Chinese consensus guidelines for therapeutic drug monitoring of polymyxin B, endorsed by the Infection and Chemotherapy Committee of the Shanghai Medical Association and the Therapeutic Drug Monitoring Committee of the Chinese Pharmacological Society / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

Polymyxin B, which is a last-line antibiotic for extensively drug-resistant Gram-negative bacterial infections, became available in China in Dec. 2017. As dose adjustments are based solely on clinical experience of risk toxicity, treatment failure, and emergence of resistance, there is an urgent clinical need to perform therapeutic drug monitoring (TDM) to optimize the use of polymyxin B. It is thus necessary to standardize operating procedures to ensure the accuracy of TDM and provide evidence for their rational use. We report a consensus on TDM guidelines for polymyxin B, as endorsed by the Infection and Chemotherapy Committee of the Shanghai Medical Association and the Therapeutic Drug Monitoring Committee of the Chinese Pharmacological Society. The consensus panel was composed of clinicians, pharmacists, and microbiologists from different provinces in China and Australia who made recommendations regarding target concentrations, sample collection, reporting, and explanation of TDM results. The guidelines provide the first-ever consensus on conducting TDM of polymyxin B, and are intended to guide optimal clinical use.

Analysis of factors influencing the medical insurance balance of hospitalization expenses for gastric cancer surgery patients under DRG payment / 中华医院管理杂志

Objective:To analyze the influencing factors of the medical insurance balance of hospitalization expenses for gastric cancer surgery patients under DRG payment, for reference for promoting the reform of DRG payment in public hospitals and controlling hospitalization expenses reasonably.Methods:The gastric cancer patients enrolled in the gastroenterology department of a tertiary comprehensive hospital from January to July 2022 were selected as the research subjects. The indicators such as patient age, medical insurance balance, hospitalization expenses and their composition were extracted from the hospital information management system and the medical insurance settlement system a certain city. Descriptive analysis was conducted for all data, and stepwise multiple linear regression was used to analyze the influencing factors of patients′ medical insurance balance. Monte Carlo simulation method was used to simulate different combination scenarios of various influencing factors to analyze the probability of medical insurance balance.Results:A total of 205 patients were contained, including 117 in the medical insurance balance group and 88 in the loss group. The difference in hospitalization expenses and medical insurance balance between the two groups of patients were statistically significant ( P<0.05). The intervention of medical insurance specialists, correct DRG enrollment, parenteral nutrition preparation costs, anti infective drug costs, examination costs, and consumables costs were the influencing factors of patient medical insurance balance ( P<0.05). Through Monte Carlo simulation verification, patients with different cost parenteral nutrition preparations, or different anti infective drug schemes had the higher probability of medical insurance balance in the scenario where the medical insurance commissioner intervenes and the DRG enrollment was correct. Conclusions:The hospital adopted interventions from medical insurance specialists to ensure the correct DRG enrollment of patients, accurate use of parenteral nutrition and anti infective drugs, and reasonable control the cost of examinations and consumables, which could increase the probability of medical insurance balance for gastric cancer surgery patients. In the future, hospitals should further promote the procurement of drug consumables in bulk, reduce unnecessary examinations, develop standardized perioperative nutritional interventions and anti infection treatment pathways, ensure the accuracy of DRG enrollment, optimize clinical diagnosis and treatment pathways to improve the efficiency of medical insurance fund utilization and provide high-quality medical services for patients.

Research progress on laboratory examination index of clinical prognosis in individualization of cyclosporine A / 中国药房

Cyclosporine A is widely used in organ transplantation and autoimmune diseases . Due to the obvious differences in metabolism between individuals ，the dosage should be adjusted according to the patient ’s blood concentration during clinical use . But the blood concentration does not reflect accurately its clinical prognosis . This article focuses on the four laboratory examination indexes following aspects ：the cyclosporine A concentration of peripheral blood mononuclear cells ，calcineurin activity ，T cell function and metabolite concentration of cyclosporine A . The relationship between them and the pharmacokinetics of cyclosporine and clinical prognosis were reviewed . It’s found that the above indicators have a certain predictive effect on the clinical prognosis of patients receiving cyclosporine A ，which can make up for the insufficiency of blood drug concentration monitoring ，and the clinical practicability needs to be further improved .

