HIV-positive men who have sex with men are at high risk of development of significant liver fibrosis after an episode of acute hepatitis C.

Acute hepatitis C virus infection remains a major health concern in human immunodeficiency virus(HIV)-infected men who have sex with men (MSM). New direct-acting antiviral agent (DAA) combination therapy has not yet been approved for the treatment for acute hepatitis C virus(HCV), thereby potentially causing deferral of HCV treatment. Therefore, we aimed to study the course of liver disease after an episode of acute HCV. This study is a retrospective single-centre cohort of HIV-positive MSM with acute HCV infection. Liver fibrosis was estimated by Fibroscan® and Fibrotest® . Liver-related and non-liver-related outcomes were documented. Overall 213 episodes of acute HCV infection in 178 men were documented. Median follow-up for all included patients was 38.7 months. Spontaneous HCV clearance was found in 10.8% of patients, which was significantly associated with older age, lower HCV RNA levels, and higher ALT levels upon initial acute HCV diagnosis. Treatment with interferon-based therapy was initiated in 86.3% of cases, resulting in a sustained virological response(SVR) rate of 70.7%. After 3 years' follow-up, significant liver fibrosis of METAVIR F2 stage or higher was found in 39.4% of patients after first acute HCV diagnosis. Higher age, physician-declared alcoholism, and nonresponse to acute HCV therapy were independently associated with higher fibrosis stages. Ten patients died during the observation period (IR 1.4/100 patient-years) and four during interferon treatment. Significant liver fibrosis is a common finding in HIV-positive MSM following acute HCV infection despite high treatment uptake and cure rates, suggesting the need for close liver disease monitoring particularly if HCV treatment is deferred.

Multiple hepatitis C virus (HCV) reinfections in HIV-positive men who have sex with men: no influence of HCV genotype switch or interleukin-28B genotype on spontaneous clearance.

OBJECTIVES: The incidence of sexually transmitted hepatitis C virus (HCV) reinfection is on the rise in HIV-infected men who have sex with men (MSM). Data on natural history of acute hepatitis C and possible factors associated with spontaneous clearance are limited. The aim of this study was to analyse the outcome of HCV reinfections in HIV-positive MSM. METHODS: A retrospective analysis was carried out on patients with more than one sexually acquired HCV infection who were diagnosed at four major German HIV and hepatitis care centres. Reinfection was defined by genotype or phylogenetic clade switch, detectable HCV RNA after a sustained virological response (SVR) or after spontaneous clearance (SC). RESULTS: In total, 48 HIV-positive MSM were identified with HCV reinfection, among them 11 with a third episode and one patient with four episodes. At the first episode, 43 and five patients had an SVR and SC, respectively. The second episode was accompanied by a genotype switch in 29 patients (60%). Whereas 30 and nine patients showed an SVR and SC, respectively, eight patients developed chronic hepatitis. Neither HCV genotype switch nor interleukin-28B genotype was associated with SC. However, SC rates at the second episode were higher for patients with SC at the first episode compared with patients without SC (60 vs. 14%, respectively; P = 0.03). Two patients with SC at the first episode were reinfected with the same genotype. CONCLUSIONS: Multiple reinfections in HIV-infected MSM do occur, with or without genotype switch, and with prior SC of previous episodes. In this large case series, except for SC at the first episode, no factor was of value in clinical decision-making for early therapeutic intervention in acute HCV reinfection.

Prediction of response to antiretroviral therapy by human experts and by the EuResist data-driven expert system (the EVE study).

