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With the exception of near-occlusion, CEA is of overall benefit for selected patients with recent symptomatic carotid stenosis =50% (NASCET method), provided surgical stroke/death risk is low. The benefit is greater with greater stenosis, men, the elderly (aged =75y), most recent ischaemic event within 2w, irregular plaque surface, and impaired cerebral perfusion reserve. Patients with recent symptomatic carotid territory ischaemic events should be screened by Doppler ultrasonography, MRA, or CTA, confirming substantial stenosis with a second non-invasive investigation. Catheter angiography may be required to confirm uncertain results. The surgical peri-operative stroke and death rate (7% in RCTs) is higher in women, hypertension, peripheral arterial disease, and occlusion of the contralateral ICA or ipsilateral ECA. The experience of the surgeon and hospital are crucial, and audited peri-operative complication rates should be publically available. Carotid stenting is less invasive than CEA and causes fewer local complications (cranial neuropathy and neck haematoma), but carries a higher procedural risk of stroke. Stenting should be considered in younger patients, or those at increased risk from CEA. While stenting is of high risk for intracranial vertebral artery stenosis, risk is low for extracranial stenosis and should be considered for recurrent symptoms despite optimal medical therapy.
To assess influenza symptoms, adherence to mask use recommendations, absenteesm and presenteeism in acute care healthcare workers (HCWs) during influenza epidemics.
The TransFLUas influenza transmission study in acute healthcare prospectively followed HCWs prospectively over 2 consecutive influenza seasons. Symptom diaries asking for respiratory symptoms and adherence with mask use recommendations were recorded on a daily basis, and study participants provided midturbinate nasal swabs for influenza testing.
In total, 152 HCWs (65.8% nurses and 13.2% physicians) were included: 89.1% of study participants reported at least 1 influenza symptom during their study season and 77.8% suffered from respiratory symptoms. Also, 28.3% of HCW missed at least 1 working day during the study period: 82.6% of these days were missed because of symptoms of influenza illness. Of all participating HCWs, 67.9% worked with symptoms of influenza infection on 8.8% of study days. On 0.3% of study days, symptomatic HCWs were shedding influenza virus while at work. Among HCWs with respiratory symptoms, 74.1% adhered to the policy to wear a mask at work on 59.1% of days with respiratory symptoms.
Respiratory disease is frequent among HCWs and imposes a significant economic burden on hospitals due to the number of working days lost. Presenteesm with respiratory illness, including influenza, is also frequent and poses a risk for patients and staff.
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.
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.
Increasing evidence suggests that symptoms of Attention Deficit Hyperactivity disorder (ADHD) could persist into adult life in a substantial proportion of cases. The aim of the present study is to investigate the impact of 1) adverse events, 2) personality traits and 3) genetic variants chosen on the basis of previous findings and 4) their possible interactions on adult ADHD severity in a sample of 110 Caucasian patients.
One hundred and ten individuals diagnosed with adult ADHD were evaluated for occurrence of adverse events in childhood and adulthood, and personality traits by the Temperament and Character Inventory (TCI). Common polymorphisms within a set of nine important candidate genes (SLC6A3, DBH, DRD4, DRD5, HTR2A, CHRNA7, BDNF, PRKG1 and TAAR9) were genotyped for each subject. Life events, personality traits and genetic variations were analyzed in relationship to severity of current symptoms, evaluated by the Brown Attention Deficit Disorder Scale (BADDS).
Genetic variations were not significantly associated with severity of ADHD symptoms and life stressors displayed only a minor effect as compared to personality traits. Indeed, symptoms’ severity was significantly correlated with the temperamental trait of Harm avoidance and the character trait of Self directedness.
The results of the present work are in line with previous evidence of a significant correlation between some personality traits and adult ADHD. However, several limitations such as the small sample size and the exclusion of patients with other severe comorbid psychiatric disorders could have influenced the significance of present findings.
