BACKGROUND Perioperative anesthesia management of obese patients presents significant challenges as traditional total body weight-based dosing fails to achieve optimal anesthetic effects due to altered pharmacokinetic...BACKGROUND Perioperative anesthesia management of obese patients presents significant challenges as traditional total body weight-based dosing fails to achieve optimal anesthetic effects due to altered pharmacokinetic characteristics including abnormal drug distribution and clearance.Rocuronium exhibits markedly different distribution patterns in obese patients,with conventional weight correction methods inadequately addressing individual muscle mass variations that critically influence drug distribution.AIM To investigate the quantitative relationship between skeletal muscle index(SMI)and rocuronium distribution volume in obese colorectal cancer patients,establish a population pharmacokinetic model,and develop individualized dosing strategies based on muscle mass.METHODS A retrospective cohort study was conducted,including 100 obese patients(body mass index≥30 kg/m^(2))who underwent elective radical colorectal cancer surgery at our hospital from June 2023 to January 2025.Skeletal muscle mass was measured using InBody 260 body composition analyzer and SMI was calculated to assess muscle mass,with male SMI<7.0 kg/m^(2) and female SMI<5.7 kg/m^(2)as diagnostic criteria for sarcopenia.Plasma rocuronium concentrations were detected by liquid chromatography-tandem mass spectrometry/mass spectrometry,and nonlinear mixed-effect modeling was used to establish population pharmacokinetic modeling.Stepwise regression was used to screen covariates,and dosing regimens were optimized through Monte Carlo simulation.The primary endpoint was targeted plasma concentration achievement rate,and the secondary endpoint was postoperative residual muscle relaxation incidence.RESULTS Among 100 patients,35(35.0%)had sarcopenia and 65(65.0%)did not.Patients in the sarcopenia group were older(64.1±9.8 years vs 54.2±10.9 years,P<0.001)and had significantly lower SMI(6.2±0.8 kg/m^(2)vs 8.4±1.2 kg/m^(2),P<0.001).SMI showed strong positive correlation with rocuronium steady-state distribution volume(r=0.718,P<0.001)and moderate negative correlation with clearance(r=-0.502,P<0.001).A two-compartment population pharmacokinetic model was successfully established,with SMI being the most important covariate affecting central compartment distribution volume(△OFV=-41.2,P<0.001).Model validation showed bootstrap successful convergence rate of 92.3%,and 92.1%of observed values fell within prediction intervals in predicted concentration versus predicted concentration.The SMI-based individualized dosing regimen improved target exposure achievement rate from 82.0%in traditional regimen to 93.5%(P=0.009),and reduced postoperative residual muscle relaxation incidence from 13.0%to 3.5%(P=0.018).The sarcopenia group showed the most significant improvement in achievement rate,from 71.4%to 93.8%(P=0.017).CONCLUSION SMI shows strong correlation with rocuronium distribution volume in obese colorectal cancer patients and is a key factor affecting drug distribution.SMI-based individualized dosing strategies can significantly improve target exposure achievement rate and reduce postoperative residual muscle relaxation incidence,providing scientific evidence for precision anesthesia management in obese patients.展开更多
Objective:Methotrexate(MTX)can be safely administered to most patients but may cause severe toxicity in others.This study aimed to summarize the characteristics of high-dose methotrexate(HD-MTX)chemotherapy and to eva...Objective:Methotrexate(MTX)can be safely administered to most patients but may cause severe toxicity in others.This study aimed to summarize the characteristics of high-dose methotrexate(HD-MTX)chemotherapy and to evaluate whether the modified dose-adjustment program was able to improve the maintenance of sufficient MTX exposure levels while minimizing toxicities.Methods:We evaluated 1172 cycles of high-dose MTX chemotherapy from 294 patients who were treated according to the CCCG-ALL-2015 protocol(clinical trial number:ChiCTR-IPR-14005706)and analyzed the data of actual MTX dosage,MTX concentration,toxicity,and prognosis.We compared data between the dose-adjustment Program 1(fixed 20%reduction in dose)and the dose-adjustment Program 2(dose-individualization based on reassessment of the creatine clearance rate and the MTX concentration-monitoring point at 16 h),which were applied if the MTX clearance was delayed in the previous cycle.Results:The patients who used Program 2 had higher actual MTX infusion doses and infusion rates and were able to better maintain the MTX concentration at 44 h at the established target value than those on Program 1(P<0.001).No significant differences in toxicities were found between these two programs except that abnormal serum potassium levels and prolonged myelosuppression in intermediate-risk/high-risk patients were more frequently observed in patients using Program 2(P<0.001).No significant correlations were observed between the MTX dose,dose-adjustment programs,or MTX concentrations and relapse-free survival.Conclusion:Adjusting the MTX dose using Program 2 is more efficient for maintaining sufficient MTX exposure without significantly increasing the toxicity.展开更多
