Cluster-randomized controlled trial of dissemination strategies of an online quality improvement programme for alcohol-related disorders.

AIMS: This project investigated different dissemination strategies of an online quality improvement programme for alcohol-related disorders into routine care in South Baden and South Württemberg in Germany. METHODS: In a cluster-randomized controlled trial, 112 general practices were randomized into three groups. The first group (n = 43) received access to the online system and a training programme for the general practitioners (GPs). The second group (n = 42) additionally received education for the whole practice team. The third group (n = 27) acted as control and received only access to the online system. RESULTS: Two thousand six hundred and forty-seven practitioners were asked to take part in the study, and it was possible to randomize 112 (4%) practices. There were no significant differences concerning the use of the system between the groups: 41.9% of the GPs in the first group, 42.9% in the second group and 44.4% in the control group used the system. In terms of only the system users, 55.6% of the GPs in the first group, 33.3% in the second group and 8.3% in the control group used the system six times or more (P = 0.019). Diagnostic assessments made by the GPs in the groups differed substantially: 72.2% of diagnoses in the first group were correct, while this figure lay at 69.7% in the second group and 36.4% in the control group (P = 0.034). CONCLUSIONS: No effect of the additional training on the primary outcome (acceptance) was identified, but on two of the secondary outcomes. Further cost-effectiveness studies should investigate whether the effort involved in providing training additionally to the system is justifiable. The study is registered at ClinicalTrials.gov: NCT00314067. This article conforms to the guidelines in the Consolidated Standards of Reporting Trials (CONSORT) statement (Moher et al., 2001; Campbell et al., 2004).

Is the risk for soil arthropods covered by new data requirements under the EU PPP Regulation No. 1107/2009?

Testing of effects on earthworms and non-target foliar arthropods is an integral part of the ecotoxicological risk assessment for the authorization of plant protection products. According to the new data requirements, which came into force in 2014 for active substances and in 2016 for plant protection products, the chronic earthworm toxicity test with Eisenia fetida based on reproductive, growth, and behavioral effects instead of the acute earthworm toxicity test based on mortality, has to be conducted routinely. Additional testing of effects on soil arthropods (Folsomia candida, Hyposaspis aculeifer) is required if the risk assessment of foliar applications raises concerns regarding non-target foliar arthropods (Aphidius rhopalosiphi, Typhlodromus pyri) or if the product is applied directly on or into the soil. Thus, it was investigated whether the sublethal earthworm endpoint is more sensitive than the sublethal soil arthropod endpoint for different types of pesticides and whether the risk assessment for non-target arthropods would trigger the testing of effects on soil arthropods in the cases where soil arthropods are more sensitive than earthworms. Toxicity data were obtained from Swiss ecotoxicological database, EFSA Conclusions and scientific literature. For insecticides and herbicides, no general conclusion regarding differences in sensitivity of either earthworms or soil arthropods based on sublethal endpoints were possible. For fungicides, the data indicated that in general, earthworms seemed to be more sensitive than soil arthropods. In total, the sublethal F. candida or H. aculeifer endpoint was lower than the sublethal E. fetida endpoint for 23 (34 %) out of 68 active substances. For 26 % of these 23 active substances, testing of soil arthropods would not have been triggered due to the new data requirement. These results based on sublethal endpoints show that earthworms and soil arthropods differ in sensitivity toward certain active substances and that the risk assessment for non-target foliar arthropods did not always trigger soil arthropod testing in the cases where soil arthropods were more sensitive than earthworms.

Molecular evaluation of vitamin D3 receptor agonists designed for topical treatment of skin diseases.

