Comparison of German，American and Japanese FORTA systems for hierarchical management of polypharmacy in elderly patients / 中国药房

OBJECTIVE To provide reference for the hierarchical management of polypharmacy in elderly patients in China. METHODS The formulation and development process of drug hierarchical management system FORTA （fit for the aged） for elderly patients was introduced. The treatment drugs for common cardiovascular system diseases and neuropsychiatric diseases in elderly patients were taken as examples， the disease types， drug types and drug hierarchy in Germany-FORTA， the U.S.-FORTA and Japan-FORTA were compared. RESULTS & CONCLUSIONS FORTA system was the first drug hierarchical system that combined positive and negative labels， formed through two rounds of Delphi method and covered a variety of diseases and drug items. The cardiovascular system diseases covered by the FORTA list mainly included acute coronary syndrome， chronic therapy following myocardial infarction， heart failure， atrial fibrillation， hypertension， stroke， etc. For acute coronary syndrome， chronic therapy following myocardial infarction and stroke， the related drugs were mostly class A， and the differences between those FORTA lists were minimal. The hierarchy of drugs used to treat other diseases was various. The neuropsychiatric diseases covered by the FORTA list included dementia， epilepsy， Parkinson’s disease， insomnia/sleep disorder， depression and bipolar disorder， etc.， and the drug’s hierarchy was mostly labelled with negative， mostly class C and class D， and only levodopa to treat Parkinson’s disease was class A. The hierarchy of antiepileptic drugs and drugs for the treatment of bipolar disorder （except lithium） was relatively uniform in three FORTA lists， while the hierarchy of other drugs was different. Compared with the FORTA system in the U.S. and Japan， the Germany-FORTA system updated the drug types and clinical evidence， optimized the hierarchy of diseases and drugs， and may be stricter in some drug hierarchies. The drugs with uniform hierarchy in those FORTA lists may have a wide application range，and our country can combine the above content with clinical practice to formulate a drug hierarchical management system for elderly patients to optimize the drug selection of elderly patients and improve their clinical outcomes.

A real-world survey of the effect of voriconazole on tacrolimus blood concentration after lung transplantation / 中国药房

OBJECTIVE To provide a reference for the dose adjustment of tacrolimus in patients who underwent lung transplantation after combined use of voriconazole. METHODS The clinical data of lung transplantation patients who used voriconazole and tacrolimus in our hospital from January 2020 to December 2022 were collected retrospectively. The effects of voriconazole on the valley concentration， daily dose and standardized blood concentration of tacrolimus were analyzed by using SPSS 21.0 software； multiple linear regression analysis was conducted for the factors that may affect the standardized blood concentration of tacrolimus. RESULTS A total of 153 lung transplantation patients were included. After the combination of voriconazole， the average daily dose of tacrolimus decreased from 3.37 mg to 0.76 mg， and valley concentration and standardized blood concentration were increased significantly （P＜0.000 1）. The average daily dose of voriconazole was negatively correlated with the standardized blood drug concentration of tacrolimus （P＝0.000 1，r＝－0.224）. The valley concentration of voriconazole was positively correlated with valley concentration （P＜0.000 1，r＝0.316） and standardized blood concentration （P＜0.000 1，r＝ 0.249） of tacrolimus. After combination with voriconazole， the standardized blood drug concentration of patients who underwent single lung transplantation was significantly higher than those who underwent double lung transplantation， and the standardized blood concentration of tacrolimus after oral administration of voriconazole was significantly higher than after intravenous drip of voriconazole （P＜0.05）. Most liver and kidney function indicators showed no significant changes. The results of multiple factor regression analysis showed that the valley concentration of voriconazole had a significant impact on the standardized blood concentration of tacrolimus （P＜0.001）. CONCLUSIONS The valley concentration of voriconazole has greatest influence on the blood concentration and dose adjustment of tacrolimus， which is an independent influencing factor. In clinical practice， the dose of tacrolimus should be reduced in combination with voriconazole， and therapeutic drug monitoring should be conducted for both drugs.

