BackgroundA target AUC0-24/MIC ratio of 400 has been associated with its clinical success when treating Staphylococcus aureus infections but is not currently supported by state-of-the-art evidence-based research.ObjectiveThis current systematic review aimed to evaluate the available evidence for the association between the AUC0-24/MIC ratio of vancomycin and its clinical effectiveness on hospitalized patients and to confirm the existing target value of 400.MethodsPubMed, Embase, Web of Sciences, the Cochrane Library and two Chinese literature databases (CNKI, CBM) were systematically searched. Manual searching was also applied. Both RCTs and observational studies comparing the clinical outcomes of high AUC0-24/MIC groups versus low AUC0-24/MIC groups were eligible. Two reviewers independently extracted the data. The primary outcomes were mortality and infection treatment failure. Risk ratios (RRs) with 95% confidence intervals (95%CIs) were calculated.ResultsNo RCTs were retrieved. Nine cohort studies were included in the meta-analysis. Mortality rates were significantly lower in high AUC0-24/MIC groups (RR = 0.47, 95%CI = 0.31–0.70, p<0.001). The rates of infection treatment failure were also significantly lower in high AUC/MIC groups and were consistent after correcting for heterogeneity (RR = 0.39, 95%CI = 0.28–0.55, p = 0.001). Subgroup analyses showed that results were consistent whether MIC values were determined by broth microdilution (BMD) method or Etest method. In studies using the BMD method, breakpoints of AUC0-24/MIC all fell within 85% to 115% of 400.ConclusionsThis meta-analysis demonstrated that achieving a high AUC0-24/MIC of vancomycin could significantly decrease mortality rates by 53% and rates of infection treatment failure by 61%, with 400 being a reasonable target.

BackgroundAdiponectin, an adipose-specific protein, is negatively correlated with pro-atherogenic low-density lipoprotein cholesterol (LDL-C) and other cardiovascular risk factors such as insulin resistance. Therefore, low levels of adiponectin are associated with a higher risk for diabetes and cardiovascular disease. Dipeptidyl peptidase-4 inhibitors (DPP4i) have been used for the treatment of type 2 diabetes mellitus (T2DM) as reversible inhibitors through interacting with DPP4 substrate and increase serum incretins such as glucagon-like peptide-1 (GLP-1). The present study aimed to evaluate the effect of DPP4i on serum adiponectin in T2DM patients.MethodsThe PubMed, Embase, and Cochrane library databases were searched from inception to February 2016. Randomized controlled trials, evaluating the DPP4i (sitagliptin and vildagliptin) versus comparator (placebo or active-comparison), in T2DM patients with duration of ≥ 12 weeks, were identified. Weighted differences in means of adiponectin levels were calculated by using a fixed or random-effects model.ResultsTen randomized controlled trials, including 1,495 subjects, were identified. Compared with placebo, DPP4i (sitagliptin and vildagliptin) treatment significantly elevated adiponectin levels by 0.74 μg/mL (95% confidence interval [CI], 0.45 to 1.03) relative to that using an active-comparison by 0.00 μg/mL (95% CI, −0.57 to 0.56). Compared with active-comparison, vildagliptin treatment increased adiponectin levels by 0.32 μg/mL (95% CI, −0.01 to 0.65), whereas sitagliptin treatment decreased adiponectin levels by −0.24 μg/mL (95% CI, −1.07 to 0.58). Trials examining effects of other DPP4i were not found.ConclusionsSitagliptin and vildagliptin increased serum adiponectin levels and had no stronger effect than traditional oral antidiabetic drugs. Further trials with larger sample size are needed to confirm the results and investigate the association between serum adiponectin levels and treatment of other DPP-4 inhibitors.Trial registrationRegistration No in PROSPERO: CRD42016037399.

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Lomitapide improved most lipid parameters but not HDL-C or ApoA-1 in patients with HoFH and in non-HoFH patients, and gastrointestinal disorders were the most common adverse event. The possible benefits of lomitapide should be further evaluated and viewed against its possible long-term side effects.