Background Negative symptoms are usually evaluated with scales based on observer ratings and up to now self-assessments have been overlooked. The aim of this paper was to validate the Self-evaluation of Negative Symptoms (SNS) in a large European sample coming from 12 countries. We wanted to demonstrate: (1) good convergent and divergent validities; (2) relationships between SNS scores and patients' functional outcome; (3) the capacity of the SNS compared to the Brief Negative Symptom Scale (BNSS) to detect negative symptoms; and (4) a five-domain construct in relation to the 5 consensus domains (social withdrawal, anhedonia, alogia, avolition, blunted affect) as the best latent structure of SNS. Methods Two hundred forty-five subjects with a DSM-IV diagnosis of schizophrenia completed the SNS, the Positive and Negative Syndrome Scale (PANSS), the BNSS, the Calgary Depression Scale for Schizophrenia (CDSS), and the Personal and Social Performance (PSP) scale. Spearman's Rho correlations, confirmatory factor analysis investigating 4 models of the latent structure of SNS and stepwise multiple regression were performed. Results Significant positive correlations were observed between the total score of the SNS and the total scores of the PANSS negative subscale (r = 0.37; P < 0.0001) and the BNSS (r = 0.43; p < 0.0001). SNS scores did not correlate with the level of insight, parkinsonism, or the total score of the PANSS positive subscale. A positive correlation was found between SNS and CDSS (r = 0.35; p < 0.0001). Among the 5 SNS subscores, only avolition subscores entered the regression equation explaining a lower functional outcome. The 1-factor and 2-factor models provided poor fit, while the 5-factor model and the hierarchical model provided the best fit, with a small advantage of the 5-factor model. The frequency of each negative dimension was systematically higher using the BNSS and the SNS vs. the PANSS and was higher for alogia and avolition using SNS vs. BNSS. Conclusion In a large European multicentric sample, this study demonstrated that the SNS has: (1) good psychometric properties with good convergent and divergent validities; (2) a five-factor latent structure; (3) an association with patients' functional outcome; and (4) the capacity to identify subjects with negative symptoms that is close to the BNSS and superior to the PANSS negative subscale.

Patients with a First-Episode of Psychosis (FEP) exhibit low-grade inflammation as demonstrated by elevated levels of C-reactive protein (CRP) and proinflammatory cytokines. The primary goal of this study was to investigate the association between proinflammatory biomarkers and clinical outcomes in unmedicated FEP patients. We used clinical data and biological samples from 289 FEP patients participating to the Optimization of Treatment and Management of Schizophrenia in Europe (OPTIMISE) clinical trial. Patients were assessed at baseline and 4-5 weeks after treatment with amisulpride. Baseline serum levels of interleukin (IL)-6, IL-8, tumor necrosis factor (TNF)-alpha, and CRP were measured. We first used multivariable regression to investigate the association between each of the 4 tested biomarkers and the following clinical outcomes: Positive and Negative Syndrome Scale (PANSS), Calgary Depression Score for Schizophrenia (CDSS), remission according to Andreasen's criteria, and Serious Adverse Events (SAEs). As a complementary approach, we used an unsupervised clustering method to stratify patients into an "inflamed" or a "non-inflamed" biotype based on baseline levels of IL-6, IL-8, and TNF-alpha. We then used linear and logistic regressions to investigate the association between the patient biotype and clinical outcomes. After adjusting for covariates and confounders, we did not find any association between IL-6, IL-8, TNF-alpha, CRP, or the patient biotype and clinical outcomes. Our results do not support the existence of an association between baseline levels of CRP and proinflammatory cytokines and early response to amisulpride in unmedicated FEP patients. ClinicalTrials.gov Identifier: NCT01248195.

