Ganglioside SSEA-4 in Ewing sarcoma marks a tumor cell population with aggressive features and is a potential cell-surface immune target.

Carbohydrate markers of immature cells during prenatal human development can be aberrantly expressed in cancers and deserve evaluation as immune targets. A candidate target in Ewing sarcoma is the globo-series ganglioside stage-specific embryonic antigen-4 (SSEA-4). We detected SSEA-4 expression on the cell surface of all of 14 EwS cell lines and in 21 of 31 (68%) primary EwS tumor biopsies. Among paired subpopulations of tumor cells with low versus high SSEA-4 expression, SSEA-4high expression was significantly and consistently associated with functional characteristics of tumor aggressiveness, including higher cell proliferation, colony formation, chemoresistance and propensity to migrate. SSEA-4low versus SSEA-4high expression was not related to expression levels of the EWSR1-FLI1 fusion transcript or markers of epithelial/mesenchymal plasticity. SSEA-4low cells selected from bulk populations regained higher SSEA-4 expression in vitro and during in vivo tumor growth in a murine xenograft model. T cells engineered to express SSEA-4-specific chimeric antigen receptors (CARs) specifically interacted with SSEA-4 positive EwS cells and exerted effective antigen-specific tumor cell lysis in vitro. In conclusion, with its stable expression and functional significance in EwS, SSEA-4 is an attractive therapeutic immune target in this cancer that deserves further evaluation for clinical translation.

Influence of health literacy on health-related quality of life after total hip arthroplasty.

INTRODUCTION: Personal knowledge about the own disease, a key component of health literacy (HL), may have a considerable impact on treatment outcomes. The purpose of this study was to investigate whether the patients' knowledge about the surgical procedure, risks, and aftercare, as well as the satisfaction with the preoperative level of information, has an influence on the health-related quality of life (HRQoL) after primary total hip arthroplasty (THA). MATERIALS AND METHODS: A total of 176 patients (68.3 ± 10.3 years, 60.8% female) were evaluated. HRQoL was assessed prior to surgery as well as one and twelve months after THA using the 12-item Short Form Questionnaire. Following standardized surgical informed consent, HL was assessed preoperatively using a self-constructed quiz score, while information satisfaction was measured with a single-item rating scale. Sociodemographic and clinical characteristics, including pain (VAS), functionality (WOMAC), and psychological distress (PHQ-4), were also assessed at baseline. Multiple linear regression analyses were performed to examine whether HL, satisfaction with information, age, social class, WOMAC, VAS, and PHQ-4 predict HRQoL at one and twelve months post-surgery. RESULTS: The average HL quiz score was 23 ± 5.1 out of a possible 33 points. Social class index significantly influenced HL (p < 0.001). A weak correlation between HL and age (r = 0.23, p = 0.01) and no correlation between HL and psychological distress (p = 0.868) were observed. One month after THA, physical HRQoL was significantly predicted by the WOMAC index (p = 0.031) and subjective satisfaction with information (p = 0.022), but not by HL. After twelve months, only the WOMAC was a significant predictor (p < 0.001) of physical HRQoL. CONCLUSION: Although subjective satisfaction with the patient's preoperative level of information had a significant effect on the physical HRQoL at one month after THA, the influence of osteoarthritis severity outweighed this effect after twelve months. HL had no direct influence on HRQoL. These results suggest that patient satisfaction, rather than knowledge, predicts HRQoL.

Mixed results for exposure and response prevention therapy in mixed reality for patients with contamination-related obsessive-compulsive disorder: A randomized controlled pilot study.

INTRODUCTION: Technology-supported exposure and response prevention (ERP) for patients with obsessive-compulsive disorder (OCD) as tested in clinical research, holds promise but also has limitations. The present study aims to overcome these limitations by using mixed reality for ERP (MERP). The objectives of this pilot study were to evaluate the safety, feasibility, and acceptance of MERP and to identify possible obstacles. METHODS: Twenty inpatients with contamination-related OCD were recruited and randomized to two conditions: MERP (six sessions in 3 weeks) and care as usual treatment. Patients were assessed before treatment (baseline), after the 3-week intervention period (post), as well as 3 months after post assessment (follow-up) regarding symptomatology (Y-BOCS). RESULTS: Results showed a similar reduction in symptomatology in both groups from baseline to post. Regarding safety, no clinically significant deterioration was detected in the MERP group. Patients' evaluation of the MERP was heterogeneous. The qualitative feedback provided helpful indications for further development of the software. Sense of presence was below the midpoint of the scales. CONCLUSION: This is the first study evaluating a MERP for patients with OCD that shows cautious evidence for the acceptance and safety of MERP. The results of the subjective evaluation suggest revisions of the software.

