OBJECTIVE To conduct a comprehensive clinical evaluation of four nucleoside （acid） analogues that have been approved and marketed in China， such as entecavir， tenofovir disoproxil fumarate， tenofovir alafenamide fumarate， and tenofovir amibufenamide. METHODS According to the Guideline for the Administration of Clinical Comprehensive Evaluation of Drugs （2021 edition， trial implementation）， a comprehensive search was conducted across databases including CNKI， Wanfang Data， VIP， PubMed， the Cochrane Library， Embase， as well as relevant official websites. Drug package inserts， guidelines， consensus statements， and relevant literature for the four drugs were collected and subjected to a comprehensive evaluation across six dimensions： safety， efficacy， cost-effectiveness， innovativeness， suitability， and accessibility. RESULTS The scores for entecavir in terms of safety， efficacy， cost-effectiveness， innovativeness， suitability， and accessibility-along with its comprehensive score-were 13， 14， 13， 10， 18， and 6， totaling 74 points. For tenofovir disoproxil fumarate， the respective scores were 13， 17， 18， 8， 18， and 7， totaling 81 points. For tenofovir alafenamide fumarate， the scores were 14， 20， 12， 8， 18， and 5， totaling 77 points. Finally， for tenofovir amibufenamide， the scores were 10.5， 17， 10， 6， 15， and 4， totaling 62.5 points. CONCLUSIONS Tenofovir disoproxil fumarate， with the highest score， is recommended as the first-line option， suitable for adults， children， and pregnant women. However， caution is warranted for potential renal impairment. Tenofovir alafenamide fumarate is recommended as a second-line alternative， particularly for individuals at high risk for bone and renal damage. Entecavir has a score similar to tenofovir alafenamide fumarate but requires dosing on an empty stomach and dose adjustment based on renal function of patients. Tenofovir amibufenamide received the lowest score and is considered a weak recommendation. The clinical application of these nucleoside （acid） analogues should be individualized based on the patient’s age， physiological status， and risk factors.

To standardize the management of high-alert medications in medical institutions and ensure their safe and ef-fective use,based on relevant national regulations and normative documents,international high-alert medication management guidelines,and expert opinions,the Pharmaceutical Specialized Committee of the Chinese Hospital Association led the develop-ment of the Pharmaceutical Supply Services—Key Drugs Management—High-alert Medications.This article elaborated on the for-mulation process of this standard and provides an in-depth analysis of its key contents.It aimed to offer guidance and reference for medical personnel,helping them to thoroughly understand and master the management requirements of high-alert medications,thereby enhancing the management level of high-alert medications and ensuring the safe and effective use of medications for pa-tients.

To standardize the management of high-alert medications in medical institutions and ensure their safe and ef-fective use,based on relevant national regulations and normative documents,international high-alert medication management guidelines,and expert opinions,the Pharmaceutical Specialized Committee of the Chinese Hospital Association led the develop-ment of the Pharmaceutical Supply Services—Key Drugs Management—High-alert Medications.This article elaborated on the for-mulation process of this standard and provides an in-depth analysis of its key contents.It aimed to offer guidance and reference for medical personnel,helping them to thoroughly understand and master the management requirements of high-alert medications,thereby enhancing the management level of high-alert medications and ensuring the safe and effective use of medications for pa-tients.