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Objective: Placebo effects remain largely unexplored in clinical trials of long-acting injectable (LAI) antipsychotics for schizophrenia. This study aims to characterize patients showing improvements after placebo injections and to search for criteria for the prediction of subsequent response based on the magnitude of score changes after the first week of treatment. Methods: Data from 450 patients with schizophrenia (DSM-IV) who received placebo injections in 4 double-blind randomized controlled trials evaluating efficacy of LAI paliperidone palmitate obtained through the Yale University Open Data Access (YODA) project were analyzed. These 4 studies were conducted from October 2003 to March 2008. Multiple logistic regression analyses were conducted to examine associations between placebo response and demographic and clinical characteristics. The predictive power of improvement at week 1 for response at week 9 was investigated; sensitivity and specificity of incremental 5% cutoff points between a 5% and 25% reduction in Positive and Negative Syndrome Scale (PANSS) total score at week 1 were calculated. Results: Percent reduction in the PANSS total score at week 1 and a lower PANSS G12 item score (ie, better in judgment and insight) at baseline were significantly associated with placebo response at week 9 (odds ratio [OR] = 1.063; 95% CI, 1.040-1.087, P <.001; and OR= 0.739; 95% CI, 0.553-0.986, P =.040, respectively, in the per-protocol analysis). Cutoffs of a 10% (accuracy = 0.724 in the per-protocol analysis) and 15% (accuracy = 0.722 in the last-observation-carried-forward analysis) reduction in the PANSS total score at week 1 showed the highest predictive power. Conclusions: The appreciation that longer-term response following placebo injections can be predicted by a 10%-15% PANSS total score reduction at week 1 could guide the design of future clinical trials of LAI antipsychotics in schizophrenia to identify and exclude potential placebo responders early during the course of the study.

Patients suffering from schizophrenia are often treated in locked psychiatric units because of psychomotor agitation, hostility and aggressive behavior, or suicidality. Because of legal conditions, investigations on these acutely ill patients are difficult, and many studies do not represent 'real-life psychiatry'. This retrospective survey was conducted at the Department of Psychiatry, Psychotherapy and Psychosomatics of the Medical University, Innsbruck, Austria. Data were collected from the records of all adult inpatients suffering from a schizophrenia spectrum disorder according to the International Classification of Diseases, 10th ed. (ICD-10) (F2x) who had been admitted to a locked unit in 1997, 2002, 2007, and 2012. In addition to demographic data, diagnoses at the time of admission, length of stay at the locked unit, and psychopharmacological treatment (3 h before and following admission) were recorded. The mean length of stay at a locked unit decreased significantly from 11.8±4.43 days (mean±SD) in 1997 to 8.5±12.96 days (mean±SD) in 2012. The use of antipsychotics decreased nonsignificantly from 1997 to 2012. Despite an increasing use of second compared with first-generation antipsychotic drugs over the course of time, haloperidol was the most frequently used single compound in all investigated years except 2012. The majority of medications were administered orally. The use of benzodiazepines did not change substantially over the course of time. All in all, pharmacological emergency treatment of patients suffering from schizophrenia spectrum disorders in locked units was in line with current treatment guidelines, which recommend the use of second-generation antipsychotic drugs, monotherapy, oral application, and cautious dosing.

BACKGROUND:Patients suffering from psychiatric disorders are often treated in locked psychiatric units owing to psychomotor agitation, hostility and aggressive behavior, or suicidality. Because of legal conditions, investigations of these acutely ill patients are difficult, and many studies do not represent real-life psychiatry. In Austria, admission to a locked psychiatric unit is regulated by a national law for involuntary admission, which came into effect in 1991. The current retrospective study investigated the management of patients who were admitted involuntarily to an academic treatment center after the inauguration of this law.METHODS:Data collection comprised all admissions to a locked unit at the Department of Psychiatry, Psychotherapy and Psychosomatics of the Medical University Innsbruck in the years 1992, 1997, 2002, 2007, and 2012. Demographics, admission diagnosis, current danger posed to self or others, and the initial psychopharmacological intervention were assessed.RESULTS:The rate of admissions to a locked unit increased significantly throughout the course of the study, and the length of stay decreased from 8.57 days in 1997 to 6.43 days in 2012. Most patients received medication orally. Dosage of antipsychotics and benzodiazepines decreased throughout the investigation period. Self-endangering patients were treated with somewhat (nonsignificantly) higher benzodiazepine and significantly lower antipsychotic mean doses than patients posing danger to others.CONCLUSIONS:Although dosage of medication was reduced, the duration of stay in a locked unit decreased significantly over the investigated years. These findings suggest that a carefully considered pharmacological treatment may be at least as effective as a more aggressive approach.