Improving adherence to unguided Internet-based therapy for obsessive-compulsive disorder: A randomized controlled trial.

BACKGROUND: Adherence to internet-based cognitive-behavioral therapy (iCBT) is often low, possibly reducing its potential. The current study set out to test whether adherence and effects of unguided iCBT for obsessive-compulsive disorder (OCD) could be improved by varying the degree of autonomy in which modules are completed (free choice vs. fixed order). METHODS: We randomized 151 individuals with OCD to either an unguided iCBT with a fixed (iCBTfixed) or a free-choice (iCBTfree+) order of the modules. We assessed participants at baseline (t0), eight weeks (t1), and 16 weeks (t2). Primary outcomes were adherence (utilization time, modules completed) and change in OCD severity (Y-BOCS). Secondary outcomes included depression, self-esteem, and treatment satisfaction. We calculated intent-to-treat (ITT) and complete case (CC) analyses. RESULTS: Analyses showed that both iCBT programs significantly reduced OCD severity. While groups did not differ on the ITT analyses, for the CC analyses, a greater improvement was found in the iCBTfixed in comparison to the iCBTfree+ group regarding OCD severity and quality of life, with medium effect sizes from t0 to t1 (ηp2 = 0.067-0.077). Time of utilization and number of modules completed did not differ between groups. LIMITATIONS: No placebo control group, short follow-up period, self-report assessment. CONCLUSIONS: iCBT is effective in improving OCD. Despite similar adherence in the fixed versus the free-choice module order, the study offers tentative evidence that a fixed order of content is associated with better effects. More research on the effects of adherence on outcome is necessary.

Efficacy of exposure and response prevention therapy in mixed reality for patients with obsessive-compulsive disorder: study protocol for a randomized controlled trial.

Many patients with obsessive-compulsive disorder (OCD) do not receive cognitive behavioral therapy with exposure and response prevention (first line treatment for OCD), for example, due to patients' fear of the exposure and reservations of the therapists. Technology-supported exposure (e.g., exposure therapy with response prevention in mixed reality [MERP]) for patients with OCD may help to overcome this obstacle. Building upon findings of our pilot study objectives of this study are to evaluate the efficacy, expectations of treatment success, feasibility, and acceptance of MERP as well as to identify possible limitations. In total, 64 outpatients with contamination-related OCD will be recruited and randomized to one of two conditions: MERP (six sessions in six weeks) and self-guided exposure therapy (six exercises in six weeks). Participants will be assessed before (baseline), after the six-week intervention period (post), as well as three months after post assessment (follow-up) regarding symptomatology (Yale-Brown Obsessive Compulsive Scale; Y-BOCS), their subjective evaluation of MERP (acceptance) and sense of presence. The planned study is the first to investigate MERP in patients with OCD.

A mobile-based aftercare intervention to increase self-esteem in inpatients diagnosed with depression: A randomized controlled trial.

OBJECTIVE: In this randomized controlled trial, we investigated the effectiveness, side effects and user satisfaction of the self-help smartphone app "MCT & More" among inpatients with a diagnosis of depression after their discharge from a psychiatric hospital over a period of 4 weeks. METHODS: A total of 159 inpatients were recruited in four German psychiatric hospitals three days before hospital discharge (intervention group: n = 79; treatment as usual: n = 80). Based on the vulnerability model (low self-esteem contributes to depression), self-esteem represented the primary outcome, quality of life and depressive symptoms the secondary outcomes. RESULTS: Intention-to-treat analyzes showed no statistical significance for the primary and secondary outcome parameters, except for the subscale self-competence in favor of the intervention group (with a small effect size of d = 0.35), in the context of an exploratory approach (post hoc). The more positive the attitude toward mobile-based interventions and the more positive the treatment expectations, the more frequently the app was used (r = .35, p = .008; r = .34, p = .009). CONCLUSION: Further symptom reduction could not be obtained. However, the results suggest that an effect on improvement in self-competence could be achieved by low-threshold aftercare programs. Future studies should include long-term assessments to examine the impact of mobile-based aftercare on relapse.Trial registration: DRKS00022559.

