In China,operational in-situ marine monitoring is the primary means of directly obtaining hydrological,meteorological,and oceanographic environmental parameters across sea areas,and it is essential for applications su...In China,operational in-situ marine monitoring is the primary means of directly obtaining hydrological,meteorological,and oceanographic environmental parameters across sea areas,and it is essential for applications such as forecast of marine environment,prevention and mitigation of disaster,exploitation of marine resources,marine environmental protection,and management of transportation safety.In this paper,we summarise the composition,development courses,and present operational status of three systems of operational in-situ marine monitoring,namely coastal marine automated network station,ocean data buoy and voluntary observing ship measuring and reporting system.Additionally,we discuss the technical development in these in-situ systems and achievements in the key generic technologies along with future development trends.展开更多
BACKGROUND With the widespread use of antimicrobial drugs,bacterial resistance has become a significant problem,posing a serious threat to public health.The prevalence of clinical infection strains in hospitals and th...BACKGROUND With the widespread use of antimicrobial drugs,bacterial resistance has become a significant problem,posing a serious threat to public health.The prevalence of clinical infection strains in hospitals and their drug sensitivities are key to the appropriate use of antibiotics in clinical practice.AIM To identify prevalent bacteria and their antibiotic resistance profiles in a hospital setting,thereby guiding effective antibiotic usage by clinicians.METHODS Specimens from across the institution were collected by the microbiology laboratory.The VITEK 2 compact fully automatic analyzer was used for bacterial identification and antibiotic sensitivity testing,and the WHONET5.6 software was utilized for statistical analysis.RESULTS A total of 12062 bacterial strains of key monitoring significance were detected.Staphylococcus aureus demonstrated widespread resistance to penicillin,but none of the strains were resistant to vancomycin or linezolid.Moreover,219 strains of methicillin-resistant coagulase-negative staphylococci and 110 strains of methicillin-resistant Staphylococcus aureus were detected.Enterococcus faecalis showed moderate resistance to the third-generation quinolones ciprofloxacin and levofloxacin,but its resistance to nitrofurantoin and tetracycline was low.Enterococcus faecium displayed significantly lower resistance to third-and fourthgeneration quinolones than Enterococcus faecalis.The resistance of two key monitoring strains,Escherichia coli and Klebsiella pneumoniae,to piperacillin/tazobactam was 5%-8%.However,none of the Escherichia coli and Klebsiella pneumoniae strains were resistant to meropenem.The resistance of Acinetobacter baumannii to piperacillin/sulbactam was nearly 90%.Nonetheless,the resistance to tigecycline was low,and Pseudomonas aeruginosa demonstrated minimal resistance in the antibiotic sensitivity test,maintaining a resistance of<10%to the cephalosporin antibiotics cefotetan and cefoperazone over the last 6 years.The resistance to amikacin remained at 0.2%over the past 3 years.CONCLUSION Our hospital’s overall antibiotic resistance rate was relatively stable from 2017 to 2022.The detection rates of key monitoring strains are reported quarterly and their resistance dynamics are monitored and communicated to the entire hospital,which can guide clinical antibiotic selection.展开更多
The spread of tuberculosis(TB),especially multidrug-resistant TB and extensively drug-resistant TB,has strongly motivated the research and development of new anti-TB drugs.New strategies to facilitate drug combination...The spread of tuberculosis(TB),especially multidrug-resistant TB and extensively drug-resistant TB,has strongly motivated the research and development of new anti-TB drugs.New strategies to facilitate drug combinations,including pharmacokinetics-guided dose optimization and toxicology studies of first-and second-line anti-TB drugs have also been introduced and recommended.Liquid chromatography-mass spectrometry(LC-MS)has arguably become the gold standard in the analysis of both endo-and exo-genous compounds.This technique has been applied successfully not only for therapeutic drug monitoring(TDM)but also for pharmacometabolomics analysis.TDM improves the effectiveness of treatment,reduces adverse drug reactions,and the likelihood of drug resistance development in TB patients by determining dosage regimens that produce concentrations within the therapeutic target window.Based on TDM,the dose would be optimized individually to achieve favorable outcomes.Pharmacometabolomics is essential in generating and validating hypotheses regarding the metabolism of anti-TB drugs,aiding in the discovery of potential biomarkers for TB diagnostics,treatment monitoring,and outcome evaluation.This article highlighted the current progresses in TDM of anti-TB drugs based on LC-MS bioassay in the last two decades.Besides,we discussed the advantages and disadvantages of this technique in practical use.The pressing need for non-invasive sampling approaches and stability studies of anti-TB drugs was highlighted.Lastly,we provided perspectives on the prospects of combining LC-MS-based TDM and pharmacometabolomics with other advanced strategies(pharmacometrics,drug and vaccine developments,machine learning/artificial intelligence,among others)to encapsulate in an all-inclusive approach to improve treatment outcomes of TB patients.展开更多
