Hospital Krefeld-Düsseldorf

Kinase inhibitors are important cancer therapeutics. Polypharmacology is commonly observed, requiring thorough target deconvolution to understand drug mechanism of action. Using chemical proteomics, we analyzed the target spectrum of 243 clinically evaluated kinase drugs. The data revealed previously unknown targets for established drugs, offered a perspective on the "druggable" kinome, highlighted (non)kinase off-targets, and suggested potential therapeutic applications. Integration of phosphoproteomic data refined drug-affected pathways, identified response markers, and strengthened rationale for combination treatments. We exemplify translational value by discovering SIK2 (salt-inducible kinase 2) inhibitors that modulate cytokine production in primary cells, by identifying drugs against the lung cancer survival marker MELK (maternal embryonic leucine zipper kinase), and by repurposing cabozantinib to treat FLT3-ITD-positive acute myeloid leukemia. This resource, available via the ProteomicsDB database, should facilitate basic, clinical, and drug discovery research and aid clinical decision-making.

Oropharyngeal dysphagia (OD) is a highly prevalent and growing condition in the older population. Although OD may cause very severe complications, it is often not detected, explored, and treated. Older patients are frequently unaware of their swallowing dysfunction which is one of the reasons why the consequences of OD, ie, aspiration, dehydration, and malnutrition, are regularly not attributed to dysphagia. Older patients are particularly vulnerable to dysphagia because multiple age-related changes increase the risk of dysphagia. Physicians in charge of older patients should be aware that malnutrition, dehydration, and pneumonia are frequently caused by (unrecognized) dysphagia. The diagnosis is particularly difficult in the case of silent aspiration. In addition to numerous screening tools, videofluoroscopy was the traditional gold standard of diagnosing OD. Recently, the fiberoptic endoscopic evaluation of swallowing is increasingly utilized because it has several advantages. Besides making a diagnosis, fiberoptic endoscopic evaluation of swallowing is applied to evaluate the effectiveness of therapeutic maneuvers and texture modification of food and liquids. In addition to swallowing training and nutritional interventions, newer rehabilitation approaches of stimulation techniques are showing promise and may significantly impact future treatment strategies.

BACKGROUND: Pyoderma gangrenosum (PG) is a rarely diagnosed ulcerative neutrophilic dermatosis with unknown origin that has been poorly characterized in clinical studies so far. Consequently there have been significant discussions about its associated factors and comorbidities. The aim of our multicenter study was to analyze current data from patients in dermatologic wound care centers in Germany in order to describe associated factors and comorbidities in patients with PG. METHODS: Retrospective clinical investigation of patients with PG from dermatologic wound care centers in Germany. RESULTS: We received data from 259 patients with PG from 20 different dermatologic wound care centers in Germany. Of these 142 (54.8%) patients were female, 117 (45.2%) were male; with an age range of 21 to 95 years, and a mean of 58 years. In our patient population we found 45.6% with anemia, 44.8% with endocrine diseases, 12.4% with internal malignancies, 9.3% with chronic inflammatory bowel diseases and 4.3% with elevated creatinine levels. Moreover 25.5% of all patients had a diabetes mellitus with some aspects of potential association with the metabolic syndrome. CONCLUSIONS: Our study describes one of the world's largest populations with PG. Beside the well-known association with chronic bowel diseases and neoplasms, a potentially relevant new aspect is an association with endocrine diseases, in particular the metabolic syndrome, thyroid dysfunctions and renal disorders. Our findings represent clinically relevant new aspects. This may help to describe the patients' characteristics and help to understand the underlying pathophysiology in these often misdiagnosed patients.

