Prevalences of mental distress and its associated factors in unaccompanied refugee minors in Germany.

Prevalences for mental disorders within minor refugees are comparatively high and heterogeneous. To reduce heterogeneity and identify high-risk subgroups, we compared unaccompanied refugee minors (URM) to accompanied refugee minors (ARM) regarding depressive symptoms and mental distress. Furthermore, we examined associative factors of mental distress in URM on a broad scale. We conducted a survey with a cross-sectional design in four German University hospitals. The sample consisted of n = 172 URM and n = 52 ARM aged 14-21. Depressive symptoms were assessed via the Patient Health Questionnaire (PHQ-9). Mental distress was assessed by the Refugee Health Screener (RHS-15). Mann-Whitney test was used to examine differences between URM and ARM. Associated factors of mental distress were evaluated via a stepwise multiple regression analysis. URM showed significantly higher mean scores for PHQ-9 (p < .001) and RHS-15 (p < .001) compared to ARM indicating medium effect sizes. Furthermore, URM were significantly more likely to surpass the cut-off for depression (61.6% vs. 30.8%) and overall mental distress (81.4% vs. 53.8%) compared to ARM. The factors Number of stressful life events (SLE), Female gender, and Fear of deportation were found to be associated with an increased mental distress in URM, whereas Weekly contact to a family member, School attendance, and German language skills were accompanied with lower distress scores. All six factors accounted for 32% of the variance of mental distress in URM (p < .001). Within minor refugees, URM are a highly vulnerable subgroup, which should receive particular attention and more targeted measures by health authorities. Our results indicate that these measures should comprise a rapid promotion of family contact, school attendance, language acquisition, and the fast processing of asylum applications. However, the cross-sectional design limits the interpretability of the results.

Increasing sample diversity in psychiatric genetics - Introducing a new cohort of patients with schizophrenia and controls from Vietnam - Results from a pilot study.

OBJECTIVES: Genome-Wide Association Studies (GWAS) of Schizophrenia (SCZ) have provided new biological insights; however, most cohorts are of European ancestry. As a result, derived polygenic risk scores (PRS) show decreased predictive power when applied to populations of different ancestries. We aimed to assess the feasibility of a large-scale data collection in Hanoi, Vietnam, contribute to international efforts to diversify ancestry in SCZ genetic research and examine the transferability of SCZ-PRS to individuals of Vietnamese Kinh ancestry. METHODS: In a pilot study, 368 individuals (including 190 SCZ cases) were recruited at the Hanoi Medical University's associated psychiatric hospitals and outpatient facilities. Data collection included sociodemographic data, baseline clinical data, clinical interviews assessing symptom severity and genome-wide SNP genotyping. SCZ-PRS were generated using different training data sets: (i) European, (ii) East-Asian and (iii) trans-ancestry GWAS summary statistics from the latest SCZ GWAS meta-analysis. RESULTS: SCZ-PRS significantly predicted case status in Vietnamese individuals using mixed-ancestry (R2 liability = 4.9%, p = 6.83 × 10-8), East-Asian (R2 liability = 4.5%, p = 2.73 × 10-7) and European (R2 liability = 3.8%, p = 1.79 × 10-6) discovery samples. DISCUSSION: Our results corroborate previous findings of reduced PRS predictive power across populations, highlighting the importance of ancestral diversity in GWA studies.

Transcranial Direct Current Stimulation (tDCS) for major depression - Interim analysis of cloud supervised technical data from the DepressionDC trial.

