Objective In order to discuss the rationality of clinical use of medication and the strategies of serious adverse reactions(SADR),the reports of SADRs caused by nedaplatin for injection were summarized and analyzed.Methods Methods Serious adverse reactions to all medicines reported to the National Adverse Reaction Monitoring Centre(NARMC)in Tongji Hospital Affiliated to Tongji Medical College,Huazhong University of Science and Technology from January 2012 to December 2021 were collected,and a retrospective analysis of 90 patients among those cases with SADR after nedaplatin injection was carried out.Results The occurrence of SADRs was not related to the gender.In monotherapy with nedaplatin,the rate of serious adverse effects was high with the first use of nedaplatin(74.3%).The incidence of adverse reactions was highest within 30 minutes and 2-14 days,including severe allergic reaction(34.4%)and grade Ⅱ-Ⅳ myelosuppression(51.2%),respectively.Drug withdrawal and symptomatic treatment were often the preferred treatment methods in clinical practice.Conclusion While using nedaplatin as a chemotherapy regimen,especially for the first time,patients should be closely monitored for the occurrence of severe anaphylaxis within 30 minutes and severe bone marrow suppression within 2 weeks.A rescue emergency plan for resuscitation and regular checking of the hemogram should be made to prevent the occurrence of serious adverse reactions.
Objective To study the relationship between health investment and economic growth in China.Methods An empirical study was conducted using threshold effect models and instrumental variable methods.Results Human capital investment in health sector can promote economic growth more than physical capital investment.Conclusion More human capital investment,such as the number of health personnel,should be added in the future health investment,and physical capital investment,such as the number of beds,should be controlled.The eastern region should increase health investment related to the elderly,which is more conducive to regional economic growth,while the central region should also increase health investment in physical capital such as the number of beds,while the western region should increase health investment in both aspects,which is more conducive to economic growth,because the economic development is relatively slow.
Objective To provide medical institutions with expert recommendations for the rational off-label use of key monitored drugs and to guide healthcare professionals in further standardizing the application of national monitored drugs.Methods The research design for reaching expert consensus on the rational clinical use of national monitored drugs beyond their approved indications followed the guidelines of the World Health Organization(WHO).A systematic search was conducted to extensively collect common issues related to the off-label use of the second batch of national monitored drugs in various provinces.The Delphi method was used to survey experts and identify common off-label use items for the key monitored drugs.Literature research and expert experience were utilized to collate and form relevant body of evidence,and quality evaluation was carried out in accordance with the GRADE approach.Consensus was reached again through the Delphi method regarding the recommended advice and evidence level,which ultimately led to the formation of the"Expert Consensus on the Rational Clinical Use of Nationally Monitored Drugs Beyond Their Approved Indications."Results A survey questionnaire was conducted among 60 experts through an online survey,and a consensus on off-label use items was reached using the Delphi method,covering drug categories such as proton pump inhibitors,antibiotics,glucocorticoids,and other medications.A total of 37 clinical issues were identified,resulting in a total of 38 recommended pieces of advice.Conclusion This consensus provides a reference and supplement for medical institutions to develop clinical application norms and prescription(medical order)review rules for national monitored drugs,to ensure the effectiveness and safety of their use.It further improves the quality of medical services,reduces the risk of adverse events related to national monitored drugs,promotes rational drug use.
Objective To comprehensively evaluate the quality of Croci Stigma from different regions by using the entropy weighted TOPSIS,and to provide evidence for the quality evaluation and regions selection of Croci Stigma.Methods The contents of picrocrocin,crocin I,crocin II and crocin III were determined by HPLC wavelength switching method.The total content of four components,loss on drying,total ash,absorbance and extract were chosen as detection indexes for Croci Stigma,and the weight was calculated by entropy weight method,and the indexes were statistically analyzed by TOPSIS method.The quality of Croci Stigma was comprehensively evaluated.Results The analysis results of entropy weighted TOPSIS method showed that the mean values of relative closeness(Ci)values of Croci Stigma from Zhejiang,Tibet,Anhui,Jiangsu provinces and shanghai city were 0.654,0.396,0.426,0.326 and 0.341,respectively.Overall,the quality of Croci Stigma in Zhejiang province was the highest.Conclusion The established entropy weighted TOPSIS method is objective,comprehensive and effective,which can be used for the comprehensive quality evaluation of Croci Stigma.
