Contact Christian G. Huber, M.D. Consultant Psychiatrist Department of Psychiatry and Psychotherapy Centre for Psychosocial Medicine University Medical Centre Hamburg-Eppendorf
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Abstract: Quality of care is essential for health services research. Therefore, our patients' preferences are of major importance and this can be illustrated by decision-making in localised prostate cancer.
Abstract: This study examined the differential effects of first- (FGAs) versus second-generation antipsychotics (SGAs) on subjective well-being in patients with schizophrenia.
Abstract: The aim of this study was to evaluate the applicability and validity of a clinical global impressions-aggression (CGI-A) scale in retrospective trials. CGI-A scores were derived from clinical records, BPRS scores were assessed prospectively in 101 patients with first-episode psychosis. CGI-A showed highly significant correlations to the brief psychiatric rating scale (BPRS) excited component (BPRS-EC; r=0.32; p=0.001) and BPRS resistance (r=0.25; p=0.011), to aggression at admission (r=0.70; p<0.001) and to involuntary treatment (r=0.55; p<0.001). The CGI-A retains high construct and face validity in retrospective trials.
Abstract: Glaucoma is a frequent ophthalmologic condition leading to chronic progressive optic neuropathy, which can result in visual impairment and blindness. In addition, glaucoma is associated with a dysregulation of circadian rhythms, as well as with a high incidence of sleep disorders, depression, and anxiety. However, because of their high comorbidity in older age, these conditions have not received much scientific attention and are often undertreated. In the current paper, we review the available literature on the role of melatonergic mechanisms in glaucoma, regulation of circadian rhythms, and depression. The literature is presented as a narrative review, providing an overview on the most important and clinically relevant publications. Recently, there has been evidence for a progressive loss of intrinsically photosensitive retinal ganglion cells (ipRGC) because of oxidative stress in glaucoma. As ipRGC are responsible for the photic transduction to the circadian system and subsequent melatonin secretion, and melatonin is involved in the pathophysiology of circadian desynchronization, sleep disorder, and depression, an impairment of photo-dependent melatonergic signaling may be a common pathway connecting glaucoma with these comorbidities. This fact, as well as the proven retinal neuroprotective role of melatonin, suggests that melatonergic drugs provide a potentially promising treatment strategy supplementing the management of intraocular pressure by pharmacological and surgical measures. Additionally, multidisciplinary treatment focusing on depression and normalization of circadian rhythms might be beneficial for glaucoma patients. Furthermore, glaucoma might be a useful model for studying the pathophysiological interactions between the melatonergic, circadian, and mood systems.
Abstract: • To investigate patient-to-patient communication with regard to decision-making in localized prostate cancer; as most of it is done in private, online support groups are a unique means for this task.
Abstract: OBJECTIVE: To systematically assess the physicians' point of view of multimedia support in preoperative patient education for radical prostatectomy. METHODS: We evaluated the view of physicians performing multimedia supported preoperative educations within a randomized controlled trial. Therein 8 physicians educated 203 patients for radical prostatectomy. RESULTS: All physicians rated multimedia supported education better than the standard procedure. Main reasons were better comprehensibility, the visual presentation, and greater ease in explaining complex issues. Objective time measurement showed no difference between both educations. The major disadvantage was the impression, that multimedia supported education lasted longer. Moreover, they had the impression that some details could be further improved. Given the choice, every physician would decide for multimedia support. CONCLUSION: Physicians appreciate multimedia support in preoperative education and contrary to their impression, multimedia support does not prolong patient education. Therefore, patients and physicians likewise profit from multimedia support for education and counseling. PRACTICE IMPLICATIONS: The readiness of physicians is a possible obstacle to this improvement, as their view is a key factor for the transition to everyday routine. Therefore, our results could alleviate this possible barrier for establishing multimedia supported education in clinical routine.
Abstract: When preparing the evaluation of a newly designed multimedia tool for supporting preoperative education before radical prostatectomy, we realized that the standard procedure has rarely been investigated. Therefore, we performed semi-structured interviews with 30 consecutive patients the day before and 15Â days after radical prostatectomy. Patients' opinion about their preoperative education is decidedly positive and demonstrates intense patient-physician interaction. All patients wanted to be informed about the procedure and possible risks. None reported to be dissatisfied. All but one of the patients (29/30) was able to ask every single question (6.5 mean). Except for signs of forgetting and a slightly altered retrospective assessment of anxiety, we have found no relevant changes over time. Preoperative education is very important to our patients. Therefore, good communication skills should be developed during medical education. A systematic patient-centered approach could further improve the quality of care.