BACKGROUND: Transcranial direct current stimulation (tDCS) of prefrontal cortex regions has been reported to exert antidepressant effects, though large scale multicenter trials in major depressive disorder (MDD) supporting this notion are still lacking. Application of tDCS in multicenter settings, however, requires measurement, storage and evaluation of technical parameters of tDCS sessions not only for safety reasons but also for quality control. To address this issue, we conducted an interim analysis of supervised technical data across study centers in order to monitor technical quality of tDCS in an ongoing multicenter RCT in MDD (DepressionDC trial). METHODS: Technical data of 818 active tDCS sessions were recorded, stored in a data cloud, and analysed without violating study blinding. Impedance, voltage and current were monitored continuously with one data point recorded every second of stimulation. RESULTS: Variability of impedance was considerable (1,42 kΩ, to 8,23 kΩ), inter-individually and even more intra-individually, but did not significantly differ between the study centre in Munich and all other sites. CONCLUSION: Measurement, centralized data storage via data cloud and remote supervision of technical parameters of tDCS are feasible and proposed for future RCTs on therapeutic tDCS in multiple settings.

Ketamine specifically reduces cognitive symptoms in depressed patients: An investigation of associated neural activation patterns.

Major depressive disorder (MDD) is characterized by heterogeneous cognitive, affective and somatic symptoms. Hence, the investigation of differential treatment effects on these symptoms as well as the identification of symptom specific biomarkers might crucially contribute to the development of individualized treatment strategies. We here aimed to examine symptom specific responses to treatment with ketamine, which repeatedly demonstrated rapid antidepressant effects in severe MDD. Additionally, we investigated working memory (WM) related brain activity associated with changes in distinct symptoms in order to identify specific response predictors. In a sample of 47 MDD patients receiving a single sub-anesthetic dose of ketamine, we applied a three-factor solution of the Beck Depression Inventory (BDI) to detect symptom specific changes 24 h post-infusion. A subsample of 16 patients underwent additional fMRI scanning during an emotional working memory task prior to ketamine treatment. Since functional aberrations in the default mode network (DMN) as well as in the dorsolateral prefrontal cortex (DLPFC) have been associated with impaired cognitive and emotional processing in MDD, we investigated neural activity in these regions. Our results showed that ketamine differentially affects MDD symptoms, with the largest symptom reduction in the cognitive domain. WM related neuroimaging results indicated that a more pronounced effect of ketamine on cognitive symptoms is predicted by lower DMN deactivation and higher DLPFC activation. Findings thereby not only indicate that ketamine's antidepressant efficacy is driven by a pro-cognitive mechanism, but also suggest that this might be mediated by increased potential for adaptive adjustment in the circumscribed brain regions.

[Psychosocial care of refugees in Germany : Insights from the emergency relief and development aid]. / Psychosoziale Versorgung von Flüchtlingen in Deutschland : Erkenntnisse aus der Not- und Entwicklungshilfe.

Approximately 1.2 million refugees have arrived in Germany since autumn 2014. They are often appraised as being a challenge for the German healthcare system because the acute need for healthcare support was large and appeared suddenly while at the same time resources were limited. This situation was previously unknown for a western European healthcare system, whereas it constitutes a typical challenge for nongovernmental organizations that are active in the field of emergency relief and development aid and that have developed a large number of successful intervention concepts. Of central importance in this context are the basic principles of equal rights, participation of those affected, the principle of nonmaleficence, the resource orientation instead of a deficit orientation as well as the need for integrated and stepped care models. These can serve as general principles not only in the setting of development aid in crisis areas worldwide but also in the health services provided to refugees in the current situation in Germany.

Endoscopic rendez-vous reconstruction of complete biliary obstruction.

BACKGROUND AND STUDY AIMS: Complete biliary strictures normally require surgical intervention. We describe an alternative, minimally invasive endoscopic/percutaneous rendez-vous technique for the reconstruction of complete benign biliary strictures. PATIENTS AND METHODS: Complete biliary strictures were reconstructed in four patients using a rendez-vous percutaneous-endoscopic or percutaneous-percutaneous route guided by fluoroscopic and visual (transillumination) control. RESULTS: All four patients were treated successfully and safely with the rendez-vous technique. Complications were caused by the preliminary creation, dilatation and maturation of the percutaneous tract. CONCLUSION: This technique may offer a good alternative to surgical bilio-enteric anastomosis in experienced hands. The long term course of the patients treated remains to be seen.

