Fibromyalgia is a chronic pain condition associated with substantial suffering and societal costs. Traditional cognitive behavior therapy (T-CBT) is the most evaluated psychological treatment, but ...exposure therapy (Exp-CBT) has shown promise with a pronounced focus on the reduction of pain-related avoidance behaviors. In a recent randomized controlled trial (N = 274), we found that Exp-CBT was not superior to T-CBT (d = −0.10) in reducing overall fibromyalgia severity. This study investigated pain-related avoidance behaviors, pain catastrophizing, hypervigilance, pacing, overdoing and physical activity as potential mediators of the treatment effect. Mediation analyses were based on parallel process growth models fitted on 11 weekly measurement points, and week-by-week time-lagged effects were tested using random intercepts cross-lagged panel models. Results indicated that a reduction in avoidance behaviors, pain catastrophizing, and hypervigilance were significant mediators of change in both treatments. An increase in pacing and a reduction in overdoing were significant mediators in T-CBT only. Physical activity was not a mediator. In the time-lagged analyses, an unequivocal effect on subsequent fibromyalgia severity was seen of avoidance and catastrophizing in Exp-CBT, and of overdoing in T-CBT. Exposure-based and traditional CBT for fibromyalgia appear to share common treatment mediators, namely pain-related avoidance behavior, catastrophizing and hypervigilance.
•Mediators in exposure-based and traditional CBT for fibromyalgia were studied.•Three of them were significant mediators in both treatments.•These were pain-related avoidance behavior, hypervigilance and pain catastrophizing.•Pacing and overdoing were mediators in traditional CBT only.•Exposure-based and traditional CBT for fibromyalgia appear to share common mediators.
Analyses of circulating metabolites in large prospective epidemiological studies could lead to improved prediction and better biological understanding of coronary heart disease (CHD). We performed a ...mass spectrometry-based non-targeted metabolomics study for association with incident CHD events in 1,028 individuals (131 events; 10 y. median follow-up) with validation in 1,670 individuals (282 events; 3.9 y. median follow-up). Four metabolites were replicated and independent of main cardiovascular risk factors lysophosphatidylcholine 18∶1 (hazard ratio HR per standard deviation SD increment = 0.77, P-value<0.001), lysophosphatidylcholine 18∶2 (HR = 0.81, P-value<0.001), monoglyceride 18∶2 (MG 18∶2; HR = 1.18, P-value = 0.011) and sphingomyelin 28∶1 (HR = 0.85, P-value = 0.015). Together they contributed to moderate improvements in discrimination and re-classification in addition to traditional risk factors (C-statistic: 0.76 vs. 0.75; NRI: 9.2%). MG 18∶2 was associated with CHD independently of triglycerides. Lysophosphatidylcholines were negatively associated with body mass index, C-reactive protein and with less evidence of subclinical cardiovascular disease in additional 970 participants; a reverse pattern was observed for MG 18∶2. MG 18∶2 showed an enrichment (P-value = 0.002) of significant associations with CHD-associated SNPs (P-value = 1.2×10-7 for association with rs964184 in the ZNF259/APOA5 region) and a weak, but positive causal effect (odds ratio = 1.05 per SD increment in MG 18∶2, P-value = 0.05) on CHD, as suggested by Mendelian randomization analysis. In conclusion, we identified four lipid-related metabolites with evidence for clinical utility, as well as a causal role in CHD development.
Health anxiety is a common and often chronic mental health problem associated with distress, substantial costs, and frequent attendance throughout the health care system. Face-to-face cognitive ...behavior therapy (CBT) is the criterion standard treatment, but access is limited.
To test the hypothesis that internet-delivered CBT, which requires relatively little resources, is noninferior to face-to-face CBT in the treatment of health anxiety.
This randomized noninferiority clinical trial with health economic analysis was based at a primary care clinic and included patients with a principal diagnosis of health anxiety who were self-referred or referred from routine care. Recruitment began in December 10, 2014, and the last treatment ended on July 23, 2017. Follow-up data were collected up to 12 months after treatment. Analysis began October 2017 and ended March 2020.
Patients were randomized (1:1) to 12 weeks of internet-delivered CBT or to individual face-to-face CBT.
Change in health anxiety symptoms from baseline to week 12. Analyses were conducted from intention-to-treat and per-protocol (completers only) perspectives, using the noninferiority margin of 2.25 points on the Health Anxiety Inventory, which has a theoretical range of 0 to 54.
