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
To analyse and understand vaccination hesitancy discourses, particularly those of people who have decided not to vaccinate their sons and daughters.
Methods
Qualitative study of five individual interviews and two focus groups with people who chose not to vaccinate their children in the province of Granada (Spain).
Results
Mothers and fathers manifest a system of health beliefs different to the biomedical paradigm. From an ethical point of view, they justify their position based on the right to autonomy and responsibility for their decisions. Alleged specific reasons: they doubt administration of several vaccines simultaneously at an early age in a systematic way and without individualising each case; they fear adverse effects and do not understand the variations of the vaccination schedule.
Conclusions
These vaccination hesitancy discourses respond to the individual vs collective conflict; parents defend their right to bring up their children without any interference from the state and focus their responsibility on the individual welfare of their sons and daughters, regardless of the consequences that their actions might have on the collective. In their management of risks, they consider those derived from vaccination more relevant than the individual or collective consequences of not doing so. The vaccines generating most doubts are the more controversial ones within the scientific world. Transparency in communication of adverse effects; authorities respect for other health/disease concepts; banishment of the term “anti-vaccines” from the media and scientific vocabulary, and developing spaces for dialogue are bridges to be built. 相似文献
To explore from a gender perspective the association with subjective health of the interaction between education and household arrangements within the framework of social determinants of health placed at the micro and mezzo levels.
Methods
The data comes from the Spanish sample of the European Union Statistics on Income and Living Conditions for 2014. Independent logistic regression models for men and women were run to analyze the association with subjective health of the interaction between education and household arrangements. An additive model was run to assess possible advantages over the interaction approach.
Results
The interaction models show a lower or even no significant effect on health of household arrangements usually negatively associated with health among individuals with high education, displaying specific patterns according to sex.
Conclusions
Health profiles of women and men are more precisely drawn if both social determinants of health are combined. Among the women, the important role was confirmed of both social determinants of health in understanding their health inequalities. Among the men, mainly those with low educational achievement, the interaction revealed that the household was a more meaningful social determinant of health. This could enable the definition of more efficient public policies to reduce health and gender inequalities. 相似文献
Since accelerated atherosclerosis has been reported in systemic lupus erythematosus (SLE), predictive biomarkers of cardiovascular disease (CVD) are needed. Among non-traditional risk factors, bone mineral density (BMD) has been related to CVD. However, its role in SLE remains controversial. This study aims to analyze the associations of subclinical atherosclerosis with traditional and non-traditional CV risk factors.
Methods and results
In a cross-sectional study, atherosclerosis burden was compared between 112 female SLE patients and 31 controls. Plaque number and carotid intima-media wall thickness (cIMT) were assessed by ultrasonography. In a retrospective study, BMD determinations obtained 5-years before the ultrasonography assessment were analyzed in a subgroup of 62 patients. Plaque frequency was increased in SLE, even in patients without CV events or carotid wall thickening. cIMT was increased in patients with CVD, positively correlated with body mass index (BMI). Interestingly, a paradoxical effect of BMI on carotid parameters was observed. Whereas underweight patients (BMI < 20) showed increased prevalence of carotid plaques with low cIMT, those with BMI > 30 showed higher cIMT and plaque burden. Overweight patients (25 < BMI<30) exhibited both elevated cIMT and plaque number. BMI was an independent predictor of BMD. In our retrospective study, patients with either clinical or subclinical CVD exhibited lower BMD levels than their CV-free counterparts. A low lumbar spine BMD independently predicted CVD development after adjusting for confounders.
Conclusion
SLE was associated with a higher subclinical atherosclerosis burden, a bimodal effect being observed for BMI. Decreased BMD can be a CV risk biomarker in SLE. 相似文献
Chronic transplant dysfunction is a complex dynamic pathogenic process. Clinically, a decrease in glomerular filtration rate (GFR) becomes apparent leading to chronic renal insufficiency and dialysis or death from cardiovascular events. Chronic transplant dysfunction can develop into a chronic alIograft nephropathy (CAN) as a specific entity with dynamic progression. CAN includes a collection of immunologic and non-immunologic factors, rejection, ischemia time, donor and recipient characteristics and toxicity of calcineurin inhibitors. Despite improvements in immunosuppression, the long-range prognosis of renal allografts has not improved. Whether modern immunosuppressive concepts with reduction or avoidance of calcineurin inhibitors and a therapy based on antimetabolites, such as mycophenolate or mTOR-inhibitors could lead to a prolongation of transplant survival, remains to be seen. 相似文献
Allergoid immunotherapy is a new form of allergen immunotherapy allowing safe administration of high allergen doses. There is limited information on the effects of allergoid immunotherapy in children with allergic rhinitis. To investigate the immunological and clinical effects of allergoid immunotherapy in children with allergic rhinitis due to grass pollen allergy. Children with allergic rhinitis were assigned to allergoid immunotherapy (n = 27) or control (n = 26, no immunotherapy) groups. Children in the immunotherapy group received seven injections of grass pollen allergoid immunotherapy before grass pollen season and continued to receive maintenance immunotherapy for 27 months. All patients were offered a pharmacotherapy regimen to be used on demand during the pollen seasons. Clinical and laboratory parameters were compared between the immunotherapy and control groups. The rhinoconjunctivitis symptom-medication score and asthma symptom score were lower in the immunotherapy group after 1 yr of maintenance immunotherapy (p < 0.01 for both). Skin test reactivity and nasal reactivity as determined by nasal provocation testing for grass pollen were significantly decreased after 1 yr of immunotherapy (p < 0.001 for both). The seasonal increase in bronchial reactivity and nasal lavage eosinophil cationic protein levels were prevented after the first year of immunotherapy (p < 0.05 for both). The seasonal increase in immunoglobulin (Ig)E decreased (p < 0.05) and grass-specific IgG, IgG(1) and IgG(4) increased significantly already at the end of the seven-injection build-up therapy (p < 0.001, for all). Interleukin (IL)-4 levels in the culture supernatants showed a steady decline from baseline at first and second year of immunotherapy (p < 0.001) but remained unchanged in the control group. Allergoid immunotherapy is an effective method in the treatment of grass pollen-induced allergic rhinitis in children and prevents the seasonal increase in bronchial hyper-reactivity. Changes in specific IgE and IgG levels and decreased IL-4 production in peripheral blood mononuclear cell culture supernatants may account for the observed clinical effects. 相似文献