A (Sub)field Guide to Quality Control in Hippocampal Subfield Segmentation on Highresolution T2-weighted MRI.

Inquiries into properties of brain structure and function have progressed due to developments in magnetic resonance imaging (MRI). To sustain progress in investigating and quantifying neuroanatomical details in vivo, the reliability and validity of brain measurements are paramount. Quality control (QC) is a set of procedures for mitigating errors and ensuring the validity and reliability of brain measurements. Despite its importance, there is little guidance on best QC practices and reporting procedures. The study of hippocampal subfields in vivo is a critical case for QC because of their small size, inter-dependent boundary definitions, and common artifacts in the MRI data used for subfield measurements. We addressed this gap by surveying the broader scientific community studying hippocampal subfields on their views and approaches to QC. We received responses from 37 investigators spanning 10 countries, covering different career stages, and studying both healthy and pathological development and aging. In this sample, 81% of researchers considered QC to be very important or important, and 19% viewed it as fairly important. Despite this, only 46% of researchers reported on their QC processes in prior publications. In many instances, lack of reporting appeared due to ambiguous guidance on relevant details and guidance for reporting, rather than absence of QC. Here, we provide recommendations for correcting errors to maximize reliability and minimize bias. We also summarize threats to segmentation accuracy, review common QC methods, and make recommendations for best practices and reporting in publications. Implementing the recommended QC practices will collectively improve inferences to the larger population, as well as have implications for clinical practice and public health.

StudiCare procrastination - Randomized controlled non-inferiority trial of a persuasive design-optimized internet- and mobile-based intervention with digital coach targeting procrastination in college students.

BACKGROUND: Academic procrastination is widespread among college students. Procrastination is strongly negatively correlated with psychological well-being, thus early interventions are needed. Internet- and mobile-based cognitive behavioral therapy (iCBT) could provide a low-threshold treatment option. Human guidance seems to be a decisive mechanism of change in iCBT. Persuasive design optimization of iCBT and guidance by a digital coach might represent a resource-saving alternative. The study evaluated the non-inferiority of a digital coach in comparison to human guidance with regard to the primary outcome procrastination. METHODS: The iCBT StudiCare procrastination was optimized by principles of the Persuasive System Design (PSD). A total of 233 college students were randomly assigned to either StudiCare procrastination guided by a digital coach (intervention group, IG) or by a human eCoach (control group, CG). All participants were assessed at baseline, 4-, 8- and 12-weeks post-randomization. Symptom change and between-group differences were assessed with latent growth curve models and supported by effect size levels. The non-inferiority margin was set at Cohen's d = - 0.3. RESULTS: The primary outcome procrastination measured by the Irrational Procrastination scale (IPS) significantly decreased across groups (γ = - 0.79, p < .001, Cohen's d = -0.43 to -0.89) from baseline to 12-weeks post-randomization. There were no significant differences between groups (γ = -0.03, p = .84, Cohen's d = -0.03 to 0.08). Regarding symptoms of depression, no significant time x group effect was found (γ = 0.26, p = .09; Cohen's d = -0.15 to 0.21). There was also no significant time x group effect on the improvement of symptoms of anxiety (γ = 0.25, p = .09). However, Cohen's ds were above the non-inferiority margin 8-weeks (Cohen's d = 0.51) and 12-weeks post-randomization (Cohen's d = 0.37), preferring the CG. Of the IG, 34% and of the CG, 36% completed 80% of the modules. CONCLUSIONS: The PSD optimized version of StudiCare procrastination is effective in reducing procrastination. The digital coach was not inferior to human guidance. Guidance by a digital coach in iCBT against procrastination for college students could be a resource-saving alternative to human guidance. TRIAL REGISTRATION: The trial was registered at the WHO International Clinical Trials Registry Platform via the German Clinical Trial Register (ID: DRKS00025209, 30/04/2021).

Safety and preliminary activity results of the GATTO study, a phase Ib study combining the anti-TA-MUC1 antibody gatipotuzumab with the anti-EGFR tomuzotuximab in patients with refractory solid tumors.

