Toward Genetic Testing of Rivaroxaban? Insights from a Systematic Review on the Role of Genetic Polymorphism in Rivaroxaban Therapy.

BACKGROUND: Investigations into the rivaroxaban response from the perspective of genetic variation have been relatively recent and wide in scope, whereas there is no consensus on the necessity of genetic testing of rivaroxaban. Thus, this systematic review aims to thoroughly evaluate the relationship between genetic polymorphisms and rivaroxaban outcomes. METHODS: The PubMed, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), and Chinese databases were searched to 23 October 2022. We included cohort studies reporting the pharmacogenetic correlation of rivaroxaban. Outcomes measured included efficacy (all-cause mortality, thromboembolic events and coagulation-related tests), safety (major bleeding, clinically relevant non-major bleeding [CRNMB] and any hemorrhage), and pharmacokinetic outcomes. A narrative synthesis was performed to summarize findings from individual studies according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses and the reporting guideline for Synthesis Without Meta-Analysis. RESULTS: A total of 12 studies published between 2019 and 2022 involving 1364 patients were included. Ten, one, and six studies focused on the ABCB1, ABCG2, and CYP gene polymorphisms, respectively. Pharmacokinetic outcomes accounted for the majority of the outcomes reported (n = 11), followed by efficacy (n = 5) [including prothrombin time (PT) or international normalized ratio (n = 3), platelet inhibition rate (PIR) or platelet reactivity units (PRUs; n = 1), thromboembolic events (n = 1)], and safety (n = 5) [including major bleeding (n = 2), CRNMB (n = 2), any hemorrhage (n = 1)]. For ABCB1 gene polymorphism, the relationship between PT and ABCB1 rs1045642 was inconsistent across studies, however there was no pharmacogenetic relationship with other efficacy outcomes. Safety associations were found in ABCB1 rs4148738 and major bleeding, ABCB1 rs4148738 and CRNMB, ABCB1 rs1045642 and CRNMB, and ABCB1 rs2032582 and hemorrhage. Pharmacokinetic results were inconsistent among studies. For ABCG2 gene polymorphism, no correlation was observed between ABCG2 rs2231142 and dose-adjusted trough concentration (Cmin/D). For CYP gene polymorphisms, PIR or PRUs have a relationship with CYP2C19 rs12248560, however bleeding or pharmacokinetic effects did not show similar results. CONCLUSIONS: Currently available data are insufficient to confirm the relationship between clinical or pharmacokinetic outcomes of rivaroxaban and gene polymorphisms. Proactive strategies are advised as a priority in clinical practice rather than detection of SNP genotyping. CLINICAL TRIALS REGISTRATION: PROSPERO registration number CRD42022347907.

The Potential of Glycyrrhizinate in the Management of COVID-19: A Systematic Review of the Efficacy and Safety of Glycyrrhizin Preparations in the Treatment of SARS and MERS.

The SARS-CoV-2 outbreak in 2019 highlighted the fact that no specific medications providing effective treatment have been identified and approved. We explored the possibilities for COVID-19 by systematically reviewing evidence on the efficacy and safety of glycyrrhizin preparations for SARS and MERS. Electronic databases were systematically searched from inception to February 2020 for eligible studies that evaluated the efficacy and safety of glycyrrhizin preparations for SARS and MERS. A quantitative analysis or descriptive analysis was applied. Five retrospective cohort studies were included, and NOS scores ranged from 5-7 points. The clinical symptoms of dry cough, chest distress and dyspnoea improved quickly, and elevated serum levels of aminotransferase decreased after compound glycyrrhizin treatment. The SARS-CoV antibody appeared earlier in the treated group than in the control group ([Formula: see text][Formula: see text]d). Compared to that with conventional medications, the average period from peak to 50% improvement of lesions, in terms of X-ray manifestations, was shorter with compound glycyrrhizin treatment ([Formula: see text]2.1[Formula: see text]d), and treatment reduced the dosage ([Formula: see text][Formula: see text]mg/d) and duration of the corticosteroids used, without other serious adverse reactions. Based on the available evidence regarding glycyrrhizin preparations for treating SARS and MERS, we infer that compound glycyrrhizin could be an optional therapeutic strategy for SARS-CoV-2 infections, especially those complicated with liver damage. Further research using well-designed randomized clinical trials (RCTs) is warranted to determine the dosage and duration of use of compound glycyrrhizin and to monitor its specific adverse effects.

Impact on Sexual Function of Endoscopic Enucleation vs Transurethral Resection of the Prostate for Lower Urinary Tract Symptoms Due to Benign Prostatic Hyperplasia: A Systematic Review and Meta-Analysis.

Introduction: Although the transurethral resection of the prostate (TURP) has been regarded as the gold standard surgical option for lower urinary tract symptoms due to benign prostatic hyperplasia, the endoscopic enucleation of the prostate (EEP) with novel techniques is also recommended. However, whether there are differences on male sexual functions after these two procedures is still controversial. We performed this meta-analysis to investigate the impact on erectile function (EF) and ejaculation of EEP and TURP, and to explore the potential superiority between these two approaches. Materials and Methods: Literature search was conducted on Medline, Embase, and the Cochrane library, to obtain all relevant randomized controlled trials published before December 13, 2018. Outcome data were pooled and analyzed with Review Manager 5.3 to compare the International Index of Erectile Function 5 (IIEF-5) scores and retrograde ejaculation (RE) rates from short- to long-term follow-ups. Results: Ten articles with 1435 patients were included. EEP group showed higher IIEF-5 scores than TURP group with mean difference (MD) = 1.00, confidence interval (95% CI): 0.95-1.05 at 48 months and MD = 1.08, 95% CI: 1.03-1.13 at ≥60 months, respectively. In subgroup analysis, the holmium laser enucleation of the prostate showed significantly better IIEF scores than TURP group at 48 months (MD = 1.00, 95% CI: 0.95-1.05) and ≥72 months (MD = 1.08, 95% CI: 1.03-1.13). Additionally, no significant difference in RE rate was found between EEP and TURP (risk ratio = 1.02, 95% CI: 0.85-1.23). Conclusions: Compared with TURP, EEP may produce a more durable benefit for postoperative preservation of EF at long-term stage.

Severe toxic effects of low-dose methotrexate treatment for placenta accreta in a patient with methylenetetrahydrofolate reductase mutations.

WHAT IS KNOWN AND OBJECTIVE: Low-dose methotrexate (LDMTX) has been widely used for many decades in clinical settings, with good safety profiles compared with those of high-dose methotrexate. LDMTX is also used as one of the off-label conservative therapies in treating placenta accreta (PA). Until now, only a few mild adverse drug reactions (ADRs) have been published after short-term use of LDMTX, and no severe cases have been reported. CASE SUMMARY: We present a case of a 30-year-old female who developed acute severe oral ulcerative mucositis with degree IV myelosuppression and degree III hepatic injury, after three doses of LDMTX to treat placenta accrete. The symptoms gradually improved after leucovorin rescue and supportive treatments. WHAT IS NEW AND CONCLUSION: The present case provides the first severe ADR report for the short-term use of LDMTX for treating PA, indicating that potentially life-threatening complications can also occur when using LDMTX. Early recognition and immediate leucovorin rescue could result in a favourable outcome.

Association between the AUC0-24/MIC Ratio of Vancomycin and Its Clinical Effectiveness: A Systematic Review and Meta-Analysis.

BACKGROUND: A 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. OBJECTIVE: This 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. METHODS: PubMed, 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. RESULTS: No 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. CONCLUSIONS: This 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.