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Michels Guido Horn Rudolf Helfen Andreas Hagendorff Andreas Jung Christian Hoffmann Beatrice Jaspers Natalie Kinkel Horst Greim Clemens-Alexander Knebel Fabian Bauersachs Johann Busch Hans-Jörg Kiefl Daniel Spiel Alexander O. Marx Gernot Dietrich Christoph F. 《Der Anaesthesist》2022,71(4):307-310
Die Anaesthesiologie - 相似文献
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Two Janus-associated kinase inhibitors (JAKi) (initially ruxolitinib and, more recently, fedratinib) have been approved as treatment options for patients who have intermediate-risk and high-risk myelofibrosis (MF), with pivotal trials demonstrating improvements in spleen volume, disease symptoms, and quality of life. At the same time, however, clinical trial experiences with JAKi agents in MF have demonstrated a high frequency of discontinuations because of adverse events or progressive disease. In addition, overall survival benefits and clinical and molecular predictors of response have not been established in this population, for which the disease burden is high and treatment options are limited. Consistently poor outcomes have been documented after JAKi discontinuation, with survival durations after ruxolitinib ranging from 11 to 16 months across several studies. To address such a high unmet therapeutic need, various non-JAKi agents are being actively explored (in combination with ruxolitinib in first-line or salvage settings and/or as monotherapy in JAKi-pretreated patients) in phase 3 clinical trials, including pelabresib (a bromodomain and extraterminal domain inhibitor), navitoclax (a B-cell lymphoma 2/B-cell lymphoma 2-xL inhibitor), parsaclisib (a phosphoinositide 3-kinase inhibitor), navtemadlin (formerly KRT-232; a murine double-minute chromosome 2 inhibitor), and imetelstat (a telomerase inhibitor). The breadth of data expected from these trials will provide insight into the ability of non-JAKi treatments to modify the natural history of MF. 相似文献
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Breanne E. Kunstler Jill L. Cook Joanne L. Kemp Paul D. O’Halloran Caroline F. Finch 《Journal of Science and Medicine in Sport》2019,22(1):2-10
Objectives
To determine: (i) the behaviour change techniques used by a sample of Australian physiotherapists to promote non-treatment physical activity; and (ii) whether those behaviour change techniques are different to the techniques used to encourage adherence to rehabilitation exercises.Design
Cross-sectional survey.Method
An online self-report survey was advertised to private practice and outpatient physiotherapists treating patients with musculoskeletal conditions. The use of 50 behaviour change techniques were measured using five-point Likert-type scale questions.Results
Four-hundred and eighty-six physiotherapists responded to the survey, with 216 surveys fully completed. Most respondents (85.1%) promoted non-treatment physical activity often or all of the time. Respondents frequently used 29 behaviour change techniques to promote non-treatment physical activity or encourage adherence to rehabilitation exercises. A similar number of behaviour change techniques was frequently used to encourage adherence to rehabilitation exercises (n = 28) and promote non-treatment physical activity (n = 26). Half of the behaviour change techniques included in the survey were frequently used for both promoting non-treatment physical activity and encouraging adherence to rehabilitation exercises (n = 25). Graded tasks was the most, and punishment was the least, frequently reported technique used to promote non-treatment physical activity and encourage adherence to rehabilitation exercises.Conclusions
Respondents reported using similar behaviour change techniques to promote non-treatment physical activity and encourage adherence to rehabilitation exercises. The variability in behaviour change technique use suggests the behaviour the physiotherapist is promoting influences their behaviour change technique choice. Including the frequently-used behaviour change techniques in non-treatment physical activity promotion interventions might improve their efficacy. 相似文献6.
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目的:建立UPLC-MS/MS分析方法同时测定玳玳果黄酮降脂提取物效应组分新橙皮苷和柚皮苷在大鼠10种脏器组织中含量,分布规律及特征。方法:采用UPLC-MS/MS技术建立提取物效应组分新橙皮苷及柚皮苷在大鼠心、肝、脾、肺、肾、脑、胃、小肠、脂质、肌肉组织中的定量分析方法;大鼠给药后分别于0.33,0.67,1,4,8 h的5个时间点,分别摘取以上10种脏器组织,测定脏器组织及血液中效应组分的质量浓度,采用DAS(V 2.0)药动学软件对各样本的药物浓度-时间数据进行房室拟合,并计算不同组织效应组分的药-时曲线下面积(AUC)及平均滞留时间(MRT)。结果:所建立的UPLC-MS/MS定量分析方法具备良好的专属性、标准曲线及线性范围良好、方法准确度与精密度、定量下限均符合有关规定;玳玳果黄酮降脂提取物效应组分在血液中的分布符合一室模型,除肾脏及脑组织外,其余脏器中提取物效应组分的房室特征多为静脉注射的二室模型,柚皮苷在肾脏中的拟合结果为非静脉注射的二室模型,新橙皮苷在脑组织拟合结果为静脉注射的三室模型,给药后8 h各组织中效应组分新橙皮苷及柚皮苷AUC值大小顺序均为小肠 > 胃 > 肾 > 脂质 ≈ 脾脏 > 肺 > 肌肉 > 肝 > 心 > 脑,效应组分在各脏器中均无明显蓄积;效应组分在血液、肾脏、肝脏中的滞留时间较长,MRT均大于2 h,脂质最短,MRT不足1 h;各脏器中新橙皮苷的药-时曲线下面积约是柚皮苷的3倍,而心、肝、肾中则是3.5,2.1和3.4倍。结论:玳玳果黄酮降脂提取物效应组分在大鼠组织中分布迅速,达峰时间早于血液;效应组分在肠道内消除缓慢,给药8 h后在各脏器中的含量均显著下降且无特异的蓄积部位。研究结果揭示玳玳果黄酮降脂提取物效应组分在大鼠体内的分布特征及规律,为进一步理解玳玳果黄酮降脂提取物在体内的作用靶点及机制奠定了基础。 相似文献
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