Rare diseases are a collective term for diseases with extremely low prevalence and incidence rates.Up to now,China has released two lists identifying a total of 207 rare diseases.Given that most rare diseases do not have drugs with corresponding indications,physicians frequently resort to using off-label drugs when treating patients with rare diseases.However,there is currently no systematic guideline or expert consensus for the use of off-label medications in China.To comprehensively collect existing evidence of off-label drug use for rare diseases,fully analyze and evaluate the rationality of off-label drug use for rare diseases,and standardize the management of off-label drug use for rare diseases,the Rare Disease Branch of Beijing Medical Association,Chinese Pharmaceutical Association,Beijing Pharmaceutical Association,and the School of Public Health,Peking University have jointly initiated the drafting of the Expert Consensus on Off-label Use of Drugs for Rare Diseases.This consensus refer to the WHO Handbook for Guideline Development,the Guidelines for Developing/Revising Clinical Diagnostic and Treatment Guidelines in China(2022 Edition),the AGREE Ⅱ and the STAR tools.This protocol outlines the background and purpose of consensus,as well as the comprehensive framework for consensus development,encompassing panel formation,clinical issue identification,evidence retrieval,data extraction,and evidence-based recommendation formulation.

Objective To establish an evaluation indicator system for pharmacovigilance(PV)work in medical institutions of Fujian province,and provide a reference for the PV work in healthcare facilities.Methods Based on literature analysis and interpretation of policies and regulations,combined with the practical pharmacovigilance work in Fujian province,a preliminary indicator system was constructed.Following this,three rounds of expert consultation were conducted,including two rounds of the Delphi method to determine the content of the index system,and one round of the Analytic Hierarchy Process(AHP)to determine the weights of each index.Results A total of 9 primary indicators,23 secondary indicators,and 59 tertiary indicators were selected for the evaluation of pharmacovigilance work in health facilities of Fujian province,including pharmacovigilance organizational structure,human resources,equipment resources,development and documentation of the quality management system's procedural documents,Performance indicators for monitoring and reporting,risk identification,assessment,control and research capabilities.The consensus coefficients for three rounds of consultation with experts were 100％,100％,and 100％.The average authority coefficient of the experts was 0.878,and the expert coordination coefficients for the two rounds of Delphi method were 0.081 and 0.343,respectively(P＜0.001).In the AHP,the weight vector for primary indicators ranged from 0.023 to 0.263,with a maximum eigenvalue of 9.195.The weight vector values of the secondary indicators were from 0.096 to 1.000,and the maximum eigenvalues were 3.018-4.061;The weight vectors of the tertiary indicators were 0.143 to 1.000,and the maximum eigenvalues were from 3.000 to 5.078.The consistency ratio(CR)of each judgment matrix was between 0 and 0.051.Conclusions The constructed indicator of capability assessment model,integrating regulatory functions and the practical situation of medical institutions,can be used by regulatory authorities to assess pharmacovigilance work in medical institutions.It provides a solid reference for improving the pharmacovigilance capabilities of medical institutions in Fujian province.

Objective To establish an evaluation indicator system for pharmacovigilance(PV)work in medical institutions of Fujian province,and provide a reference for the PV work in healthcare facilities.Methods Based on literature analysis and interpretation of policies and regulations,combined with the practical pharmacovigilance work in Fujian province,a preliminary indicator system was constructed.Following this,three rounds of expert consultation were conducted,including two rounds of the Delphi method to determine the content of the index system,and one round of the Analytic Hierarchy Process(AHP)to determine the weights of each index.Results A total of 9 primary indicators,23 secondary indicators,and 59 tertiary indicators were selected for the evaluation of pharmacovigilance work in health facilities of Fujian province,including pharmacovigilance organizational structure,human resources,equipment resources,development and documentation of the quality management system's procedural documents,Performance indicators for monitoring and reporting,risk identification,assessment,control and research capabilities.The consensus coefficients for three rounds of consultation with experts were 100％,100％,and 100％.The average authority coefficient of the experts was 0.878,and the expert coordination coefficients for the two rounds of Delphi method were 0.081 and 0.343,respectively(P＜0.001).In the AHP,the weight vector for primary indicators ranged from 0.023 to 0.263,with a maximum eigenvalue of 9.195.The weight vector values of the secondary indicators were from 0.096 to 1.000,and the maximum eigenvalues were 3.018-4.061;The weight vectors of the tertiary indicators were 0.143 to 1.000,and the maximum eigenvalues were from 3.000 to 5.078.The consistency ratio(CR)of each judgment matrix was between 0 and 0.051.Conclusions The constructed indicator of capability assessment model,integrating regulatory functions and the practical situation of medical institutions,can be used by regulatory authorities to assess pharmacovigilance work in medical institutions.It provides a solid reference for improving the pharmacovigilance capabilities of medical institutions in Fujian province.