Objective:To share related knowledge and experiences with countries along the line, literature regarding current cohort studies was summarized. Distribution, establishment and development of cohort studies among large prospective general population were analyzed in 17 countries of Western Asia and the 16 countries of Central and Eastern Europe.Methods:Literature review was conducted to collect basic information on cohort studies, with descriptive study used to analyze the characteristics of these cohort studies.Results:There were 562 cohort studies with sample size as more than 1 000 stated in Western Asia and Central and Eastern Europe, including 468 (83.27 %) carried out in the nation itself and 94 (16.73 %) with international multicentered collaboration. According to the nature of cohort studies, 347 (61.74 %) were etiologically based. As for the contents involved, 310 (55.16 %) of them targeted on chronic/non-communicable diseases, 125 (22.24 %) concentrated on maternal and child health. Among those on chronic/non-communicable diseases, 51 (16.45 %) were on cancers and 83 (26.77 %) on cardiovascular disease studies. There appeared 10 large prospective cohort studies targeting on general population, mainly ongoing in Iran and European countries, with a duration of 8-29 years, including 4 of them with sample size as more than 50 000. In terms of the contents, epidemiological investigation, physical examination and biological samples collection took the major parts. Few papers were published in 9 out of the 10 cohort studies at the early stage of those projects but the number of papers increased annually and stabilized to certain extent. Conclusions:The regional distribution of cohort studies carried out in countries from the Western Asia and Central and Eastern European areas appeared unbalanced. Contents of these designs would mainly involve etiological studies, with focus on non-communicable diseases as cancer, cardiovascular disease, diabetes, respiratory diseases, mental and psychological diseases, and maternal and infant health etc.. However, only few large prospective cohort studies would base on general population.

OBJECTIVE: To establish a clinically applicable model of rapid identification of adverse drug reaction program (RiADP) for risk management and decision-making of clinical drug use. METHODS: Based on the theory of disproportion analysis, frequency method and Bayes method, a clinically applicable RiADP model in R language background was established, and the parameters of the model were interpreted by MedDRA coding. Based on the actual monitoring data of FDA, the model was validated by the assessing hepatotoxicity of lopinavir/ritonavir (LPV/r). RESULTS: The established RiADP model included four parameters: standard value of adverse drug reaction signal information, empirical Bayesian geometric mean value, ratio of reporting ratio and number of adverse drug reaction cases. Through the application of R language parameter package "phViD", the model parameters could be output quickly. After being encoded by MedDRA, it was converted into clinical terms to form a clinical interpretation report of adverse drug reactions. In addition, the evaluation results of LPV/r hepatotoxicity by the model were matched with the results reported in latest literature, which also proved the reliability of the model results. CONCLUSIONS In this study, a rapid identification method of adverse reactions based on post marketing drug monitoring data was established in R language environment, which is capable of sending rapid warning of adverse reactions of target drugs in public health emergencies, and providing intuitive evidence for risk management and decision-making of clinical drugs.
Databases, Pharmaceutical ; Decision Making, Computer-Assisted ; Drug Monitoring ; Drug-Related Side Effects and Adverse Reactions ; HIV Protease Inhibitors ; adverse effects ; pharmacology ; Humans ; Liver ; drug effects ; Lopinavir ; adverse effects ; toxicity ; Models, Statistical ; Reproducibility of Results ; Software ; standards

Objective To analyze the risks of high alert drug concentrated potassium chloride injection in clinical application using failure mode and effect analysis (FMEA) method and make the relevant prevention measures.Methods A study team was established in the First Affiliated Hospital,Zhejiang University.The risk points in the application process of concentrated potassium chloride injection through literature search,questionnaires,and on-the-spot investigations were collected.Severity (S),frequency of occurrence(O),and likelihood of detection(D) of the risks related to these failure modes were scored and the risk priority numbers (RPN) were determined.The failure modes with RPN ＞ 10.0 or their severity up to 5.0 were screened out and the corresponding prevention strategies were formulated.Results Five risk points were collected through literature search;10 risk points were obtained through questionnaires,including 3 from physicians,3 from pharmacists,and 4 from nurses;and 5 risk points were obtained through on-the-spot investigations.Sixteen risk points with RPN ＞ 10.0 or severity up to 5.0 were further screened from the above links,including 3 from information system links,2 from drug storage links,4 from doctor prescription links,4 from pharmacist dispensing links,and 3 from nurse administration links.According to the selected risk points,22 prevention strategies were formulated.The prevention measures for the above 5 links were 4,4,6,5,and 3,respectively,including 11 mandatory strategies,9 recommended strategies,and 2 conditional strategies.Conclusion The risk points of concentrated potassium chloride injection application can be screened using FMEA method,which is helpful to formulate the preventive strategies for medication errors related to the drug.