The Dimensional Structure of the Gambling Attitudes and Beliefs Survey: Challenging the Assumption of the Unidimensionality of Gambling-Specific Cognitive Distortions.

The aim of the present study was to examine the dimensional structure of the Gambling Attitudes and Beliefs Survey (GABS). The GABS was administered to a sample of 415 individuals with self-reported problem or pathological gambling who were taking part in two different treatment studies preregistered with the German Clinical Trials Register (DRKS00013888) and ClinicalTrials.gov (NCT03372226). Exploratory factor analyses revealed a three-factor structure. We labeled the factors sensation seeking/illusion of control, luck/gambler's fallacy, and attitude/emotions. Subsequent confirmatory factor analyses proved the three-factor model superior to the one-factor model proposed by the developers of the GABS. All dimensions were significantly correlated with symptom severity scores. Group comparisons showed significantly higher factor scores on the first factor (sensation seeking/illusion of control) for individuals reporting both skill-based and chance-based gambling compared to those reporting only chance-based gambling. The present study questions the unidimensionality of the GABS. A multidimensional assessment of gambling-related cognitive biases, beliefs, and positively valued attitudes may be useful in determining treatment outcomes and goals and in the development of novel interventions.

Motive-Oriented, Personalized, Internet-Based Interventions for Depression: Nonclinical Experimental Study.

BACKGROUND: The low level of adherence in internet-based self-help interventions for depression suggests that in many existing programs, the motivational fit between the program and the user is unsatisfactory (eg, the user seeks autonomy, but the program provides directive guidance). Personalized, motive-oriented, self-help interventions could enable participants who interact with a program and its contents to have more engaging and less aversive experiences and thus increase adherence. OBJECTIVE: In an experimental study with a nonclinical analogue sample, we aimed to test the hypotheses that a better motivational person-program fit is linked with higher anticipated adherence, working alliance, and satisfaction with the program. METHODS: Motivational person-program fit was examined with respect to the 2 contrasting motives being autonomous and being supported. The hypotheses were tested by specifically varying the motivational person-program fit in a nonclinical sample (N=55), where participants were asked to work on, and subsequently evaluate, a limited set of individual pages of a self-help program with guidance (in the form of text messages) for depression. The sections of the self-help program were redesigned to either particularly address the autonomy motive or the support motive. For the quasi-experimental variation of the motivational person-program characteristics, we divided the 55 participants into 2 groups (autonomy group: n=27, 49%; support group: n=28, 51%) by screening method (using the Inventory of Approach and Avoidance Motivation), corresponding to the 2 motives. Both groups evaluated (in randomized order) 2 excerpts of the program-one that matched their motive (fit) and one that was contrary to it (no fit). Immediately after the evaluation of each excerpt, anticipated adherence, working alliance, and treatment satisfaction were assessed. RESULTS: Regarding being supported, the satisfaction with or violation of this motive had an impact on (optimal) anticipated adherence as well as working alliance and satisfaction with the intervention; a congruent person-program fit resulted in significantly higher anticipated adherence (t27=3.00; P=.006), working alliance (t27=3.20; P=.003), and satisfaction (t27=2.86; P=.008) than a noncongruent fit. However, a similar impact could not be found for the motive being autonomous. Several correlations were found that supported our hypotheses (eg, for the congruent person-program fit autonomy motive and autonomy group, support satisfaction negatively correlated with optimal anticipated adherence). CONCLUSIONS: This first experimental study gives reason to assume that motive orientation may have a positive influence on adherence, working alliance, and satisfaction in internet-based self-help interventions for depression and other mental disorders. Future studies should conduct randomized controlled trials with clinical samples and assess clinical outcomes.

CDH1 (E-cadherin) Gene Methylation in Human Breast Cancer: Critical Appraisal of a Long and Twisted Story.

