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Aim: This meta‐analysis was carried out to explore if a personalized antiplatelet strategy based on genotyping is superior to conventional therapy. Methods: PubMed, Web of Science, EMBASE and the Cochrane Library were searched from the inception of each database to 5 May 2020. Studies reporting endpoints in genotype‐guided treatment group and conventional treatment group were included. The endpoint results were presented as the risk ratio (RR), with 95% confidence interval (CI). Results: A total of 10 561 patients from 16 studies (eight randomized controlled trials [RCT] and eight cohort studies) were included in the meta‐analysis. The rates of major adverse cardiovascular events (MACE), stent thrombosis and myocardial infarction (MI) were significantly lower in the genotype‐guided group than in the conventional treatment group (RR 0.56, 95% CI 0.44‐0.73, P <.0001; RR 0.40, 95% CI 0.24‐0.67, P =.0005; RR 0.45, 95% CI 0.35‐0.58, P <.00001, respectively). A significant difference was found between the two groups in major bleeding (RR 0.73, 95% CI 0.55‐0.98, P =.04), which was not robust after sensitivity analysis. Conclusion: Genotype‐guided antiplatelet treatment could decrease the risk of MACE, stent thrombosis and MI in patients with coronary artery disease or undergoing percutaneous coronary intervention, without increasing the risk of bleeding over a long follow‐up period. The decreased risk of efficacy outcomes was more obvious in cohort studies. Well‐organized RCTs and clinical trials are required to verify the benefit of genotype‐guided therapy. [ABSTRACT FROM AUTHOR]

Cigarette smoking is an important cardiovascular risk factor, causing morbidity and mortality. There are many original studies on the impact of smoking, but its influence on platelet ADP-P2Y12 receptor inhibitors lack consistency. Thus, we conducted a systematic review and meta-analysis of already existing data/studies to further explore this issue. PubMed, Web of science, EMBASE, Clinical Trials, and the Cochrane Library were searched from inception to March 2018. Studies investigating the residual platelet reactivity categorized by smoking status and patients treated with platelet ADP-P2Y12 receptor inhibitors qualified the inclusion criteria. The primary outcome was P2Y12 reaction unit (PRU) value measured by VerifyNow P2Y12 assay, compared with different smoking status in ADP-P2Y12 receptor inhibitors treatment groups. Secondary outcome was post-treatment with 5 μmol/L ADP-inhibition of platelet aggregation (ADP-IPA) measured by light transmittance aggregometry (LTA). Of the 4954 citations retrieved, 12 studies involving 16 296 patients with acute coronary syndrome and/or stent deployment using platelet ADP-P2Y12 receptor inhibitors were included for meta-analysis. Pooled analysis revealed that PRU values of current smokers were 25.70 lower than nonsmokers (95% CI −38.81 to −12.60, p = 0.0001), getting better effects of antiplatelet treatment. In the smoking extent subgroup analysis, patients smoking >10 cigarettes/day shown about 46.49 lower of PRU values than patients smoking <10 cigarettes/day (p < 0.00001). Racial subgroup analyses found that smokers had increased platelet inhibition in the Caucasian population. Further, pooled analysis of ADP-IPA values for 1658 patients from five studies showed a significantly lower residual platelet reactivity in current smokers compared to that in nonsmokers (MD = −4.19; 95% CI −6.55 to −1.83; p = 0.0005). This systematic review and meta-analysis suggested that smokers have increased platelet inhibition and lower aggregation in response to clopidogrel than nonsmokers. These residual platelet reactivity observations may help to explain differential clinical outcomes in smokers vs. nonsmokers in large scale clinical trials. [ABSTRACT FROM AUTHOR]

