This study established a population pharmacokinetics-pharmacodynamics model of clopidogrel in patients with acute coronary syndrome. Fifty-nine patients were enrolled. The plasma concentration of clopidogrel active metabolite and vasodilator stimulated phosphoprotein platelet reactivity index (VASP-PRI) were selected as the pharmacokinetics index and the pharmacodynamics index, respectively. The covariates including demographic characteristics, laboratory indexes, combined medication, complications and genetic polymorphisms of related enzymes were screened for their influence on the pharmacokinetic and pharmacodynamics parameters. Population pharmacokinetic and pharmacodynamics data analysis was performed using NONMEM software. The general linear model and the indirectly effect model-turnover model for pharmacokinetic and pharmacodynamic analysis were selected as the basic model, respectively. The population typical values of K12, CL/F, V/F, EC50, K(in), and E(max) were 0.259 h(-1), 179 L x h(-1), 632 L, 1.57 ng x mL(-1), 4.29 and 0.664, respectively. CYP2C19 was the covariate in the final pharmacokinetic model, and the model was to design a prior dosage regimen.

ObjectiveTo find out the incidence of triple-negative breast cancer(TNBC) in all kinds of breast cancers.To compare and analyze the clinicopathological features,recurrence,metastasis,and prognosis of patients with TNBC and non-triple negative breast cancer (non-TNBC).MethodsThe clinicopathological features and follow-up data of 387 patients with primary breast cancer histopathologically conffirmed in our hospital from Sep.2004 to Sep.2006 were retrospectively analyzed.The 387 patients were divided into 2 groups:79 cases of TNBC and 308 cases of non-TNBC.The clinical features and prognosis of the 2 groups were compared.Results Compared with non-TNBC group,patients in TNBC group had their special features:1.higher ratio of patients ＜ 35 years( P =0.012 ) ; 2.higher ratio of patients with family history of breast cancer( P =0.031 ) ; 3.higher ratio of tumors with maximum diameter ≥ 5 cm ( P =0.044 ) ; 4. higher ratio of patients with positive lymph nodes(P =0.011 ) ; 5.higher ratio of tumors in clinical stage Ⅲ(P =0.007) ; 6.higher ratio of tumors in histological stage Ⅲ(P =0.028 ).The 5-year-disease-free survival (DFS) and overall survival (OS) rate for patients with TNBC were 72.15％ and 88.61％ respectively,lower than those of non-TNBC ( P =0.003 and 0.031 respectively).ConclusionsCompared with non-TNBC patients,patients with TNBC have the features of younger age,more advanced clinical stage upon diagnose,higher rate of lymph node metastasis,larger tumors,higher histological grade,faster and easier recurrence and metastasis,and lower rate of DFS and OS.The information of age,the maximum diameter of the tumor,lymph node status,clinical stage,histological grade and pathological types,especially the age and lymph node status,play an important role in predicting the prognosis of TNBC.

AIM: By analyzing the teicoplannin serum concentration in patients with severe infection and comparing the monitoring results in patients with hyperrenal function and non-hyperrenal function, to provide reference for clinical rational drug use. METHODS: A retrospective analysis was conducted on 64 patients admitted to the department of critical care medicine of a tertiary level hospital from August 2019 to March 2021, and statistical analysis was performed on the monitoring results of teicoplannin, together with medication information and other biochemical indicators of these patients. RESULTS: Sixty-four patients had total 110 times of drug monitoring. 32.7% of ICU patients had renal hyperfunction, and the average serum concentration was 13.6 mg/L. Nearly half of blood concentrations of the monitored patients could not reach the therapeutic target of teicoplanin. For patients without argumented real clearance, increasing the maintenance dose of teicoplanin can significantly increase the blood concentration. While for those with argumented real clearance, the blood concentration of teicoplanin had no significant difference in different maintenance dose groups. Further correlation study found that the serum concentration of teicoplanin in patients with argumented real clearance was significantly positively correlated to cystatin C level, and significantly negatively correlated to albumin level. CONCLUSION: The incidence of renal hyperfunction in ICU patients is high, and the maintenance dose of teicoplanin 600 mg may not be effective for severe infection. To improve the effect of teicoplanin in severe patients, the drug concentration should be monitored to adjust the dose.