Analysis of Influential Factors for Acute Kidney Injury after Lung Transplantation / 中国药房

OBJECTIVE：To analyze the occurrence of acute kidney injury （AKI）after lung transplantation and its possible influential factors . METHODS ：Medical records of 64 patients who received lung transplantation in our hospital from April 2017 to June 2018 were included in this retrospective study. Patients were divided into AKI group （44 cases）and non-AKI group （20 cases），according to whether AKI occurred after operation. According to diagnostic criteria for lung transplantation in our hospital ， all patients were given Methylprednisolone sodium succinate for injection or Methylprednisolone sodium succinate for injection combined with Basiliximab for injection ，and triple immunosuppressive therapy of Tacrolimus capsules+Mycophenolate mofetil dispersible tablets or Mycophenolate mofetil capsules or Mycophenolate sodium enteric-coated tablets+Methylprednisolone tablets or Prednisone acetate tablets were given after operation. The occurrence of AKI in AKI group within a week after operation were recorded. Intraoperative influential factors （operation type ， operation duration ， ECMO support ， immune inhibitor use ， intraoperative blood loss ），postoperative influential factors [days of ICU ，mechanical ventilation and ECMO support ，median value of Scr within one week after operation ，median tacrolimus concentration and the use of potential nephrotoxic drugs （≥4 kinds）， hospitalization days] and survival rate one year after operation were observed in 2 groups. RESULTS ：Within one week after lung transplantation，44 patients（68.8％）had experienced at least one episode of AKI ，among which 19 cases（29.7％）were stage 1， 17 cases（26.5％）were stage 2 and 8 cases（12.5％）were stage 3. The incidence of AKI was the highest on post-operative day 4 （57.4％）. The incidence of AKI at stage 3 exhibited growth trend within the first week after operation ，and reached the highest on median post-operative day 5（8.7％）. Operation duration ，median value of Scr within one week after operation ，median tacrolimus concentration in non-AKI group were significantly shorter or lower than AKI group ；there was no significant difference in operation type， ECMO support ， use of immunosuppressive agents ， intraoperative blood loss ，ICU days ，mechanical ventilation days，ECMO support days ，the utilization rate of potential nephrotoxic drugs （ ≥4 kinds） and hospitalization days between 2 groups （P＞0.05）. There was no statistical significance in the survival rate at stage 1 and 2 one year after operation between AKI group and non-AKI group （P＞0.05）. One year after operation ，survival rate of AKI group at stage 3 was significantly lower than that of non-AKI group （P＜0.05）. CONCLUSIONS：The incidence of AKI is high after lung transplantation. Operation duration ，median value of Scr within one week after operation ，median tacrolimus concentration were possible factors for the occurrence of AKI after operation.

Association Research between CYP3A5，CYP3A4，ABCB1 and POR*28 Genetic Polymorphisms and Individualized Use of Tacrolimus in Lung Transplant Recipients after One Year of Tacrolimus Administration / 中国药房

ABSTRACT OBJECTIVE：To study the association between CYP3A5，CYP3A4，ABCB1 and POR*28 genetic polymorphisms and drug dosage（D）and steady blood concentration/dosage（c0/D）of tacrolimus in lung transplant recipients after one year of tacrolimus administration. METHODS：By retrospective analysis，a total of 46 recipients who underwent lung transplantation in China-Japan Friendship Hospital during May 2017-May 2018 were selected. The c0 and D of tacrolimus were measured and collected after one year of tacrolimus administration，and c0/D was calculated. Recipients’genotypes of CYP3A5（rs776746）， CYP3A4（rs2242480，rs28371759），ABCB1（rs1045642，rs2032582，rs1128503）and POR*28（rs1057868）were collected. The relationship between genetic polymorphism and D，c0/D was analyzed statistically. RESULTS：The genotype frequency in this study were all in accordance with Hardy-Weinberg equilibrium （P＞0.05）. While maintaining tacrolimus c0 within therapeutic range， genetic polymorphism of CYP3A5（rs776746）and CYP3A4（rs2242480）influenced D and c0/D of tacrolimus significantly（P＜ 0.05）. There was no statistical significance in D or c0/D among different genotypes of other sites（P＞0.05）. There was statistical significance in D or c0/D among extensive metabolism type recipients with CYP3A5（rs776746）*1 and CYP3A4（rs2242480）*1G alleles，normal metabolism type recipients with only CYP3A5 （rs776746） *1 or CYP3A4 （rs2242480） *1G alleles and poor metabolism type recipients without CYP3A5（rs776746）*1 and CYP3A4（rs2242480）* 1G alleles（P＜0.05）. D of tacrolimus was the highest in extensive metabolism type recipient and the lowest in poor metabolism type recipient. CONCLUSIONS：The detection of genetic polymorphism of CYP3A5（rs776746）and CYP3A4（rs2242480）has guiding significance for individualized medication of tacrolimus after one year of tacrolimus administration.

