Functional somatic symptoms in preschool attention-deficit/hyperactivity disorder: a secondary analysis of data from a randomized controlled trial of parent training.

Children with attention-deficit/hyperactivity disorder (ADHD) can be more stress-vulnerable, and thereby, it has been suggested, prone to develop functional somatic symptoms (FSS) compared to their peers. In this paper, using data from 160 children aged 3-7 years with ADHD from the D'SNAPP study, a randomized controlled trial testing a parent training intervention, we addressed a number of questions about the role of FSS in ADHD. First, are FSS levels higher in an ADHD sample than in the children of the general population. Second, do FSS levels predict psychopathology and health-related quality of life (HRQoL) in ADHD samples. Third, does FSS levels moderate the effect of parent training on ADHD symptoms. We found that preschoolers with ADHD experienced more severe FSS than a general population-based sample (18.80% vs. 2.11%). Severe FSS were associated with increased psychopathology and impaired daily function and lower HRQoL. Level of baseline FSS did not moderate the effect of parent training on ADHD. FSS in preschool children with ADHD is associated with impaired daily functioning, but further research is warranted to determine the clinical impact of FSS in children with ADHD.

What matters and influence resuscitation preference? Development, field testing, and structural validation of items among older patients in the emergency department.

BACKGROUND: Decisions about resuscitation preference is an essential part of patient-centered care but a prerequisite is having an idea about which questions to ask and understand how such questions may be clustered in dimensions. The European Resuscitation Council Guidelines 2021 encourages resuscitation shared decision making in emergency care treatment plans and needs and experiences of people approaching end-of-life have been characterized within the physical, psychological, social, and spiritual dimensions. We aimed to develop, test, and validate the dimensionality of items that may influence resuscitation preference in older Emergency Department (ED) patients. METHODS: A 36-item questionnaire was designed based on qualitative interviews exploring what matters and what may influence resuscitation preference and existing literature. Items were organized in physical, psychological, social, and spiritual dimensions. Initial pilot-testing to assess content validity included ten older community-dwelling persons. Field-testing, confirmatory factor analysis and post-hoc bifactor analysis was performed on 269 older ED patients. Several model fit indexes and reliability coefficients (explained common variance (ECV) and omega values) were computed to evaluate structural validity, dimensionality, and model-based reliability. RESULTS: Items were reduced from 36 to 26 in field testing. Items concerning religious beliefs from the spiritual dimension were misunderstood and deemed unimportant by older ED patients. Remaining items concerned physical functioning in daily living, coping, self-control in life, optimism, overall mood, quality of life and social participation in life. Confirmatory factor analysis displayed poor fit, whereas post-hoc bifactor analysis displayed satisfactory goodness of fit (χ2 =562.335 (p<0.001); root mean square error of approximation=0.063 (90% CI [0.055;0.070])). The self-assessed independence may be the bifactor explaining what matters to older ED patients' resuscitation preference. CONCLUSIONS: We developed a questionnaire and investigated the dimensionality of what matters and may influence resuscitation preference among older ED patients. We could not confirm a spiritual dimension. Also, in bifactor analysis the expected dimensions were overruled by an overall explanatory general factor suggesting independence to be of particular importance for clinicians practicing resuscitation discussions in EDs. Studies to investigate how independence may relate to patients' choice of resuscitation preference are needed.

Efficacy of internet-delivered acceptance and commitment therapy for severe health anxiety: results from a randomized, controlled trial.

BACKGROUND: Health anxiety is common, disabling and costly due to patients' extensive use of health care services. Internet-delivered treatment may overcome barriers of accessibility to specialized treatment. We aimed to evaluate the efficacy of internet-delivered acceptance and commitment therapy (iACT). METHODS: A randomized, controlled trial of iACT versus an internet-delivered discussion forum (iFORUM), performed in a Danish university hospital setting. Patients self-referred and underwent video-diagnostic assessment. Eligible patients (≥18 years) with health anxiety were randomized to 12 weeks of intervention. The randomization was blinded for the assessor. The primary outcome was between-group unadjusted mean differences in health anxiety symptoms measured by the Whiteley-7 Index (WI-7, range 0-100) from baseline to 6-month follow-up (6-MFU) using intention to treat and a linear mixed model. The study is registered at clinicaltrials.gov, number NCT02735434. RESULTS: A total of 151 patients self-referred, and 101 patients were randomized to iACT (n = 53) or iFORUM (n = 48). A mean difference in change over time of 19.0 points [95% confidence interval (CI) 10.8-27.2, p < 0.001] was shown on the WI-7, and a large standardized effect size of d = 0.80 (95% CI 0.38-1.23) at 6-MFU. The number needed to treat was 2.8 (95% CI 1.8-6.1, p < 0.001), and twice as many patients in iACT were no longer clinical cases (35% v. 16%; risk ratio 2.17, 95% CI 1.00-4.70, p = 0.050). Adverse events were few and insignificant. CONCLUSIONS: iACT for health anxiety led to sustained effects at 6-MFU. The study contributes to the development of easily accessible treatment options and deserves wider application.

