Effectiveness of metagenomic next-generation sequencing in the diagnosis of infectious diseases: A systematic review and meta-analysis.

OBJECTIVES: Early diagnosis of infectious diseases remains a challenge. This study assessed the diagnostic value of mNGS in infections and explored the effect of various factors on the accuracy of mNGS. METHODS: An electronic article search of PubMed, Cochrane Library, and Embase was performed. A total of 85 papers were eligible for inclusion and analysis. Stata 12.0 was used for statistical calculation to evaluate the efficacy of mNGS for the diagnosis of infectious diseases. RESULTS: The AUC of 85 studies was 0.88 (95%CI, 0.85-0.90). The AUC of the clinical comprehensive diagnosis and conventional test groups was 0.92 (95%CI, 0.89-0.94) and 0.82 (95%CI, 0.78-0.85), respectively. The results of subgroup analysis indicated that the PLR and NLR were 12.67 (95%CI, 6.01-26.70) and 0.05 (95%CI, 0.03-0.10), respectively, in arthrosis infections. The PLR was 24.41 (95%CI, 5.70-104.58) in central system infections and the NLR of immunocompromised patients was 0.08 (95%CI, 0.01-0.62). CONCLUSION: mNGS demonstrated satisfactory diagnostic performance for infections, especially for bone and joint infections and central system infections. Moreover, mNGS also has a high value in the exclusion of infection in immunocompromised patients.

Efficacy of anti-fungal agents for invasive fungal infection prophylaxis in liver transplant recipients: A network meta-analysis.

At present, there is still a lack of effective invasive fungal prophylaxis therapy in liver transplant recipients (LTRs). This study aimed to analysis the latest evidence on efficacy of current prophylactic anti-fungal therapy, and systematically compare between anti-fungal agents and placebo by a fixed-effects meta-analysis in all randomised controlled trials. A network meta-analysis was performed for invasive fungal infection (IFI) among different agents in 14 randomised controlled trials, in which 10 anti-fungal approaches were identified. Overall, anti-fungal prophylaxis reduced the rate of IFI (RR 0.30, 95% CI 0.18-0.52) and proven IFI (RR 0.27, 95% CI 0.14-0.53) when compared to placebo. In the network meta-analysis, an equivalent reduction in the rate of IFI was observed in fluconazole (OR 4.70, 95% CI 1.22-18.10), itraconazole (OR 5.82, 95% CI 1.10-30.71) and Liposomal amphotericin B (LAmB, OR 5.74, 95% CI 1.29-25.58) groups when compared with placebo. Anidulafungin might be the most effective agents in IFI prevention; however, this superiority did not meet statistically significance. Our study indicated that fluconazole, echinocandins and LAmB are equivalent in efficacy. Of which, fluconazole is recommended for the prevention of IFI in LTRs due to its efficacy, economics and compliance.

The impact of the clinical pharmacist-led interventions in China: A systematic review and Meta-Analysis.

Background The clinical pharmacist has been an important partner in clinical treatment team. In China, there is no systematic review to evaluate the effectiveness of clinical pharmacy services on patients' outcomes such as hospitalization days, readmission rate and mortality. Aim of the review To investigate the impact of clinical pharmacist services on patients' length of hospitalization, readmission and mortality in China. Methods A literature search was performed in PubMed, EMBASE, Cochrane Library, clinicaltrials.gov, and a Chinese database (up to January 2019). Randomized control trials or pre- to post-intervention comparison studies were included to investigate the impact of clinical pharmacist-led interventions on the length of stay, readmission rate and mortality of inpatients. Basic information, intervention and therapeutic area were extracted. Results After screening all articles from the mentioned databases, 14 studies were included for meta- analysis and subgroup analysis. Most studies focused on cardiology and respiratory diseases. Results show that clinical pharmacist services can reduce the length of stay of inpatients (MD: - 3.00, 95% CI - 4.72 to - 1.29, P < 0.01) and the readmission rate (RR 0.44, 95% CI 0.35-0.56, P < 0.01) as well as the mortality of patients during hospitalization (RR 0.57, 95% CI 0.35-0.92, P = 0.02). Conclusions Clinical pharmacist-led interventions could significantly reduce Chinese patients' length of hospitalization and readmission rate. More studies are needed to confirm the relationship between the clinical pharmacist-led interventions and patients' mortality.

Cost-effectiveness of CYP2C19 LOF-guided antiplatelet therapy in Chinese patients with acute coronary syndrome.