OBJECTIVE: The objective of this study is to determine the feasibility of computerized evaluation of resident performance using hand motion analysis on a virtual reality temporal bone (VR TB) simulator. We hypothesized that both computerized analysis and expert ratings would discriminate the performance of novices from experienced trainees. We also hypothesized that performance on the virtual reality temporal bone simulator (VR TB) would differentiate based on previous drilling experience. STUDY DESIGN: The authors conducted a randomized, blind assessment study. METHODS: Nineteen volunteers from the Otolaryngology-Head and Neck Surgery training program at the University of Toronto drilled both a cadaveric TB and a simulated VR TB. Expert reviewers were asked to assess operative readiness of the trainee based on a blind video review of their performance. Computerized hand motion analysis of each participant's performance was conducted. RESULTS: Expert raters were able to discriminate novices from experienced trainees (P < .05) on cadaveric temporal bones, and there was a trend toward discrimination on VR TB performance. Hand motion analysis showed that experienced trainees had better movement economy than novices (P < .05) on the VR TB. CONCLUSION: Performance, as measured by hand motion analysis on the VR TB simulator, reflects trainees' previous drilling experience. This study suggests that otolaryngology trainees could accomplish initial temporal bone training on a VR TB simulator, which can provide feedback to the trainee, and may reduce the need for constant faculty supervision and evaluation.

OBJECTIVES: To define a practice guideline for biological treatment of dementia and to make transparent the development of the guideline connecting the original data with the resulting recommendations. METHODS: This guideline includes pharmacologic treatment considerations for patients with Alzheimer's disease, vascular dementia, DLB, and fronto-temporal dementia. Studies were selected that represent double-blind placebo-controlled trials of at least 3 months duration in patients with a diagnosis of dementia according to accepted international diagnostic criteria (for example the NINCDS/ADRDA or NINDS/AIREN criteria). Moreover, to be included studies had to fulfill a restrictive set of methodological criteria. Original studies and not meta-analyses determined the evaluation and the development of recommendations. RESULTS: Antidementia pharmaceuticals neither cure nor arrest the disease. A modest effect of improvement of symptoms compared with placebo can be observed. Antidementia pharmaceuticals show different efficacy and side effect profiles. The type of dementia, the individual symptom constellation and the tolerability should determine what medication should be used. There are hints that combination therapy of drugs with different therapeutic mechanisms might improve the efficacy. In treating neuropsychiatric symptoms (NPS), psychosocial intervention should be the treatment of first choice. Pharmaceuticals can only be recommended when psychosocial interventions is not adequate. However, even then the side effects of pharmaceuticals limit their use. CONCLUSIONS: Depending on the diagnostic entity and the pathology treated different anti-dementia drugs can be recommended to improve symptoms. In the management of NPS, side effects limit the use of medications even when psychosocial interventions have failed. Thus, there is an urgent need to develop more efficacious medications for the treatment of dementia.

OBJECTIVE: A reduction of diabetes-related blindness was declared a primary objective for Europe (St. Vincent Declaration). We collected data about incidence rates of blindness in the diabetic population compared with the nondiabetic population. Up to now, such data are scarce-even worldwide. RESEARCH DESIGN AND METHODS: A complete list of newly registered blindness allowance recipients was drawn up in the district of Württemberg-Hohenzollern, Germany, between 1990 and 1993. From these data, we estimated age-specific and standardized incidence rates of blindness in the entire, the diabetic, and the nondiabetic population, as well as relative and attributable risks due to diabetes. RESULTS: There were 2,714 people meeting the inclusion criteria; 1,823 (67.2%) were female and 781 (28.8%) had diabetes. In 318 subjects, diabetes was likely to be the only cause of blindness; in 192 subjects, it was one of several contributory causes. Age of women was 73.9 +/- 19.4 years (mean +/- SD) and of men 63.3 +/- 25.5 years. Results standardized to the (West) German population are as follows: incidence rates (per 100,000 person-years): total population: 13.5; diabetic population: 60.6; nondiabetic population: 11.6; relative risk: 5.2; attributable risk among exposed: 0.81; and population attributable risk: 0.14. The relative risks decreased considerably with increasing age. When the study is repeated to monitor the St. Vincent targets, a reduction in the incidence rate of blindness in the diabetic population by 17% will be detected with 95% power. CONCLUSIONS: Great relative and attributable risks, especially in younger age-groups, indicate the need for increased attention to preventive measures for microvascular complications.

