Development of software for individualizing dosage regimens of vancomycin based on population pharmacokinetics models / 中国临床药理学与治疗学

AIM: To develop software for individualizing dosage regimens of vancomycin (VCM) according to the established population pharmacokinetics (PPK) models. METHODS: VCM dosing software was developed using MyEclipse, SQL Server, and JRE. The software developing schemes included requirement analysis, general design, detailed design, software coding, software test, software maintenance and software redevelopment. RESULTS: The developed software achieved the functions such as input and management of patient information, prediction of trough concentrations under various dosing regimens which could help initial dosage design, and prediction of trough concentrations more accurately based on therapeutic drug monitoring results and Bayesian method which could help dosage adjustment. The software was utilized in the interpretation of VCM serum concentration, pharmacists proposed the suggestions for adjusting dosage regimens. The rechecked serum concentrations all reached the expected target blood concentration range in the group of adopting advice. CONCLUSION: The new developed software based on our established PPK models can provide a useful tool in the clinical setting to facilitate the individualized therapy for the adult and elderly infected patients.

The performance evaluation of unassayed biochemistry serum controls / 中华检验医学杂志

Objective@#To evaluate the inter-bottle variations, stability in consumption and interchangeability of unassayed biochemistry serum controls.@*Methods@#Comparison between unassayed serum controls from a domestic "Pretrol®" and an international "Bio-Rad" manufacturer was conducted in department of laboratory, in May 2016, with Roche Cobas 8000, Roche Hitachi 7600 and Siemens 2400 modular analyzer. The inter-bottle variation was determined by monitoring the inter-batch variation of 10 bottles of control samples after eliminating the intra-batch variation from the same bottle. Stability in consumption was determined as the precision after 7 days storage under 2 ℃ to 8 ℃ or 30 days of storage under -20 ℃ since reconstitution. The interchangeability was determined as the precisionbetween the controls from different manufacturers for the same test.@*Results@#The inter-bottle imprecision of controls from domestic manufacturer for 13 biochemistry tests (CV concentration 1/CV concentration 2) were potassium (0.26%/0.42%), sodium (0.26%/0.21%), phosphorus (0.00%/0.62%), cholesterol (0.56%/0.54%), total protein (0.52%/0.33%), albumin (0.44%/2.00%), alanine aminotransferase (1.72%/0.57%), γ-glutamylaminotransferase (0.52%/0.62%), aspartate aminotransferase (3.10%/1.09%), lactate dehydrogenase (0.76%/0.91%), alkaline phosphatase (1.13%/0.97%), amylase (0.30%/0.39%) and glucose (0.00%/0.40%). The stability in consumption of the controls from the domestic manufacturer (CV concentration 1/CV concentration 2 under 2 ℃ to 8 ℃storage; CV concentration 1/CV concentration 2 under -20 ℃ storage) were potassium (1.06%/0.36%; 0.74%/0.48%), sodium (0.49%/0.59%; 0.72%/0.65%), phosphorus (0.95%/0.80%; 1.43%/0.84%), cholesterol (1.49%/1.58%; 2.17%/1.80%), total protein (0.84%/0.75%; 1.60%/1.68%), albumin (1.33%/2.28%; 1.94%/2.43%), alanine aminotransferase (1.41%/0.51%; 3.24%/1.60%) γ-glutamylaminotransferase (1.16%/1.16%; 2.85%/2.49%), aspartate aminotransferase (4.37%/2.14%; 2.99%/1.31%), lactate dehydrogenase (2.70%/2.54%; 3.84%/2.97%), alkaline phosphatase (2.63%/1.96%; 2.31%/2.10%), amylase (0.95%/2.19%; 1.58%/1.38%) and glucose (0.60%/0.48%; 1.41%/1.55%). The Inter-bottle variation and stability in consumption of biochemistry test unassayed controls from the domestic manufacturer were compatible for clinical assay according to the CV% specification from the Clinical Biochemistry Test Quality Requirement (WS/T 403-2012). The imprecision of the controls from both the domestic and international manufacturers (CVp concentration 1/CVp concentration2; CVq concentration 1/CVq concentration 2) were potassium (0.52%/0.46%; 2.39%/0.47%), sodium (0.30%/0.17%; 0.81%/0.47%), phosphorus (2.72%/1.11%; 4.57%/2.07%), cholesterol (0.29%/1.38%; 2.94%/1.81%), total protein (0.66%/2.46%; 1.85%/2.54%), alkaline phosphatase (2.67%/4.66%; 3.58%/8.55%), total bilirubin (5.71%/5.09%; 9.55%/7.41%), albumin (1.10%/2.61%; 4.79%/1.93%), alanine aminotransferase (6.42%/1.25%; 5.74%/1.63%), γ-glutamylaminotransferase (2.27%/4.35%; 4.38%/0.74%), aspartate aminotransferase (0.56%/2.84%; 0.91%/2.11%) and lactate dehydrogenase (2.36%/2.47%; 3.10%/1.52%). The interchangeability of serum controls from domestic manufacturer was better than clinical serum samples.@*Conclusion@#The unassayed serum biochemistry test controls from domestic manufacturer are suitable for the intra-laboratory quality control and showed a promising compatibility for inter-laboratory quality control usage.

