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Although well researched and praised in academic publications, function modelling (FM) does not have gained much traction in industrial application. To investigate into possible reasons for this, this publication researches literature of nine different projects where enhanced function-means modelling has been applied. The projects are analysed for their purpose of FM-use, applied benefits and discovered challenges of the FM approach. From this, the main challenges for FM application are the abstraction level of the modelling language as well as the lack of an interface to CAD modelling.
Fluoroquinolones (FQs) and extended-spectrum cephalosporins (ESCs) are associated with higher risk of Clostridioides difficile infection (CDI). Decreasing the unnecessary use of FQs and ESCs is a goal of antimicrobial stewardship. Understanding how prescribers perceive the risks and benefits of FQs and ESCs is needed.
We conducted interviews with clinicians from 4 hospitals. Interviews elicited respondent perceptions about the risk of ESCs, FQs, and CDI. Interviews were audio recorded, transcribed, and analyzed using a flexible coding approach.
Interviews were conducted with 64 respondents (38 physicians, 7 nurses, 6 advance practice providers, and 13 pharmacists). ESCs and FQs were perceived to have many benefits, including infrequent dosing, breadth of coverage, and greater patient adherence after hospital discharge. Prescribers stated that it was easy to make decisions about these drugs, so they were especially appealing to use in the context of time pressures. They described having difficulty discontinuing these drugs when prescribed by others due to inertia and fear. Prescribers were skeptical about targeting specific drugs as a stewardship approach and felt that the risk of a negative outcome from under treatment of a suspected bacterial infection was a higher priority than the prevention of CDI.
Prescribers in this study perceived many advantages to using ESCs and FQs, especially under conditions of time pressure and uncertainty. In making decisions about these drugs, prescribers balance risk and benefit, and they believed that the risk of CDI was acceptable in compared with the risk of undertreatment.
Pharmacogenetics in schizophrenia comprises pharmacokinetical and pharmacodynamical aspects as well as an approach to identify candidate genes associated with therapy response or side effects. Firstly focussing on classical drug targets like dopaminergic or serotonergic receptors, currently also developmental and regulatory genes presumably associated with effects of antipsychotic therapy are identified. The aim of this study was to investigate associations between therapy response in schizophrenic patients and different polymorphisms previously been identified within a genome wide array in rodents treated with MK-801 and/or haloperidol combined with some well-known schizophrenia candidate genes. We genotyped for 200 different polymorphisms in 285 schizophrenic patients, who were treated with different antipsychotics within randomized controlled trials. Psychopathology was measured weekly using the PANSS scale. Correlations between psychopathology and genotypes were calculated by using a linear model (ANCOVA).
We found significant associations between some well-known candidate genes (e.g. D2-, 5HT1A-, and α1A-receptors) and different PANSS subscales at baseline and after four weeks of antipsychotic treatment considered as therapy response. Furthermore we also identified several significant associations between some genes introduced from the animal model and psychopathology at baseline and towards therapy response. Some of them were formerly described in the literature (e.g. Homer1, Phospholipase C and Transthyretin), but most of them have not been related to schizophrenia or antipsychotic treatment by now (e.g. PLEKHA6, CLIC6 and SOSTDC1).
This indicates an involvement of genes in the pathophysiology of schizophrenia apart from yet known candidate genes and might further help in detecting differential therapy response in individuals with schizophrenia.
Until now, no studies have been published about the prevalence and needs of children with a mentally ill parent nor about interventions for this vulnerable group in the federal state of Saxony, Germany.
Therefore, the multi-centre study HELP-S for Children was initiated by the University of Leipzig in cooperation with the Technical University of Dresden. The aim of HELP-S for Children is to identifiy the prevalence and specific needs of children with a mentally ill parent.
All psychiatric outpatients of Leipzig and Dresden at an appointed date will be asked to participate in the study. Patients with minor children will be asked to fill out a detailed questionnaire about the perceived needs of their children and the existing and lacking support possibilities. Because there is no adequate instrument to assess the needs of the children with a mentally ill parent, we will develop a standardized questionnaire by using expert interviews and a pre-test with mentally ill parents.
The standardized questionnaire, which we will develop for this study, will be useable in other studies about needs of children with a mentally ill parent. Furthermore, we will gather information about the prevalence of children of mentally ill parents who are outpatients and about the specific needs of these children in the age of 0 to 18. These results will be presented and discussed during an expert workshop at the end of the project to explore ways to improve the situation of children with a mentally ill parent.
At present, limited quantitative data about computer addiction of young people are available. The study was designed to obtain the prevalence rate of computer addiction of children. A further objective was to increase the know-how about cyber-related addictions and their comorbidity of mental disorders.
Survey among children/young people and their parents using questionnaires CBCL, YSR, CSVK, OSV and View. The children answered the questions of CSVK and OSV, adolescents over the age of 11 further filled in YSR. The parents were interviewed using CBCL and View.
Data collection was in the paediatric psychiatry in Munich, data analysis in the University of Mainz.
