Should the trough concentration of vancomycin be abandoned in therapeutic drug monitoring? A multicentre, retrospective study of critically ill patients without any form of dialysis.

BACKGROUND: There are conflicts in guideline recommendations about the value and range of vancomycin trough concentration during therapeutic drug monitoring (TDM). This multicentre, retrospective study was conducted to explore the usefulness of trough concentration in specific patients who were critically ill and without any form of dialysis. METHODS: Patient information from five centres was retrospectively collected and the 24-hour area under the curve (AUC) was estimated by a Bayesian method. Patients were categorised into four groups according to trough concentration: < 10, 10-15, 15-20 and > 20 mg/L, and the corresponding AUC was analysed. A multivariable logistic regression model was used to investigate the relationship between trough concentration and AUC. RESULTS: Overall, 645 trough concentrations available from 416 patients were included in this study. The results indicated that the AUC was always < 400 mg/L∙h or > 600 mg/L∙h in the < 10 or > 20 mg/L groups, whereas the ratios of vancomycin AUC target attainment (400-600 mg/L∙h) were 48.8% and 92.3% in the 10-15 mg/L and 15-20 mg/L groups, respectively. Augmented renal clearance, low daily dose and non-q12h administration were found to be independent risk factors associated with AUC target non-attainment for patients with trough concentrations of 10-15 mg/L. CONCLUSION: Vancomycin trough concentration is a good marker of AUC for critically ill adults without any form of dialysis. However, AUC-guided TDM may be needed for patients with trough concentrations of 10-15 mg/L, especially for those with risk factors.

Trends of ambulatory oral anticoagulant prescription in five major cities of China, 2012-2017.

BACKGROUND: The introduction of non-VKA oral anticoagulants (NOACs) has changed the landscape of preventing thromboembolism events in many countries. However, the prescription trends of oral anticoagulant (OAC) in China are still unclear, which were evaluated in this study through data extracted and summarized from 5 major cities as representatives. METHODS: This study was designed as a time-series study which was based on pharmacy prescription data. Analysis was performed on yearly aggregated visits and expenditure. The results were also stratified by indications and specialties. RESULTS: A total of 189,006 prescriptions of 67 hospitals in 6 years were included in the study. The average growth rates of overall visit and expenditure of OAC were 15.8 and 57.5%, respectively. The share of warfarin decreased and NOACs had taken 92% of cost, covering 28% of patients in 2017. The more frequently used NOACs were rivaroxaban and dabigatran. The use of OAC was differed by indication and specialty. CONCLUSION: The use of NOACs was found increasing rapidly in both visits and cost, sharing a majority of cost with a minority of patients. Attentions should be paid on the rational use of NOACs.

Efficacy of Houttuynia eye drops for the treatment of vernal keratoconjunctivitis: A systemic review and meta-analysis protocol.

BACKGROUND: Vernal keratoconjunctivitis (VKC) is a common eye disease and can result in permanent decrease or loss of vision. Houttuynia eye drops (HED) is used for the treatment of VKC. However, the clinical evidence of HED has not been well concluded. Herein, we described a proposed systemic review and meta-analysis to evaluate the clinical efficacy of HED for the treatment of VKC. METHODS: Six electronic databases (Medline, Embase, the Cochrane database, Chinese National Knowledge Infrastructure, Wanfang database, and Chinese Biology and Medicine database) will be searched for randomized controlled trials (RCTs) which evaluating the clinical efficacy of HED for the treatment of VKC. Studies meet the eligibility criteria will be included. Data of the included studies will be extracted and the quality will also be evaluated. Data synthesis will be performed using RevMan software. Sensitivity analysis and publication bias will also be investigated. RESULTS: This study will provide high-quality systemic review and synthesis of RCTs on efficacy of HED for the treatment of VKC. CONCLUSION: This systemic review and meta-analysis will conclude the efficacy of HED for the treatment of VKC. REGISTRATION: PROSPERO CRD42019124737.

Cardioprotective effects of Glycyrrhiza uralensis extract against doxorubicin-induced toxicity.

