OBJECTIVE To standardize the main processes and related technical links of the clinical comprehensive evaluation of drugs， and provide guidance and reference for improving the quality of comprehensive evaluation evidence and its transformation and application value. METHODS The construction of Guideline for the Workflow of Clinical Comprehensive Evaluation of Drugs was based on the standard guideline formulation method of the World Health Organization （WHO）， strictly followed the latest definition of guidelines by the Institute of Medicine of the National Academy of Sciences of the United States， and conformed to the six major areas of the Guideline Research and Evaluation Tool Ⅱ. Delphi method was adopted to construct the research questions； research evidence was established by applying the research methods of evidence-based medicine. The evidence quality classification system of the Chinese Evidence-Based Medicine Center was adopted for evidence classification and evaluation. The recommendation strength was determined by the recommendation strength classification standard formulated by the Oxford University Evidence-Based Medicine Center， and the recommendation opinions were formed through the expert consensus method. RESULTS & CONCLUSIONS The Guideline for the Workflow of Clinical Comprehensive Evaluation of Drugs covers 4 major categories of research questions， including topic selection， evaluation implementation， evidence evaluation， and application and transformation of results. The formulation of this guideline has standardized the technical links of the entire process of clinical comprehensive evaluation of drugs， which can effectively guide the high-quality and high-efficient development of this work， enhance the standardized output and transformation application value of evaluation evidence， and provide high-quality evidence support for the scientific decision-making of health and the rationalization of clinical medication.

BACKGROUND: The use of potentially inappropriate medications (PIMs) is a major concern for medication safety as it may entail more harm than potential benefits for older adults. This study aimed to explore the prescribing rate, healthcare utilization, and expenditure of older adults using PIMs in China. METHODS: A cross-sectional analysis was conducted using a national representative database of all medical insurance beneficiaries across China, extracting ambulatory visit records of adults aged 65 years and above between 2015 and 2017. Descriptive analysis was conducted to measure the rate of patients exposed to PIM, prescribing rate of each PIM, average annual outpatient visits per patient, average total medication costs for each visit, average annual cost of PIMs for each patient, and average annual medication costs for each patient. Generalized linear model with logit link function and binomial distribution was used to examine the adjusted associations between PIMs and independent variables. RESULTS: In total, 845,278 (33.2%) participants were identified to be exposed to at least one PIM. Patients aged 75-84 years (38.1%, 969,809/2,545,430) and ≥85 years (37.9%, 964,718/2,545,430) were more likely to be prescribed with PIMs. Beneficiaries of the Urban Employee Basic Medical Insurance (UEBMI) and living in eastern and southern regions were more frequently prescribed with PIMs. Compared with patients without PIM exposure (7.5 visits, drug cost of RMB 1545.0 Yuan), patients with PIM exposure showed higher adjusted average annual number of outpatient visits (10.7 visits, β = 3.228, 95% confidence interval [CI] = 3.196-3.261) and higher annual drug costs (RMB 2461.8 Yuan, Coef. = 916.864, 95% CI = RMB 906.292-927.436 Yuan). CONCLUSIONS The results showed that the use of PIM among older adults was common in China. This study suggests that the use of PIM could be considered as a clear target, pending multidimensional efforts, to promote rational prescribing for older adults.
Humans ; Aged ; Cross-Sectional Studies ; Aged, 80 and over ; Male ; Female ; China ; Inappropriate Prescribing/economics* ; Patient Acceptance of Health Care/statistics & numerical data* ; Potentially Inappropriate Medication List/statistics & numerical data* ; Health Expenditures/statistics & numerical data*