Epigenetic inactivation of a tumor suppressor gene by aberrant DNA methylation is a well-established defect in human tumor cells, complementing genetic inactivation by mutation (germline or somatic). In human breast cancer, aberrant gene methylation has diagnostic, prognostic, and predictive potential. A prominent example is the hypermethylation of the CDH1 gene, encoding the adhesion protein E-Cadherin ("epithelial cadherin"). In numerous publications, it is reported as frequently affected by gene methylation in human breast cancer. However, over more than two decades of research, contradictory results concerning CDH1 gene methylation in human breast cancer accumulated. Therefore, we review the available evidence for and against the role of DNA methylation of the CDH1 gene in human breast cancer and discuss in detail the methodological reasons for conflicting results, which are of general importance for the analysis of aberrant DNA methylation in human cancer specimens. Since the loss of E-cadherin protein expression is a hallmark of invasive lobular breast cancer (ILBC), special attention is paid to CDH1 gene methylation as a potential mechanism for loss of expression in this special subtype of human breast cancer. Proper understanding of the methodological basis is of utmost importance for the correct interpretation of results supposed to demonstrate the presence and clinical relevance of aberrant DNA methylation in cancer specimens.

Exposure and Response Prevention in Virtual Reality for Patients with Contamination-Related Obsessive-Compulsive Disorder: a Case Series.

Exposure therapy in virtual reality is successful in treating anxiety disorders. Studies on exposure and response prevention in virtual reality (VERP) in obsessive-compulsive disorder (OCD) are rare, and it is unclear whether distress associated with other emotions than anxiety (e.g., disgust) can be evoked. The present study aimed to investigate whether distress can be induced during VERP in patients with contamination-related OCD (C-OCD) and a primary feeling of disgust. We treated eight female patients with C-OCD with the primary emotion of disgust over six weeks with VERP and assessed their OC symptoms before and after the intervention period with the Y-BOCS. We measured subjective units of distress (SUD), heart rate and skin conductivity (arousal), sense of presence, and simulator sickness during four consecutive exposure sessions. VERP was able to induce distress and arousal. The qualitative feedback was heterogeneous and sense of presence moderate. Patients' OC symptoms reduced over the treatment period with medium to large effect sizes, but only two patients were considered responders; two patients discontinued treatment due to lack of treatment success. Although VERP was able to induce distress and arousal associated with disgust and evoked a moderate sense of presence, the low rate of symptom reduction diminishes the positive results. Possible reasons for the heterogeneous results and implications are discussed. Trial registration: German Registry for Clinical Studies (DRKS00016929), 10.04.2019.

Correction: A Mobile-Based Intervention to Increase Self-esteem in Students with Depressive Symptoms: Randomized Controlled Trial.

[This corrects the article DOI: 10.2196/26498.].

A Mobile-Based Intervention to Increase Self-esteem in Students With Depressive Symptoms: Randomized Controlled Trial.

BACKGROUND: Depressive symptoms are one of the most common and ever-increasing mental health problems among students worldwide. Conventional treatment options, particularly psychotherapy, do not reach all students in need of help. Internet- and mobile-based interventions are promising alternatives for narrowing the treatment gap. OBJECTIVE: In the framework of a randomized controlled trial, we aim to investigate the effectiveness, acceptance, and side effects of a self-help smartphone app (MCT & More) based on cognitive behavioral therapy, mindfulness, acceptance and commitment therapy, and metacognitive training in a sample of students with self-reported depressive symptoms. Furthermore, we were interested in examining the influence of treatment expectations and attitudes toward internet- and mobile-based interventions on treatment adherence and effectiveness. METHODS: A total of 400 students were recruited via open access websites and randomized to either the intervention group (n=200), who received access to the self-help smartphone app MCT & More for a period of 4 weeks, or to a wait-list control group (n=200). The Patient Health Questionnaire-9 (depression) served as the primary outcome parameter, and the Rosenberg Self-esteem Scale (self-esteem) and the global item of the World Health Organization Quality of Life-abbreviated version (quality of life) served as the secondary outcome parameters. The Attitudes Towards Psychological Online Interventions was used to measure attitudes toward internet- and mobile-based interventions. Outcome expectations were assessed using the Patient Questionnaire on Therapy Expectation and Evaluation, and side effects were assessed using the Inventory for Assessing Negative Effects of Psychotherapy. RESULTS: Per-protocol (PP), complete-case, and intention-to-treat analyses showed a significantly higher reduction in depressive symptoms (PP: F1,222=3.98; P=.047; d=0.26) and a significantly higher increase in self-esteem (PP: F1,220=8.79; P=.003; d=0.40) in the intervention group than in the wait-list control group. Most participants regularly used the self-help smartphone app (91/120, 75.8%, at least once a week). The more positive the attitude toward internet- and mobile-based interventions (r=0.260; P=.004) and the more positive the outcome expectation (r=0.236; P=.009), the more frequently the self-help smartphone app was used. CONCLUSIONS: The effectiveness of the self-help smartphone app MCT & More was demonstrated among students with depressive symptoms compared with a wait-list control group. The app could be offered regularly as a low-threshold intervention to enhance students' health. TRIAL REGISTRATION: German Clinical Trials Register DRKS00020941; https://tinyurl.com/pr84w6er.

