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-OBJECTIVES:We performed this systematic review and meta-analysis to confirm whether patients benefit more from pharmacist-led anticoagulation management than other models. METHODS: We searched PubMed, Embase, Cochrane Library and reference lists of yielded results conducted up to April 25, 2017. RCTs and observational cohort studies and case-control studies which compared the percentage of time within the target therapeutic range (TTR), the percentage of time within the expanded therapeutic range (TER), haemorrhage events, thrombosis events, mortality, patient satisfaction and/or medicine cost saving of pharmacist-led anticoagulation management with other models, and species were limited to humans. Two investigators evaluated methodology and extracted data from included studies independently. Data analysis were performed by STATA 12.0 software and quality of evidence assessment was performed by GRADEprofiler software. RESULTS: 8 RCTs and 9 observational cohort studies with 9919 patients were included eventually with high quality and no publication bias. In RCTs pooled results, TTR (p=0.548 moderate-quality), TER (p=0.285, moderate-quality), total haemorrhage events (p=0.140, low-quality), minor haemorrhage events (p=0.162, low-quality), major haemorrhage events (p=0.237, low-quality), thrombosis events (p=0.615, low-quality) and mortality (p=0.876, low-quality) was not significant between two groups.

Background: Voriconazole primary metabolism is catalysed by CYP2C19. A large variability of trough concentrations in patients with invasive fungal infection treated with voriconazole has been observed in clinical practice. It remains controversial whether the CYP2C19 polymorphisms are responsible for voriconazole metabolism in the individual variation. Objectives:The primary aim of this study was to assess the effect of CYP2C19 polymorphisms on voriconazole trough concentrations.Methods: Following a systematic literature review, we performed a meta-analysis for mean differences (MD) of voriconazole trough concentrations (C min ), voriconazole dosage adjusted trough concentrations (C min /D) and for risk ratio (RR) of the proportion of patients in the target therapeutic range between pairwise comparisons of CYP2C19 phenotypes.Results: Compared with normal metabolisers (NMs), intermediate metabolisers (IMs) (MD: 0.82, 95% CI: 0.57 to 1.07, I 2 = 44%, p < .00001) or poor metabolisers (PMs) (MD:1.59, 95% CI: 1.14 to 2.05, I 2 = 46%, p < .00001) had significantly higher voriconazole C min (μg•ml −1 ), while rapid metabolisers (RMs) had significantly lower voriconazole C min (MD: −0,87, 95% CI: −1.35 to −0.38, I 2 = 0%, p = .0004). In addition, IMs had significantly lower C min than PMs (MD: −0.59, 95% CI: −0.97 to −0.20, I 2 = 22%, p = .003).Similarly, the C min /D (μg•kg•ml −1 •mg −1 ) was significantly higher in IMs (MD: 0.13, 95% CI: 0.05 to 0.22, I 2 = 0%, p = .002) and PMs (MD: 0.20, 95% CI: 0.07 to 0.34, I 2 = 0%, p = .003) than that in NMs, and also, IMs had significantly lower C min /D than PMs (MD: −0.11, 95% CI: −0.14 to −0.08, I 2 = 0%, p < .00001). Furthermore, PMs had a significantly higher proportion of the target therapeutic range than NMs (RR: 1.34, 95% CI:1.09 to 1.64, I 2 = 50%, p = .005). Conclusions:Compared to NMs, IMs and PMs had higher voriconazole trough concentrations, especially in Asians, while RMs had lower voriconazole trough concentrations. In addition, PMs had a higher proportion of the target therapeutic range than NMs, especially in Asians. CYP2C19 genotyping is expected to be used to preemptively guide the individualisation of voriconazole in clinical practice.

Background: Sirolimus (SRL) is an immunosuppressive drug and substrate of the P-glycoprotein (P-GP) encoded by ABCB1. The relationship between ABCB1 polymorphism and the pharmacokinetics of SRL in different studies were conflicting in renal transplant recipients. Thus, this meta-analysis aims to investigate the influence of ABCB1 C3435T, C1236T, and G2677T/A polymorphisms on the dose-adjusted trough level (C/D) of SRL in renal transplant recipients.Methods: PubMed, Embase, and the Cochrane Library were searched for relevant studies. The quality of each eligible study was assessed according to Newcastle-Ottawa Scale. The STATA 15.0 was adopted to perform the meta-analysis. The fixed-effects model was used for pooled results with low heterogeneity (I 2 ≤50%); otherwise, the random-effects model was used.Results: A total of 6 studies were included in the meta-analysis. Results of pooled analysis showed no significant association of SRL C/D ratio with ABCB1 C3435T polymorphism. The subgroup analysis based on different ethnic groups and different time-points after SRL initiation in renal transplant recipients were also conducted. No significant association was observed in these subgroups. Significant associations were showed between ABCB1 C1236T polymorphism and the C/D ratio of SRL in the homozygous model