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.

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

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

What brings meaning to life in a highly secular society? A study on sources of meaning among Danes.

This study presents psychometric properties of the Danish version of the Sources of Meaning and Meaning in Life Scale (SoMe-Da) and associations to socio-demographic and religious characteristics. Participants were 554 Danes, 66% women ranging in age between 15 and 91 years. Exploratory factor analysis (EFA) suggested a five factor structure for the 26 sources if meaning. Construct validity within the SoMe-Da and between mental health variables were established. Generativity associated most strongly with meaningfulness followed by spirituality, attentiveness, and explicit religiosity. We found religious characteristics to be more strongly associated with meaningfulness than socio-demographic variables. Finally, we found distinct patterns of preferred sources of meaning between Christians, agnostics, and atheists. Christians and agnostics seemed to be more motivated by self-transcendance, whereas atheists may be more motivated by self-actualization. Results indicate that the SoMe-Da appears to be a valid instrument for measuring the content and degree of personal meaning in life.

Health anxiety symptoms in children and adolescents diagnosed with OCD.

Health anxiety (HA) is an overlooked area in paediatric research. Little is known about the occurrence of HA symptoms in a child and adolescent psychiatric setting, and there are no age-appropriate diagnostic criteria and only limited number of assessment tools. It is therefore likely that HA is seen as part of obsessive-compulsive disorder (OCD) due to construct overlap and the diagnostic uncertainty of HA in this age group. In the present study, the extent of HA symptoms was investigated in 94 children and adolescents with a primary ICD-10 diagnosis of OCD. Self-reported HA symptoms were assessed using the Childhood Illness Attitude Scales. Clinician-rated OCD symptoms and severity were measured using the Children's Yale Brown Obsessive Compulsive Scale. Information on socio-demographics was obtained from the child's/adolescent's medical record. The distribution of HA symptoms resembled a normal curve shifted to the right compared with a normal population of Danish children, and 30 % presented with high HA symptoms. Chi-squared tests were used to examine the proportion of children and adolescents with high HA symptoms in relation to various clinical characteristics. Clinician-rated illness worries and comorbid anxiety disorder were associated with high self-reported HA symptoms. The results contribute to the understanding of how HA and OCD overlap conceptually in young patients and bring attention to the need for improved recognition of OCD patients dominated by illness worries. Further research in the description of childhood HA is important in order to understand whether HA is a distinct disorder early in life.

Effects of maternal health anxiety on children's health complaints, emotional symptoms, and quality of life.

Little is known about family risk factors and intergenerational transmission of psychological disturbance in the development of health anxiety (HA). This study investigated HA and related concepts in 8- to 17-year-old children who had been exposed to different maternal health status. Using a family case-control design, three family groups were included: (1) 50 case children of mothers with severe (HA); (2) 49 control children of mothers with rheumatoid arthritis (RA); and (3) 51 control children of healthy mothers. Children and mothers completed a battery of standardised questionnaires. Case children reported significantly higher level of HA symptoms than children of mothers with RA but not compared to children of healthy mothers. There was no significant difference between the children's self-reports in the three groups with regard to anxiety symptoms in general, physical complaints, or quality of life. In contrast, mothers with HA reported their children as having more emotional and physical symptoms than mothers in one or both control groups. Compared to mothers with RA but not healthy mothers, mothers with HA also reported more visits to the general practitioner with their children during the past year. The findings suggest that maternal HA only weakly affects children's own report of HA and thereby may not be a strong risk factor for the development of HA symptoms in childhood. However, mothers with severe HA seem to conceive their children as more ill and present them more often in the health care system which could, therefore, be an important target for intervention in adult patients.

Exploring the interplay between psychotic experiences, functional somatic symptoms and health anxiety in childhood and adolescence - A longitudinal cohort study.