Objective To analyze the risks of high alert drug concentrated potassium chloride injection in clinical application using failure mode and effect analysis (FMEA) method and make the relevant prevention measures.Methods A study team was established in the First Affiliated Hospital,Zhejiang University.The risk points in the application process of concentrated potassium chloride injection through literature search,questionnaires,and on-the-spot investigations were collected.Severity (S),frequency of occurrence(O),and likelihood of detection(D) of the risks related to these failure modes were scored and the risk priority numbers (RPN) were determined.The failure modes with RPN ＞ 10.0 or their severity up to 5.0 were screened out and the corresponding prevention strategies were formulated.Results Five risk points were collected through literature search;10 risk points were obtained through questionnaires,including 3 from physicians,3 from pharmacists,and 4 from nurses;and 5 risk points were obtained through on-the-spot investigations.Sixteen risk points with RPN ＞ 10.0 or severity up to 5.0 were further screened from the above links,including 3 from information system links,2 from drug storage links,4 from doctor prescription links,4 from pharmacist dispensing links,and 3 from nurse administration links.According to the selected risk points,22 prevention strategies were formulated.The prevention measures for the above 5 links were 4,4,6,5,and 3,respectively,including 11 mandatory strategies,9 recommended strategies,and 2 conditional strategies.Conclusion The risk points of concentrated potassium chloride injection application can be screened using FMEA method,which is helpful to formulate the preventive strategies for medication errors related to the drug.

OBJECTIVETo provide a scientific basis for the drug-combination and aim to examine whether astragaloside IV has the impact on the cytochrome P450 enzymes.

METHODTolbutamide, chlorzoxazone, coumarin, nifedipine, and phenacetin were as probe substrates of rat CYP2C9, CYP2E1, CYP2A6, CYP3A4, and CYP1A2, and were incubated in rat liver microsomes with astragaloside IV. Triplicate samples were run to generate IC50 value by incubating P450 probe substrates in the presence of five concentrations of astragaloside IV in the incubation mixture. The K(i) values were determined by fitting the probe substrate at various inhibitor concentrations to the equations for competitive inhibition, noncompetitive inhibition, noncompetitive inhibition, and mixed-type inhibition.

RESULTIC50 and K(i) values were estimated, and the types of inhibition were determined. Among the five probe substrates, astragaloside IV might not significantly affect CYP2E1, CYP2A6 and CYP1A2-mediated metabolism in rats, but was a competitive inhibitor of CYP2C9 (IC50 35.40 micromol x L(-1), K(i) 42.88 micromol x L(-1)), and was a uncompetitive inhibitor of CYP3A4 (IC50 88.24 micromol x L(-1), K(i) 33.31 micromol x L(-1)).

CONCLUSIONThese results suggested that astragaloside IV inhibited CYP2C9 and CYP3A4, which provided useful information for safe and effective use of astragaloside IV.

Animals ; Cytochrome P-450 Enzyme Inhibitors ; Cytochrome P-450 Enzyme System ; chemistry ; metabolism ; Drugs, Chinese Herbal ; chemistry ; pharmacology ; Enzyme Inhibitors ; chemistry ; pharmacology ; Kinetics ; Male ; Microsomes, Liver ; chemistry ; drug effects ; enzymology ; Rats ; Rats, Sprague-Dawley ; Saponins ; pharmacology ; Triterpenes ; pharmacology