Aim: This study aimed to evaluate the cost-effectiveness of CYP2C19 loss-of-function(LOF) allele-guided antiplatelet therapy compared with the universal use of clopidogrel or ticagrelor among Chinese patients with acute coronary syndrome undergoing percutaneous coronary intervention. Methods: A two-part cost-effectiveness model comprising of a 1-year decision tree and a long-term Markov model was utilized to simulate outcomes of three treatment strategies: universal use of clopidogrel (75 mg daily) or universal use of ticagrelor 90 mg twice daily for all patients and CYP2C19 LOF-guided therapy (LOF allele carriers receiving ticagrelor, LOF allele noncarriers receiving clopidogrel). Model outcomes included quality-adjusted life years (QALYs) gained, direct medical costs and incremental cost-effectiveness ratios (ICERs). ICERs less than one-time gross domestic product per capita in China 59,660 yuan/QALY were considered cost-effective. Results: Base-case analysis showed 'universal ticagrelor use' was cost-effective for an ICER of 33,875 yuan per QALY gained compared with 'universal clopidogrel use' of which gained a 1.6932 QALYs at lowest life-long cost of 2450 yuan. CYP2C19 LOF-guided therapy had an effectiveness of 1.6975 QALYs at a cost of 2812 yuan, for an ICER of 84,118 yuan per QALY gained relative to 'universal clopidogrel use'. Sensitivity analysis demonstrated that base-case results were significantly affected by five factors: the risk ratio of 'non-fatal myocardial infarction', 'non-fatal stroke' and 'cardiovascular death' in ticagrelor versus clopidogrel and the annual costs of clopidogrel and ticagrelor. According to the results of Monte Carlo simulation, when willing to pay is about 32,000 yuan, patients willing to receive clopidogrel or ticagrelor are approximately equal. Conclusion: Optimal antiplatelet treatment is affected by lots of factors. The results of our study demonstrated that 'universal ticagrelor use' was cost-effective compared with 'universal clopidogrel use' for Chinese acute coronary syndrome patients with percutaneous coronary intervention.

Association between P2RY12 gene polymorphisms and adverse clinical events in coronary artery disease patients treated with clopidogrel: A systematic review and meta-analysis.

OBJECTIVE: Investigate the association between P2Y12 Purinoceptor (P2RY12) polymorphisms and adverse clinical events in coronary artery disease (CAD) patients treated with clopidogrel. METHODS: We performed a comprehensive database search, with a particular focus on P2RY12 polymorphisms and their effects on clopidogrel-treated CAD patients, in the PubMed, EMBASE, Cochrane Library, clinicaltrials.gov, Web of Science, and Chinese databases from their inceptions to April 8, 2017. The primary endpoints were composite ischemic events (including cardiovascular and cerebrovascular ischemic events), the secondary endpoints were independent cardiovascular events (mortality, non-fatal myocardial infarction, stent thrombosis, unstable angina, and target vessel revascularization) and the safety endpoints were bleeding events. RESULTS: Overall 10 studies and 10,810 clopidogrel-treated CAD patients were studied in the present work. Subjects of the common alleles of P2RY12 polymorphisms showed higher risk for composite ischemic events compared to non-carriers (n = 434 of 3268[13.3%] vs. n = 646 of 6133[10.5%]; RR: 1.39, 95%CI: 1.14-1.69; p = 0.001). These allele carriers also showed increased risk for stent thrombosis (RR: 2.67, 95%CI: 1.03-6.91; p = 0.04), myocardial infarction (RR: 1.60, 95%CI: 1.06-2.42; p = 0.03), and unstable angina (RR: 1.72, 95%CI: 1.37-2.16; p < 0.00001) (vs. non-carriers). There was no significant difference between two groups in terms of mortality risk, target vessel revascularization or bleeding (p = 0.29; p = 0.48, respectively). CONCLUSIONS: P2RY12 gene polymorphisms might associate with higher risk of composite ischemic events, stent thrombosis, non-fatal myocardial infarction, unstable angina. While we found no significant effect on mortality, target vessel revascularization or bleeding.

Genetic mutations in PEAR1 associated with cardiovascular outcomes in Chinese patients with acute coronary syndrome.

OBJECTIVE: To investigate the association between PEAR1 (platelet endothelial aggregation receptor-1) polymorphisms and cardiovascular outcomes in acute coronary syndrome (ACS) in patients treated with aspirin and clopidogrel. METHODS: We genotyped eight common PEAR1 SNPs (rs2768759, rs12566888, rs12041331, rs11264579, rs2644592, rs822441, rs822442, and rs4661012), also CYP2C19*2 (rs4244285) and CYP2C19*3 (rs4986893) in 196 Chinese patients with ACS. We assessed the association between PEAR1 polymorphisms and platelet inhibition rate (PIR) measured by thromboelastography (TEG). The ischemic events over 12 months were recorded, and the relationship between PEAR1 polymorphisms and ischemic events was analyzed. RESULTS: Genetic mutations in rs822441, rs822442, and CYP2C19⁎2/⁎3 alleles were significantly associated with a decrease in PIR induced by adenosine diphosphate (ADP). Carriers of the T allele in rs11264579 were less likely to have ischemic events compared with non-carriers (HR: 0.53, 95% CI: 0.30-0.94, P = .031). By contrast, carriers of the A allele in rs822442 had increased risk of ischemic events (HR: 1.82, 95% CI: 1.02-3.24, P = .043). However, these significant associations disappeared after controlling family-wise error rate. CONCLUSIONS: For Chinese patients with ACS treated with aspirin and clopidogrel, genetic mutations in rs822441/rs822442 in PEAR1 correlated significantly with platelet activity after adjusting for CYP2C19 *2/*3 alleles. The rs11264579 T allele might be a protective factor for ischemic events; rs11264579, rs822441, and rs822442 might be genetic markers worthy of further research.