The impact of integrating emotion focused components into psychological therapy: A randomized controlled trial.

OBJECTIVES: This paper presents a randomized controlled trial on assimilative integration, which is aimed at integrating elements from other orientations within one approach to enrich its conceptual and practical repertoire. Elements from Emotion-Focused Therapy (EFT) were integrated into a form of cognitive behavior therapy: Psychological Therapy (PT). In one treatment condition, EFT was added to PT (+EFT) with the intent to enhance therapists' working with emotions. In the other condition, concepts and interventions based on the socialpsychological self-regulation approach were added to PT (+SR). Our assumption was that the +EFT would lead to greater and deeper change, particularly in the follow-up assessments. METHOD: Patients (n = 104) with anxiety, depression, or adjustment disorders were randomized to the two conditions and treated by 38 therapists who self-selected between the conditions. Primary outcome was symptom severity at 12-month follow-up; secondary outcomes included several measures such as interpersonal problems and quality of life. Variables were assessed at baseline, after 8 and 16 sessions, at posttreatment, and at 6- and 12-month follow-up. RESULTS: Contrary to our hypothesis, no significant between-group effects were found. CONCLUSION: The findings first suggest the difficulty of topping an already very effective approach to psychotherapy. Alternative interpretations were that the EFT training, while corresponding to regular practice in AI, was not sufficient to make a difference in outcome, or that while profiting from the enhancement of abilities for working with emotions, this was outbalanced by negative effects of difficulties related to the implementation of the new elements.

Enriched stable 204Pb as tracer at ultra-low levels in clinical investigations.

The potential of enriched Pb (204Pb) was assessed to monitor pathways of trace levels of Pb in the pg range within the human body via isotope pattern variation in situations where natural lead cannot be used as a tracer due to regulatory limitations. Isotope ratio measurements were accomplished by means of (multi-collector) inductively coupled plasma mass spectrometry including a comparison of single and multi-collector ICP-MS for low-level 204Pb assessment. Isotopic pattern results from a blend of a large quantity of the element with a natural isotopic composition and an enriched stable isotope at orders of magnitude lower levels pose a nontrivial analytical problem. Isotope pattern deconvolution was successfully applied as mathematical tool based on multiple linear regressions. The method allowed for deconvolving the isotope pattern from measured isotope ratios without knowing the quantities of different isotope sources incorporated and mixed into the sample at levels of < 1 pg 204Pb/g blood. The objective of this manuscript is to evaluate and summarize the analytical aspects for Pb isotope pattern deconvolution based on the results of a clinical trial, where a 204Pb-enriched isotope tracer was applied to investigate the bioavailability of orally applied Pb along with purified clinoptilolite tuff as potential supplement. This unique approach allows to reduce tracer amounts to harmless levels to human health, which are in accordance with the legal regulative to study enrichment levels of < 0.01% in human blood.

Bright light therapy as a non-pharmacological treatment option for multiple sclerosis-related fatigue: A randomized sham-controlled trial.

Background: Fatigue is a common symptom in people with multiple sclerosis (pwMS) that significantly impairs quality of life. Bright light therapy may be a cheap treatment option with little to no adverse events. Objectives: To evaluate the effectiveness of bright light therapy as a treatment option for MS-related fatigue. Methods: This was randomized sham-controlled trial including 26 pwMS with a Fatigue Severity Scale (FSS) Score ≥36. Participants were assigned to receive either bright white light therapy (n = 13) or dim red light (sham-intervention; n = 13). Participants used the respective intervention for 30 min each morning for two weeks, followed by a two-week washout period. The primary endpoint was the difference in FSS scores following light treatment as calculated by analysis of covariance. Results: There was no significant difference in FSS (F(1,23) = 2.39, p = .136, partial ⴄ2 = .094). However, FSS scores generally improved over the course of the study in a clinically relevant manner. Conclusion: Bright light therapy decreased FSS scores over the course of this study. However, this effect was not significant in comparison to a sham intervention.

Extensive Brain Pathologic Alterations Detected with 7.0-T MR Spectroscopic Imaging Associated with Disability in Multiple Sclerosis.