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.
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.
Childhood Attention deficit hyperactivity disorder (ADHD) symptomatology persists in a substantial proportion of cases into adult life. ADHD is highly heritable but the etiology of ADHD is complex and heterogeneous, involving both genetic and non-genetic factors. In the present paper we analyzed the influence of both genetics and adverse life events on severity of ADHD symptoms in 110 adult ADHD patients. Subjects were genotyped for the norepinephrine transporter (NET), the Catechol-O-methyltransferase (COMT), the serotonin transporter promoter polymorphism (SERTPR) and the more rare A/G variant within SERTPR. Three main outcomes were obtained: (1) adverse events showed a small but positive correlation with current ADHD severity; (2) NET, COMT and the A/G variant within SERTPR were not associated with ADHD severity; (3) taking into account stressors, the long (L) SERTPR variant showed a mild effect on ADHD, being associated with an increased severity, particularly as regard affective dysregulations; on the other hand, in subjects exposed to early stressors, it showed a protective effect, as compared to the S variant (see table). In conclusion, our data support the role of environmental factors in adult ADHD symptomatology. SERTPR may be involved in some features of the illness and act as a moderator of environmental influences in ADHD.
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.
Clinical studies point toward a potential role of the serotonin transporter (SERT) binding as a predictor of clinical outcome in the treatment of depression. After long-term treatment with clinical doses of SSRIs the expected SERT occupancy is about 80%. Here, we were interested to investigate the relationship of SERT occupancy values between short- and longterm treatment.
To test if the SERT occupancy at steady-state can be predicted based on the single dose occupancy by escitalopram (S-citalopram) or citalopram (racemate of S-citalopram and R-citalopram).
18 patients with major depressive disorder received either escitalpram (10 mg/d) or citalopram (20 mg/d) in a double-blind, randomized, longitudinal study. They underwent three PET scans using the radioligand [11C]DASB: PET1 baseline, PET2 6 hours after first drug intake and PET3 after three weeks of daily oral treatment. Occupancy of SERT was quantified in six subcortical regions: thalamus, N. caudatus, putamen, mibrain, dorsal raphe and median raphe nuclei. Data was analyzed by means of multiple linear regression models corrected for baseline SERT availability values using SPSS 15.0.
Single dose occupancy of the SERT significantly predicted steady-state occupancy after three weeks in three regions: thalamus (r2 = 0.45, p = 0.009), N. caudatus (r2 = 0.4, p = 0.006) and putamen (r2 = 0.43, p = 0.005). Other regions did not show significant relationships.
In this study we demonstrated that single-dose occupancy in SERT rich regions such as thalamus, N. caudatus and the putamen could serve as reliable predictors for steady-state occupancy. However, a linear model failed to explain the relationship in regions known for serotonergic cell origin.
The influence of repetitive transcranial magnetic stimulation (rTMS) on mood in healthy people is uncertain, as former studies show divergent results. Previous studies in healthy volunteers focused exclusively on the immediate effect of a single session of rTMS on mood.
The aim of this study was to analyse the influence on mood of a series of 9 High Frequency (HF) rTMS stimulations of the left dorsolateral prefrontal cortex (DLPFC).
44 young healthy male volunteers were randomly assigned to receive 9 sessions of active HF-rTMS (n = 22) or sham rTMS (n = 22) over the left DLPFC. Each session in the active group consisted of 15 trains of 25 Hz starting with 100% of motor threshold. Sham stimulation was performed following the same protocol, but using a sham coil. The variables of interest were the Beck Depression Inventory (BDI) and Visual Analogue Scales (VAS) which quantified “mood”, “enjoyment” and “energy”.
We found a significant reduction of the BDI score in the active group (GLM, p < 0.001) whereas no significant changes of the BDI score were caused by sham stimulation (GLM, p = 0.109). We did not find significant differences caused by active or sham stimulation in VAS scales except for the VAS labelled lively/gloomy immediately after stimulation. The active group was found to be more “gloomy” (p = 0.001).