100 patients between 8 and 18 years of age, who asked for an outpatient or inpatient treatment of various mental disorders, filled in the questionnaires from July to November 2009 (63% male and 37% female).
The prevalence of computer addiction was 3%. The prevalence of computer abuse was 7%.
The study exhibited a significant difference in gender: boys showed to be mainly addicted, girls mainly improper users.
It was further observed that the young cyber junkies use games, chats, emails and communities more frequently than average users.
In accordance with other studies it was determined that possible comorbidities are depression, anxiety disorders and aggressive behaviour.
In addition to other mental disorders, 3-6% of the patients in a German psychiatry were found to be computer addicted. It is important to do research for a better diagnostic and therapeutic treatment or implementation of preventive interventions.
Since the introduction of second generation antipsychotics (SGA) extrapyramidal-motor symptoms (EPS) have become a lesser problem in the treatment of schizophrenic patients. Yet, some SGAs display these adverse events and first generation antipsychotics are still widely used. Several genetic polymorphisms have been found to be associated with the occurance of EPS.
In this study we tried to identify genes related to EPS from an animal model and then replicated the findings in schizophrenic patients.
To identify new genes and show their relevance in the treatment of schizophrenic patients.
Rats were treated with haloperidol or saline and differential gene expression was assessed by using microarrays. We genotyped 285 schizophrenic patients for candidate genes and differentially expressed genes derived from the animal model. All patients were treated monotherapeutically with different antipsychotics within randomized controlled trials. EPS were assessed weekly using the ESRS and BAS. We used a linear model (ANCOVA) with PANSS total at baseline, type of medication and premedication as covariates for all investigated SNP's.
We found several SNPs to be associated with the occurance of EPS. The best results were obtained for SNPs within the genes of Phospholipase C epsilon 1 (PLCe1), Methionine Sulfoxide Reductase B3 (MSRB3), Chloride Intracellular Channel 6 (CLIC6), Prolactin Receptor (PRLR) and Dopamine Receptor D4 (DRD4). Effect sizes were between 1.7 and 4.9.
We could replicate some findings of the literature and identified four new genes possibly related to EPS. Some of these genes were recently related to schizophrenia.
Cognitive behavioural therapy (CBT) is an important treatment in conjunction with psychopharmacotherapy in schizophrenia. However, there is only very little research on the effects of such interventions on brain function.
Recent studies have suggested that jumping to conclusions and a specific attributional bias is a predominant cognitive style in patients which might lead to the development of delusions. In this multi-centre fMRI trial, we investigated the effect of nine months of CBT on neural correlates of “jumping to conclusions” and the “attributional style” in patients with psychosis. Eighty patients and 80 control subjects were recruited in six centres and measured with 3-Tesla functional magnetic imaging (fMRI) before and after CBT.
It could be shown that CBT ameliorates differences in brain activations between patients and controls after nine months.
These results support the feasibility of fMRI multicenter trials and sheds further light into the mechanisms relating psychotherapy to brain function in Schizophrenia.
At present there is a paucity of standardised group behaviour therapy approaches targeting different kinds of personality disorders. On this background, our research group developed a new manualised treatment approach ("Schema-focused Emotive Behavioral Therapy"; SET), which integrates schematherapeutic, emotion-focused, cognitive and behavioural therapy methods. A multi-centre RCT-study evaluated SET based on a sample of 93 patients with personality disorders of clusters B and C. This study compared SET (n=47) with a classical Social Skills Training (SST, n=46) over 30 sessions. Patients were assessed before and after treatment and one year after study intake (follow-up). SET showed significantly higher improvements in several domains such as interpersonal behaviour, emotional coping, and symptomatic impairments. Clinically relevant effects on the SET occurred both in a reduction of the suffering from the disorder, severeness of the disorder, and hope for improvement. Furthermore, SET obtained a highly significant reduction of the dropout rate and a significantly increased use of therapy. Similar results for both comparison groups were found regarding behavioural coping and self-effectiveness. Results indicate that SET both entails a high acceptance of treatment and offers an adequate and effective group therapy for patients with personality disorders. From a clinical and economic point of view, SET promises to significantly contribute to mental health care.
Structural and functional deviations in schizophrenic patients with formal thought disorder (FTD) point towards a dysfunction within left sided language network.
Independent component analysis (ICA), a new approach to fMRI analysis, enables to target the question of a network dysfunction directly. Using this method in healthy controls it was possible to identify the language networks separately for the left and the right hemispheres In the present study we use ICA analysis to examine changes of the language network separate for each hemisphere in relation to the severity of FTD.
We hypothesize increasing disintegration with increasing severity of FTD only in the left sided language network while the right language network should remain unaffected.
We investigated 16 schizophrenic patients with different severity of FTD and matched healthy controls using ICA decomposition of the BOLD signal. The spatial similarity of the individual language networks was correlated to the severity of FTD.
The integrity of the left language network decrease with increasing severity of FTD (r = -0.79, p < 0.01), while the integrity of the right language network show no significant correlation to the severity of FTD.
