Effect of ABCB1 Genotypes on the Pharmacokinetics and Clinical Outcomes of New Oral Anticoagulants: A Systematic Review and Meta-analysis

2018 ◽  
Vol 24 (30) ◽  
pp. 3558-3565 ◽  
Author(s):  
Qiufen Xie ◽  
Qian Xiang ◽  
Guangyan Mu ◽  
Lingyue Ma ◽  
Shuqing Chen ◽  
...  

Background: New Oral Anticoagulants (NOACs) are effective and widely used to prevent and treat thromboembolic diseases, but the response to NOACs differs according to ABCB1 genotypes. Objective: We investigated the effects of ABCB1 genotypes on the pharmacokinetics and clinical outcomes of NOACs. Methods: We searched PubMed, Embase, and the Cochrane Library for studies on ABCB1 genotypes published from the inception of these databases until May 23, 2018. The Weighted Mean Difference (WMD) and Odds Ratio (OR) with 95% Confidence Interval (CI) were calculated for continuous and dichotomous data, respectively. Summary results were calculated using a random effects model. Results: Ten studies involving 2609 individuals were included in the systematic review, and three studies involving 535 individuals were included in the meta-analysis. Overall, four ABCB1 single-nucleotide polymorphisms were identified in the review. Carriers of the ABCB1 rs1045642 CC genotype had lower maximum plasma concentration (Cmax) than those of TT (WMD = −16.99 ng/mL; 95% CI = −33.39 to −0.59; P = 0.04), and carriers of the rs2032582 GG genotype showed lower Cmax than those of the A/T allele (WMD = −19.21 ng/mL; 95% CI = −36.62 to −1.80; P = 0.03). Carriers of the rs1045642 CC genotype showed lower area under the curve from time 0 to infinity (AUC0–∞) than those of the T allele (WMD = −78.58 ng·h/mL; 95% CI = −151.14 to −6.01; P = 0.03). ABCB1 rs4148738 genotypes did not affect the risks of ischemic stroke or systemic embolism (OR = 0.88), ischemic events (OR = 0.98), bleeding (OR = 0.94), major bleeding (OR = 1.14), or minor bleeding (OR = 0.94) in patients treated with dabigatran. Conclusion: Cmax was lower in carriers of ABCB1 rs1045642 CC than in those of TT and in carriers of rs2032582 GG than in those of the A/T allele, and AUC0–∞ was lower in carriers of rs1045642 CC than in those of TT. Conversely, ABCB1 rs4148738 genotypes did not affect primary clinical endpoints in dabigatran-administered patients. Future studies should analyze the relationships of ABCB1 genotypes with the pharmacokinetics and clinical outcomes of specific NOACs.

2021 ◽  
Vol 12 ◽  
Author(s):  
Dong Wang ◽  
Zhen Ruan ◽  
Rongchao Zhang ◽  
Xuejing Wang ◽  
Ruihui Wang ◽  
...  

Background: Earthworm, also called dilong (Chinese language), has been used as a traditional Chinese medicine for thousands of years. Recently, some scientists believe that earthworm extracts (EE) can promote wound healing. However, its effectiveness remains controversial. We conducted a meta-analysis to evaluate the effect of EE on wound healing based on the healing rate.Methods: We comprehensively reviewed literature that mentioned EE for wound healing in the PubMed, Cochrane Library, Embase, Web of Science, China National Knowledge Infrastructure (CNKI), VIP database for Chinese Technical Periodicals, and WanFang database that have been published until January 2021. We computed weighted mean difference (WMD) for analysis with RevMan 5.3 software in animal and human models groups. Two researchers independently selected studies and evaluated the risk of bias with the Cochrane Collaboration tool. The quality of the evidence was assessed with the Cochrane risk of bias tool. This study is registered on PROSPERO (CRD42020168400).Results: From 2,486 articles, we selected 16 studies for analysis. EE treatment was associated with improvements in wound healing performance based on wound healing rate (mouse model: weighted mean difference (WMD) = 3.55, 95% confidence interval (CI): 2.34–4.77, p < 0.00001; rat model: WMD = 17.29, 95% CI: 5.75–28.82, p = 0.003; rabbit model: WMD = 19.29, 95% CI: 9.95–28.64, p < 0.0001). Clinical studies also confirmed that EE could reduce healing time in hospital (WMD = −8.94, 95% CI: −17.75 to −0.14, p = 0.05).Conclusion: The results of this meta-analysis demonstrated the efficacy of EE on wound healing process. As a corollary, EE can be a useful natural product for wound healing drug development.Systematic Review Registration:https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=168400, identifier CRD42020168400.


2020 ◽  
Vol 40 (6) ◽  
Author(s):  
Shiqi Yi ◽  
Jiawei Xu ◽  
Hao Shi ◽  
Wenbo Li ◽  
Qian Li ◽  
...  