The purpose of the present study was to investigate the cardioprotective effects of Glycyrrhiza uralensis extract (GUE) against doxorubicin (DOX)-induced cardiotoxicity. Imprinting control region (ICR) mice were treated with saline, DOX (20 mg/kg intraperitoneal [ip] for once), GUE (100 mg/kg intragastric [ig] for 8 days), co-treatments with DOX and GUE (100 mg/kg ig for 8 days), and amifostine (100 mg/kg intravenous [iv] for once), respectively. Serum levels of lactate dehydrogenase (LDH) and creatine kinase isoenzyme (CK-MB), glutathione peroxidase (GSH-P(X)) activity, and glutathione (GSH) level in heart tissue were measured. Histopathologic analysis of heart tissue was also performed. Treatment with GUE significantly protected the mice from DOX-induced cardiotoxicity, indicated by decreased levels of serum LDH and CK-MB, improved heart morphology and increased GSH-P(X) activity and GSH level. Additionally, GUE did not compromise the tumor-inhibitory effect of DOX. In conclusion, our studies imply the potentially clinical application of GUE to overcome the cardiotoxicity of doxorubicin.

A novel methodology for multicomponent drug design and its application in optimizing the combination of active components from Chinese medicinal formula Shenmai.

Traditional Chinese Medicine has become an important resource for searching the effective drug combinations in multicomponent drug designs. In this article, we investigate the methodology on how to efficiently optimize the combination of several active components from traditional Chinese formula. A new method based upon lattice experimental design and multivariate regression was applied to model the quantitative composition-activity relationship (QCAR) in this study. As a result, multi-objective optimization was achieved by Derringer function using extensive search algorithm. This newly proposed QCAR-based strategy for multicomponent drug design was then successfully applied on search optimal combination of three components from Chinese medicinal formula Shenmai. The result validated the effectiveness of the presented method for multicomponent drug design.

[An approach to predicting antioxidative activities of natural products based on near infrared spectroscopy].

The aim of present study is to develop a new approach to predicting antioxidative activities of flavonoid extracts from traditional Chinese medicine based on near-infrared spectroscopy (NIR). The 1,1-diphenyl-2-picryl-hydrazyl (DPPH) method was employed to assay the antioxidative activities of twenty-eight extracts. Then, the near infrared diffuse reflectance spectra of those samples were acquired in the range of 4000-10,000 cm(-1). The partial least square (PLS) algorithm was used to generate the calibration model that correlates the spectra and the antioxidative activities of those natural products. The optimal wavenumber ranges and the preprocessing method of original spectrum data were selected during the establishment of calibration model according to the root mean square error of cross-validation (RMSECV). The established model has been successfully applied to predict bioactivities of six samples in the validation set. The value of RMSECV of the proposed model was 9.50% with R2 of 0.9017, and the value of RMSEP was 14.8%. The result indicated that the method can be used for the fast determination of the antioxidative activities of flavonoids as well as other active components of natural products.

[Discovering active components from traditional Chinese medicine by component-knockout approach].

OBJECTIVE: A component-knockout approach was established to discover active components from traditional Chinese medicine. METHOD: According to the principle of gene knockout technique, an experiment workflow for component-knockout method was developed, which is distinct from the bio-guided screening method. The differences of therapeutic efficacies between different combinations of individual components were analyzed by some statistical methods including Analysis of Variance (ANOVA), whilst a set of criterias were established to assess active components. By comparing the difference of drug efficacy between the original formulae and the mixture being knockout certain component, the active components can be identified. RESULT: The presented component-knockout method was applied to discover the active components of Shenmai formulae for the synergistic effects on the cyclophosphamide chemotherapy for S180 tumor-bearing mice. The results indicated that panoxadiol, a type of ginsenosides, were the effective components of Shenmai formulae. CONCLUSION: A new method for identifying effective components from Chinese medicinal formulae was developed and successfully applied to discover the active components of Shenmai Formulae, which possesses the synergistic actions towards chemotherapy process.