A randomized controlled trial on a self-guided Internet-based intervention for gambling problems.

The majority of individuals with problematic and pathological gambling remain untreated, and treatment barriers are high. Internet-based interventions can help to address existing barriers, and first studies suggest their potential for this target group. Within a randomized controlled trial (N = 150) with two assessment times (baseline and post-intervention), we aimed to investigate the feasibility, acceptance, and effectiveness of a self-guided Internet-based intervention targeted at gambling problems. We expected a significant reduction in gambling symptoms (primary outcome) and depressive symptoms as well gambling-specific dysfunctional thoughts (secondary outcomes) in the intervention group (IG) compared to a wait-list control group with access to treatment-as-usual (control group, CG) after the intervention period of 8 weeks. Results of the complete cases, per protocol, intention-to-treat (ITT), and frequent user analyses showed significant improvements in both groups for primary and secondary outcomes but no significant between-group differences (ITT primary outcome, F(1,147) = .11, p = .739, ηp2 < .001). Moderation analyses indicated that individuals in the IG with higher gambling and depressive symptoms, older age, and comorbid anxiety symptoms showed significant improvement relative to the CG. The intervention was positively evaluated (e.g., 96.5% rated the program as useful). Possible reasons for the nonsignificant between-group differences are discussed. Future studies should include follow-up assessments and larger samples to address limitations of the present study. Trial Registration ClinicalTrials.gov (NCT03372226), http://clinicaltrials.gov/ct2/show/NCT03372226 , date of registration (13/12/2017).

Dismantling, optimising, and personalising internet cognitive behavioural therapy for depression: a systematic review and component network meta-analysis using individual participant data.

BACKGROUND: Internet cognitive behavioural therapy (iCBT) is a viable delivery format of CBT for depression. However, iCBT programmes include training in a wide array of cognitive and behavioural skills via different delivery methods, and it remains unclear which of these components are more efficacious and for whom. METHODS: We did a systematic review and individual participant data component network meta-analysis (cNMA) of iCBT trials for depression. We searched PubMed, PsycINFO, Embase, and the Cochrane Library for randomised controlled trials (RCTs) published from database inception to Jan 1, 2019, that compared any form of iCBT against another or a control condition in the acute treatment of adults (aged ≥18 years) with depression. Studies with inpatients or patients with bipolar depression were excluded. We sought individual participant data from the original authors. When these data were unavailable, we used aggregate data. Two independent researchers identified the included components. The primary outcome was depression severity, expressed as incremental mean difference (iMD) in the Patient Health Questionnaire-9 (PHQ-9) scores when a component is added to a treatment. We developed a web app that estimates relative efficacies between any two combinations of components, given baseline patient characteristics. This study is registered in PROSPERO, CRD42018104683. FINDINGS: We identified 76 RCTs, including 48 trials contributing individual participant data (11 704 participants) and 28 trials with aggregate data (6474 participants). The participants' weighted mean age was 42·0 years and 12 406 (71%) of 17 521 reported were women. There was suggestive evidence that behavioural activation might be beneficial (iMD -1·83 [95% credible interval (CrI) -2·90 to -0·80]) and that relaxation might be harmful (1·20 [95% CrI 0·17 to 2·27]). Baseline severity emerged as the strongest prognostic factor for endpoint depression. Combining human and automated encouragement reduced dropouts from treatment (incremental odds ratio, 0·32 [95% CrI 0·13 to 0·93]). The risk of bias was low for the randomisation process, missing outcome data, or selection of reported results in most of the included studies, uncertain for deviation from intended interventions, and high for measurement of outcomes. There was moderate to high heterogeneity among the studies and their components. INTERPRETATION: The individual patient data cNMA revealed potentially helpful, less helpful, or harmful components and delivery formats for iCBT packages. iCBT packages aiming to be effective and efficient might choose to include beneficial components and exclude ones that are potentially detrimental. Our web app can facilitate shared decision making by therapist and patient in choosing their preferred iCBT package. FUNDING: Japan Society for the Promotion of Science.

Internet-Based Cognitive Behavioral Therapy for Depression: A Systematic Review and Individual Patient Data Network Meta-analysis.