OBJECTIVES: The EuResist expert system is a novel data-driven online system for computing the probability of 8-week success for any given pair of HIV-1 genotype and combination antiretroviral therapy regimen plus optional patient information. The objective of this study was to compare the EuResist system vs. human experts (EVE) for the ability to predict response to treatment. METHODS: The EuResist system was compared with 10 HIV-1 drug resistance experts for the ability to predict 8-week response to 25 treatment cases derived from the EuResist database validation data set. All current and past patient data were made available to simulate clinical practice. The experts were asked to provide a qualitative and quantitative estimate of the probability of treatment success. RESULTS: There were 15 treatment successes and 10 treatment failures. In the classification task, the number of mislabelled cases was six for EuResist and 6-13 for the human experts [mean±standard deviation (SD) 9.1±1.9]. The accuracy of EuResist was higher than the average for the experts (0.76 vs. 0.64, respectively). The quantitative estimates computed by EuResist were significantly correlated (Pearson r=0.695, P<0.0001) with the mean quantitative estimates provided by the experts. However, the agreement among experts was only moderate (for the classification task, inter-rater κ=0.355; for the quantitative estimation, mean±SD coefficient of variation=55.9±22.4%). CONCLUSIONS: With this limited data set, the EuResist engine performed comparably to or better than human experts. The system warrants further investigation as a treatment-decision support tool in clinical practice.

Evaluating depressive symptoms and their impact on outcome in schizophrenia applying the Calgary Depression Scale.

OBJECTIVE: To examine depressive symptoms, their course during treatment, and influence on outcome. METHOD: Weekly Calgary Depression Scale for Schizophrenia ratings were performed in 249 inpatients with schizophrenia. Early response was defined as a 20% reduction in the total score of the Positive and Negative Syndrome Scale for Schizophrenia from admission to week 2, response as a 50% reduction in the total score of the Positive and Negative Syndrome Scale for Schizophrenia (PANSS) from admission to discharge and remission according to the consensus criteria. RESULTS: Thirty six per cent of the patients were depressed at admission, with 23% of them still being depressed at discharge. Depressed patients scored significantly higher on the PANSS negative and general psychopathology subscore, featured more impairments in subjective well-being (P < 0.0001) and functioning (P < 0.0001). They suffered from more suicidality (P = 0.0021), and had greater insight into their illness (P = 0.0105). No significant differences were found regarding early response, response, and remission. CONCLUSION: Patients with depressive symptoms should be monitored closely, given the burden of negative symptoms, their impairments in well-being and functioning and the threat of suicidality.

The RSM-scale: a pilot study on a new specific scale for self- and observer-rated quality of life in patients with schizophrenia.

PURPOSE: To develop and evaluate a self- and observer-rating scale on quality of life in patients suffering from schizophrenia with regard to the efficacy of atypical antipsychotics based on different dimensions and to apply within a pilot study. METHODS: Following review of existing scales and a prevalidation phase, the Riedel-Spellmann-Musil (RSM) scale was developed comprising 36 items assigned to different subscales. As reference scales, the Quality of Life Scale (QLS) and the Subjective Well-being Under Neuroleptic Treatment Scale-short version (SWN-K) were performed, psychopathology and adverse events were measured at all visits. Reliability was assessed using Cronbach's alpha, Pearson's correlation coefficients were used to assess construct validity, and Intraclass Correlation Coefficients (ICCs) were used for test-retest reliability. T tests were performed in normal distributed samples; otherwise Wilcoxon tests were used. RESULTS: One hundred and thirty-six patients were included in the study. Cronbach`s α was 0.917 for the self-rating and 0.915 for the interviewer-rating part. ICCs were >0.70 for all subscales. The self-rating part correlated strongly with the SWN-K and the observer part with the QLS. Changes in psychopathology over the study period and different levels of functioning were detected. CONCLUSION: The RSM-scale is a new scale to assess the quality of life in different dimensions of patients with schizophrenia treated with antipsychotics and shows good internal consistency, test-retest reliability, construct and discriminant validity.

Relationship between baseline severity of depression and antidepressant treatment outcome.

INTRODUCTION: Assessment of depression severity is of key importance, since several clinical guidelines recommend choice of treatment dependent on the depression severity grade. Using different tools to assess baseline severity may result in different outcomes. METHODS: This paper describes the results of a multicentre, naturalistic study investigating the relationship between depression symptom severity (using 4 different measures of symptom severity) and clinical outcome among patients hospitalised for depression (N=1 014). Moreover, the impact of differences between methods of measuring depression severity has been investigated. Statistical analyses (univariate measurements, logistic regression models) were conducted to detect coherences and differences between the various methods of severity categorisation. RESULTS: Results revealed different associations between outcome and classification methods. Response or remission rates varied if baseline severity was assessed by different instruments. Moreover, the number of responders increased with higher baseline severity grades of depression, whereas the number of remitters decreased. Additional analyses dependent on outcome criteria using continuous instead of categorical data revealed similar results. DISCUSSION: Baseline severity may be only one of many other important clinical variables that mediate clinical outcome, but it is surely an important one deserving further research and consideration.