BACKGROUND: Similarities exist between contemporary explanatory models underlying psychosis development, functional somatic symptoms, and health anxiety. The current study aimed to examine the potential interplay between psychotic experiences (and alternate measures of anomalous self-experiences and aberrant attribution of salience) and functional somatic symptoms on the outcome of health anxiety in youths. METHODS: In a prospective general-population birth cohort, the Copenhagen Child Cohort 2000 (CCC2000), data from two time-points were available for 1122 individuals. We assessed the associations between psychotic experiences and functional somatic symptoms with health anxiety both cross-sectionally at ages 11- and 16-years, and longitudinally from age 11 to 16. Further, we examined if there was an interaction between these two domains on the outcome of health anxiety using the interaction contrast ratio. RESULTS: Functional somatic symptoms and psychotic experiences were strongly cross-sectionally associated with health anxiety at both ages 11 and 16, even after adjustment for general psychopathology. In the longitudinal analyses, functional somatic symptoms, and psychotic experiences at age 11 were not individually associated with health anxiety at age 16 but having both functional somatic symptoms and psychotic experiences was: odds ratio 3.90, 95%CI 1.7-8.9, with suggestion of evidence for interaction beyond the additive effects. This association was attenuated after adjustment for general psychopathology: odds ratio 2.6, 95 % CI 1.0-6.4. CONCLUSION: The strong associations between the domains support the idea of possible overlapping mechanisms underlying psychotic experiences, functional somatic symptoms, and health anxiety.

A Phase 1b PK/PD Study to Demonstrate Antigen Elimination with RLYB212, a Monoclonal Anti-HPA-1a Antibody for FNAIT Prevention.

BACKGROUND: Fetal and neonatal alloimmune thrombocytopenia (FNAIT) is a rare bleeding disorder of the fetus/newborn caused by development of maternal alloantibodies against fetal human platelet antigens (HPAs), predominantly HPA-1a. Currently there are no treatments available to prevent maternal alloimmunization to HPAs or FNAIT. METHODS: This proof-of-concept study (EudraCT Number: 2021-005380-49) was designed to assess the ability of subcutaneous (SC) RLYB212, a monoclonal anti-HPA-1a antibody, to eliminate HPA-1a-positive platelets in an antigen challenge model of a 30 mL fetal-maternal hemorrhage. Subjects were randomized to receive a single SC dose of RLYB212 or placebo on day 1 in a single-blinded manner, followed by transfusion of 10 × 109 HPA-1a-positive platelets on day 8. RESULTS: Four subjects received 0.09 mg SC RLYB212, five received 0.29 mg SC RLYB212, and two received placebo. RLYB212 achieved rapid elimination of HPA-1a-positive platelets in a concentration-dependent manner, with concentrations as low as 3.57 ng/mL meeting the prespecified proof-of-concept criterion of ≥90% reduction in platelet elimination half-life versus placebo. Following HPA-1a-positive platelet transfusion, a rapid decline was observed in the concentration of RLYB212 over a period of 2 to 24 hours, corresponding to the time needed for RLYB212 to bind to ∼10% of HPA-1a on cell surfaces. RLYB212 was well tolerated with no reports of drug-related adverse events. CONCLUSION: The data from this study are consistent with preclinical efficacy data and support the potential use of RLYB212 as a prophylactic treatment for FNAIT that prevents maternal HPA-1a alloimmunization during at-risk pregnancies.

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.

Persistence of protective anti-poliovirus antibody levels in 4-year-old children previously primed with Picovax®, a trivalent, aluminium-adjuvanted reduced dose inactivated polio vaccine.