Importance: Personalized treatment choices would increase the effectiveness of internet-based cognitive behavioral therapy (iCBT) for depression to the extent that patients differ in interventions that better suit them. Objective: To provide personalized estimates of short-term and long-term relative efficacy of guided and unguided iCBT for depression using patient-level information. Data Sources: We searched PubMed, Embase, PsycInfo, and Cochrane Library to identify randomized clinical trials (RCTs) published up to January 1, 2019. Study Selection: Eligible RCTs were those comparing guided or unguided iCBT against each other or against any control intervention in individuals with depression. Available individual patient data (IPD) was collected from all eligible studies. Depression symptom severity was assessed after treatment, 6 months, and 12 months after randomization. Data Extraction and Synthesis: We conducted a systematic review and IPD network meta-analysis and estimated relative treatment effect sizes across different patient characteristics through IPD network meta-regression. Main Outcomes and Measures: Patient Health Questionnaire-9 (PHQ-9) scores. Results: Of 42 eligible RCTs, 39 studies comprising 9751 participants with depression contributed IPD to the IPD network meta-analysis, of which 8107 IPD were synthesized. Overall, both guided and unguided iCBT were associated with more effectiveness as measured by PHQ-9 scores than control treatments over the short term and the long term. Guided iCBT was associated with more effectiveness than unguided iCBT (mean difference [MD] in posttreatment PHQ-9 scores, -0.8; 95% CI, -1.4 to -0.2), but we found no evidence of a difference at 6 or 12 months following randomization. Baseline depression was found to be the most important modifier of the relative association for efficacy of guided vs unguided iCBT. Differences between unguided and guided iCBT in people with baseline symptoms of subthreshold depression (PHQ-9 scores 5-9) were small, while guided iCBT was associated with overall better outcomes in patients with baseline PHQ-9 greater than 9. Conclusions and Relevance: In this network meta-analysis with IPD, guided iCBT was associated with more effectiveness than unguided iCBT for individuals with depression, benefits were more substantial in individuals with moderate to severe depression. Unguided iCBT was associated with similar effectiveness among individuals with symptoms of mild/subthreshold depression. Personalized treatment selection is entirely possible and necessary to ensure the best allocation of treatment resources for depression.

Feasibility, Acceptance, and Safety of Metacognitive Training for Problem and Pathological Gamblers (Gambling-MCT): A Pilot Study.

Approximately 90% of problem and pathological gamblers remain untreated. This treatment gap may be diminished by the implementation of low-threshold treatment programs. As cognitive distortions play a crucial role in the development and maintenance of gambling problems, interventions targeting gambling-related biases may be particularly effective. The aim of the present study was to examine the feasibility, acceptance, and safety of a novel metacognitive training for individuals with gambling problems (Gambling-MCT). Twenty-five participants were included in an uncontrolled pilot trial with two assessment points (intervention). The intervention comprised eight training modules targeting gambling-specific cognitive distortions. At baseline and post assessment, symptom severity, as measured with the PG-YBOCS, and gambling-related cognitive distortions, as measured with the GABS, were assessed. In addition, interim assessments measuring session-specific changes were conducted. Subjective appraisal was examined after each module and also post treatment. On average, participants took part in 4.16 (SD = 2.84) training sessions. Both intent-to-treat and per protocol analyses showed significant improvements on the PG-YBOCS and the GABS (dz = 0.37-1.37). After Bonferroni correction for multiple testing, linear mixed models for the analysis of session-specific changes showed no deterioration in participants' mental state after any of the modules. Subjective appraisal of Gambling-MCT was good. The present pilot study provides first evidence for the feasibility, acceptance, and safety of Gambling-MCT. Recruitment of participants remains challenging, emphasizing the importance of overcoming patient-related treatment barriers. Future studies need to investigate the efficacy of Gambling-MCT in randomized controlled trials.

Diminishing Effects After Recurrent Use of Self-Guided Internet-Based Interventions in Depression: Randomized Controlled Trial.

