Recurrent event data with a terminal event are commonly encountered in longitudinal followup studies.In this paper,we investigate regression analysis of the weighted composite endpoint of recurrent and terminal events...Recurrent event data with a terminal event are commonly encountered in longitudinal followup studies.In this paper,we investigate regression analysis of the weighted composite endpoint of recurrent and terminal events with a semiparametric mixed model.Particularly,the weighted composite endpoint is constructed by the severity of all events while leaving the dependence structure among the recurrent and terminal events unspecified.The semiparametric mixed model is flexible since it allows the covariate effects on the rate function of the weighted composite endpoint to be proportional or convergent.For inference on the model parameters,the estimating equation approach and the inverse probability weighting technique are developed.The asymptotic properties of the resulting estimators are established and the finite sample performance of the proposed procedure is evaluated through Monte Carlo simulation studies.We apply the proposed method to a real data set on a medical cost study of chronic heart failure patients for illustration.展开更多
Recurrent event data are commonly encountered in many scientific fields,including biomedical studies,clinical trials and epidemiological surveys,and many statistical methods have been proposed for their analysis.In th...Recurrent event data are commonly encountered in many scientific fields,including biomedical studies,clinical trials and epidemiological surveys,and many statistical methods have been proposed for their analysis.In this paper,we consider to use a weighted composite endpoint of recurrent and terminal events,which is weighted by the severity of each event,to assess the overall effects of covariates on the two types of events.A flexible additive-multiplicative model incorporating both multiplicative and additive effects on the rate function is proposed to analyze such weighted composite event process,and more importantly,the dependence structure among the recurrent and terminal events is left unspecified.For the estimation,we construct the unbiased estimating equations by virtue of the inverse probability weighting technique,and the resulting estimators are shown to be consistent and asymptotically normal under some mild regularity conditions.We evaluate the finite-sample performance of the proposed method via simulation studies and apply the proposed method to a set of real data arising from a bladder cancer study.展开更多
Severe alcoholic hepatitis remains one of hepatology’s most urgent challenges,with rapid clinical deterioration and high early mortality.This manuscript comments on and contextualizes the recent systematic review by ...Severe alcoholic hepatitis remains one of hepatology’s most urgent challenges,with rapid clinical deterioration and high early mortality.This manuscript comments on and contextualizes the recent systematic review by Quiñones-Calvo et al,which redirects attention from short-term endpoints toward 90-day survival,integrating evidence from associated clinical studies.For decades,corticosteroids have been the mainstay of treatment,reducing 28-day mortality but offering limited benefit for three months.The review emphasizes that the most critical threats to recovery,late infections,renal decline,and relapse,often emerge after the first month.By synthesizing recent studies,it highlights promising interventions such as fecal microbiota transplantation(FMT),which improved 90-day survival in a small randomized trial,and granulocyte colony-stimulating factor(G-CSF),which showed a robust survival benefit in a large retrospective cohort,alongside emerging strategies like plasma exchange and targeted biologics.These findings support a shift toward a two-phase care model:Early stabilization followed by recovery consolidation.For clinicians,such a model may help guide treatment decisions,with therapies like FMT or G-CSF warranting consideration in corticosteroid non-responders,pending further validation in larger randomized controlled trials.Adoption of 90-day survival as a central metric could bridge the gap between initial rescue and sustained remission,providing a more realistic measure of therapeutic success in one of hepatology’s most unforgiving conditions.展开更多
BACKGROUND The clinical impact of post-percutaneous coronary intervention (PCI) quantitative flow ratio (QFR) in patients treated with PCI for chronic total occlusion (CTO) was still undetermined.METHODS All CTO vesse...BACKGROUND The clinical impact of post-percutaneous coronary intervention (PCI) quantitative flow ratio (QFR) in patients treated with PCI for chronic total occlusion (CTO) was still undetermined.METHODS All CTO vessels treated with successful anatomical PCI in patients from PANDA Ⅲ trial were retrospectively measured for postPCI QFR.The primary outcome was 2-year vessel-oriented composite endpoints (VOCEs,composite of target vessel-related cardiac death,target vessel-related myocardial infarction,and ischemia-driven target vessel revascularization).Receiver operator characteristic curve analysis was conducted to identify optimal cutoff value of post-PCI QFR for predicting the 2-year VOCEs,and all vessels were stratified by this optimal cutoff value.Cox proportional hazards models were employed to calculate the hazard ratio (HR) with 95% CI.RESULTS Among 428 CTO vessels treated with PCI,353 vessels (82.5%) were analyzable for post-PCI QFR.31 VOCEs (8.7%) occurred at 2 years.Mean value of post-PCI QFR was 0.92±0.13.Receiver operator characteristic curve analysis shown the optimal cutoff value of post-PCI QFR for predicting 2-year VOCEs was 0.91.The incidence of 2-year VOCEs in the vessel with post-PCI QFR<0.91 (n=91) was significantly higher compared with the vessels with post-PCI QFR≥0.91 (n=262)(22.0%vs.4.2%,HR=4.98,95%CI:2.32–10.70).CONCLUSIONS Higher post-PCI QFR values were associated with improved prognosis in the PCI practice for coronary CTO.Achieving functionally optimal PCI results (post-PCI QFR value≥0.91) tends to get better prognosis for patients with CTO lesions.展开更多
