Acceptance and Commitment group Therapy for patients with multiple functional somatic syndromes: a three-armed trial comparing ACT in a brief and extended version with enhanced care.

BACKGROUND: Psychological treatment for functional somatic syndromes (FSS) has been found moderately effective. Information on how much treatment is needed to obtain improvement is sparse. We assessed the efficacy of a brief and extended version of group-based Acceptance and Commitment Therapy (ACT) v. enhanced care (EC) for patients with multiple FSS operationalised as Bodily Distress Syndrome multi-organ type. METHODS: In a randomised controlled three-armed trial, consecutively referred patients aged 20-50 with multiple FSS were randomly assigned to either (1) EC; (2) Brief ACT: EC plus 1-day workshop and one individual consultation; or (3) Extended ACT: EC plus nine 3-h group-based sessions. Primary outcome was patient-rated overall health improvement on the five-point clinical global improvement scale 14 months after randomisation. A proportional odds model was used for the analyses. RESULTS: A total of 180 patients were randomised; 60 to EC, 61 to Brief ACT, and 59 to Extended ACT. Improvement on the primary outcome after Extended ACT was significantly greater than after EC with an unadjusted OR of 2.9 [95% CI (1.4-6.2), p = 0.006]. No significant differences were found between Brief ACT and EC. Of the 18 secondary outcomes, the only significant difference found was for physical functioning in the comparison of Extended ACT with EC. CONCLUSIONS: Patients rated their overall health status as more improved after Extensive ACT than after EC; however, clinically relevant secondary outcome measures did not support this finding. Discrepancies between primary and secondary outcomes in this trial are discussed.

Precollision Medical Diagnoses Predict Chronic Neck Pain Following Acute Whiplash Trauma.

OBJECTIVES: The reason why some individuals develop chronic symptoms, whiplash-associated disorder, following whiplash trauma is poorly understood. We explored whether precollision pain-related diagnoses, medically unexplained symptoms, and psychiatric diagnoses are related to whiplash-associated disorder. MATERIALS AND METHODS: A cohort of 719 individuals exposed to whiplash trauma and subsequently experiencing symptoms within 72 hours (whiplash-exposed cohort) and 3595 matched controls were included in this observational prospective study. At 12 months postcollision, the whiplash-exposed cohort rated their neck pain using the Visual Analog Scale. Data on health were obtained from the Danish National Patient Register for the whiplash-exposed cohort and for the controls for a 5-year period before collision. RESULTS: The whiplash-exposed cohort had significantly increased incidences of precollision pain-related diagnoses: χ(1)=17.42, P<0.001 and medically unexplained symptoms: χ(1)=22.2, P<0.001 but not psychiatric diagnoses: χ(1)=3.60, P>0.05 compared with controls in the 5-year period. Participants from the whiplash-exposed cohort with precollision pain-related diagnoses (odds ratio=2.46; 95% confidence interval, 1.39; 4.35) and medically unexplained symptoms (odds ratio, 1.72; 95% confidence interval, 1.04; 2.84) had significantly increased odds for neck pain at follow-up. DISCUSSION: Precollision pain and medically unexplained symptoms predict chronic neck pain following whiplash trauma. This may indicate that a sensitization process was initiated before the collision or that individuals with precollision low threshold for contacting health care services maintain this behavior postcollision. The collision may trigger existing individual vulnerabilities that constitute to be a risk factor for chronic whiplash.

The use of prescription medication in 239 patients with multiple functional somatic syndromes.

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.

Intervening variables in group-based acceptance & commitment therapy for severe health anxiety.

