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Purpose: To investigate the pharmacokinetic changes of linezolid in patients with hepatic impairment and to explore a method to predict linezolid exposure. Methods: Patients with hepatic impairment who received linezolid were recruited. A population pharmacokinetic model (PPK) was then built using NONMEM software. And based on the final model, virtual patients with rich concentration values was constructed through Monte Carlo simulations (MCS), which were used to build machine learning (ML) models to predict linezolid exposure levels. Finally, we investigated the risk factors for thrombocytopenia in patients included. Results: A PPK model with population typical values of 3.83 L/h and 34.1 L for clearance and volume of distribution was established, and the severe hepatic impairment was identified as a significant covariate of clearance. Then, we built a series of ML models to predict the area under 0 -24 h concentration-time curve (AUC0-24) of linezolid based on virtual patients from MCS. The results showed that the Xgboost models showed the best predictive performance and were superior to the methods for estimating linezolid AUC0-24 based on though concentration or daily dose. Finally, we found that baseline platelet count, linezolid AUC0-24, and combination with fluoroquinolones were independent risk factors for thrombocytopenia, and based on this, we proposed a method for calculating the toxicity threshold of linezolid. Conclusion: In this study, we successfully constructed a PPK model for patients with hepatic impairment and used ML algorithm to estimate linezolid AUC0-24 based on limited data. Finally, we provided a method to determine the toxicity threshold of linezolid. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of this retrospective observational study conducted in patients with hepatic impairment was to assess the variability of linezolid trough concentrations, to determine the risk factors for linezolid overexposure, and to investigate the effect of linezolid overexposure on linezolid-induced thrombocytopenia. Methods: All enrolled patients received a standard dose (600 mg every 12 h) of linezolid and underwent therapeutic drug monitoring. The Child–Pugh-Turcotte score was used to divide patients into three groups: mild, moderate, and severe hepatic impairment. The risk factors for linezolid overexposure (Cmin > 8 mg/L) and linezolid-induced thrombocytopenia were examined using logistic regression. And the Kaplan–Meier curve was used to describe the association between linezolid overexposure and linezolid-induced thrombocytopenia. Results: Seventy-seven patients were included, 37 (48.1%) of whom experienced linezolid overexposure. Patients with severe hepatic impairment had a substantially higher median Cmin of linezolid than those with mild (20.7 mg/L vs 5.51 mg/L, P < 0.001) or moderate (20.7 mg/L vs 6.70 mg/L, P = 0.001) hepatic impairment. Severe hepatic impairment was significantly associated with linezolid overexposure (OR 7.037, 95%CI 1.426–34.727, P = 0.017). After linezolid treatment, linezolid-induced thrombocytopenia occurred in 32 (41.6%) patients, and Cmin > 8 mg/L was a significant predictor of linezolid-induced thrombocytopenia (OR 3.024, 95%CI 1.083–8.541, P = 0.035). Conclusion: Patients with hepatic impairment who received standard doses of linezolid are at greater risk of linezolid overexposure, which may lead to a higher incidence of linezolid-induced thrombocytopenia. [ABSTRACT FROM AUTHOR]

What Is Known and Objective: There are few reports on the distribution of the plasma trough concentration (Cmin) of teicoplanin in patients with augmented renal clearance (ARC) and on the safety of a high‐dose regimen (HD; 800 mg loading dose for q12h three times followed by an 800 mg qd maintenance dose). The objective of this study was to determine the Cmin values of teicoplanin in ARC patients using HD teicoplanin to provide a reference for individualized medication. Methods: Data on patients treated with teicoplanin from January 2019 to January 2021 were collected retrospectively and divided into ARC (creatinine clearance rate [CCr] >130 ml/min, n = 22) and non‐ARC (60 ml/min ≤ CCr ≤130 ml/min, n = 24) groups. The Cmin values in the two patient groups were analysed during the HD and the low‐dose regimen (LD; all other regimens) on the third day of medication and during the dose maintenance period. Liver and kidney function indexes were also analysed before and after medication. Results and Discussions: On the third day of the HD, Cmin did not differ significantly between the ARC and non‐ARC groups (17.3 ± 9.2 mg/L [mean ± SD] vs. 15.5 ± 7.9 mg/L, p = 0.663), while Cmin in the ARC group was significantly lower for the LD (6.8 ± 3.9 mg/L, p = 0.039). During the dose maintenance period, Cmin in the ARC group when receiving the HD (18.3 ± 5.1 mg/L) was significantly lower than that in the non‐ARC group (25.5 ± 11.9 mg/L, p = 0.016) and significantly higher than that for the LD (12.2 ± 6.3 mg/L, p = 0.022). Nephrotoxicity and hepatotoxicity incidence rates did not differ significantly between these groups. What Is New and Conclusion: These results suggest that it is necessary to apply a loading dose of 800 mg (but not higher) q12h three times for patients with ARC, with 800 mg needed as a maintenance dose during severe infection, and 600 mg or 400 mg for mild infection. [ABSTRACT FROM AUTHOR]