BACKGROUND: The phase I GATTO study (NCT03360734) explored the feasibility, tolerability and preliminary activity of combining gatipotuzumab, a novel humanized monoclonal antibody binding to the tumor-associated epitope of mucin 1 (TA-MUC1) and an anti-epidermal growth factor receptor (anti-EGFR) antibody in refractory solid tumors. PATIENTS AND METHODS: Initially the study enrolled primary phase (PP) patients with EGFR-positive metastatic solid tumors, for whom no standard treatment was available. Patients received gatipotuzumab administered at 1400 mg every 2 weeks, 6 weeks after the start of the glyco-optimized anti-EGFR antibody tomuzotuximab at 1200 mg every 2 weeks. As this regimen was proven safe, enrollment continued in an expansion phase (EP) of patients with refractory metastatic colorectal cancer, non-small-cell lung cancer, head and neck cancer and breast cancer. Tomuzotuximab and gatipotuzumab were given at the same doses and gatipotuzumab treatment started 1 week after the first dose of the anti-EGFR antibody. Additionally, investigators could use a commercial anti-EGFR antibody in place of tomuzotuximab. RESULTS: A total of 52 patients were enrolled, 20 in the PP and 32 in the EP. The combined treatment was well tolerated and no dose-limiting toxicity was observed in the whole study, nor related serious adverse event or death. Preliminary activity of the combination was observed, with one and four RECIST partial responses in the PP and EP, all in colorectal cancer patients. The trial was accompanied by a comprehensive translational research program for identification of biomarkers, including soluble TA-MUC1 (sTA-MUC1) in serum. In the EP, patients with baseline sTA-MUC1 levels above the median appeared to have improved progression-free survival and overall survival. CONCLUSIONS: Combination of a TA-MUC1-targeting antibody and an EGFR-targeting antibody is safe and feasible. Interesting antitumor activity was observed in heavily pretreated patients. Future studies should test this combination together with chemotherapy and explore the potential of sTA-MUC1 as a companion biomarker for further development of the combination.

Standardized evaluation of the quality and persuasiveness of mobile health applications for diabetes management.

This study evaluates diabetes self-management mobile health applications available from European app stores with respect to quality, concordance with recommended self-management tasks and implementation of persuasive system design principles. The European Play Store and Apple App Store were systematically searched and relevant apps were tested. Two raters independently assessed app quality using the Mobile Application Rating Scale and conducted a content analysis of provided persuasive system design principles and self-management tasks. A total of 2,269 mobile health applications were identified and 120 could be included in the evaluation. The overall quality was rated as moderate M = 3.20 (SD = 0.39, min = 2.31, max = 4.62), with shortcomings in the subcategories of engagement (M = 2.80, SD = 0.67) and information quality (M = 2.26, SD = 0.48). Scientific evidence is available for 8% of the apps. The reviewed apps implemented a median of three persuasive system design principles (range 0-15) and targeted a median of 4.5 (range 1-8) self-management tasks, however, with a lack of information about psychosocial coping strategies. Most available diabetes self-management apps lack a scientific evidence base. Persuasive system design features are underrepresented and may form a promising tool to improve app quality. Furthermore, the interaction of physical and behavioral health should be improved in existing diabetes self-management mobile health applications.

Feasibility and potential efficacy of a guided internet- and mobile-based CBT for adolescents and young adults with chronic medical conditions and comorbid depression or anxiety symptoms (youthCOACHCD): a randomized controlled pilot trial.

