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ObjectiveTo achieve high-dimensional prediction of class imbalanced of adverse drug reaction（ADR） of traditional Chinese medicine（TCM） and to classify and identify risk factors affecting the occurrence of ADR based on the post-marketing safety data of TCM monitored centrally in real world hospitals. MethodThe ensemble clustering resampling combined with regularized Group Lasso regression was used to perform high-dimensional balancing of ADR class-imbalanced data， and then to integrate the balanced datasets to achieve ADR prediction and the risk factor identification by category. ResultA practical example study of the proposed method on a monitoring data of TCM injection performed that the accuracy of the ADR prediction， the prediction sensitivity， the prediction specificity and the area under receiver operating characteristic curve（AUC） were all above 0.8 on the test set. Meanwhile， 40 risk factors affecting the occurrence of ADR were screened out from total 600 high-dimensional variables. And the effect of risk factors on the occurrence of ADR was identified by classification weighting. The important risk factors were classified as follows：past history， medication information， name of combined drugs， disease status， number of combined drugs and personal data. ConclusionIn the real world data of rare ADR with a large amount of clinical variables， this paper realized accurate ADR prediction on high-dimensional and class imbalanced condition， and classified and identified the key risk factors and their clinical significance of categories， so as to provide risk early warning for clinical rational drug use and combined drug use， as well as scientific basis for reevaluation of safety of post-marketing TCM.
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OBJECTIVE：To establish the method for simultaneous determination of 5-fluorouracil（5-FU）and its metabolites 5-fluoro-5，6-dihydrouracil （5-FUH2） in human plasma ，and apply it in the clinic. METHODS ：After plasma samples were processed twice by ethyl acetate ，UPLC-MS/MS method was adopted using 5-bromouracil （5-Bru） as internal standard. The determination was performed on Acquity UPLC HSS T 3 column with mobile phase consisted of methanol-water （30 ∶ 70，V/V）at the flow rate of 0.3 mL/min. The column temperature was 20 ℃，and sample size was 5 μL. An electrospray ion source was used to carry out negative ion scanning with multiple reaction monitoring. The capillary voltage was 1.5 kV；the taper hole voltage was 20 V；the desolvent temperature was 450 ℃；the desolvent air flow was 850 L/h；the cone hole gas velocity was 50 L/h. The ion transitions for quantitative analysis were m/z 129.00→41.90（5-FU），m/z 130.87→82.92（5-FUH2），m/z 189.00→42.10（5-Bru）， respectively. From Aug. to Oct. 2020，10 patients with advanced colorectal cancer were treated with continuous intravenous drip of 5-FU for 46 hours were collected from Harbin Medicinal University Cancer Hospital. Steady-state plasma concentration of 5-FU and plasma concentration of 5-FUH2 were determined at 18-30 h of continuous intravenous drip. The area under the curve （AUC）for 5-FU and concentration ratio of 5-FUH2/5-FU were calculated. RESULTS ：The linear range of 5-FU and 5-FUH2 were 20 to 1 000 μg/mL（R 2＞0.990）. The quantification limits were 20 ng/mL. RSDs of precision test were all lower than 20％，and relative error ranged ±10％. The extraction recovery and matrix effects didn ’t affect the determination of substance to be measured. Among 10 patients with advanced colorectal cancer ，the steady-state concentration of 5-FU were 180.04-622.83 ng/mL，and AUC of 5-FU ranged from 8.28 to 28.65 mg·h/L. The concentration of 5-FUH2 ranged 336.48-948.43 ng/mL，and concentration ratio of 5-FUH2/ 5-FU ranged 0.93-4.21. AUC of 5-FU in 10 patients had about 3-4 fold individual differences. CONCLUSIONS ：The established method has good precision and accuracy ，high sensitivity ，and simple operation. It can be used for plasma monitoring of 5-FU in patients with advanced colorectal cancer.
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In recent years,capecitabine is widely used in clinical practice.Hand-foot syndrome is a dose-limiting toxicity, often manifested as numbness in the hands and feet,sensation of dullness,tingling,skin swelling or erythema,scaling,blisters or seri-ous pain.Its occurrence has seriously affected the chemotherapy effect and daily life of patients.Genetic mutations of capecitabine met-abolic enzymes play an important role in the drug efficacy and side-effect.In particular,the relationship between gene polymorphisms of CDA,CES,TP,DPD,TYMS,MTHFR and hand-foot syndrome has been widely investigated and achieved by researchers.This arti-cle reviews the relationship between capecitabine metabolizing enzymes and hand-foot syndrome in order to provide a reference for i-dentifying the biological target of hand-foot syndrome caused by capecitabine chemotherapy.
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Objective:To explore the role of clinical pharmacists in the development of individualized drug treatment regimens for the osteosarcoma children with irregular body weight .Methods:Clinical pharmacists involved in the calculation of body weight surface area increased to that of adult for one case of osteosarcoma child during the chemotherapy , comparatively analyzed the suitable calcula-tion formula of surface area for the children in our country and helped clinicians make accurate dose of chemotherapy drugs .Mean-while, according to the pathological and physiological characteristics of the child , clinical pharmacist also provided advice on adjuvant drug use such as antiemetic regimen etc .Results:Physicians adopted the suggestions of clinical pharmacists and the chemotherapy was successfully completed .Overdose adverse reactions were avoided without the use of foreign general calculation formula of body surface area for the overweight child , and inadequate dose was also avoided for the conservative treatment , which could lower the risk of re-duced potential anticancer efficacy .Conclusion:Clinical pharmacists can help doctors perform safer and more effective drug treatment program and reduce adverse drug reactions in the treatment of special patients through participation in the development of individualized medication for cancer children to obtain maximum profit .
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OBJECTIVE:To explore the role of clinical pharmacists in the treatment of pan-drug resistant Acinetobacter bau-mannii infection. METHODS:Clinical pharmacists participated in the treatment for a severe pneumonia case of pan-drug resistant A. baumannii infection. Clinical pharmacists supplied overall pharmaceutical care and suggestions with respects to initial medication scheme evaluation,pathogen judgment,therapy drug selection,ADR disposal,etc.,including anti-infective treatment of moxifloxa-cin 0.4 g,ivgtt,qd+meropenem 0.5 g,ivgtt,q8 h+linezolid 0.6 g,ivgtt,q12 h;anti-pan-drug resistant A. baumannii infection of cefoperazone sodium and sulbactam sodium 3.0 g,ivgtt,q8 h+tigecycline 50 mg,ivgtt,q12 h;liver protection of ademetionine 1, 4-Butanedisulfonate 1.0 g,ivgtt,qd+reduced glutathione 1.8 g,ivgtt,qd. RESULTS:After 25 d treatment,the patient hadn’t been fe-vered,and hemogram and hepatic function index decreased to normal value. CONCLUSIONS:Clinical pharmacist should be en-gage in anti-infective treatment and pharmaceutical care,and provide physicians reasonable medication suggestion so as to promote care rate in the clinic.
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OBJECTIVE:To investigate thinking and working skill of clinical pharmacist working in the tumor hospital. METHODS:Medical care can be improved by strengthening theoretical learning and clinical practice,exploring thinking and skill in the working. RESULTS:The way that clinical pharmacists participated in the treatment can improve the curative effect and reduce incidence of ADR. CONCLUSION:Clinical pharmacists should direct medication according to patients’condition to guarantee safety and effectiveness of drug use.