[Surgical treatment of esophageal diverticula : Endoscopic or open approach?] / Operative Therapie von Divertikeln der Speiseröhre : Endoskopisch oder offen?

Esophageal diverticula are comparatively rare. The majority are Zenker's diverticula but parabronchial and epiphrenic diverticula can also occur. Parabronchial diverticula are of low clinical relevance, whereas Zenker's and epiphrenic diverticula both belong to the group of pulsion diverticula and can become clinically apparent by dysphagia and regurgitation. Approximately 100 years after the first surgical treatment, peroral approaches (e.g. stapler dissection and flexible endoscopic diverticulotomy) have now achieved a certain level of importance. Both approaches are less invasive than the open approach but are evidently more prone to recurrences. Accordingly, traditional open diverticulectomy with cervical myotomy should be recommended to patients with a reasonable life expectancy and an acceptable operative risk. This holds particularly true for Brombart stages I-III of the disease, as complete myotomy cannot be achieved via the peroral access. The classical surgical treatment of epiphrenic diverticula is open or laparoscopic/thoracoscopic diverticulectomy with distal myotomy, mostly combined with an anterior partial fundoplication; however, the leakage rate is high and several alternative options are currently being evaluated.

Esophageal bougination: a novel ex vivo endoscopic training model correlated with clinical data.

BACKGROUND: Esophageal bougination is a worldwide standard endoscopic procedure. Clinical methods and recommendations are based on clinical experiences only. Mechanical properties have never been described. Aim of the study was to establish a realistic ex vivo training model. Therefore, detailed assessment of relevant mechanical features of esophageal bougination should be evaluated ex vivo and in patient setting and correlated against. PATIENTS AND METHODS: A three-step concept was used to evaluate mechanical properties at stenosis level. First, insertion forces were evaluated in an ex vivo linear single stenosis model during steady mechanical insertion. Second, adding friction and properties of the pharynx and upper esophagus, the model was integrated in an artificial endoscopic training model (ELITE training model). Third, in vivo measurements were taken to correlate ex vivo data with parameters of a realistic patient setting. RESULTS: With the presented setup, we were able to assess insertion force and pressure levels in an artificial stricture using different sizes of commercially available standard bougies. In all models, there was a relevant increase in insertion force with higher stricture pressure levels. Insertion force levels in the ELITE model show higher levels compared to the linear stenosis model. Having regard to the maximum forces in patients, there is also a constant increase in mean insertion force according to higher bougie sizes, but lower forces were measured as in the ELITE model. DISCUSSION: The applied models are suitable to appraise mechanical properties of esophageal bougination in an ex vivo model and patient setting. Forces could be constituted reliable, significant increase was documented according to stenosis level and results were comparable to patient data. This was comparable to patient data. Further clinical evaluation in different kinds of stenosis is necessary.

[Mental treatment of refugees in Germany : Model for a stepped approach]. / Psychische Versorgung von Flüchtlingen in Deutschland : Modell für ein gestuftes Vorgehen.

The recent influx of refugees and asylum seekers into Germany poses a challenge for the national healthcare system. In compliance with the present Asylum Seekers Benefits Act, the national healthcare system can be expected to have 1.5 million new members by early 2017. Providing adequate care particularly for people with mental illnesses or disorders will represent an immense challenge for all actors in the system. The circumstances of the flight combined with the foreign linguistic and socio-cultural background increase the severity of the cases and the difficulties of treatment. No procedures or guidelines for treatment have yet been established to ensure a standardized, cost-efficient and therapeutically effective treatment of patients with this background. This article describes the components of a stepped treatment procedure and proposes a stepped and collaborative care model (SCCM) that could be evaluated in nationwide studies. This approach is based on national and international treatment guidelines and aims to provide target-group specific, culturally sensitive methods of diagnosis and treatment. The various steps of the model build on each other, with the first steps relying on technological aids (e.g. online or smartphone options) and support from lay helpers and the more expensive specialist psychiatric and psychotherapeutic therapy only being initiated in cases of more severe mental disorders.

