regression (LUR) models developed for the European Study of Cohorts for Air Pollution Effects (ESCAPE) and using European wide LUR models. Depressed mood was assessed with interviews and questionnaires. Logistic regression analyses were used to investigate the cohort specific associations between air pollution and depressed mood. RESULTS: A total of 70,928 participants were included in our analyses. Depressed mood ranged from 1.6% (KORA) to 11.3% (FINRISK). Cohort specific associations of the air pollutants and depressed mood showed heterogeneous results. For example, positive associations were found for NO2 in LifeLines (odds ratio [OR]=1.34; 95% CI: 1.17, 1.53 per 10 µg/m(3) increase in NO2), whereas negative associations were found in HUNT (OR=0.79; 95% CI: 0.66, 0.94 per 10 µg/m(3) increase in NO2). CONCLUSIONS: Our analyses of four European general population cohorts found no consistent evidence for an association between ambient air pollution and depressed mood.

Stressful life events and leukocyte telomere attrition in adulthood: a prospective population-based cohort study.

BACKGROUND: Telomere attrition might be one of the mechanisms through which psychosocial stress leads to somatic disease. To date it is unknown if exposure to adverse life events in adulthood is associated with telomere shortening prospectively. In the current study we investigated whether life events are associated with shortening of telomere length (TL). METHOD: Participants were 1094 adults (mean age 53.1, range 33-79 years) from the PREVEND cohort. Data were collected at baseline (T1) and at two follow-up visits after 4 years (T2) and 6 years (T3). Life events were assessed with an adjusted version of the List of Threatening Events (LTE). TL was measured by monochrome multiplex quantitative PCR at T1, T2, and T3. A linear mixed model was used to assess the effect of recent life events on TL prospectively. Multivariable regression analyses were performed to assess whether the lifetime life events score or the score of life events experienced before the age of 12 predicted TL cross-sectionally. All final models were adjusted for age, sex, body mass index, presence of chronic diseases, frequency of sports, smoking status, and level of education. RESULTS: Recent life events significantly predicted telomere attrition prospectively (B = -0.031, p = 0.007). We were not able to demonstrate a significant cross-sectional relationship between the lifetime LTE score and TL. Nor did we find exposure to adverse life events before the age of 12 to be associated with TL in adulthood. CONCLUSIONS: Exposure to recent adverse life events in adulthood is associated with telomere attrition prospectively.