Objective To analyze the pathogenic bacteria and drug resistance of peritoneal dialysis-associated peritonitis(PDAP),and provide a clinical reference for the rational use of antibiotics.Methods The demographic data of PDAP patients admitted to the peritoneal dialysis(PD)Center of the First Affiliated Hospital of Soochow University from July 1,2015 to December 30,2021 were collected,and the pathogens,drug resistance and prognosis were retrospectively analyzed.Results A total of 150 episodes of PDAP occurred in 92 patients.The positive rate of PD fluid culture was 61.33％,including 65 cases(70.65％)of Gram-positive(G+)bacteria,mainly Staphylococcus and Streptococcus.Gram-negative(G-)bacteria were in 16 cases(17.39％),mainly Escherichia coli and Enterobacter cloacae.There were 11 cases(11.96％)of multiple infections,including 5 cases of combined fungal infection.From 2016 to 2021,the incidence of G+bacteria-related PDAP decreased from 14 to 8 cases.G+strains were resistant to methicillin(35.00％),and were sensitive to linezolid(100.00％),teicoplanin(100.00％)and rifampicin(100.00％).The sensitivity rate to vancomycin was 98.59％.G-strains were sensitive to ceftazidime(86.36％),ceftizoxime(88.89％)and amikacin(100.00％).The MIC of vancomycin against Staphylococcus showed an upward trend in 2019-2021.The overall cure rate of PDAP was 81.33％in patients who responded to antibiotic treatment,and the cure rate of G+bacteria was higher than that of multiple infections(89.23％vs.36.36％,P＜0.01).The outcome of patients with multiple infections,especially those with concurrent fungal infection was poor.Conclusion The incidence of PDAP in the PD center has shown a decreasing trend in recent years.G+bacteria are still the main pathogenic bacteria causing PDAP,and they are highly resistant to methicillin,so vancomycin should be used as empirical therapy.For G-bacteria,cefotaxime and amikacin can be chosen as empirical therapy.There is a drift in the MIC values of vancomycin against Staphylococcus in the study period,so it is necessary to monitor the MIC of vancomycin against Staphylococcus and its changing trend.

OBJECTIVE： To evaluate efficacy and safety of individualized antiplatelet therapy in patients with coronary artery disease （CAD） systematically according to the results of laboratory examination， and to provide reference for individualized antiplatelet therapy in clinic. METHODS： Retrieved from PubMed， Embase and the Cochrane library during the establishment of database to Feb. 2018， RCTs about individualized antiplatelet therapy vs. routine antiplatelet therapy in CAD patients based on the results of laboratory examination were collected. Meta-analysis was conducted for the incidence of main adverse cardiovascular adverse events （MACE）， all-cause death， cardiovascular death， myocardial infarction， stent thrombosis， stroke and severe bleeding by using Rev Man 5.3 statistical software after data extraction and quality evaluation with Cochrane system evaluator manual 5.2.0. Subgroup analysis was carried out for different races， laboratory testing methods and intervention courses. RESULTS： Totally 7 RCTs involving 8 615 patients were included. Results of Meta-analysis showed that compared with routine antiplatelet therapy， there was no significant difference in the incidence of MACE [RR＝0.93， 95％CI （0.74， 1.16）， P＝0.51]， all-cause death [RR＝0.89， 95％CI （0.56， 1.41）， P＝0.61]， cardiovascular death [RR＝0.68， 95％CI （0.36， 1.25）， P＝0.21]， myocardial infarction [RR＝1.03， 95％CI （0.92， 1.16）， P＝0.56]， stent thrombosis [RR＝0.52， 95％CI （0.22， 1.24）， P＝0.14]， stroke [RR＝1.03， 95％CI （0.65， 1.63）， P＝0.90]， and severe bleeding [RR=0.78，95％CI （0.53， 1.14）， P＝0.20] based on the results of laboratory examination. Subgroup analysis showed according to CYP2C19 genotype， individualized medication could reduce the incidence of MACE [RR＝0.29， 95％CI （0.14， 0.64）， P＝0.002] and all-cause death [RR＝0.11， 95％CI （0.01， 0.87）， P＝0.04]， and trials with intervention duration of 6 months could significantly decrease the incidence of all-cause death [RR＝0.11， 95％CI （0.01， 0.87）， P＝0.04]， there were no significant difference between 2 groups in other subgroup analysis. CONCLUSIONS： Compared with routine antiplatelet therapy， individualized antiplatelet therapy based on the results of laboratory examination cannot reduce the incidence of MACE and bleeding event risk in real-world patients with CAD. Although subgroup analysis show that individualized medication on the basis of CYP2C19 genotype can significantly reduce the incidence of MACE and cardiovascular death. But more large-scale samples and high-quality studies are needed to confirm this conclusion.