Acute hepatitis C in persons infected with the human immunodeficiency virus (HIV): the "real-life setting" proves the concept.

OBJECTIVES: Outbreaks of sexually transmitted acute HCV infection have been described recently in several cities in the western world. The epidemic affects mainly MSM who are coinfected with HIV and is supposably linked to certain sexual risk practices. Here, we compared our findings with current knowledge and recommendations. METHODS: HIV-positive patients with the diagnosis of acute HCV infection were included in the retrospective analysis. The patients came from outpatient infectious disease centers in northern German cities. We looked at markers of HIV and HCV infection and compared patients who received treatment and those who did not. Treated patients were followed up to 72 weeks. RESULTS: Three hundred nineteen HIV-positive patients with the diagnosis of acute hepatitis C between 2001 and 2008 and were included in the analysis. All patients were male, 315 (99%) patients were of caucasian origin, 296 (93%) declared homosexual contacts as a risk factor for HCV infection, intravenous drug use was declared in 3 (1%) cases. Median age at HCV diagnosis was 40 years (range 20-69 years). Median HCV viral load was 1.2 x 106 IU/mL, 222 patients (70%) had HCV genotype 1, 59 (18%) genotype 4. The median time of HIV infection was 5.5 years (range 0 to 22.4 years). Median HIV viral load was 110 copies/mL (range 25 to 10x106 copies/mL). The median CD 4 count was 461 cells/mm3 (range 55-1331 cells/mm3). Two hundred and fourty-six patients (77%) received anti-HCV treatment, and 175 (55%) had completed therapy by the time of the analysis. Median treatment duration was 33 weeks (IQR 24.1-49.9). 93 of the 175 treated patients (53%) reached a sustained virological response (SVR). In the multivariate analysis, ART at diagnosis, HCV RNA drop at week 12, hemoglobin levels and higher platelets were associated with SVR. Treatment duration was significantly higher in the SVR group (40.6 weeks vs 26.6 weeks, p<0.0001). Seventy-three patients (23%) did not receive anti-HCV treatment. In 19 of the untreated patients (26%) the hepatitis C virus was cleared spontaneously. CONCLUSIONS: Our findings confirm that acute hepatitis C in HIV infected patients affects mainly MSM who acquire HCV sexually. Patients had a short duration of HIV infection and a stable immunological situation. In this real-life setting from urban regions in northern Germany, treatment rates appear to be high and effective.

In vitro characterization and pharmacokinetics of dapagliflozin (BMS-512148), a potent sodium-glucose cotransporter type II inhibitor, in animals and humans.

(2S,3R,4R,5S,6R)-2-(3-(4-Ethoxybenzyl)-4-chlorophenyl)-6-hydroxymethyl-tetrahydro-2H-pyran-3,4,5-triol (dapagliflozin; BMS-512148) is a potent sodium-glucose cotransporter type II inhibitor in animals and humans and is currently under development for the treatment of type 2 diabetes. The preclinical characterization of dapagliflozin, to allow compound selection and prediction of pharmacological and dispositional behavior in the clinic, involved Caco-2 cell permeability studies, cytochrome P450 (P450) inhibition and induction studies, P450 reaction phenotyping, metabolite identification in hepatocytes, and pharmacokinetics in rats, dogs, and monkeys. Dapagliflozin was found to have good permeability across Caco-2 cell membranes. It was found to be a substrate for P-glycoprotein (P-gp) but not a significant P-gp inhibitor. Dapagliflozin was not found to be an inhibitor or an inducer of human P450 enzymes. The in vitro metabolic profiles of dapagliflozin after incubation with hepatocytes from mice, rats, dogs, monkeys, and humans were qualitatively similar. Rat hepatocyte incubations showed the highest turnover, and dapagliflozin was most stable in human hepatocytes. Prominent in vitro metabolic pathways observed were glucuronidation, hydroxylation, and O-deethylation. Pharmacokinetic parameters for dapagliflozin in preclinical species revealed a compound with adequate oral exposure, clearance, and elimination half-life, consistent with the potential for single daily dosing in humans. The pharmacokinetics in humans after a single dose of 50 mg of [(14)C]dapagliflozin showed good exposure, low clearance, adequate half-life, and no metabolites with significant pharmacological activity or toxicological concern.