Objective To evaluate the differences in efficacy,safety and economics of vancomycin hydrochloride for injection between two manufacturers based on real-world data.Methods A total of 6 757 cases of intravenous use of vancomycin hydrochloride for injection from different manufacturers between January 1,2013 and December 31,2019 in the Affiliated Drum Tower Hospital of Nanjing University Medical School were retrospectively analyzed,and 5308 cases were matched by 1∶1 propensity score method,including 2 654 cases in the group A(domestic drug group)and 2 654 cases in group B(the innovator drug group).The differences in efficacy and safety between the two groups were compared.Cost-effectiveness analysis was used to compare the drug economics of the two groups.Results There were no significant differences in clinical cure rate,bacterial clearance rate,and incidence of adverse events between the two groups(P>0.05).In terms of economics,the average cost of vancomycin per capita,average daily cost of vancomycin and average cost of antibiotics per capita were significantly different between the two groups(P<0.05),and the cost of group B was higher than that of group A.Conclusion The efficacy and safety of vancomycin hydrochloride for injection were consistent between the two manufacturers.
Objective The metabolites of tolvaptan in rats were identified by ultra-performance liquid chromatography-quadrupole-exactive orbitrap high-resolution mass spectrometry(UFLC-Q-Exactive Orbitrap MS),and the possible metabolic pathways of tolvaptan in rats were discussed.Methods Plasma,urine and fecal samples from rats were collected after a single oral administration of 60 mg·kg-1 tolvaptan solid dispersion solution.The protein in the samples was precipitated with acetonitrile.UFLC-Q-exactive orbitrap MS technology was adopted for the sample analysis and the data were processed by Xcalibur 2.0 software.Results According to the retention time,precise relative molecular mass,characteristic fragment ions and related literature reports of each compound,35 metabolites were identified in rat biological samples.Moreover,23,26 and 30 metabolites in the plasma,urine and feces were identified,respectively.The major metabolic pathways of tolvaptan were identified as hydroxylation,carboxylation,hydrolysis,dehydrogenation,glucuronidation and acetylation.Conclusion Our study confirmed the major metabolites of tolvaptan in rats,enriched the metabolite spectrum of tolvaptan in vivo,and provided an experimental basis for the in-depth study of the pharmacodynamic substance basis of tolvaptan.
Objective To evaluate the effect of pharmaceutical care provided by clinical pharmacists during the administration of Paxlovid for the treatment of COVID-19 in heart transplant patients.Methods During the treatment of COVID-19 with Paxlovid in 3 heart transplant patients,the clinical pharmacist provided pharmaceutical care in terms of the medicine indication,dosage,drug adjustment,drug interaction,adverse reaction etc,to develop individualised dosing regimens for patients.Results Clinical pharmacists are active in anticipating,identifying and resolving problems with Paxlovid in heart transplant patients,and monitoring the medication process to assist doctors in solving difficult problems.Conclusion Clinical pharmacists have explored the pharmaceutical monitoring methods for heart transplant patients during the use of Paxlovid to ensure the patients'safety and efficacy of patient medication and to improve the clinical cure rates.
Objective To establish a high-performance liquid chromatography-tandem mass spectrometry(LC-MS/MS)method for the simultaneous determination of seven vitamin Bs(VBs)in rat plasma.Methods The plasma samples were pretreated using the protein precipitation method.The chromatographic separation was achieved using an Agilent ZORBAX SB-Aq column(2.1 mm×150 mm,3.5 μm),with a mobile phase composed of 0.01%formic acid(A)and methanol(B)in a gradient elution mode.The flow rate was set at 0.3 mL·min-1 and the column temperature was maintained at 30℃.Mass spectrometric detection was performed using positive ion mode in multiple reaction monitoring.2,4,5,6-Deuteronicotinamide was used as the internal standard.Results Methodological validation results showed that the lowest limits of quantitation(LOQs)for the seven VBs ranged from 7.5 to 300 ng/mL,while the highest LOQs ranged from 1 000 to 20 000 ng·mL-1.Within a certain concentration range,all compounds showed a good linearity(r2>0.992 2).The accuracies ranged from 86.0%to 117.6%,and both intra-and inter-batch precision were less than 20%.Additionally,all analytes demonstrated extraction recoveries greater than 86.1%.No significant matrix effects were observed,and the stability was good.The established validation method was successfully applied to the pharmacokinetics study of single intragastric administration of VB solution in SD rats.Conclusion The analytical method established in this study is simple,rapid,sensitive,and exclusive for the simultaneous determination of VB in real plasma samples.This LC-MS/MS method provides a new analytical tool for further exploring the physiological and pathological effects of VB.