BACKGROUND: Adolescents and young adults (AYA) with a chronic medical condition show an increased risk for developing mental comorbidities compared to their healthy peers. Internet- and mobile-based cognitive behavioral therapy (iCBT) might be a low-threshold treatment to support affected AYA. In this randomized controlled pilot trial, the feasibility and potential efficacy of youthCOACHCD, an iCBT targeting symptoms of anxiety and depression in AYA with chronic medical conditions, was evaluated. METHODS: A total of 30 AYA (Mage 16.13; SD= 2.34; 73% female), aged 12-21 years either suffering from cystic fibrosis, juvenile idiopathic arthritis or type 1 diabetes, were randomly assigned to either a guided version of the iCBT youthCOACHCD (IG, n=15) or to a waitlist control group (CG, n=15), receiving an unguided version of the iCBT six months post-randomization. Participants of the IG and the CG were assessed before (t0), twelve weeks after (t1) and six months after (t2) randomization. Primary outcome was the feasibility of the iCBT. Different parameters of feasibility e.g. acceptance, client satisfaction or potential side effects were evaluated. First indications of the possible efficacy with regard to the primary efficacy outcome, the Patient Health Questionnaire Anxiety and Depression Scale, and further outcome variables were evaluated using linear regression models, adjusting for baseline values. RESULTS: Regarding feasibility, intervention completion was 60%; intervention satisfaction (M = 25.42, SD = 5.85) and perceived therapeutic alliance (M = 2.83, SD = 1.25) were moderate and comparable to other iCBTs. No patterns emerged regarding subjective and objective negative side effects due to participation in youthCOACHCD. Estimates of potential efficacy showed between group differences, with a potential medium-term benefit of youthCOACHCD (ß = -0.55, 95%CI: -1.17; 0.07), but probably not short-term (ß = 0.20, 95%CI: -0.47; 0.88). CONCLUSIONS: Our results point to the feasibility of youthCOACHCD and the implementation of a future definitive randomized controlled trial addressing its effectiveness and cost-effectiveness. Due to the small sample size, conclusions are premature, however, further strategies to foster treatment adherence should be considered. TRIAL REGISTRATION: The trial was registered at the WHO International Clinical Trials Registry Platform via the German Clinical Trials Register (ID: DRKS00016714 , 25/03/2019).

Maintenance therapy of patients with recurrent epithelial ovarian carcinoma with the anti-tumor-associated-mucin-1 antibody gatipotuzumab: results from a double-blind, placebo-controlled, randomized, phase II study.

BACKGROUND: Gatipotuzumab is a humanized monoclonal antibody recognizing the carbohydrate-induced epitope of the tumor-associated mucin-1 (TA-MUC1). This study aimed to evaluate the efficacy and safety of switch maintenance therapy with gatipotuzumab in patients with TA-MUC1-positive recurrent ovarian, fallopian tube, or primary high-grade serous peritoneal cancer. PATIENTS AND METHODS: In this double-blind, randomized, placebo-controlled, phase II trial, patients with at least stable disease (SD) following chemotherapy were randomized 2:1 to receive intravenous gatipotuzumab (500 mg followed by 1700 mg 1 week later) or placebo every 3 weeks until tumor progression or unacceptable toxicity occurred. Stratification factors were the number of prior chemotherapy lines (2 versus 3-5), response versus SD after the most recent chemotherapy, and progression-free survival (PFS) <6 versus 6-12 months following the prior therapy. Primary endpoint was PFS according to modified immune-related RECIST 1.1 response criteria. Secondary endpoints were PFS at 6 months, safety, overall response rate, CA-125 progression, overall survival, quality of life, and pharmacokinetics. RESULTS: Overall, 216 patients were randomized to gatipotuzumab (n  = 151) or placebo (n  = 65). Median PFS with gatipotuzumab was 3.5 months as compared with 3.5 months with placebo (hazard ratio 0.96, 95% confidence interval 0.69-1.33, P  = 0.80). No advantage for gatipotuzumab over placebo was seen in the secondary efficacy endpoints or in any stratified subgroups. Gatipotuzumab was well tolerated, with mild to moderate infusion-related reactions being the most common adverse events. CONCLUSIONS: Gatipotuzumab switch maintenance therapy does not improve outcome in TA-MUC1-positive ovarian cancer patients. TRIAL REGISTRATION: ClinicalTrials.govNCT01899599; https://clinicaltrials.gov/ct2/show/NCT01899599.

A randomized phase II study comparing the efficacy and safety of the glyco-optimized anti-EGFR antibody tomuzotuximab against cetuximab in patients with recurrent and/or metastatic squamous cell cancer of the head and neck - the RESGEX study.