Objective To develop an individual noise exposure dose estimation model based on spatial distribution of noise in order to provide reference for occupational health management and hearing loss risk assessment caused b...Objective To develop an individual noise exposure dose estimation model based on spatial distribution of noise in order to provide reference for occupational health management and hearing loss risk assessment caused by noise in workplace.Methods From July 2018 to October 2019,10 noise-exposed positions and 48 employees in 3 high-noise workplaces of a manufacturing enterprise in Sichuan Province were selected as the research subjects.Occupational health survey,fixed-point measurement of workplace noise and individual noise measurement were used to obtain noise intensity and employee exposure information.The mean noise intensity and the corresponding exposure time were weighed to estimate the individual noise exposure dose estimation model based on the spatial distribution of workplace noise,and the paired t-test was used to evaluate the accuracy of the individual noise exposure dose estimate(8 h equivalent sound level,Lex,8 h)based on the spatial distribution of workplace,noise and the measured value of individualnoise exposure dose.And the least square regression model was used to correct it.Results The daily noise exposure dose of 44(91.7%)of 48 workers in 10 types of work in 3 sites of the manufacturing enterprise exceeded the standard,and the maximum noise exposure intensity was up to 108.3 dB(A).The measured value of individual noise exposure dose was higher than Lex,s h,and the difference was statistically significant(P<0.001).The noise difference distribution was mostly positive and symmetrical(P=0.958).The measured noise exposure dose of 6 out of 10 work types in 3 sites was higher than Lex,8 h(all P<0.05),and there was a linear correlation between the measured dose and Lex.8 h(r=0.373,P<0.05).Considering the influence of systematic error and the construction,diagnosis and screening of adaptive assessment model,an individual noise exposure dose estimation model based on the spatial distribution of workplace noise was finally obtained:y=0.574x+45.250,where y was the measured value of individual noise exposure dose,x was Lex,s h value.Conclusion The high noise hazard in manufacturing industry is more serious,and the noise exposure assessment of single fixed-point detection is relatively rough.The individual noise exposure dose estimation model based on the spatial distribution of workplace noise has a certain role in the occupational health managementofworkplacenoise hazard in manufacturing industry.展开更多
文摘BACKGROUND Perioperative anesthesia management of obese patients presents significant challenges as traditional total body weight-based dosing fails to achieve optimal anesthetic effects due to altered pharmacokinetic characteristics including abnormal drug distribution and clearance.Rocuronium exhibits markedly different distribution patterns in obese patients,with conventional weight correction methods inadequately addressing individual muscle mass variations that critically influence drug distribution.AIM To investigate the quantitative relationship between skeletal muscle index(SMI)and rocuronium distribution volume in obese colorectal cancer patients,establish a population pharmacokinetic model,and develop individualized dosing strategies based on muscle mass.METHODS A retrospective cohort study was conducted,including 100 obese patients(body mass index≥30 kg/m^(2))who underwent elective radical colorectal cancer surgery at our hospital from June 2023 to January 2025.Skeletal muscle mass was measured using InBody 260 body composition analyzer and SMI was calculated to assess muscle mass,with male SMI<7.0 kg/m^(2) and female SMI<5.7 kg/m^(2)as diagnostic criteria for sarcopenia.Plasma rocuronium concentrations were detected by liquid chromatography-tandem mass spectrometry/mass spectrometry,and nonlinear mixed-effect modeling was used to establish population pharmacokinetic modeling.Stepwise regression was used to screen covariates,and dosing regimens were optimized through Monte Carlo simulation.The primary endpoint was targeted plasma concentration achievement rate,and the secondary endpoint was postoperative residual muscle relaxation incidence.RESULTS Among 100 patients,35(35.0%)had sarcopenia and 65(65.0%)did not.Patients in the sarcopenia group were older(64.1±9.8 years vs 54.2±10.9 years,P<0.001)and had significantly lower SMI(6.2±0.8 kg/m^(2)vs 8.4±1.2 kg/m^(2),P<0.001).SMI showed strong positive correlation with rocuronium steady-state distribution volume(r=0.718,P<0.001)and moderate negative correlation with clearance(r=-0.502,P<0.001).A two-compartment population pharmacokinetic model was successfully established,with SMI being the most important covariate affecting central compartment distribution volume(△OFV=-41.2,P<0.001).Model validation showed bootstrap successful convergence rate of 92.3%,and 92.1%of observed values fell within prediction intervals in predicted concentration versus predicted concentration.The SMI-based individualized dosing regimen improved target exposure achievement rate from 82.0%in traditional regimen to 93.5%(P=0.009),and reduced postoperative residual muscle relaxation incidence from 13.0%to 3.5%(P=0.018).The sarcopenia group showed the most significant improvement in achievement rate,from 71.4%to 93.8%(P=0.017).CONCLUSION SMI shows strong correlation with rocuronium distribution volume in obese colorectal cancer patients and is a key factor affecting drug distribution.SMI-based individualized dosing strategies can significantly improve target exposure achievement rate and reduce postoperative residual muscle relaxation incidence,providing scientific evidence for precision anesthesia management in obese patients.