Our data support the hypothesis that a 9-day long series of HF-rTMS of the left DLPFC improves mood, analysed by BDI in healthy young men.
26.5% of psychiatric patients in Germany have minor children. More than half of these children have specific needs, which are seldom met.
To examine problems, needs and used interventions for families with a mentally ill parent in the federal state of Saxony, Germany. The study focused on outpatients and included mothers and fathers and all psychiatric disorders.
We asked all psychiatrists in the federal state of Saxony to take part in our study. All patients with minor children who came to one of the 58 participating psychiatrist's practices at an appointed date were asked to fill out a detailed questionnaire including sociodemographic data, the Strengths and Difficulties Questionnaire (SDQ), specific needs, used interventions and reasons for not using interventions. The questionnaire was developed using data from 26 expert interviews.
128 psychiatric outpatients took part in our study (78% female). The most common diagnoses were depression and anxiety disorders. More than 40% of the patients rated their children in the SDQ in an abnormal or borderline range. 22% of the children have been treated because of emotional or behavioural problems. Reasons not to use interventions were missing knowledge and fear of stigmatisation.
HELP-S for children is the first study which examines the situation of children with a mentally ill parent in an outpatient setting. Therefore, our results are an improvement in research in the field of families with a mentally ill parent and heading towards the improvement of care.
En psychiatrie, la contention médicale reste une pratique courante qui peut s’avérer traumatisante pour le patient. Elle doit toujours être associée à une sédation. Nous avons voulu réaliser un état des lieux de cette prise en charge médicamenteuse dans notre établissement.
Matériels et méthodes
Pendant 1 mois (janvier 2015), nous avons ciblé les patients sous énoxaparine sodique en préventif grâce au logiciel de prescription (Pharma®). Pour chaque patient, nous avons vérifié qu’il s’agissait bien d’une contention physique. Puis, une analyse des traitements prescrits était réalisée (médicaments, associations, posologies…).
Quatorze patients ont été inclus dans l’étude (8 hommes et 6 femmes, âge moyen : 33 ans). En moyenne, les patients ont été contenus 4 jours [1–10], l’énoxaparine sodique a été initié 24 h [0–72] après le début de la contention et administré pendant 2 jours [0–6]. Les patients ont reçu entre 0 et 3 antipsychotiques différents (cyamémazine, lévomépromazine et halopéridol) indiqués dans les états psychotiques aigus dont le plus prescrit était le cyamémazine (10/14 patients) à une posologie moyenne de 50 mg à j1, 115 mg à j2 et j3. Concernant les benzodiazépines, les patients ont reçu en moyenne une seule benzodiazépine et principalement le lorazépam (7/14) à une posologie de 4 mg à j1, 5,5 mg à j2 et j3 ou le diazépam (4/14) à une posologie de 7,5 mg à j1, 22,5 mg à j2 et 27,5 mg à j3.
Discussion et conclusion
Les patients contenus reçoivent donc peu de psychotropes, à posologies faibles par rapport aux doses habituelles en psychiatrie (exemple : cyamémazine jusqu’à 600 mg). Un groupe de travail sur la contention en psychiatrie est actuellement en cours dans l’établissement afin d’émettre des recommandations sur les modalités de prescription des psychotropes pour éviter une contention physique durable.
Depression and obesity are highly prevalent major public health problems that frequently co-occur. Shared aetiological factors have been found between depression and obesity. The role of the fat mass and obesity associated (FTO) gene in body mass index (BMI) and obesity has been confirmed in many independent studies. Recently, we reported the first study implicating FTO in the association between depression and obesity.
We aimed to confirm these findings by investigating the FTO rs9939609 polymorphism in a meta-analysis of 13,701 individuals.