The performance evaluation of unassayed biochemistry serum controls / 中华检验医学杂志

Objective To evaluate the inter-bottle variations, stability in consumption and interchangeability of unassayed biochemistry serum controls. Methods Comparison between unassayed serum controls from a domestic "Pretrol?" and an international "Bio-Rad" manufacturer was conducted in department of laboratory, in May 2016, with Roche Cobas 8000, Roche Hitachi 7600 and Siemens 2400 modular analyzer. The inter-bottle variation was determined by monitoring the inter-batch variation of 10 bottles of control samples after eliminating the intra-batch variation from the same bottle. Stability in consumption was determined as the precision after 7 days storage under 2℃ to 8℃ or 30 days of storage under -20 ℃ since reconstitution. The interchangeability was determined as the precisionbetween the controls from different manufacturers for the same test. Results The inter-bottle imprecision of controls from domestic manufacturer for 13 biochemistry tests (CV concentration 1/CV concentration 2) were potassium (0.26％/0.42％), sodium (0.26％/0.21％), phosphorus (0.00％/0.62％), cholesterol (0.56％/0.54％), total protein (0.52％/0.33％), albumin (0.44％/2.00％), alanine aminotransferase (1.72％/0.57％),γ-glutamylaminotransferase (0.52％/0.62％), aspartate aminotransferase (3.10％/1.09％), lactate dehydrogenase (0.76％/0.91％), alkaline phosphatase (1.13％/0.97％), amylase (0.30％/0.39％) and glucose (0.00％/0.40％). The stability in consumption of the controls from the domestic manufacturer (CV concentration 1/CV concentration 2 under 2℃to 8℃storage;CV concentration 1/CV concentration 2 under-20℃ storage) were potassium (1.06％/0.36％; 0.74％/0.48％), sodium (0.49％/0.59％; 0.72％/0.65％), phosphorus (0.95％/0.80％;1.43％/0.84％), cholesterol (1.49％/1.58％;2.17％/1.80％), total protein (0.84％/0.75％; 1.60％/1.68％), albumin (1.33％/2.28％; 1.94％/2.43％), alanine aminotransferase (1.41％/0.51％;3.24％/1.60％) γ-glutamylaminotransferase (1.16％/1.16％; 2.85％/2.49％), aspartate aminotransferase (4.37％/2.14％; 2.99％/1.31％), lactate dehydrogenase (2.70％/2.54％; 3.84％/2.97％), alkaline phosphatase (2.63％/1.96％; 2.31％/2.10％), amylase (0.95％/2.19％; 1.58％/1.38％) and glucose (0.60％/0.48％; 1.41％/1.55％). The Inter-bottle variation and stability in consumption of biochemistry test unassayed controls from the domestic manufacturer were compatible for clinical assay according to the CV％ specification from the Clinical Biochemistry Test Quality Requirement (WS/T 403-2012). The imprecision of the controls from both the domestic and international manufacturers (CVp concentration 1/CVp concentration2;CVq concentration 1/CVq concentration 2) were potassium (0.52％/0.46％; 2.39％/0.47％), sodium (0.30％/0.17％; 0.81％/0.47％), phosphorus (2.72％/1.11％;4.57％/2.07％), cholesterol (0.29％/1.38％;2.94％/1.81％), total protein (0.66％/2.46％;1.85％/2.54％), alkaline phosphatase (2.67％/4.66％;3.58％/8.55％), total bilirubin (5.71％/5.09％; 9.55％/7.41％), albumin (1.10％/2.61％; 4.79％/1.93％), alanine aminotransferase (6.42％/1.25％;5.74％/1.63％), γ-glutamylaminotransferase (2.27％/4.35％; 4.38％/0.74％), aspartate aminotransferase (0.56％/2.84％; 0.91％/2.11％) and lactate dehydrogenase (2.36％/2.47％; 3.10％/1.52％). The interchangeability of serum controls from domestic manufacturer was better than clinical serum samples. Conclusion The unassayed serum biochemistry test controls from domestic manufacturer are suitable for the intra-laboratory quality control and showed a promising compatibility for inter-laboratory quality control usage .