基金supported by the National Natural Science Foundation of China(No.81700147 and No.82070172).
文摘Objective:Methotrexate(MTX)can be safely administered to most patients but may cause severe toxicity in others.This study aimed to summarize the characteristics of high-dose methotrexate(HD-MTX)chemotherapy and to evaluate whether the modified dose-adjustment program was able to improve the maintenance of sufficient MTX exposure levels while minimizing toxicities.Methods:We evaluated 1172 cycles of high-dose MTX chemotherapy from 294 patients who were treated according to the CCCG-ALL-2015 protocol(clinical trial number:ChiCTR-IPR-14005706)and analyzed the data of actual MTX dosage,MTX concentration,toxicity,and prognosis.We compared data between the dose-adjustment Program 1(fixed 20%reduction in dose)and the dose-adjustment Program 2(dose-individualization based on reassessment of the creatine clearance rate and the MTX concentration-monitoring point at 16 h),which were applied if the MTX clearance was delayed in the previous cycle.Results:The patients who used Program 2 had higher actual MTX infusion doses and infusion rates and were able to better maintain the MTX concentration at 44 h at the established target value than those on Program 1(P<0.001).No significant differences in toxicities were found between these two programs except that abnormal serum potassium levels and prolonged myelosuppression in intermediate-risk/high-risk patients were more frequently observed in patients using Program 2(P<0.001).No significant correlations were observed between the MTX dose,dose-adjustment programs,or MTX concentrations and relapse-free survival.Conclusion:Adjusting the MTX dose using Program 2 is more efficient for maintaining sufficient MTX exposure without significantly increasing the toxicity.
文摘Objective To develop an individual noise exposure dose estimation model based on spatial distribution of noise in order to provide reference for occupational health management and hearing loss risk assessment caused by noise in workplace.Methods From July 2018 to October 2019,10 noise-exposed positions and 48 employees in 3 high-noise workplaces of a manufacturing enterprise in Sichuan Province were selected as the research subjects.Occupational health survey,fixed-point measurement of workplace noise and individual noise measurement were used to obtain noise intensity and employee exposure information.The mean noise intensity and the corresponding exposure time were weighed to estimate the individual noise exposure dose estimation model based on the spatial distribution of workplace noise,and the paired t-test was used to evaluate the accuracy of the individual noise exposure dose estimate(8 h equivalent sound level,Lex,8 h)based on the spatial distribution of workplace,noise and the measured value of individualnoise exposure dose.And the least square regression model was used to correct it.Results The daily noise exposure dose of 44(91.7%)of 48 workers in 10 types of work in 3 sites of the manufacturing enterprise exceeded the standard,and the maximum noise exposure intensity was up to 108.3 dB(A).The measured value of individual noise exposure dose was higher than Lex,s h,and the difference was statistically significant(P<0.001).The noise difference distribution was mostly positive and symmetrical(P=0.958).The measured noise exposure dose of 6 out of 10 work types in 3 sites was higher than Lex,8 h(all P<0.05),and there was a linear correlation between the measured dose and Lex.8 h(r=0.373,P<0.05).Considering the influence of systematic error and the construction,diagnosis and screening of adaptive assessment model,an individual noise exposure dose estimation model based on the spatial distribution of workplace noise was finally obtained:y=0.574x+45.250,where y was the measured value of individual noise exposure dose,x was Lex,s h value.Conclusion The high noise hazard in manufacturing industry is more serious,and the noise exposure assessment of single fixed-point detection is relatively rough.The individual noise exposure dose estimation model based on the spatial distribution of workplace noise has a certain role in the occupational health managementofworkplacenoise hazard in manufacturing industry.