Fanconi anaemia (FA), a model syndrome of genome instability, is caused by a deficiency in DNA interstrand crosslink repair resulting in chromosome breakage1–3. The FA repair pathway protects against endogenous and exogenous carcinogenic aldehydes4–7. Individuals with FA are hundreds to thousands fold more likely to develop head and neck (HNSCC), oesophageal and anogenital squamous cell carcinomas8 (SCCs). Molecular studies of SCCs from individuals with FA (FA SCCs) are limited, and it is unclear how FA SCCs relate to sporadic HNSCCs primarily driven by tobacco and alcohol exposure or infection with human papillomavirus9 (HPV). Here, by sequencing genomes and exomes of FA SCCs, we demonstrate that the primary genomic signature of FA repair deficiency is the presence of high numbers of structural variants. Structural variants are enriched for small deletions, unbalanced translocations and fold-back inversions, and are often connected, thereby forming complex rearrangements. They arise in the context of TP53 loss, but not in the context of HPV infection, and lead to somatic copy-number alterations of HNSCC driver genes. We further show that FA pathway deficiency may lead to epithelial-to-mesenchymal transition and enhanced keratinocyte-intrinsic inflammatory signalling, which would contribute to the aggressive nature of FA SCCs. We propose that the genomic instability in sporadic HPV-negative HNSCC may arise as a result of the FA repair pathway being overwhelmed by DNA interstrand crosslink damage caused by alcohol and tobacco-derived aldehydes, making FA SCC a powerful model to study tumorigenesis resulting from DNA-crosslinking damage. Defective DNA interstrand crosslink repair in Fanconi anaemia drives extensive genomic rearrangements, thereby substantially increasing the risk of cancer development.

SHOX mutations causing haploinsufficiency were reported in Leri-Weill dyschondrosteosis (LWD), which is characterized by mesomelic short stature and Madelung deformity of the wrists. The aim of this study was to determine the prevalence of SHOX mutations in LWD and to investigate the degree of growth failure in relation to mutation, sex, age of menarche, and wrist deformity. We studied 20 families with 24 affected children (18 females) and nine affected parents (seven females). All patients presented with bilateral Madelung deformity and shortening of the limbs. Height, sitting height, parental height, birth length, age of menarche, and presence of minor abnormalities were recorded. The degree of Madelung deformity was estimated by analysis of left hand radiographs. Microsatellite typing of the SHOX locus was used for detection of SHOX deletions and PCR direct sequencing for the detection of SHOX point mutations. In 14 of 20 families (70%), SHOX mutations were detected, with seven deletions (four de novo) and seven point mutations (one de novo). The latter included five missense mutations of the SHOX homeodomain, one nonsense mutation (E102X) truncating the whole homeodomain, and one point mutation (X293R) causing a C-terminal elongation of SHOX. Median age of the affected children was 13.4 yr (range, 6.1-18.3), mean height sd score (SDS) (sd in parentheses) was -2.85 (1.04), and mean sitting height/height ratio SDS was +3.06 (1.09). Mean birth length SDS was -0.59 (1.26). Growth failure occurred before school age. Height change during a median follow-up of 7.4 yr (range, 2.3-11.3) was insignificant with a mean change in height SDS of -0.10 (0.52). Mean height SDS of affected parents was -2.70 (0.85) vs. -0.91 (1.10) in unaffected parents. Height loss due to LWD was estimated calculating delta height defined by actual height SDS minus target height SDS of the unaffected parent(s). In the children, mean delta height SDS was -2.16 (1.06), the loss being greater in girls at -2.30 (1.02) than in boys at -1.72 (1.09) (P = 0.32). In patients with SHOX deletions, it was -2.14 (1.15) vs. -1.67 (0.73) for the SHOX point mutation group (P = 0.38). Mean delta height SDS was -2.26 (0.68) for the girls with early menarche (<12 yr) vs. -2.08 (0.91) for the other postmenarcheal girls (P = 0.72). Height loss in patients with radiologically severe wrist deformities in comparison with those having milder radiological signs was -2.81 (1.01) vs. -1.70 (1.04) (P = 0.03). GH treatment in five children during a median duration of 3.4 yr (range, 1.5-9.8 yr) with a median dosage of 0.23 mg/kg.wk (range, 0.14-0.25) resulted in a mean height SDS gain of +0.82 (0.34). In conclusion, SHOX defects were the main cause of LWD. Growth failure occurred during the first years of life with a mean height loss of 2.16 SDS whereas pubertal growth may only be mildly or not affected. Children with a severe degree of wrist deformity were significantly shorter than those with mild deformities. No statistically significant effects of type of mutation, age of menarche, or sex on height were observed. The effect of GH therapy varied between individuals and needs to be examined in controlled studies.