BACKGROUND: Self-guided internet-based interventions have several advantages over guided interventions and are generally effective in treating psychiatric symptoms. OBJECTIVE: We aimed to investigate whether the use of a new self-guided internet-based intervention (MOOD) would lead to a significant reduction in depressive symptoms compared with a care-as-usual (CAU) control group in a sample of individuals with depressive symptoms, most of whom had already used a different self-guided internet-based intervention in a previous trial. METHODS: A total of 125 individuals were randomized to the intervention condition (MOOD) and received access to the intervention for a period of six weeks or a CAU group. After six weeks, all participants were invited to take part in the post assessment. The Beck Depression Inventory-II served as the primary outcome. RESULTS: Both intention-to-treat as well as per-protocol analyses indicated that the depressive symptomatology decreased in both conditions but showed no advantage for those who had used MOOD. Subsequent moderation analyses suggested that those individuals who had less experience with psychotherapy benefitted to a greater extent compared with those with more experience. CONCLUSIONS: Self-guided internet-based interventions are deemed a suitable first-step approach to the treatment of depression. However, our results indicate that they are more efficacious in those with less psychotherapy experience. TRIAL REGISTRATION: ClinicalTrials.gov NCT03795480; http://clinicaltrials.gov/ct2/show/NCT03795480.

A self-guided Internet-based intervention for individuals with gambling problems: study protocol for a randomized controlled trial.

BACKGROUND: Only a small fraction of individuals with pathological or problematic gambling seek professional help despite available evidence-based treatments such as cognitive behavioral therapy (CBT). Anonymous Internet-based interventions may help to overcome treatment barriers. Results of a pilot study using an Internet-based intervention for depression in a sample of individuals with problematic or pathological gambling behavior show that both depressive and gambling-related symptomatology can be reduced with a generic depression program compared with a wait-list control group. Based on encouraging results of the pilot study, we developed a low-threshold, anonymous and cost-free online self-help program ("Restart") to test whether a program tailored to the needs of gamblers yields better results compared to the effects of the intervention evaluated in the pilot study. The online self-help program is based on CBT, targeting emotional problems and gambling-related symptoms and is accompanied by a smartphone application to sustain treatment benefits. METHOD: A randomized controlled trial with two conditions (intervention group and wait-list control group), two assessment times (reassessment after 8 weeks) and a total of 136 participants is planned. The primary outcome will be change in pathological gambling measured with the Pathological Gambling Adaptation of Yale-Brown Obsessive-Compulsive Scale from pre to post intervention. The change in depressive symptoms (assessed with the Patient Health Questionnaire - 9 depression module) and gambling-related dysfunctional thoughts (assessed with the Gambling Attitudes and Beliefs Survey) will represent secondary outcomes. The intervention includes modules on debt management, impulse control, gambling-specific cognitive biases, self-esteem, social competence, sleep hygiene, mindfulness and positive activities. DISCUSSION: This study is one of the first investigations of Internet-based self-help programs in a sample of problematic gamblers. Self-guided Internet-based interventions represent a promising possibility to narrow the existing treatment gap while saving expensive and scarce resources (e.g., psychotherapists). The expected findings will add substantial knowledge in the development of effective Internet-based treatments for individuals with gambling problems. The empirical and clinical implications (e.g., broader use and promotion of such interventions in the future) and the limitations of the study will be discussed. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03372226 . Registered on 13 December 2017.

A randomized controlled trial on a smartphone self-help application (Be Good to Yourself) to reduce depressive symptoms.

Depressive symptoms are common, yet only a subgroup of individuals receive adequate treatment. To reduce the treatment gap, several online self-help programs have been developed, yielding small to moderate effects. We developed a smartphone self-help application addressing depressive symptoms. We sought to evaluate its feasibility and efficacy in participants reporting a subjective need for help (a diagnosis of depression was not mandatory). We conducted a randomized controlled trial (N = 90). The primary outcome was a reduction of depressive symptoms measured with the Patient Health Questionnaire-9 (PHQ-9). Secondary outcomes included improved self-esteem (Rosenberg Self-Esteem Scale) and quality of life (WHOQOL-BREF). The intervention group obtained access to the application for four weeks, the wait-list group received access after the post assessment. No group differences emerged in either outcome in intention-to-treat analyses. Per protocol analyses with frequent users (i.e., several times a week or more) yielded a small effect size (η2p = 0.049) at trend level on the reduction of depressive symptoms in favor of the treatment group. However, 39% of the participants did not use the application frequently. Mobile self-help applications represent a promising addition to existing treatments, but it is important to increase patients' motivation to use them.

Correction: Effects of a depression-focused internet intervention in slot machine gamblers: A randomized controlled trial.

[This corrects the article DOI: 10.1371/journal.pone.0198859.].