Meta-analysis of the Therapeutic Efficacy of Sodium Hyaluronate Combined with Compound Betamethasone versus Sodium Hyaluronate in the Treatment of Knee Osteoarthritis / 中国药房

OBJECTIVE： To systematically evaluate therapeutic efficacy of sodium hyaluronate combined with Compound betamethasone versus sodium hyaluronate in the treatment of knee osteoarthritis （KOA）， and to provide evidence-based reference for clinical drug use. METHODS： Randomized controlled clinical trials （RCTs） about sodium hyaluronate combined with Compound betamethasone （observation group） versus sodium hyaluronate （control group） in the treatment of KOA were collected from Cochrane Library， PubMed， Embase， Web of Science， CNKI， Wanfang database and Baidu academics database， etc. By literature screening， data extraction and quality evaluation of included literatures with Jadad scale， Meta-analysis was carried out by using Rev Man 5.3 software. RESULTS： Totally 24 RCTs were included， involving 2 929 patients. Meta-analysis showed that total response rate [OR＝5.33， 95％CI（3.85， 7.38）， P＜0.000 01]， knee joint score of American Special Surgical Hospital [SMD＝1.63， 95％CI（1.32， 1.93）， P＜0.000 01]， knee function score [SMD＝1.22， 95％CI（0.84， 1.59）， P＜0.000 01] of the observation group were significantly higher than those of the control group； visual analogue score was significantly lower than that of control group [SMD＝－1.44， 95％CI（－1.76，－1.11）， P＜0.000 01].  CONCLUSIONS： In the treatment of KOA， therapeutic efficacy of sodium hyaluronate combined with Compound betamethasone is significantly better than sodium hyaluronate， and it can significantly improve knee function.

A correlation study of necrotizing enterocolitis and encephalopathy of prematurity in premature infants with gestational age ＜ 32 weeks / 中国新生儿科杂志

Objective To study the correlation of necrotizing enterocolitis (NEC) and encephalopathy of prematurity (EOP) in premature infants with gestational age (GA) ＜ 32 weeks.Method From January 2009 to December 2014,clinical data of preterm infants (GA ＜ 32 weeks) admitted to department of neonatology of Children's Hospital of Fudan University and received brain magnetic resonance imaging (MRI) at corrected GA of full term or near full term were collected.NEC patients were assigned into the NEC group.At the same time,patients with similar GA and birth weight without NEC were assigned into the control group.The incidence and MRI characteristics of EOP were studied using Chi-square method.Result A total of312 preterm infants were included in our study,104 in the NEC group,and 208 in the control group.The incidence of EOP in the NEC group was higher than the control group (27.9％ vs.17.3％).The difference between the two groups were statistically significant (P =0.030).The incidence of non-cystic EOP in the NEC group was significantly higher than the control group (89.7％ vs.63.9％,P =0.017).Conclusion NEC and EOP may be correlated in preterm infants with GA ＜32 weeks.Most of EOP were non-cystic injury.

Formulation and Analysis of Individualized Treatment Plan for a Patient with Cardiogenic Ischemic Stroke / 中国药房

OBJECTIVE:To provide reference for the formulation of individualized treatment plan for patients with cardiogenic ischemic stroke. METHODS:For a patient with cardiogenic ischemic stroke,clinical pharmacists adjusted lipid-lowering scheme according to disease progress combined with treatment principle of ischemic stroke and cardiogenic ischemic stroke;recommended second-level prevention and assisted physicians to adjust anti-infective plan according to individual situation of patient. When patients suffered from liver dysfunction,it was recommended to stop using drugs that may cause liver dysfunction,detect renal function damage early,analyze renal function impairment caused by insufficient fluid circulation,timely supplement fluid and provide whole-process pharmaceutical care in respects of anticoagulation, lipid-lowering and anti infection treatment, etc. RESULTS:Physician adopted the recommend of pharmacists and they formulated individualized treatment plan for cardiogenic ischemic stroke patients together;liver and kidney function recovered,and the condition of patient was improved. INR control (1.8)was better at discharge,and discharged education was provided for the patients at the same time. CONCLUSIONS:Clinical pharmacists participate in the treatment for the patient with cardiogenic ischemic stroke and assist physicians to optimize treatment plan according to disease condition. When ADR occurs,timely adjustment of treatment plan ensures the safety and effectiveness of patient medication.