BACKGROUND: To meet the demand for effective and affordable inactivated polio vaccines (IPVs), a reduced dose, aluminium hydroxide (Al(OH)3)-adjuvanted IPV vaccine was developed (IPV-Al, Picovax®) and evaluated in clinical trials. The present trial is an extension of two previous trials (a primary and a booster trial). The aim was to evaluate the persistence of seroprotective antibodies (poliovirus type-specific antibody titre ≥ 8) in 4-year-old children who previously received IPV-Al as primary and booster vaccine doses and to determine the potential booster response and safety profile of an additional dose of IPV-Al. METHODS: Children participating in the two previous trials were invited to receive one additional dose of IPV-Al at 4 years of age (2.5 years after the booster dose) and to have their blood samples collected to measure the pre- and post-vaccination antibody titres. Systemic adverse events (AEs) and local reactogenicity were recorded. RESULTS: At study entry, the seroprotection rates were 89.2%, 100% and 91.1% against poliovirus type 1, 2 and 3, respectively. The additional vaccination with IPV-Al boosted the level of poliovirus type 1, 2 and 3 antibodies to above the seroprotection threshold for all but one subject, i.e., 99.4% for type 1 and 100% for types 2 and 3. The additional dose induced a robust booster response of a 26.3-, 13.9- and 30.9-fold increase in titre for poliovirus types 1, 2 and 3, respectively. The vaccine was well tolerated, with only mild and transient AEs reported. CONCLUSIONS: The present trial demonstrated that the primary vaccination with an aluminium-adjuvanted reduced dose IPV induced a persistent immune memory as evidenced by the robust anamnestic response when the subjects were re-exposed to the antigen 2.5 years after the last dose. Thus, the IPV-Al is an efficient and safe addition to increase the availability of inactivated polio vaccines globally. (ClinicalTrials.gov reg no. NCT04448132).

Self-Rated Executive Function and Health-Related Quality of Life in Young Adults With Persistent Post-Concussion Symptoms: A Cross-Sectional Study.

OBJECTIVE: To assess self-reported executive dysfunction in young adult patients with persistent post-concussion symptoms (PCS) 2-6 months post-injury, and the association with self-reported Health-Related Quality of Life (HRQoL). METHOD: This cross-sectional study carried out in a hospital setting was a secondary analysis of data from a separate randomized trial testing the effect of a novel intervention, "Get going After concussIoN " (GAIN), for persistent PCS. Patients (18-30 years) were recruited from a clinical cohort of patients with a hospital diagnosis of concussion or referred by primary care physicians. Main measures were The Behaviour Rating Inventory of Executive Function-Adult Version providing two index scores, that is, the Metacognitive Index (MI) and the Behavioural Regulation Index (BRI), and the Quality of Life after Brain Injury-Overall Scale. RESULTS: Compared with normative data, patients had elevated scores (i.e., worse functioning) on both the MI and the BRI. In linear regression analysis, the MI score, but not the BRI score, was negatively associated with self-reported HRQoL (MI: slope = -.27, 95% confidence interval, CI [-.53, -.02], p = .03; BRI: slope = -.19, 95% CI [-.49, .13], p = .24), suggesting a positive association of subjective executive dysfunction and lower HRQoL. However, the association was attenuated after adjustment for self-reported psychological distress (MI: slope = -.09, 95% CI [-.34, .17], p = .51). CONCLUSION: Self-reported executive dysfunction is common in young adult patients with persistent PCS, but not strongly associated with decreased HRQoL after adjusting for concurrent psychological distress.

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.

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

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

Novel interdisciplinary intervention, GAIN, vs. enhanced usual care to reduce high levels of post-concussion symptoms in adolescents and young adults 2-6 months post-injury: A randomised trial.

BACKGROUND: Evidence for effective interventions to prevent long-term sequelae after concussion is sparse. This study aimed to test the efficacy of Get going After concussIoN (GAIN), an interdisciplinary, individually-tailored intervention of 8 weeks duration based on gradual return to activities and principles from cognitive behavioural therapy. METHODS: We conducted an open-label, parallel-group randomised trial in a hospital setting in Central Denmark Region. Participants were 15-30-year-old patients with high levels of post-concussion symptoms (PCS) 2-6 months post-concussion (i.e., a score ≥20 on the Rivermead Post-concussion Symptoms Questionnaire (RPQ)). They were randomly assigned (1:1) to either enhanced usual care (EUC) or GAIN+EUC. Masking of participants and therapists was not possible. The primary outcome was change in RPQ-score from baseline to 3-month FU. All analyses were done on an intention-to-treat basis using linear mixed-effects models. This trial is registered with ClinicalTrials.gov, number NCT02337101. FINDINGS: Between March 1, 2015, and September 1, 2017, we included 112 patients. Patients allocated to GAIN+EUC (n=57) reported a significantly larger reduction of PCS than patients allocated to EUC (n=55) with a mean adjusted difference in improvement of 7·6 points (95% confidence interval (CI) 2·0-13·1, p=0·008), Cohen's d=0·5 (95% CI 0·1-0·9). Number needed to treat for prevention of one additional patient with RPQ ≥20 at 3-month FU was 3·6 (95% CI 2·2-11·3). No adverse events were observed. INTERPRETATION: Compared with EUC, GAIN+EUC was associated with a larger reduction of post-concussion symptoms at 3-month FU. FUNDING: Central Denmark Region and the foundation "Public Health in Central Denmark Region - a collaboration between municipalities and the region".