Outcome of suicidal patients with schizophrenia: results from a naturalistic study.

OBJECTIVE: Purpose was to assess suicidality before and at the time of admission in patients with schizophrenia and compare outcome differences. METHOD: Biweekly PANSS (Positive and Negative Syndrome Scale), HAMD (Hamilton Depression Rating Scale) and UKU (Udvalg for Klinske Undersogelser Side Effect Rating Scale) ratings were evaluated in 339 in-patients with schizophrenic spectrum disorders. Response was defined as an initial 20% PANSS total score reduction at discharge, remission was defined according to the proposed consensus criteria by the Remission in Schizophrenia Working Group. RESULTS: Suicidal patients (22%) scored significantly higher on the PANSS negative subscore, PANSS insight item and HAMD total score at admission and at discharge. They developed significantly more side effects. No differences were found concerning response and remission between the two patient subgroups. CONCLUSION: Despite receiving significantly more antidepressants the suicidal patients suffered from significantly more depressive symptoms up to discharge, yet without differing regarding response and remission.

Neurocognition and its influencing factors in the treatment of schizophrenia-effects of aripiprazole, olanzapine, quetiapine and risperidone.

BACKGROUND: To examine influencing variables of neurocognition in patients with schizophrenia and to predict cognition during antipsychotic treatment. METHODS: Data were obtained from patients with an acute episode of schizophrenia participating in two double-blind and one open label trial comparing the effects of different atypical antipsychotics on cognition. In total, 129 patients were enrolled in this analysis. Cognitive function was assessed at admission, week 4 and 8. Efficacy and tolerability were assessed weekly using the Positive and Negative Syndrome Scale (PANSS) and the Simpson Angus Sale (SAS). Patients were treated with aripirazole, olanzapine, quetiapine and risperidone. Regression analysis including mixed effect models was performed. RESULTS: A significant improvement in all cognitive domains was observed from baseline to week 8. Regarding the antipsychotic treatment applied quetiapine seemed to achieve the most favourable cognitive improvement. Negative and depressive symptoms, the patient's age and the concomitant and antipsychotic treatment applied were observed to significantly influence and predict neurocognition. CONCLUSION: The results may indicate that schizophrenia is a static disorder with trait and state dependent cognitive components especially in the memory domains. The influence of negative and depressive symptoms should be considered in daily clinical routine.

Effect of aripiprazole on cognition in the treatment of patients with schizophrenia.

BACKGROUND: The aim of this study was to assess the cognitive effects of aripiprazole in inpatients with schizophrenia. METHODS: This was an investigator-initiated, open label eight-week trial evaluating 56 inpatients with the DSM-IV diagnosis of schizophrenia. Efficacy was assessed weekly using the Positive and Negative Syndrome Scale (PANSS) and tolerability was assessed each week using the Udvalg for Klinske Undersogelser side effect rating scale (UKU). Cognitive function was assessed at baseline, week 4 and week 8. RESULTS: Aripiprazole showed significant improvement in PANSS total score and all subscores between baseline and endpoint visit. The substance was very well tolerated. Patients improved significantly in verbal memory, reaction time and reaction quality/attention from baseline to week eight. Furthermore, mean z-values of individual cognitive domains summarized in a global cognitive index improved significantly from baseline to week eight. DISCUSSION: Our results suggest that aripiprazole provides a valuable treatment option for patients with schizophrenia.