For the first time the isolated breakdown of the left sided language network was linked specifically to schizophrenic FTD. This result unites older manly left hemispheric findings of structural and functional abnormalities in schizophrenic FTD.
In neuroleptic long-term medication, only part of the patients accept regular intake of neuroleptic drugs. The question is whether an interval medication regimen as opposed to continuous medication can help to reduce drop outs in patients with critical attitudes towards long-term medication. In a 2-year prospective study, 122 patients were randomised to an interval and 164 to a continuous neuroleptic medication regimen. The drop out rates were 62.5% in the interval and 53.7% in the continuous medication group. Drop outs generally show more negative attitudes towards treatment. Patients with negative attitudes do not do better under interval medication. Moreover, this regimen even requires more cooperation and trust in terms of the necessity of medication on the part of the patient compared to the continuous medication regimen. Interval medication therefore is a strategy which can only be successful in highly cooperative, but not in treatment-reluctant patients.
Recent data support the view that the neurodegeneration underlying sporadic Alzheimer's Disease (AD) is in part related to brain insulin deficiency and brain insulin resistance. There is a higher incidence of AD in patients with diabetes mellitus type II (T2D) and both diseases show a decline in memory function. In a preceding trial intranasal insulin improved memory function in healthy volunteers so that an increase of central-nervous insulin concentration may improve cognitive function in both amnestic patient groups.
We want to analyse the effects of intranasal insulin on patients with early Alzheimers's disease (eAD) and patients with T2D in the state of amnestic mild cognitive impairment (aMCI).
Recruitment of 30 patients with eAD, 30 patients with T2D in aMCI state and 30 age-matched healthy controls. All patients undergo a run-in period of 2 weeks with 4 × daily administration of placebo. It follows a double blinded trial with daily intranasal administration of 4 × 40 I.U. insulin vs. placebo for 8 weeks and another 8 weeks of follow-up. At 4 defined time points memory function is assessed by word lists comprising 30 items of emotional, nutritional and neutral content which have to be memorized and are recalled after one week. To assess structural changes of the brain, a quantitative analysis for hippocampal N-acetyl-aspartate, choline and creatine is performed by 3 Tesla magnetic resonance spectroscopy.
Results: Since the study has not finished yet, we present experiences from the initiation and the beginning phase.
During recent years the treatment of personality disorders has increasingly come into focus. As the psychotherapeutic interventions are still limited with respect to these demanding disorders there is a considerable need for further efficacy and, particularly, therapy process investigations. A promising approach is the development of integrated psychotherapy which combines cognitive-behavioral interventions with further change mechanisms such as the clarification of maladaptive schemata. On top of that, interventions should maintain a focus on emotional aspects of the therapeutic alliance (emotion regulation). In a study on “Schema-focused Emotive Behavioral Therapy” (SET), 93 patients with personality disorders of clusters B (predominantly narcissistic and Borderline PS) and C (avoidant and dependent PS) were randomised into one arm with SET group therapy and a control arm with manualised social skills training (SST). Therapies lasted for approximately 30 two-hour sessions.
Therapy process was closely monitored using therapy session reports both from the patients' and therapists' perspectives. Therapy outcome was assessed prior to and after therapy.
We report here on the change mechanisms, which were derived from modeling therapy session reports with novel time series methods (vector autoregression based on the estimation of session-to-session changes). It was found that the two therapy approaches differed with respect to change mechanisms. In SET (yet not in SST) therapy groups, clarification and insight reduced feelings of being rejected and disrespected, which was a major concern of many patients. In addition to this, a contrast was found between the prototypical therapy processes of cluster B and C patients. In conclusion, these results lay the ground for a disorder-specific application of integrated psychotherapy in personality disorders.
In acquired peripheral demyelinating disease only few publications point out the possibility of simultaneous involvement of the CNS. We describe two patients with chronic polyneuropathy and monoclonal gammopathy of undetermined significance (MGUS) developing a progressive dementia syndrome with extensive cerebral white matter alterations.
Low platelet MAO-B activity has been associated with various forms of impulsive behaviour and suicidality. The present study investigated the relationship between MAO-B activity in platelets and aspects of suicidality in depressed patients and controls.
In 87 patients with affective spectrum disorders (58% suffering from a Major Depressive Episode - MDE) the potential association between platelet MAO-B activity and suicidality was examined. 59 of the patients had committed suicide attempt recently (SA - “suicide attempters”), 28 patients were acutely depressed without having shown suicidal thoughts or suicidal behaviour in the past (NA - “non suicide attempters”).
SA and NA were comparable as to their diagnoses and general demographic and psychopathological parameters. MAO-B activity did not differ between SA and NA. No systematic correlations existed between MAO-B activity and any dimensions of suicidal behaviour or psychopathology. As a single finding only a weak positive association of higher MAO-B activity in SA with a fatal intention of the suicide attempt was observed.
Our findings do not support a consistent association of platelet MAO-B activity and suicidal behaviour in general, but specific facts of suicidality might be associated.