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Background: Posaconazole therapeutic drug monitoring (TDM) is increasingly used in clinical practice. However, the utility of posaconazole TDM and the target of posaconazole plasma concentration for clinical successful prophylaxis remain uncertain and controversial. The aim of this study was to evaluate posaconazole exposure-response relationship and determine an optimum posaconazole concentration for prophylaxis against invasive fungal infections (IFIs).Methods: Bibliographic databases were searched (from inception to September 2017) to select studies including the clinical outcomes below and above concentration cut-off value of 0.5 mg/L and 0.7 mg/L. The reliability of the results were evaluated with trial sequential analysis (TSA).Results: Twenty-eight studies with 1930 patients included were analyzed. The results of our pooled analysis demonstrated that patients with posaconazole plasma concentrations over 0.5 mg/L were twice more likely to achieve successful responses compared with those with lower concentrations (odds ratio, OR = 1.98, 95% confidence interval, CI 1.09-3.58, P = 0.02) while the threshold, 0.7 mg/L showed no significant difference (OR = 1.84, 95% CI 0.94-3.63, P = 0.08). The TSA results showed that there was sufficient information to support these findings.Conclusions: An optimal posaconazole concentration target of 0.5 mg/L is suggested to ensure the clinical prophylactic efficacy and may help reduce the dosage and dose-dependent toxicity comparing with the target of 0.7 mg/L. [ABSTRACT FROM AUTHOR]

Background: As a novel biomarker of inflammation, procalcitonin (PCT) has proven useful to guide antibiotic therapy in intensive care unit (ICU). However, there are controversial on mortality. The aim of this study was to evaluate the utility of PCT-guided antibiotic therapy in critically ill adults and determine whether studies are sufficient.Methods: A systematic search in PubMed, Embase and Cochrane was performed. We included only randomized controlled trials which compared the safety and efficacy between PCT-guided or standard antibiotic therapy groups in ICU adults. Trial sequential analysis and GARDE approach were performed.Results: Fifteen studies met our criteria for inclusion finally, with a cumulative number of 5486 ICU patients. There was no difference in 28-day mortality between two compared groups (P = 0.626), but significant decreases were observed in the duration of antibiotic therapy for the first episode of infection (P < 0.001) and length of hospitalization (P = 0.049). No significant deference was found in secondary endpoints except total duration of antibiotic therapy (P < 0.001). TSA revealed that the pooled sample sizes of 28-day mortality and the duration of antibiotic therapy for the first episode of infection exceeded the estimated required information size, but not the length of hospitalization.Conclusions: PCT-guided therapy is a better and safer algorithm to be applied into ICU patients, which appears no effect on 28-day mortality while performing preferable utility in reducing the duration of antibiotic therapy for the first episode of infection. More studies on these endpoints were not recommended. [ABSTRACT FROM AUTHOR]

After publication of the original article [1], the authors have reported that the software developers had used a new amended version of the software called "v0.9.5.10" instead of "v0.9.5.5", which is referred to in the original article. [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]