Background: The effect of risperidone treatment in patients with schizophrenia varies according to the dopamine receptor genes. This study aimed to evaluate the relationship between genes of the dopamine receptors (D1, D2, and D3) and the effect of risperidone treatment. Methods: Three electronic databases (PubMed, Embase, and Cochrane Library) were searched for relevant cohort or case‐control studies published before 9 May 2018. A systematic review and meta‐analysis was performed for qualitative and quantitative assessment of the relationship between the dopamine receptors D1, D2, and D3 (DRD1, 2, and 3) and the effect of risperidone treatment. The summary odds ratio (OR) and weighted mean difference (WMD) in a random‐effects model were used to measure these relationships. Results: Twelve studies involving 24 SNPs were included. DRD2 (Ser311Cys, rs1801028 Ser/Ser) significantly lowered the improvement rate (determined by the PANSS score) unlike Ser/Cys (WMD: −11.58, 95% CI: −17.35 to −5.18). For Asian patients, A241G (rs1799978) AA carriers showed greater improvement after risperidone therapy (P < 0.05). The polymorphisms of 141C Ins/Del (rs1799732), T939C (rs6275), rs6277, and TaqID (rs1800498) may also influence the treatment effect. TaqIA (rs1800497) and TaqIB (rs17294542) were not associated with the rate of response to risperidone. DRD3 was not associated with an improvement in the PANSS total score; however, Ser9Gly might be related to a change in negative symptoms. No significant effect of DRD1 (rs5326, rs4867798, rs4532, and rs11749676) was found. Conclusions: Our result supported the hypothesis that DRD2 affected risperidone treatment. DRD1 had no significant effect on the response to risperidone, whereas DRD3 might be associated with an improvement in negative symptoms. Larger observational studies are warranted to verify these findings and identify other genetic factors involved. [ABSTRACT FROM AUTHOR]

Abstract: A novel optical Rhodamine-Furan type chemosensor (RF) was easily synthesized and characterized as a revisable switch. It dispalyed high selectivity toward Al3+ among 19 metal ions and the resultant complex [RF–Al3+] as a sequential chemosensor toward F− among 16 anions in neutral aqueous media (ethanol/water, v/v=2/3, Tris–HNO3, 10mM, pH 7.0). Moreover, detecting fluoride at concentration below the maximum contaminant level in drinking water defined by the U.S. Environmental Protection Agency (4.0mgL−1, 211μM) could be achieved with a detection limit (LOD) estimated down to 1.6μM. Both sensors were very easily to construct and only required simple synthesis. The reversible ring-open mechanism of the rhodamine spirolactam induced by Al3+ binding and the 1:1 stoichiometric structure between RF and Al3+ were adequately supported by job plot evaluation, optical titration, and 1H NMR study. Finally, it could be conveniently used for the determination of fluorides in dental products such as toothpastes with “naked eye” due to the obvious color change of testing solution, showing its potentially practical application. [Copyright &y& Elsevier]

Aims: To improve the understanding of pharmacokinetic/pharmacodynamic (PK/PD) profiles of apixaban, supporting personalised drug prescriptions for future patients., Background: Genetic as well as nongenetic factors can affect the predictable PK and PD characteristics of apixaban., Objective: Establish a integrated popPK/PD model that adjusts for critical genetic variant., Methods: The integrated PK/PD models was characterized on the basis of PK (apixaban blood concentration) and PD (prothrombin time (PT), activated partial thromboplastin time (APTT), and anti-FXa activity) data from 181 healthy Chinese volunteers. Other investigated covariate variables included: Meaningful intrinsic and extraneous determinants, correlated markers (ABCG2, F13A1, C3, etc.). A total of 2877 PK concentration observations were included in the modeling dataset., Results: The PK model of apixaban is adopted by single compartment model with first-order oral absorption. The estimated values of total clearance rate (CL/F), apparent distribution volume (V/F), and absorption rate constant (KA) in the final model are 3.37 l/h, 28.2 l, and 0.781 l/h, respectively. The PK model includes significance covariates such as FOOD, RBC, WT, and gene (ABCG2). The PD model of apixaban is adopted by a linear direct effect model with additive error, which was used to describe the relationship between markers such as APTT, PT, anti-FXa, versus plasma concentration. PK simulation within the modelled dose range is similar to clinical real date, while PD simulation results also show that the simulated exposure parameters is within the range of the literature., Conclusion: We established a comprehensive PK/PD model and used it to simulate markers level such as APTT, PT, and anti-FXa of apixaban. Individual predictive values with a dose of 2.5 mg are basically within the expected recommended range., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)