Overall, 204 patients (mean SD age, 39 12 years; 143 women 70%) contributed with 2386 data points on the Health Anxiety Inventory over the treatment period. Of 204 patients, 102 (50%) were randomized to internet-delivered CBT, and 102 (50%) were randomized to face-to-face CBT. The 1-sided 95% CI upper limits for the internet-delivered CBT vs face-to-face CBT difference in change were within the noninferiority margin in the intention-to-treat analysis (B = 0.00; upper limit: 1.98; Cohen d = 0.00; upper limit: 0.23) and per-protocol analysis (B = 0.01; upper limit: 2.17; Cohen d = 0.00; upper limit: 0.25). The between-group effect was not moderated by initial symptom level, recruitment path, or patient treatment preference. Therapists spent 10.0 minutes per patient per week in the online treatment vs 45.6 minutes for face-to-face CBT. The net societal cost was lower in the online treatment (treatment period point difference: $3854). There was no significant group difference in the number of adverse events, and no serious adverse event was reported.
In this trial, internet-delivered CBT appeared to be noninferior to face-to-face CBT for health anxiety, while incurring lower net societal costs. The online treatment format has potential to increase access to evidence-based treatment for health anxiety.
ClinicalTrials.gov Identifier: NCT02314065.
Fibromyalgia is a debilitating pain condition for which treatment effects are typically modest. The most evaluated psychological treatment is traditional cognitive behavior therapy (T-CBT), but ...promising effects have recently been seen in exposure-based cognitive behavior therapy (Exp-CBT). We investigated whether Exp-CBT was superior to T-CBT in a randomized controlled trial. Self-referred participants with fibromyalgia (N = 274) were randomized (1:1) to 10 weeks of Exp-CBT or T-CBT. Treatments were delivered online and presented as "CBT for fibromyalgia." Participants were assessed at baseline, weekly during treatment, posttreatment, and at 6- and 12-month follow-up. Primary outcome was the difference in reduction in fibromyalgia severity as measured using the Fibromyalgia Impact Questionnaire (FIQ) over 11 assessment points from baseline to posttreatment, modelled within an intention-to-treat framework using linear mixed effects models fitted on multiple imputed data. Approximately 91% of weekly FIQ scores were collected over the main phase. There was no significant difference between Exp-CBT and T-CBT in the mean reduction of fibromyalgia severity from pretreatment to posttreatment (b = 1.3, 95% CI -3.0 to 5.7, P = 0.544, d = -0.10). Minimal clinically important improvement was seen 60% in Exp-CBT vs 59% in T-CBT. Effects were sustained up to 12 months posttreatment. This well-powered randomized trial indicated that Exp-CBT was not superior to T-CBT for fibromyalgia. Both treatments were associated with a marked reduction in fibromyalgia severity, and the online treatment format might be of high clinical utility. T-CBT can still be regarded a reference standard treatment that remains clinically relevant when compared to novel treatment approaches.
Background
A recent randomized controlled trial (N = 140) was indicative of large and sustained average improvements of Internet‐based exposure for fibromyalgia, as compared to a waitlist. However, ...little is known about who benefits the most from this treatment.
Objectives
To test for potential moderating effects of age, educational attainment, the duration of fibromyalgia, baseline overall fibromyalgia severity, pain intensity, fibromyalgia‐related avoidance behaviour and symptom preoccupation on the waitlist‐controlled effect of 10 weeks of Internet‐based exposure for fibromyalgia.
Methods
Secondary analysis of a randomized controlled trial (ClinicalTrials.gov NCT02638636). We used linear mixed effects models to determine whether the waitlist‐controlled effect of exposure therapy on overall fibromyalgia severity (Fibromyalgia Impact Questionnaire) differed as a function of the potential moderators.
Results
Only pain intensity (0–10) was found to be a significant moderator, where a higher baseline pain intensity predicted a more limited waitlist‐controlled effect of Internet‐based exposure (B = 3.48, 95% CI: 0.84–6.13). Standardized point estimates of effects were small for the sociodemographic variables, and in the moderate range for some clinical variables that did not reach statistical significance such as behavioural avoidance and time with the fibromyalgia diagnosis.
Conclusions
Results suggest that Internet‐based exposure treatment was more useful for participants with lower baseline levels of pain, and less so for participants with higher baseline levels of pain. The treatment had relatively similar effects across the other tested moderators.
Significance
This study evaluated potential effect moderators in exposure‐based treatment for fibromyalgia. Results indicated that a higher level of pain intensity at baseline was predictive of a less favourable outcome. It may be extra important to monitor progression for these patients and to provide additional therapeutic support when needed.