Objective To enhance the efficiency and accuracy of post-marketing safety monitoring and evaluation of drugs in China by studying large language models-based patient medical record pharmacovigilance profiling techniques,providing scientific methods and technical support to ensure the safe use of drugs for patients.Methods This study constructs a pharmacovigilance profile that includes individual patient differences,medication details,and adverse reaction manifestations.It enhances a large language model with a knowledge graph in the field of pharmacovigilance and designs targeted prompts to guide the model to output pharmacovigilance profiles.Results Large language models demonstrate significant advantages in active monitoring,effectively processing and analyzing medical text data,and improving the monitoring and prediction capabilities of drug adverse reactions.Through the design of prompts,the model can more accurately depict patient pharmacovigilance profiles,providing decision support for medical professionals.Conclusions The study of large language model-based patient medical record pharmacovigilance profiling technology provides scientific evidence and technical support for the early detection and prevention of drug adverse reactions,helping to reduce medical costs,improve medical outcome prognoses,and opens new paths to ensure patient drug safety.

Rare diseases are a collective term for diseases with extremely low prevalence and incidence rates.Up to now,China has released two lists identifying a total of 207 rare diseases.Given that most rare diseases do not have drugs with corresponding indications,physicians frequently resort to using off-label drugs when treating patients with rare diseases.However,there is currently no systematic guideline or expert consensus for the use of off-label medications in China.To comprehensively collect existing evidence of off-label drug use for rare diseases,fully analyze and evaluate the rationality of off-label drug use for rare diseases,and standardize the management of off-label drug use for rare diseases,the Rare Disease Branch of Beijing Medical Association,Chinese Pharmaceutical Association,Beijing Pharmaceutical Association,and the School of Public Health,Peking University have jointly initiated the drafting of the Expert Consensus on Off-label Use of Drugs for Rare Diseases.This consensus refer to the WHO Handbook for Guideline Development,the Guidelines for Developing/Revising Clinical Diagnostic and Treatment Guidelines in China(2022 Edition),the AGREE Ⅱ and the STAR tools.This protocol outlines the background and purpose of consensus,as well as the comprehensive framework for consensus development,encompassing panel formation,clinical issue identification,evidence retrieval,data extraction,and evidence-based recommendation formulation.

Objective To enhance the efficiency and accuracy of post-marketing safety monitoring and evaluation of drugs in China by studying large language models-based patient medical record pharmacovigilance profiling techniques,providing scientific methods and technical support to ensure the safe use of drugs for patients.Methods This study constructs a pharmacovigilance profile that includes individual patient differences,medication details,and adverse reaction manifestations.It enhances a large language model with a knowledge graph in the field of pharmacovigilance and designs targeted prompts to guide the model to output pharmacovigilance profiles.Results Large language models demonstrate significant advantages in active monitoring,effectively processing and analyzing medical text data,and improving the monitoring and prediction capabilities of drug adverse reactions.Through the design of prompts,the model can more accurately depict patient pharmacovigilance profiles,providing decision support for medical professionals.Conclusions The study of large language model-based patient medical record pharmacovigilance profiling technology provides scientific evidence and technical support for the early detection and prevention of drug adverse reactions,helping to reduce medical costs,improve medical outcome prognoses,and opens new paths to ensure patient drug safety.