High-resolution manometry in patients with eosinophilic esophagitis under topical steroid therapy-a prospective observational study (HIMEOS-study).

BACKGROUND: In eosinophilic esophagitis (EoE), dysphagia, which might reflect esophageal dysmotility, is the most common symptom. High-resolution manometry (HRM) has become widely accepted for evaluating esophageal motility disorders, but to date has been sparsely examined in EoE patients, particularly under therapy. The aim of this study was to evaluate HRM in symptomatic EoE-patients under topical steroid treatment. METHODS: In this prospective observational study, symptomatic EoE patients received HRM-examinations before and after 8 weeks of topical steroid treatment with budesonide. All HRM-abnormalities were assessed and interpreted according to the Chicago classification. The primary endpoint was the influence of topical steroid treatment on the intrabolus pressure (IBP). Clinical symptoms, endoscopic findings and histological esophageal eosinophilic load were also reported. KEY RESULTS: Twenty symptomatic EoE patients were included. Overall success of budesonide therapy was 85% regarding complete histologic remission and 80% regarding complete clinical remission. High-resolution manometry showed abnormal esophageal motility in 35% of patients at baseline, which was resolved after therapy in 86% of these patients. Most frequent HRM-findings were early pan-esophageal pressurizations and weak persitalsis. There was no significant reduction of the IBP under therapy (before: 12.5 ± 4.9 mmHg, after: 10.9 ± 2.9 mmHg; p = 0.119). CONCLUSIONS & INFERENCES: Although dysphagia is the leading symptom of EoE, HRM is able to identify esophageal motility disorders in only some EoE patients. Observed motility disorders resolve after successful treatment in almost all of these patients. Intrabolus pressure does not seem an optimal parameter for the monitoring of successful treatment response in EoE patients.

[Transcranial direct current stimulation for depressive disorders]. / Transkranielle Gleichstromstimulation bei depressiven Störungen.

Major depressive disorders are one of the most prevalent psychiatric disorders worldwide but approximately 20-30 % of patients do not respond to standard guideline conform treatment. Recent neuroimaging studies in depressive patients revealed altered activation patterns in prefrontal brain areas and that successful cognitive behavioral therapy and psychopharmacological interventions are associated with a reversal of these neural alterations. Therefore, a direct modulation of prefrontal brain activation by non-invasive brain stimulation techniques, such as transcranial direct current stimulation (tDCS) seems to be a promising and innovative approach for the treatment of depressive disorders. In addition, recent neuropsychological findings indicated an augmentation of positive tDCS effects by simultaneous external activation of the stimulated brain area, for example by cognitive training tasks. Based on these findings, the possibility to augment cognitive-emotional learning processes during cognitive behavioral therapy by simultaneous tDCS to increase antidepressive therapeutic effects is discussed in this article.

Peripheral blood eosinophils and other non-invasive biomarkers can monitor treatment response in eosinophilic oesophagitis.

BACKGROUND: Monitoring of the treatment response in eosinophilic oesophagitis (EoE) requires structured endoscopical and histological examination of the oesophagus. Less invasive methods would be highly desirable. AIM: To evaluate the utility of several EoE-associated blood and serum markers in order to non-invasively monitor the response to treatment with swallowed topical corticosteroids in adult EoE patients. METHODS: In a randomised, controlled double-blind trial blood samples of EoE patients (n = 69) were collected at baseline and after 14 days of treatment with budesonide (n = 51) or placebo (n = 18) respectively. Absolute blood eosinophil count (AEC) as well as serum levels of CCL-17, CCL-18, CCL-26, eosinophil-cationic-protein (ECP) and mast cell tryptase (MCT) were determined and correlated with oesophageal eosinophil density and with symptom and endoscopy scores. RESULTS: Histological remission, defined as mean number of <16 eos/mm(2) hpf at end-of-treatment, was achieved in 98% of the budesonide and 0% of the placebo recipients. AEC [380.2 vs. 214.7/mm(3) (P = 0.0001)], serum-CCL-17 [294.3 vs. 257.9 pg/mL (P = 0.0019)], -CCL-26 [26.7 vs. 16.2 pg/mL (P = 0.0058)], -ECP [45.5 ± 44.7 vs. 27.5 ± 25.0 µg/L (P = 0.0016)] and -MCT [5.3 ± 2.9 vs. 4.5 ± 2.6 µg/L (P = 0.0019)] significantly decreased under budesonide but not under placebo. AEC significantly correlated with oesophageal eosinophil density before (r = 0.28, P = 0.0236) and after (r = 0.42, P = 0.0004) budesonide treatment. In ROC-AUC analyses post-treatment values of AEC were significantly associated with histological remission (ROC-AUC 0.754; 95% CI: 0.617-0.891; P = 0.0003). CONCLUSIONS: The budesonide-induced treatment response in EoE is mirrored by several blood and serum markers, and the absolute blood eosinophil count is the most valuable as it shows correlation with the oesophageal eosinophil density.

