Background: Eating disorders are serious conditions associated with an impaired health-related quality of life and increased healthcare utilization and costs. Despite the existence of evidence-based treatments, access to treatment is often delayed due to insufficient health care resources. Internet-based self-help interventions may have the potential to successfully bridge waiting time for face-to-face outpatient treatment and, thus, contribute to overcoming treatment gaps. However, little is known about the feasibility of implementing such interventions into routine healthcare. The aim of this study is to analyze the effects and feasibility of an Internet-based selfhelp intervention (everyBody Plus) specifically designed for patients with Bulimia Nervosa, Binge Eating Disorder and other specified feeding and eating disorders (OSFED) on a waiting list for outpatient face-to-face treatment. The aim of this paper is to describe the study protocol. Methods: A multi-country randomized controlled trial will be conducted in Germany and the UK. N=275 female patients awaiting outpatient treatment will be randomly allocated either to the guided online self-help intervention “everyBody Plus” or a waitlist control group condition without access to the intervention. everyBody Plus comprises eight weekly sessions that cover topics related to eating and exercise patterns, coping with negative emotions and stress as well as improving body image. Participants will receive weekly individualized feedback based on their self-monitoring and journal entries. Assessments will take place at baseline, post-intervention as well as at 6- and 12-months follow up. In addition, all participants will be asked to monitor core eating disorder symptoms weekly to provide data on the primary outcome. The primary outcome will be number of weeks after randomization until a patient achieves a clinically relevant improvement in core symptoms (BMI, binge eating, compensatory behaviors) for the first time. Secondary outcomes include frequency of core symptoms and eating disorder related attitudes and behaviors, as well as associated psychopathology. Additional secondary outcomes will be the participating therapists' confidence in treating eating disorders as well as perceived benefits of everyBody Plus for patients. Discussion: To the best of our knowledge, this is the first randomized controlled trial examining the effects of Internet-based self-help for outpatients with eating disorders awaiting face-to-face outpatient treatment. If proven to be effective and successfully implemented, Internet-based self-help programs might be used as a first step of treatment within a stepped-care approach, thus reducing burden and cost for both patients and health care providers.

Background: Depression is one of the most frequent and costly mental disorders. While there is increasing evidence for the efficacy of online self-help to improve depression or prevent relapse, there is little evidence in blended care settings, especially combined with inpatient face-to-face psychotherapy. Therefore, we evaluated whether an evidencebased online self-help program improves the efficacy of inpatient psychotherapy. Methods: A total of 229 depressed patients were randomly allocated either to an online selfhelp program (intervention group [IG]; Deprexis) or an active control group (CG; weekly online information on depression) in addition to inpatient psychodynamic psychotherapy. Both groups had access to their respective experimental intervention for 12 weeks, regardless of inpatient treatment duration. Reduction of depressive symptoms, as measured with the Beck Depression Inventory-II, was the primary outcome at the end of the intervention (T2). Results: Depressive symptoms were statistically significantly lower in the IG compared to the active CG at T2 with a moderate betweengroup effect size of d = 0.44. The same applied to anxiety ( d = 0.33), quality of life ( d = 0.34), and self-esteem ( d = 0.38) at discharge from inpatient treatment (T1). No statistically significant differences were found regarding dysfunctional attitudes ( d = 0.14) and work ability ( d = 0.08) at T1. Conclusions: This is the first evidence for blended treatment combining online self-help with inpatient psychotherapy. The study opens new and promising avenues for increasing the efficacy of inpatient psychotherapy. Future studies should determine how integration of online self-help into the therapeutic process can be developed further.