BACKGROUND The efficacy and safety of anti-tumor necrosis factor-α(TNF-α)monoclonal antibody therapy[adalimumab(ADA)and infliximab(IFX)]with therapeutic drug monitoring(TDM),which has been proposed for inflammatory ...BACKGROUND The efficacy and safety of anti-tumor necrosis factor-α(TNF-α)monoclonal antibody therapy[adalimumab(ADA)and infliximab(IFX)]with therapeutic drug monitoring(TDM),which has been proposed for inflammatory bowel disease(IBD)patients,are still controversial.AIM To determine the efficacy and safety of anti-TNF-αmonoclonal antibody therapy with proactive TDM in patients with IBD and to determine which subtype of IBD patients is most suitable for proactive TDM interventions.METHODS As of July 2023,we searched for randomized controlled trials(RCTs)and observa-tional studies in PubMed,Embase,and the Cochrane Library to compare anti-TNF-αmonoclonal antibody therapy with proactive TDM with therapy with reactive TDM or empiric therapy.Pairwise and network meta-analyses were used to determine the IBD patient subtype that achieved clinical remission and to determine the need for surgery.RESULTS This systematic review and meta-analysis yielded 13 studies after exclusion,and the baseline indicators were balanced.We found a significant increase in the number of patients who achieved clinical remission in the ADA[odds ratio(OR)=1.416,95%confidence interval(CI):1.196-1.676]and RCT(OR=1.393,95%CI:1.182-1.641)subgroups and a significant decrease in the number of patients who needed surgery in the proactive vs reactive(OR=0.237,95%CI:0.101-0.558)and IFX+ADA(OR=0.137,95%CI:0.032-0.588)subgroups,and the overall risk of adverse events was reduced(OR=0.579,95%CI:0.391-0.858)according to the pairwise meta-analysis.Moreover,the network meta-analysis results suggested that patients with IBD treated with ADA(OR=1.39,95%CI:1.19-1.63)were more likely to undergo TDM,especially in comparison with patients with reactive TDM(OR=1.38,95%CI:1.07-1.77).CONCLUSION Proactive TDM is more suitable for IBD patients treated with ADA and has obvious advantages over reactive TDM.We recommend proactive TDM in IBD patients who are treated with ADA.展开更多
Background: Use of inappropriate amikacin dose is one of the most important factors in inducing toxicity, prolonged hospitalization as well as in increasing patient’s mortality. Objective: The aims of this study are ...Background: Use of inappropriate amikacin dose is one of the most important factors in inducing toxicity, prolonged hospitalization as well as in increasing patient’s mortality. Objective: The aims of this study are the analysis of amikacin dose, serum level and the examination of the effectiveness of the clinical pharmacologist (CP) therapeutic drug monitoring (TDM) intervention to guarantee the safety of amikacin use. Methods: This is a one-year retrospective observational chart review study, which evaluates amikacin dose, serum drug level, development of adverse effects in patients on amikacin with or without CP TDM consultation. Results: Amikacin was prescribed for 393 complex patients, with median age 83. Amikacin group (AG) included 140 (32%) courses with CP consultation (AG1) and 292 (68%) courses without CP consultation (AG2). The distribution of most study characteristics in both groups was similar including amikacin dose (9-10 mg/kg/day), renal failure (14%) and mortality (12%). Acceptance for CP consultation was in 46% of amikacin courses and dose changes were done in 63% after CP intervention. Prolonged antibiotic course (4.6 ± 1.5 vs 3.8 ± 1.6 days, p < 0.0001) and the patient’s hemodynamic instability (15% vs 7%, p = 0.01) were more frequent in the AG1 compared to the AG2. There was a strong association between CP consultation and prolonged hospitalization (p = 0.005), while no association between it and amikacin adverse effects, renal failure or mortality. Conclusions: There was no trend to reducing amikacin toxicity, days of hospitaliza tion or mortality in patients with CP consultation. CP TDM intervention was more in the management of complicated clinical situations. However, it is necessary to optimize it.展开更多
In this short review paper, the significant and profound impacts of the distorted key theory for developing peptide drugs have been briefly recalled with crystal clear convincingness.
