[Mobile applications for smoking cessation in primary care]. / Applications mobiles et désaccoutumance au tabac avec l'aide du praticien.

Primary care physicians are in an excellent position to address smoking during routine consultations. To this end, physicians have assessment tools and brief interventions appropriate for the duration of consultations. However, these tools are difficult to use consistently in practice. Mobile applications (apps) aimed at stopping smoking could help solve this problem, provided they meet certain quality criteria. This article provides criteria for evaluating these apps to facilitate their identification and use by clinicians. Five French-speaking apps are described. If integrated into routine Primary Care, these apps could facilitate smoking cessation.

Le médecin de premier recours a une place privilégiée pour aborder le problème du tabagisme en consultation de routine. Il dispose, à cet effet, d'outils d'évaluations et d'interventions brèves compatibles avec le temps de consultation. Ces outils sont difficiles à implémenter systématiquement. Les applications mobiles (apps) visant à l'arrêt du tabac pourraient contribuer à résoudre ce problème pour autant qu'elles satisfassent à certains critères de qualité. Le présent article propose des critères d'évaluation de ces apps pour faciliter leur identification et leur utilisation par le clinicien. Cinq apps francophones sont décrites. Intégrées à la consultation de médecine générale, de telles apps, pourraient faciliter la désaccoutumance au tabac.

Building legitimacy by criticising the pharmaceutical industry: a qualitative study among prescribers and local opinion leaders.

PRINCIPLES: The literature has described opinion leaders not only as marketing tools of the pharmaceutical industry, but also as educators promoting good clinical practice. This qualitative study addresses the distinction between the opinion-leader-as-marketing-tool and the opinion-leader-as-educator, as it is revealed in the discourses of physicians and experts, focusing on the prescription of antidepressants. We explore the relational dynamic between physicians, opinion leaders and the pharmaceutical industry in an area of French-speaking Switzerland. METHODS: Qualitative content analysis of 24 semistructured interviews with physicians and local experts in psychopharmacology, complemented by direct observation of educational events led by the experts, which were all sponsored by various pharmaceutical companies. RESULTS: Both physicians and experts were critical of the pharmaceutical industry and its use of opinion leaders. Local experts, in contrast, were perceived by the physicians as critical of the industry and, therefore, as a legitimate source of information. Local experts did not consider themselves opinion leaders and argued that they remained intellectually independent from the industry. Field observations confirmed that local experts criticised the industry at continuing medical education events. CONCLUSIONS: Local experts were vocal critics of the industry, which nevertheless sponsor their continuing education. This critical attitude enhanced their credibility in the eyes of the prescribing physicians. We discuss how the experts, despite their critical attitude, might still be beneficial to the industry's interests.

Fusion of the BCL9 HD2 domain to E1A increases the cytopathic effect of an oncolytic adenovirus that targets colon cancer cells.

BACKGROUND: The Wnt signaling pathway is activated by mutations in the APC and beta-catenin genes in many types of human cancer. beta-catenin is stabilized by these mutations and activates transcription in part by acting as a bridge between Tcf/LEF proteins and the HD2 domain of the BCL9 coactivator. We have previously described oncolytic adenoviruses with binding sites for Tcf/LEF transcription factors inserted into the early viral promoters. These viruses replicate selectively in cells with activation of the Wnt pathway. To increase the activity of these viruses we have fused the viral transactivator E1A to the BCL9 HD2 domain. METHODS: Luciferase assays, co-immunoprecipitation and Western blotting, immunofluorescent cell staining and cytopathic effect assays were used to characterize the E1A-HD2 fusion protein and virus in vitro. Growth curves of subcutaneous SW620 colon cancer xenografts were used to characterize the virus in vivo. RESULTS: The E1A-HD2 fusion protein binds to beta-catenin in vivo and activates a Tcf-regulated luciferase reporter better than wild-type E1A in cells with activated Wnt signaling. Expression of the E1A-HD2 protein promotes nuclear import of beta-catenin, mediated by the strong nuclear localization signal in E1A. Tcf-regulated viruses expressing the fusion protein show increased expression of viral proteins and a five-fold increase in cytopathic effect (CPE) in colorectal cancer cell lines. There was no change in viral protein expression or CPE in HeLa cells, indicating that E1A-HD2 viruses retain selectivity for cells with activation of the Wnt signaling pathway. Despite increasing the cytopathic effect of the virus in vitro, fusion of the HD2 domain to E1A did not increase the burst size of the virus in vitro or the anti-tumor effect of the virus in an SW620 xenograft model in vivo. CONCLUSION: Despite an increase in the nuclear pool of beta-catenin, the effects on viral activity in colon cancer cells were small, suggesting that factors acting downstream of beta-catenin are limiting for viral replication and toxicity in these cells. The approach of fusing E1A to a protein domain implicated in oncogenic signaling could be used to selectively increase the activity of oncolytic viruses targeting several other pathways defective in cancer.