Multi-centre survey and analysis of individual therapy of antimicrobial agents in children / 中国药房

OBJECTIVE To investigate the development of individual therapy of antimicrobial agents in pediatric patients. METHODS A questionnaire survey was conducted to investigate the individual therapy of antimicrobial agents in 30 children’s hospitals and pediatric departments of general hospitals in China. The survey data was analyzed statistically by Microsoft Excel 2007 and SPSS 26.0 software. RESULTS In this survey， 75 questionnaires were collected， and 53 of them were valid with an effective rate of 70.7%. The results showed that 86.7% （26/30） of the hospitals carried out individual therapy of antimicrobial agents in different forms. Clinical needs primarily contributed to the individual therapy in these hospitals， while the insufficient personnel and equipment were the biggest obstacles for individual therapy. The proportions of hospitals， who implemented evidence- based pharmacy， therapeutic drug monitoring （TDM）， model-informed precision dosing （MIPD） and antimicrobial-related genetic tests were 70.0%， 80.0%， 30.0% and 33.3%， respectively. Various detection methods of TDM were carried out in various hospitals， and the antimicrobial agents which needed TDM focused on vancomycin and voriconazole. Moreover， nearly half of pharmacists did not know much about MIPD. CONCLUSIONS At present， TDM is the main way to develop individual therapy of antimicrobial agents in various hospitals， but its monitoring coverage and testing standards need to be improved. MIPD and antimicrobial-related gene tests still need to be further promoted in clinical practice.

Current research status on pharmacological treatments for children with tic disorders / 中华实用儿科临床杂志

Tic disorders, which are mainly characterized by motor and/or vocal tics, are common pediatric neuropsychiatric disorders.Pharmacotherapy is an important part of the management of tic disorders.In addition to the individualized grasp of its indications, medicine selection also needs to weigh the risks and benefits.This article made an overview and evaluation of pharmacological treatments for children with tic disorders, so as to acquire the best available evidence on the efficacy and safety of the relevant medicines and to improve clinical decision-making.

Relationship Between Serum Concentration of the Active Metabolite and the Efficacy and Safety of Oxcarbazepine / 医药导报

Objective To investigate the relationship between serum 10-hydroxycarbazepine (MHD, the main active metabolite of oxcarbazepine) concentration and oxcarbazepine efficacy and safety, and to optimize rational use of oxcarbazepine. Methods A total of 553 patients were enrolled in a self-controlled and open-label trial to assess the efficacy and safety of oxcarbazepine as monotherapy. The steady state serum MHD trough concentrations after dose were determined by SPE-HPLC. The relationship between MHD level and efficacy were evaluated by logistic regression model and receiver operating characteristic (ROC) curve. Results A total of 498 patients (90.1%) were effective and 404 patients (73.1%) were seizure free after oxcarbazepine monotherapy in this study. The clinical therapeutic range of steady state serum MHD trough concentrations observed in this study was 5 - 20 mg ? L-1 , and the corresponding 95% distribution interval of oxcarbazepine daily dose was 9. 0 -34.5 mg?kg-1?d-1 . Logistic regression results indicated a positive correlation of antiepileptic efficacy with serum MHD trough concentration within 0.9-30.0 mg?L-1 . The ROC area (95% confidence interval) of MHD trough concentration as the predictor for efficacy was 0.964 (0.938- 0.990), which showed accurate predictions. Most of patients whould have good antiepileptic efficacy while the steady-state serum MHD trough concentration remains above 8 mg?L-1 . Adverse effects were observed in 104 patients (18.8%) during oxcarbazepine dose escalation phase, and 23 patients (4.2%) during maintenance phase. There were no severe adverse effects associated with oxcarbazepine in this study. Patients with serum MHD concentrations >20 mg?L-1 were at greater risk of developing adverse effects. Conclusion Oxcarbazepine therapeutic efficacy and safety are associated with MHD trough level closely, so it is necessary to monitor MHD concentration.

Relationship between SLCO1B1 521T ＞ C genovariation and severe toxicity during high-dose methotrexate chemotherapy / 中华实用儿科临床杂志