The transmission loss of photons during quantum key distribution(QKD)process leads to the linear key rate bound for practical QKD systems without quantum repeaters.Phase matching quantum key distribution(PM-QKD)protoc...The transmission loss of photons during quantum key distribution(QKD)process leads to the linear key rate bound for practical QKD systems without quantum repeaters.Phase matching quantum key distribution(PM-QKD)protocol,an novel QKD protocol,can overcome the constraint with a measurement-device-independent structure,while it still requires the light source to be ideal.This assumption is not guaranteed in practice,leading to practical secure issues.In this paper,we propose a modified PM-QKD protocol with a light source monitoring,named PM-QKD-LSM protocol,which can guarantee the security of the system under the non-ideal source condition.The results show that our proposed protocol performs almost the same as the ideal PM-QKD protocol even considering the imperfect factors in practical systems.PMQKD-LSM protocol has a better performance with source fluctuation,and it is robust in symmetric or asymmetric cases.展开更多
Objective: To examine therapeutic drug monitoring in managing hyperbilirubinemia caused by capecitabine in patients with gastric adenocarcinoma with extensive liver metastases. Results: The initial liver function test...Objective: To examine therapeutic drug monitoring in managing hyperbilirubinemia caused by capecitabine in patients with gastric adenocarcinoma with extensive liver metastases. Results: The initial liver function tests showed an elevation of transaminases (aspartate amino transferase 615 UI/l, alanine aminotransferase 385.9 UI/l), hyperbilirubinemia (total bilirubin at 246.1 μmol/l), and alkaline phosphatase at 694.6 UI/l. We initiated capecitabine based combination chemotherapy, and the clinical pharmacist conducted a full-course medication monitoring of the patient’s treatment including design of individualized dosing regimens and monitoring of bilirubin, infection, cancer pain, parenteral nutrition support and adverse events. After 21 days of supervision by clinical pharmacist and clinicians, the patient’s bilirubin and transaminase decreased progressively, with aspartate aminotransferase, total bilirubin and alkaline phosphatase falling back to 57 UI/l, 69.8 μmol/l, 307.2 UI/l, respectively. The patient’s condition improved significantly at the time of discharge, with the jaundice subsided, and the bloating relieved. Conclusion: Due to adverse reactions, capecitabine requires medication monitoring during use. The relationship between effectiveness and adverse effects is controversial. Adverse reactions should not be the sole criterion for the use of drugs. Clinical pharmacists can improve the safety and effectiveness of patients’ medications and promote rational drug use by monitoring patients, which may be useful to help the doctors identify the high-risk patients for taking efficient treatment strategy decisions.展开更多
In vivo lung perfusion(IVLP)is a novel isolated lung technique developed to enable the local,in situ administration of high-dose chemotherapy to treat metastatic lung cancer.Combination therapy using folinic acid(FOL)...In vivo lung perfusion(IVLP)is a novel isolated lung technique developed to enable the local,in situ administration of high-dose chemotherapy to treat metastatic lung cancer.Combination therapy using folinic acid(FOL),5-fluorouracil(F),and oxaliplatin(OX)(FOLFOX)is routinely employed to treat several types of solid tumours in various tissues.However,F is characterized by large interpatient variability with respect to plasma concentration,which necessitates close monitoring during treatments using of this compound.Since plasma drug concentrations often do not reflect tissue drug concentrations,it is essential to utilize sample-preparation methods specifically suited to monitoring drug levels in target organs.In this work,in vivo solid-phase microextraction(in vivo SPME)is proposed as an effective tool for quantitative therapeutic drug monitoring of FOLFOX in porcine lungs during pre-clinical IVLP and intravenous(IV)trials.The concomitant extraction of other endogenous and exogenous small molecules from the lung and their detection via liquid chromatography coupled to high resolution mass spectrometry(LC-HRMS)enabled an assessment of FOLFOX's impact on the metabolomic profile of the lung and revealed the metabolic pathways associated with the route of administration(IVLP vs.IV)and the therapy itself.This study also shows that the immediate instrumental analysis of metabolomic samples is ideal,as long-term storage at80℃ results in changes in the metabolite content in the sample extracts.展开更多
