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AIM: To provide reference for clinical application of warfarin PPK/PD model, the prediction accuracy of warfarin PPK/PD model and 6 dose models established by multiple linear regression were compared. METHODS: Clinical data of inpatients who took warfarin tablets for oral anticoagulant therapy in our hospital were collected, and the predictive values were simulated by PPK/PD model and other 6 models, respectively. SPSS 23.0 software was used for paired t-test of measured value and predicted value. MAE and percentage of prediction deviation were used to evaluate the results, and the prediction deviation box-plot was drawn to compare the total data, different dose groups and different genotypes. RESULTS: A total of 50 patients were included in the study. Among 7 models, only PPK/PD model, Wen et al., and Du Liping et al.'s model had no statistical difference in predicted values and measured values (P>0.05). The prediction accuracy of PPK/PD model was higher among the total data, low and medium doses, and patients with different genotypes.The prediction accuracy of Wen et al. 's model and Li Chuanbao et al.'s model was higher in the high-dose group. CONCLUSION: The PPK/PD model of warfarin has good clinical prediction performance, which is expected to provide reference for accurate administration of warfarin.
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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.
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AIM: To investigate the correlations of genetic polymorphisms, infliximab(IFX) serum trough concentration, immunogenicity and clinical outcome in patients with Crohn's disease(CD) to provide reference for optimizing IFX treatment in CD patients. METHODS: The clinical data of CD patients treated with IFX in our hospital from September 2017 to September 2019 were prospectively collected. The genotypes TNF-α-308, TNF-α-238, TNF-α-857, TNFRSF1B, ABCB1, FCGR3A were detected by targeted sequencing using multiple PCR combined with high throughput sequencing before administration. The IFX steady-state concentration was determined by ELISA. SPSS 20.0 software was used for statistical analysis and ROC curve was drawn for clinical efficacy and antibody threshold. RESULTS: A total of 111 patients were included in the study, the IFX trough concentration of patients with TNF-α-238GA was significantly lower than that of GG (0.55±0.52) vs. (1.75±1.46) μg/mL (P=0.003), while there was no significant difference in IFX trough concentration among TNF-α-308, TNF-α-857, TNFRSF1B, ABCB1, FCGR3 Agenotypes. Clinical response rate of TNFRSF1B (TG+GG) was significantly higher than that of the wild type (TT) (75.0% vs. 42.3%) (P=0.001), and there was no statistically significant difference in clinical efficacy among patients with different genotypes of other genes (P>0.05). The efficacy of IFX in the treatment of CD and the production of antibody to IFX were significantly correlated with maintenance trough concentration (P1.33 μg/mL had certain predictive significance for biological response, while ≤0.51 μg/mL can be used as a predictor of antibody production.
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Objective@#To explore the effect of early pulmonary rehabilitation on stroke associated pneumonia by the ICU specialist nurses.@*Methods@#Totally 40 cases of stroke patients from January 2017 to June 2017 were selected into the control group, and 44 cases of stroke patients from July 2017 to December 2017 were set as the intervention group. The patients in the control group were given routine care, and those in the experimental group were given early pulmonary rehabilitation in addition to routine care by ICU specialist nurses. The clinical outcome such as the occurrence of SAP, the length of intensive care units (ICU) stay and the duration of mechanical ventilation were compared.@*Results@#The incidence of SAP in the intervention group was 13.64%(6/44), significantly lower than that 32.50(13/40) in the control group (χ2=4.26, P<0. 05), and the length of ICU stay the duration of mechanical ventilation were (5.59±3.93), (3.2±0.84)days, which were lower than (8.50±7.89), ((13.13±9.58)days in the control group (t=2.106,2.678, P<0.05) , the prealbumin levels was (219.43±59.71) mg/L,higher than (192.20±54.85) mg/L in the control group (t=-2.170, P<0.05) , the difference was statistically significant.@*Conclusion@#Early pulmonary rehabilitation can effectively reduce the incidence of SAP and better clinical outcome. And we also should improve the SAP risk assessment and the management of swallowing and nutrition.
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Objective To explore the effect of early pulmonary rehabilitation on stroke associated pneumonia by the ICU specialist nurses. Methods Totally 40 cases of stroke patients from January 2017 to June 2017 were selected into the control group, and 44 cases of stroke patients from July 2017 to December 2017 were set as the intervention group. The patients in the control group were given routine care, and those in the experimental group were given early pulmonary rehabilitation in addition to routine care by ICU specialist nurses. The clinical outcome such as the occurrence of SAP, the length of intensive care units (ICU) stay and the duration of mechanical ventilation were compared. Results The incidence of SAP in the intervention group was 13.64% (6/44), significantly lower than that 32.50(13/40) in the control group ( χ2=4.26﹐P＜0. 05)﹐and the length of ICU stay the duration of mechanical ventilation were (5.59±3.93), (3.2±0.84)days﹐which were lower than (8.50±7.89),((13.13±9.58)days in the control group (t=2.106,2.678﹐P＜0.05), the prealbumin levels was(219.43±59.71)mg/L,higher than(192.20±54.85) mg/L in the control group(t=-2.170﹐P＜0.05), the difference was statistically significant. Conclusion Early pulmonary rehabilitation can effectively reduce the incidence of SAP and better clinical outcome. And we also should improve the SAP risk assessment and the management of swallowing and nutrition.
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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.