A critical analysis and discussion of the appropriateness of the schizophrenia consensus remission criteria in clinical pharmaceutical trials.

BACKGROUND: The aim of this paper is to apply the proposed consensus remission criteria to an acutely ill inpatient sample at admission and evaluate their adaptability in this patient population and pharmaceutical trials. METHODS: The Remission in Schizophrenia Working Group's consensus criteria were applied to 272 acutely ill schizophrenia patients. Patients were examined using the PANSS, HAMD, UKU and SWN-K total scales at admission as well as the GAF, SOFAS and the Strauss-Carpenter Prognostic Scale. Sociodemographic and clinical baseline variables were assessed using a standardized documentation system. RESULTS: 33 patients (12%) fulfilled the symptom severity component of the proposed remission criteria already at baseline. Almost no significant differences were found when comparing patients with achieved and failed symptom severity component that would explain the hospitalization of the patients with achieved criteria despite their apparently mild psychopathological symptoms. The only explainable difference was that patients with an achieved symptom severity component had received significantly more antipsychotics and had suffered from significantly more life events before admission. CONCLUSION: The present results raise the question whether the symptom severity threshold is adequate to identify patients in remission when applied in clinical trials.

Intensify production, transform biomass to energy and novel goods and protect soils in Europe-A vision how to mobilize marginal lands.

The rapid increase of the world population constantly demands more food production from agricultural soils. This causes conflicts, since at the same time strong interest arises on novel bio-based products from agriculture, and new perspectives for rural landscapes with their valuable ecosystem services. Agriculture is in transition to fulfill these demands. In many countries, conventional farming, influenced by post-war food requirements, has largely been transformed into integrated and sustainable farming. However, since it is estimated that agricultural production systems will have to produce food for a global population that might amount to 9.1 billion by 2050 and over 10 billion by the end of the century, we will require an even smarter use of the available land, including fallow and derelict sites. One of the biggest challenges is to reverse non-sustainable management and land degradation. Innovative technologies and principles have to be applied to characterize marginal lands, explore options for remediation and re-establish productivity. With view to the heterogeneity of agricultural lands, it is more than logical to apply specific crop management and production practices according to soil conditions. Cross-fertilizing with conservation agriculture, such a novel approach will provide (1) increased resource use efficiency by producing more with less (ensuring food security), (2) improved product quality, (3) ameliorated nutritional status in food and feed products, (4) increased sustainability, (5) product traceability and (6) minimized negative environmental impacts notably on biodiversity and ecological functions. A sustainable strategy for future agriculture should concentrate on production of food and fodder, before utilizing bulk fractions for emerging bio-based products and convert residual stage products to compost, biochar and bioenergy. The present position paper discusses recent developments to indicate how to unlock the potentials of marginal land.

Persisting hepatitis E virus infection leading to liver cirrhosis despite recovery of the immune system in an HIV-infected patient.

Chronic hepatitis E has been described several times in strongly immunosuppressed HIV-patients. We describe the persistence of HEV-infection in an HIV-patient despite a restored immune response. This case demonstrates that HEV-infection can persist in formerly immunosuppressed individuals irrespective of the current immune status. Persisting HEV-infection can lead to chronic inflammation and liver cirrhosis. Physicians should be aware of the possibility of chronic hepatitis E even in patients that are not any longer immunocompromised. However, ribavirin is an efficient treatment option.

Heart rate variability and Omega-3 Index in euthymic patients with bipolar disorders.