A sensitive, accurate and robust Liquid Chromatography Tandem Mass Spectrometry method has been developed and validated to measure voriconazole trough levels in human plasma. The plasma samples were mixed with flucona...A sensitive, accurate and robust Liquid Chromatography Tandem Mass Spectrometry method has been developed and validated to measure voriconazole trough levels in human plasma. The plasma samples were mixed with fluconazole as an Internal Standard and directed to protein precipitation and drug extraction. An aliquot of 1 μl was injected into the chromatographic system and separated by the Acquity BEH C18 column at a flow rate of 0.30 ml/min in a gradient mobile phase consisting of acetonitrile, Ultrapure water (UPW), methanol and formic acid. Voriconazole was detected by a Triple Quadrupole Detector (TQD) operating on Multiple Reaction Monitoring (MRM) and a positive ion mode Electrospray ionization (ESI) Q1 mass: 350.1 m/z, Q3 mass: 281.1 m/z. Method linearity of the calibration curve (0.10 - 8.00 μg/ml) indicated a correlation coefficient r ≥ 0.99. The intra and inter-assay accuracy was within 85% - 115% and the intra and inter-assay precision was ≤5.76%. Voriconazole recovery percentage was between 97.69 - 119.62%. The method was successively applied in routine voriconazole TDM.展开更多
Objective:Voriconazole(VCZ)is a triazole antifungal agent widely used in immunocompromised patients with suspected or proven invasive fungal infections.The achievement of therapeutic range(1-5 mg/L)is essential to max...Objective:Voriconazole(VCZ)is a triazole antifungal agent widely used in immunocompromised patients with suspected or proven invasive fungal infections.The achievement of therapeutic range(1-5 mg/L)is essential to maximize VCZ efficacy,as its pharmacokinetics is characterized by a wide inter-and intra-individual variability.This study aims to quantify the variability of VCZ trough concentrations in children and adolescents with haematological diseases and optimize therapeutic drug monitoring in clinical practice.Methods:We analysed the monitoring concentrations of all children(<18 years old)treated with VCZ in the Haematology Department of Robert DebréHospital between January 2014 and December 2016.Demographic,clinical data,and VCZ dosing and monitoring concentrations measured by high-performance liquid chromatography with ultraviolet detection(HPLC-UV)were analysed.Non-parametric tests were performed using SPSS IBM 24.0.Results:380 trough VCZ concentrations at steady-state(Ctrough,ss)were available in 79 children:45.6%had first Ctrough,ss in the therapeutic range at first monitoring,46.8%had Ctrough,ss below 1 mg/L and 7.6%had Ctrough,ss over 5 mg/L.Forty-one patients were treated with recommended doses but only 53%of them reached the therapeutic range.There was no impact of age,sex,biological parameters,or indication of VCZ on Ctrough,ss values.The number of Ctrough,ss in the therapeutic range increases with the number of monitoring per patient following dosage adaptations.Conclusion:The wide inter-and intra-individual variability of VCZ trough concentrations at recommended doses confirm the need to standardize VCZ monitoring and identify factors to be considered to prospectively adapt treatment for each patient.展开更多
HIV and AIDS has continued to be a major public health concern, and hence one of the epidemics that the world resolved to end by 2030 as highlighted in sustainable development goals (SDGs). A colossal amount of effort...HIV and AIDS has continued to be a major public health concern, and hence one of the epidemics that the world resolved to end by 2030 as highlighted in sustainable development goals (SDGs). A colossal amount of effort has been taken to reduce new HIV infections, but there are still a significant number of new infections reported. HIV prevalence is more skewed towards the key population who include female sex workers (FSW), men who have sex with men (MSM), and people who inject drugs (PWID). The study design was retrospective and focused on key population enrolled in a comprehensive HIV and AIDS programme by the Kenya Red Cross Society from July 2019 to June 2021. Individuals who were either lost to follow up, defaulted (dropped out, transferred out, or relocated) or died were classified as attrition;while those who were active and alive by the end of the study were classified as retention. The study used density analysis to determine the spatial differences of key population attrition in the 19 targeted counties, and used Kilifi county as an example to map attrition cases in smaller administrative areas (sub-county level). The study used synthetic minority oversampling technique-nominal continuous (SMOTE-NC) to balance the datasets since the cases of attrition were much less than retention. The random survival forests model was then fitted to the balanced dataset. The model correctly identified attrition cases using the predicted ensemble mortality and their survival time using the estimated Kaplan-Meier survival function. The predictive performance of the model was strong and way better than random chance with concordance indices greater than 0.75.展开更多
基金The National Key Research and Development Program of China under contract No.2022YFC3104200the Key R&D Program of Shandong Province,China under contract No.2023ZLYS01+3 种基金the Consulting and Research Project of the Chinese Academy of Engineering under contract Nos 2022-XY-21,2022-DFZD-35,2023-XBZD-09 and 2021-XBZD-13the Major Innovation Special Project of Qilu University of Technology(Shandong Academy of Sciences),Science Education Industry Integration Pilot Project under contract No.2023HYZX01Special Funds for“Mount Taishan Scholars”Construction Projectthe Special Funds of Laoshan Laboratory.