Objective:To investigate the efficacy and safety of oral maintenance therapy with tegafur for residual lesions in patients with locally advanced esophageal squamous cell carcinoma (ESCC) after chemoradiotherapy.Methods:A retrospective cohort study was conducted. A total of 38 patients with locally advanced ESCC who had residual lesions after receiving albumin bound paclitaxel combined with platinum chemoradiotherapy from March 2019 to September 2021 in Jiangsu Province Suqian Hospital were selected. All patients were divided into the maintenance treatment group (20 cases) and the non-maintenance treatment group (18 cases) based on whether they received oral maintenance therapy with tegafur after chemoradiotherapy. The progression-free survival (PFS) of both groups was compared and the adverse reactions of the maintenance treatment group were analyzed.Results:There were no statistically significant differences in baseline data between the 2 groups (both P > 0.05). The 1, 2, 3-year PFS rates for the maintenance treatment group were 95.0%, 78.1%, and 58.3%, respectively, with a median PFS time of 33.65 months (95% CI: 29.04-38.26 months); the 1, 2, 3-year PFS rates in the non-maintenance treatment group were 88.9%, 54.5%, and 12.1%, respectively, with a median PFS time of 25.08 months (95% CI: 20.97-29.18 months); there was a statistically significant difference in PFS between the 2 groups ( χ2 = 5.36, P = 0.021). The common adverse reactions in the maintenance treatment group included hematological adverse reactions, hand foot syndrome, decreased appetite, and fatigue. The more common adverse reactions were neutropenia [85.0% (17/20)] and leukopenia [65.0% (13/20)]; 9 cases experienced grade 3-4 adverse reactions, which were relieved by adjusting the dosage or discontinuing the medication. Conclusions:Oral maintenance therapy with tegafur may improve the survival of ESCC patients with residual lesions after chemoradiotherapy and the adverse reactions are controllable.

Objective To investigate the optimal cutoff values of Kyoto gastritis score based on gastroscopy,pepsinogen(PG)combined with gastrin-17(G-17)for predicting Helicobacter pylori positive atrophic gastritis in middle-aged and elderly patients.Methods The subjects of this study were 120 middle-aged and elderly patients admitted,diagnosed with atrophic gastritis through gastroscopy examination and pathological biopsy and proved to be Hp positive via 14C urea breath test from August 2022 to June 2023.All patients were divided into atrophic gastritis group(AG group)with 68 cases and non atrophic gastritis group(non-AG group)with 52 cases according to atrophic gastritis results.The AG group was further divided per Kimura-Takemoto classification into mild AG group(n=12),moderate AG group(n=32)and severe AG group(n=24).Kyoto gastritis score based on gastroscopy was performed in all patients.And test their serum pepsinogen Ⅰ(PGⅠ),pepsinogen Ⅱ(PGⅡ),G-17 levels via chemiluminescence and calculate the PGR=PGⅠ/PGⅡ.Receiver operator characteristic curve(ROC curve)was adopted to assess the value of Kyoto gastritis score and serum PG and G-17 for predicting Hp positive atrophic gastritis in middle-aged and elderly patients.Results There were statistically significant differences in Kyoto gastritis score,serum PGⅠ,PGR and G-17 levels between AG group and non-AG group(t=13.38,P=0.000;t=50.84,P=0.000;t=26.44,P=0.000;t=9.44,P=0.000).The Kyoto score of gastritis in AG group was higher than that in non-AG group(P<0.05).The levels of serum PGⅠ,PGR and G-17 in AG group were lower than those in non-AG group(P<0.05).There was no significant difference in serum PGⅡ level between AG group and non-AG group(t=1.24,P=0.219).There were statistically significant differences in Kyoto gastritis score,serum PGⅠ,PGR and G-17 levels among mild AG group,moderate AG group and severe AG group(F=33.95,P=0.000;F=81.99,P=0.000;F=67.36,P=0.001;F=33.50,P=0.004).The mild AG group had a significantly lower Kyoto gastritis score than the moderate AG group and severe AG group(P<0.05),and the moderate AG group had a significantly lower Kyoto gastritis score than the severe AG group(P<0.05).The mild AG group and moderate AG group had significantly higher serum PGⅠ and PGR levels than the severe AG group(P<0.05),and the mild AG group was higher than moderate AG group(P<0.05).The mild AG group had a significantly lower serum G-17 level than the moderate AG group and severe AG group(P<0.05),and there was no significant difference between the moderate AG group and severe AG group(P>0.05).There was no significant difference in serum PGⅡ levels among mild AG group,moderate AG group and severe AG group(F=1.03,P=0.364).The optimal cutoff values of Kyoto gastritis score and serum PGⅠ,PGR and G-17 for predicting atrophic gastritis in middle-aged and elderly patients with Hp positive were 2.78,38.26 μg/L,1.92 and 9.54 pmol/L,respectively.The AUC of Kyoto gastritis score for predicting Hp positive atrophic gastritis in middle-aged and elderly patients was 0.780,the sensitivity was 71.42%,and the specificity was 78.62%.The AUC of PGⅠ for predicting Hp positive atrophic gastritis in middle-aged and elderly patients was 0.757,the sensitivity was 66.27%,and the specificity was 83.25%.The AUC of PGR for predicting Hp positive atrophic gastritis in middle-aged and elderly patients was 0.792,the sensitivity was 76.23%,and the specificity was 87.35%.The AUC of G-17 for predicting Hp positive atrophic gastritis in middle-aged and elderly patients was 0.672,the sensitivity was 60.24%,and the specificity was 74.28%.The AUC of the combination of the four markers for predicting Hp positive atrophic gastritis in middle-aged and elderly patients was 0.871,the sensitivity was 81.28%,and the specificity was 87.36%.Conclusion The Kyoto gastritis score based on gastroscopy,serum PGⅠ,PGR combined with G-17 have good predictive value for Hp positive atrophic gastritis in middle-aged and elderly patients,and the optimal cutoff values for the four markers are 2.78 points,38.26 μg/L,1.92 and 9.54 pmol/L in turn.