Abstract Background: Polycystic ovarian syndrome (PCOS) is a kind of common gynecological endocrine disorder. And the mutations of melatonin receptor (MTNR) genes are related to the occurrence of PCOS. But previous researches have shown opposite results. So, the object of our systematic review and meta-analysis is to investigate the relationship between MTNR 1A/B polymorphisms and PCOS. Methods: PubMed, Embase, Ovid, the Cochrane Library, Web of Science and three Chinese databases (VIP, CNKI and Wanfang) were used to retrieve eligible articles published between January 1980 and February 2020. And we used the odds ratio (OR) and its 95% confidence interval (CI) to investigate the strength of the association by six genetic models, allelic, codominant (homozygous and heterozygous), dominant, recessive and superdominant models. Review Manager 5.3, IBM SPSS statistics 25 and Stata MP 16.0 software were used to do this meta-analysis. Results: Our meta-analysis involved 2553 PCOS patients and 3152 controls, for two single nucleotide polymorphisms (rs10830963 C> G in MTNR1B and rs2119882 T> C in MTNR1A) and significant associations were found in some genetic models of these single nucleotide polymorphisms (SNPs). For rs10830963, strongly significant was found in the heterozygote model (GC vs. CC, P=0.02). Additionally, a slight trend was detected in the allelic (G vs. C), homozygote (GG vs. CC) and dominant (GG+GC vs. CC) model of rs10830963 (P=0.05). And after further sensitivity analysis, a study with high heterogeneity was removed. In the allelic (P=0.000), homozygote (P=0.001), dominant (P=0.000) and recessive (GG vs. GC+CC, P=0.001) model, strong associations between rs10830963 and PCOS were found. Moreover, for rs2119882, five genetic models, allelic (C vs. T, P=0.000), codominant (the homozygote (CC vs. TT, P=0.000) and heterozygote model (CT vs. TT, P=0.02), dominant (CC + CT vs. TT, P=0.03) and recessive model (CC vs. CT + TT, P=0.000) showed significant statistical associations with PCOS. Conclusion: MTNR1B rs10830963 and MTNR1B rs2119882 polymorphisms are associated with PCOS risk. However, the above conclusions still require being confirmed by much larger multi-ethnic studies.


BMJ Open ◽  
2020 ◽  
Vol 10 (10) ◽  
pp. e039898
Author(s):  
Weijing Fan ◽  
Baozhong Yang ◽  
Xiaoming Hu ◽  
Xiao Yang ◽  
Chenyan Shi ◽  
...  

IntroductionLeg ulcers (LUs) not only seriously affect life and work of patients, but also bring huge economic burden to the society. As a potential underused biological debridement, larval therapy provides help for the treatment of LUs. The purpose of our research is to assess whether patients with LUs can benefit from larval therapy.Methods and analysisThe following electronic databases will be searched: PubMed, EMBASE, Web of Science, the Cochrane Library, China National Knowledge Infrastructure Database, Wanfang Database and Chinese Biological Medicine. Randomised controlled trials are eligible for inclusion. There will be no restrictions with respect to language and search date is up to June 2020. Primary outcomes investigated are complete healing rate after treatment, time to ulcer healing, reduction of wound surface area and adverse events. Risk ratios will be used for categorical data; weighted mean difference will be used for measurement data. Subgroup analysis and sensitivity analysis will be considered if heterogeneity exists. The results of data synthesis will be performed by narrative summary and quantitative analysis.Ethics and disseminationThis systematic review does not require the approval of the ethics committee because individual data on patients are not collected. The results of the study will be disseminated in peer-reviewed journals.PROSPERO registration numberCRD42020176953.


2019 ◽  
Vol 122 (9) ◽  
pp. 1021-1032
Author(s):  
Amir Hadi ◽  
Arman Arab ◽  
Sajjad Moradi ◽  
Ana Pantovic ◽  
Cain C. T. Clark ◽  
...  

AbstractA number of clinical trials have examined the effect of l-arginine on lipid profile in recent years; however, the results remain equivocal. Therefore, the present study aims to summarise and quantitatively examine the available evidence on the effectiveness l-arginine supplementation on lipid parameters using a systematic review and meta-analytic approach. Online databases including PubMed, Scopus, ISI Web of Science, Cochrane Library and Google Scholar were searched up to April 2019 for randomised controlled trials that examined the effect of l-arginine supplementation on lipid profile in adults. Treatment effects were expressed as weighted mean difference (WMD) and the corresponding standard error in concentrations of serum lipids. To estimate the overall effect of l-arginine supplementation, we used the random-effects model. In total, twelve studies were included in the systematic review. The meta-analysis revealed that l-arginine supplementation did not significantly change the concentrations of total cholesterol (WMD: –5·03 mg/dl; 95 % CI –10·78, 0·73; P = 0·08; inconsistency index (I2) = 39·0 %), LDL (WMD: –0·47 mg/dl; 95 % CI –3·61, 2·66; P = 0·76; I2 = 0·0 %), or HDL (WMD: 0·57 mg/dl; 95 % CI –1·28, 2·43; P = 0·54; I2 = 68·4 %). A significant reduction was observed only in serum TAG levels (WMD: –7·04 mg/dl; 95 % CI –11·42, –2·67; P < 0·001; I2 = 0·0 %). This meta-analysis concludes that l-arginine supplementation can significantly reduce blood TAG levels; however, there is insufficient evidence to support its hypocholesterolaemic effects. To draw straightforward conclusions regarding generalised recommendations for l-arginine supplementation for improving lipid profile, there is a need for more well-controlled trials targeting exclusively patients with dyslipidaemia.