文摘In China,operational in-situ marine monitoring is the primary means of directly obtaining hydrological,meteorological,and oceanographic environmental parameters across sea areas,and it is essential for applications such as forecast of marine environment,prevention and mitigation of disaster,exploitation of marine resources,marine environmental protection,and management of transportation safety.In this paper,we summarise the composition,development courses,and present operational status of three systems of operational in-situ marine monitoring,namely coastal marine automated network station,ocean data buoy and voluntary observing ship measuring and reporting system.Additionally,we discuss the technical development in these in-situ systems and achievements in the key generic technologies along with future development trends.
文摘BACKGROUND With the widespread use of antimicrobial drugs,bacterial resistance has become a significant problem,posing a serious threat to public health.The prevalence of clinical infection strains in hospitals and their drug sensitivities are key to the appropriate use of antibiotics in clinical practice.AIM To identify prevalent bacteria and their antibiotic resistance profiles in a hospital setting,thereby guiding effective antibiotic usage by clinicians.METHODS Specimens from across the institution were collected by the microbiology laboratory.The VITEK 2 compact fully automatic analyzer was used for bacterial identification and antibiotic sensitivity testing,and the WHONET5.6 software was utilized for statistical analysis.RESULTS A total of 12062 bacterial strains of key monitoring significance were detected.Staphylococcus aureus demonstrated widespread resistance to penicillin,but none of the strains were resistant to vancomycin or linezolid.Moreover,219 strains of methicillin-resistant coagulase-negative staphylococci and 110 strains of methicillin-resistant Staphylococcus aureus were detected.Enterococcus faecalis showed moderate resistance to the third-generation quinolones ciprofloxacin and levofloxacin,but its resistance to nitrofurantoin and tetracycline was low.Enterococcus faecium displayed significantly lower resistance to third-and fourthgeneration quinolones than Enterococcus faecalis.The resistance of two key monitoring strains,Escherichia coli and Klebsiella pneumoniae,to piperacillin/tazobactam was 5%-8%.However,none of the Escherichia coli and Klebsiella pneumoniae strains were resistant to meropenem.The resistance of Acinetobacter baumannii to piperacillin/sulbactam was nearly 90%.Nonetheless,the resistance to tigecycline was low,and Pseudomonas aeruginosa demonstrated minimal resistance in the antibiotic sensitivity test,maintaining a resistance of<10%to the cephalosporin antibiotics cefotetan and cefoperazone over the last 6 years.The resistance to amikacin remained at 0.2%over the past 3 years.CONCLUSION Our hospital’s overall antibiotic resistance rate was relatively stable from 2017 to 2022.The detection rates of key monitoring strains are reported quarterly and their resistance dynamics are monitored and communicated to the entire hospital,which can guide clinical antibiotic selection.
基金sponsored by the National Research Foundation of Korea(NRF)Grant funded by the Korean government(MSIT)(Grant No.:2018R1A5A2021242).