Abstract: Encoding and retrieval of relational information requires interaction between the hippocampus and various neocortical regions, but it is unknown whether the connectivity of hippocampal-neocortical networks is different at input and output stages. To examine this, we conducted a network analysis of event-related fMRI data collected during a face-recognition, remember/know paradigm. Directed analyses in the medial temporal lobe identified a small region in the left hippocampus that showed differential activation for encoding and retrieval of recollected versus familiar items. Multivariate seed partial least squares (PLS) analysis was used to identify brain regions that were functionally connected to this hippocampal region at encoding and retrieval of 'remembered' items. Anatomically based structural equation modeling (SEM) was then used to test for differences in effective connectivity of network nodes between these two memory stages. The SEM analysis revealed a reversal of directionality between the left hippocampus (LHC) and left inferior parietal cortex (LIPC) at encoding and retrieval. During encoding, activation of the LHC had a positive influence on the LIPC, whereas during retrieval the reverse pattern was found, i.e., the LIPC activation positively influenced LHC activation. These findings emphasize the importance of hippocampal-parietal connections and underscore the complexity of their interactions in initial binding and retrieval/reintegration of relational memory. We also found that, during encoding, the right hippocampus had a positive influence on the right retrospenial cortex, whereas during retrieval this influence was significantly weaker. We submit that examining patterns of connectivity can be important both to elaborate and constrain models of memory involving hippocampal-neocortical interactions.
Abstract: BACKGROUND/AIMS: There is growing evidence that the validity of diagnostic methods for personality disorders (PD) may be insufficient. Although the ICD-10 classification system is widely used, there is little data concerning its validity for diagnosing PD. METHODS: To examine convergent and discriminant validity of ICD-10 PD, corresponding dimensions were calculated using the Inventory of Clinical Personality Accentuations (self-rating) and the International Personality Disorder Examination ICD-10 module (interview and screening questionnaire). These were administered to 42 psychiatric patients. A multitrait-multimethod analysis of the 2 self-administered questionnaires and the structured interview was conducted. RESULTS: Correspondence between methods is significant at the level of 0.01 for the schizoid, borderline, anankastic, anxious and dependent PD dimensions. The investigation of discriminant validity within and between instruments reveals several strong relationships between different PD dimensions. CONCLUSION: Convergent validity can be considered sufficient for 5 of the 9 examined PD dimensions. Non-convergence must partly be interpreted as caused by poor discriminant validity inherent in the ICD-10 classification. Conceptualization of PD as completely distinguishable entities may not reflect the clinical reality of a partial overlap between personality disorders.
Abstract: In localized prostate cancer individual treatment decisions cannot be reached relying exclusively on medical data. Therefore, social interaction is of considerable importance and online support groups allow us to get to know a facet of this communication.
Abstract: The ACCESS trial examined the 12-month effectiveness of continuous therapeutic assertive community treatment (ACT) as part of integrated care compared to standard care in a catchment area comparison design in patients with schizophrenia spectrum disorders treated with quetiapine immediate release.
Abstract: OBJECTIVE: To examine the effect of diagnosis, mood state, and anxiety on subjective wellbeing in patients with affective and non-affective psychotic disorders treated with quetiapine IR. METHODS: 2175 patients with schizophrenia-spectrum (SZ, n=1681), schizoaffective (SA, n=249), and bipolar disorder (BPD, n=245) were treated with quetiapine over 6 months and assessed with the Clinical Global Impression-Severity of illness Scale (CGI-S) and the Subjective Wellbeing under Neuroleptic Treatment Scale (SWN-K). Diagnostic group differences and effects of mood state and anxiety on subjective wellbeing were analyzed using multi-factorial linear regression analysis and mixed models repeated measures. RESULTS: At baseline, despite similar CGI-S scores, significant SWN-K score differences between SZ (57.7 points), SA (64.1 points), and BPD (79.5 points) were detected. At baseline, depression (p<0.001) and anxiety (p<0.001) were independently associated with a worse and mania (p<0.001) with a better subjective wellbeing. Subjective wellbeing improved significantly in all groups (p<0.001; 27.6 points), and endpoint subjective wellbeing was not predicted by baseline depression or anxiety, but by endpoint depression and anxiety. CONCLUSION: Interventions to improve subjective wellbeing should take into account the course of mood state and anxiety. Assessment of subjective wellbeing and subjective quality of life in acute mania may need adapted tools.
