It has been not been updated for nearly 5 years since the Pharmacoepidemiology Professional Committee of the Chinese Pharmaceutical Association released the Guide on Methodological Standards in Pharmacoepidemiology in China(1st edition)in 2019,and an update is urgently needed.This study adopts a systematic review approach to comprehensively search for global pharmacoepidemiology methodological guidelines and analyze their development status.By extracting the frameworks and key elements of the guidelines,the China's guide was compared with other included guidelines,its shortcomings were analysed,and pragmatic and feasible suggestions for improvement in line with China's national conditions,were proposed in order to provide references for updating China's guide.A systematic search was conducted by searching PubMed,Embase,CNKI,WanFang Data and 17 official websites of international academic organizations for pharmacoepidemiology and regulatory agencies from countries or regions including Europe,the United States,Japan,and China,etc.,and relevant guidelines or standards were screened based on predefined inclusion and exclusion criteria,resulting in the inclusion of 33 methodological guidelines or standards for pharmacoepidemiological studies.A qualitative synthesis approach was then employed to extract core elements from the guidelines through thematic categorization and content summarization,followed by a descriptive comparative analysis.The results indicate that the 1st edition of the China's guide provides relatively comprehensive guidance on adverse drug reaction reporting and publication of research findings.However,there are gaps in study protocol development,data analysis during study implementation,study reporting,and specific study scenarios.By integrating and drawing upon the latest international pharmacoepidemiology methodology guidelines while balancing comprehensiveness,practicality,and user-friendliness,this study provides recommendations for updating the China's guide.

Pharmacoepidemiology is a scientific discipline that applies epidemiological principles and methods to study the utilization and effects of pharmaceuticals in populations.It plays a crucial role in promoting rational drug use and improving public health outcomes.High-quality pharmacoepidemiological research relies on rigorous methodological frameworks.Chinese Pharmaceutical Association(CPA)has officially initiated the development/revision of the of the Guide on Methodological Standards in Pharmacoepidemiology in China(2nd edition)in 2024.This revision project was supported by the Pharmacoepidemiology Committee of CPA,and was led by the Department of Epidemiology and Biostatistics at Peking University School of Public Health,which provided methodological guidance,in collaboration with multidisciplinary experts from across the country.Building on the experience of the 1st edition's development,the working group conducted a qualitative systematic review,to extract key information from global pharmacoepidemiology-related guidelines,laying the foundation for the development/revision proposals of the 2nd edition.Subsequently,through two rounds of Delphi method expert consultations and qualitative interviews,alongside extensive discussions within the working group,the draft revision of the guideline was created.Finally,through an expert consensus meeting using the Nominal Group Technique(NGT),a consensus was reached,resulting in a methodological guideline that integrates international perspectives with local applicability for pharmacoepidemiological research in China.The 2nd edition consists of 41 entries,including 8 primary entries,20 secondary entries,and 13 tertiary entries.It comprehensively covers key aspects such as study protocol development,study implementation,adverse event reporting,research report writing,and dissemination of study findings.Additionally,it addresses specific application scenarios and topics,as well as the application of artificial intelligence and real-world studies.

Pharmacoepidemiology is an interdisciplinary discipline that applies epidemiological research methods to evaluate the application and effect of drugs within population.Standardizing pharmacoepidemiological research methods is crucial for ensuring the quality of research and promoting the development of the discipline.The Pharmacoepidemiology Professional Committee of Chinese Pharmaceutical Association developed the Guide on Methodological Standards in Pharmacoepidemiology(1st edition),in 2019,but has not been updated in over five years.Other,countries/regions such as Europe,America,Japan and South Korea have made a lot of progress in developing and updating the guidelines.Therefore,the rapid development of pharmacoepidemiology in our country and the growing need to align with international standards make it essential to update the guidelines.The second edition of the guidelines was developed through a process that included systematic reviews,practical surveys,and multidisciplinary collaboration.Compared with the first edition,the updated version has made many important changes in research design,data sources,specific application scenarios and more,and added new contents such as the application of artificial intelligence.The purpose of this paper is to emphasize the necessity of updating the guidelines,selecting important changes and formulating interpretation plans.It aims to provide references for relevant professionals to comprehensively understand and apply the new guidelines,and to promote the standardized development and quality of pharmacoepidemiologic research in our country,further advancing the field.