文摘The spread of tuberculosis(TB),especially multidrug-resistant TB and extensively drug-resistant TB,has strongly motivated the research and development of new anti-TB drugs.New strategies to facilitate drug combinations,including pharmacokinetics-guided dose optimization and toxicology studies of first-and second-line anti-TB drugs have also been introduced and recommended.Liquid chromatography-mass spectrometry(LC-MS)has arguably become the gold standard in the analysis of both endo-and exo-genous compounds.This technique has been applied successfully not only for therapeutic drug monitoring(TDM)but also for pharmacometabolomics analysis.TDM improves the effectiveness of treatment,reduces adverse drug reactions,and the likelihood of drug resistance development in TB patients by determining dosage regimens that produce concentrations within the therapeutic target window.Based on TDM,the dose would be optimized individually to achieve favorable outcomes.Pharmacometabolomics is essential in generating and validating hypotheses regarding the metabolism of anti-TB drugs,aiding in the discovery of potential biomarkers for TB diagnostics,treatment monitoring,and outcome evaluation.This article highlighted the current progresses in TDM of anti-TB drugs based on LC-MS bioassay in the last two decades.Besides,we discussed the advantages and disadvantages of this technique in practical use.The pressing need for non-invasive sampling approaches and stability studies of anti-TB drugs was highlighted.Lastly,we provided perspectives on the prospects of combining LC-MS-based TDM and pharmacometabolomics with other advanced strategies(pharmacometrics,drug and vaccine developments,machine learning/artificial intelligence,among others)to encapsulate in an all-inclusive approach to improve treatment outcomes of TB patients.
基金Supported by National College Students Innovation and Entrepreneurship Training Program of Shenyang Pharmaceutical University,No.202210163003.
文摘BACKGROUND The efficacy and safety of anti-tumor necrosis factor-α(TNF-α)monoclonal antibody therapy[adalimumab(ADA)and infliximab(IFX)]with therapeutic drug monitoring(TDM),which has been proposed for inflammatory bowel disease(IBD)patients,are still controversial.AIM To determine the efficacy and safety of anti-TNF-αmonoclonal antibody therapy with proactive TDM in patients with IBD and to determine which subtype of IBD patients is most suitable for proactive TDM interventions.METHODS As of July 2023,we searched for randomized controlled trials(RCTs)and observa-tional studies in PubMed,Embase,and the Cochrane Library to compare anti-TNF-αmonoclonal antibody therapy with proactive TDM with therapy with reactive TDM or empiric therapy.Pairwise and network meta-analyses were used to determine the IBD patient subtype that achieved clinical remission and to determine the need for surgery.RESULTS This systematic review and meta-analysis yielded 13 studies after exclusion,and the baseline indicators were balanced.We found a significant increase in the number of patients who achieved clinical remission in the ADA[odds ratio(OR)=1.416,95%confidence interval(CI):1.196-1.676]and RCT(OR=1.393,95%CI:1.182-1.641)subgroups and a significant decrease in the number of patients who needed surgery in the proactive vs reactive(OR=0.237,95%CI:0.101-0.558)and IFX+ADA(OR=0.137,95%CI:0.032-0.588)subgroups,and the overall risk of adverse events was reduced(OR=0.579,95%CI:0.391-0.858)according to the pairwise meta-analysis.Moreover,the network meta-analysis results suggested that patients with IBD treated with ADA(OR=1.39,95%CI:1.19-1.63)were more likely to undergo TDM,especially in comparison with patients with reactive TDM(OR=1.38,95%CI:1.07-1.77).CONCLUSION Proactive TDM is more suitable for IBD patients treated with ADA and has obvious advantages over reactive TDM.We recommend proactive TDM in IBD patients who are treated with ADA.
文摘Background: Use of inappropriate amikacin dose is one of the most important factors in inducing toxicity, prolonged hospitalization as well as in increasing patient’s mortality. Objective: The aims of this study are the analysis of amikacin dose, serum level and the examination of the effectiveness of the clinical pharmacologist (CP) therapeutic drug monitoring (TDM) intervention to guarantee the safety of amikacin use. Methods: This is a one-year retrospective observational chart review study, which evaluates amikacin dose, serum drug level, development of adverse effects in patients on amikacin with or without CP TDM consultation. Results: Amikacin was prescribed for 393 complex patients, with median age 83. Amikacin group (AG) included 140 (32%) courses with CP consultation (AG1) and 292 (68%) courses without CP consultation (AG2). The distribution of most study characteristics in both groups was similar including amikacin dose (9-10 mg/kg/day), renal failure (14%) and mortality (12%). Acceptance for CP consultation was in 46% of amikacin courses and dose changes were done in 63% after CP intervention. Prolonged antibiotic course (4.6 ± 1.5 vs 3.8 ± 1.6 days, p < 0.0001) and the patient’s hemodynamic instability (15% vs 7%, p = 0.01) were more frequent in the AG1 compared to the AG2. There was a strong association between CP consultation and prolonged hospitalization (p = 0.005), while no association between it and amikacin adverse effects, renal failure or mortality. Conclusions: There was no trend to reducing amikacin toxicity, days of hospitaliza tion or mortality in patients with CP consultation. CP TDM intervention was more in the management of complicated clinical situations. However, it is necessary to optimize it.