Abstract: OBJECTIVE: To study the longitudinal patterns of subjective wellbeing in schizophrenia using cluster analysis and their relation to recovery criteria, further to examine predictors for cluster affiliation, and to evaluate the sensitivity and specificity of baseline subjective wellbeing cut-offs for cluster affiliation. METHODS: Data was collected in an observational 36-month follow-up study of 2842 patients with schizophrenia in Germany. Subjective wellbeing was assessed using the SWN-K scale. Cluster analyses were applied based on Ward's procedure. Predictors were analyzed using logistic regression models. Optimal SWN-K total score cut-off points for cluster affiliation were analyzed using Cohen's kappa. RESULTS: 4 distinct clusters were identified: a stable low (33%), a stable moderate (31%), a stable high (16%), and a cluster with distinct initial improvement and then stable high subjective wellbeing (20%). Highly concordant patterns were also observed for symptoms, social functioning, and quality of life. Sensitivity and specificity of SWN-K total score cut-offs at baseline were 82.8% and 63.8% for <or=60 points for the stable low cluster and 84.7% and 95.4% for >or=80 points for the stable high cluster. Affiliation to the stable low cluster was related to a 0.6% chance of being in recovery at 3-year endpoint. CONCLUSIONS: Long-term patterns of subjective wellbeing are stable and highly concordant with course of symptoms, functioning level, and quality of life. Baseline subjective wellbeing cut-off points were found to be sufficient predictors of outcome, which, particularly in case of impaired subjective wellbeing and low baseline functioning level, make early treatment adaptations mandatory.
Abstract: PURPOSE: Whereas ethical considerations on imaging techniques and interpretations of neuroimaging results flourish, there is not much work on their preconditions. In this paper, therefore, we discuss epistemological considerations on neuroimaging and their implications for neuroethics. RESULTS: Neuroimaging uses indirect methods to generate data about surrogate parameters for mental processes, and there are many determinants influencing the results, including current hypotheses and the state of knowledge. This leads to an interdependence between hypotheses and data. Additionally, different levels of description are involved, especially when experiments are designed to answer questions pertaining to broad concepts like the self, empathy or moral intentions. Interdisciplinary theoretical frameworks are needed to integrate findings from the life sciences and the humanities and to translate between them. While these epistemological issues are not specific for neuroimaging, there are some reasons why they are of special importance in this context: Due to their inferential proximity, 'neuro-images' seem to be self-evident, suggesting directness of observation and objectivity. This has to be critically discussed to prevent overinterpretation. Additionally, there is a high level of attention to neuroimaging, leading to a high frequency of presentation of neuroimaging data and making the critical examination of their epistemological properties even more pressing. CONCLUSIONS: Epistemological considerations are an important prerequisite for neuroethics. The presentation and communication of the results of neuroimaging studies, the potential generation of new phenomena and new 'dysfunctions' through neuroimaging, and the influence on central concepts at the foundations of ethics will be important future topics for this discipline.
Abstract: OBJECTIVE: Overview on the current knowledge concerning sexual dysfunctions in patients with schizophrenia and implications for treatment, compliance, quality of life and partnership. METHOD: Selective literature research on classification, occurrence, effects and therapy. RESULTS: Frequency and subjective distress of sexual problems in patients with schizophrenia are widely underestimated. Pharmacogenic and morbogenic causes of the sexual problems are often difficult to differentiate. The low awareness of health care professionals for sexual problems and their persistence have significant negative impact on patients' satisfaction with the treatment, compliance, quality of life and partnership. CONCLUSIONS: It is important to consider patients' sexuality as an integral part of a treatment approach to achieve compliance and mental stabilization as well as an improvement in quality of life.
Abstract: INTRODUCTION: 'Early-onset' studies have shown that symptomatic response often occurs early and that early symptomatic response is predictive for later outcome. Limiting factors of these studies include the restriction on symptomatic outcome, the inclusion of mostly moderately ill patients, and the use of various antipsychotics. METHODS: Response and remission rates were assessed in 528 severely ill patients with schizophrenia at baseline, week 2, 4 and 12 using PANSS, SWN-K, CGI-S, and SOFAS. The clinical measures were combined to one outcome criterion (CombOut). Predicitive validity was analyzed for CombOut using linear regression models. RESULTS: Rate and time to response differed markedly between outcome measures. 32% reached positive symptom response at week 2, 58% at week 4 and 85% at week 12. Non-response at week 4, but not at week 2 was predictive for later non-response. The combined outcome criterion was best predicted by early response in subjective wellbeing (T=-7.88, p<0.001) and social functioning (T=-7.43, p<0.001). DISCUSSION: Rate and time to response might depend on sample characteristics and outcome measure. In severely ill patients early antipsychotic response is possibly delayed from the first 2 to the first 4 weeks. Early response in subjective wellbeing and social functioning are strong predictors for overall outcome, which make them a useful supplementation to the assessment of symptomatic response.