Background MR spectroscopic imaging (MRSI) allows in vivo assessment of brain metabolism and is of special interest in multiple sclerosis (MS), where morphologic MRI cannot depict major parts of disease activity. Purpose To evaluate the ability of 7.0-T MRSI to depict and visualize pathologic alterations in the normal-appearing white matter (NAWM) and cortical gray matter (CGM) in participants with MS and to investigate their relation to disability. Materials and Methods Free-induction decay MRSI was performed at 7.0 T. Participants with MS and age- and sex-matched healthy controls were recruited prospectively between January 2016 and December 2017. Metabolic ratios were obtained in white matter lesions, NAWM, and CGM regions. Subgroup analysis for MS-related disability based on Expanded Disability Status Scale (EDSS) scores was performed using analysis of covariance. Partial correlations were applied to explore associations between metabolic ratios and disability. Results Sixty-five participants with MS (mean age ± standard deviation, 34 years ± 9; 34 women) and 20 age- and sex-matched healthy controls (mean age, 32 years ± 7; 11 women) were evaluated. Higher signal intensity of myo-inositol (mI) with and without reduced signal intensity of N-acetylaspartate (NAA) was visible on metabolic images in the NAWM of participants with MS. A higher ratio of mI to total creatine (tCr) was observed in the NAWM of the centrum semiovale of all MS subgroups, including participants without disability (marginal mean ± standard error, healthy controls: 0.78 ± 0.04; EDSS 0-1: 0.86 ± 0.03 [P = .02]; EDSS 1.5-3: 0.95 ± 0.04 [P < .001]; EDSS ≥3.5: 0.94 ± 0.04 [P = .001]). A lower ratio of NAA to tCr was found in MS subgroups with disabilities, both in their NAWM (marginal mean ± standard error, healthy controls: 1.46 ± 0.04; EDSS 1.5-3: 1.33 ± 0.03 [P = .03]; EDSS ≥3.5: 1.30 ± 0.04 [P = .01]) and CGM (marginal mean ± standard error, healthy controls: 1.42 ± 0.05; EDSS ≥3.5: 1.23 ± 0.05 [P = .006]). mI/NAA correlated with EDSS (NAWM of centrum semiovale: r = 0.47, P < .001; parietal NAWM: r = 0.43, P = .002; frontal NAWM: r = 0.34, P = .01; frontal CGM: r = 0.37, P = .004). Conclusion MR spectroscopic imaging at 7.0 T allowed in vivo visualization of multiple sclerosis pathologic findings not visible at T1- or T2-weighted MRI. Metabolic abnormalities in the normal-appearing white matter and cortical gray matter were associated with disability. © RSNA, 2022 Online supplemental material is available for this article. See also the editorial by Barker in this issue.

Insight and the number of completed modules predict a reduction of positive symptoms in an Internet-based intervention for people with psychosis.

Emerging evidence suggests that Internet-based interventions for people with psychosis (ICBTp) are feasible and efficacious. However, predictors of adherence and treatment outcomes are largely unknown. To narrow this research gap, we conducted secondary analyses on data from a randomized controlled trial, which evaluated an eight-week ICBTp intervention targeting topics, such as voice hearing, mindfulness, and others. In n = 100 participants with psychosis, we aimed at identifying sociodemographic, psychopathological, and treatment-related predictor variables of post-treatment symptoms and adherence (i.e., at least four completed modules). We followed a two-stage approach. First, we conducted regression analyses to examine the effect of single candidate predictors on post-treatment symptoms as well as adherence. Subsequently, we selected variables that met a significance threshold of p < .1 and entered them into linear and logistic multiple regression models. Whereas no variable was able to predict adherence, the number of completed modules was negatively associated with self-reported delusion severity at post-treatment. Additionally, higher pre-treatment insight predicted fewer hallucinations after treatment. Because this was one of the first studies to investigate predictors in ICBTp, more research is needed to customize future interventions to the needs of users.

Mindfulness Mediates the Effect of a Psychological Online Intervention for Psychosis on Self-Reported Hallucinations: A Secondary Analysis of Voice Hearers From the EviBaS Trial.