2017 ◽  
Vol 46 (12) ◽  
pp. 3047-3056 ◽  
Author(s):  
Bum-Sik Lee ◽  
Hyun-Jung Kim ◽  
Chang-Rack Lee ◽  
Seong-Il Bin ◽  
Dae-Hee Lee ◽  
...  

Background: While additional procedures correcting accompanying pathological conditions can improve the clinical outcomes of meniscal allograft transplantation (MAT), whether those outcomes are comparable or poorer than those of isolated MAT has yet to be clarified. Purpose:  To evaluate whether there is a difference in clinical outcomes between isolated MAT and MAT combined with other procedures (combined MAT). Study Design: Meta-analysis and systematic review. Methods: For the comparison of clinical outcomes between isolated MAT and combined MAT, the authors searched MEDLINE, Embase, and the Cochrane Library. Studies that separately reported the clinical outcomes of isolated MAT and combined MAT were included. Clinical outcomes were evaluated in terms of patient-reported outcomes (PROs) and complication, reoperation, survivorship, and failure rates. We conducted a meta-analysis of the PROs that were used in more than 3 studies. Results: A total of 24 studies were included in this study. In the meta-analysis, no significant differences in Lysholm scores (95% CI, –5.92 to 1.55; P = .25), Tegner activity scores (95% CI, –0.54 to 0.22; P = .41), International Knee Documentation Committee subjective scores (95% CI, –5.67 to 3.37; P = .62), and visual analog scale scores (95% CI, –0.15 to 0.94; P = .16) were observed between isolated MAT and combined MAT. For PROs that were not included in the meta-analysis, most studies reported no significant difference between the 2 groups. As for the survivorship and failure rates, studies showed varying outcomes. Four studies reported that additional procedures did not affect MAT failure or survivorship. However, 3 studies reported that ligament surgery, realignment osteotomy, and osteochondral autograft transfer were risk factors of failure. One study reported that the medial MAT group in which high tibial osteotomy was performed showed a higher survival rate than the isolated medial MAT group. Conclusion: Overall, there seems to be no significant difference between the postoperative PROs in terms of isolated MAT and combined MAT. However, more data are required to verify the effects of osteotomy and cartilage procedures on the clinical outcomes of MAT. We could not draw conclusions about the differences in complication, reoperation, survivorship, and failure rates between the 2 groups because we did not obtain sufficient data.


2021 ◽  
Author(s):  
Li Jia ◽  
Mingming Zhou ◽  
Li Sun ◽  
Luhai Yu ◽  
Xiangyan He

Abstract Atrial fibrillation(AF) increases the risk of ischemic stroke and systemic embolism in patients. Moreover, Asian patients with AF are more likely to have ischemic stroke than non-Asian patients. Oral anticoagulants could effectively prevent thrombotic events. Dabigatran and Rivaroxaban are two most commonly used novel oral anticoagulants (NOACs) in Asia, but those clinicial studies in relation with them are mostly in American and European countries. Therefore, whether there are differences between Dabigatran and Rivaroxaban among Asian patients with AF in terms of efficacy and safety is still unknown. This systematic review and meta-analysis will mainly assess clinical efficacy and safety of Dabigatran versus Rivaroxaban in Asian patients with AF by a pooled analysis. We will follow the PRISMA (preferred reporting items for systematic reviews and meta-analyses) and the reporting MOOSE (Meta-analyses of Observational Studies in Epidemiology) when performing this study. Then Cochrane Library,Web of Science, PubMed and China national knowledge infrastructure will be searched for eligible retrospective investigation that report the efficacy and safety outcomes of AF patients who utilised Dabigatran or Rivaroxaban for stroke prevention in Asian countries. The abovementioned database will be comprehensively searched from inception to September 30, 2019 to locate all potentially eligible studies. Outcome measures will include safety and efficacy indicators. Safety indicators include intracranial hemorrhage, major bleeding and gastrointestinal bleeding. Efficacy indicators include systemic embolism and stroke. New evidence for clinical profile of Dabigatran versus Rivaroxaban in AF patients will be provided for decision-making of Asian patients.PROSPERO registration number: CRD42020156197


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