1 病例介绍 患者,男性,84 岁,入院8 天前无明显诱因下出现发热,体温最高38.3 ℃,伴咳嗽、咳白色黏性痰,痰量少不易咳出,自测新型冠状病毒抗原阳性,服用抗病毒颗粒及橘红化痰冲剂等药物治疗,症状未改善,入院 3天前在外院行胸部CT提示:双肺多发斑片状、条索状密度增高影,边界不清,考虑双肺炎症(病毒性肺炎可能性较大),患者未重视. 入院前 2 天患者再次发热,体温最高达39.2℃,退热治疗(具体药物不详)后体温恢复正常,入院前1 天患者自感胸闷、气短,因多次测指尖血氧饱和度示 88～93％,于 2023 年 1 月 5 日入院. 入院诊断:①新型冠状病毒感染;②原发性高血压3 级(高危组). 既往有高血压 20 年余,血压最高达170/112 mmHg(1 mmHg=0.133 kPa),平素给予非洛地平缓释片(5 mg,po,qd)降压治疗,血压控制良好.
Objective To rapidly evaluate the efficacy,safety and economics of empagliflozin in the treatment of type 2 diabetes mellitus(T2DM)and to provide evidence-based medical evidence for clinical decision.Methods PubMed,Embase,the Cochrane Library,CNKI,Wangfang,VIP database and major health technology assessment(HTA)websites were searched from the construction of the databases to Nov 30th,2022.Two researchers independently screened,extracted the data,evaluated the quality and analyzed the results according to inclusion and exclusion criteria.Results A total of 23 literatures were included,including 3 HTA reports,10 systematic review/Meta-analyses and 10 pharmacoeconomic studies.The results of efficacy showed that empagliflozin reduced HbA1c,blood pressure,body weight and all-cause mortality compared with the control group.Safety studies showed that empagliflozin was generally well tolerated,and significantly reduced MACEs and the relative risk of the renal primary outcomes,but increased the risk of genital infections and electrolyte abnormality compared with placebo and other oral antidiabetic drugs.The economic evaluation results showed that empagliflozin was more cost-effective in high risk patients with comorbid cardiovascular or kidney disease.Conclusion Empagliflozin is effective and safe in the treatment of T2DM,but the pharmacoeconomic studies focusing on chinese populations are urgently needed.
Objective To understand the current situation of quality management and implementation of risk-based quality management in clinical trial institutions.Methods In the form of questionnaires,Questionnaire Star was used to create the questionnaire,which was sent to clinical trial organisations in all provinces and cities to fill in through emails and institutional WeChat groups.Results The questionnaire results from 123 clinical trial institutions from 25 provinces were included for analysis.The quality management status was as follows:104(84.6%)institutions of the main quality management mode were the internal quality control by GCP department.On average,each institution had 3、4 full-time staff for quality management,with an average of 1 full-time staff to manage 16.8 projects and 10.9 specialties.In the last three years,65(52.8%)institutions conducted training for researchers 2-3 times/year.Ninety-five(77.2%)institutions had established a clinical trial funding allocation system.Forty-nine(39.2%)institutions had established GCP informatization management system and 44(35.2%)institutions had established risk-based quality management model.In the case of coordination between the clinical trial institution and the sponsor,47(41.2%)institutions did not not aware of the sponsor's/CRO's quality management plan in their collaboration with the sponsor.Conclusion The surveyed institutions have weaknesses,such as insufficient dedicated personnel for quality management,low utilization rate of GCP information systems.The collaborative capacity between clinical trial institutions and sponsors needs to be improved,and the implementation rate of risk-based quality management is also low.