Purpose This randomized, double-blind (DB), non-inferiority phase 3 study was conducted to assess the efficacy and safety of paliperidone palmitate 3-month (PP3M) vs 1-month formulation (PP1M) in European and non-European patients with schizophrenia. Patients and methods In this randomized, DB, parallel-group study, adult patients (18–70 years) with schizophrenia (per DSM-IV-TR) having Positive and Negative Syndrome Scale (PANSS) total score between 70 and 120; previously stabilized on PP1M were enrolled. The study had 4 phases: screening (3 weeks), open-label (OL) stabilization (17 weeks), DB (48 weeks) and follow-up (4–12 weeks) phase. Patients were treated with fixed-dose PP3M (175–525 mg eq deltoid/gluteal) or PP1M (50–150 mg eq deltoid/gluteal) for 48 weeks in DB phase. Results In total, 487 European (PP3M, n=242; PP1M, n=245) and 508 non-European patients (PP3M, n=241; PP1M, n=267) entered DB phase (modified intent-to-treat (mITT) [DB] analysis set). Among the 508 non-European patients in mITT set, 67.7% were from Asia (n=344) and 32.3% were from rest of world (ROW, n=164). During the DB phase, similar percentage of Europeans (PP3M: 7%; PP1M: 8%) and non-Europeans (PP3M: 9%; PP1M: 10%) experienced relapse (Kaplan–Meier estimate PP3M–PP1M [95% CI] of percentage of relapse-free patients at the end of DB phase [primary endpoint]: European: 1.0% [−4.3%; 6.2%]; non-European: 1.4% [−4.4%; 7.1%]; Asian: 1.6% [−5.7%; 9.0%]; and ROW: 1.4% [−7.0%, 9.8%], per-protocol analysis set). Incidence of treatment-emergent adverse events (TEAEs) was lower in Europeans (PP3M: 56%, PP1M: 59%) than non-Europeans (PP3M: 80%, PP1M: 73%). The most commonly reported TEAE was weight gain. Conclusion PP3M showed similar efficacy to PP1M in Europeans and non-Europeans, consistent with non-inferiority of PP3M to PP1M observed in overall population. Rates of AEs were higher in non-Europeans. However, weight gain was greater in non-Europeans, especially the Asian population.

Background Burnout is a syndrome characterized by emotional exhaustion, depersonalization and low personal accomplishment. The primary objective of this study was to investigate both the prevalence and severity of burnout symptoms in a sample of clinical physicians from different speciality disciplines.Methods A total of 69 clinical physicians <= 55 years who are working at the Medical University/regional Hospital Innsbruck were included into a cross-sectional study. Next to the assessment of sociodemographic and work-related variables the Maslach Burnout Inventory (MBI) was used to investigate burnout symtoms.Results Overall, 8.8% of the study population showed high emotional exhaustion with high or moderate depersonalization and low personal accomplishment and therefore had a high risk to develop a burnout syndrom. 11.8% showed a moderade burnout risk. Neither sociodemographic variables nor the degree of educational qualification or speciality discipline had an influence on burnout symptoms. However, there was a positive correlation between scientific activity and personal accomplihment.Conclusion Our results suggest that the dimension of burnout symtoms among clinical physicians in Austria has be taken seriously. Further research is needed to develop specific programs in terms of burnout prevention and burnout therapy.

Herein a NiCrBSi coating with 800 μm thickness was fabricated via plasma spraying on AISI 1045 steel, whereupon gas tungsten arc welding (GTA) process was employed to remelt the coating. The microstructure and mechanical properties of the coating before and after remelting were investigated. The results indicate that microstructural inhomogeneity in the as-sprayed coating were almost completely eliminated by GTA remelting. The main phases in the as-sprayed coating are γ-Ni, Cr7C3 and Cr2B. While, the remelted coating is mainly composed of fine dendrite γ-(Ni,Fe,Cr) and thin interdendritic lamellar eutectic (Fe,Cr)23C6. Moreover, there are some submicron particles Ni3B, CrB and Ni3Si in the grain interior of γ-(Ni,Fe,Cr), and a large number of nanocrystallines in the grain boundary of γ-(Ni,Fe,Cr). After remelting, a compact and complete solid solution γ-(Ni,Fe,Cr) is formed at the interface between the remelted coating and substrate, hence the interface is transformed from mechanical bonding to metallurgical bonding. In addition, remelting the coating was found to induce a 84.4% increase in the elastic modulus, a 18.5 times increase in the fracture toughness, and a 42.8% increase in the microhardness. Therefore, GTA remelting is found a feasible method to significantly improve the microstructure and mechanical properties of the coating.