Practice of pharmacy consultation on dosage regimen for pediatric epilepsy patient with PPK model / 药学实践杂志

Objective In order to provide a reference for optimizing the dosage regimen of carbamazepine and valproate in pediatric epilepsy patients .Methods Pharmacist consulted one pediatric epilepsy patient with traumatic brain injury for post operation epilepsy treatments .The abnormal plasma concentration of carbamazepine and valproic acid was analyzed with the population pharmacokinetic (PPK) model built by this team .New medication regimen was proposed and the predictive capabili-ty of this model was evaluated .Results Seizures in this patient have been effectively controlled .Conclusion Pharmacist can optimize the antiepileptic drug treatment with PPK model and achieve rational drug use clinically .

Comparison of accuracy of Marsh model versus Schnider model for propofol target-controlled infu-sion system / 中华麻醉学杂志

Objective To compare the accuracy of Marsh model and Schnider model for propofol target?controlled infusion ( TCI) system. Methods Eighty patients, aged 20-60 yr, of American Society of Anesthesiologists physical status ⅠorⅡ, with body mass index of 17?5-28?0 kg∕m2 , scheduled for e?lective gynecological operation under general anesthesia, were equally and randomly divided into either Marsh model group ( group M) or Schnider model group ( group S) using a random number table. The target plasma concentration was set at 3 μg∕ml in both groups. During TCI and at different time points after the end of TCI, the blood samples were collected for determination of blood propofol concentrations by high per?formance liquid chromatography with fluorescence detector. The difference between measured and predicted concentrations (△C) at each time point was calculated. The median performance error ( MDPE) , median absolute performance error ( MDAPE) , and wobble of propofol TCI system were calculated in each group. Results In M and S groups, the MDPE was 9. 90% and 14?00%, respectively; the MDAPE was 11?43% and 14?49%, respectively;the wobble was 7?77% and 7?79%, respectively. There was no sig?nificant difference in △C at each time point during TCI between group M and group S (P>0?05). After TCI was stopped, △C at each time point was significantly lower in group M than in group S ( P<0?05) . Conclusion Marsh model provides higher accuracy than Schnider model for propofol TCI system in the pa?tients undergoing gynecological operation.

Population pharmacokinetic/pharmacodynamic modeling of warfarin by nonlinear mixed effects model / 药学学报

The study aimed to establish a population pharmacokinetic/pharmacodynamic (PPK/PD) model of warfarin. PCR-RFLP technique was used to genotype the CYP2C9 and VKORC1 polymorphisms of 73 patients. RP-HPLC-UV method was used to determine the 190 plasma concentrations of warfarin. Application of NONMEM, the clinical information and 263 international normalized ratio (INR) monitoring data were used to investigate the effect of genetic, physiological, pathological factors, other medication on clearance and anticoagulant response. The final model of warfarin PPK/PD was described as follows: CL = θCL · (WT/60)θWT · θCYP · eηCL (if CYP2C9*1/*1, θCYP = 1; if *1/*3, θCYP = 0.708); EC50 = θEC50 · θVKOR · eηEC50 (if VKORC1- 1639AA, θVKOR = 1; if GA, θVKOR = 2.01; V = θV; K(E0) = θK(E0); Emax = θEmax; E0 = θE0 · eηE0. Among them, the body weight (WT), CYP2C9 and VKORC1 genotype had conspicuous effect on warfarin PK/PD parameters. The goodness diagnosis, Bootstrap, NPDE verification showed that the final model was stable, effective and predictable. It may provide a reference for opitimizing the dose regimen of warfarin.

Detection of cadmium by a double-promoters based Escherichia coli biosensor / 生物工程学报

To detect cadmium ions, we constructed a specific microbial sensor and screened detecting cassettes and different fluorescence proteins. Blue fluorescence protein mTagBFP2 was selected as a reporter and a double-promoters model was used in the construction of the fusion reporter vector Pmer::merR-m-Pmer::mTagBFP2-pMD19-T. The reporter vector was then transformed into Escherichia coli MC4100 wild type strain. The medium, incubation time, initial density for induction, and the optimal detection range were determined. The specificity of the biosensor was also checked. The biosensor responded specifically to cadmium irons with low background, and the linear concentration range detection ranged from 0.1 to 75 μmol/L at the initial OD600 = 0.1 with 2 h incubation in IHMM medium. Thus we successfully constructed a specific biosensor to detect cadmium irons and provided useful strategies for development and optimization of microbial sensors to detect heavy metals.