Objective To investigate the efficacy and safety of new oral anticoagulants(NOACs)rivaroxaban and dabigatran versus warfarin in the treatment of the patients with non-valvular atrial fibrillation combined with diabetes mellitus.Methods A retrospective study was performed on 119 cases of patients with non-valvular atrial fibrillation combined with diabetes mellitus from outpatient and inpatient of the Ninth People's Hospital of Suzhou City from Jan 2019 to June 2021.According to the use of anticoagulants,patients were divided into rivaroxaban 10 mg group(Group A,n=25),rivaroxaban 15 mg group(Group B,n=30),dabigatran group(Group C,n=29),and warfarin group(Group D,n=35).All patients were treated continuously for at least 6 months.The incidence of embolism and bleeding events,the changes of coagulation indicator,blood glucose,liver and kidney function indexes were compared before and after treatment among the four groups.Results Thromboembolic events:1 cases(4.00%)of stoke or thromboembolic events occurred in Group A;2 cases(6.67%)occurred in Group B;2 cases(6.90%)occurred in Group C,and 5 cases(14.28%)occurred in Group D.Bleeding events:1 cases(4.00%)of bleeding events occurred in Group A;1 cases(3.33%)occurred in Group B;2 cases(6.90%)occurred in Group C,and 8 cases(22.85%)occurred in Group D.There was no statistically significant difference among the four groups of stoke or thromboembolic events(P>0.05).The incidence of bleeding events in Group A and B were both statistically lower than Group D(P<0.05),and the risk of bleeding events of Group C was similar to Group D(P>0.05)and there was also no statistically significant difference among Group A,B and C(P>0.05).The activated partial thromboplastin time(APTT)of all patients was significantly prolonged after treatment compared with before treatment(P<0.05),but none of them exceeded the upper limit of the normal value by 2 times.The APTT and international normalized ratio(INR)values of Group A and B,INR values of Group C were all statistically better than those of Group D(P<0.05)after the treatment.There were no statistically significant difference in the comparison of blood glucose,liver and kidney function index as well(P>0.05).Conclusion The new oral anticoagulants rivaroxaban and dabigatran showed similar effects in prevention of stroke or thromboembolic events,but better safety profiles with lower risks of bleeding events compared to warfarin in patients with non-valvular atrial fibrillation combined with diabetes mellitus.Dabigatran is comparable in efficacy and safety when compared with rivaroxaban and deserves to be promoted for clinical use.
Objective To investigate the medical expense control model of rational drug use based on the China healthcare security diagnosis related groups(CHS-DRG)simulation in Beijing in 2021.Methods By analyzing the simulated operation data from January to March 2021 before the intervention,the groups with rational drug management improving potential among the top three surgical disease groups in terms of the number of cases enrolled in the surgical department were selected.Then,the targeted intervention and guidance were implemented to the selected disease groups.Finally,the analysis was obtained by comparing the changes in several key indicators such as the average drug cost,average antibacterial drug cost,average surplus and average length of stay during June to August 2021.Moreover,the differences in antimicrobial drug use intensity and hospital infection reporting of the department as a whole where the problematic groups were located were also investigated.Results Before the intervention,the otolaryngology related groups(including DD29 and DE19),urology surgery related groups(including LD19 and LJ13)could be improved in antibacterial drug use during the perioperative period.Meanwhile,the chest surgery related group(including EB19)had space to be improved in auxiliary medication.After the intervention,the five groups'average drug cost and average antibacterial drug cost in the otolaryngology and urology surgery departments are all decreased.The antibiotics use intensity is also declined in otolaryngology and urology surgery departments.The average surplus of otolaryngology and urology surgery related groups are increased,with the DE19 disease group in ENT also achieving a profit turnaround.As for the indicators related to the quality of care,there were no significant differences in the groups'average length of stay and nosocomial infection reporting of these departments.Conclusion The hospital operation based on CHS-DRG payment is both an opportunity and a challenge.The all-inclusive payment model has prompted hospitals to take the initiative in controlling costs,and the exploration of a rational medication management and cost-control model related to disease groups has begun to show results in terms of cost reductions without affecting the quality of medical care.The research can also provide a solid foundation for the CHS-DRG actual payment and sustainable development of medical insurance fund.