What is known and objective: Caspofungin is commonly used in kidney transplant patients for prophylaxis or treatment of invasive fungal infections (IFIs) caused by Candida spp. and Aspergillus spp. Factors such as concomitant medications, co‐morbidity and rejection often cause caspofungin pharmacokinetic parameters alterations in kidney transplant patients. Here, we aimed to investigate factors influencing caspofungin plasma concentrations and evaluate its prophylaxis and treatment efficiency for IFIs in kidney transplant patients. Methods: The prophylaxis and treatment efficiency of caspofungin for IFIs were assessed in 164 kidney transplant patients in the study. Six hundred and fifty‐two caspofungin trough concentrations (Cmin) from the 164 patients were monitored by the liquid chromatography‐tandem mass spectrometry method. Basic demographic variables, baseline disease, surgery, rejection, indwelling catheter, coinfection, concomitant medication and other caspofungin‐related factors were collected. Univariate and multivariate analyses were used to assess factors influencing caspofungin plasma concentrations. Results and discussion: The success rates were 94.96% (132/139) for caspofungin prevention and 80% (20/25) for caspofungin for IFIs. Caspofungin Cmin in the kidney recipients varied largely compared with healthy volunteers (0.10‐12.25 mg/L vs. 1.12‐1.78 mg/L). Caspofungin Cmin significantly increased in patients with continuous renal replacement therapy before transplantation (P =.001), concomitant medication of cyclosporine A (CsA, P =.009), ALB concentration of > 30 g/L (P =.019). What is new and conclusion: This is an uncontrolled observational study of caspofungin as prophylaxis or treatment for IFIs in kidney transplant patients. Caspofungin could be an effective and well‐tolerated option for antifungal prophylaxis and treatment in kidney transplant patients, and a number of factors could influence caspofungin Cmin in these patients. [ABSTRACT FROM AUTHOR]

Purpose: The substantial variability in the antiplatelet efficacy of clopidogrel has raised major concerns. Molecular epidemiological research suggests that ABCB1 C3435T polymorphism may be associated with clopidogrel response, but results remain controversial. To derive a more precise evaluation of the associations between ABCB1 C3435T polymorphism and the clinical efficacy of clopidogrel, we have conducted a PRISMA-compliant meta-analysis. Methods: The PubMed and EMBASE databases were searched for eligible studies up to 25 October 2016. The odds ratio (OR), the standard mean difference (SMD) and 95% confidence interval (CI) were applied to assess the strength of the relationship. Results: Overall, 28 related studies involving 23,243 patients were analyzed. No association was found between the ABCB1 polymorphisms and the primary outcome. In the subgroup analysis, the C3435T mutation significantly reduced platelet activity as tested by the LTA assay in the dominant (SMD −0.140, 95% CI −0.272 to −0.009, P = 0.036) and heterozygous (SMD −0.154, 95% CI −0.290 to −0.017, P = 0.027) models, but the result lacked robustness in the sensitivity analysis. A significant association between the C3435T polymorphism and bleeding risk was also observed with low heterogeneity in the dominant (OR 1.805, 95% CI1.124-2.900, P =0.015, I = 0%), homozygous (OR 1.952, 95% CI 1.055-3.611, P = 0.033, I = 13.2%) and heterozygous (OR 1.793, 95% CI 1.091-2.946, P = 0.021, I = 0%) models in Asian patients. Conclusions: The results of the meta-analysis suggest that ABCB1 C3435T polymorphism may increase the risk of bleeding in Asian patients treated with clopidogrel. The implied relationship needs to be verified in future basic genetic pharmacology studies. [ABSTRACT FROM AUTHOR]