We treated two patients with recurrent glioblastoma multiforme using Nd:YAG laser irradiation in the framework of a salvage therapy. The underlying concept is to achieve cytoreduction by partial coagulation of the tumor. Magnetic resonance imaging (MRI) follow-up examinations revealed a volume reduction of the laser-irradiated areas, while the untreated parts of the tumor exhibited a progression. The survival time after the diagnosis of the recurrence was 16 and 20 months, respectively, which is substantially (about four times) longer than the natural history of the disease would suggest. In conclusion, cytoreduction by laser irradiation may be a promising option for patients suffering from recurrent glioblastoma multiforme. Future work should optimize the therapeutic regimen and evaluate this treatment approach in controlled clinical trials.

Abstract Forest canopies are highly diverse ecosystems, but despite several decades of intense research, there remain substantial gaps in our knowledge of their biodiversity and ecological interactions. One fundamental challenge in canopy research is the limited accessibility of the ecosystem. Consequently, previous studies have relied on the application of either highly invasive methods such as chemical knockdown, or on time‐consuming and expensive setups such as canopy walkways or cranes. Therefore, time‐ and cost‐efficient, ideally minimally invasive yet comprehensive applications are required to help close this knowledge gap. High‐throughput metabarcoding of environmental DNA (eDNA) collected from water, soil, or air provides a minimally invasive method for biodiversity assessment, yet its potential for canopy biodiversity monitoring has not been explored. Herein, we conducted metabarcoding of eDNA washed off the canopy via rainwater to explore its potential for biodiversity monitoring and ecological research. We placed four 1 m 2 rain samplers beneath the canopies of four different trees (beech, oak, larch, and pine) prior to a major rain event, filtered eDNA from the collected rainwater, and performed cytochrome c oxidase subunit I (COI) gene metabarcoding to profile the invertebrate community. Additionally, we collected and identified all specimens present in the rainwater to assess if eDNA only came from specimens physically present in the rainwater. We detected 50 invertebrate species by eDNA metabarcoding, of which 43 were not physically present in the water sample, thus likely representing true canopy biodiversity signals. Furthermore, we observed distinct species occurrence patterns corresponding to the four trees, suggesting that ecological patterns such as host specificity can potentially be assessed using the method. In conclusion, our study provides a proof of principle that rainwash eDNA metabarcoding offers a minimally invasive and comprehensive method for biodiversity monitoring in tree canopies.

BACKGROUND AND PURPOSE: An unknown connective tissue defect might predispose for the development and rupture of intracranial aneurysms in some patients. This study of connective tissue samples of a series of patients with intracranial aneurysms investigates the morphology of the extracellular matrix with methods that are currently used in the routine diagnosis of inherited connective tissue disorders. METHODS: Skin biopsies from 21 patients with intracranial aneurysms, many with multiple aneurysms, were studied by electron microscopy. None of the patients included in this study showed clinical signs of a known connective tissue disorder. RESULTS: In 7 patients (33%), we observed repetitive aberrations in the morphology of collagen fibrils and elastic fibers of the reticular dermis. The observed ultrastructural findings were somewhat similar to those typically observed in patients with Ehlers-Danlos syndrome (EDS) and in a subgroup of patients with spontaneous cervical artery dissections. The patterns of abnormalities fell into 2 classes: 4 patients displayed abnormalities that resembled those found in patients with EDS type III, and the electron microscopic findings in the skin biopsies from 3 patients resembled those of EDS type IV patients. The sequence of the COL3A1 gene from the patients with EDS type IV-like alterations of the connective tissue morphology was analyzed. No mutation was detected. CONCLUSIONS: Connective tissue alterations were found in skin biopsies from a minority of patients with intracranial aneurysms. Electron microscopic investigation of skin biopsies from patients and their relatives might become valuable for clinical diagnostics, identification of persons at risk, and basic studies of the pathogenesis of this vascular disease.