BACKGROUND: Psychological online interventions (POIs) could represent a promising approach to narrow the treatment gap in psychosis but it remains unclear whether improving mindfulness functions as a mechanism of change in POIs. For the present study, we examined if mindfulness mediates the effect of a comprehensive POI on distressing (auditory) hallucinations. METHODS: We conducted a secondary analysis on voice hearers (n = 55) from a randomized controlled trial evaluating a POI for psychosis (EviBaS; trial registration NCT02974400, clinicaltrials.gov). The POI includes a module on mindfulness and we only considered POI participants in our analyses who completed the mindfulness module (n = 16). RESULTS: Participants who completed the mindfulness module reported higher mindfulness (p = 0.015) and lower hallucinations (p = 0.001) at post assessment, compared to controls, but there was no effect on distress by voices (p = 0.598). Mindfulness mediated the POI's effect on hallucinations (b = -1.618, LLCI = -3.747, ULCI = -0.054) but not on distress by voices (b = -0.057, LLCI = -0.640, ULCI = 0.915). LIMITATIONS AND DISCUSSION: Completion of the mindfulness module was not randomized. Hence, we cannot draw causal inferences. Even if we assumed causality, it remains unclear which contents of the POI could have resulted in increased mindfulness and reduced hallucinations, as participants completed other modules as well. In addition, confounding variables could explain the mediation and the sample size was small. Nonetheless, the overall pattern of results indicates that the POI is likely to improve mindfulness, and that increased mindfulness could partially explain the POI's efficacy.

An Internet-Based Compassion-Focused Intervention for Increased Self-Criticism: A Randomized Controlled Trial.

Increased levels of self-criticism and a lack of self-compassion have been associated with the development and maintenance of a range of psychological disorders. In the current study, we tested the efficacy of an online version of a compassion-focused intervention, mindfulness-based compassionate living (MBCL), with guidance on request. A total of 122 self-referred participants with increased levels of self-criticism were randomly assigned to care as usual (CAU) or the intervention group (CAU + online intervention). Primary endpoints were self-reported depressive, anxiety and distress symptoms (DASS-21) and self-compassion (SCS) at 8 weeks. Secondary endpoints were self-criticism, mindfulness, satisfaction with life, fear of self-compassion, self-esteem, and existential shame. At posttreatment, the intervention group showed significant changes with medium to large effect sizes compared to the control group regarding primary outcomes (Cohen's d: 0.79 [DASS] and -1.21 [SCS]) and secondary outcomes (Cohen's ds: between 0.40 and 0.94 in favor of the intervention group). The effects in the intervention group were maintained at 6-months postrandomization. Adherence measures (number of completed modules, self-reported number of completed exercises per week) predicted postintervention scores for self-compassion but not for depressive, anxiety, and distress symptoms in the intervention group. The current study shows the efficacy of an online intervention with a transdiagnostic intervention target on a broad range of measures, including depressive and anxiety symptoms and self-compassion.

Feasibility of a blended group treatment (bGT) for major depression: uncontrolled interventional study in a university setting.

OBJECTIVE: This study investigated the feasibility of a novel blended (face-to-face and computer-based) group intervention for the reduction of depressive symptoms in major depression. DESIGN: Patient-centred uncontrolled interventional study. SETTING: University setting in a general community sample. A multimodal recruitment strategy (public health centres and public areas) was applied. PARTICIPANTS: Based on independent interviews, 26 participants, diagnosed with major depressive disorder (81% female; 23% comorbidity >1 and 23% comorbidity >2), entered treatment. INTERVENTION: Acceptance and mindfulness based, as well as self-management and resource-oriented psychotherapy principles served as the theoretical basis for the low-threshold intervention. The blended format included face-to-face sessions, complemented with multimedia presentations and a platform featuring videos, online work sheets, an unguided group chat and remote therapist-patient communication. MAIN OUTCOME MEASURES: The Center for Epidemiological Studies-Depression scale and the 12-item General Health Questionnaire. RESULTS: Large to very large within group effect sizes were found on self-reported depression (F(2, 46.37)=25.69, p<0.001; d=1.80), general health (F(2,46.73)=11.47, p<0.001; d=1.32), personal resources (F(2,43.36)=21.17, p<0.001; d=0.90) and mindfulness (F(2,46.22)=9.40, p<0.001; d=1.12) after a follow-up period of 3 months. Treatment satisfaction was high, and 69% ranked computer and multimedia use as a therapeutic factor. Furthermore, participants described treatment intensification as important advantage of the blended format. Half of the patients (48%) would have preferred more time for personal exchange. CONCLUSION: The investigated blended group format seems feasible for the reduction of depressive symptoms in major depression. The development of blended interventions can benefit from assuring that highly structured treatments actually meet patients' needs. As a next step, the intervention should be tested in comparative trials in routine care. TRIAL REGISTRATION NUMBER: DRKS00010894; Pre-results.