文摘In this short review paper, the significant and profound impacts of the distorted key theory for developing peptide drugs have been briefly recalled with crystal clear convincingness.
基金Project supported by the National Natural Science Foundation of China(Grant Nos.61871234 and 62001249)Open Research Fund Program of the State Key Laboratory of Low-Dimensional Quantum Physics,Tsinghua University(Grant No.KF201909)。
文摘The transmission loss of photons during quantum key distribution(QKD)process leads to the linear key rate bound for practical QKD systems without quantum repeaters.Phase matching quantum key distribution(PM-QKD)protocol,an novel QKD protocol,can overcome the constraint with a measurement-device-independent structure,while it still requires the light source to be ideal.This assumption is not guaranteed in practice,leading to practical secure issues.In this paper,we propose a modified PM-QKD protocol with a light source monitoring,named PM-QKD-LSM protocol,which can guarantee the security of the system under the non-ideal source condition.The results show that our proposed protocol performs almost the same as the ideal PM-QKD protocol even considering the imperfect factors in practical systems.PMQKD-LSM protocol has a better performance with source fluctuation,and it is robust in symmetric or asymmetric cases.
文摘Objective: To examine therapeutic drug monitoring in managing hyperbilirubinemia caused by capecitabine in patients with gastric adenocarcinoma with extensive liver metastases. Results: The initial liver function tests showed an elevation of transaminases (aspartate amino transferase 615 UI/l, alanine aminotransferase 385.9 UI/l), hyperbilirubinemia (total bilirubin at 246.1 μmol/l), and alkaline phosphatase at 694.6 UI/l. We initiated capecitabine based combination chemotherapy, and the clinical pharmacist conducted a full-course medication monitoring of the patient’s treatment including design of individualized dosing regimens and monitoring of bilirubin, infection, cancer pain, parenteral nutrition support and adverse events. After 21 days of supervision by clinical pharmacist and clinicians, the patient’s bilirubin and transaminase decreased progressively, with aspartate aminotransferase, total bilirubin and alkaline phosphatase falling back to 57 UI/l, 69.8 μmol/l, 307.2 UI/l, respectively. The patient’s condition improved significantly at the time of discharge, with the jaundice subsided, and the bloating relieved. Conclusion: Due to adverse reactions, capecitabine requires medication monitoring during use. The relationship between effectiveness and adverse effects is controversial. Adverse reactions should not be the sole criterion for the use of drugs. Clinical pharmacists can improve the safety and effectiveness of patients’ medications and promote rational drug use by monitoring patients, which may be useful to help the doctors identify the high-risk patients for taking efficient treatment strategy decisions.
基金Institutes of Health Research(CIHR)-Natural Sciences and Engineering Research Council(NSERC)of the Canada Collaborative Health Research Projects program for their financial support(Grant No.:355935)the Natural Sciences and Engineering Research Council of Canada Industrial Research Chair(IRC)program。
文摘In vivo lung perfusion(IVLP)is a novel isolated lung technique developed to enable the local,in situ administration of high-dose chemotherapy to treat metastatic lung cancer.Combination therapy using folinic acid(FOL),5-fluorouracil(F),and oxaliplatin(OX)(FOLFOX)is routinely employed to treat several types of solid tumours in various tissues.However,F is characterized by large interpatient variability with respect to plasma concentration,which necessitates close monitoring during treatments using of this compound.Since plasma drug concentrations often do not reflect tissue drug concentrations,it is essential to utilize sample-preparation methods specifically suited to monitoring drug levels in target organs.In this work,in vivo solid-phase microextraction(in vivo SPME)is proposed as an effective tool for quantitative therapeutic drug monitoring of FOLFOX in porcine lungs during pre-clinical IVLP and intravenous(IV)trials.The concomitant extraction of other endogenous and exogenous small molecules from the lung and their detection via liquid chromatography coupled to high resolution mass spectrometry(LC-HRMS)enabled an assessment of FOLFOX's impact on the metabolomic profile of the lung and revealed the metabolic pathways associated with the route of administration(IVLP vs.IV)and the therapy itself.This study also shows that the immediate instrumental analysis of metabolomic samples is ideal,as long-term storage at80℃ results in changes in the metabolite content in the sample extracts.