BACKGROUND: The aim of the RESGEX study was to compare the efficacy and safety of the anti-epidermal growth factor receptor (anti-EGFR) antibody tomuzotuximab against cetuximab both in combination with chemotherapy in patients with recurrent and/or metastatic squamous cell cancer of the head and neck in the first-line treatment. PATIENTS AND METHODS: In this phase II trial 240 patients were equally randomized for six cycles to receive either tomuzotuximab (initial dose 990 mg then 720 mg) weekly and cisplatin 100 mg/m2 and fluorouracil (5-FU; 1000 mg/m2/day, days 1-4) every 3 weeks or cetuximab (400 mg/m2 subsequent 250 mg/m2) weekly with the same chemotherapeutic backbone followed by antibody maintenance treatment. The primary endpoint was progression-free survival. RESULTS: Median progression-free survival was 6.5 months [95% confidence interval (CI) 5.9-7.9 months] in the tomuzotuximab group and 6.2 months (95% CI 5.8-7.3 months) in the cetuximab group (P = 0.86). The median overall survival (OS) estimate was 11.6 months (95% CI 9.5-17.2 months) in the tomuzotuximab group and 13.8 months (95% CI 12.3-16.4 months) in the cetuximab group (P = 0.96). In an exploratory analysis a small subgroup of p16-positive patients had a significantly longer OS compared with p16-negative patients (hazard ratio 1.860, 95% CI 1.09-3.16, P = 0.02). CONCLUSIONS: The glyco-engineered antibody tomuzotuximab failed to demonstrate improved efficacy with a chemotherapeutic backbone in the first-line treatment of recurrent or metastatic head and neck squamous cell carcinoma. It remains a so far unanswered question whether such antibody would partner better with different drugs such as checkpoint inhibitors.

Patients' experiences in a guided Internet- and App-based stress intervention for college students: A qualitative study.

INTRODUCTION: Academic education is often associated with increased stress and adverse effects on mental health. Internet-based interventions have shown to be effective in reducing stress-related symptoms. However, college students as target group so far have not been reached appropriately with psychological interventions and little is known about college students' perception of Internet-based stress management interventions. The objective of this study was to explore the experiences of students participating in an Internet- and App-based stress management intervention originally developed for stressed employees and subsequently adapted and tailored to college students. METHOD: Semi-structured interviews were conducted with ten participants selected from a randomized controlled trial that evaluated the effectiveness of an Internet- and App-based stress training. The selection of participants aimed to include students with different levels of treatment success. In order to enable an in-depth examination of intervention elements causing dissatisfaction, the interviews were systematically adapted regarding participants' statements in a precedent questionnaire. The interview material was analyzed based on the grounded theory method and thematic analysis. RESULTS: Results suggest students perceive a necessity to adapt Internet-based interventions to their particular needs. Students' statements indicate that a scientific perspective on the intervention and instable life circumstances could be student-specific factors affecting treatment experience. General themes emerging from the data were attitudes towards individualization and authenticity as well as demands towards different functions of feedback. DISCUSSION: Participants' experiences hint at certain intellectual and lifestyle-related characteristics of this population. Future studies should explore whether adaptions to these characteristics lead to a higher acceptance, adherence and effectiveness in the target population.

[Psychotherapy of depressive disorders : Procedures, evidence and perspectives]. / Psychotherapie depressiver Störungen : Verfahren, Evidenz und Perspektiven.

BACKGROUND: Depressive disorders are associated with a high burden of suffering and significantly reduce the well-being and the self-esteem of affected patients. Psychotherapy is one of the main treatment options for depressive disorders. OBJECTIVE: The aim of this article is to present the current evidence for antidepressive psychotherapeutic treatments. MATERIAL AND METHODS: During the revision of the German S3- and National Disease Management Guideline (NDMG) on unipolar depression in 2015, a comprehensive and systematic evidence search was conducted. The results of this search along with a systematic update are summarized. RESULTS: The most intensively investigated psychotherapeutic method is cognitive behavioral therapy (CBT), which proved to be effective in many trials. Evidence also exists for psychodynamic psychotherapy and interpersonal therapy (IPT), followed by systemic therapy and client-centered psychotherapy; however, the evidence is less robust. CONCLUSION: Psychotherapy alone or in combination with pharmacotherapy was shown to be an effective treatment option. Psychotherapy represents a key element in the treatment of depressive disorders.