The effect of rhythmic-cued motor imagery on walking, fatigue and quality of life in people with multiple sclerosis: A randomised controlled trial.

BACKGROUND: Motor imagery and rhythmic auditory stimulation are physiotherapy strategies for walking rehabilitation. OBJECTIVES: To investigate the effect of motor imagery combined with rhythmic cueing on walking, fatigue and quality of life (QoL) in people with multiple sclerosis (MS). METHODS: Individuals with MS and Expanded Disability Status Scale scores of 1.5-4.5 were randomised into one of three groups: 17 minutes of motor imagery, six times per week, for 4 weeks, with music (A) or metronome cues (B), both with verbal cueing, and (C) controls. Primary outcomes were walking speed (Timed 25-Foot Walk) and distance (6-Minute Walk Test). Secondary outcomes were walking perception (Multiple Sclerosis Walking Scale-12), fatigue (Modified Fatigue Impact Scale) and QoL (Short Form-36 Health Survey, Multiple Sclerosis Impact Scale-29, Euroquol-5D-3L Questionnaire). RESULTS: Of the 112 participants randomised, 101 completed the study. Compared to controls, both interventions significantly improved walking speed, distance and perception. Significant improvements in cognitive but not psychosocial fatigue were seen in the intervention groups, and physical fatigue improved only in the music-based group. Both interventions improved QoL; however, music-cued motor imagery was superior at improving health-related QoL. CONCLUSION: Rhythmic-cued motor imagery improves walking, fatigue and QoL in people with MS, with music-cued motor imagery being more effective.

Porphyrin Metalation at MgO Surfaces: A Spectroscopic and Quantum Mechanical Study on Complementary Model Systems.

We show that both single-crystalline and nanostructured MgO surfaces convert free-base tetraphenyl porphyrin (2HTPP) into magnesium tetraphenyl porphyrin (MgTPP) at room temperature. The reaction can be viewed as an ion exchange between the two aminic protons of the 2HTPP molecule with a Mg(2+) ion from the surface. The driving force for the reaction is the strong stability of the formed hydroxyl groups along the steps and at defects on the MgO surface. We have used an integrated characterization approach that includes UV/Vis diffuse reflectance measurements on nanostructured powders, X-ray photoelectron spectroscopic investigation of atomically clean MgO(100) single-crystalline thin films, and density functional theory (DFT) calculations on model systems. The DFT calculations demonstrate that MgTPP formation is strongly exothermic at the corners, edges and steps, but slightly endothermic on terrace sites. This agrees well with the UV/Vis diffuse reflectance, which upon adsorption of 2HTPP shows a decrease in the absorption band associated with corner and edge sites on MgO nanocube powders.

Non-invasive imaging of cardiac electrophysiology in a cardiac resynchronization therapy defibrillator patient with a quadripolar left ventricular lead.

AIMS: The present study was aimed to assess epi- and endocardial ventricular electroanatomical activation during cardiac resynchronization therapy (CRT) by means of non-invasive imaging of cardiac electrophysiology (NICE) in a patient with a novel quadripolar LV lead. METHODS AND RESULTS: Non-invasive imaging of cardiac electrophysiology is a novel imaging tool which works by fusing data from high-resolution electrocardiogram (ECG) mapping with a model of the patient's individual cardiothoracic anatomy created from magnetic resonance imaging. This was performed in a cardiac resynchronization therapy defribrillator (CRT-D) patient with a quadripolar left ventricular (LV) lead. Beat-to-beat endocardial and epicardial ventricular activation sequences were computed using NICE during intrinsic conduction as well as during different pacing modes with different LV and biventricular (biV) pacing vectors. The spatial resolution of NICE enabled discrimination of the different pacing vectors during LV and biV pacing. Biventricular pacing resulted in a marked shortening of the total activation duration (TAD) of both ventricles when compared with intrinsic conduction and RV and LV pacing. CONCLUSION: Non-invasive imaging of cardiac electrophysiology facilitates non-invasive imaging of ventricular activation, which may be useful in CRT patients to locate the area of latest ventricular activation as the target area for LV lead placement. Moreover, especially in non-responders to CRT NICE may be further useful to determine the best electrical repositioning option.