Different patterns of local field potentials from limbic DBS targets in patients with major depressive and obsessive compulsive disorder.

The role of distinct limbic areas in emotion regulation has been largely inferred from neuroimaging studies. Recently, the opportunity for intracranial recordings from limbic areas has arisen in patients undergoing deep brain stimulation (DBS) for neuropsychiatric disorders including major depressive disorder (MDD) and obsessive compulsive disorder (OCD). Here we test the hypothesis that distinct temporal patterns of local field potential (LFP) activity in the human limbic system reflect disease state and symptom severity in MDD and OCD patients. To this end, we recorded LFPs via implanted DBS electrodes from the bed nucleus of stria terminalis (BNST area) in 12 patients (5 OCD, 7 MDD) and from the subgenual cingulate cortex in 7 MDD patients (CG25 area). We found a distinct pattern of oscillatory activity with significantly higher α-power in MDD compared with OCD in the BNST area (broad α-band 8-14 Hz; P<0.01) and a similar level of α-activity in the CG25 area as in the BNST area in MDD patients. The mean α-power correlated with severity of depressive symptoms as assessed by the Beck depression inventory in MDD (n=14, r=0.55, P=0.042) but not with severity of obsessive compulsive symptoms in OCD. Here we show larger α-band activity in MDD patients compared with OCD recorded from intracranial DBS targets. Our results suggest that α-activity in the limbic system may be a signature of symptom severity in MDD and may serve as a potential state biomarker for closed loop DBS in MDD.

Argon plasma coagulation of gastric inlet patches for the treatment of globus sensation: it is an effective therapy in the long term.

AIM: To determine the long-term effect of argon plasma coagulation (APC) of gastric inlet patches in the cervical esophagus for patients suffering from globus sensation. METHODS: We intended to follow up all patients between 2004 and 2011 (n = 49) who received argon plasma ablation of gastric inlet patches for globus sensation at our clinic. Symptoms were assessed by a visual analogue scale (VAS) in 31 of 49 patients. Follow-up endoscopy of the upper gastrointestinal tract was performed to confirm residual or relapsed cervical inlet patches. RESULTS: After a median period of 27 months, APC was assessed as a successful therapy in 23 of 31 patients (74%). VAS scores decreased significantly from 7.6 to 4.0 in the long term. Twenty-two of 31 patients were willing to undergo follow-up endoscopy. Endoscopy revealed recurrent/residual gastric inlet patches after APC in 11 of 22 cases. These patients suffered from a significant relapse of symptoms in the postinterventional period (p < 0.001). CONCLUSION: This retrospective study indicates that APC of gastric inlet patches for the treatment of globus sensation might be a sufficient therapy option. Recurrences or residual heterotopic gastric mucosa are possible and seem to be associated with a relapse of symptoms. Therefore, endoscopic follow-up and retreatment might be necessary if globus sensation is not sufficiently eliminated.

[Diagnosis and therapy of atypical reflux symptoms when PPI therapy fails]. / Diagnostik und Therapie atypischer Refluxsymptome bei fehlendem PPI-Ansprechen.