Objective To investigate the optimal cutoff values of Kyoto gastritis score based on gastroscopy,pepsinogen(PG)combined with gastrin-17(G-17)for predicting Helicobacter pylori positive atrophic gastritis in middle-aged and elderly patients.Methods The subjects of this study were 120 middle-aged and elderly patients admitted,diagnosed with atrophic gastritis through gastroscopy examination and pathological biopsy and proved to be Hp positive via 14C urea breath test from August 2022 to June 2023.All patients were divided into atrophic gastritis group(AG group)with 68 cases and non atrophic gastritis group(non-AG group)with 52 cases according to atrophic gastritis results.The AG group was further divided per Kimura-Takemoto classification into mild AG group(n=12),moderate AG group(n=32)and severe AG group(n=24).Kyoto gastritis score based on gastroscopy was performed in all patients.And test their serum pepsinogen Ⅰ(PGⅠ),pepsinogen Ⅱ(PGⅡ),G-17 levels via chemiluminescence and calculate the PGR=PGⅠ/PGⅡ.Receiver operator characteristic curve(ROC curve)was adopted to assess the value of Kyoto gastritis score and serum PG and G-17 for predicting Hp positive atrophic gastritis in middle-aged and elderly patients.Results There were statistically significant differences in Kyoto gastritis score,serum PGⅠ,PGR and G-17 levels between AG group and non-AG group(t=13.38,P=0.000;t=50.84,P=0.000;t=26.44,P=0.000;t=9.44,P=0.000).The Kyoto score of gastritis in AG group was higher than that in non-AG group(P<0.05).The levels of serum PGⅠ,PGR and G-17 in AG group were lower than those in non-AG group(P<0.05).There was no significant difference in serum PGⅡ level between AG group and non-AG group(t=1.24,P=0.219).There were statistically significant differences in Kyoto gastritis score,serum PGⅠ,PGR and G-17 levels among mild AG group,moderate AG group and severe AG group(F=33.95,P=0.000;F=81.99,P=0.000;F=67.36,P=0.001;F=33.50,P=0.004).The mild AG group had a significantly lower Kyoto gastritis score than the moderate AG group and severe AG group(P<0.05),and the moderate AG group had a significantly lower Kyoto gastritis score than the severe AG group(P<0.05).The mild AG group and moderate AG group had significantly higher serum PGⅠ and PGR levels than the severe AG group(P<0.05),and the mild AG group was higher than moderate AG group(P<0.05).The mild AG group had a significantly lower serum G-17 level than the moderate AG group and severe AG group(P<0.05),and there was no significant difference between the moderate AG group and severe AG group(P>0.05).There was no significant difference in serum PGⅡ levels among mild AG group,moderate AG group and severe AG group(F=1.03,P=0.364).The optimal cutoff values of Kyoto gastritis score and serum PGⅠ,PGR and G-17 for predicting atrophic gastritis in middle-aged and elderly patients with Hp positive were 2.78,38.26 μg/L,1.92 and 9.54 pmol/L,respectively.The AUC of Kyoto gastritis score for predicting Hp positive atrophic gastritis in middle-aged and elderly patients was 0.780,the sensitivity was 71.42%,and the specificity was 78.62%.The AUC of PGⅠ for predicting Hp positive atrophic gastritis in middle-aged and elderly patients was 0.757,the sensitivity was 66.27%,and the specificity was 83.25%.The AUC of PGR for predicting Hp positive atrophic gastritis in middle-aged and elderly patients was 0.792,the sensitivity was 76.23%,and the specificity was 87.35%.The AUC of G-17 for predicting Hp positive atrophic gastritis in middle-aged and elderly patients was 0.672,the sensitivity was 60.24%,and the specificity was 74.28%.The AUC of the combination of the four markers for predicting Hp positive atrophic gastritis in middle-aged and elderly patients was 0.871,the sensitivity was 81.28%,and the specificity was 87.36%.Conclusion The Kyoto gastritis score based on gastroscopy,serum PGⅠ,PGR combined with G-17 have good predictive value for Hp positive atrophic gastritis in middle-aged and elderly patients,and the optimal cutoff values for the four markers are 2.78 points,38.26 μg/L,1.92 and 9.54 pmol/L in turn.