Objective: To assess effects of EGb 761® on cognition and quality of life in subjects with very mild cognitive impair-ment. Methods: We randomized 300 subjects aged 45 to 65 with cognitive complaints and low functioning (more than one standard deviation below appropriate norm) in at least one cognitive test to double-blind treatment with once daily 240 mg EGb 761® or placebo for 12 weeks. Results: The exploratory intention-to-treat analysis showed significant im-provement (p < 0.025, one-sided) beyond practice effects for EGb 761® in a measure of attention (Vienna Test System - Work Performance Series) and trends in favour of EGb 761® in measures of memory (Wechsler Memory Scale III - Faces I, Appointments Test – delayed recall), and perceived physical health (SF36 - factor score Physical Health). Cognitive effects were more pronounced and more consistent (p < 0.025 in 4 of 5 tests) in subjects with lower memory function at baseline. Specifically, practice effects in the more demanding tests were attenuated or absent in these sub-jects. Conclusion: Ginkgo biloba extract EGb 761® improved cognitive functioning and aspects of quality of life in sub-jects with very mild cognitive impairment.

BACKGROUND: The aim of this study was to investigate whether bullying among students is associated with symptoms of posttraumatic stress disorder (PTSD), and whether associations are comparable to other traumatic events leading to PTSD. METHODS: Data were collected from 219 German children and adolescents: 150 students from grade six to ten and 69 patients from an outpatient clinic for PTSD as a comparison group. Symptoms of PTSD were assessed using the Children's Revised Impact of Event Scale (CRIES) and the Posttraumatic Symptom Scale (PTSS-10). A 2 × 5 factorial analysis of variance (ANOVA) with the factors gender (male, female) and group (control, conflict, moderate bullying, severe bullying, traumatized) was used to test for significant differences in reported PTSD symptoms. RESULTS: Results showed that 69 (46.0%) students from the school sample had experienced bullying, 43 (28.7%) in a moderate and 26 (17.3%) in a severe way. About 50% of the severe bullying group reached the critical cut-off point for suspected PTSD. While the scores for symptoms of PTSD were significantly higher in bullied versus non-bullied students, no significant differences were found between patients from the PTSD clinic and students who experienced severe bullying. CONCLUSIONS: Our findings suggest that bullying at school is highly associated with symptoms of PTSD. Thus, prevention of bullying in school may reduce traumatic experiences and consequent PTSD development.

BACKGROUND: Language impairment is one of the most troublesome manifestations of Alzheimer's disease (AD). The objective of this post hoc analysis was to assess the treatment effects of Memantine on language in patients with moderate to severe AD, using the recently developed Severe Impairment Battery-Language (SIB-L) scale. METHODS: From a combined database including four Memantine clinical trials in moderate-to-severe AD, we analyzed 801 patients with SIB-L scores of <38 and Mini-Mental State Examination scores of <15. Patients were treated with either 20 mg Memantine per day or placebo. Mean changes in SIB-L scores from baseline were calculated. For responder analyses, a change in SIB-L score greater than or equal to the SIB-L measurement error of 3.7 points was considered a clinically relevant response. RESULTS: The mean change from baseline in SIB-L score at week 12 and weeks 24/28 (study end) significantly favored Memantine over placebo treatment (P < .0001 and P = .0182, respectively). Overall, more Memantine-treated patients than placebo-treated patients benefited from treatment. The effect was especially pronounced in patients with substantial language impairment on the SIB-L (baseline score, <or=20). At weeks 24/28, significantly more Memantine-treated patients experienced a clinically relevant improvement (25.4% vs. 10.8%, P = .0414), and significantly fewer patients experienced clinically relevant worsening (32.8% vs. 60.0%, P = .0029). CONCLUSIONS: Memantine treatment of AD patients results in significant benefits for language function. Our results suggest that it is worth considering this therapeutic option, even for AD patients with marked language impairment.