Correlationship between ATP binding cassette subfamily B member 1 2677G>T/A gene polymorphism and cyclosporine blood concentration in patients with autoimmune diseases / 中华风湿病学杂志

Objective:To investigate the distribution of blood concentration of cyclosporine (CsA) in patients with autoimmune disease in China, and analyze the effect of genetic polymorphisms of CsA-metabolizing enzymes, transporters and target enzymes on CsA levels.Methods:Steady-state trough blood concentrations (CsA C 0) of 193 patients' were detected by enzyme multiplied immunoassay technique. The genotype of the following sites in the included patients were sequenced by reverse transcription-polymerase chain reaction (RT-PCR): cytochrome P450 (CYP) 3A420230C>T, CYP3A56986A>G, ATP binding cassette subfamily B member 1 (ABCB1)1236C>T, ABCB12677G>T/A, ABCB13435C>T, cytochrome P450 oxidoreductase (POR) 1508 C>T and formyl peptide receptor 1 (FPR1) C>G were sequenced by RT-PCR. The influence of the gene polymorphism of the above-mentioned sites on the blood concentration of CsA was analyzed by using One-way analysis of variance (ANOVA), LSD- t test, Chi-square test. Results:One hundred and ninety-three patients included took CsA. The doses ranged from 75-200 mg/d and the patients' blood concentration distribution span was wide (33.0-313.8 ng/ml). The daily dose ( χ2=21.908, P=0.001) and age( F=4.262, P=0.006) had significant effect on the plasma concentration of CsA. ABCB12677G>T/A (rs2032582) gene polymorphism impacted on the unit dose of CsA C 0 (CsA C 0/d), CsA C 0/d [(0.81±0.42) ng·ml -1·mg -1] in wild type (GG) was higher than heterozygous mutant [GT/GA, (0.65±0.30) ng·ml -1·mg -1, P=0.023) and homozygous mutant (TT/AA/TA, (0.66±0.34) ng·ml -1·mg -1, P=0.039). Conclusion:The blood concentration of patients varies greatly among individuals. The Cold of CsA in wild type patients with ABCB12677G>T/A gene is signifficantly higher than that in mutant patients.

Liver function changes in rheumatoid arthritis patients treated with tofacitinib: systematic review / 中华风湿病学杂志

Objective To evaluate the effects of tofacitinib on liver function in rheumatoid arthritis (RA) patients.Methods Literature search was performed in databases including PubMed,Cochrane Library,China National Knowledge Infrastructure and Wanfang to identify randomized controlled trials about RA treated with tofacitinib.The retrieval time was up to August 2016.Meta-analysis was conducted by Revman 5.5 software.Results A total of 7 studies were included,involving 2 965 patients.The results of Meta-analysis revealed that the incidence of alanine transaminase (ALT)＞1 upper limit of normal (ULN) in patients receiving both 5 mg and 10 mg bid tofacitinib was significantly higher than placebo [5 mg bid tofacitinib:RR=1.48,95％CI (1.20,1.82),P=0.000 2;10 mg bid tofacitinib:RR=1.67,95％CI (1.37,2.05),P＜0.01];there was no significant difference in the incidence of ALT＞3 ULN [5 mg bid tofacitinib:RR=1.81,95％CI (0.57,5.79),P=0.32;10 mg bid tofacitinib:RR=1.36,95％CI (0.57,5.25),P=0.49];the incidence of aspartate transaminase (AST)＞1 ULN was significantly higher than placebo [5 mg bid tofacitinib:RR=1.59,95％CI (1.25,2.03),P=0.000 2;10 mg bid tofacitinib:RR=1.90,95％CI(1.50,2.40),P＜0.01],there was no significant difference in the incidence of AST＞3 ULN [5 mg bid tofacitinib:RR=1.17,95％CI (0.27,5.17),P=0.83;10 mg bid tofacitinib:RR=0.95,95％CI (0.26,3.44),P=0.94].Conclusion Tofacitinib slightly increases ALT and AST in patient with RA.Due to the limited sources and lack of domestic studies,more randomized controlled trials are still needed to verify the above conclusion.

