A model-based analysis of pharmacokinetic–pharmacodynamic (PK/PD) indices of avibactam against Pseudomonas aeruginosa

ObjectiveThe aim of the present work was to use a semi-mechanistic pharmacokinetic–pharmacodynamic (PK/PD) model developed from in vitro time–kill measurements with P. aeruginosa to compare different pharmacodynamic indices derived from simulated human avibactam exposures, with respect to their degree of correlation with the modelled bacterial responses.MethodsA mathematical model of the effect of ceftazidime–avibactam on the growth dynamics of P. aeruginosa was used to simulate bacterial responses to modelled human exposures from fractionated avibactam dosing regimens with a fixed ceftazidime dosing regimen (2 or 8 g q8h as a 2-h infusion). The relatedness of the 24-h change in bacterial density and avibactam exposure parameters was evaluated to determine exposure parameter that closely correlated with bacterial growth/killing responses.ResultsFrequent dosing was associated with higher efficacy, resulting in a reduction of avibactam daily dose. The best-fit PD index of avibactam determined from the simulation was fT > C_T of 1 mg/L avibactam and q8h was the longest dosing interval able to achieve 2-log kill: 41–87% (3.3 h to 7.0 h out of 8-h interval, respectively). The avibactam exposure magnitude required to achieve a 2-log kill in the simulations was dependent on the susceptibility of the bacterial isolate to ceftazidime.ConclusionsAvibactam activity in combination with ceftazidime against multidrug resistant P. aeruginosa correlated with fT > C_T. Setting a threshold avibactam concentration to 1 mg/L, superimposed over a simulated human-like exposure of ceftazidime, achieved at least 2-log kill for the clinical dose of 500 mg q8h avibactam as a 2-h infusion, depending on the minimum inhibitory concentration of ceftazidime alone.     

高血压合并冠心病患者血浆致动脉硬化指数与同型半胱氨酸表达水平的相关性分析

目的探究高血压合并冠心病患者血浆致动脉硬化指数(AIP)与同型半胱氨酸(Hcy)表达水平的相关性。方法采用机械随机抽样法选择2018年1月至2019年3月本院收治的142例高血压患者作为研究对象,依据是否合并冠心病将其分为对照组(单纯高血压,67例)和研究组(高血压合并冠心病,75例)。比较两组的TG、LDL-C、HDL-C、AIP、Hcy、UA、Cr、BUN、IMT,采用Pearson相关性法分析AIP与Hcy、UA及Cr的相关性。结果研究组TG、Hcy、UA、Cr水平明显高于对照组,HDL-C水平明显低于对照组,AIP值和IMT明显大于对照组(P<0.05)。相关性分析显示,高血压合并冠心病患者AIP值与血浆Hcy、UA、Cr水平呈显著正相关(P<0.05)。结论高血压合并冠心病患者血浆Hcy水平与AIP呈正相关,可作为高血压合并冠心病早期预测因子。     

BNT162b2 mRNA COVID-19 vaccine Reactogenicity: The key role of immunity

We examined the impact of pre-existing SARS-CoV-2-specific cellular immunity on BNT162b2 mRNA COVID-19 vaccine reactogenicity. Of 96 healthcare workers (HCWs), 76% reported any vaccine reaction (first dose: 70%, second dose: 67%), none of which was severe. Following first dose, systemic reactions were significantly more frequent among HCWs with past infection than in infection-naïve individuals, and among HCWs with pre-existing cellular immunity than in those without it. The rate of systemic reactions after second dose was 1.7 and 2.0-times higher than after first dose among infection-naïve HCWs and those without pre-existing cellular immunity, respectively. Levels of SARS-CoV-2-specific T-cells before vaccination were higher in HCWs with systemic reactions after the first dose than in those without them. BNT162b2 vaccine reactogenicity after first dose is attributable to pre-existing cellular immunity elicited by prior COVID-19 or cross-reactivity. Reactogenicity following second dose suggests an immunity-boosting effect. Overall, these data may reduce negative attitudes towards COVID-19 vaccines.Study Registration.The study was registered on clinicaltrials.gov, NCT04402827.     

Real-world cost-effectiveness of drug-eluting stents vs. bare-metal stents for coronary heart disease—A five-year follow-up study

Objective

To evaluate the cost-effectiveness of using drugeluting stents (DES) compared to bare-metal stents (BMS) for coronary heart disease (CHD).

早产儿脑损伤发病机制研究进展

随着新生儿重症监护病房的监护技术和治疗技术的进步,极低出生体重儿及超低出生体重儿的存活率有了明显提高,但早产儿因出现脑损伤遗留后遗症的比例并没有降低,除了较为明确的缺氧缺血和感染两个上游机制外,最新的研究提示脑损伤尚存在三个下游机制,分别为氧自由基的攻击、小胶质细胞的激活、兴奋性谷氨酸的毒性作用。其中小胶质细胞介导的毒性作用主要通过Toll样受体4起作用。     

Genomic damage as a biomarker of chronic kidney disease status

Patients suffering from chronic kidney disease (CKD) exhibit a high incidence of cancer and cardiovascular diseases, as well as high levels of genomic damage. To confirm the association of CKD with genomic damage we have carried out the largest study to date addressing this issue, using a total of 602 subjects (187 controls, 206 pre‐dialysis CKD patients and 209 CKD patients in hemodialysis). DNA oxidative damage was measured in all individuals using the comet assay. Our results indicate that CKD patients have significantly higher levels of DNA damage than controls, but no significant differences were observed between pre‐hemodialysis (pre‐HD) and hemodialysis (HD) patients. When oxidative damage was measured, no differences were observed between patients and controls, although HD patients showed significantly higher levels of oxidative damage than pre‐HD patients. In addition, a positive relationship was demonstrated between genomic damage and all‐cause mortality. Our study confirms that genomic damage can be predictive of prognosis in CKD patients, with high levels of DNA damage indicating a poor prognosis in HD patients. Environ. Mol. Mutagen. 56:301–312, 2015. © 2014 Wiley Periodicals, Inc.     

噻托溴铵粉吸入剂治疗148例支气管扩张症的效果评定

目的观察噻托溴铵粉吸入剂应用于临床治疗支气管扩张症的效果。方法选取我院治疗的148例支气管扩张症患者,随机分为观察组和对比组,对比组给予常规的支气管扩张症治疗;观察组在进行常规治疗的同时给予噻托溴铵粉吸入剂进行治疗。结果治疗后观察组和对比组的BODE指数和临床症状均有改善,但观察组优于对比组,P0.05,差异具有统计学意义。结论使用噻托溴铵粉吸入剂治疗支气管扩张症疗效显著。     

Empagliflozin restores chronic kidney disease–induced impairment of endothelial regulation of cardiomyocyte relaxation and contraction

1. Download : Download high-res image (468KB)
2. Download : Download full-size image