•The heritability for bipolar disorder was 60% using a novel statistical approach taking into account available time of follow-up, and controlling for sex and year of birth.•The heritability was ...similar to previous family studies performed on the Swedish register data, using traditional twin-modeling methods, indicating that previous methodology have been sufficient.•We detected no influence from common environmental factors in our heritability analysis, due to lack of power. Future studies using transnational twin cohorts to expand the sample-size are needed.•The prevalence for bipolar disorder was higher in females, but genetic factors did not contribute to those sex-differences.
Twin- and family studies have shown variations in the heritability estimates of bipolar disorder (BPD). The current study uses an updated statistical methodology for heritability estimation in BPD by taking available time of follow-up into account while controlling for co-variates. We identified monozygotic and dizygotic same and different sex twins with BPD (n = 804) or unaffected from BPD (n = 91,604) from the Swedish Twin Register and the National Patient Register. We applied structural equational modeling with inversed probability weighting to estimate the heritability, taking into account censoring and truncation of data. Sex-limitation models were constructed to analyze qualitative or quantitative sex-differences in BPD. Heritability for BPD was 60.4% (95% Confidence Interval: 50.3–70.5) after age, sex, left-hand truncation and censoring of the data was taken into account. A larger proportion of females were affected from BPD (females 62.2%; males 37.8%, p < 0.001), but no sex-difference in BPD heritability was found, nor any sex-specific genetic effects. We demonstrated a robust 60% heritability for BPD with no evidence of sex-specific genetic effects on disease liability.
Depression is common in primary care, and most patients prefer psychological treatment over pharmacotherapy. Cognitive behaviour therapy (CBT) is an effective treatment, but there are gaps in current ...knowledge about CBT in the primary care context, especially with regard to long-term effects and the efficacy of specific delivery formats. This is an obstacle to the integration of primary care and specialist psychiatry. We conducted a systematic review and meta-analysis of randomised controlled trials of CBT for primary care patients with depression to investigate the effect of CBT for patients with depression in primary care. A total of 34 studies, with 2543 patients in CBT and 2815 patients in control conditions, were included. CBT was more effective than the control conditions g = 0.22 (95% confidence interval (CI) 0.15-0.30), and the effect was sustained at follow-up g = 0.17 (95% CI 0.10-0.24). CBT also led to a higher response rate odds ratio (OR) = 2.47 (95% CI 1.60-3.80) and remission rate OR = 1.56 (95% CI 1.15-2.14) than the control conditions. Heterogeneity was moderate. The controlled effect of CBT was significant regardless of whether patients met diagnostic criteria for depression, scored above a validated cut-off for depression, or merely had depressive symptoms. CBT also had a controlled effect regardless of whether the treatment was delivered as individual therapy, group therapy or therapist-guided self-help. We conclude that CBT appears to be effective for patients with depression in primary care, and recommend that patients with mild to moderate depression be offered CBT in primary care.
Vascular endothelial growth factor (VEGF) has been shown to stimulate angiogenesis and myocardial perfusion. The short-term safety of VEGF gene therapy is excellent. However, there are only limited ...results regarding the long-term effects. The Kuopio Angiogenesis Trial (KAT) studied the efficiency and short-term safety of the local VEGF-A(165) gene transfer in 103 patients with coronary artery disease. Three patient groups received either VEGF as an adenoviral (n=37), or as a plasmid/liposome vector (n=28), or as a placebo (n=38), during coronary angioplasty and stenting (percutaneous coronary intervention, PCI)AQ1. The aim of this study was to examine the long-term effects and safety of VEGF gene therapy. Patients were interviewed by telephone or with a questionnaire on their current status of health, coronary and other cardiovascular events and symptoms, working ability, exercise tolerance, other diseases, such as cancer and diabetes, as well as their personal experience of the treatment. Causes of death were clarified from hospital records. The total follow-up time was 8.1 years (range 6.9-9.7 years). Overall 82% of the patients were reached across the study. Eight (7.5%) of the patients died during the follow-up, but there was no significant difference in mortality between the groups (3/32 vs 2/26 vs 3/31 VEGF-adenovirus vs VEGF-plasmid/liposome vs placebo, respectively; P=0.88). The incidence of major adverse cardiovascular events (MACEs) (10 vs 11 vs 15; P=0.85), cancer (1 vs 4 vs 2; P=0.38) or diabetes (2 vs 2 vs 2; P=0.97) did not differ between the groups. Local intracoronary VEGF gene transfer is safe and does not increase the risk of MACE, arrhythmias, cancer, diabetes or other diseases.
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