Background: The association between cytochrome P450 2C19 (CYP2C19) polymorphisms and neurological deterioration in stroke or transient ischemic attack (TIA) patients is not completely understood. Hence, we performed a systematic review and meta-analysis of prospective cohort studies to quantify this association. Methods: PubMed, Cochrane Library, Excerpta Medica Database, China National Knowledge Infrastructure and WanFang databases were searched for studies published up to April 2019. Prospective cohort studies that reported an association between CYP2C19 polymorphisms and neurological deterioration in stroke/TIA patients were included. Data on risk ratio (RR) and 95% confidence intervals (CI) were extracted and pooled by the authors. Preferred Reporting Items for Systematic reviews and Meta-Analyses guidelines were followed. Results: Twelve eligible studies were included. Twelve studies reported CYP2C19∗2, ∗3 loss-of-function alleles and 5 studies reported CYP2C19∗17 gain-of-function allele. Compared to non-carriers, carriers of CYP2C19∗2, ∗3 loss-of-function alleles had a significantly higher risk of neurological deterioration (RR, 1.63; 95%CI, 1.32–2.02). Conversely, carriers of CYP2C19∗17 gain-of-function allele had a significantly lower risk of neurological deterioration (RR, 0.520; 95%CI, 0.393–0.689) compared to non-carriers. Conclusions: This meta-analysis demonstrated that the carriers of CYP2C19∗2, ∗3 loss-of-function alleles have an increased risk of neurological deterioration compared to non-carriers in stroke or TIA patients. Additionally, CYP2C19∗17 gain-of-function allele can reduce the risk of neurological deterioration.
IntroductionClopidogrel and aspirin are routine drugs for the treatment of ischemic stroke (IS) and transient ischemic attack (TIA). However, with the increase of clinical application, a large number of patients have displayed clopidogrel resistance and/or aspirin resistance. At present, the effect of genetically tailored medication has not been prospective evaluated in a large sample.Methods and analysisThis study is an investigator-initiated, multicentre, large sample, prospectively, randomized controlled study evaluating the effects of precision antiplatelet medication based on the cytochrome P450 2C19 (CYP2C19) genetic test and the 11-dehydroxetane B2 (11-dhTxB2) test on IS/TIA patients over a duration of 12 months. Outcomes of interest including stroke recurrence, neurologic disabilities defined by the Modified Rankin Scale (mRS), bleeding events, other adverse events, and all-cause mortality will be assessed at the 1st, 3rd, 6th and 12th month post discharge. Demographics, risk factors, laboratory investigations, medications, physiological tests, and brain imaging will be assessed as well.Ethics and disseminationThe study was approved by the Medical Ethics Committee of the Second Affiliated Hospital of Nanchang University: (2018) Medical Research Review No.05. In this study, a pre-experiment was carried out in April 2019. Formal recruitment of patients began in June 2019 and will continue until December 2020. Participants will be followed for one-year and the study will end in December 2021. The results of the study will be disseminated through peer-reviewed publications and conference reports.Trial registration numberChiCTR1900026492.Trial registration date2019.10.12Trial registry name“Establishment of intelligent decision-making system for treatment of neurological impairment in cerebrovascular disease”. Tt is a prospectively study.Protocol versionV5.0, 2019/02/19.
The objective of the study is to determine the risks and benefits of treating idiopathic short stature (ISS) with aromatase inhibitors (AIs). We comprehensively searched PubMed, Embase, and the China National Knowledge Infrastructure between establishment year and January 31, 2020. Mean difference (MD)/Standardized mean differences (SMD) with 95% confidence intervals (CI) of individual studies were pooled using fixed or random effects models. Subgroup and sensitivity analyses were also performed. Publication bias was estimated using funnel plots and Egger tests. Fourteen studies including 388 participants were included. The meta-analysis results showed that AIs significantly increased final height (MD=2.46, 95% CI: 0.8–4.12) and predicted adult height (MD=0.34, 95% CI: 0.11–0.57). Changes in bone age (MD=–0.1, 95% CI: –0.86–0.66) and bone mineral density (MD=–0.05, 95% CI: –0.19–0.1) were not different between intervention and control group. AI significantly increased testosterone level (SMD=2.01, 95% CI: 0.8–3.23) and reduced estradiol level (SMD=–1.13, 95% CI: –1.87 to –0.40); The intervention and control group had no significant differences in the levels of high-density lipoprotein-cholesterol (SMD=–0.31, 95%CI: –0.68–0.06) and IGF-1 (SMD=0.7, 95% CI: –0.66–2.06) levels. Adverse events were more frequent in the intervention group than in the control group (odds ratio=3.12, 95% CI: 1.44–6.73). In conclusion, both AI monotherapy and AI combination therapy can increase predicted adult height and testosterone levels.
Background: Clopidogrel and aspirin are conventional drugs for treating ischemic stroke (IS) and transient ischemic attack (TIA). However, with the increase of clinical application, many patients have shown clopidogrel resistance (CR) and/or aspirin resistance (AR). clopidogrel resistance is related with cytochrome P450-2C19 (CYP2C19) polymorphism, and aspirin resistance is related to urine concentration of 11-dehydroxetane B2. At present, the effect of precision antiplatelet medication based on the cytochrome CYP2C19 genotype test and the 11-dhTxB2 test has not been evaluated prospectively in a large sample. Methods: This is a randomized controlled trial evaluating the effects of precision antiplatelet medication based on the CYP2C19 genotype test and the 11-dhTxB2 test on IS/TIA patients over 12 months. Outcomes of interest including stroke recurrence, neurologic disabilities defined by the Modified Rankin Scale (mRS), bleeding events, other adverse events, and all-cause mortality will be assessed at the 1st, 3rd, 6th and 12th-month post-discharge. Demographics, risk factors, laboratory investigations, medications, physiological tests, and brain imaging will also be assessed.Discussion: Some stroke patients have resistance to clopidogrel or aspirin, but there is still no personalized medicine. Our study will conduct free antiplatelet resistance tests and individualized antiplatelet medication for patients in the intervention group, ultimately evaluating individualized medication effectiveness through a one-year follow-up. The research results will help to assess the impact of personalized antiplatelet drug therapy on the prognosis of stroke, thus providing a reference for precise clinical treatment.Trial registration: Chinese Clinical Trial Registry, ChiCTR1900026492. Registered on 12 October 2019.
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