Impact of Implementing CYP2C19 Genotype-Guided Antiplatelet Therapy on P2Y12 Inhibitor Selection and Clinical Outcomes in Acute Coronary Syndrome Patients After Percutaneous Coronary Intervention: A Real-World Study in China.

Background: CYP2C19 loss-of-function (LOF) alleles reduce the effectiveness of clopidogrel in patients undergoing percutaneous coronary intervention for acute coronary syndrome. However, the clinical impact of implementing CYP2C19 gene-guided pharmacotherapy is unclear, especially among the Chinese population. The purpose of this study was to evaluate P2Y12 receptor inhibitor selection and clinical outcomes upon implementation of CYP2C19 genotype-guided pharmacotherapy in current clinical practice. Methods: This was a single-center observational cohort study. Adult percutaneous coronary intervention patients who received CYP2C19 genetic testing (*2, *3, *17 alleles) were included. Ticagrelor was recommended for patients with a LOF allele. Factors related to P2Y12 inhibitor selection were determined by logistic regression. The primary endpoint was major cardiac or cerebrovascular adverse events (MACCE) within 12 months. MACCE and clinically significant bleeding events (BARC ≥2) in the LOF-clopidogrel group, non-LOF-clopidogrel group, and non-LOF-ticagrelor group were compared with those in the LOF-ticagrelor group. The inverse probability of treatment weighting (IPTW) was adjusted in a Cox regression analysis to eliminate confounding factors. Results: Among 1,361 patients, 826 (60.7%) had a LOF allele. Patients with a LOF allele were more likely to be prescribed ticagrelor (multivariate-adjusted OR 1.349; 95% CI 1.040 to 1.751; p = 0.024). The MACCE rate was higher in the LOF-clopidogrel group than in the LOF-ticagrelor group (7.8 vs. 4.0%; log-rank p = 0.029; IPTW-adjusted HR 2.138; 95% CI 1.300-3.515). Compared with the LOF-ticagrelor group, the non-LOF-clopidogrel group showed no significant difference in MACCE rate (5.8 vs. 4.0%; log-rank p = 0.272; IPTW-adjusted HR 1.531; 95% CI 0.864-2.714). Among the patients treated with ticagrelor, there was no significant difference in the MACCE rate between the LOF group and non-LOF group (4.3 vs. 4.0%; log-rank p = 0.846; IPTW-adjusted HR 1.184; 95% CI 0.582-2.410). There was no significant difference in the incidence of clinically significant bleeding events among the four groups. Conclusion: This study confirms that efficiently returned CYP2C19 genotype results did partially guide cardiologists to prescribe ticagrelor for patients with a LOF allele, and that clopidogrel had a higher risk of MACCE than ticagrelor in these patients, which provides support for the implementation of CYP2C19 gene-guided antiplatelet therapy in clinical practice.

[A meta-analysis of aprepitant for prevention of chemotherapy-induced nausea and vomiting].

OBJECTIVE: To assess the efficacy and safety of aprepitant for the prevention of chemotherapy-induced nausea and vomiting (CINV) after moderately or highly emetogenic chemotherapy. METHODS: Studies were identified by searching PubMed (1980 to March, 2010), EMbase (1980 to March, 2010), Cochrane Libraries (Issue 2, 2010), CNKI (1980 to March, 2010), CBMdisc (1980 to March, 2010), and WanFang Data (1982 to March, 2010). Randomized controlled trials of aprepitant for the prevention of CINV were included. The quality of included studies was assessed and meta-analysis was performed for the results of homogeneous studies by RevMan 5.0.23 software. RESULTS: Ten studies involving 4 376 oncology patients were included. They were all high quality studies, with Jadad scores more than 5. The results of meta-analysis were as follows: (1) Acute CINV: The overall complete response rate was improved by 14.21% when aprepitant was combined with ondansetron and dexamethasone (83.33% vs 72.96%; P<0.001). Subgroup analysis showed the patients receiving AC (anthracycline/cyclophosphamide) regimen benefited less than the patients receiving cisplatin chemotherapy. The rate of no significant nausea was only improved by 3.92% (P=0.04). (2) Delayed CINV: Compared with ondansetron, aprepitant could improve vomiting by 14.98% (P=0.004). When aprepitant was added with dexamethasone, the response rate of vomiting and nausea was improved by 37.72% (P<0.001) and 11.24% (P=0.008) respectively. (3) Adverse reactions: The incidence of fatigue/asthenia was higher in the aprepitant regimen (P=0.001), while the incidence of constipation was lower (P=0.002). CONCLUSION: Aprepitant can improve the control of vomiting, but has slight effect on nausea. Patients receiving AC regimen benefit less than patients receiving cisplatin chemotherapy. In view of its high cost, pharmacoeconomics researches of aprepitant should be considered.