BACKGROUND: Affective disorders are associated with an increased risk of cardiovascular disease, which, at least partly, appears to be independent of psychopharmacological treatments used to manage these disorders. Reduced heart rate variability (SDNN) and a low Omega-3 Index have been shown to be associated with increased risk for death after myocardial infarction. Therefore, we set out to investigate heart rate variability and the Omega-3 Index in euthymic patients with bipolar disorders. METHODS: We assessed heart rate variability (SDNN) and the Omega-3 Index in 90 euthymic, mostly medicated patients with bipolar disorders (Bipolar-I, Bipolar-II) on stable psychotropic medication, free of significant medical comorbidity and in 62 healthy controls. Heart rate variability was measured from electrocardiography under a standardized 30 minutes resting state condition. Age, sex, BMI, smoking, alcohol consumption and caffeine consumption as potential confounders were also assessed. RESULTS: Heart rate variability (SDNN) was significantly lower in patients with bipolar disorders compared to healthy controls (35.4 msec versus 60.7 msec; P<0.0001), whereas the Omega-3 Index did not differ significantly between the groups (5.2% versus 5.3%). In a linear regression model, only group membership (patients with bipolar disorders versus healthy controls) and age significantly predicted heart rate variability (SDNN). CONCLUSION: Heart rate variability (SDNN) may provide a useful tool to study the impact of interventions aimed at reducing the increased risk of cardiovascular disease in euthymic patients with bipolar disorders. The difference in SDNN between cases and controls cannot be explained by a difference in the Omega-3 Index.

What are depressive symptoms in acutely ill patients with schizophrenia spectrum disorder?

BACKGROUND: Aim was to examine depressive symptoms in acutely ill schizophrenia patients on a single symptom basis and to evaluate their relationship with positive, negative and general psychopathological symptoms. METHODS: Two hundred and seventy-eight patients suffering from a schizophrenia spectrum disorder were analysed within a naturalistic study by the German Research Network on Schizophrenia. Using the Calgary Depression Scale for Schizophrenia (CDSS) depressive symptoms were examined and the Positive and Negative Syndrome Scale (PANSS) was applied to assess positive, negative and general symptoms. Correlation and factor analyses were calculated to detect the underlying structure and relationship of the patient's symptoms. RESULTS: The most prevalent depressive symptoms identified were depressed mood (80%), observed depression (62%) and hopelessness (54%). Thirty-nine percent of the patients suffered from depressive symptoms when applying the recommended cut-off of a CDSS total score of >6 points at admission. Negligible correlations were found between depressive and positive symptoms as well as most PANSS negative and global symptoms despite items on depression, guilt and social withdrawal. The factor analysis revealed that the factor loading with the PANSS negative items accounted for most of the data variance followed by a factor with positive symptoms and three depression-associated factors. LIMITATIONS: The naturalistic study design does not allow a sufficient control of study results for the effect of different pharmacological treatments possibly influencing the appearance of depressive symptoms. CONCLUSION: Results suggest that depressive symptoms measured with the CDSS are a discrete symptom domain with only partial overlap with positive or negative symptoms.

Benzazepinone calcium channel blockers. 5. Effects on antihypertensive activity associated with N1 and aromatic substituents.

We have shown that the pyrrolidinylmethyl substituent on the lactam nitrogen (N1) of benzazepinone and benzothiazepinone calcium channel blocking agents is resistant to metabolic deamination and generally increases the duration and potency of antihypertensive activity in spontaneously hypertensive rats (SHR) relative to (N,N-dimethylamino)ethyl analogs. Additionally, compounds possessing a substituent on the fused aromatic ring are more resistant to metabolic deacylation of the C3 hydroxy function, which may explain why aromatic substituents also frequently increase the potency and/or duration of antihypertensive activity. Our data also indicate the increased antihypertensive activity associated with these structural modifications is independent of any effects of potency in vitro. Overall, we interpret these results to indicate that these structural modifications improve antihypertensive activity as a result of increased metabolic stability and, consequently, oral bioavailability.

Prodrugs of BMS-183920: metabolism and permeability considerations.

