Feasibility of Azacitidine Added to Standard Chemotherapy in Older Patients with Acute Myeloid Leukemia — A Randomised SAL Pilot Study

Introduction: Older patients with acute myeloid leukemia (AML) experience short survival despite intensive chemotherapy. Azacitidine has promising activity in patients with low proliferating AML. The aim of this dose-finding part of this trial was to evaluate feasibility and safety of azacitidine combined with a cytarabine- and daunorubicin-based chemotherapy in older patients with AML. Trial Design: Prospective, randomised, open, phase II trial with parallel group design and fixed sample size. Patients and Methods: Patients aged 61 years or older, with untreated acute myeloid leukemia with a leukocyte count of ,20,000/ml at the time of study entry and adequate organ function were eligible. Patients were randomised to receive azacitidine either 37.5 (dose level 1) or 75 mg/sqm (dose level 2) for five days before each cycle of induction (7+3 cytarabine plus daunorubicine) and consolidation (intermediate-dose cytarabine) therapy. Dose-limiting toxicity was the primary endpoint. Results: Six patients each were randomised into each dose level and evaluable for analysis. No dose-limiting toxicity occurred in either dose level. Nine serious adverse events occurred in five patients (three in the 37.5 mg, two in the 75 mg arm) with two fatal outcomes. Two patients at the 37.5 mg/sqm dose level and four patients at the 75 mg/sqm level achieved a complete remission after induction therapy. Median overall survival was 266 days and median event-free survival 215 days after a median follow up of 616 days. Conclusions: The combination of azacitidine 75 mg/sqm with standard induction therapy is feasible in older patients with AML and was selected as an investigational arm in the randomised controlled part of this phase-II study, which is currently halted due to an increased cardiac toxicity observed in the experimental arm. Trial Registration: This trial is registered at clinical trials.gov (identifier: NCT00915252)

Integration of e-Health Tools Into Face-to-Face Psychotherapy for Borderline Personality Disorder:A Chance to Close the Gap Between Demand and Supply?

Borderline personality disorder (BPD) is a severe, highly prevalent mental disorder. Effective psychological treatments for BPD are available. However, most patients do not receive evidence-based treatments partly because of high treatment delivery costs and lack of specialized therapists. By integrating specialized e-health tools into BPD-specific treatments, treatment intensity can be increased, frequency of face-to-face sessions and burden for psychotherapists can be reduced, and implementation of new skills and experiences in the everyday life of these patients can be promoted. This bears great potential to increase the availability of evidenced-based psychotherapy for BPD patients and close the gap between demand and supply. In this article we present such an innovative e-health tool, priovi, which has been developed for schema therapy. The concept and application of priovi are described and illustrated with a case example

Treatment of Tourette syndrome with attention training technique—a case series

The existing therapeutic strategies of Tourette syndrome (TS) do not lead to sufficient improvement in a significant number of patients. Recently published studies show that paying attention to tics increases whereas directing attention away decreases tic frequency. The aim of the present case series in three patients with TS was to investigate the effect of attention training technique (ATT) on TS symptoms. ATT is a technique derived from metacognitive therapy that aims on training patients to consciously (re-)focus their attention away from themselves. Friedman’s chi-square test indicated a trend regarding the reduction of tic frequency and tic severity and a significant reduction of positive metacognitions from pre-baseline to follow-up. Reliable Change Indices (RCIs) are given for each measure and patient. Given the small number of patients, further studies including randomized controlled trials appear warranted

The mediating effect of difficulties in emotion regulation on the association between childhood maltreatment and borderline personality disorder

Background: Childhood maltreatment and difficulties in emotion regulation are common in patients with Borderline Personality Disorder (BPD) and Depressive Disorders (DD). Objective: This study examines differences between patients with BPD and patients with DD, regarding childhood maltreatment and difficulties in emotion regulation as well as the mediating effect of different aspects of emotion regulation deficits on the association between childhood maltreatment and BPD-symptoms. Method: A total of 305 participants, 177 with BPD and 128 with DD completed an assessment including the Childhood Trauma Questionnaire (CTQ), the Emotion Regulation Scale (DERS), the Brief Symptom Inventory (BSI), and the Structured Clinical Interview for DSM-IV (SCID). Data was analyzed using multiple analyses of variances and mediation analyses. Results: Patients with BPD reported more childhood maltreatment and more difficulties in emotion regulation than patients with DD. When general symptom severity, age, and gender were included in the analysis as covariates only group differences regarding ‘impulse control difficulties’ (F(1,299) = 38.97, p < .001, ηp2 = .115), ‘limited access to emotion regulation strategies’ (F(1,299) = 4.66, p = .032, ηp2 = .015), and ‘lack of emotional clarity’ (F(1,299) = 9.38, p = .002, ηp2 = .030) remained statistically significant. A mediation analysis, including above-mentioned covariates, indicated an association between emotional abuse and BPD-symptoms, which was mediated by difficulties in emotion regulation (indirect effect B = .012, 95% CI [.001; .031], R2 = .429). Subscale analyses revealed ‘impulse control difficulties’ as the aspect of difficulties in emotion regulation that has the greatest impact on this association (B = .021, 95% CI [.003; .045]). Conclusions: Patients with BPD display more childhood maltreatment and difficulties in emotion regulation than patients with DD. Difficulties in emotion regulation, especially difficulties in impulse control, seem to play an important role in the association between childhood emotional abuse and BPD-symptoms

Association of Genetic Variation at AQP4 Locus with Vascular Depression

Despite its substantial clinical importance, specific genetic variants associated with depression have not yet been identified. We sought to identify genetic variants associated with depression by (a) focusing on a more homogenous subsample (vascular depression) and (b) applying a three-stage approach. First, we contacted 730 participants with a confirmed atherosclerotic disease (coronary artery disease) from a population-based study population (German Myocardial Infarction Family Study IV) for psychiatric assessment with the Mini International Neuropsychiatric Interview. Second, we genotyped these patients using genome-wide single nucleotide polymorphism (SNP) arrays. Third, we characterized the SNP via in-silico analysis. The final sample consisted of 342 patients (78.3% male, age = 63.2 &plusmn; 9.9 years), 22.8% with a severe depressive disorder. Variant rs528732638 on chromosome 18q11.2 was a genome-wide significant variant and was associated with 3.6-fold increase in the odds of lifetime depression. The locus belongs to a linkage disequilibrium block showing expression quantitative trait loci effects on three putative cis-regulated genes, including the aquaporin 4 (AQP4) locus. AQP4 is already known to mediate the formation of ischemic edema in the brain and heart, increasing the size and extent of resulting lesions. Our findings indicate that AQP4 may also play a role in the etiopathology of vascular depression