Influence of Calcineurin Gene Polymorphisms on the Efficacy of Cyclosporine A / 中国药房

OBJECTIVE:To study the influence of calcineurin gene polymorphism on the efficacy of cyclosporine A (CsA). METHODS:The blood samples of patients treated with CsA were collected. The trough blood concentration of CsA was detected by EMIT. The genotype of PPP3CA and PPP3CB was assayed by RFLP-PCR method. The expression of NFAT-regulated gene IL-2, IFN-γand GM-CSF were measured by RT-qPCR,which were used to define the index of indirect efficacy of CsA. The relationship of gene polymorphism with CsA efficacy was study by relationship analysis and multiple factor regression method,etc. RESULTS:A to-tal of 100 blood samples were collected. There was no significant correlation between the expression of CsA efficacy-related NFAT-reg-ulated gene GM-CSF and trough concentration of CsA(rGM-CSF=-0.04,P=0.238);the expression of IL-2 and IFN-γ were negatively correlated with trough concentration of CsA significantly(rIL-2=-0.384 3,P0.05). Stratified analysis showed that among patients with immune disease underwent renal transplantation,efficacy of patients with PPP3CB rs3763679 genovariation(TC+TT) were better than those with wild-type gene (CC)(P<0.05). After the efficacy was normalized by CsA trough concentration, multivariate analysis showed that normalized efficacy of CsA was negatively correlated with gender,PPP3CB rs3763679,lactate dehy-drogenase and creatinine significantly,but positively correlated with PPP3CA rs3804358,leucocyte count,usea nitrogen,glycerin trilaurate,etc. CONCLUSIONS:PPP3CB rs3763679 gene polymorphism influence the efficacy of CsA;among patients with immune disease underwent renal transplantation,efficacy of patients with PPP3CB rs3763679 TT+TC is better than that of CC type. At the same time,gender,PPP3CA rs3804358,leucocyte count,usea nitrogen,glycerin trilaurate and other factors all can influence the nor-malized efficacy of CsA to different extent. Multiple factors should be considered when using CsA.

Comparison of epidural anesthesia and combined spinal-epidural anesthesia in elderly patients with hip arthroplasty:hemodynamic difference / 中国组织工程研究

BACKGROUND:Epidural anesthesia and combined spinal-epidural anesthesia are commonly used approaches for surgical anesthesia in elderly patients, and each has their advantages and disadvantages. Suitable anesthesia approach can stabilize the cycle, reduce the surgical risk and complications, and improve the success rate of treatment. OBJECTIVE:To analyze and compare the anesthesia effect of epidural anesthesia and combined spinal-epidural anesthesia in the elderly patients during hip arthroplasty, and explore the effect of different approaches on the on hemodynamics. METHODS:80 elderly patients undergoing hip arthroplasty were randomly divided into experimental group and control group, with 40 cases in each group. The experimental group received combined spinal-epidural anesthesia. The control group received epidural anesthesia. The mean arterial pressure, central venous pressure, and heart rate variability at each time point, sensory and motor block onset and recovery times, each block plane after 30 minutes of anesthesia, Bromage score of motor block, and anesthetic effects in both groups of patients were compared. RESULTS AND CONCLUSION:The mean arterial pressure at 5 minutes, 30 minutes of anesthesia and after surgery in the control group was significantly lower than the experimental group at the same time point and before anesthesia (P0.05). Anesthetic effect in the experimental group was significantly better than the control group(χ2=5.691 7, P=0.017 0<0.05). Compared with epidural anesthesia, the combined spinal-epidural anesthesia can reduce hemodynamic changes in patients with hip replacement surgery, and has better anesthesia effect.

Application of a population pharmacokinetic model for vancomycin in patients with severe neurosurgical disease / 中国感染与化疗杂志

Objective This study was designed to validate the utility of a population pharmacokinetic model established for vancomycin in patients with severe neurosurgical disease . Methods The clinical data including patient gender , age , body weight ,serum creatinine and albumin were collected retrospectively from patients in Nanjing Drum Tower Hospital to calculate the steady trough concentration of vancomycin using the previously established pharmacokinetic model .The predicted value was compared with the actual value .Results During the period from March 2013 to March 2014 ,53 blood samples with serum trough concentration of vancomycin were collected from 42 patients .The average trough concentration of vancomycin was 10 .9 mg/L (range from 1 .6 to 49 .1 mg/L) .The predicted trough level of vancomycin based on the population pharmacokinetic model was significantly correlated to the actual value(r=0 .857 ,P<0 .001) .The mean absolute percentage error was 0 .407 9 . The confidence interval was 9 .36‐14 .07 for the predicted values ,and 8 .92‐14 .32 for the actual values .Conclusions The pharmacokinetic model is valid and useful for planning intravenous dose of vancomycin in patients with severe neurosurgical disease .Large error (about 30% ) was observed in estimation of body weight due to coma .Reduced renal function following contrast agent and/or diuretic drug has an impact on the predicted results . The accuracy of prediction can be increased to nearly 70% after adjusting the covariates .