Background：Entecavir （ETV） has been shown to be effective in randomized controlled trials in highly selected patients with hepatitis B virus （HBV） infection.This study aimed to evaluate the efficacy of ETV in chr...Background：Entecavir （ETV） has been shown to be effective in randomized controlled trials in highly selected patients with hepatitis B virus （HBV） infection.This study aimed to evaluate the efficacy of ETV in chronic hepatitis B （CHB） patients in the real-world setting.Methods：A total of 233 treatment-na（i）ve,CHB patients who received at least 12 months of ETV treatment were included in this retrospective study.Rates of virological response （VR）,hepatitis B s antigen （HBsAg） loss,hepatitis B e antigen （HBeAg） clearance/seroconversion,virological breakthrough,cirrhosis,and hepatocellular carcinoma were evaluated.Results：Of 233 patients,175 patients were male,with mean age of 43 years old,and 135 patients were HBeAg positive.The mean baseline levels of serum alanine aminotransferase and HBV DNA in all patients were 230 U/L and 6.6 log 10 IU/ml,respectively.The mean follow-up period was 28 months.The cumulative rates of achieving VR increased from 3.4% at 3 months to 94.4% at 60 months.Primary nonresponse occurred in 3 （1.3%） patients.Partial VR （PVR） occurred in 61 （26.2%） patients at 12 months.The baseline serum HBV DNA level （hazard ratio [HR],2.054;P 〈 0.001） was an independent risk factor for PVR.HBsAg loss did not occur.The cumulative rates of HBeAg clearance increased from 2.2% at 3 months to 28.2% at 60 months.PVR was the significant determinant of HBeAg clearance （HR,0.341;P =0.026）.Age （HR,1.072;P =0.013） and PVR （HR,5.131;P =0.017） were the significant determinants of cirrhosis.Conclusions：ETV treatment was effective for HBV DNA suppression in this study,but HBsAg loss and HBeAg clearance/seroconversion rates were lower compared with previous clinical trials.PVR was associated with HBeAg clearance and cirrhosis.展开更多
Tumor necrosis factor-α(TNF-α)antagonists,the first biologics approved for treating patients with inflammatory bowel disease(IBD),are effective for the induction and maintenance of remission and significantly improv...Tumor necrosis factor-α(TNF-α)antagonists,the first biologics approved for treating patients with inflammatory bowel disease(IBD),are effective for the induction and maintenance of remission and significantly improving prognosis.However,up to one-third of treated patients show primary nonresponse(PNR)to anti-TNF-αtherapies,and 23%-50%of IBD patients experience loss of response(LOR)to these biologics during subsequent treatment.There is still no recognized predictor for evaluating the efficacy of anti-TNF drugs.This review summarizes the existing predictors of PNR and LOR to anti-TNF in IBD patients.Most predictors remain controversial,and only previous surgical history,disease manifestations,drug concentrations,antidrug antibodies,serum albumin,some biologic markers,and some genetic markers may be potentially predictive.In addition,we also discuss the next steps of treatment for patients with PNR or LOR to TNF antagonists.Therapeutic drug monitoring plays an important role in treatment selection.Dose escalation,combination therapy,switching to a different anti-TNF drug,or switching to a biologic with a different mechanism of action can be selected based on the concentration of the drug and/or antidrug antibodies.展开更多
BACKGROUND Many patients with ulcerative colitis(UC)do not respond well to,or tolerate conventional and biological therapies.There is currently no consensus on the treatment of refractory UC.Studies have demonstrated ...BACKGROUND Many patients with ulcerative colitis(UC)do not respond well to,or tolerate conventional and biological therapies.There is currently no consensus on the treatment of refractory UC.Studies have demonstrated that the selective Janus kinase 1 inhibitor upadacitinib,a small-molecule drug,is effective and safe for treating UC.However,no studies have revealed that upadacitinib is effective in treating refractory UC with primary nonresponse to infliximab and vedolizumab.CASE SUMMARY We report the case of a 44-year-old male patient with a chief complaint of bloody diarrhoea with mucus and pus,in addition to dizziness.The patient had recurrent disease after receiving mesalazine,prednisone,azathioprine,infliximab and vedolizumab over four years.Based on the endoscopic findings and pathological biopsy,the patient was diagnosed with refractory UC.In particular,the patient showed primary nonresponse to infliximab and vedolizumab.Based on the patient’s history and recurrent disease,we decided to administer upadacitinib.During hospitalisation,the patient was received upadacitinib under our guidance.Eight weeks after the initiation of upadacitinib treatment,the patient’s symptoms and endoscopic findings improved significantly.No notable adverse reactions have been reported to date.CONCLUSION Our case report suggests that upadacitinib may represent a valuable strategy for treating refractory UC with primary nonresponse.展开更多