[Psychotherapy of depressive disorders: Evidence in chronic depression and comorbidities]. / Psychotherapie depressiver Störungen: Evidenz bei chronischer Depression und bei Komorbidität.

BACKGROUND: Psychotherapy has been shown to be an effective treatment option for depressive disorders; however, its effectiveness varies depending on patient and therapist characteristics and the individual form of the depressive disorder. OBJECTIVES: The aim of this article is to present the current evidence for psychotherapeutic antidepressive treatments for patients with chronic and treatment-resistant depression as well as for patients with mental and somatic comorbidities. MATERIAL AND METHODS: During the revision of the currently valid German S3- and National Disease Management Guideline (NDMG) on unipolar depression published in 2015, a comprehensive and systematic evidence search including psychotherapy for specific patient groups was conducted. The results of this search along with a systematic update are summarized. RESULTS: Psychotherapy has been shown to be effective in reducing depressive symptoms in patients suffering from chronic and treatment-resistant depression and in patients with mental and somatic comorbidities. The evidence is insufficient particularly for patients with mental comorbidities. CONCLUSION: Based on the current evidence and clinical expertise the NDMG recommends psychotherapy alone or in combination with pharmacotherapy to treat most of these depressive patient groups. Evidence gaps were identified, which highlight the need for further research.

Effectiveness and cost-effectiveness of a guided Internet- and mobile-based intervention for the indicated prevention of major depression in patients with chronic back pain-study protocol of the PROD-BP multicenter pragmatic RCT.

BACKGROUND: Reducing the disease burden of major depressive disorder (MDD) is of major public health relevance. The prevention of depression is regarded as one possible approach to reach this goal. People with multiple risk factors for MDD such as chronic back pain and subthreshold depressive symptoms may benefit most from preventive measures. The Internet as intervention setting allows for scaling up preventive interventions on a public mental health level. METHODS: This study is a multicenter pragmatic randomized controlled trial (RCT) of parallel design aiming to investigate the (cost-) effectiveness of an Internet- and mobile-based intervention (IMI) for the prevention of depression in chronic back pain patients (PROD-BP) with subthreshold depressive symptoms. eSano BackCare-DP is a guided, chronic back pain-specific depression prevention intervention based on cognitive behavioral therapy (CBT) principles comprising six weekly plus three optional modules and two booster sessions after completion of the intervention. Trained psychologists provide guidance by sending feedback messages after each module. A total of 406 patients with chronic back pain and without a depressive disorder at baseline will be recruited following orthopedic rehabilitation care and allocated to either intervention or treatment-as-usual (TAU). Primary patient-relevant endpoint of the trial is the time to onset of MDD measured by the telephone-administered Structured Clinical Interview for DSM (SCID) at baseline and 1-year post-randomization. Key secondary outcomes are health-related quality of life, depression severity, pain intensity, pain-related disability, ability to work, intervention satisfaction and adherence as well as side effects of the intervention. Online assessments take place at baseline and 9 weeks as well as 6 and 12 months post-randomization. Cox regression survival analysis will be conducted to estimate hazard ratio at 12-month follow-up. Moreover, an economic analysis will be conducted from a societal and public health perspective. DISCUSSION: This is the first study examining an IMI for depression prevention in a sample of chronic pain patients. If this implementation of a depression prevention IMI into orthopedic aftercare proves effective, the intervention could be integrated into routine care with minimal costs and extended for use with other chronic diseases. Results will have implications for researchers, health care providers and public health policy makers. TRIAL REGISTRATION: The trial is registered at the WHO International Clinical Trials Registry Platform via the German Clinical Studies Trial Register (DRKS): DRKS00007960 . Registered 12 August 2015.

The 6-month effectiveness of Internet-based guided self-help for depression in adults with Type 1 and 2 diabetes mellitus.