The sample consists of 6,902 depressed cases and 6,799 controls from five studies (Radiant, PsyCoLaus, GSK, MARS and NESDA/NTR). Common inclusion criteria were information available on a lifetime DSM-IV diagnosis of major depressive disorder (MDD), BMI and genotype data. Linear regression models for quantitative traits assuming an additive genetic model were performed to test for association and interaction between rs9939609, BMI and depression. Fixed and random-effects meta-analyses were performed.
Fixed-effects meta-analyses support a significant association between rs9939609 polymorphism and BMI (whole-sample: ß=0.07, p=1.29×10-12, depressive-cases: ß=0.12, p=6.92×10-12). No association was found in controls (ß=0.02, p=0.15). Meta-analyses further support a significant interaction between FTO, BMI and depression (fixed-effects: ß=0.13, p=3.087×10-7; random-effects: ß=0.12, p=0.027), wherein depressed carriers of the risk allele have an additional increase of 2.2% in BMI.
This meta-analysis demonstrates a significant interaction between FTO, depression and BMI, indicating that depression increases the effect of FTO on BMI. Depression-related alterations in key biological processes may interact with the rs9939609 FTO risk allele to increase obesity risk.
Transcranial direct current stimulation (tDCS) is currently discussed as a therapeutic intervention in various psychiatric disorders. Based on the report about the effectiveness of tDCS in a patient with catatonic schizophrenia, we applied bilateral prefrontal tDCS in a patient with corpus callosum aplasia (CCA) and severe catatonia instead of maintenance electroconvulsive therapy (ECT).
To investigate whether tDCS can replace ECT in a largely treatment-resistant patient.
The 41 year-old male patient showed severe catatonic symptoms since adolescence and was treated by weekly ECT for almost 6 years. Due to cardiac complications and increasing cognitive deficits caused by long-term ECT and weekly anesthesia, tDCS was suggested. The anode was positioned over the left dorsolateral prefrontal cortex (DLPFC), the cathode over the right DLPFC. 2mA tDCS was delivered for 2x 20 minutes (90 minutes break in between), three times a week for the first two weeks, thereafter once to twice weekly. Concomitant medication (clozapine 600 mg/d, aripiprazole 10 mg/d, pirenzepine 50 mg/d, lorazepam 3 mg/d) was continued.
So far, more than 20 double sessions of tDCS were applied. ECT was needed once after a period of hospitalisation for 10 days due to pneumonia. Since then the patient has solely received tDCS for more than 13 weeks. Catatonic symptoms resolved further under tDCS compared to ECT (Bush-Francis Catatonia Rating Scale: 27/69 points during ECT, 5/69 during tDCS).
tDCS in combination with neuroleptic treatment could be an alternative to ECT in organic catatonia. Further studies are needed to support our hypothesis.
A proinflammatory state in a subgroup of depressed patients has been reported repeatedly, for example an increase in interleukin-6 and tumour necrosis factor-a is well documented. Treatment with COX-2 inhibitors down-regulate increased inflammatory markers. Therefore an adjunctive treatment of depression with COX-2 in combination with an antidepressant might lead to a better clinical outcome.
To prove or disapprove the hypothesis of a better clinical outcome in the group with add-on celecoxib to sertraline in terms of improvement of HamD-17 and MADRS scores from baseline to endpoint.
This is a dual-center, randomized, double-blind, placebo-controlled, parallel group phase IIa study to investigate the mean change in clinical outcome and in serum expression of inflammation markers from baseline to endpoint (week 6) in patients with major depression (HAMD-17 ≥ 22) treated with celecoxib in combination with sertraline compared to sertraline combined with placebo. 51 depressed patients of both gender, aged between 18 and 60 without any recent inflammatory related disease were enrolled. The study comprises six study visits (6x ratings including HAMD-17 and MADRS, 3x blood collections) during six weeks of treatment and a follow-up visit 10 weeks after baseline.
Results and Conclusion
The study was completed quite recently and the results are in progress.