OBJECTIVE:To explore the efficacy of integrating Traditional Chinese Medicine(TCM)and anti-retroviral therapy(ART),a customized combination of different classes of medications which was also called cock-tail treatment...OBJECTIVE:To explore the efficacy of integrating Traditional Chinese Medicine(TCM)and anti-retroviral therapy(ART),a customized combination of different classes of medications which was also called cock-tail treatment,on the immunological nonresponse(INR)in people living with human immunodeficiency virus(HIV)(PLWH).METHODS:Relevant literature in databases such as China National Knowledge Infrastructure Database(CNKI),Wanfang Digital Journal,Chinese Medical Journal Database(CMJD),Chinese Biomedical Literature Database(CBM),Pub Med,Cochrane,and Embase was reviewed by two independent investigators.Data were extracted from the studies according to the eligible criteria and analyzed using Review Manager 5.3.RESULTS:Nine randomized controlled trials(RCTs)with 1078 patients were analyzed.Our analyses showed that CD4 T cell counts in the treatment group improved compared with that in the control group[mean difference(MD)=13.51,95%confidence interval(CI):7.42-19.60,P<0.0001].There was no significant difference between the treated and control groups after 3 months(MD=25.31,95%CI:-2.78 to 53.41,P=0.08).However,after 6 and 12 months,the response of the treatment group was superior to the control group(MD=27.45,95%CI:7.09-47.81,P=0.008 and MD=27.34,95%CI:6.31–48.37,P=0.01,respectively).The clinical efficacy of the treatment group was also higher than that of the control group(RR=1.75,95%CI:1.16-2.65,P=0.007).However,CD45 RO and CD45 RA T cell counts did not differ significantly between the two groups(MD=12.37,95%CI:-6.71 to 31.45,P=0.20 and MD=5.67,95%CI:-3.00 to14.35,P=0.20,respectively).CONCLUSION:The combined treatment strategy of integrated TCM and Western Medicine promotes long-term reconstitution of the immune system and thus,is beneficial and has potential use for improving INR in PLWH.However,large-scale RCTs are required to provide evidence for optimal intervention strategies.展开更多
Assessing the influence of individual observations of the functional linear models is important and challenging,especially when the observations are subject to missingness.In this paper,we introduce three case-deletio...Assessing the influence of individual observations of the functional linear models is important and challenging,especially when the observations are subject to missingness.In this paper,we introduce three case-deletion diagnostic measures to identify influential observations in functional linear models when the covariate is functional and observations on the scalar response are subject to nonignorable missingness.The nonignorable missing data mechanism is modeled via an exponential tilting semiparametric functional model.A semiparametric imputation procedure is developed to mitigate the effects of missing data.Valid estimations of the functional coefficients are based on functional principal components analysis using the imputed dataset.A smoothed bootstrap samplingmethod is introduced to estimate the diagnostic probability for each proposed diagnostic measure,which is helpful to unveil which observations have the larger influence on estimation and prediction.Simulation studies and a real data example are conducted to illustrate the finite performance of the proposed methods.展开更多
In practical survey sampling, nonresponse phenomenon is unavoidable. How to impute missing data is an important problem. There are several imputation methods in the literature. In this paper, the imputation method of ...In practical survey sampling, nonresponse phenomenon is unavoidable. How to impute missing data is an important problem. There are several imputation methods in the literature. In this paper, the imputation method of the mean of ratios for missing data under uniform response is applied to the estimation of a finite population mean when the PPSWR sampling is used. The imputed estimator is valid under the corresponding response mechanism regardless of the model as well as under the ratio model regardless of the response mechanism. The approximately unbiased jackknife variance estimator is also presented. All of these results are extended to the case of non-uniform response. Simulation studies show the good performance of the proposed estimators.展开更多