OBJECTIVE: The present study is based on a previously reported successful randomized controlled trial (RCT) on Acceptance and Commitment Group therapy (ACT-G) for severe health anxiety (HA) and investigates intervening variables of ACT for HA. The process primarily targeted by ACT is psychological flexibility (PF). No randomized study has yet examined the possible intervening variables of ACT for HA. METHODS: 126 patients diagnosed with severe HA were enrolled in the RCT of which 107 were included in the analyses. The outcome measure was illness worry (Whiteley Index) and included process variables were PF and facets of mindfulness. RESULTS: Statistically significant indirect effects (IE) of ACT-G on the outcome of illness worry 6 months after treatment were found for PF (IE = -5.5, BCa 99% CI -12.3;-1.2) and one mindfulness subscale, namely 'non-react' (IE = -6.5 BCa 99% CI -15.3: 1.0). CONCLUSION: In line with the ACT model of change, PF may have a small to moderate IE on decrease in illness worry. Of the mindfulness scales, only 'non-react' showed a significant IE. Although tentative, due to no active comparison control condition, these results support that PF is a intervening variable in ACT treatment aimed at reducing illness worry in patients with severe HA.

Long-term economic evaluation of cognitive-behavioural group treatment versus enhanced usual care for functional somatic syndromes.

OBJECTIVE: Patients with functional somatic syndromes (FSS) such as fibromyalgia and chronic fatigue syndrome have a poor outcome and can incur high healthcare and societal costs. We aimed to compare the medium-term (16months) cost-effectiveness and the long-term (40months) economic outcomes of a bespoke cognitive-behavioural group treatment (STreSS) with that of enhanced usual care (EUC). METHODS: We obtained complete data on healthcare and indirect costs (i.e. labour marked-related and health-related benefits) from public registries for 120 participants from a randomised controlled trial. Costs were calculated as per capita public expenses in 2010 €. QALYs gained were estimated from the SF-6D. We conducted a medium-term cost-effectiveness analysis and a long-term cost-minimization analysis from both a healthcare (i.e. direct cost) and a societal (i.e. total cost) perspective. RESULTS: In the medium term, the probability that STreSS was cost-effective at thresholds of 25,000 to 35,000 € per QALY was 93-95% from a healthcare perspective, but only 50-55% from a societal perspective. In the long term, however, STreSS was associated with increasing savings in indirect costs, mainly due to a greater number of patients self-supporting. When combined with stable long-term reductions in healthcare expenditures, there were total cost savings of 7184 € (95% CI 2271 to 12,096, p=0.004) during the third year after treatment. CONCLUSION: STreSS treatment costs an average of 1545 €. This cost was more than offset by subsequent savings in direct and indirect costs. Implementation could both improve patient outcomes and reduce costs.

Imipramine versus placebo for multiple functional somatic syndromes (STreSS-3): a double-blind, randomised study.

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.

Long-term consequences of severe health anxiety on sick leave in treated and untreated patients: Analysis alongside a randomised controlled trial.

Health anxiety (HA) is prevalent and costly for health services. However, little is known about the full societal burden of HA. Based on complete register data, we (1) compared weeks on sickness-related benefits (SB) in untreated patients with severe HA (n=126) with a matched population sample (n=12,600); and (2) tested whether Acceptance & Commitment group Therapy (ACT-G) (n=63) reduced weeks on SB during the first year after randomisation compared to a waitlist (n=63). We found that (1) HA patients showed a six-monthly increment of 2 weeks on SB compared with the general population (p<0.0001), and (2) that ACT-G and the waitlist showed no difference in their ability to reduce SB during the first year (p=0.246). We conclude that HA is associated with a considerable societal burden. A possible beneficial effect of psychotherapy on SB needs further investigation.

Optimizing colour quality of modified atmosphere packed sliced meat products by control of critical packaging parameters.

To study the influence of different packaging and storage parameters on the colour stability of modified atmosphere packed, cured, cooked ham, a multiplicative analysis of variance model (GEMANOVA) was developed. The critical parameters investigated were % residual-O(2), product to headspace volume ratio (P/H volume ratio), temperature, light intensity and oxygen transmission rate (OTR). The model illustrated that all the investigated parameters interacted, but especially % residual-O(2) and P/H volume ratio - i.e., the absolute O(2) content, influenced the degree of discoloration. The complex interactions of the parameters justified the selected model, as it emphasised the necessity of evaluating the parameters simultaneously instead of considering them individually. The importance of absolute O(2) content was further validated through an industrial experiment including three different kinds of sliced meat products.