OBJECTIVE: To evaluate the effect of palliative care on drug use, medical service utilization and medical expenditure of patients with advanced cancer. METHODS: A cohort of patients including pal-liative care and standard care was constructed using the medical records of the patients in Peking University Cancer Hospital from 2018 to 2020, and coarsened exact matching was used to match the two groups of patients. The average monthly opioid consumption, hospitalization rate, intensive care unit (ICU) rate and operation rate, and the average monthly total cost were selected to evaluate drug use, medical service utilization and medical expenditure. Chi-square test and Wilcoxon signed rank test were used to compare the differences between the two groups before and after exposure and the change in the palliative care group. The net impact of palliative care on the patients was calculated using the difference-in-differences analysis. RESULTS: In this study, 180 patients in the palliative care group and 3 101 patients in the stan-dard care group were finally included in the matching, and the matching effect of the two groups was good (L₁ < 0.1). Before and after exposure, the average monthly opioid consumption in the palliative care group was significantly higher than that in the standard care group (Before exposure: 0.3 DDD/person-month vs. 0.1 DDD/person-month, P < 0.01; After exposure: 0.7 DDD/person-month vs. 0.1 DDD/person-month, P < 0.01; DDD refers to defined daily dose), palliative care significantly increased the average monthly opioid consumption in the patients (0.3 DDD/person-month, P < 0.01). The hospitalization rate (48.9% vs. 74.3%, P < 0.01) and operation rate (3.9% vs. 8.8%, P < 0.01) of the patients in palliative care group were significantly lower than those in standard care group, and the ICU rate became similar between the two groups (1.1% vs. 1.6%, P=0.634). Palliative care significantly reduced the patients ' hospitalization rate (-25.6%, P < 0.01), ICU rate (-4.9%, P < 0.01) and operation rate (-14.5%, P < 0.01). Before and after exposure, the average monthly total costs of pal-liative care group were slightly higher than those of standard care group (Before exposure: 20 092.3 yuan vs. 19 132.8 yuan, P=0.725; After exposure: 9 719.8 yuan vs. 8 818.8 yuan, P=0.165). Palliative care increased the average monthly total cost by 2 208.8 yuan, but it was not statistically significant (P=0.316). CONCLUSION Palliative care can increase the opioid consumption in advanced cancer patients, reduce the rates of hospitalization, ICU and surgery, but has no significant effect on medical expenditure.
Humans ; Palliative Care/economics* ; Neoplasms/drug therapy* ; Analgesics, Opioid/economics* ; Male ; Female ; Middle Aged ; Aged ; Hospitalization/economics* ; Intensive Care Units/statistics & numerical data* ; Health Expenditures/statistics & numerical data* ; Adult ; Drug Utilization/statistics & numerical data* ; Patient Acceptance of Health Care/statistics & numerical data*

Drug use monitoring and evaluation play a key role in promoting drugs to return to clinical value,optimizing the basic medicine system,and improving the drug supply guarantee system.In order to promote the implementation of drug use monitoring and evaluation in medical institutions,the Pharmaceutical Affairs Committee of the Chinese Hospital Association led the efforts of organizing relevant domestic experts to follow the group standard development process.It successfully formulated the group standard of Drug Use Monitoring and Evaluation through the steps of problem sorting,framework construction,evidence collection,draft writing,opinion consultation,and standard formation.This article introduces the standard formulation process in detail,and explains and analyzes the content of the standard,aiming to help readers better understand the connotation of drug use monitoring and evaluation,and provide practical guidance.

Objective:To investigate the effects of fluoride exposure on autophagy and the expression levels of adenosine monophosphate activated protein kinase (AMPK), mammalian target of rapamycin (mTOR) and Unc-51-like kinase 1 (ULK1) in mouse neuroblastoma and rat glioma fusion cells (NG108-15 cells).Methods:NG108-15 cells were cultured in vitro and divided into control group (0 mg/L), low fluoride group (20 mg/L), medium fluoride group (40 mg/L) and high fluoride group (80 mg/L) according to the final concentration of sodium fluoride, and the cells were collected after 24 h of treatment for standby. NG108-15 cells autophagy was detected by immunofluorescence/immunocytochemistry (IF/ICC method, the autophagy positive control group was treated with chloroquine phosphate); the mRNA expression levels of AMPK, mTOR and ULK1 in each group were detected by real-time fluorescent quantitative polymerase chain reaction (qRT-PCR); the protein expression levels of autophagy related protein microtubule-associated protein 1 light chain 3B (LC3B), AMPK, mTOR, ULK1, phosphorylation (p)-AMPK, p-mTOR, p-ULK1 in each group were detected by Western blotting. Results:No autophagosome was detected in the control group, and autophagosomes were detected in all the fluoride groups. The protein expression level of LC3B in the low, medium and high fluoride groups (1.80 ± 0.59, 2.16 ± 0.60, 2.30 ± 0.57) was significantly higher than that in the control group (1.00 ± 0.29, P < 0.05). The results of qRT-PCR showed that compared with the control group, the mRNA expression levels of AMPK in medium and high fluoride groups were higher (2.30 ± 0.57, 4.41 ± 1.05 vs 1.00 ± 0.01, P < 0.05); the mRNA expression levels of mTOR in the low, medium and high fluoride groups were lower (0.79 ± 0.04, 0.76 ± 0.09, 0.64 ± 0.10 vs 1.00 ± 0.01, P < 0.05), and the mRNA expression levels of ULK1 were higher (1.81 ± 0.39, 1.96 ± 0.35, 4.22 ± 1.03 vs 1.00 ± 0.01, P < 0.05). The results of Western blotting showed that compared with the control group, the protein expression levels of AMPK (1.21 ± 0.05, 1.20 ± 0.04, 1.30 ± 0.07 vs 1.00 ± 0.03), p-AMPK (1.12 ± 0.05, 1.20 ± 0.06, 1.49 ± 0.07 vs 1.00 ± 0.02), ULK1 (1.16 ± 0.05, 1.26 ± 0.05, 1.15 ± 0.05 vs 1.00 ± 0.04) and p-ULK1 (1.19 ± 0.04, 1.17 ± 0.02, 1.24 ± 0.05 vs 1.00 ± 0.05) in the low, medium and high fluoride groups were higher ( P < 0.05), and the protein expression levels of mTOR were lower (0.77 ± 0.03, 0.60 ± 0.03, 0.55 ± 0.04 vs 1.00 ± 0.04, P < 0.05); the protein expression levels of p-mTOR in the medium and high fluoride groups were lower (0.93 ± 0.05, 0.48 ± 0.02 vs 1.00 ± 0.02, P < 0.05). Conclusion:Fluoride exposure can induce autophagy in NG108-15 cells, and the expression of AMPK and ULK1 are up-regulated, while the expression of mTOR is down-regulated.