The oral bioavailability of BMS-183920, a diacidic, potent angiotensin II receptor antagonist, is low in rats (approximately 11%). In vivo studies in bile duct-cannulated rats indicated that BMS-183920 was metabolically stable and that the low bioavailability was due to incomplete intestinal absorption. Five acyl-ester prodrugs were synthesized which were 5-15 times more permeable than BMS-183920 through Caco-2 cells. However, limited studies in rats indicated that the oral bioavailability of BMS-183920 was improved only 2-fold, in the best case. The lack of a substantial increase in bioavailability was apparently due to presystemic prodrug hydrolysis or metabolism via N-glucuronidation. Bioavailability of BMS-183920 after oral dosing of a tetrazole-ester prodrug averaged 37%, the most significant improvement within this prodrug series. Interestingly, in vitro studies indicated that the tetrazole-ester prodrug was a substrate for glucuronosyl transferase; however, its rate of bioactivation (hydrolysis) was sufficiently high to provide a substantial increase in bioavailability of BMS-183920. Therefore, while prodrug modification of BMS-183920 improved Caco-2 cell permeability and oral absorption in vivo, the relative extents of hydrolysis (bioactivation) vs metabolism of the prodrug determined whether a substantial improvement in bioavailability was achieved.

Transcranial direct current stimulation in treatment resistant depression: a randomized double-blind, placebo-controlled study.

BACKGROUND: Anodal transcranial direct current stimulation (tDCS) of the prefrontal cortex has been proposed as therapeutic intervention in major depression. According to clinical needs, this study addresses the question whether tDCS is effective in treatment resistant major depressive episodes. METHODS: Twenty-two patients with a major depressive episode were randomly assigned to a cross-over protocol comparing tDCS and placebo stimulation add-on to a stable antidepressant medication. The parameters of active tDCS were: 1 or 2 mA for 20 minutes/day, anode over the left dorsolateral prefrontal cortex, cathode over the contralateral supraorbital region. Active and placebo tDCS was applied for 2 weeks using indistinguishable DC stimulators. Patients, raters, and operators were blinded to treatment conditions. RESULTS: There was no significant difference in depression scores after 2 weeks of real compared with 2 weeks of sham tDCS. Scores on the Hamilton Depression Rating Scale were reduced from baseline by 14.7% for active tDCS and 10% for placebo tDCS. In contrast, subjective mood ratings showed an increase in positive emotions after real tDCS compared with sham tDCS. CONCLUSIONS: Anodal tDCS, applied for 2 weeks, was not superior to placebo treatment in patients with treatment resistant depression. However, secondary outcome measures are pointing to a positive effect of tDCS on emotions. Therefore, modified and improved tDCS protocols should be carried out in controlled pilot trials to develop tDCS towards an efficacious antidepressant intervention in therapy-resistant depression.

The validity of self-rated psychotic symptoms in depressed inpatients.

BACKGROUND: Self-ratings of psychotic experiences might be biased by depressive symptoms. METHOD: Data from a large naturalistic multicentre trial on depressed inpatients (n=488) who were assessed on a biweekly basis until discharge were analyzed. Self-rated psychotic symptoms as assessed with the 90-Item Symptom Checklist (SCL-90) were correlated with the SCL-90 total score, the SCL-90 depression score, the Beck Depression Inventory (BDI), the Hamilton Depression Rating Scale 21 item (HAMD-21) total score, the Montgomery Åsberg Depression Rating Scale (MADRS) total score and the clinician-rated paranoid-hallucinatory score of the Association for Methodology and Documentation in Psychiatry (AMDP) scale. RESULTS: At discharge the SCL-90 psychosis score correlated highest with the SCL-90 depression score (0.78, P<0.001) and with the BDI total score (0.64, P<0.001). Moderate correlations were found for the MADRS (0.34, P<0.001), HAMD (0.37, P<0.001) and AMDP depression score (0.33, P<0.001). Only a weak correlation was found between the SCL-90 psychosis score and the AMDP paranoid-hallucinatory syndrome score (0.15, P<0.001). Linear regression showed that change in self-rated psychotic symptoms over the treatment course was best explained by a change in the SCL-90 depression score (P<0.001). The change in clinician-rated AMDP paranoid-hallucinatory score had lesser influence (P=0.02). CONCLUSIONS: In depressed patients self-rated psychotic symptoms correlate poorly with clinician-rated psychotic symptoms. Caution is warranted when interpreting results from epidemiological surveys using self-rated psychotic symptom questionnaires as indicators of psychotic symptoms. Depressive symptoms which are highly prevalent in the general population might influence such self-ratings.