Beyond words: sensory properties of depressive thoughts.

Verbal thoughts (such as negative cognitions) and sensory phenomena (such as visual mental imagery) are usually conceptualised as distinct mental experiences. The present study examined to what extent depressive thoughts are accompanied by sensory experiences and how this is associated with symptom severity, insight of illness and quality of life. A large sample of mildly to moderately depressed patients (N = 356) was recruited from multiple sources and asked about sensory properties of their depressive thoughts in an online study. Diagnostic status and symptom severity were established over a telephone interview with trained raters. Sensory properties of negative thoughts were reported by 56.5% of the sample (i.e., sensation in at least one sensory modality). The highest prevalence was seen for bodily (39.6%) followed by auditory (30.6%) and visual (27.2%) sensations. Patients reporting sensory properties of thoughts showed more severe psychopathological symptoms than those who did not. The degree of perceptuality was marginally associated with quality of life. The findings support the notion that depressive thoughts are not only verbal but commonly accompanied by sensory experiences. The perceptuality of depressive thoughts and the resulting sense of authenticity may contribute to the emotional impact and pervasiveness of such thoughts, making them difficult to dismiss for their holder.

Single-beat noninvasive imaging of ventricular endocardial and epicardial activation in patients undergoing CRT.

BACKGROUND: Little is known about the effect of cardiac resynchronization therapy (CRT) on endo- and epicardial ventricular activation. Noninvasive imaging of cardiac electrophysiology (NICE) is a novel imaging tool for visualization of both epi- and endocardial ventricular electrical activation. METHODOLOGY/PRINCIPAL FINDINGS: NICE was performed in ten patients with congestive heart failure (CHF) undergoing CRT and in ten patients without structural heart disease (control group). NICE is a fusion of data from high-resolution ECG mapping with a model of the patient's individual cardiothoracic anatomy created from magnetic resonance imaging. Beat-to-beat endocardial and epicardial ventricular activation sequences were computed during native rhythm as well as during ventricular pacing using a bidomain theory-based heart model to solve the related inverse problem. During right ventricular (RV) pacing control patients showed a deterioration of the ventricular activation sequence similar to the intrinsic activation pattern of CHF patients. Left ventricular propagation velocities were significantly decreased in CHF patients as compared to the control group (1.6±0.4 versus 2.1±0.5 m/sec; p<0.05). CHF patients showed right-to-left septal activation with the latest activation epicardially in the lateral wall of the left ventricle. Biventricular pacing resulted in a resynchronization of the ventricular activation sequence and in a marked decrease of total LV activation duration as compared to intrinsic conduction and RV pacing (129±16 versus 157±28 and 173±25 ms; both p<0.05). CONCLUSIONS/SIGNIFICANCE: Endocardial and epicardial ventricular activation can be visualized noninvasively by NICE. Identification of individual ventricular activation properties may help identify responders to CRT and to further improve response to CRT by facilitating a patient-specific lead placement and device programming.

Effectiveness of a novel integrative online treatment for depression (Deprexis): randomized controlled trial.