Impact of functional somatic symptoms on 5-7-year-olds' healthcare use and costs.

OBJECTIVE: Knowledge about childhood functional somatic symptoms (FSS) and healthcare costs is scarce. This study aims to assess whether FSS in children aged 5-7 years are associated with increased future primary healthcare. DESIGN: At baseline of the observational cohort study, between years 2005 and 2007, 1327 children from the Copenhagen Child Cohort were assessed at ages 5-7 years for FSS and chronic physical diseases using the Soma Assessment Interview. Information on primary healthcare use was obtained from the National Health Insurance Service Register, and measured as the price of all medical services outside the hospital during a 4.5-year follow-up period from the day of assessment. Regression with bootstrap bias-corrected and accelerated CIs were performed. RESULTS: 1018 (76.8%) children had no FSS with primary healthcare use adjusted for other child health problems, maternal education and family changes of €448.2, 388.2-523.8 and number of face-to-face contacts: 11.90, 10.71-13.25; 250 (18.9%) had FSS with healthcare use €441.0, 355.0-550.3 and face-to-face contacts: 11.22, 9.60-12.91, and 58 (4.4%) had impairing FSS with healthcare use: €625.9, 447.9-867.8 and face-to-face contacts: 14.65, 11.20-19.00. In unadjusted regression analysis, impairing FSS were associated with increased healthcare use (increased costs: €246.0, 67.6-494.3). The adjusted association was slightly attenuated (increased costs: €177.8, 1.3-417.0). CONCLUSIONS: Impairing FSS in children aged 5-7 years is a predictor for the child's future primary healthcare use. More research on complex predictive models is needed to further explore the clinical significance of these results, and to contribute to the underpinning of early interventions towards impairing FSS in children.

The effect of a lay-led, group-based self-management program for patients with chronic pain: a randomized controlled trial of the Danish version of the Chronic Pain Self-Management Programme.

The Stanford Chronic Pain Self-Management Programme (CPSMP) consists of 6 2½-hour weekly workshops focusing on how to manage pain in daily life. The workshops are facilitated by 2 workshop leaders of whom at least 1 must suffer from a long-term pain condition. The program is highly structured and manualized. Only few controlled trials testing the effect of CPSMP exist. Enrolled in the study were 424 adults from 19 Danish municipalities, (72% women; age: 25-93 years) with pain of any etiology and great variation in pain history (0-50 yrs). Of these, 216 were randomized to a lay-led version of the CPSMP. The primary outcome was pain-related disability. Secondary outcomes were pain, pain catastrophizing, self-efficacy, emotional distress, physical symptoms, and illness worry. Outcomes were measured before randomization, immediately after the CPSMP (response rate: 94%), and at 3-month follow-up (response rate: 92%). National register data on health expenditure were obtained to examine effects on health care use. ClinicalTrials.gov Identifier: NCT01306747. The CPSMP had no effect on the primary outcome pain-related disability or on health expenditure during intervention and follow-up period. Small positive effects on emotional distress and illness worry 3 months after CPSMP were observed. Lay-led CPSMP is not recommended as treatment for chronic pain-related disability. This heterogeneous group of patients with pain did not benefit from the CPSMP except for a small, but clinically insignificant improvement in psychological well-being.

Health anxiety by proxy in women with severe health anxiety: A case control study.

Health anxiety (HA) refers to excessive worries and anxiety about harbouring serious illness based on misinterpretation of bodily sensations or changes as signs of serious illness. Severe HA is associated with disability and high health care costs. However, the impact of parental HA on excessive concern with their children's health (health anxiety by proxy) is scantly investigated. The aim of this study is to investigate HA by proxy in mothers with severe HA. Fifty mothers with severe HA and two control groups were included, i.e. mothers with rheumatoid arthritis (N=49) and healthy mothers (N=51). All participants completed self-report questionnaires on their own HA and illness perceptions and on illness worries and illness behaviour related to their children. The results showed that mothers with severe HA reported significantly more negative illness perceptions and more HA on behalf of their child (i.e. by proxy) compared to both control groups. HA by proxy may be an overlooked treatment target in mothers with severe HA, and improving our understanding of this condition can have important preventive and clinical implications.