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
Objective: A multidisciplinary vocational rehabilitation programme, the Vocational Enablement Protocol (VEP) was developed to address the specific needs of employees with hearing difficulties. In the current study we evaluated the process of implementing the VEP in audiologic care among employees with hearing impairment. Design: In conjunction with a randomized controlled trial, we collected and analysed data on seven process parameters: recruitment, reach, fidelity, dose delivered, dose received and implemented, satisfaction, and perceived benefit. Study sample: Sixty-six employees with hearing impairment participated in the VEP. The multidisciplinary team providing the VEP comprised six professionals. Results: The professionals performed the VEP according to the protocol. Of the recommendations delivered by the professionals, 31% were perceived as implemented by the employees. Compliance rate was highest for hearing-aid uptake (51%). Both employees and professionals were highly satisfied with the VEP. Participants rated good perceived benefit from it. Conclusions: Our results indicate that the VEP could be a useful treatment for employees with hearing difficulties from a process evaluation perspective. Implementation research in the audiological setting should be encouraged in order to further provide insight into parameters facilitating or hindering successful implementation of an intervention and to improve its quality and efficacy. 相似文献
It is not known whether non alcoholic fatty liver disease (NAFLD) is a risk factor for diabetes in non obese, non centrally-obese subjects. Our aim was to investigate relationships between fatty liver, insulin resistance and a biomarker score for liver fibrosis with incident diabetes at follow up, in subjects who were neither obese nor centrally-obese.
Methods and results
As many as 70,303 subjects with a body mass index (BMI) < 25 kg/m2 and without diabetes were followed up for a maximum of 7.9 years. At baseline, fatty liver was identified by liver ultrasound, insulin resistance (IR) by homeostatic model assessment of insulin resistance (HOMA-IR) ≥2.0, and central obesity by waist circumference (waist circumference ≥90 cm (men) and ≥85 cm (women). The Fibrosis-4 (FIB-4 score) was used to estimate extent of liver fibrosis. Cox proportional hazards models adjusted for confounders were used to estimate hazard ratios (aHRs) for incident diabetes. As many as 852 incident cases of diabetes occurred during follow up (median [IQR] 3.71 [2.03] years). Mean ± SD BMI was 22.8 ± 1.8 and 21.7 ± 2.0 kg/m2 in subjects with and without diabetes at follow up. In subjects without central obesity and with fatty liver, aHRs (95% CI) for incident diabetes at follow up were 2.17 (1.56, 3.03) for men, and 2.86 (1.50,5.46) for women. Similar aHRs for incident diabetes occurred with fatty liver, IR and the highest quartile of FIB-4 combined, in men; and there was a non significant trend toward increased risk in women.
Conclusions
In normal weight, non-centrally obese subjects NAFLD is an independent risk factor for incident diabetes. 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
According to the current nutritional recommendations issued by professional diabetes and nutrition associations, diabetic patients should keep to a diet consisting of 45–60% carbohydrates, 10–20% protein, and not more than 35% fat. However, not all of these nutritional recommendations are evidence based. For example, current studies show that the intake of insoluble roughage may be underrepresented. It is also possible that diabetic patients could benefit from keeping to the lower end of the recommended range for carbohydrates (45%) and the upper end of the range advised for protein (20%). 相似文献
OBJECTIVE: To determine if there is a diurnal pattern in the clinical symptoms of HELLP (Hemolysis, Elevated Liver enzymes, Low Platelets) syndrome. STUDY DESIGN: A retrospective study was performed in 134 pregnancies complicated by HELLP syndrome. The medical records were reviewed to describe each HELLP episode. Time of day was divided into three periods, day, evening, and night. The following parameters were categorized according to the time of day: onset of symptoms, consultation by the doctor, initial blood sampling, diagnosis and decrease of symptoms. Biochemical parameters at clinical presentation and consecutive changes within 24 h were recorded. RESULTS: In 65 pregnancies 77 HELLP episodes were well documented. Times of onset of symptoms and consultation by the doctor were significantly higher during the evening and night (p < 0.001), whereas times of diagnosis and decrease of symptoms occurred significantly more during the day (p < 0.001). In only 49.3% of the cases were diagnostic laboratory criteria met at clinical presentation. This was mainly due to platelet values in excess of 100 x 10(9)/l. Several hours later (median 8 h, range 2-23) the decrease in platelets occurred. CONCLUSIONS: A diurnal pattern exists in the clinical symptoms of HELLP syndrome that is characterized by an exacerbation during the night and recovery during the day. There is a considerable delay between the onset of symptoms and the fulfillment of diagnostic laboratory criteria. 相似文献
Coronary magnetic resonance angiography (CMRA) is a technique in clinical evolution. Current clinical applications include assessment for coronary anomalies, aneurysms, bypass graft patency, and, in experienced centers, the exclusion of proximal and multivessel coronary artery disease (CAD). As local expertise increases and more extensive multicenter data become available, additional applications will be established. CMRA promises to supplement and in some cases obviate the need for X-ray contrast angiography, and to expand our understanding of the pathophysiology of CAD. Zusammenfassung Die Magnetresonanzangiographie der Koronargefäße (CMRA) ist eine sich ständig weiterentwickelnde Technik. Etablierte Anwendungen sind zurzeit die Beurteilung von koronaren Anomalien, Aneurysmen und der Durchgängigkeit von Bypasses. Auch der Ausschluss proximaler Koronarstenosen und einer koronaren Mehrgefäßerkrankung ist in einigen spezialisierten Zentren möglich. Mit zunehmender Erfahrung der jeweiligen Anwender und der Verfügbarkeit von Ergebnissen großer multizentrischer Studien können zukünftig weitere klinische Anwendungen etabliert werden. In der Zukunft könnte die CMRA ergänzende Informationen zur Indikationsstellung einer konventionellen Röntgenangiographie bringen und in einigen Fällen diese Untersuchung sogar ersetzen. Die CMRA wird unseren Einblick in die Pathophysiologie der koronaren Herzerkrankung sicher erweitern. 相似文献