Abstract: INTRODUCTION: Agitation is a common phenomenon in schizophrenia or acute mania. Because of the inability of patients to give informed consent in such situations, data from consenting studies are limited. METHODS: This observational prospective 5-day study evaluated the effectiveness of olanzapine in a sample of highly agitated patients with aggression. Primary endpoint was mean change of the PANSS-Excited Component (PANSS-EC) score. RESULTS: Mean PANSS-EC score at baseline was 25.5 points, 60.2% were severely agitated and 41.6% severely aggressive. A significant decrease in PANSS-EC total score (-13.3 points) was observed with rapid dose escalation and an average daily dose of 21.2 mg/day of olanzapine. 40 patients (24.1%) required treatment with another antipsychotic and 21 patients (12.7%) were not treated with olanzapine at day 5. At endpoint, 64.2% of patients were in remission of agitation. PANSS-EC reduction was not significantly different in patients with or without concurrent benzodiazepine use. DISCUSSION: Severe agitation with aggression may be well controlled with olanzapine in many cases, possibly by higher initial and overall doses of olanzapine. Controlled studies are needed to confirm these findings.
Abstract: OBJECTIVE: Few studies have prospectively examined remission and recovery as well as their predictors in schizophrenia simultaneously. Aims of the study were to identify remission and recovery rates as well as their predictors in schizophrenia. METHOD: 392 never-treated patients with schizophrenia were assessed over 3 years. Combined remission and recovery required concurrent achievement of symptomatic and functional remission as well as adequate quality of life for at least 6 and 24 months respectively. Predictors were analysed using stepwise logistic regression models. RESULTS: At 3 years, remission rates for symptoms, functioning and subjective wellbeing were 60.3%, 45.4% and 57.0%; recovery rates were 51.7%, 35.0% and 44.3%. Of those, 28.1% were in combined remission and 17.1% in combined recovery. Predictors mainly included the baseline functional status and early remission within the first 3 months. CONCLUSION: The proportion of patients who met combined remission or recovery criteria is low. Early treatment adaptations in case of early non-remission are mandatory.
Abstract: PURPOSE OF REVIEW: To give an overview of recent developments in neuroimaging in psychiatry and on the current discussion about the relationship between theoretical concepts and data from neuroimaging studies. RECENT FINDINGS: In psychiatric neuroimaging, broad concepts such as the self, well being, insight, empathy and volition form an integral part of the questions to be answered and cannot be avoided. Although, currently, the intradisciplinary discussion in neuroscience is mainly focused at the methodological and neurobiological level, psychological and philosophical theories are also needed for the interpretation of results. This raises questions regarding the epistemic priority of neuroimaging data and theories. SUMMARY: In the current paper, we present the hypothesis that there is an interdependence of neuroimaging data and theoretical concepts. An approach to 'correlational neuroscience' with an awareness of this issue may help in avoiding misunderstandings and oversimplifications as well as building an interdisciplinary theoretical framework that is able to integrate findings from life sciences, mind sciences and humanities.
Abstract: BACKGROUND: Incomplete remission and treatment resistance are common even in first-episode psychosis patients. OBJECTIVE: The aim of this review was to provide an overview of the available interventions and treatment pathways for the management of incomplete remission and treatment resistance in first-episode psychosis. METHODS: The review undertook a computerized and manual literature search for relevant articles published within recent years. RESULTS: Standard therapy has to be optimized in order to prevent treatment non-response. The early detection strategies of incomplete remission and treatment resistance include re-evaluation of the diagnosis and optimization of pharmacological and non-pharmacological interventions including the treatment of co-morbid disorders. If partial or non-response is confirmed, pharmacological and psychosocial treatment adaptations should be applied stepwise as presented in the current review. Interventions have to be offered in a timely manner because early adaptation of treatment is associated with a greater probability of remission.