We consider multivariate small area estimation under nonignorable, not missing at random(NMAR) nonresponse. We assume a response model that accounts for the different patterns ofthe observed outcomes, (which values ar...We consider multivariate small area estimation under nonignorable, not missing at random(NMAR) nonresponse. We assume a response model that accounts for the different patterns ofthe observed outcomes, (which values are observed and which ones are missing), and estimatethe response probabilities by application of the Missing Information Principle (MIP). By this principle, we first derive the likelihood score equations for the case where the missing outcomes areactually observed, and then integrate out the unobserved outcomes from the score equationswith respect to the distribution holding for the missing data. The latter distribution is definedby the distribution fitted to the observed data for the respondents and the response model. Theintegrated score equations are then solved with respect to the unknown parameters indexingthe response model. Once the response probabilities have been estimated, we impute the missing outcomes from their appropriate distribution, yielding a complete data set with no missingvalues, which is used for predicting the target area means. A parametric bootstrap procedure isdeveloped for assessing the mean squared errors (MSE) of the resulting predictors. We illustratethe approach by a small simulation study.展开更多
The study focuses on the imputation for the longitudinal survey data which often has nonignorable nonrespondents. Local linear regression is used to impute the missing values and then the estimation of the time-depend...The study focuses on the imputation for the longitudinal survey data which often has nonignorable nonrespondents. Local linear regression is used to impute the missing values and then the estimation of the time-dependent finite populations means. The asymptotic properties (unbiasedness and consistency) of the proposed estimator are investigated. Comparisons between different parametric and nonparametric estimators are performed based on the bootstrap standard deviation, mean square error and percentage relative bias. A simulation study is carried out to determine the best performing estimator of the time-dependent finite population means. The simulation results show that local linear regression estimator yields good properties.展开更多
This paper studies how the sample rotation method is applied to the case where item nonresponse occurs in surveys. The two cases where the response to the first occasion is complete or incomplete are considered. Using...This paper studies how the sample rotation method is applied to the case where item nonresponse occurs in surveys. The two cases where the response to the first occasion is complete or incomplete are considered. Using ratio imputation method, the estimators of the current population mean are proposed, which are valid under uniform response regardless of the model and under the ratio model regardless of the response mechanism. Under uniform response, the variances of the proposed estimators are derived. Interestingly, although their expressions are similar, the estimator for the case of incomplete response on the first occasion can have smaller variance than the one for the case of complete response on the first occasion under uniform response. The linearized jackknife variance estimators are also given. These variance estimators prove to be approximately design-unbiased under uniform response. It should be noted that similar property on variance estimators has not been discussed in literature.展开更多
文摘Background：Entecavir （ETV） has been shown to be effective in randomized controlled trials in highly selected patients with hepatitis B virus （HBV） infection.This study aimed to evaluate the efficacy of ETV in chronic hepatitis B （CHB） patients in the real-world setting.Methods：A total of 233 treatment-na（i）ve,CHB patients who received at least 12 months of ETV treatment were included in this retrospective study.Rates of virological response （VR）,hepatitis B s antigen （HBsAg） loss,hepatitis B e antigen （HBeAg） clearance/seroconversion,virological breakthrough,cirrhosis,and hepatocellular carcinoma were evaluated.Results：Of 233 patients,175 patients were male,with mean age of 43 years old,and 135 patients were HBeAg positive.The mean baseline levels of serum alanine aminotransferase and HBV DNA in all patients were 230 U/L and 6.6 log 10 IU/ml,respectively.The mean follow-up period was 28 months.The cumulative rates of achieving VR increased from 3.4% at 3 months to 94.4% at 60 months.Primary nonresponse occurred in 3 （1.3%） patients.Partial VR （PVR） occurred in 61 （26.2%） patients at 12 months.The baseline serum HBV DNA level （hazard ratio [HR],2.054;P 〈 0.001） was an independent risk factor for PVR.HBsAg loss did not occur.The cumulative rates of HBeAg clearance increased from 2.2% at 3 months to 28.2% at 60 months.PVR was the significant determinant of HBeAg clearance （HR,0.341;P =0.026）.Age （HR,1.072;P =0.013） and PVR （HR,5.131;P =0.017） were the significant determinants of cirrhosis.Conclusions：ETV treatment was effective for HBV DNA suppression in this study,but HBsAg loss and HBeAg clearance/seroconversion rates were lower compared with previous clinical trials.PVR was associated with HBeAg clearance and cirrhosis.