Objective To investigate the association of radial arterial calcification damage with bone mineral density (BMD) and bone metabolism biomarkers in uremia patients.Methods Sixty-seven incident hemodialysis patients were recruited into uremic group.Serum creatinine,calcium,phosphorus,lumbar spine and femoral neck BMD were measured.Parathyroid hormone (iPTH),25OHD,1,25(OH)2D,fibroblast growth factor (FGF) 23,bone specific alkaline phosphates (BAP) and osteocalcin (BGP),type Ⅰ collagen pyridine crosslinked C-telopcptidc (ICTP) were detected.Radial artery calcification was analyzed by von Kossa staining and transmission electron microscopy.Arterial type Ⅰ collagen (Col Ⅰ) expression was examined.Twenty-three healthy cases received serum and BMD examination only as control.Results Uremic patients presented higher serum phosphate,iPTH,FGF23,lower serum calcium,25OHD,1,25 (OH)2D (all P ＜ 0.05),and lower lumbar spine and femoral neck BMD (all P ＜ 0.01) compared to controls.Significant calcium deposit was observed in radial arteries in 24 uremic cases (35.8％),including 10 cases of diabetes.Immunohistochemistric assay confirmed that Col Ⅰ expression increased around calcification site and electron microscope revealed that more calcium and phosphorus plaque attached among collagen fibers.No correlation was showed between iPTH and radial artery calcification (r =-0.08,P =0.306),but after stratified by iPTH levels,correlation of iPTH and calcification was found in low iPTH (＜ 150 ng/L) group and high iPTH group (＞ 300 ng/L) (r =-0.41,0.31,P=0.044,0.023).Diabetes,lumbar spine and femoral neck BMD,ICTP,FGF23 were correlated with arterial calcification (r =0.62,-0.25,-0.43,0.34,0.86,P =0.000,0.001,0.012,0.018,0.000).Multiple regression analysis showed femoral neck BMD,ICTP,FGF23 levels were independently associated with radial arterial calcification (β =-0.221,0.181,0.260,P =0.021,0.024,0.036).Conclusion In uremic patients,reduced BMD,abnormal bone turnover rate,especially accelerated bone reabsorption,and increased serum FGF23 level are independently associated with radial artery calcification.

Objective To examine the changes of histological parameters of radial artery in uremia,and to explore their effects on arterial stiffness.Methods Sixty uremic patients underwent arteriovenous fistula surgery for hemodialysis and 20 healthy subjects received healthy examination were collected as uremia group and control group, respectively.Segments of radial arteries were obtained from all of uremic subjects and were evaluated by HE, Masson, van Kossa staining and electron microscopy.The expressions of osteopontin (OPN), α-SMA and elastin in arterial wall were detected by immunostaining, and apoptotic cells were determined by TUNEL assay.All of the subjects in the two groups received brachial ankle pulse wave velocity (baPWV) examination and the results were compared.The associations among histological parameters and baPWV were analyzed.Results More than one half (34/60) of artery samples presented uniformly thickening intima, in which most of cells expressed α-SMA and a few cells underwent apoptosis.The subendothelial matrix was abundant in collagen fibers, and no calcium deposition was found.The media thickened obviously, with increased collagen fibers, reduced elastin, unchanged α-SMA expression, and a few apoptotic smooth muscle cells.Two thirds uremic arteries expressed OPN, of which only one half had significant calcium deposition.The adventitia thickened and no calcium deposition was found.The baPWV level in uremic subjects was ( 18.5 ± 3.2 ) m/s, far greater than that in control subjects ( P ＜ 0.001 ).Statistical analysis showed that baPWV value was correlated with media thickness, calcification degree, and collagen content positively, and with elastin expression negatively.For diabetic uremic subjects, the OR values of vascular calcium deposition and remarkably-elevated baPWV value were 3.1, 2.3, respectively.Conclusions Radial arterial intima often presents hyperplasia which is not related with baPWV increment in uremia.Arterial media calcification and collagen content incremental are the most two protuberant characteristics in uremia, especially in ones accompanied with diabetes.Medical calcification, collagen accumulation, and e]astin reduction may contribute to the increased arterial stiffness in uremia.