AIM: The aim of this research is to examine the 6-month effects of an Internet-based guided self-help intervention for comorbid depressive symptoms in people with diabetes. METHODS: Participants (n = 260) with Type 1 or 2 diabetes and elevated depressive symptoms [Center for Epidemiological Studies Depression Scale (CES-D) ≥ 23] were randomly assigned to a guided Internet-based self-help intervention or a control condition (treatment as usual + online psychoeducation about depression). The primary outcome was a change in depressive symptom severity (CES-D) from baseline to 6-month follow-up. The secondary outcomes included numbers of people achieving treatment response (reliable change of depressive symptoms) and remission (CES-D ≤ 16), as well as the effects on glycaemic control, diabetes-related emotional distress and diabetes acceptance. Repeated measures analysis of variance examined between-group differences using intent-to-treat principles. RESULTS: Both conditions showed improvements in depression severity: intervention condition, d = 1.48 [95% confidence interval (95% CI): 1.21 to 1.76]; control condition d = 0.55 (95% CI: 0.30 to 0.80). Changes were significantly greater in the intervention condition with a large between-group effect size (d = 0.83, 95% CI: 0.57 to 1.08). Accordingly, effects on response [relative risk (RR) = 2.60 (95% CI: 2.01 to 3.36), P < 0.001] and remission [RR = 3.36 (95% CI: 2.98 to 5.44), P < 0.001] were in favour of the intervention group, as were differences in change in diabetes emotional distress (d = 0.50, 95% CI: 0.04 to 0.54), and physical and mental functioning [Short Form Health Survey (SF-12) Physical d = 0.27 (95% CI: 0.01 to 0.51) and SF-12 Mental d = 0.68 (95% CI: 0.11 to 0.40)]. The intervention group was not superior with regard to glycaemic control, diabetes self-management and diabetes acceptance. CONCLUSIONS: The trial indicates that Internet-based guided self-help treatments for depression in people with diabetes can have sustained effects on depressive symptoms, well-being and emotional distress associated with diabetes.

[Screening for Anxiety in Cardiovascular Rehabilitation Patients: Concurrent Validity and Cut-off Values of the ACAT-cardio]. / Angst-Screening bei kardiologischen Rehabilitanden: Übereinstimmungsvalidität und Cut-Off-Werte des ACAT-cardio.

OBJECTIVE: The computer adaptive test ACAT-cardio has been developed in order to screen cardiovascular rehabilitation patients for anxiety. This study aims at investigating the criterion validity, and identifying appropriate cut-off values for its use in cardiac rehabilitation. METHODS: 106 cardiovascular rehabilitation patients were tested for anxiety disorders using the instruments ACAT-cardio and SKID-I. Receiver operating characteristics were employed to analyse the results of 3 stopping rules of the ACAT-cardio. RESULTS: ROC analyses for the stopping rules yielded areas under the curve (AUC) between 0.80 and 0.84. The ideal cut-off values of the ACAT-cardio (theta scores) were - 0.20 (sensitivity: 86%),-0.23 (sensitivity: 71%) and - 0.35 (sensitivity: 86%). CONCLUSIONS: The ACAT-cardio has proven to be a valid instrument that can be used for screening anxiety disorders in cardiac rehabilitation.

A phase I study of PankoMab-GEX, a humanised glyco-optimised monoclonal antibody to a novel tumour-specific MUC1 glycopeptide epitope in patients with advanced carcinomas.