Degradation of 2,6-di-tert-butylphenol by an isolated high-efficiency bacterium strain.

An aerobic bacterium strain, F-3-4, capable of effectively degrading 2, 6-ditert-butylphenol (2, 6-DTBP), was isolated and screened out from an acrylic fiber wastewater and the biofilm in the wastewater treatment facilities. This strain was identified as Alcaligenes sp. through morphological, physiological and biochemical examinations. After cultivation, the strain was enhanced by 26.3% in its degradation capacity for 2,6-DTBP. Results indicated that the strain was able to utilize 2,6-DTBP, lysine, lactamine, citrate, n-utenedioic acid and malic acid as the sole carbon and energy source, alkalinize acetamide, asparagine, L-histidine, acetate, citrate and propionate, but failed to utilize glucose, D-fructose, D-seminose, D-xylose, serine and phenylalanine as the sole carbon and energy source. The optimal growth conditions were determined to be: temperature 37 degrees C, pH 7.0, inoculum size 0.1% and shaker rotary speed 250 r/min. Under the optimal conditions, the degradation kinetics of 2,6-DTBP with an initial concentration of 100 mg/L was studied. Results indicated that 62.4% of 2,6-DTBP was removed after 11 d. The degradation kinetics could be expressed by Eckenfelder equation with a half life of 9.38 d. In addition, the initial concentration of 2,6-DTBP played an important role on the degradation ability of the strain. The maximum initial concentration of 2,6-DTBP was determined to be 200 mg/L. Above this level, the strain was overloaded and exhibited significant inhibition.

[The degradation characteristics of degrading bacterium of 2,6-di-tert-butylphenol].

A degrading bacterial strain F-3-4 for 2,6-Di-tert-butylphenol (2,6-DTBP) was isolated from biofilm in acrylic fiber wastewater treatment structures. By acclimation, its capacity for degradation of 2,6-DTBP was enhanced by 26%. It was identified as Alcaligenes sp. according to morphological, physiological and biochemical characters. By tests in shaking flasks, the effects of the conditions of growth was studied, and it was determined that the optimum conditions of growth for the strain was 37 degrees C, pH 7.0 and inoculum amount 0.1%. Under these conditions, the kinetics of degradation for 2,6-DTBP of initial concentration 100 mg/L was studied, and the result indicated that the removal rate of 2,6-DTBP within 11 days was 62.4%, and the degradation process followed Eckenfelder kinetics. The half life of 2,6-DTBP was 9.38 days. The effect of initial concentration on degradation ability of the strain also was investigated. The results showed that the optimum initial concentration was 200 mg/L. When the initial concentrations were below it, the growth of strain and removal of 2,6-DTBP increased with the increase of initial concentration, while when above the value, they were inhibited.

[Application of PCR technique in genetic diagnosis of Duchenne/Becker muscular dystrophy].

OBJECTIVE: To study the application of PCR technique in genetic detection of Duchenne/Becker muscular dystrophy (DMD/BMD). METHODS: A multiple PCR system is established according to the multiple sites of DMD/BMD exon deletion. Under different PCR conditions, multiple exon deletions, single-strand conformation polymorphism, allopolyploid, chain labeling, restriction fragment length polymorphism and microsatellite phenomenon were examined in 23 DMD/BMD patients and 57 suspected carriers of these genes. RESULTS: Fourteen of the 23 DMD/BMD patients were identified as having gene deletion, with another 2 carried gene duplicates. Forty female relatives of these 23 DMD/BMD patients were diagnosed as carriers of the genes. CONCLUSION: This PCR system can be applied in detecting gene mutation of DMD/BMD, screening the carriers and in appropriate genealogical analysis of the patients with DMD/BMD.