This meta-analysis showed trough concentrations of 0.5 mg/L to be the lower limit of voriconazole during treatment, whereas trough concentrations of 3.0 mg/L were associated with an increased risk of moderate to severe hepatotoxicity, particularly for the Asian population.

Conclusions/interpretation Current evidence from short-term RCTs did not indicate a significantly increased risk of overall cancer among individuals with type 2 diabetes using SGLT2 inhibitors.Given the short-term trial durations and uncertainty of evidence, future long-term prospective studies and post-marketing surveillance studies are warranted.

Background Clinical practice guidelines or recommendations often require timely and regular updating as new evidence emerges, because this can alter the risk-benefit trade-off. The scientific process of developing and updating guidelines accompanied by adequate implementation can improve outcomes. To promote better management of patients receiving vancomycin therapy, we updated the guideline for the therapeutic drug monitoring (TDM) of vancomycin published in 2015. Methods Our updated recommendations complied with standards for developing trustworthy guidelines, including timeliness and rigor of the updating process, as well as the use of the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach. We also followed the methodology handbook published by the National Institute for Health and Clinical Excellence and the Spanish National Health System. Results We partially updated the 2015 guideline. Apart from adults, the updated guideline also focuses on pediatric patients and neonates requiring intravenous vancomycin therapy. The guideline recommendations involve a broadened range of patients requiring TDM, modified index of TDM (both 24-hour area under the curve and trough concentration), addition regarding the necessity and timing of repeated TDM, and initial dose for specific subpopulations. Overall, 1 recommendation was deleted and 3 recommendations were modified. Eleven new recommendations were added, and no recommendation was made for 2 clinical questions. Conclusions We updated an evidence-based guideline regarding the TDM of vancomycin using a rigorous and multidisciplinary approach. The updated guideline provides more comprehensive recommendations to inform rational and optimized vancomycin use and is thus of greater applicability.

. (2016). Lack of evidence for a harmful effect of sodium-glucose co-transporter 2 (SGLT2) inhibitors on fracture risk among type 2 diabetes patients: a network and cumulative meta-analysis of randomized controlled trials. Diabetes, Obesity and Metabolism, 18(12), 1199-1206. https://doi.org/10.1111/dom.12742 2 Abstract Aim: Given the conflicting evidence of sodium-glucose cotransporter 2 (SGLT2) inhibitors on bone health in patients with type 2 diabetes Mellitus (T2DM), we aimed to evaluate the comparative effects of SGLT2 inhibitors on risk of bone fracture.Methods: PubMed, EMBASE, CENTRAL, and ClinicalTrials.gov were systematically searched from inception to January 27, 2016 to identify RCTs reporting the outcome of fracture in T2DM patients with the use of SGLT2 inhibitors. A pairwise and network meta-analyses, as well as a cumulative meta-analysis were performed to calculate their odds ratios (ORs) and 95% confidence intervals (CIs).Results: A total of 38 eligible RCTs (10 canagliflozin, 15 dapagliflozin, and 13 empagliflozin) involving 30,384 patients with periods of follow-up ranged from 24 to 160 weeks were included. The fracture event rates were 1.59% in the SGLT2 inhibitor groups and 1.56% in the control groups. The incidence of fracture event was similar among these three SGLT2 inhibitor groups. Compared with placebo, canagliflozin (OR, 1.15; 95%CI, 0.71 to 1.88), dapagliflozin (OR, 0.68; 95%CI, 0.37 to 1.25), and empagliflozin (OR, 0.93; 95%CI, 0.74 to 1.18) was not significantly associated with an increased risk of fracture. Our cumulative meta-analysis indicated the robustness of our null findings of SGLT2 inhibitors. Conclusions:Our meta-analysis based on available RCT data does not support the harm effect of SGLT2 inhibitors on fracture, although future safety monitoring from RCT and real-world data with detailed information on bone health is warranted.

Aims/hypothesis By analysing available evidence from randomised controlled trials (RCTs), we aimed to examine whether and to what extent sodium-glucose cotransporter 2 (SGLT2) inhibitors affect serum electrolyte levels in type 2 diabetes patients. Methods We searched PubMed, EMBASE, Cochrane Central Register of Controlled Trials (CENTRAL) a nd ClinicalTrials.gov up to 24 May 2016 for published RCTs of SGLT2 inhibitors that reported changes in serum electrolyte levels. Weighted mean differences (WMD) between each SGLT2 inhibitor and placebo were calculated using a randomeffects model. Dose-dependent relationships for each SGLT2 inhibitor were evaluated using meta-regression analysis.Results Eighteen eligible RCTs, including 15,309 patients and four SGLT2 inhibitors (canagliflozin, dapagliflozin, empagliflozin and ipragliflozin) were evaluated. In patients without chronic kidney disease, each SGLT2 inhibitor significantly increased serum magnesium levels compared with placebo (canagliflozin: WMD 0.06 mmol/l for 100 mg and 0.09 mmol/l for 300 mg; dapagliflozin: WMD 0.1 mmol/l for 10 mg; empagliflozin: WMD 0.04 mmol/l for 10 mg and 0.07 mmol/l for 25 mg; and ipragliflozin: WMD 0.05 mmol/l for 50 mg). Canagliflozin increased serum magnesium in a linear dose-dependent manner (p = 0.10). Serum phosphate was significantly increased by dapagliflozin. Serum sodium appeared to significantly differ by SGLT2 inhibitor type. No significant changes in serum calcium and potassium were observed. Findings were robust after including trials involving patients with chronic kidney disease. Conclusions/interpretation SGLT2 inhibitors marginally increased serum magnesium levels in type 2 diabetes patients indicating a drug class effect. Further investigations are required to examine the clinical significance of elevated magnesium levels in individuals with type 2 diabetes.