BACKGROUND: A phase I open-label dose-escalation study was conducted to define the safety, tolerability, and pharmacokinetics (PK) of PankoMab-GEX, a glyco-optimised humanised IgG1, with high affinity to a novel tumour-specific glycopeptide epitope of MUC1 (TA-MUC1) with excellent preclinical anti-tumour activity. PATIENTS AND METHODS: Seventy-four patients with advanced TA-MUC1-positive carcinomas received PankoMab-GEX intravenously every 3 (Q3W), 2 (Q2W), or 1 (QW) week in doses of 1-2200 mg in a three-plus-three dose-escalation design until disease progression (NCT01222624). RESULTS: No maximum tolerated dose was reached. Adverse events were mainly mild-to-moderate infusion-related reactions (IRRs) by the first infusion in 45% of patients. Only one dose-limiting toxicity, a grade III IRR, was observed. PankoMab-GEX exhibited linear PK over all doses. Mean terminal half-life was 189 ± 66 h (Q3W), without dose dependency. A target trough level ≥50 µg/mL was reached after one infusion with doses ≥1700 mg Q3W in 80% of patients. Clinical benefit in 60 evaluable patients included one complete response in a patient with ovarian cancer treated 483 d and confirmed disease stabilisation in 19 patients lasting a median (range) of 23 (10-109) weeks. All but two of the patients with clinical benefit had received a compounded total dose ≥700 mg over a 3-week period, including 8 of 12 (67%) patients with ovarian cancer. CONCLUSION: PankoMab-GEX is safe, well tolerated, and showed promising anti-tumour activity in advanced disease. A phase IIb study is ongoing evaluating the efficacy of PankoMab-GEX as a maintenance therapy in advanced ovarian cancer.

Panic disorder and incident coronary heart disease: a systematic review and meta-regression in 1131612 persons and 58111 cardiac events.

BACKGROUND: Substantial healthcare resources are devoted to panic disorder (PD) and coronary heart disease (CHD); however, the association between these conditions remains controversial. Our objective was to conduct a systematic review of studies assessing the association between PD, related syndromes, and incident CHD. METHOD: Relevant studies were retrieved from Medline, EMBASE, SCOPUS and PsycINFO without restrictions from inception to January 2015 supplemented with hand-searching. We included studies that reported hazard ratios (HR) or sufficient data to calculate the risk ratio and 95% confidence interval (CI) which were pooled using a random-effects model. Studies utilizing self-reported CHD were ineligible. Twelve studies were included comprising 1 131 612 persons and 58 111 incident CHD cases. RESULTS: PD was associated with the primary incident CHD endpoint [adjusted HR (aHR) 1.47, 95% CI 1.24-1.74, p < 0.00001] even after excluding angina (aHR 1.49, 95% CI 1.22-1.81, p < 0.00001). High to moderate quality evidence suggested an association with incident major adverse cardiac events (MACE; aHR 1.40, 95% CI 1.16-1.69, p = 0.0004) and myocardial infarction (aHR 1.36, 95% CI 1.12-1.66, p = 0.002). The risk for CHD was significant after excluding depression (aHR 1.64, 95% CI 1.45-1.85) and after depression adjustment (aHR 1.38, 95% CI 1.03-1.87). Age, sex, length of follow-up, socioeconomic status and diabetes were sources of heterogeneity in the primary endpoint. CONCLUSIONS: Meta-analysis showed that PD was independently associated with incident CHD, myocardial infarction and MACE; however, reverse causality cannot be ruled out and there was evidence of heterogeneity.

Increasing the acceptance of internet-based mental health interventions in primary care patients with depressive symptoms. A randomized controlled trial.

BACKGROUND: Internet-based interventions (IBI) are effective in treating depression. However, uptake rates in routine care are still limited. Hence, this study aimed to (1) assess the acceptance of IBIs in primary care patients with depressive symptoms and to (2) examine the effects of a brief acceptance facilitating intervention in the form of an informational video on patients' acceptance of IBIs. METHODS: Primary care patients (N=128) with Minor or Major Depression were randomly assigned to an intervention (IG) or control group (CG). Patients in the IG were shown a brief informational video about IBIs before receiving a questionnaire that assessed their acceptance of IBIs and other secondary outcomes. Patients of the CG filled out the questionnaire immediately. RESULTS: Baseline acceptance of IBIs in the CG was high for 6.3%, moderate for 53.1% and low for 40.6% of patients. Acceptance of IBIs was significantly higher in the IG when compared to the CG (d=.71, 95%-CI:.09-2.91). Except for social influence and the general attitude towards psychological treatment, all secondary outcomes were also significantly improved (e.g. effort- (d=.40) and performance-expectancy: d=.65; knowledge about Internet interventions d=.35). LIMITATIONS: Depression of the participants was only assessed using a self-report measure (PHQ-9). CONCLUSION: Primary care patients' acceptance of IBIs for depressive symptoms was low but could be increased significantly using a brief acceptance facilitating intervention on the basis of an informational video. Future studies should further examine the potential of acceptance facilitating interventions for patients and health care providers to exploit the public health impact of IBIs.