Background: Tinnitus and dizziness are frequent in old age and often seen as concomitant symptoms in patients with dementia. In earlier clinical trials, Ginkgo biloba extract EGb 761 ® was found to alleviate tinnitus and dizziness in elderly patients. Consequently, a meta-analysis was conducted to evaluate the effects of EGb 761 ® at a daily dose of 240 mg on tinnitus and dizziness associated with dementia. Methods: Randomized, placebo-controlled clinical trials of G. biloba extract EGb 761 ® identified by a systematic database search were included in a meta-analysis if they met all of the following selection criteria: 1) diagnosis of dementia according to generally accepted criteria, 2) treatment period of at least 20 weeks, 3) outcome measures covering at least two of the three conventional domains of assessment, 4) presence and severity of dizziness and tinnitus were assessed, and 5) assessment was done before and after randomized treatment. Results: Five trials that met the inclusion criteria were included in the meta-analysis. The risk of bias was judged as low, with Jadad scores of 3 and 5. In all trials, 11-point box scales were used to assess the severity of tinnitus and dizziness. Overall, EGb 761 ® was superior to placebo, with weighted mean differences for change from baseline, calculated in meta-analyses using random effects models, of -1.06 (95% CI: -1.77, -0.36) for tinnitus ( p = 0.003) and -0.77 (95% CI: -1.44, -0.09) for dizziness ( p = 0.03). Conclusion: Our findings support the notion that EGb 761 ® is also effective in alleviating concomitant neurosensory symptoms in patients with dementia. Keywords: neurodegenerative disorders, gait, unsteadiness, inner ear, hearing, review

Ovarian cancer is currently the most lethal gynecologic malignancy in Europe and the US. Platin analogues and paclitaxel demonstrate high remission rates, but unfortunately the efficacy of cytostatic agents is limited by the development of multidrug resistance (mdr). Clinical paclitaxel resistance is often associated with mdr1 overexpression. In a recent study, we introduced a highly specific quantitative real-time reverse transcriptase polymerase chain reaction for the quantification of mdr1 transcripts. In the present study, we demonstrate that primary tumor cells from patients with recurrent ovarian cancer overexpress mdr1. To evaluate mdr1 expression, we collected tumor cells from 77 ovarian cancer patients (13 chemotherapy-naive ovarian cancer, 64 recurrent ovarian cancer). Cancer cells were aspirated from 49 solid specimens (63%) and 28 ascitic fluids (37%). Subsequently, cancer cells were exposed in 221 short-term cultures either to blank medium (control) or to a single anticancer drug, cisplatin, doxorubicin or paclitaxel. The drug concentrations applied referred to clinical relevant doses. mdr1 mRNA expression was significantly higher in specimens from recurrent ovarian cancer incubated in paclitaxel than in specimens from chemotherapy-naive ovarian cancer. No significant differences were detectable between the mean value of mdr1 mRNA expression in tumor specimens from recurrent ovarian cancer incubated in cisplatin or doxorubicin. Differences within the untreated patients group were also not statistically significant. The result of this study confirms clinical observations, as well as in-vitro studies based on tumor cell lines, that paclitaxel resistance is correlated with mdr1 overexpression.