Background: Controversy surrounds the questions whether co-occurring depression has negative effects on cognitivebehavioral therapy (CBT) outcomes in patients with panic disorder (PD) and agoraphobia (AG) and whether treatment for PD and AG (PD/AG) also reduces depressive symptomatology. Methods: Post-hoc analyses of randomized clinical trial data of 369 outpatients with primary PD/AG (DSM-IV-TR criteria) treated with a 12-session manualized CBT (n = 301) and a waitlist control group (n = 68). Patients with comorbid depression (DSM-IV-TR major depression, dysthymia, or both: 43.2% CBT, 42.7% controls) were compared to patients without depression regarding anxiety and depression outcomes (Clinical Global Impression Scale [CGI], Hamilton Anxiety Rating Scale [HAM-A], number of panic attacks, Mobility Inventory [MI], Panic and Agoraphobia Scale, Beck Depression Inventory) at post-treatment and follow-up (categorical). Further, the role of severity of depressive symptoms on anxiety/depression outcome measures was examined (dimensional). Results: Comorbid depression did not have a significant overall effect on anxiety outcomes at post-treatment and follow-up, except for slightly diminished post-treatment effect sizes for clinician-rated CGI (p = 0.03) and HAM-A (p = 0.008) when adjusting for baseline anxiety severity. In the dimensional model, higher baseline depression scores were associated with lower effect sizes at post-treatment (except for MI), but not at follow-up (except for HAM-A). Depressive symptoms improved irrespective of the presence of depression. Conclusions: Exposure-based CBT for primary PD/AG effectively reduces anxiety and depressive symptoms, irrespective of comorbid depression or depressive symptomatology. / Dieser Beitrag ist mit Zustimmung des Rechteinhabers aufgrund einer (DFG-geförderten) Allianz- bzw. Nationallizenz frei zugänglich.

Background: Research suggests that a low omega-3 index may contribute to the low heart rate variability and the increased risk of cardiovascular morbidity and mortality in bipolar disorders. However, so far, no intervention trial with EPA and DHA has been conducted in bipolar patients attempting to increase their heart rate variability. - Methods: 119 patients with bipolar disorder according to DSM-IV were screened, with 55 euthymic bipolar patients—owing to inclusion criteria (e.g. low omega-3 index (< 6%), SDNN < 60 ms.)—being enrolled in a randomized, double-blind, 12-week parallel study design with omega-3 fatty acids (4 capsules of 530 mg EPA, 150 mg DHA) or corn oil as a placebo, in addition to usual treatment. Heart rate variability as well as the omega-3 index were measured at baseline and at the endpoint of the study. - Results: A total of 42 patients (omega-3: n = 23, corn oil: n = 19) successfully completed the study after 12 weeks. There was a significant increase in the omega-3 index (value at endpoint minus value at baseline) in the omega-3 group compared to the corn oil group (p < 0.0001). However, there was no significant difference in the change of the SDNN (value at endpoint minus value at baseline) between the treatment groups (p = 0.22). In addition, no correlation between changes in SDNN and change in the omega-3 index could be detected in the omega-3 group (correlation coefficient = 0.02, p = 0.94) or the corn oil group (correlation coefficient = − 0.11, p = 0.91). Similarly, no significant differences between corn oil and omega-3 group regarding the change of LF (p = 0.19), HF (p = 0.34) and LF/HF ratio (p = 0.84) could be demonstrated. - Conclusions: In our randomized, controlled intervention trial in euthymic bipolar patients with a low omega-3 index and reduced heart rate variability no significant effect of omega-3 fatty acids on SDNN or frequency-domain measures HF, LF and LF/HF ratio could be detected. Possible reasons include, among others, the effect of psychotropic medication present in our trial and/or the genetics of bipolar disorder itself. Further research is needed to test these hypotheses.

Background: In the treatment of diabetes mellitus, the challenge is to integrate adequate self-management into clinical care. Customization including goal setting, monitoring, and feedback could be achieved through digitization. Digital linking between different devices could simplify and promote self-management. The aim of this study is to evaluate the outcome of diabetes treatment assisted by a digital health application compared with standard diabetes therapy. - Methods: The DAVOS study is a 6-month-period prospective, multicentric, randomized controlled trial. In total, 154 diabetes patients (age ≥18; treated with insulin) will be recruited and randomized into control group or intervention group. Both groups will receive standard diabetes care. The intervention group will additionally use a diabetes app. HbA1c value will be monitored on three separate defined visits. Primary endpoint is the overall reduction of HbA1c value. Secondary endpoints (eg, usability of the app) will be determined through patient-reported outcome questionnaires. - Discussion: Through enhanced interaction of health care professionals, providers of the app, and patients, the study aims to demonstrate improvement in the self-management of diabetes. As part of the closure management, all patients will be invited to use the examined application after completion of the study. The DAVOS study will be conducted in accordance with the valid version of the present study protocol and the internationally recognized International Conference on Harmonization–Good Clinical Practice (ICH-GCP) Guidelines. Special attention will be paid to European, national, and regional requirements for the approval, provision, and use of medical devices. The study was registered in the German Register of Clinical Trials (DRKS) with number DRKS00025996.