Impact of an acceptance facilitating intervention on diabetes patients' acceptance of Internet-based interventions for depression: a randomized controlled trial.

AIMS: To (1) determine diabetes patients' acceptance of Internet-based interventions (IBIs) for depression, to (2) examine the effectiveness of an acceptance facilitating intervention (AFI) and to (3) explore subgroup specific effects. METHODS: 141 diabetes patients from two inpatient rehabilitation units and one outpatient clinic in Germany were randomly allocated to an intervention (IG) and a no-intervention control group (CG). The IG received an AFI consisting of a personal information session before filling-out a questionnaire on patients' acceptance of IBIs, predictors of acceptance (performance expectancy, effort expectancy, social influence, facilitating conditions, and Internet anxiety) as well as sociodemographic, depression-related and diabetes-related variables. The CG filled out the questionnaire immediately. Patients' acceptance of IBIs was measured with a four-item scale (sum-score ranging from 4 to 20). RESULTS: The CG showed a low (50.7%) to medium (40.8%) acceptance with only 8.5% of all diabetes patients reporting a high acceptance of IBIs for depression. The AFI had no significant effect on acceptance (IG: M=10.55, SD=4.69, n=70; KG: M=9.65, SD=4.27, n=71; d=0.20 [95%-CI: -0.13;0.53]) and the predictors of acceptance. Yet, subgroup analyses yielded a trend for depressed, diabetes-related distressed, female and younger (<59) participants and for those who do not frequently use the Internet to profit from the AFI. CONCLUSION: Diabetes patients show a rather low acceptance toward IBIs for depression. Findings indicate that the AFI is likely to be effective in the subgroup of depressed, diabetes-related distressed, female or younger diabetes patients, but not in the whole target population. Hence, AFIs might need to be tailored to the specific needs of subpopulations.

Psychological and pharmacological interventions for depression in patients with diabetes mellitus: an abridged Cochrane review.

AIMS: To summarize and critically evaluate the effectiveness of psychological and pharmacological interventions for depression in patients with both diabetes and depression. METHODS: Randomized controlled trials investigating psychological and pharmacological interventions for depression in adults with diabetes and depression were included. A comprehensive search of primary studies according to Cochrane were conducted. Primary outcomes were depression and glycaemic control. Further, treatment adherence, diabetes complications, mortality, healthcare costs and quality of life were investigated. Two reviewers identified primary studies and extracted data independently. Random-effects model meta-analyses were conducted to compute overall estimates of treatment outcomes. RESULTS: The database search resulted in 3963 references, of which 19 trials were included. Randomized controlled trials of psychological interventions showed positive effects on short- and medium-term depression severity [standardized mean difference short-term range -1.47; -0.14, n = 7; medium-term standardized mean difference -0.42 (95% CI -0.70 to -0.14), n = 3] and depression remission [odds ratio short term 2.88 (95% CI 1.58-5.25), n = 4; odds ratio medium term 2.49 (95% CI 1.44-4.32), n = 2]. Effects on glycaemic control in psychological intervention trials varied substantially (standardized mean difference range -0.97 to 0.47, n = 4). Selective serotonin reuptake inhibitors showed a moderate beneficial effect on short-term depression severity [standardized mean difference -0.39 (95% CI -0.64 to -0.13], n = 5) and depression remission [odds ratio 2.52 (95% CI 1.11-5.75), n = 2]. Glycaemic control improved in randomized controlled trials comparing selective serotonin reuptake inhibitors with placebo at the end of treatment [standardized mean difference -0.38 (95% CI -0.64 to -0.12), n = 5]. CONCLUSIONS: Psychological and pharmacological interventions positively affect depression outcomes in patients with diabetes at the end of treatment. Furthermore, short-term glycaemic control improved moderately in pharmacological trials. Most outcomes have not been investigated sufficiently. Moreover, there is a lack of follow-up data for pharmacological trials limiting the evidence on the sustainability of treatment effects.