Pharmacokinetics changes of antimicrobial agents in adult patients receiving extracorporeal membrane oxygenation: an updated literature review / 中华危重病急救医学

Extracorporeal membrane oxygenation (ECMO) is a viable ultimate support therapy for patients with severe cardiorespiratory failure. Antimicrobial agents are commonly prescribed in critically ill patients with ECMO. However, an increasing number of studies have shown that ECMO circuit is associated with significant pharmacokinetic (PK) alterations, including the increased volume of distribution and reduced the clearance. In addition, the critical illness pathophysiology can also influence PK of antimicrobial, such as systemic inflammation, excessive fluid resuscitation, hypo-albuminemia, worsening hepatic or renal function. These PK alterations may increase the possibility of therapeutic failure or toxicity. Therefore, this study reviews published studies of the effects of ECMO on PK of antimicrobial agents in adults and makes preliminary recommendations on possible dosing regimen.

Correlation of Tacrolimus Concentrations among Transplant Patients ’Whole Blood ，Plasma and Blood Cells / 中国药房

OBJECTIVE： To study the correlation of tacrolimus concentrations among transplant patients’ whole blood， plasma and blood cells， analyze the effects of transplant types and ages on the their correlation， and to provide reference for rational drug use in clinic. METHODS： Totally 20 patients receiving tacrolimus anti-rejection therapy after transplantation and undergoing therapeutic drug monitoring （TDM） were randomly selected. According to the type of transplantation， they were divided into renal transplantation group and lung transplantation group （10 cases for each group）.  According to age， they were divided into three groups： 20-40 years old group， 41-60 years old group and 61-80 years old group （4， 9， 7 cases for each group）. Their residual blood after TDM was collected. Chemiluminescence microparticle immuno assay  （CMIA） was used to detect the concentration of tacrolimus in whole blood. UPLC-MS/MS was used to measure the concentrations of tacrolimus in plasma and blood cells. Pairs plots and Spearman rank correlation analysis were used to analyze the correlation of tacrolimus between whole blood and plasma， between whole blood and blood cells， between plasma and blood cells as well as the effects of transplant types and ages on tacrolimus concentrations among tansplant patient’s whole blood， plasma and blood cells. RESULTS： The correlation of tacrolimus concentrations in whole blood and plasma （r＝0.623，P＜0.01） was slightly stronger than that of whole blood and blood cells （r＝0.591， P＜0.01）； while  the correlation of tacrolimus concentration in plasma and blood cells was relatively weak （r＝0.497，P＜0.05）. Transplant type and age had an effect on the correlation of tacrolimus concentrations among patients’ whole blood， plasma， blood cells. The correlation of tacrolimus concen- tration in whole blood， blood cells and plasma in renal transplantation group was also weak （all r＜0.5）， and was weaker than that in lung transplantation group. The correlation of tacrolimus concentration among whole blood， plasma and blood cells was weak in patients of aged 20-40 years old group （all r＜0.3）， and was weaker than that of patients of aged 41-60 years old group and 61-80 years old group. CONCLUSION： Post-transplantation patients’ tacrolimus concentrations in whole blood， plasma and blood cell have a weak correlation. Rejections and adverse effects should be monitored in these patients， especially those renal transplantation patients or those patients aged 20 to 40.