OBJECTIVE To provide reference and suggestions for dynamic adjustment of classification management lists for clinical use of antibiotics and the promotion of rational use of antibiotics. METHODS The latest version of provincial classification management lists for clinical use of antibiotics were aggregated into the “national list”， which was compared with 2021 WHO AWaRe classification list of antibiotics （hereinafter referred as to “AWaRe classification list”） to make a descriptive statistical analysis about the number of different classes of antibiotics in the two lists and their differences. RESULTS Based on the different classification principles， 262 kinds of antibiotic preparations in the national list were classified into non-restricted （84）， restricted （83） and highly-restricted classes （95）， and 258 kinds in the AWaRe classification list were classified into access （87）， watch （142） and reserve classes （29）； 182 kinds of antibiotic preparations were both included in the two lists. In the national list， among the non-restricted antibiotic preparations， 36 kinds belonged to access class， 30 belonged to watch class and 1 belonged to reserve class； among restricted antibiotic preparations， 7 belonged to access class， 46 kinds belonged to watch class and 3 belonged to reserve class； among highly-restricted antibiotic 82805019。E-mail：yyy211anne@163.com preparations， 9 belonged to access class， 35 belonged to watch class and 15 kinds belonged to reserve class. Among them， 91 kinds of antibiotic preparations were not recommended by WHO （20 kinds） or not included in the AWaRe classification list （71 kinds）. CONCLUSIONS The classification methods of two lists are different in classification principles and grading of some similar drugs. The classification management list of antibiotics is one of the key points of antibiotics management， more research is needed in the future to provide sufficient evidence for optimizing antibiotics classification management.

OBJE CTIVE To inv estigate the antibiotic use and rationality for children in community health service institutions from Beijing ，and to provide reference for promoting rational use of antibiotics in primary healthcare institutions. METHODS All the prescriptions for children from primary healthcare institutions in 2019 were extracted from prescription review system of community health service institutions in Beijing. The use of antibiotics was described according to the related indicators of the World Health Organization/International Network for Rational Use of Drug （WHO/INRUD）. The structure of antibiotics use was analyzed according to the anatomical therapeutic chemical （ATC）classification as well as the WHO AWaRe classification and diagnosis. RESULTS A total of 288 primary healthcare institutions and 10 422 prescriptions for children were included. The number of institutions in high-income areas ，middle-income areas and low-income areas were 119，80 and 89 respectively，and the number of prescriptions involved were 2 430，2 163 and 5 829 respectively，including 1 447 prescriptions involving antibiotics （13.9％）. Among 1 447 prescriptions，the rate of prescriptions involving combined use of antibiotics was 1.4％（20 pieces）；the rate of prescriptions involving antibiotics injection was 9.7％（141 pieces）；4.8％ antibiotics prescriptions were rated as unreasonable （69 pieces）. The three most commonly used antibiotics were the macrolides （40.2％），the second-generation cephalosporins （26.5％） and the third-generati on cephalosporins （23.4％）. The proportion of antibioti cs prescriptions from groups of access ，caution， reserve and not recommended were 9.1％，92.1％，0.3％，and 0， respectively. The rate of antibiotics prescriptions fortonsillitis was the highest （31.9％ ）. Among 69 irrationalantibiotics prescriptions ，main of them were irrational drug use （56 pieces，81.2％）. CONCLUSIONS The rate of antibiotics prescriptions for children in primary healthcare institutions from Beijing is lower than the standard of WHO antibiotics prescription rate （20.0％-26.8％），but the use rate of antibiotics at caution grade is too high.