Burnout ist kein akuter Zustand sondern eine anhaltende Stressreaktion, gekennzeichnet durch emotionale Erschöpfung, Depersonalisation und fehlende persönliche Erfüllung. Ziel dieser Studie war es, Prävalenz und Ausprägung der Burnout-Symptomatik in einer Population von KlinikärztInnen zu untersuchen und einen möglichen Zusammenhang zwischen Burnout-Symptomatik und soziodemografischen und berufsbezogenen Variablen zu ermitteln.

Problem: Exercise programs may increase abstinence rate in patients with alcohol use disorder (AUD). However, adherence to exercise programs is influenced by acute affective responses during the activity and preferences regarding the type of exercise. Thus, the aim of the present study was to assess the effects of two different exercise types on affective responses, cravings and heart rate variability (HRV).Method: Sixteen inpatients with diagnosed AUD were recruited during regular withdrawal treatment and took part in a randomized cross-over trial. Fifteen participants completed three 60-min interventions: a Nordic-walking condition (NW), a Yoga-Gymnastics condition (YG) and a passive control condition (PC). Affective responses, cravings and HRV were assessed before, during, immediately after, as well as 10 and 180 min after each intervention.Results: Repeated measures ANOVAs revealed a significantly higher increase in perceived activation during NW vs. PC (partial eta(2) = 0.34) as well as during YG vs. PC (partial eta(2) = 033). Affective valence significantly increased during NW vs. YG (partial eta(2) = 0.34). For cravings and HRV, no significant differences between treatment conditions were found.Conclusions: Results demonstrated that an acute exercise bout improved affective responses in inpatients with alcohol use disorder and indicated preferences towards NW compared to YG regarding affective valence during exercise. However, there were no differences after the interventions. Related to results of current literature, exercise bouts may provide some short-term motivation for abstinence in therapeutic settings and help preventing alcohol relapse through establishing alternative behavioural patterns. (C) 2017 Elsevier Ltd. All rights reserved.

BACKGROUNDDespite growing evidence for neurobehavioral deficits in social cognition in alcohol use disorder (AUD), the clinical relevance remains unclear, and little is known about its impact on treatment outcome. This study prospectively investigated the impact of neurocognitive social abilities at treatment onset on treatment completion.METHODSFifty-nine alcohol-dependent patients were assessed with measures of social cognition including 3 core components of empathy via paradigms measuring: (i) emotion recognition (the ability to recognize emotions via facial expression), (ii) emotional perspective taking, and (iii) affective responsiveness at the beginning of inpatient treatment for alcohol dependence. Subjective measures were also obtained, including estimates of task performance and a self-report measure of empathic abilities (Interpersonal Reactivity Index). According to treatment outcomes, patients were divided into a patient group with a regular treatment course (e.g., with planned discharge and without relapse during treatment) or an irregular treatment course (e.g., relapse and/or premature and unplanned termination of treatment, "dropout").RESULTSCompared with patients completing treatment in a regular fashion, patients with relapse and/or dropout of treatment had significantly poorer facial emotion recognition ability at treatment onset. Additional logistic regression analyses confirmed these results and identified poor emotion recognition performance as a significant predictor for relapse/dropout. Self-report (subjective) measures did not correspond with neurobehavioral social cognition measures, respectively objective task performance. Analyses of individual subtypes of facial emotions revealed poorer recognition particularly of disgust, anger, and no (neutral faces) emotion in patients with relapse/dropout.CONCLUSIONSSocial cognition in AUD is clinically relevant. Less successful treatment outcome was associated with poorer facial emotion recognition ability at the beginning of treatment. Impaired facial emotion recognition represents a neurocognitive risk factor that should be taken into account in alcohol dependence treatment. Treatments targeting the improvement of these social cognition deficits in AUD may offer a promising future approach.