Analysis of the Quality of Pharmaceutical Care for Cancer Pain Therapy in 64 Hospitals from Beijing / 中国药房

OBJECTIVE： To investigate pharmaceutical care of cancer pain therapy in medical institutions from Beijing area， and to provide reference for improving the quality of pharmaceutical care for cancer pain in medical institutions and formulating cancer pain therapy decision by public health administration departments at different levels. METHODS： Inspection results of standardized diagnosis and treatment for cancer pain were analyzed retrospectively in Beijing Pain Therapy Quality Control and Improvement Center during Feb.-Mar. 2018. Scoring results of pharmaceutical care （20 points） and its 5 sub-items （personnel participation， drug supply， drug management， outpatient prescription comment and inpatient prescription comment， 4 points each item） were analyzed statistically and classified according to hospital level and pharmaceutical care inspection results. RESULTS： A total of 64 hospitals in Beijing participated in the inspection， including 27 tertiary A hospitals （42.19％）， 21 tertiary B hospitals （32.81％）， 16 secondary hospitals or first-level hospitals （25.00％）. Pharmaceutical care in all hospitals met the inspection requirements with qualified rate of 100％. 52 hospitals performed excellently （81.25％）， and 12 hospitals were qualified for pharmaceutical care （18.75％）. Among 5 sub-items of personnel participation， drug supply， drug management， outpatient prescription comment and inpatient prescription comment， the average score of drug supply item was the highest （3.83±0.05）； the lowest was the personnel participation item （2.93±0.13）. The results of pharmaceutical care inspection in tertiary A hospitals （17.80±0.28） and tertiary B hospitals （17.78±0.30） were significantly better than those in secondary hospitals or first-level hospitals（16.16±0.50）（P＜0.01 or P＜0.05）； there was statistical significance only in the score of outpatient prescription comment among 5 sub-items（P＝0.026）. Total scores of the hospitals with excellent pharmaceutical care were significantly higher than those of the hospitals with qualified pharmaceutical care in terms of personnel participation， outpatient prescription comment and inpatient prescription comment （P＜0.01 or P＜0.05）. There was significant difference in the inspection results of pharmaceutical care among the excellent group， the qualified group and the unqualified group classified by the results of personnel participation item （P＜0.01 or P＜0.05）. CONCLUSIONS： The quality of pharmaceutical care for cancer pain therapy in medical institutions from Beijing area has reached the qualified level， but the participation of clinical pharmacists in cancer pain therapy and outpatient prescription comment still need improvement in further. The training of clinical pharmacists and information construction of narcotic drug management should be strengthened so as to improve the overall quality of pharmaceutical care for cancer pain.

Analysis of genetic mutation of UGT1A1 * 28 and UGT1A1 * 6 in renal transplant patients with unconjugated hyperbilirubinemia / 中华器官移植杂志

Objective To explore the clinical significance and gene mutation profiles of renal transplant patients with unconjugated hyperbilirubinemia (Gilbert's syndrome).Methods Genomic DNA was extracted from peripheral blood samples of 8 renal transplant patients with Gilbert'S syndrome.UGT1A1 * 6 and UGT1A1 * 28 genotypes were identified through digital fluorescence molecular hybridization and DNA sequencing.Results There are 2 cases of UGT1A1 * 28 heterozygous mutant,3 cases of UGT1A1 * 6 homozygous mutant,2 case of UGT1A1 * 6 heterozygous mutant,1 case of UGT1A1 * 28 heterozygous mutant combined with UGT1A1 * 6 heterozygous mutant.Conclusion There is a higher heterozygous or homozygous gene mutation rate of UGT1A1 * 6 and UGT1A1 * 28 in renal transplant patients with Gilbert's syndrome.Genetic mutation of UGT1A1 * 6 and UGT1A1 * 28 may be the reason of Gilbert's syndrome after renal transplant.