OBJECTIVE To comprehensively evaluate the three oral Janus kinase inhibitors （JAKi） such as upadacitinib， abrocitinib and baricitinib in the treatment of atopic dermatitis. METHODS The six dimensions of safety， efficacy， economy， appropriateness， accessibility and innovativeness were used for evaluation. Meta-analysis was conducted to evaluate the safety and efficacy of three oral JAKi； pharmacoeconomic studies were searched， and the treatment costs were calculated to evaluate the economy of each JAKi. Appropriateness was described based on literature review and drug labels. Accessibility of three oral JAKi was assessed by using a questionnaire survey. The innovation of JAKi was elucidated from the perspective of its mechanism of action. RESULTS In terms of safety， the incidence of upper respiratory tract infection （OR＝1.47， 95%CI of 1.04-2.08， P＝0.03） and nasopharyngitis （OR＝1.44， 95%CI of 1.06-1.95， P＝0.02） in the upadacitinib 30 mg group was significantly higher than that in the placebo group； the incidence of nasopharyngitis in baricitinib 4 mg group was significantly higher than that in the placebo group （OR＝2.24， 95%CI of 1.39-3.61， P＝0.000 8） and baricitinib 2 mg group （OR＝0.48， 95%CI of 0.31-0.74，P＝0.001）. In terms of efficacy， regardless of the dosage， all three JAKi groups were superior to the placebo group， and the high-dose groups of upadacitinib and abrocitinib were superior to the low-dose groups （P＜0.000 1）. In terms of economy， the annual treatment cost of baricitinib was the lowest （13 870.0 yuan）， but it has not been approved for atopic dermatitis indication in China； next was upadacitinib （27 192.5 yuan）. In terms of appropriateness， the overall appropriateness of the three JAKis was good， but none of them was suitable for patients with severe liver injury. In terms of accessibility， baricitinib had the highest availability rate （59.4%）， but the affordability of upadacitinib was relatively good under China’s medical insurance system. In terms of innovation， among the three types of JAKi， upadacitinib and abrocitinib had better innovation. CONCLUSIONS Three oral JAKi treatments for atopic dermatitis have controllable safety and good efficacy. Considering the issue of medical insurance reimbursement， it is recommended that Chinese patients use upadacitinib.

OBJECTIVE To develop a whole-process intelligent model of pharmaceutical care for peritoneal dialysis （PD） patients， and to provide a reference for clinical pharmacists to provide standardized PD pharmaceutical care. METHODS The pharmaceutical care mode of PD patients at home and abroad was investigated and analyzed. Based on the actual situation of the First Affiliated Hospital of Soochow University （hereinafter referred to as “our hospital”）， with “home→PD center outpatient→ inpatient department” as the main node， the recycling process of medication reconciliation was optimized. The whole-process intelligent pharmaceutical care model of PD was illustrated by improving the Chinese version of the drug-related problems （DRPs） classification tool， developing the corresponding pharmaceutical care process， and presenting specific cases. RESULTS Based on the medication therapy management （MTM） platform， our hospital had built a closed-loop PD whole-process intelligent pharmaceutical care model of “in-hospital pharmaceutical care （building document）-PD outpatient MTM-home pharmaceutical care （online App management）”. A “double cycle” workflow of “admission→discharge→outpatient” medication reconciliation cycle and “discovery-analysis-intervention-follow-up-record-evaluation” DRPs cycle was formed. CONCLUSIONS The establishment of the whole-process intelligent pharmaceutical care model for PD in our hospital provides experience for standardizing pharmaceutical care for PD patients， and can reduce DRPs.