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AimsThe aims were to 1) develop the pharmacokinetics model to describe and predict observed tanezumab concentrations over time, 2) test possible covariate parameter relationships that could influence clearance and distribution and 3) assess the impact of fixed dosing vs. a dosing regimen adjusted by body weight.MethodsIndividual concentration–time data were determined from 1608 patients in four phase 3 studies conducted to assess efficacy and safety of intravenous tanezumab. Patients received two or three intravenous doses (2.5, 5 or 10 mg) every 8 weeks. Blood samples for assessment of tanezumab PK were collected at baseline, 1 h post‐dose and at weeks 4, 8, 16 and 24 (or early termination) in all studies. Blood samples were collected at week 32 in two studies. Plasma samples were analyzed using a sensitive, specific, validated enzyme‐linked immunosorbent assay.ResultsA two compartment model with parallel linear and non‐linear elimination processes adequately described the data. Population estimates for clearance (CL), central volume (V 1), peripheral volume (V 2), inter‐compartmental clearance, maximum elimination capacity (VM) and concentration at half‐maximum elimination capacity were 0.135 l day–1, 2.71 l, 1.98 l, 0.371 l day–1, 8.03 μg day–1 and 27.7 ng ml–1, respectively. Inter‐individual variability (IIV) was included on CL, V 1, V 2 and VM. A mixture model accounted for the distribution of residual error. While gender, dose and creatinine clearance were significant covariates, only body weight as a covariate of CL, V 1 and V 2 significantly reduced IIV.ConclusionsThe small increase in variability associated with fixed dosing is consistent with other monoclonal antibodies and does not change risk : benefit.  相似文献   
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Purpose

Robotic approaches have been steadily replacing laparoscopic approaches in metabolic and bariatric surgeries (MBS); however, their superiority has not been rigorously evaluated. The main goal of the study was to evaluate the 5-year utilization trends of robotic MBS and to compare to laparoscopic outcomes.

Methods

Retrospective analysis of 2015–2019 MBSAQIP data. Kruskal-Wallis test/Wilcoxon and Fisher’s exact/chi-square were used to compare continuous and categorical variables, respectively. Generalized linear models were used to compare surgery outcomes.

Results

The use of robotic MBS increased from 6.2% in 2015 to 13.5% in 2019 (N= 775,258). Robotic MBS patients had significantly higher age, BMI, and likelihood of 12 diseases compared to laparoscopic patients. After adjustment, robotic MBS patients showed higher 30-day interventions and 30-day readmissions alongside longer surgery time (26–38 min).

Conclusion

Robotic MBS shows higher intervention and readmission even after controlling for cofounding variables.

Graphical Abstract
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Pancreatic cancer is a lethal disease characterized by early metastasis, local invasion, and resistance to conventional therapies. To understand its etiology and eventually make prevention of it possible and effective, appropriate carcinogenesis models will certainly help us understand the effects of environmental and genetic elements on pancreatic carcinogenesis. The development of new treatment strategies to control cancer metastasis is of immediate urgency. Fulfillment of this task relies on our knowledge of the cellular and molecular biology of pancreatic cancer metastasis and the availability of biologically and clinically relevant model systems. Many of the existing pancreatic cancer carcinogenesis and metastasis animal models are described in this review. The advantages and disadvantages of each model and their clinical implications are discussed, and special attention is focused on experimental therapeutic strategies targeting pancreatic cancer metastasis.  相似文献   
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An OUR-QGD gamma ray stereotactic body radiotherapy system (body knife), made in China, is described. According to its structure and the principle of gamma radiation revolved on a focus, the energy distribution of scattered radiation in its treatment room is calculated. The structural shielding of the wall, roof, and door for a certain treatment room is calculated according to the local radiation protection law.  相似文献   
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百年乐与人参黄芪合剂对心血管系统的药理作用比较   总被引:1,自引:1,他引:0  
百年乐和人参黄芪合剂对心血管系统的作用研究表明:百年乐能加速小鼠肠系膜微循环障碍的恢复,增加离体兔耳血管的流量,使主动脉平滑肌松弛,对抗心肌缺氧,抑制血栓形成,其作用强于人参黄芪合剂。  相似文献   
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本文从12379枚离体牙上观测了釉珠的发生率、发生部位、形态、直径大小。结果釉珠的发生率为2.49%,以上颌第三磨牙发生率最高,下颌第一磨牙次之。最常发生的部位是在冠颈部的根分叉处,上颌磨牙的釉珠多呈园形,下颌磨牙釉珠多呈梭形。釉珠最大直径为3.2mm,最小为0.5mm,平均为1.56mm。结合文献认为釉珠是一种牙齿形态发育异常,它对牙周病的发生、发展、治疗与预后有重要影响,口腔科医师对这种牙齿形态变异应予以重视。  相似文献   
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报告12例疸性腔皮病患者的性别与年龄构成、并发症、实验室检查、治疗经过和结果,对该病的病因、治疗和预后进行了讨论。  相似文献   
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