Abstract: BACKGROUND: Up to 50% of first-episode psychosis patients suffer from long-term incomplete remission or treatment resistance. Different definitions for these terms have been used in psychiatric research, making generalized statements about the prevalence and predictors of treatment resistance difficult. OBJECTIVE: The aim of this study was to give an overview on state-of-the-art definitions of treatment resistance for each of the diagnoses making up the inhomogeneous diagnostic entity 'psychosis' and to analyze the factors leading to treatment resistance. METHODS: A computerized and manual literature search for relevant articles published within recent years was undertaken. RESULTS: In addition to symptomatic criteria, patients' functional level and quality of life have to be considered in the definition of treatment resistance. Patient-related, illness-related and treatment-related predictors of treatment resistance and incomplete remission might help to identify subjects at risk and optimize interventions.
Abstract: INTRODUCTION: To assess the impact of duration of untreated psychosis (DUP) on baseline and 18-month follow-up characteristics controlling for relevant confounders in an epidemiological first-episode psychosis (FEP) cohort. METHOD: The Early Psychosis Prevention and Intervention Centre (EPPIC) in Australia admitted 786 FEP patients from January 1998 to December 2000. Data were collected from medical files using a standardized questionnaire. Data from 636 patients were analyzed. RESULTS: Median DUP was 8.7 weeks. Longer DUP was associated with worse premorbid functioning (p<0.001), higher rate of schizophrenia-spectrum disorders (p<0.001), and younger age at onset of psychosis (p=0.004). Longer DUP was not associated with baseline variables but with a lower rate of remission of positive symptoms (p<0.001) and employment/occupation (p<0.001), a higher rate of persistent substance use (p=0.015), worse illness severity (p<0.001) and global functioning (p<0.001) at follow-up after controlling for relevant confounders, explaining approximately 5% of variance of remission of positive symptoms (p<0.001) in the total sample and 3% in schizophrenia-spectrum disorders excluding bipolar I disorder (p=0.002). Outcome was significantly worse when DUP exceeded 1-3 months. CONCLUSION: Avoiding pitfalls of non-epidemiological studies, DUP appears to be a modest independent predictor of prognosis in the medium-term. Results support the need for assertive early detection strategies.
Abstract: OBJECTIVE: Clinical management of aggression depends on the availability of easily administrable measurements allowing reliable evaluation. The present study's aim is to validate a Clinical Global Impression-Severity of Aggression scale (CGI-A). METHOD: 558 inpatients with psychiatric disorders and an agitated-aggressive syndrome at baseline were continuously assessed over 5 days using CGI-A and the Positive and Negative Syndrome Scale-Excited Component (PANSS-EC). Equipercentile linking, correlation analyses and linear regression were applied. RESULTS: Relationship between CGI-A and PANSS-EC total score was found to be linear. On a 5-level CGI-A scale, values of 1 to 5 points were found to correspond to PANSS-EC scores of 12.2, 16.7, 21.3, 25.8, and 30.4, respectively (average increase: 4.6). All findings remained stable when only data from patients with schizophrenia spectrum disorders were analyzed. CONCLUSIONS: The CGI-A is proposed as a quickly administrable scale for the assessment of patients' aggressiveness.
Abstract: Gastric enterochromaffin-like (ECL) cells are histamine-producing cells in the gastric epithelium which are responsible for the peripheral regulation of acid secretion. The gastric mucosa is frequently infected with Helicobacter pylori, leading to increased levels of the pro-inflammatory cytokine tumor necrosis factor-alpha (TNF-alpha). The aim of our current study was to identify the effect of TNF-alpha on programmed cell death. ECL cells were isolated from the rat corpus mucosa to a purity >90%. TNF receptor and adapter protein presence were determined using RT-PCR, Western blot and immunocytochemistry. Apoptosis was measured by Tdt-mediated dUTP nick end labeling reaction and by DNA fragmentation based ELISA. Isolated ECL cells were found to express the TNF receptor p55 and IFN-gamma receptor, but not the TNF receptor p75 or CD95. TNF-alpha (25 ng/ml) increased apoptosis in ECL cells approximately 4-fold, IFN-gamma had no effect. Western blot analysis revealed that TNF-alpha caused degradation of I kappa B alpha within 10 min. EMSA demonstrated that TNF-alpha led to increased DNA-binding activity of NF kappa B and that proteasome inhibitors counteracted NF kappa B activation. Proteasome inhibitors, specific antisense oligodeoxynucleotides against the p65 subunit of the NF kappa B complex and the NO synthase inhibitor N(G)-monomethyl-L-arginine completely prevented TNF-alpha-induced apoptosis. Our data suggest that TNF-alpha induces apoptosis of isolated gastric ECL cells via activation of NF kappa B and the generation of NO.