BACKGROUND: Depression is associated with immense suffering and costs, and many patients receive inadequate care, often because of the limited availability of treatment. Web-based treatments may play an increasingly important role in closing this gap between demand and supply. We developed the integrative, Web-based program Deprexis, which covers therapeutic approaches such as behavioral activation, cognitive restructuring, mindfulness/acceptance exercises, and social skills training. OBJECTIVE: To evaluate the effectiveness of the Web-based intervention in a randomized controlled trial. METHODS: There were 396 adults recruited via Internet depression forums in Germany, and they were randomly assigned in an 80:20 weighted randomization sequence to either 9 weeks of immediate-program-access as an add-on to treatment-as-usual (N = 320), or to a 9-week delayed-access plus treatment-as-usual condition (N = 76). At pre- and post-treatment and 6-month follow-up, we measured depression (Beck Depression Inventory) as the primary outcome measure and social functioning (Work and Social Adjustment Scale) as the secondary outcome measure. Complete analyses and intention-to-treat analyses were performed. RESULTS: Of 396 participants, 216 (55%) completed the post-measurement 9 weeks later. Available case analyses revealed a significant reduction in depression severity (BDI), Cohen's d = .64 (CI 95% = 0.33 - 0.94), and significant improvement in social functioning (WSA), Cohen's d = .64, 95% (CI 95% = 0.33 - 0.95). These improvements were maintained at 6-month follow-up. Intention-to-treat analyses confirmed significant effects on depression and social functioning improvements (BDI: Cohen's d = .30, CI 95% = 0.05 - 0.55; WSA: Cohen's d = .36, CI 95% = 0.10 - 0.61). Moreover, a much higher percentage of patients in the intervention group experienced a significant reduction of depression symptoms (BDI: odds ratio [OR] = 6.8, CI 95% = 2.90 - 18.19) and recovered more often (OR = 17.3, 95% CI 2.3 - 130). More than 80% of the users felt subjectively that the program had been helpful. CONCLUSIONS: This integrative, Web-based intervention was effective in reducing symptoms of depression and in improving social functioning. Findings suggest that the program could serve as an adjunctive or stand-alone treatment tool for patients suffering from symptoms of depression.

Long-term results of high vs. normal impedance ventricular leads on actual (Real-Life) pacemaker generator longevity.

AIM: The long-term effects of high impedance vs. standard impedance pacing leads on actual generator longevity were studied. METHODS AND RESULTS: In 40 patients (21 females, age 73 +/- 13 years) with standard dual-chamber pacemaker indication, bipolar standard impedance ventricular leads and high-impedance leads were implanted in a randomized fashion. Identical pacemaker generators and atrial pacing leads were implanted in all patients. Patients were observed during a mean follow-up of 89.8 +/- 8.8 months before pacemaker replacement. Initially, the patients who received the high-impedance leads had a lower current drain as compared with standard pacing impedance leads, and the estimated pacemaker longevity was significantly prolonged, too. But this pattern disappeared after 6 years of follow-up, and finally the actual pacemaker generators' replacement time was 86.7 +/- 6.8 months in standard impedance lead group vs. 91.2 +/- 10.3 months in high-impedance lead group (P = 0.17). CONCLUSION: Implantation of high pacing impedance leads for ventricular stimulation does not result in a benefit with respect to pacemaker longevity as compared with standard impedance leads.

Artesunate in the treatment of metastatic uveal melanoma--first experiences.

Artesunate (ART) is a derivative of artemisinin, the active principle of the Chinese herb Artemisia annua L. Artesunate is approved for the treatment of multidrug-resistant malaria and has an excellent safety profile. It has been shown that Artesunate, apart from its anti-malarial activity, has cytotoxic effects on a number of human cancer cell lines, including leukemia, colon cancer and melanoma. We report on the first long-term treatment of two cancer patients with ART in combination with standard chemotherapy. These patients with metastatic uveal melanoma were treated on a compassionate-use basis, after standard chemotherapy alone was ineffective in stopping tumor growth. The therapy-regimen was well tolerated with no additional side effects other than those caused by standard chemotherapy alone. One patient experienced a temporary response after the addition of ART to Fotemustine while the disease was progressing under therapy with Fotemustine alone. The second patient first experienced a stabilization of the disease after the addition of ART to Dacarbazine, followed by objective regressions of splenic and lung metastases. This patient is still alive 47 months after first diagnosis of stage IV uveal melanoma, a situation with a median survival of 2-5 months. Despite the small number of treated patients, ART might be a promising adjuvant drug for the treatment of melanoma and possibly other tumors in combination with standard chemotherapy. Its good tolerability and lack of serious side effects will facilitate prospective randomized trials in the near future.