Objective To investigate the organic components in cefmetazole sodium butyl rubber clousures for injection and their migration into drugs,and to evaluate the compatibility of pharmaceutical butyl rubber clousures with cefmetazole sodium.Methods The structures of volatile components in butyl rubber clousures of cefmetzole sodium for injection and those migrated into drugs were identified by GC/MS SCAN mode and National Institute of Standard and Technology(NIST)spectrum library.An HPLC method was established to quantitatively analyse the antioxidants and vulcanizing agents transferred from butyl rubber clousures into drugs.Results Organic compounds such as antioxidant BHT and silicone oil were identified by GC/MS.The HPLC was used to determine the peak area of antioxidant(168,264,330,1 076,1 010)and vulcanizing agent in the range of 0.5-100 μg·mL-1 with good linear relationship with the peak area.The average recoveries(low,medium,and high)of antioxidant and vulcanizing agents ranged from 90.0%to 110.0%,and the corresponding RSD were all less than 2%(n=9).It was found that the antioxidant BHT and silicone oil in cefmetazole sodium butyl rubber clousures for injection would migrate into the drug and affect the clarity of the solution.Conclusion GC-MS/HPLC method can be used as an effective method for quality control of packing materials(butyl rubber clousures)and drug compatibility studies,so as to ensure the safety of drug use by the public.
Objective To develop an accurate,rapid and sensitive flow cytometry method for the determination of anti-mesenchymal stem cell antibody in cynomolgus monkey serum.Methods After the solutions of mesenchymal stem cell were centrifuged and washed,and the suspension was taken,positive controls or actual samples were added and incubated with mesenchymal stem cell,then were incubated with protein L-PE solution.After the removal of the free protein L-PE,the mean fluorescence intensity of the PE was detected by flow cytometry.Results The method sensitivity is 115.54 ng·mL-1,far higher than the non-clinical research recommended sensitivity of 250-500 ng·mL-1.The precision of intra-assay and inter-assay were less than 20%.Assay cut points,low positive control concentration determination,sensitivity,precision and stability were validated in this study.Conclusion The method is proved to be sensitive,specific,rapid and suitable for the determination of anti-mesenchymal stem cell antibody in monkey serum and immunogenicity study.
Objective To comprehensively assess the strengths and weaknesses of the 24 antihypertensive drugs procured as Volume-based Procurement(VBP)and innovator drugs by using quantitative evaluation system,and to provide a reference for doctors and patients in medication guidance and pharmaceutical decision-making.Methods The Quantitative Evaluation Criteria in the"Quick Guide to Drug Evaluation and Selection in Chinese Medical Institutions"were refined and optimized.The 24 selected VBP and innovator antihypertensive drugs were quantitatively evaluated according to the optimized quantitative evaluation system with the help of Chinese and English databases such as China Knowledge Network,Wanfang data,Wipunet,Embased,PubMed,and Metstr,as well as guideline search tools such as Meikang MCDEX,Drugwise Data,Up To Date,Medical Pulse and other databases etc.Results Among the 24 antihypertensive drugs,only four innovator drug evaluation scores were higher than those of drugs selected as VBP,namely felodipine tablets,Fosinopril sodium tablets,indapamide extended-release capsules,Irbesartan hydrochlorothiazide tablets.there were five main differences in the evaluation scores,namely economy,consistency evaluation,drug expiry date,global use,and the status of manufacturing enterprises.It was found that 83%of the VBP drugs had higher evaluation scores than those of the innovator drugs.The economic score of the innovator drug was low,and the difference in the scores was between 1-11 points.Conclusion By using the quantitative evaluation system to evaluate the antihypertensive drugs,the advantages and disadvantages of the innovator and VBP antihypertensive drugs can be assessed comprehensively,and the digital characteristics of antihypertensive drugs can be given,and the evaluation score can provide the reference basis for the guidance and decision-making of medication for doctors and patients.
