A reversible gene-targeting strategy identifies synthetic lethal interactions between MK2 and p53 in the DNA damage response in vivo.

A fundamental limitation in devising new therapeutic strategies for killing cancer cells with DNA damaging agents is the need to identify synthetic lethal interactions between tumor-specific mutations and components of the DNA damage response (DDR) in vivo. The stress-activated p38 mitogen-activated protein kinase (MAPK)/MAPKAP kinase-2 (MK2) pathway is a critical component of the DDR network in p53-deficient tumor cells in vitro. To explore the relevance of this pathway for cancer therapy in vivo, we developed a specific gene targeting strategy in which Cre-mediated recombination simultaneously creates isogenic MK2-proficient and MK2-deficient tumors within a single animal. This allows direct identification of MK2 synthetic lethality with mutations that promote tumor development or control response to genotoxic treatment. In an autochthonous model of non-small-cell lung cancer (NSCLC), we demonstrate that MK2 is responsible for resistance of p53-deficient tumors to cisplatin, indicating synthetic lethality between p53 and MK2 can successfully be exploited for enhanced sensitization of tumors to DNA-damaging chemotherapeutics in vivo.

[Information needs of physicians, professional carers and family carers for an evidence-based dementia website]. / Informationsbedarf von Ärzten, Pflegepersonal und Angehörigen für eine evidenzbasierte Internetseite zum Thema Demenz.

OBJECTIVE: Despite the demographically driven rapid growth of the number of persons with dementia, in Germany a website is lacking that provides evidence based information about the disease, its burden and therapeutic options to family and professional carers as well as physicians. A website was developed with the objective to give free access to evidence based information concerning the disease and care for patients with dementia. METHODS: In order to meet the expectations of the user groups an analysis of information needs was performed with 80 physicians, 163 professional carers and 104 family carers. RESULTS: All user groups rated information on symptoms, course and treatment of dementia and support for family carers as important topics. Group differences were found for the need to be informed on financial support, daily care and interaction with patients. CONCLUSIONS: The contents of the website will be accommodated to the specific needs of the user groups.

General practitioners and online continuing medical education - which factors influence its use?

INTRODUCTION: Although several online continuing medical education (CME) offers exist, the utilization of these by physicians is still low. In this study, we aimed to investigate the attitude towards and use of the Internet and online CME in German general practitioners (GPs) and to identify potential starting points to increase the use of online CME. METHODS: In June 2006, a standardized 6-page questionnaire with 27 questions on the topic "Internet and online continuing education" was sent to all general practitioners in 6 districts (n=1304) of South Baden and South Württemberg in Germany. Data were analyzed using descriptive statistics, and exploratory regression analyses were performed to identify predictors of online CME usage. Furthermore, selected barriers were investigated in detail. RESULTS: A total of 351 questionnaires were sent back, of which 349 could be included in the analysis (27% response rate). The sample is representative of the population contacted with respect to gender and qualifications. Univariate analyses showed that users of online CME were two years younger than non-users on average. Users spent two hours more on the Internet per week than non-users, and had been using the Internet for one year longer. Finally, users had better Internet skills, more often had previous experiences with online CME, and assessed the effectiveness of online CME to be higher and perceived fewer problems than non-users. DISCUSSION: Measures to implement and increase the use of online CME can be aimed at different levels. The most important starting points are likely to be offering GPs the possibility to gain experience with online CME and improving their attitudes towards online CME. But for some physician populations, e.g. elderly or physicians with less Internet experience, e-learning might be an inferior option in comparison to traditional CME.

[General practitioners online: the conditions are good, but use of the Internet for continuing medical education found to be poor]. / Hausärzte online: Gute Voraussetzungen, aber geringe Nutzung des Internets zur Fortbildung.

BACKGROUND AND OBJECTIVE: In recent years, there has been an increasing trend towards the development of e-learning-modules for general medical training and continuing medical education (CME). The majority of these offerings make use of the Internet. The aim of this study was to examine general practitioners' attitude towards and their use of the Internet and online CME, their demand for such offerings and the problems associated with it on the basis of a representative survey. METHODS: In June 2006, a standardized 6-page questionnaire with 27 questions about "The Internet and online CME" was sent out to all general practitioners in six districts (n = 1304) of South-Baden and South-Württemberg in Germany. Data were subjected to descriptive statistical analysis. RESULTS: 351 physicians (27%) returned the questionnaire. The majority (94.5%) reported to have Internet access, but mostly at home, and not in the office. 45.9% of the respondents rated their Internet skills as "moderate", and 31.9% as "good" or "very good". The physicians' rating of the effectiveness of online CME was similar: 39% rated it as "moderate", and 31.1% as "high" or "very high". Usage of online CME was low: only 19.9% reported "frequent" or "very frequent" use. CONCLUSION: The technical conditions for using the Internet are quite favourable. The effectiveness of online CME was rated between "moderate" and "high". However, the use of such offerings is poor. Further analyses of the data will provide possible starting points for implementing online CME services or for increasing its use.

Detection and management of alcohol use disorders in German primary care influenced by non-clinical factors.

AIMS: The primary objective was to assess the proportion of detected and correctly referred patients in German primary care. The secondary objective was to identify patient and practitioner characteristics that predict detection and correct referral. METHODS: In this clustered cross-sectional survey in German primary care, 3003 patients were consecutively invited to participate, and were asked to fill in a standardized health questionnaire. They were then screened for problematic alcohol consumption using the Alcohol Use Disorders Identification Test. The physicians recorded their assessment of the presence of any alcohol use disorder and documented the treatment course of all identified patients for 3 months. RESULTS: Correctly identified problem drinkers were 38.6% in a per-protocol analysis and 33.6% using a worst-case scenario. Referral behaviour of physicians was in conformity with current practice guidelines in 64.6% of the documented cases and 27.0% in a worst-case scenario. Several patient (e.g. sex, age) and practitioner characteristics (e.g. age), which influence the diagnosis and referral of patients, could be identified. CONCLUSIONS: There is a clear need to increase the special diagnostic and therapeutic skills of general practitioners so that they may be able to indicate and perform secondary prevention. Further research should focus on the likely effects of the implementation of these diagnostic and management tools.