文摘Tumor necrosis factor-α(TNF-α)antagonists,the first biologics approved for treating patients with inflammatory bowel disease(IBD),are effective for the induction and maintenance of remission and significantly improving prognosis.However,up to one-third of treated patients show primary nonresponse(PNR)to anti-TNF-αtherapies,and 23%-50%of IBD patients experience loss of response(LOR)to these biologics during subsequent treatment.There is still no recognized predictor for evaluating the efficacy of anti-TNF drugs.This review summarizes the existing predictors of PNR and LOR to anti-TNF in IBD patients.Most predictors remain controversial,and only previous surgical history,disease manifestations,drug concentrations,antidrug antibodies,serum albumin,some biologic markers,and some genetic markers may be potentially predictive.In addition,we also discuss the next steps of treatment for patients with PNR or LOR to TNF antagonists.Therapeutic drug monitoring plays an important role in treatment selection.Dose escalation,combination therapy,switching to a different anti-TNF drug,or switching to a biologic with a different mechanism of action can be selected based on the concentration of the drug and/or antidrug antibodies.
基金Supported by Shenzhen Science and Technology Program,No.JCYJ20220530154013031Guangdong Province Health and Health Appropriate Technology Promotion Project,No.2023385Guangdong Province Grassroots Science Popularization Action Plan,No.20240205.
文摘BACKGROUND Many patients with ulcerative colitis(UC)do not respond well to,or tolerate conventional and biological therapies.There is currently no consensus on the treatment of refractory UC.Studies have demonstrated that the selective Janus kinase 1 inhibitor upadacitinib,a small-molecule drug,is effective and safe for treating UC.However,no studies have revealed that upadacitinib is effective in treating refractory UC with primary nonresponse to infliximab and vedolizumab.CASE SUMMARY We report the case of a 44-year-old male patient with a chief complaint of bloody diarrhoea with mucus and pus,in addition to dizziness.The patient had recurrent disease after receiving mesalazine,prednisone,azathioprine,infliximab and vedolizumab over four years.Based on the endoscopic findings and pathological biopsy,the patient was diagnosed with refractory UC.In particular,the patient showed primary nonresponse to infliximab and vedolizumab.Based on the patient’s history and recurrent disease,we decided to administer upadacitinib.During hospitalisation,the patient was received upadacitinib under our guidance.Eight weeks after the initiation of upadacitinib treatment,the patient’s symptoms and endoscopic findings improved significantly.No notable adverse reactions have been reported to date.CONCLUSION Our case report suggests that upadacitinib may represent a valuable strategy for treating refractory UC with primary nonresponse.
基金Supported by National Science and Technology Major Project of China During the 13th Five-year Plan Period:New Adjuvant Strategies of Traditional Chinese Medicine on Immune Reconstruction for Long-term ART-treated People Living with HIV(No.2017ZX10205501)Study of AIDS-related Early Biomarkers for Disease Progression and Epidemic Predicting Model(No.2017ZX10201101)the Beijing Excellent Talent Plan(No.2018000021223ZK04)。
文摘OBJECTIVE:To explore the efficacy of integrating Traditional Chinese Medicine(TCM)and anti-retroviral therapy(ART),a customized combination of different classes of medications which was also called cock-tail treatment,on the immunological nonresponse(INR)in people living with human immunodeficiency virus(HIV)(PLWH).METHODS:Relevant literature in databases such as China National Knowledge Infrastructure Database(CNKI),Wanfang Digital Journal,Chinese Medical Journal Database(CMJD),Chinese Biomedical Literature Database(CBM),Pub Med,Cochrane,and Embase was reviewed by two independent investigators.Data were extracted from the studies according to the eligible criteria and analyzed using Review Manager 5.3.RESULTS:Nine randomized controlled trials(RCTs)with 1078 patients were analyzed.Our analyses showed that CD4 T cell counts in the treatment group improved compared with that in the control group[mean difference(MD)=13.51,95%confidence interval(CI):7.42-19.60,P<0.0001].There was no significant difference between the treated and control groups after 3 months(MD=25.31,95%CI:-2.78 to 53.41,P=0.08).However,after 6 and 12 months,the response of the treatment group was superior to the control group(MD=27.45,95%CI:7.09-47.81,P=0.008 and MD=27.34,95%CI:6.31–48.37,P=0.01,respectively).The clinical efficacy of the treatment group was also higher than that of the control group(RR=1.75,95%CI:1.16-2.65,P=0.007).However,CD45 RO and CD45 RA T cell counts did not differ significantly between the two groups(MD=12.37,95%CI:-6.71 to 31.45,P=0.20 and MD=5.67,95%CI:-3.00 to14.35,P=0.20,respectively).CONCLUSION:The combined treatment strategy of integrated TCM and Western Medicine promotes long-term reconstitution of the immune system and thus,is beneficial and has potential use for improving INR in PLWH.However,large-scale RCTs are required to provide evidence for optimal intervention strategies.