Changes in alveolar bone height due to retraction of anterior teeth in adult patients / 实用口腔医学杂志

Objective:To investigate the alveolar bone height change before and after retraction of anterior teeth in adult patients. Methods:A total of 15 adult patients with angle class I bimaxillary protrusion had 4 first premolars extracted followed by othodontic treatment for retraction of anterior teeth with straight arch wire techniques.Cone beam computed tomography(CBCT)scans were made before and 3 months after retraction.The labial and the lingual alveolar bone height around central and lateral incisors was measured and analyzed before and after treatment.Results:Significant increase of labial alveolar bone height around anterior teeth was found in both maxilla and mandible(P ＜0.05),however,lingual alveolar bone height was decreased(P ＜0.05).Conclusion:For bimaxillary protrusion patients,the lingual alveolar bone height decreased due to obvious incisors retraction in adults which should be considered carefully in orthodontic clinic.

Population pharmacokinetic modeling of flurbiprofen / 药学学报

The paper is to report the establishment of a population pharmacokinetic model for flurbiprofen (FP), an active metabolite of flurbiprofen axetil (FA). 246 FP serum concentration and clinical data were perspectively collected from 23 general anaesthesia patients receiving FA intravenously before operation in Dentofacial Surgery and Otorhinolaryngology Department of the First Affiliated Hospital of Fujian Medical University. Population pharmacokinetic data analysis was performed using NONMEM software. The measure of Bootstrap was applied for internal validation, while Visual Predictive check was adopted for external validation. The data of FP correspond with two-compartment model. The body weight (WT) had conspicuous effect on clearance and volume of central compartment, while sex, age and daily dose of administration had no marked effect on pharmacokinetic parameter of FP. The basic model was described as follows: CL (L x h(-1)) = 1.28x EXP(ETA(1)), V1 (L) = 5.03x EXP(ETA(2)), Q (L x h(-1)) = 8.5 x EXP(ETA(3)), V2 (L) = 4.39 x EXP(ETA(4)). The final model was described as follows: CL (L x h(-1)) = 1.32 x (WT/60) x EXP(ETA(1)), V1 (L) = 5.23 x (WT/60) x EXP(ETA(2)), Q (L x h(-1)) = 8.45 x EXP(ETA(3)), V2 (L) = 4.37 x EXP(ETA(4)). The population typical value of CL, V1, Q and V2 were: 1.32 L x h(-1), 5.23 L, 8.45 L x h(-1) and 4.37 L, respectively. Bootstrap and visual predictive check show that the final model of FP is stable, effective and predictable. A novel population pharmacokinetic model is developed to estimate the individual pharmacokinetic parameter for patients intravenous injecting FA in terms of patients' characteristics and dosing history, and to design a prior dosage regimen.

Construction and evaluation of the technology course of biological light microscopic sample / 中华医学教育探索杂志

We set up the technology course of biological light microscopic sample according to medical postgraduates’desire of urgent need to know the principles,procedures and application of the course. This article described the setting and organization of this course for postgraduates in Nantong University,and some experiences about the planning content of courses,the teaching management and the training of the research competence of students were introduced separately.

Study of adhesive characteristics of two kinds of orthodontical light-curing adhesive agents / 实用口腔医学杂志

Objective: To investigate the adhesive characteristics of two kinds of light-curing resin that was used to bond teeth and orthodontics brackets. Methods: A total of 60 premolar teeth were randomly divided into six groups, and brackets were bonded according to the manufacturers' instructions. In group A1, A2 and A3, the teeth were prepared using 100 ml/L polyacrylic acid, and the brackets were bonded using Fuji Ortho LC. In group B1, B2 and B3, the teeth were using self-etching primer, and the brackets were bonded using Transbond Plus Self Etching Primer (TPSEP). After 30 min and 24 h under room temperature and received cold-heat cycle treatment respectively, bond strength was measured using a testing instrument (2000S, Lloyds Instruments, Fareham, England) at a speed of 1 mm/min, and the residual adhesive was quantified using a stereomicroscope. The adhesive interface was observed by scanning electron microscope. Results: The bond shear strength of TPSEP and Ortho Glass LC are more than 5 MPa. The bond shear strength of TPSEP is stronger than that of Ortho Glass LC after 24 h. However,The adhesive remnant index (ARI)of TPSEP is higher than that of Ortho Glass LC. Conclusion: Transbond Plus Self Etching Primer and Ortho Glass LC can satisfy the clinic need of orthodontics.