MC903 (calcipotriol) is a synthetic, low calcemic analog of the nuclear hormone 1alpha,25-dihydroxyvitamin D3 and used in the treatment of psoriasis. The beneficial effects of MC903 on psoriasis are based on gene regulatory events. The genomic actions of 1alpha,25-dihydroxyvitamin D3 and its analogs are primarily mediated by a complex of the vitamin D3 receptor and the retinoid X receptor bound to a 1alpha,25-dihydroxyvitamin D3 response element that can be considered as the molecular switch of 1alpha,25-dihydroxyvitamin D3 signaling. In this study, the interaction of MC903 and two new analogs, GS1500 and EB1213, with this molecular switch was compared with that of 1alpha,25-dihydroxyvitamin D3. In DNA-dependent limited protease digestion assays, ligand-dependent gel shift assays and mammalian-one-hybrid assays, all four ligands appeared to be equally sensitive VDR agonists that activated vitamin D3 receptor-retinoid X receptor-1alpha,25-dihydroxyvitamin D3 response element complexes at a concentration of approximately 0.2 nM. The analyzed VDR agonists, however, also showed individual molecular properties, such as a reduced sensitivity in HaCaT cells (MC903), a selectivity for DNA-bound vitamin D3 receptor-retinoid X receptor heterodimers (GS1500) and a long-lasting stabilization of vitamin D3 receptor-retinoid X receptor-1alpha,25-dihydroxyvitamin D3 response element complexes (EB1213). This molecular evaluation demonstrated that the sensitivity in activating the vitamin D3 receptor is already optimal for MC903, but the analog may not be ideal in keeping the receptor active and in selectively triggering 1alpha,25-dihydroxyvitamin D3 signaling pathways.

[E-Learning--an important contribution to general medical training and continuing education?]. / E-Learning--eine wichtige Unterstützung in der medizinischen Aus-, Fort- und Weiterbildung?

There is increasing activity in the development of e-learning modules for general medical training and continuing education. One of the central advantages of e-learning is flexibility regarding time and place of its use. The quality of the available e-learning opportunities varies quite considerably. For users it is often not easy to assess the quality of e-learning modules or to find offers of high quality. This could be a reason for the fact that despite the huge number of e-learning modules still only few students and physicians are using them. This is although e-learning has proven to be as effective as and even more efficient than learning in the classroom or with paper-based materials. This article summarizes the different models of e-learning, how and where to find offers of high quality, advantages of using e-learning, and the effectiveness and efficiency of such offers. In addition problems of e-learning and possibilities to overcome these problems are shown.

Quantitative scanning near-field microwave microscopy for thin film dielectric constant measurement.

We combine a scanning near-field microwave microscope with an atomic force microscope for use in localized thin film dielectric constant measurement, and demonstrate the capabilities of our system through simultaneous surface topography and microwave reflection measurements on a variety of thin films grown on low resistivity silicon substrates. Reflection measurements clearly discriminate the interface between approximately 38 nm silicon nitride and dioxide thin films at 1.788 GHz. Finite element simulation was used to extract the dielectric constants showing the dielectric sensitivity to be Deltaepsilon(r)=0.1 at epsilon(r)=6.2, for the case of silicon nitride. These results illustrate the capability of our instrument for quantitative dielectric constant measurement at microwave frequencies.

[Diagnostic and treatment of alcohol-related disorders. Results of a representative survey in counseling centers]. / Diagnostik und Behandlung alkoholbezogener Störungen - Ergebnisse einer repräsentativen Umfrage in Suchtberatungsstellen.