Objective To investigate the relationship between severe toxicity during high-dose methotrexate (HD-MTX) chemotherapy and 29 related factors including SLCO1B1 521T ＞ C genovariation,and to enhance drug safety.Methods Eighty-two children with acute lymphoblastic leukemia (ALL) received HD-MTX chemotherapy.The regimen was MTX 3-5 g/m2 continuous infusion for 24 hours.The polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique was used to detect the patients' genotypes of SLCO1B1 T521C polymorphism,which was the coding gene of organic anion transporting polypeptide 1 B1 (OATP1 B1).Haematological,gastrointestinal and hepatic toxicities in 1-10 days after HD-MTX administration were observed and graded according to Common Terminology Criteria for Adverse Events (CTCAE,version 4.02).The patients were divided into two groups based on toxicity grades:case group (grades Ⅲ-Ⅴ) and normal group (grades 0-]]).The differences of 29 variates including biology features,biochemical indicators,SLCO1B1 T521 C polymorphism and etc.were compared between the two groups by univariate analysis,and the significant factors were found out.The final predictive model of severe HD-MTX-related toxicity was set up through Logistic regression analysis.Receiver operating characteristic (ROC) curve of predictor was drawn based on final model in order to evaluate its predictive ability.Results There were only 4 significant different variates between case group and normal group (P ＜ 0.05),including SLCO1B1 T521C polymorphism,serum MTX concentrations at 72 hours after starting MTX infusion (C72h),the ratios of 7-hydroxy-MTX (the metabolin of MTX) to MTX concentrations at 48 hours (k48 h),and frequency of k48 h ≤2.Based on a multivariate logistic regression analysis,only SLCO1B1 521T＞ C genovariation (odds ratio 18.489,95％ confidence interval 5.413-63.157)was the significant independent predictor for severe HD-MTX-related toxicity.The area under ROC (95％ confidence interval) of SLCO1B1 521T ＞ C genovariation as the predictor for severe HD-MTX-related toxicity was 0.776 (0.653-0.899),which had significant diagnositic value (P ＜ 0.05).Conclusions There is higher risk of severe HD-MTX-related toxicity while patients having SLCO1B1 521T ＞ C genovariation.Clinician should consider it and take some protective measures.

Relationship Between Serum Concentration at 48 h and Pharmacokinetic Characteristics and Toxic Reactions at Terminal Elimination Phase After Starting High Dose Methotrexate Infusion / 医药导报

Objective To recheck the reliability of methotrexate ( MTX) serum concentration at 48 h ( C48 h ) in predicting the pharmacokinetic characteristics and toxic reactions at terminal elimination phase after high dose MTX infusion and to provide a reference for determination of rational rescue regimen in clinic practice. Methods In total,114 cases of children with acute lymphoblastic leukemia (ALL) received 176 courses of high dose MTX chemotherapy treatment. The regimen was continuous infusion of MTX[3 -5 g·( m2 ) -1 ] in 24 h. Plasma samples were treated with solid phase extraction and serum concentrations of MTX were determined by HPLC at 24,48 and 72 h (C24 h ,C48 h and C72 h ) after starting MTX infusion. All data were divided into C48 h≥1 μmol·L-1 group and C48 h<1 μmol·L-1 group. The pharmacokinetic parameters of the two groups at elimination phase were estimated by residual method and the toxic reactions after MTX infusion of two groups were compared by Ridit analysis. Results The C72 h and AUC48-∞ were significantly higher in C48 h ≥1 μmol · L-1 group than in C48 h <1 μmol·L-1 group (P<0. 01). The MTX toxicities to the blood,digestive and hepatic systems were significantly higher in C48 h≥1 μmol·L-1 group than in C48 h < 1 μmol · L-1 group ( P < 0. 05). Conclusion C48 h can predict the pharmacokinetic characteristics and toxic reactions at ther terminal elimination phase. Therefore,C48 h≥1 μmol·L-1 can be used as a marker of MTX elimination delay event to guide later rescue regimen.

Comparison of sequence diversity in genotype Ⅱ and Ⅲ hepatitis C virus(HCV) hypervariable region 1(HVR1) in Chinese / 第二军医大学学报

Objective: To compare the sequence diversity of HVR1 in the putative envelope protein E2 of the genotypeⅡand genotype Ⅲ HCV in Chinese. Methods: The cDNAs[nucleotide(nt)1449-1586(HCV-J) or nt1460-1582(HCV-J6)] derived from plasma of 55 patients infected with genotype Ⅱ HCV and 38 patients infected with genotype Ⅲ HCV were amplified,purified and directly sequenced by RT-nested polymerase chain reaction(PCR) and dideoxynucleotide chain termination method. Results: The HVR1 was found in amino acid(aa) 384-408 positions of both types HCV E2 protein. There were 5 similar conserved amino acids in 2 types HCV HVR1:aa385(Thr), aa389, 390, 406(Gly)and aa403(Phe).Besides, 401(Ser) was also highly conserved in genotype Ⅱ HCV HVR1. Although the variation characteristic of 2 types was similar, but the sequence diversity(SD),the kinds and frequency of some amino acids in some HVR1 positions and the conserved region near the HVR1 had some differences between 2 genotypes. Conclusion: Further study on the diversity of HVR1 and its biological significance will be helpful to understand the mechanism of HCV persistent infection and the development of HCV vaccine.