AIMS: Conventional approaches to the management of neuropathic pain (NeP) often yield unsatisfactory results. We aimed to investigate pregabalin, a gamma-aminobutyric acid (GABA)-analogue, in a wide range of pregabalin naive patients with treatment refractory NeP. METHODS: Investigator-initiated, 4-week, open, prospective multicentre study in tertiary care. Pregabalin was prescribed at physicians' discretion based on patients' individual responses and tolerability, with or without concomitant analgesics. Consecutive patients were requested to fill in questionnaires at baseline and after 14 and 28 days with numerical pain rating scales (0, none; 10, worst possible), sleep rating scales, parts of the Brief Pain Inventory, Pain Experience Scale, Short Questionnaire on Current Burden and the SF-12 health-related quality of life scale. RESULTS: In 55 patients, the mean pregabalin dose was 142 +/- 26 mg at day 1 and 348 +/- 161 mg at day 28. The mean pain score decreased from 6.5 +/- 1.7 to 5.5 +/- 1.9 at day 14 and to 4.9 +/- 1.8 at day 28 (-24.6%, p < 0.0001). Significant and rapid improvements were noted in the sleep interference score (p < 0.00001), Short Questionnaire on Current Burden (p < 0.01) and SF-12 (somatic score p < 0.001; psychological score p < 0.01). Pregabalin was well tolerated, and only three patients (5%) discontinued treatment prematurely. CONCLUSIONS: Our findings suggest that pregabalin is an effective and well-tolerated drug in difficult-to-treat NeP patients under daily clinical practice conditions. A flexible dosing approach appears appropriate to ensure patient compliance and treatment success.

The World Psychiatric Association (WPA) Section of Old Age Psychiatry, since 1997, has developed Consensus Statements relevant to the practice of Old Age Psychiatry. Since 2006 the Section has worked to develop a Consensus Statement on Ethics and Capacity in older people with mental disorders, which was completed in Prague, September 2008, prior to the World Congress in Psychiatry. This Consensus meets one of the goals of the WPA Action Plan 2008-2011, "to promote the highest ethical standards in psychiatric practice and advocate the rights of persons with mental disorders in all regions of the world". This Consensus Statement offers to mental health clinicians caring for older people with mental disorders, caregivers, other health professionals and the general public the setting out of and discourse in ethical principles which can often be complex and challenging, supported by practical guidance in meeting such ethical needs and standards, and to encouraged good clinical practice.

PURPOSE: Persons in lower occupational positions experience higher rates of morbidity compared to workers in higher advantaged positions. Working conditions may explain this occupational health gradient. Most studies consider either psychosocial or physical work demands at one point in time. In our study, we examine both physical and psychosocial work demands and their association with health status differentiated by job requirement level. We further distinguish between constant and changing work demands. METHODS: Using data from the first two waves of the German cohort study on work, age and health, we analyse a sample of 3644 older workers born in 1959 and 1965. We test direct and mediating effects of high physical and psychosocial work demands on functional physical and mental health. For this, we estimate a prospective path model using multiple linear regression models. RESULTS: Our results show that (1) constant high physical and psychosocial work demands affect physical and mental health negatively and (2) high physical workload partly mediates the relationship between job requirement level and physical health. Moreover, at least for men, a reduction of physical and psychosocial workload improves mental health status. CONCLUSIONS: Research and prevention measures currently focus particularly on psychosocial work demands. Our study shows that high physical workload is still present among older workers. Its negative health effect refers to occupational safety and health measures that take into account both the physical and psychosocial work environment as well as workers' occupational positions.

OBJECTIVE: To define a practice guideline for biological treatment of dementias for general practitioners in primary care. METHODS: This paper is a short and practical summary of the World Federation of Biological Psychiatry (WFSBP) guidelines for the Biological treatment of Alzheimer's disease and other dementias for treatment in primary care ( Ihl et al. 2011 ). The recommendations were developed by a task force of international experts in the field and are based on randomized controlled studies. RESULTS: Anti-dementia medications neither cure, nor arrest, or alter the course of the disease. The type of dementia, the individual symptom constellation and the tolerability and evidence for efficacy should determine what medications should be used. In treating neuropsychiatric symptoms, psychosocial intervention should be the treatment of first choice. For neuropsychiatric symptoms, medications should only be considered when psychosocial interventions are not adequate and after cautious risk-benefit analysis. CONCLUSIONS: Depending on the diagnostic entity and clinical presentation different anti-dementia drugs can be recommended. These guidelines provide a practical approach for general practitioners managing dementias.