Establishment and application of drug utilization evaluation applying the weighted TOPSIS method: A study based on real-world data of tislelizumab.

BACKGROUND: How to comprehensively evaluate the rationality of drug use is a challenging issue. OBJECTIVE: To establish the evaluation index of the effective use of tislelizumab, so as to ensure its higher rationality and normalization in clinical application. METHODS: Based on the indications, drug instructions, and relevant guidelines of the National Basic Medical Insurance Restriction Catalogue, a retrospective analysis and evaluation of 286 cases of using tislelizumab injection in our hospital from January to December 2022 were conducted using the weighted technique for order of preference by similarity to ideal solution (TOPSIS) method. RESULTS: Among the 286 medical records evaluated, the main irrational manifestations were inappropriate indications (90 cases, 31.47%), auxiliary examination and laboratory examination did not meet the minimum requirements of combination chemotherapy drugs (40 cases, 13.99%), the drug course was not standard (39 cases, 13.64%). Among the included cases, 57.34% were reasonable cases (Ci⩾ 0.8), 10.84% were basic reasonable cases (0.6 ⩽Ci< 0.8), and 31.82% were unreasonable cases (Ci< 0.6). CONCLUSION: The TOPSIS method, with its attribute hierarchical model (AHM)-weighted approach, can be employed as the rational assessment technique for the injection of tislelizumab. The clinical application of tislelizumab in our hospital is still insufficient, which needs to be further improved management.

Trends and correlation between antibacterial consumption and carbapenem resistance in gram-negative bacteria in a tertiary hospital in China from 2012 to 2019.

BACKGROUND: To investigate the trends and correlation between antibacterial consumption and carbapenem resistance in Gram-negative bacteria from 2012 to 2019 in a tertiary-care teaching hospital in southern China. METHODS: This retrospective study included data from hospital-wide inpatients collected between January 2012 and December 2019. Data on antibacterial consumption were expressed as defined daily doses (DDDs)/1000 patient-days. Antibacterials were classified according to the Anatomical Therapeutic Chemical (ATC) classification system. The trends in antimicrobial usage and resistance were analyzed by linear regression, while Pearson correlation analysis was used for assessing correlations. RESULTS: An increasing trend in the annual consumption of tetracyclines, ß-lactam/ß-lactamase inhibitor (BL/BLI) combinations, and carbapenems was observed (P < 0.05). Carbapenem resistance in Acinetobacter baumannii (A. baumannii) significantly increased (P < 0.05) from 18% in 2012 to 60% in 2019. Moreover, significant positive correlations were found between resistance to carbapenems in A. baumannii (P < 0.05) and Escherichia coli (E. coli; P < 0.05) and consumption of carbapenems, while the resistance rate of A. baumannii to carbapenems was positively correlated with cephalosporin/ß-lactamase inhibitor (C/BLI) combinations (P < 0.01) and tetracyclines usage (P < 0.05). We also found that use of quinolones was positively correlated with the resistance rate of Burkholderia cepacia (B. cepacia) to carbapenems (P < 0.05), and increasing uses of carbapenems (P < 0.01) and penicillin/ß-Lactamase inhibitor (P/BLI) combinations (P < 0.01) were significantly correlated with reduced resistance of Enterobacter cloacae (E. cloacae) to carbapenems. CONCLUSION: These results revealed significant correlations between consumption of antibiotics and carbapenem resistance rates in Gram-negative bacteria. Implementing proper management strategies and reducing the unreasonable use of antibacterial drugs may be an effective measure to reduce the spread of carbapenem-resistant Gram-negative bacteria (CRGN), which should be confirmed by further studies.

Simultaneous Quantification of Methotrexate and Its Metabolite 7-Hydroxy-Methotrexate in Human Plasma for Therapeutic Drug Monitoring.

OBJECTIVE: To establish and validate a simple, sensitive, and rapid liquid chromatography tandem mass spectrometry (LC-MS/MS) method for the determination of methotrexate (MTX) and its major metabolite 7-hydroxy-methotrexate (7-OH-MTX) in human plasma. METHOD: The chromatographic separation was achieved on a Zorbax C18 column (3.5 µm, 2.1 × 100 mm) using a gradient elution with methanol (phase B) and 0.2% formic acid aqueous solution (phase A). The flow rate was 0.3 mL/min with analytical time of 3.5 min. Mass spectrometry detection was performed in a triple-quadruple tandem mass spectrometer under positive ion mode with the following mass transitions: m/z 455.1/308.1 for MTX, 471.0/324.1 for 7-OH-MTX, and 458.2/311.1 for internal standard. The pretreatment procedure was optimized with dilution after one-step protein precipitation. RESULTS: The calibration range of methotrexate and 7-OH-MTX was 5.0-10000.0 ng/mL. The intraday and interday precision and accuracy were less than 15% and within ±15% for both analytes. The recovery for MTX and 7-OH-MTX was more than 90% and the matrix effect ranged from 97.90% to 117.60%. CONCLUSION: The method was successfully developed and applied to the routine therapeutic drug monitoring of MTX and 7-OH-MTX in human plasma.

[Effects of electroacupuncture at "Zusanli" (ST 36) on Pharmacokinetics of paracetamol in rates].

OBJECTIVE: To investigate influence of electroacupuncture at "Zusanli" (ST 36) on pharmacokinetics after oral administration of Paracetamol in rats and explore the effect and mechanism of acupuncture combined with medicinal drugs. METHODS: Forty-eight SD rats, in half respectively male and female, were randomly divided into 6 groups: Paracetamol groups of low, moderate, and high doses (oral dose of Paracetamol 300, 600 or 1200 mg/kg, respectively), and electroacupuncture plus Paracetamol groups of low, moderate, and high doses (electroacupuncture at "Zusanli" (ST 36) acupoint for 20 min after oral dose of Paracetamol 300, 600 or 1 200 mg/kg, respectively). Serum specimens of rats in each group were obtained at different time points to determine the concentrations of Paracetamol by RP-HPLC after oral administration of Paracetamol at different dosage, and the pharmacokinetic parameters were calculated by software 3P87, so as to observe the influence of electroacupuncture on absorption and metabolism of Paracetamol. RESULTS: Except in electroacupuncture plus Paracetamol groups of high doses group showing a non-linear dynamics model, the pharmacokinetics parameters of Paracetamol in the other fives groups were all fitted to first order grade absorption of two-compartment open model. Compared with the Paracetamol groups of low and moderate doses, the time to peak concentration (T(max)) was advanced (P < 0.01), the peak values of plasma concentration (C(max)) were significantly higher (P < 0.01), and the absorption half-life (T1/2ka) speeded up apparently (P < 0.01), but the elimination half-life (T1/2ke) remained basically unchanged (P > 0.05), and the area under the curve (AUC) increased significantly (P < 0.01), and plasma clearance (Cl(s)) was lower (P < 0.01) in the electroacupuncture plus Paracetamol groups of low and moderate doses. Compared with the Paracetamol group of high doses, the AUC also increased significantly (P < 0.01) and the mean residence time (MRT) postponed relatively (P < 0.05) in the electroacupuncture plus Paracetamol group of high doses. CONCLUSION: It indicates that clinical consideration must be given to the drug dosage and the possible influence of electroacupuncture on the metabolism of some drugs in order to avoid and reduce adverse reactions.