Purpose: The optimal therapy involving linezolid or vancomycin for suspected methicillin-resistant Staphylococcus aureus (MRSA) nosocomial pneumonia (NP) remains controversial. This study compared the efficacy and safety of linezolid and vancomycin therapies in patients with NP. Methods: A systematic review of randomized controlled trials with meta-analyses performed by searching PubMed, EMBASE, MEDLINE, and the Cochrane Central Register of Controlled Trials. We screened for relevant randomized controlled studies in which patients with NP were enrolled and linezolid and vancomycin therapies were compared. Results: Nine trials involving 2618 pneumonia patients were reviewed. Linezolid was not found to be superior to vancomycin for clinical cure when categories of pathogen were not considered and in a subgroup of NP patients with MRSA infection [relative risk (RR) = 1.16, 95 % confidence interval (CI) = 0.95-1.43, P = 0.15]. Compared with vancomycin, linezolid has no difference in the overall microbiological eradication rate (RR = 1.12, 95 % CI = 0.96-1.30, P = 0.15) and specific MRSA eradication rate (RR = 1.16, 95 % CI = 0.93-1.45, P = 0.19) in NP patients. In addition, nephrotoxicity was more frequent with vancomycin (RR = 0.50, 95 % CI = 0.31-0.81, P = 0.005), but no differences between the treatments were found for all-cause mortality, thrombocytopenia, gastrointestinal effects, and drug discontinuation due to adverse events. Conclusion: These results suggest that linezolid is not superior to vancomycin with respect to both clinical and microbiological cure rates in patients with MRSA NP. [ABSTRACT FROM AUTHOR]

Non-small-cell lung cancer (NSCLC) remains the most common malignant cancer. We identified 43140 advanced NSCLC patients from the SEER database to develop and validate a new prognostic model. The prognostic performance was evaluated by P value, concordance index, net reclassification index, integrated discrimination improvement, and decision curve analysis. The following variables were contained in the final prognostic model: age, sex, race, TNM stage, and grade and treatment options. Compared to the AJCC staging system, this prognostic model is conducive to the implementation of individualized clinical treatment schemes and can be an important part of the precise medical care of NSCLC tumors. [ABSTRACT FROM AUTHOR]

Ethnopharmacological relevance Astragalus is a traditional Chinese medicine that is widely used for tonifying Qi (Qi mainly means life energy) to treat diabetes mellitus and its complications. Aim of the study We performed a meta-analysis to evaluate the effect of Astragalus in adjuvant treatment of type 2 diabetes mellitus (T2DM), and to provide novel information to improve clinical decision-making. Materials and methods We conducted an exhaustive database search (PubMed, EMbase, Cochrane Library, China Knowledge Resource Integrated Database (CNKI), Wanfang data and SinoMed) of studies associated with “Astragalus” and “type 2 diabetes mellitus” until December 2015. Following quality assessment of study eligibility, the extracted data were statistically analyzed using STATA, ver. 12.0 (Stata Corp.). Results A total of 13 studies with 1054 participants were included in this meta-analysis. Two subgroups were identified, based on Astragalus dosing regimens: control group vs. Astragalus injection (AI); control group vs. Astragalus aqueous decoction (AAD). The pooled results showed that, in comparison with control group, Astragalus administration significantly reduced fasting plasma glucose (FPG) in both the AI group (WMD=−0.28, 95% CI=−0.46 to −0.10, P=0.002, I 2 =18.5%) and the AAD group (WMD=−0.83, 95% CI=−1.07 to −0.58, P=0.000, I 2 =0.0%); postprandial plasma glucose (PPG) was also significantly reduced in the AI group (WMD=−0.47, 95% CI=−0.77 to −0.17, P=0.002, I 2 =46.8%) and the AAD group (WMD=−1.19, 95% CI=−1.63 to −0.75, P=0.000, I 2 =49.3%). Fasting insulin (Fins) was significantly reduced only in the AAD treatment group (SMD=−0.33, 95% CI=−0.55 to −0.10, P=0.005, I 2 =1.0%) as was the homeostasis model assessment insulin resistance index (HOMA-IRI) levels (SMD=−1.66, 95% CI=−3.24 to −0.09, P=0.038, I 2 =94.0%). Although AAD treatment significantly reduced levels of glycated hemoglobin A1c (HbA1c) (WMD=−1.77, 95% CI=−3.06 to −0.47, P=0.007, I 2 =90.8%), AI treatment failed to show significant efficacy (WMD=−0.28, 95% CI=−0.63 to 0.06, P=0.102, I 2 =83.8%). Sensitivity analysis failed to detect outliers in all studies while Egger's linear regression test revealed a lack of publication bias in this meta-analysis (P=0.771, 95%CI =−3.51 to 4.56). Conclusions Astragalus may be beneficial as an adjuvant therapy in the treatment of type 2 diabetes. However, due to the limited quality of existing studies, further high-quality studies are warranted before definitive conclusions may be reached. [ABSTRACT FROM AUTHOR]