Gastroesophageal reflux disease (GERD) is a frequent chronic disorder occurring in two forms: on the one hand, typical symptoms such as heartburn and acid regurgitation are seen, while on the other hand atypical (extraesophageal) symptoms such as chronic cough, hoarseness, recurrent sinusitis, globus sensations in the throat, a burning feeling on the tongue, dental erosions and the constant need to clear the throat can be associated with gastroesophageal reflux. The standard therapeutic medical procedure comprises the administration of acid-suppressive agents, proton pump inhibitors (PPI). However, this therapy has proved to be ineffective in a number of patients, especially in atypical GERD. Only after reliable identification of the GERD patient by using valid diagnostic tools medical or interventional therapeutic options can be applied individually. In the absence of atypical GERD symptoms, the diagnosis of GERD becomes very unlikely and other causes of the symptoms need to be taken into consideration.

Bispectral index monitoring of midazolam and propofol sedation during endoscopic retrograde cholangiopancreatography: a randomized clinical trial (the EndoBIS study).

INTRODUCTION: Bispectral index (BIS) monitoring provides a non-invasive measure of the level of sedation. The purpose of this randomized, single-blind clinical trial was to evaluate whether BIS monitoring of sedation would lead to improved oxygenation and a reduced rate of cardiopulmonary complications during endoscopy. PATIENTS AND METHODS: Patients undergoing endoscopic retrograde cholangiopancreatography (ERCP) under procedural sedation with a combination of low dose midazolam and propofol were randomly assigned to either standard monitoring of sedation only (BIS-blinded arm) or an open arm in which additional BIS monitoring was available (BIS-open arm). In the BIS-open arm, propofol administration was to be withheld if BIS values were <55. The primary study end point was the mean oxygen saturation per patient. Secondary end points were the rates of cardiopulmonary complications, propofol dose, quality of sedation (patient cooperation as rated by the endoscopist and patient satisfaction), and recovery. RESULTS: A total of 144 patients were enrolled and included in the intention-to-treat analysis. Mean oxygen saturation per patient was 97.7% in the BIS-open arm and 97.6% in the BIS-blinded arm (P=0.71). Total rates of cardiopulmonary complications, single numbers of hypoxemic, bradycardic, and hypotensive events, mean propofol doses, and quality of sedation also showed no statistically significant differences between the groups. However, BIS monitoring did result in faster recovery of patients as reflected by shorter times to eye opening (P=0.001), first verbal response (P=0.02), and leaving the procedure room (P<0.001). CONCLUSIONS: The use of additional BIS monitoring did not lead to improved oxygenation or a reduced rate of cardiopulmonary complications. Recovery times after the procedure were shorter than with standard monitoring alone, but the clinical benefit for daily practice may be limited.

Multimodal endoscopic therapy for multifocal intraepithelial neoplasia and superficial esophageal squamous cell carcinoma - a case series.

Local endoscopic procedures are increasingly used and accepted treatments for unifocal superficial esophageal squamous cell carcinoma (SESCC). In multifocal SESCC, esophagectomy with or without chemoradiotherapy is often regarded as standard therapy. However, a combination of local endoscopic resection and new techniques such as radiofrequency ablation may play an increasing role in the treatment of selected patients with multifocal SESCC. The aim of this series was to evaluate the feasibility of a multimodal endoscopic approach. We report a case series of six consecutive patients from a European tertiary center who underwent endoscopic treatment for multifocal SESCC. The treatment comprised endoscopic mucosal resection using the cap technique or endoscopic submucosal dissection, in combination with radiofrequency ablation. The main outcome measure was complete tumor eradication after therapy and during the follow-up period. Using such an approach, complete eradication of cancer was achieved in all patients during follow-up. No major adverse events occurred. In conclusion, in selected patients with multifocal or residual SESCC, local resection techniques in combination with radiofrequency ablation may be safe and potentially curative alternative treatments.