基金supported by the General Project of National Natural Science Foundation of China(Grant No.12071416).
文摘Assessing the influence of individual observations of the functional linear models is important and challenging,especially when the observations are subject to missingness.In this paper,we introduce three case-deletion diagnostic measures to identify influential observations in functional linear models when the covariate is functional and observations on the scalar response are subject to nonignorable missingness.The nonignorable missing data mechanism is modeled via an exponential tilting semiparametric functional model.A semiparametric imputation procedure is developed to mitigate the effects of missing data.Valid estimations of the functional coefficients are based on functional principal components analysis using the imputed dataset.A smoothed bootstrap samplingmethod is introduced to estimate the diagnostic probability for each proposed diagnostic measure,which is helpful to unveil which observations have the larger influence on estimation and prediction.Simulation studies and a real data example are conducted to illustrate the finite performance of the proposed methods.
基金Supported by NationalNatural Science Foundation of China (Grant Nos. 70625004, 10721101 and 70933003)
文摘In practical survey sampling, nonresponse phenomenon is unavoidable. How to impute missing data is an important problem. There are several imputation methods in the literature. In this paper, the imputation method of the mean of ratios for missing data under uniform response is applied to the estimation of a finite population mean when the PPSWR sampling is used. The imputed estimator is valid under the corresponding response mechanism regardless of the model as well as under the ratio model regardless of the response mechanism. The approximately unbiased jackknife variance estimator is also presented. All of these results are extended to the case of non-uniform response. Simulation studies show the good performance of the proposed estimators.
文摘We consider multivariate small area estimation under nonignorable, not missing at random(NMAR) nonresponse. We assume a response model that accounts for the different patterns ofthe observed outcomes, (which values are observed and which ones are missing), and estimatethe response probabilities by application of the Missing Information Principle (MIP). By this principle, we first derive the likelihood score equations for the case where the missing outcomes areactually observed, and then integrate out the unobserved outcomes from the score equationswith respect to the distribution holding for the missing data. The latter distribution is definedby the distribution fitted to the observed data for the respondents and the response model. Theintegrated score equations are then solved with respect to the unknown parameters indexingthe response model. Once the response probabilities have been estimated, we impute the missing outcomes from their appropriate distribution, yielding a complete data set with no missingvalues, which is used for predicting the target area means. A parametric bootstrap procedure isdeveloped for assessing the mean squared errors (MSE) of the resulting predictors. We illustratethe approach by a small simulation study.
文摘The study focuses on the imputation for the longitudinal survey data which often has nonignorable nonrespondents. Local linear regression is used to impute the missing values and then the estimation of the time-dependent finite populations means. The asymptotic properties (unbiasedness and consistency) of the proposed estimator are investigated. Comparisons between different parametric and nonparametric estimators are performed based on the bootstrap standard deviation, mean square error and percentage relative bias. A simulation study is carried out to determine the best performing estimator of the time-dependent finite population means. The simulation results show that local linear regression estimator yields good properties.
基金This work was supported by the National Natural Science Foundation of China (Grnat Nos. 10071091 and 19831010).
文摘This paper studies how the sample rotation method is applied to the case where item nonresponse occurs in surveys. The two cases where the response to the first occasion is complete or incomplete are considered. Using ratio imputation method, the estimators of the current population mean are proposed, which are valid under uniform response regardless of the model and under the ratio model regardless of the response mechanism. Under uniform response, the variances of the proposed estimators are derived. Interestingly, although their expressions are similar, the estimator for the case of incomplete response on the first occasion can have smaller variance than the one for the case of complete response on the first occasion under uniform response. The linearized jackknife variance estimators are also given. These variance estimators prove to be approximately design-unbiased under uniform response. It should be noted that similar property on variance estimators has not been discussed in literature.