OBJECTIVE To provide emp irical evidence for relevant decision makers in China to formulate and improve policies related to children ’s medicine use . METHODS Based on the purchase data （Jul. 2016-Jun. 2019）of 18 tertiary children ’s hospitals，the availability of medicines included in the 7th edition of WHO Model List of Essential Medicines for Children （WHO EMLc）and their influential factors were investigated according to standard medicine investigation method recommended by the WHO and Health Action International . RESULTS A totally 189 active ingredients listed in the 7th edition of WHO EMLc were available at 18 tertiary children ’s hospitals in China ，which referred to 229 medicines. The availability of Budesonide inhalation suspension，oral rehydration salt ，Immunoglobulin for injection and Water for injection was 100%. In each quarter from Jul . 2016 to Jun . 2019，the availability of more than half of the medicines exceeded 50%，and the availability of the medicines remained basically stable in each quarter . The overall availability of cardiovascular system medicines and blood system medicines was the highest，while that of antiparasitic medicines and dermatology medicines was lower . There were 28 medicines（12.2%）that were not approved for use in children in China ，the use of which were off -label. The medicines which had been approved for children and which were included in national essential medicine list had a significantly higher availability （P＜0.05）. CONCLUSIONS The availability of essential medicines for children is generally better at tertiary children ’s hospitals in China . But the use of some essential medicines in children are off -label. In order to ensure the safety and the availability of essential medicines for children ，it is suggested to introduce China ’s essential medicines list for children ，to promote clinical trials in children for commonly used medicines，and to updete the drug manual in time .

OBJECTIVE To explore wheth er there is a relationship between the judgment results of medical damage liability disputes related to off-label drug use and evidence-based evidence. METHODS By searching for medical damage liability disputes related to off-label drug use up to 2021 on pkulaw.cn ，documents were extracted to record objective factors ，subjective factors and judgment results ；whether there was evidence-based evidence was judged according to Off-label Drug Use List and Evidence-based Evaluation Standards for Off-label Drug Use of Guangdong Pharmaceutical Association ；univariate analysis was adopted to test the relationship between the judgment results and evidence-based evidence. RESULTS A total of 57 cases were included. Cases mainly occurred in the eastern China （63.2％）and tertiary hospitals （64.9％），the main appraisal agency was the appraisal center or institute（61.4％），and the most common type of off-label drug use was overdose drug use （45.6％）. Among the judgment results ， 23 cases（40.4％）of off-label drug use had a causal relationship with medical damage ，most of the responsibility of doctors was secondary responsibility （28.1％），and the actual compensation amount of the most cases were less than 100，000 yuan（54.4％）. There were 25 cases（43.9％）with evidence-based evidence. Univariate analysis found that for off-label drug use the claim amount of the case with evidence-based evidence was significantly higher than that of the case without evidence-based evidence （P＝ 0.040），and there was no significant correlation between evidence-based evidence and the actual compensation amount of the case （P＝0.741），causality determination （P＝0.256），liability type （P＝0.598）or appraisal agency （P≥0.260）. CONCLUSIONS There is no significant correlation between the judgment results of medical damage liability disputes related to off-label drug use and evidence-based evidence ，indicating that there may be certain differences between judicial trials and medical science. The off-label drug use should be regulated by establishing a complete off-label drug use management system and standardizing informed consent procedure for off-label drug use. 1610307322@pku.edu.cn

OBJECTIVE：To provide scientific basis for evaluating the burden caused by antibiotic resistance （AbR）and reference for policy making on crubing AbR in China. METHODS ：Databases including CNKI ，Wanfang database ，VIP，PubMed， Scopus，Medline and EconoLite from Jan. 1st 2016 to Aug. 10th 2020 were searched to collect studies on burden caused by AbR in China . After independent literature screening anddata extraction ，Newcastle-Ottawa scale （NOS）was used to evaluate the literature quality ，and a descriptive analysis was conduced to evaluate the health and economic burden caused by AbR. RESULTS ：A total of 27 Chinese and English literatures were included. The NOS scores of i ncluded literatures were 4-6，and all of them were retrospective case-control study ； the patients were divided into case group （resistance infection ） and control group （susceptible infection or non-infection ）； mortality，length of stay and medical expenditure were commonly applied as the measurement indexes. In the included studies ，the mortality of patients infected with AbR bacteria was 0.7-12.0 times that of patients infected with susceptible bacteria ；the mean or medium value of total length of stay was 0.9-2.5 times that of patients infected with susceptible bacteria ；the mean or medium of total medical expenditure was 1.0-2.7 times that of patients with susceptible bacteria infection. The differences in these indicators were greater between patients infected with AbR infections and those without becterial infections. CONCLUSIONS ：Bacterial drug resistance could increase the health and economic burden. However ，the existing relevant studies were mainly single center researches，the sample representation was insufficient ；the research design did not adjust for time-dependent bias ；the repeatability was low ，and the perspective of evalution was limited. It is urgent to carry out multicenter studies with higher quality to comprehensively evaluate the health and economic burden caused by AbR in China.