Introduction: Tamoxifen dominates the anti-estrogenic therapy in the early and metastatic breast cancer setting. Tamoxifen has a complex metabolism, being mainly metabolized by CYP2D6 into its 30–100 times more potent metabolite, endoxifen. Recently, a phase I study in which endoxifen as an orally z-endoxifen hydrochloride has been successfully evaluated.
Areas covered: the principal pharmacogenetic and non-genetic differences in the pharmacology of tamoxifen and endoxifen are evaluated. To this end, references from PubMed, Embase or Web of Science, among others, were reviewed As non-genetic factors, important differences and similarities such age, or adherence to tamoxifen therapy are comprehensively illustrated. Additionally, since CYP2D6 genotypes are considered the main limitation of tamoxifen, many studies have investigated the association between the worsened clinical outcomes in patients with non-functional CYP2D6 genotypes. In this review, an overview of the research on this field is presented. Also, a summary describing the literature about individualizing tamoxifen therapy with endoxifen concentrations and its limitations is listed.
Expert opinion: z-endoxifen hydrochloride is only investigated in the metastatic setting, still more research is required before its place in therapeutics is known. Similarly, monitoring tamoxifen efficacy based on endoxifen concentrations might not be overall recommended due to the limited evidence available. 相似文献
ABSTRACTForest workers, including loggers, foresters, and wildland firefighters, are regularly exposed to some of the most fatal occupational environments in the United States. These hazardous work environments may become even more complex and dynamic when subject to bark beetle outbreaks that have resulted in significant tree mortality. The impacts of tree death from bark beetles are significant, with the cumulative 17-year (2000–2016) footprint for bark beetle caused tree mortality estimated at 54 million acres. However, how workers think about and act in these environments is understudied. This study, therefore, approaches the issue of beetle kill and forest worker safety by examining the perspectives or workers themselves. Its contribution is to leverage ethnographic research to provide insights that can generate new research questions, better inform outreach, and ultimately improve worker safety outcomes. The resulting insights show that beetle kill was understood by workers as a hazard that increased the complexity and dynamism of the work environment, making situational awareness both more necessary and more difficult to maintain. While much research about situational awareness focuses on hazardous situations, it is suggested that building adequate situational awareness should also include broader considerations of organizational communication, as well as training and experience considered over the course of entire careers. 相似文献
ABSTRACTAdolescents and young adults smoke waterpipe tobacco (WT) and cigarillos, at least in part, based on erroneous beliefs that these products are safer than cigarettes. To address this challenge, we used a systematic, three-phase process to develop a health communication campaign to discourage WT and cigarillo smoking among at-risk (tobacco users and susceptible non-users) 16- to 25-year-olds. In Phase 1, we used a national phone survey (N = 896) to determine salient message beliefs. Participants reported constituents (i.e., harmful chemicals) emitted by the products were worrisome. In Phase 2, we developed and evaluated four message executions, with varying imagery, tone, and unappealing products with the same constituents, using focus groups (N = 38). Participants rated one execution highly, resulting in our development of a campaign where each message: (1) identified a tobacco product and constituent in the smoke; (2) included an image of an unappealing product containing the constituent (e.g., pesticides, gasoline) to grab attention; and (3) used a humorous sarcastic tone. In Phase 3, we tested the campaign messages (17 intervention and six control) with a nationally representative online survey (N = 1,636). Participants rated intervention and control messages highly with few differences between them. Exposure to messages resulted in significant increases in all risk beliefs from pre to post (p < 0.05). For WT, intervention messages increased beliefs about addiction more than control messages (p < 0.05). This systematic, iterative approach resulted in messages that show promise for discouraging WT and cigarillo use. 相似文献
The nature of community pharmacy is changing, shifting from the preparation and distribution of medicines to the provision of cognitive pharmaceutical services (CPS); however, often the provision of traditional services leaves little time for innovative services. This study investigated the time community pharmacists spend on the tasks and activities of daily practice and to what extent they are able to implement CPS-related services in daily practice.
Methods
Self-reporting work sampling was used to register the activities of community pharmacists. A smartphone application, designed specifically for this purpose, alerted participants to register their current activity five times per working day for 6 weeks. Participants also completed an online survey about baseline characteristics.
Results
Ninety-one Dutch community pharmacists provided work-sampling data (7848 registered activities). Overall, 51.5% of their time was spent on professional activities, 35.4% on semi-professional activities, and 13.1% on non-professional activities. The proportion of time devoted to CPS decreased during the workweek, whereas the time spent on traditional task increased.
Discussion and conclusion
This study shows it is feasible to collect work-sampling data using smartphone technology. Community pharmacists spent almost half of their time on semi-professional and non-professional activities, activities that could be delegated to other staff members. In practice, the transition to CPS is hampered by competing traditional tasks, which prevents community pharmacists from profiling themselves as pharmaceutical experts in daily practice. 相似文献