Objective:To establish a flow cytometric bead assay (FCBA) for detecting von Willebrand factor (vWF) activity based on mutant GPⅠbα and to perform its clinical validation.Methods:Recombinant GPⅠbα protein with M239V, D235Y, and C65A point mutations was constructed and bound to flow cytometric beads. vWF in samples bound to the recombinant protein, and FITC-labeled rabbit anti-human vWF polyclonal antibody was added for detection and analysis using flow cytometry. A total of 32 patients with von Willebrand disease (10 males and 22 females, aged 26.81±6.96 years) admitted to the Department of Hematology at the First Affiliated Hospital of Soochow University from January 1, 2022, to November 30, 2023, were enrolled. Additionally, 51 healthy controls (17 males and 34 females, aged 31.56±8.98 years) were included. Plasma from 20 healthy controls was pooled in equal proportions to create standard plasma. Fourteen dilutions were prepared, ranging from the original plasma to a 1∶8, 192 dilution, and a curve was plotted according to the FCBA protocol to determine the optimal dilution. Plasma from one healthy control was aliquoted and frozen, and FCBA was performed on days 1, 5, 15, 30, 45, and 60 after bead coating to evaluate stability. The same healthy control plasma sample was tested 20 times using both FCBA and vWF enzyme-linked immunesorbent assay (ELISA) to calculate within-batch precision. The same sample was tested daily for 10 consecutive days using both FCBA and vWF-ELISA to calculate between-batch precision. All samples were tested using FCBA, and the same samples were also tested using vWF-ELISA. The χ2 test was used to compare the positive rates, negative rates, and accuracy of the two methods. One sample was used as the base sample, and another sample with a known activity of 100% was diluted to high, medium, and low activities and added to the base sample. Recovery rates were calculated using both FCBA and vWF-ELISA. Re-collected 11 cases of vWD patient samples and 10 cases of healthy subjects, and detected vWF activity using the FCBA method to validate the concordance of FCBA in clinical applications. Results:The optimal dilution for standard plasma was determined to be 1∶64. The coated beads remained stable for detection up to 60 days, with correlation coefficients of the standard curve on days 1, 5, 15, 30, 45, and 60 being 0.98, 0.98, 0.97, 0.95, 0.95, and 0.95, respectively. The within-batch coefficients of variation for FCBA and vWF-ELISA were 5.35% and 6.08%, respectively, while the between-batch coefficients of variation were 7.02% and 7.98%, respectively. The correlation coefficient between FCBA and vWF-ELISA was R2=0.798 ( P0.01). The positive rates were 90.63% and 84.38% ( χ2=0.571, P0.05), the negative rates were 92.16% and 94.12% ( χ2=0.153, P0.05), and the accuracy rates were 91.57% and 90.36% ( χ2=0.073, P0.05) for FCBA and vWF-ELISA, respectively. In the recovery experiment, the high-value recovery rates for FCBA and ELISA were 102.11% and 99.32%, respectively, the medium-value recovery rates were 98.50% and 95.66%, and the low-value recovery rates were 95.34% and 88.51%. The FCBA method achieved a 100% concordance rate in detecting type 1, type 2, and type 3 vWD, as well as healthy subjects. Conclusion:A ristocetin-independent FCBA method for detecting vWF activity based on mutant GPⅠbα is successfully established.

Objective:To compare the effects of using cone beam CT (CBCT) and oral scanning registration on implant positional accuracy during robot-assisted implant surgery, and to provide a basis for selecting the appropriate registration for robot-assisted implant surgical options.Methods:One patient with dentition defect, specifically missing teeth at positions 21 and 26 and having natural teeth adjacent mesially and distally to the edentulous area, who visited the Department of Oral Implantology, School of Hospital of Stomatology Wuhan University in 2024 were selected. Based on reconstructed imaging data, 30 identical jaw models were printed. These models were divided into a CBCT registration group and an intra-oral scanning registration group (15 models per group). An associate chief physician with extensive experience in implant surgery performed preoperative registration using the implant robot and completed the implant surgeries. Postoperative CBCT scans were used to determine the three-dimensional position of the implants. The deviations between the planned implant position and the actual position were evaluated, including deviations at the implantation point, apical point, and angular deviation. The differences between the two groups were compared.Results:The implantation deviation was 0.675 (0.490) mm, apical deviation was (0.680±0.272) mm, and the angular deviation was 0.566°±0.147° in the CBCT registration group, and in the intra-oral scanning registration group, implantation deviation was 0.695 (0.313) mm, apical deviation was (0.667±0.217) mm, and the angular deviation was 0.523°±0.168°. There was no statistically significant error in implant precision between the two groups ( P>0.05). Conclusions:This in vitro experiment found that the use of intra-oral scanning registration in robot-assisted implant surgery can achieve similar implant placement accuracy as CBCT registration.