Background Primary radiochemotherapy with photons is the standard treatment for locally advanced-stage non-small cell lung cancer (NSCLC) patients. Acute radiation-induced side effects such as oesophagitis and radiation pneumonitis limit patients’ quality of life, and the latter can be potentially life-threatening. Due to its distinct physical characteristics, proton therapy enables better sparing of normal tissues, which is supposed to translate into a reduction of radiation-induced side effects. Methods/design This is a single-centre, prospective, randomised controlled, phase II clinical trial to compare photon to proton radiotherapy up to 66 Gy (RBE) with concomitant standard chemotherapy in patients with locally advanced-stage NSCLC. Patients will be allocated in a 1:1 ratio to photon or proton therapy, and treatment will be delivered slightly accelerated with six fractions of 2 Gy (RBE) per week. Discussion The overall aim of the study is to show a decrease of early and intermediate radiation-induced toxicity using proton therapy. For the primary endpoint of the study we postulate a decrease of radiation-induced side effects (oesophagitis and pneumonitis grade II or higher) from 39 to 12%. Secondary endpoints are locoregional and distant failure, overall survival and late side effects. Trial registration Registered at ClinicalTrials.gov with Identifier NCT02731001 on 1 April 2016.

Background Primary radiochemotherapy with photons is the standard treatment for locally advanced-stage non-small cell lung cancer (NSCLC) patients. Acute radiation-induced side effects such as oesophagitis and radiation pneumonitis limit patients’ quality of life, and the latter can be potentially life-threatening. Due to its distinct physical characteristics, proton therapy enables better sparing of normal tissues, which is supposed to translate into a reduction of radiation-induced side effects. Methods/design This is a single-centre, prospective, randomised controlled, phase II clinical trial to compare photon to proton radiotherapy up to 66 Gy (RBE) with concomitant standard chemotherapy in patients with locally advanced-stage NSCLC. Patients will be allocated in a 1:1 ratio to photon or proton therapy, and treatment will be delivered slightly accelerated with six fractions of 2 Gy (RBE) per week. Discussion The overall aim of the study is to show a decrease of early and intermediate radiation-induced toxicity using proton therapy. For the primary endpoint of the study we postulate a decrease of radiation-induced side effects (oesophagitis and pneumonitis grade II or higher) from 39 to 12%. Secondary endpoints are locoregional and distant failure, overall survival and late side effects. Trial registration Registered at ClinicalTrials.gov with Identifier NCT02731001 on 1 April 2016.

Diese Dissertation befasst sich in drei voneinander unabhängigen Kapiteln mit dem Forschungsfeld des ökonomischen Designs. Das "Design" von Situationen wirtschaftlicher Interaktion hat zum Ziel, den Verlauf und das Ergebnis der jeweiligen Interaktion zu steuern. In dieser Arbeit werden mathematisch-theoretische "Designs" zum einen formal entwickelt und diese zum anderen durch politische oder soziale Institutionen realisiert. Das erste Kapitel thematisiert die Implementierung von Sozialwahlfunktionen in einem kollusiven Umfeld. Es wird gezeigt, wie die gezielte Schaffung von asymmetrischer Information zwischen den kolludierenden Parteien deren Koordination erschweren und die Implementierung erleichtern kann. Im zweiten Kapitel wird dieser Ansatz im Kontext der Bestechlichkeit bei Finanzaudits angewendet. Korruption kann verhindert werden, wenn der bestechliche Akteure eine Warnung über anstehende Kontrollen erhält, nicht jedoch der bestechende Akteur. Das dritte Kapitel wiederum untersucht "Design" in Form von Markt- und Wettbewerbsregulierung. Eine Beschränkung des Wettbewerbs - durch eine Begrenzung der Zahl miteinander konkurrierender Firmen - kann entgegen der ökonomischen Intuition wohlfahrtsoptimierend sein. / This thesis contributes to the field of economic design in three independent chapters. Taking the perspective of a "designer", it derives formal solutions in the framework of economic theory and suggests political as well as social institutions to put these solutions to practice. The first chapter employs mechanism design to mitigate the problem of collusion. It shows how the implementation of social choice functions can be achieved by introducing asymmetric information into a system prone to collusion. In the second chapter, this methodology is applied to the context of corruption in auditing. Bribery is impeded by selectively warning one - and only one - of the corruptive parties about upcoming inspections. Finally, the third chapter studies market regulation as a means of "design". Contrary to economic intuition, it may be beneficial in terms of welfare to limit competition by restricting the number of firms allowed to enter a market.