BACKGROUND: Due to the high prevalence of alcohol related disorders (dependent, harmful and at risk drinking) the improvement of the outpatient treatment situation in this area is of major importance. The aim of this study was to examine the treatment structure and modalities of patients with alcohol related disorders in counseling centers for substance abusers based on the questioning of the counselors. METHODS: A 3-page questionnaire to characterize the institution and six standardized 10-page questionnaires (for the counselors) were sent to all counseling centers (n = 123) in Baden-Württemberg. The counselors were asked about diagnostic and therapeutic procedures they had employed in the last patient seen. Further questions regarded patient related and structural problems. RESULTS: The results are related to a representative sample of 262 counselors of 73 counseling centers (59.5 %). Further 28 counseling centers (22.6 %) were not able to take part in the survey because they do not care for people with alcohol related disorders. The sample complies with respect of relevant dimensions (sponsoring institution, profession of the counselors, age distribution of patients, accomplished interventions) with the population of counseling centers in Baden-Württemberg. The reported patients were predominantly male (80.5 %) and nearly all patients were addicted to alcohol (95.8 %). They had a mean age of 41,9 +/- 10 years, high acceptance of diagnosis (79.2 %) and treatment (80.3 %) and only 6.4 % used multiple substances. The results with respect of the diagnostic procedure refer to a structured, broad and professional procedure. 63.4 % of the counsellors are geared to formal diagnostic criteria when making a diagnosis. All relevant history elements are observed. But the study pointed towards some deficits in recognising suicidal tendencies. The own responsibility related to the supply of people with alcohol problems is predominantly seen in educational advertising and counselling, but also in numerous other areas the own responsibility is judged very high. Further training is particularly seen regarding relapse prevention and suicidality. The co-operation with several institutions, e. g. general practitioners, is judged to be relatively low. DISCUSSION: The majority of patients described by the counselors were dependent drinkers. This indicates that harmful and at risk drinkers are hardly reached by counseling centers. So there is clear space for optimizing the care for people with alcohol-related disorders.

Effects of fibrogenic mediators on the development of pancreatic fibrosis in a TGF-beta1 transgenic mouse model.

The pancreas morphology of transgenic mice that overexpress transforming growth factor-beta1 (TGF-beta1) in the pancreas resembles partially morphological features of chronic pancreatitis, such as progressive accumulation of extracellular matrix (ECM). Using this transgenic mouse model, we characterized the composition of pancreatic fibrosis and involved fibrogenic mediators. On day 14 after birth, fibrotic tissue was mainly composed of collagen type I and III. At this time, mRNA levels of TGF-beta1 were increased. On day 70, the ECM composition was expanded by increased deposition of fibronectin, whereas connective tissue growth factor, fibroblast growth factor (FGF)-1, and FGF-2 mRNA expression levels were elevated in addition to TGF-beta1. In parallel, the number of pancreatic stellate cells (PSC) increased over time. In vitro, TGF-beta1 stimulated collagen type I expression but not fibronectin expression in PSC, in contrast to FGF-2, which stimulated both. This confirms that TGF-beta1 mediates pancreatic fibrosis through activation of PSC and deposition of collagen type I and III at early time points. Furthermore, this points to an indirect mechanism in which TGF-beta regulates pancreatic ECM assembly by induction of additional growth factors.

Different molecular mechanisms of vitamin D(3) receptor antagonists.

Two structurally different antagonists of the nuclear hormone 1alpha,25-dihydroxyvitamin D(3) [1alpha,25(OH)(2)D(3)], the 25-carboxylic ester ZK159222 and the 26,23-lactone TEI-9647, have recently been described. In this study, the molecular mechanisms and the efficacy of both antagonists were compared. ZK159222 showed similar potency and sensitivity to 1alpha,25(OH)(2)D(3) in ligand-dependent gel shift assays using the vitamin D receptor (VDR), the retinoid X receptor, and specific DNA binding sites, whereas TEI-9647 displayed reduced potency and >10-fold lower sensitivity in this assay system. Limited protease digestion and gel shift clipping assays showed that the two antagonists stabilized individual patterns of VDR conformations. Both antagonists prevented the interaction of the VDR with coactivator proteins, as demonstrated by GST-pull-down and supershift assays; like the natural hormone, however, they were able to induce a dissociation of corepressor proteins. Interestingly, ZK159222 demonstrated functional antagonism in reporter gene assays both in HeLa and MCF-7 cells, whereas TEI-9647 functioned as a less sensitive antagonist only in MCF-7 cells. In conclusion, the two 1alpha,25(OH)(2)D(3) analogs act in part via different molecular mechanisms, which allows us to speculate that ZK159222 is a more complete antagonist and TEI-9647 a more selective antagonist.