Objective:To explore the effects of deep hyperthermia on chemotherapy-related adverse effects and immune-inflammatory indicators in the patients undergoing postoperative adjuvant chemotherapy for colorectal cancer.Methods:This retrospective study included 52 patients who underwent surgery for colorectal cancer at the Affiliated Zhongshan Hospital of Dalian University from September 2021 to December 2023. The patients were divided into two groups based on treatment method: the combination group ( n=29) received postoperative adjuvant chemotherapy combined with deep hyperthermia, while the chemotherapy group ( n=23) received postoperative adjuvant chemotherapy alone. Both groups were treated with the XELOX regimen (oxaliplatin + capecitabine). The degree of bone marrow suppression during treatment was assessed by analyzing peripheral blood parameters, including hemoglobin, leukocyte count, neutrophil count, and platelet count. Immune-inflammatory indicators, including complement, procalcitonin (PCT), interleukin-6 (IL-6), systemic immune-inflammation index (SII), neutrophil-to-lymphocyte ratio (NLR), and platelet-to-lymphocyte ratio (PLR), were compared before and after treatment in both groups to evaluate the effects of deep hyperthermia on the immune-inflammatory response. Chi-square test or Fisher's exact test (two-tailed) was used to compare bone marrow suppression rates, and the immune-inflammatory indicators between the two groups were compared using t-tests or non-parametric tests, depending on whether the data conformed to a normal distribution. Results:In terms of myelosuppression, the incidence rates of moderate to severe decreases in leukocytes, neutrophils, platelets, and hemoglobin in the combination group were 31%, 31%, 21%, and 14%, respectively, compared to 52%, 61%, 48%, and 9% in the chemotherapy group. The change in PCT levels before and after treatment was significantly greater in the combination group than in the chemotherapy group ( P = 0.010). Both the combination group and the chemotherapy group showed significant reductions in SII, NLR and PLR after treatment, and the differences were statistically significant (all P < 0.05). The change in NLR before and after treatment was significantly greater in the combination group than in the chemotherapy group ( P = 0.031). Conclusions:Deep hyperthermia can alleviate chemotherapy-induced adverse effects such as thrombocytopenia and neutropenia in patients undergoing postoperative adjuvant chemotherapy for colorectal cancer. It also appears to improve the inflammatory response in these patients.

Objective:To compare the effects of using cone beam CT (CBCT) and oral scanning registration on implant positional accuracy during robot-assisted implant surgery, and to provide a basis for selecting the appropriate registration for robot-assisted implant surgical options.Methods:One patient with dentition defect, specifically missing teeth at positions 21 and 26 and having natural teeth adjacent mesially and distally to the edentulous area, who visited the Department of Oral Implantology, School of Hospital of Stomatology Wuhan University in 2024 were selected. Based on reconstructed imaging data, 30 identical jaw models were printed. These models were divided into a CBCT registration group and an intra-oral scanning registration group (15 models per group). An associate chief physician with extensive experience in implant surgery performed preoperative registration using the implant robot and completed the implant surgeries. Postoperative CBCT scans were used to determine the three-dimensional position of the implants. The deviations between the planned implant position and the actual position were evaluated, including deviations at the implantation point, apical point, and angular deviation. The differences between the two groups were compared.Results:The implantation deviation was 0.675 (0.490) mm, apical deviation was (0.680±0.272) mm, and the angular deviation was 0.566°±0.147° in the CBCT registration group, and in the intra-oral scanning registration group, implantation deviation was 0.695 (0.313) mm, apical deviation was (0.667±0.217) mm, and the angular deviation was 0.523°±0.168°. There was no statistically significant error in implant precision between the two groups ( P>0.05). Conclusions:This in vitro experiment found that the use of intra-oral scanning registration in robot-assisted implant surgery can achieve similar implant placement accuracy as CBCT registration.