Objective:To investigate the efficacy and safety of oral maintenance therapy with tegafur for residual lesions in patients with locally advanced esophageal squamous cell carcinoma (ESCC) after chemoradiotherapy.Methods:A retrospective cohort study was conducted. A total of 38 patients with locally advanced ESCC who had residual lesions after receiving albumin bound paclitaxel combined with platinum chemoradiotherapy from March 2019 to September 2021 in Jiangsu Province Suqian Hospital were selected. All patients were divided into the maintenance treatment group (20 cases) and the non-maintenance treatment group (18 cases) based on whether they received oral maintenance therapy with tegafur after chemoradiotherapy. The progression-free survival (PFS) of both groups was compared and the adverse reactions of the maintenance treatment group were analyzed.Results:There were no statistically significant differences in baseline data between the 2 groups (both P > 0.05). The 1, 2, 3-year PFS rates for the maintenance treatment group were 95.0%, 78.1%, and 58.3%, respectively, with a median PFS time of 33.65 months (95% CI: 29.04-38.26 months); the 1, 2, 3-year PFS rates in the non-maintenance treatment group were 88.9%, 54.5%, and 12.1%, respectively, with a median PFS time of 25.08 months (95% CI: 20.97-29.18 months); there was a statistically significant difference in PFS between the 2 groups ( χ2 = 5.36, P = 0.021). The common adverse reactions in the maintenance treatment group included hematological adverse reactions, hand foot syndrome, decreased appetite, and fatigue. The more common adverse reactions were neutropenia [85.0% (17/20)] and leukopenia [65.0% (13/20)]; 9 cases experienced grade 3-4 adverse reactions, which were relieved by adjusting the dosage or discontinuing the medication. Conclusions:Oral maintenance therapy with tegafur may improve the survival of ESCC patients with residual lesions after chemoradiotherapy and the adverse reactions are controllable.