文摘A sensitive, accurate and robust Liquid Chromatography Tandem Mass Spectrometry method has been developed and validated to measure voriconazole trough levels in human plasma. The plasma samples were mixed with fluconazole as an Internal Standard and directed to protein precipitation and drug extraction. An aliquot of 1 μl was injected into the chromatographic system and separated by the Acquity BEH C18 column at a flow rate of 0.30 ml/min in a gradient mobile phase consisting of acetonitrile, Ultrapure water (UPW), methanol and formic acid. Voriconazole was detected by a Triple Quadrupole Detector (TQD) operating on Multiple Reaction Monitoring (MRM) and a positive ion mode Electrospray ionization (ESI) Q1 mass: 350.1 m/z, Q3 mass: 281.1 m/z. Method linearity of the calibration curve (0.10 - 8.00 μg/ml) indicated a correlation coefficient r ≥ 0.99. The intra and inter-assay accuracy was within 85% - 115% and the intra and inter-assay precision was ≤5.76%. Voriconazole recovery percentage was between 97.69 - 119.62%. The method was successively applied in routine voriconazole TDM.
文摘Objective:Voriconazole(VCZ)is a triazole antifungal agent widely used in immunocompromised patients with suspected or proven invasive fungal infections.The achievement of therapeutic range(1-5 mg/L)is essential to maximize VCZ efficacy,as its pharmacokinetics is characterized by a wide inter-and intra-individual variability.This study aims to quantify the variability of VCZ trough concentrations in children and adolescents with haematological diseases and optimize therapeutic drug monitoring in clinical practice.Methods:We analysed the monitoring concentrations of all children(<18 years old)treated with VCZ in the Haematology Department of Robert DebréHospital between January 2014 and December 2016.Demographic,clinical data,and VCZ dosing and monitoring concentrations measured by high-performance liquid chromatography with ultraviolet detection(HPLC-UV)were analysed.Non-parametric tests were performed using SPSS IBM 24.0.Results:380 trough VCZ concentrations at steady-state(Ctrough,ss)were available in 79 children:45.6%had first Ctrough,ss in the therapeutic range at first monitoring,46.8%had Ctrough,ss below 1 mg/L and 7.6%had Ctrough,ss over 5 mg/L.Forty-one patients were treated with recommended doses but only 53%of them reached the therapeutic range.There was no impact of age,sex,biological parameters,or indication of VCZ on Ctrough,ss values.The number of Ctrough,ss in the therapeutic range increases with the number of monitoring per patient following dosage adaptations.Conclusion:The wide inter-and intra-individual variability of VCZ trough concentrations at recommended doses confirm the need to standardize VCZ monitoring and identify factors to be considered to prospectively adapt treatment for each patient.
文摘HIV and AIDS has continued to be a major public health concern, and hence one of the epidemics that the world resolved to end by 2030 as highlighted in sustainable development goals (SDGs). A colossal amount of effort has been taken to reduce new HIV infections, but there are still a significant number of new infections reported. HIV prevalence is more skewed towards the key population who include female sex workers (FSW), men who have sex with men (MSM), and people who inject drugs (PWID). The study design was retrospective and focused on key population enrolled in a comprehensive HIV and AIDS programme by the Kenya Red Cross Society from July 2019 to June 2021. Individuals who were either lost to follow up, defaulted (dropped out, transferred out, or relocated) or died were classified as attrition;while those who were active and alive by the end of the study were classified as retention. The study used density analysis to determine the spatial differences of key population attrition in the 19 targeted counties, and used Kilifi county as an example to map attrition cases in smaller administrative areas (sub-county level). The study used synthetic minority oversampling technique-nominal continuous (SMOTE-NC) to balance the datasets since the cases of attrition were much less than retention. The random survival forests model was then fitted to the balanced dataset. The model correctly identified attrition cases using the predicted ensemble mortality and their survival time using the estimated Kaplan-Meier survival function. The predictive performance of the model was strong and way better than random chance with concordance indices greater than 0.75.