Objective To establish a method for the determination of related substances in foscarnet sodium by HPLC.Methods The chromatography separation was performed on a CAPCELL PAK C18 chromatography column(250 mm×4.6 mm,5 μm)with mobile phase of a mixture of solution[Solution A:dissolve 3.2 g of sodium sulfate decahydrate in water,add 3 mL of glacial acetic acid and 6 mL of 0.1 mol·L-1 sodium pyrophosphate,dilute with water to 1 000 mL.Solution B:dissolve 3.2 g of sodium sulfate decahydrate in water,add 6.8 g of sodium acetate and 6 mL of 0.1 mol·L-1 sodium pyrophosphate,dilute with water to 1000mL.Solution A and Solution B(70∶30)(the pH of this mixture is about 4.4).To 1 000 mL of this solution add 0.25 g of tetrahexylammonium hydrogen sulfate and 100 mL of methanol]at a flow rate of 1.0 mL·min-1.The column temperature was 35℃.The detection wavelength was 230 nm and the injection volume was 50 μL.Results Under the chromatography conditions,the peaks of foscarnet sodium,impurityⅠ,impurity Ⅱ and other individual impurities were separated effectively.The foscarnet sodium and impurity Ⅱ showed good liner relationships(r=0.999 9)in the range of 5-248 μg·mL-1 and 1.6-9.1 μg·mL-1,respectively.The limits of detection(LODs)of foscarnet sodium and impurity Ⅱ were 23 ng and 62 ng respectively.The average recovery of impurity Ⅰ was 100.8%,RSD= 2.0%(n= 6).The average recovery of impurity Ⅱ was 98.6%,RSD=2.7%(n=12).Conclusion The method is simple,sensitive and accurate.It is suitable for the determination of related substances in foscarnet sodium.
Objective A simple,specific and rapid LC-MS/MS method was established to determine flumatinib and its two major metabolites in human plasma for clinical therapeutic drug monitoring.Methods The determination was performed on an ACQUITY UPLC HSS T3 column(2.1 mm×50 mm,1.8 μm)with mobile phases consisting of acetonitrile and 10 mmol·L-1 ammonium formate(containing 0.1%formic acid)with gradient elution at the flow rate of 0.5 mL·min-1.The elution time was 6 min.The temperature of the column was 38℃.The ion source was electrospray ion source and the scanning mode was multiple reaction monitoring scanning in positive ion mode.Results The mass concentrations of flumatinib and its metabolites(flumatinib M1 and flumatinib M3)have a good linear relationship within the concentration range investigated.The precision and stability of the method are good.The precision is less than 15%,and the relative deviation is within±15%.The extraction recoveries of flumatinib and its metabolites approach nearly 100%.Conclusion The method is simple and sensitive,and can accurately determine the plasma concentration of flumatinib and its metabolites,providing a basis for clinical rational drug use.
Objective To optimize the extraction process parameters of digestive Funing decoction.Methods Taking fingerprint similarity index(C,A),the total content of multiple components and extract yield as indexes,the extraction process parameters of Xiaohua Funing Tang were optimized by central composite design response surface methodology(RSCCD).Results The extraction times had a significant effect on the comprehensive score.The optimum extraction parameters were adding 9 times of water,decocting for 1.5 hour and extracting for 3 times.Under this condition,the predicted value of the comprehensive score was 100.333,and the verified mean value was 96.75,which was not significantly different from the predicted value.Conclusion The extraction process of Xiaohua Funing Tang determined in this paper is scientific,reasonable,stable and feasible.It lays a foundation for the research and development of later preparations.
Objective To promote the pharmacist's ability to identify and resolve drug-related problems(DRPs)in Physician-and pharmacist-managed clinic of interstitial lung disease using pharmaceutical care network Europe(PCNE)classification system.Methods Patients of physician-and pharmacist-managed clinic from February 1,2022 to February 1,2023 were included.Problems,causes,intervention types,intervention acceptability,and solution state of DRPs were analyzed using the PCNE classification system.Results A total of 128 patients were included and 178 DRPs were identified,with an average of 1.39 DRPs per patient.The main types of problems were effectiveness(127 cases,71.35%)and safety(39 cases,21.91%);The main causes classification were patient-related(85 cases,47.75%),drug selection(30 cases,16.85%)and dose selection(27 cases,15.17%);The main intervention type was patient-level(176 cases,54.32%).A total of 243 interventions were provided to physicians and patients by pharmacists,in which 231 interventions were accepted with the overall acceptance rate of 95.06%.Ultimately,152(85.39%)DRPs were resolved.Conclusion The PCNE classification system is helpful to improve the efficiency of DRP recognition and resolution in the joint outpatient clinic,promote the standardization,convenience,and precision of the pharmaceutical care model,and improve the rationality,safety,and effectiveness of patients'drug use.