Objective:To evaluate the efficacy and safety of nebulized inhalation of recombinant human interferon (IFN) α1b injection in the treatment of respiratory syncytial virus (RSV) associated lower respiratory tract infections (pneumonia and bronchiolitis) in children.Methods:A randomized, double-blind, parallel, placebo-controlled add-on design was used.Children with pneumonia or bronchiolitis aged 2 months to 5 years who tested positive for RSV antigen within 72 hours of onset from 30 clinical trial sites including Beijing Children′s Hospital, Capital Medical University between February 2021 and December 2022 were included in this study and randomly divided into 2 groups at a ratio of 1∶1 based on a stratified-block method.Both groups received basic treatments such as cough control, asthma relieving, expectorant treatment, fever reduction, oxygen therapy, etc.The experimental group received additional nebulized inhalation of IFN α1b injection at a dose of 2.0 μg/(kg·time), twice a day.The control group received nebulized inhalation of placebo twice a day.Clinical efficacy was evaluated based on indicators such as the duration of clinical symptoms and signs, and the Kaplan-Meier method was used to calculate the median and 95% CI of the duration of clinical symptoms and signs.The Log-rank test was used to compared data between groups.Safety was assessed through the incidence of adverse reactions and laboratory tests, and the Chi-square test was used to analyze the difference between groups. Results:There were 123 children in the experimental group and 122 children in the control group.The median durations of all the 5 clinical symptoms and signs [including shortness of breath, wheezing, dyspnea (visible retractions), decreased transcutaneous oxygen saturation, and abnormal mental state] in the experimental group after treatment were slightly shortened than those in the control group [2.7 d(95% CI: 1.9-3.0 d)] vs.[2.9 d(95% CI: 2.6-3.6 d), P=0.027].The improvement in dyspnea (retractions) was especially pronounced in the experimental group, with a relief rate of 50.0% (0, 100%) on the first day of administration[compared with 0 (0, 50.0%) in the control group ( Z=2.002, P=0.025)].The median duration of dyspnea in the experimental group was nearly 1 day shorter than that in the control group [1.0 d(95% CI: 0.7-1.7 d) vs.1.8 d(95% CI: 1.0-2.5 d), P=0.046].There were no significant difference in hospital stay [6.0(5.0, 8.0) d vs.6.5(5.0, 8.0) d, Z=0.675, P=0.500], oxygen therapy duration [32.0(14.0, 96.3) h vs.39.0 (24.0, 83.2) h, Z=0.094, P=0.925], the recovery rate from clinical symptoms during treatment [(105/106, 99.1%) vs.(96/101, 95.0%)], and recurrence rate [(0/106, 0) vs.(2/101, 2.0%)] between the 2 groups (all P>0.05).However, the above-mentioned four indicators in the experimental group showed a trend of clinical benefits.The quantitative virus detection results showed that the RSV viral load in both groups decreased after treatment compared to before treatment.After 2 days of treatment, the decline rate of RSV viral load from the baseline was 0.90 lg copies/(mL·d) in the experimental group and 0.25 lg copies/(mL·d)in the control group, with a statistically significant difference ( P<0.05).Furthermore, there was no statistically significant difference in the incidence of adverse reactions between the 2 groups ( P>0.05).Importantly, no drug-related serious adverse reactions occurred in both groups. Conclusions:The nebulized inhalation therapy of IFN α1b demonstrates efficacy and safety in treating pediatric RSV associated lower respiratory tract infections.It particularly offers outstanding clinical therapeutic value for severe children.

It has been not been updated for nearly 5 years since the Pharmacoepidemiology Professional Committee of the Chinese Pharmaceutical Association released the Guide on Methodological Standards in Pharmacoepidemiology in China(1st edition)in 2019,and an update is urgently needed.This study adopts a systematic review approach to comprehensively search for global pharmacoepidemiology methodological guidelines and analyze their development status.By extracting the frameworks and key elements of the guidelines,the China's guide was compared with other included guidelines,its shortcomings were analysed,and pragmatic and feasible suggestions for improvement in line with China's national conditions,were proposed in order to provide references for updating China's guide.A systematic search was conducted by searching PubMed,Embase,CNKI,WanFang Data and 17 official websites of international academic organizations for pharmacoepidemiology and regulatory agencies from countries or regions including Europe,the United States,Japan,and China,etc.,and relevant guidelines or standards were screened based on predefined inclusion and exclusion criteria,resulting in the inclusion of 33 methodological guidelines or standards for pharmacoepidemiological studies.A qualitative synthesis approach was then employed to extract core elements from the guidelines through thematic categorization and content summarization,followed by a descriptive comparative analysis.The results indicate that the 1st edition of the China's guide provides relatively comprehensive guidance on adverse drug reaction reporting and publication of research findings.However,there are gaps in study protocol development,data analysis during study implementation,study reporting,and specific study scenarios.By integrating and drawing upon the latest international pharmacoepidemiology methodology guidelines while balancing comprehensiveness,practicality,and user-friendliness,this study provides recommendations for updating the China's guide.

Pharmacoepidemiology is an interdisciplinary discipline that applies epidemiological research methods to evaluate the application and effect of drugs within population.Standardizing pharmacoepidemiological research methods is crucial for ensuring the quality of research and promoting the development of the discipline.The Pharmacoepidemiology Professional Committee of Chinese Pharmaceutical Association developed the Guide on Methodological Standards in Pharmacoepidemiology(1st edition),in 2019,but has not been updated in over five years.Other,countries/regions such as Europe,America,Japan and South Korea have made a lot of progress in developing and updating the guidelines.Therefore,the rapid development of pharmacoepidemiology in our country and the growing need to align with international standards make it essential to update the guidelines.The second edition of the guidelines was developed through a process that included systematic reviews,practical surveys,and multidisciplinary collaboration.Compared with the first edition,the updated version has made many important changes in research design,data sources,specific application scenarios and more,and added new contents such as the application of artificial intelligence.The purpose of this paper is to emphasize the necessity of updating the guidelines,selecting important changes and formulating interpretation plans.It aims to provide references for relevant professionals to comprehensively understand and apply the new guidelines,and to promote the standardized development and quality of pharmacoepidemiologic research in our country,further advancing the field.