Background: Randomized controlled trials (RCTs) and observational studies frequently differ with regard to study dropouts. The present naturalistic follow-up investigation aimed to shed a light on this issue by evaluating the time to and the reasons for study dropout in patients suffering from schizophrenia who started monotherapy with an oral new-generation antipsychotic. Methods: From October 1997 to September 2010, patients aged between 18 and 65 years who were treated in an in- or outpatient unit of the Department of Psychiatry, Psychotherapy and Psychosomatics of the Medical University Innsbruck were allocated to a naturalistic drug monitoring program when starting monotherapy with an oral new-generation antipsychotic except for clozapine. Patients were followed up to a maximum observation period of 12 months, and psychopathological symptoms as well as safety data were assessed regularly. The reasons for study dropout were collected using a clinical report form and were categorized into “poor response,” “noncompliance,” “side effects,” “suicide,” “withdrawal of written consent,” “logistic reasons” (i.e., relocation or continuing treatment at another facility), and “nonappearance.” Results: To this end, 194 patients were enrolled in this trial. In all, 9.3% of study participants completed the study. The mean time to study dropout was 2.6 ± 2.7 months with almost two-thirds of patients dropping out within 3 months; 44.3% discontinued medication at the date of study dropout, and the remainders dropped out due to withdrawal of written consent, logistic reasons, or nonappearance to the study visit, which were not necessarily to be equated with cessation of the antipsychotic. Conclusion: These findings indicate that in contrast to RCTs, dropout from observational studies is not necessarily associated with drug discontinuation. Accordingly, systematic differences between trial designs need to be considered when interpreting the results of clinical trials.

In the past decade, four main topics have shaped research and clinical practice. 1) In randomized controlled trials, researchers have investigated whether treating prodromal symptoms of schizophrenia helps to reduce the conversion risk to full-blown schizophrenia. Results are ambiguous and the discussion on whether or not an intervention at the stage is justified is ongoing. 2) Following the enhanced understanding of the pathophysiology of schizophrenia, also with respect to specific symptom domains, pharmacological targets beyond D2 receptor antagonism have been explored. Much work and enthusiasm has revolved around nicotinergic and glutamatergic compounds, so far with mostly discouraging results. 3) Several new-generation antipsychotics have become available as long-acting formulations. All of them have demonstrated a significant positive impact on relapse rates in placebo controlled studies. Whether these compounds also have advantages over first-generation depots and/or oral antipsychotics is still debated. The development of an inhalable antipsychotic has complemented the treatment options for the management of acutely agitated patients. 4) Lastly, attempts from various perspectives, including genetics and neuroimaging, have investigated whether it is possible to predict treatment response and drug safety. Although some look promising, they have not yet reached a stage in which they can be applied to everyday clinical practice. What has become clear, though, is that early non response predicts late non response, leading to the recommendation to switch antipsychotics much earlier than stated in most treatment guidelines.

Objective: The primary objective of this study was to investigate whether the choice and dosage of antipsychotic medication differ between patients with schizophrenia starting treatment in an inpatient or outpatient unit. In addition, we investigated whether the reason for the introduction of new antipsychotic medication had an impact on the treatment setting and whether the use of benzodiazepines differed between inpatients and outpatients.Method: From October 1997 to September 2010, patients with a schizophrenia spectrum disorder according to the International Classification of Diseases, Tenth Revision aged between 18 and 65 years were allocated to a naturalistic drug-monitoring program when starting treatment with a second-generation antipsychotic drug. Psychopathological symptoms were rated at baseline and after 1, 2, 4, and 8 weeks of treatment using the Positive and Negative Syndrome Scale. Inpatients and outpatients were compared with regard to the use of antipsychotics and benzodiazepines. To compare different drugs, chlorpromazine and diazepam equivalents were calculated.Results: Lack of efficacy and side effects were the main reasons for initiating new antipsychotic medication. Combined evaluation of all antipsychotic compounds by meta-analysis resulted in a significant effect of the treatment setting, with inpatients receiving higher doses than outpatients. In addition, inpatients were prescribed benzodiazepines more often and in higher doses than outpatients.Conclusions: Both antipsychotics and benzodiazepines were prescribed at higher doses in an inpatient setting. Moreover, benzodiazepines were prescribed more frequently to inpatients. Accordingly, the treatment setting needs to be taken into consideration in treatment recommendations for schizophrenia spectrum disorders.

Phase 1 of the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) study enrolled a sample of 1493 chronic schizophrenia patients. The European First Episode Schizophrenia Trial (EUFEST) enrolled 498 patients. We have combined these two samples to study the effects of hostility on study discontinuation as well as to examine correlates and predictors of hostility. Individual data from 1154 patients with complete data were used for analyses. Survival analysis demonstrated that higher hostility was associated with earlier all-cause treatment discontinuation. Furthermore, regression analysis indicated that increased hostility was associated with more severe positive symptoms, lower adherence to pharmacological treatment, younger age, impaired insight, and more drug or alcohol consumption. The clinical implications of the results point to the importance of establishing therapeutic alliance while managing patient's symptoms of hostility with antipsychotics such as olanzapine combined with psychosocial interventions to improve insight and reduce substance use.