Objective To explore associations between lipoprotein-associated phospholipase A2(Lp-PLA2)and the risk of cardiovascular events in a Chinese population,with a long-term follow-up.Methods A random sample of 2,031 parti...Objective To explore associations between lipoprotein-associated phospholipase A2(Lp-PLA2)and the risk of cardiovascular events in a Chinese population,with a long-term follow-up.Methods A random sample of 2,031 participants(73.6%males,mean age=60.4 years)was derived from the Asymptomatic Polyvascular Abnormalities Community study(APAC)from 2010 to 2011.Serum Lp-PLA2 levels were determined by enzyme-linked immunosorbent assay(ELISA).The composite endpoint was a combination of first-ever stroke,myocardial infarction(MI)or all-cause death.Lp-PLA2 associations with outcomes were assessed using Cox models.Results The median Lp-PLA2 level was 141.0 ng/m L.Over a median follow-up of 9.1 years,we identified 389 events(19.2%),including 137 stroke incidents,43 MIs,and 244 all-cause deaths.Using multivariate Cox regression,when compared with the lowest Lp-PLA2 quartile,the hazard ratios with95%confidence intervals for developing composite endpoints,stroke,major adverse cardiovascular events,and all-cause death were 1.77(1.24–2.54),1.92(1.03–3.60),1.69(1.003–2.84),and 1.94(1.18–3.18)in the highest quartile,respectively.Composite endpoints in 145(28.6%)patients occurred in the highest quartile where Lp-PLA2(159.0 ng/m L)was much lower than the American Association of Clinical Endocrinologists recommended cut-off point,200 ng/m L.Conclusion Higher Lp-PLA2 levels were associated with an increased risk of cardiovascular event/death in a middle-aged Chinese population.The Lp-PLA2 cut-off point may be lower in the Chinese population when predicting cardiovascular events.展开更多
基金supported by the Science and Technology Program of Guangzhou of China(No.202102010512)the National Nature Science Foundation of China(No.11901128)the Nature Science Foundation of Guangdong Province of China(No.2021A1515010044)。
文摘Recurrent event data with a terminal event are commonly encountered in longitudinal followup studies.In this paper,we investigate regression analysis of the weighted composite endpoint of recurrent and terminal events with a semiparametric mixed model.Particularly,the weighted composite endpoint is constructed by the severity of all events while leaving the dependence structure among the recurrent and terminal events unspecified.The semiparametric mixed model is flexible since it allows the covariate effects on the rate function of the weighted composite endpoint to be proportional or convergent.For inference on the model parameters,the estimating equation approach and the inverse probability weighting technique are developed.The asymptotic properties of the resulting estimators are established and the finite sample performance of the proposed procedure is evaluated through Monte Carlo simulation studies.We apply the proposed method to a real data set on a medical cost study of chronic heart failure patients for illustration.
基金the National Natural Science Foundation of China(Grant Nos.11771431,11690015,11926341,11731015,11901128 and 11601097)Key Laboratory of RCSDS,CAS(Grant No.2008DP173182)+2 种基金Natural Science Foundation of Guangdong Province of China(Grant Nos.2018A030310068,2021A1515010044)University Innovation Team Project of Guangdong Province(Grant No.2020WCXTD018)Science and Technology Program of Guangzhou,China(Grant Nos.202102020368,202102010512)。
文摘Recurrent event data are commonly encountered in many scientific fields,including biomedical studies,clinical trials and epidemiological surveys,and many statistical methods have been proposed for their analysis.In this paper,we consider to use a weighted composite endpoint of recurrent and terminal events,which is weighted by the severity of each event,to assess the overall effects of covariates on the two types of events.A flexible additive-multiplicative model incorporating both multiplicative and additive effects on the rate function is proposed to analyze such weighted composite event process,and more importantly,the dependence structure among the recurrent and terminal events is left unspecified.For the estimation,we construct the unbiased estimating equations by virtue of the inverse probability weighting technique,and the resulting estimators are shown to be consistent and asymptotically normal under some mild regularity conditions.We evaluate the finite-sample performance of the proposed method via simulation studies and apply the proposed method to a set of real data arising from a bladder cancer study.
文摘Severe alcoholic hepatitis remains one of hepatology’s most urgent challenges,with rapid clinical deterioration and high early mortality.This manuscript comments on and contextualizes the recent systematic review by Quiñones-Calvo et al,which redirects attention from short-term endpoints toward 90-day survival,integrating evidence from associated clinical studies.For decades,corticosteroids have been the mainstay of treatment,reducing 28-day mortality but offering limited benefit for three months.The review emphasizes that the most critical threats to recovery,late infections,renal decline,and relapse,often emerge after the first month.By synthesizing recent studies,it highlights promising interventions such as fecal microbiota transplantation(FMT),which improved 90-day survival in a small randomized trial,and granulocyte colony-stimulating factor(G-CSF),which showed a robust survival benefit in a large retrospective cohort,alongside emerging strategies like plasma exchange and targeted biologics.These findings support a shift toward a two-phase care model:Early stabilization followed by recovery consolidation.For clinicians,such a model may help guide treatment decisions,with therapies like FMT or G-CSF warranting consideration in corticosteroid non-responders,pending further validation in larger randomized controlled trials.Adoption of 90-day survival as a central metric could bridge the gap between initial rescue and sustained remission,providing a more realistic measure of therapeutic success in one of hepatology’s most unforgiving conditions.
基金supported by the CAMS Innovation Fund for Medical Sciences(No.2021-I2M-1-008)the National High Level Hospital Clinical Research Funding(No.2023-GSP-GG-2&No.2023-GSP-QN-34&No.2023-GSPRC-05).
文摘BACKGROUND The clinical impact of post-percutaneous coronary intervention (PCI) quantitative flow ratio (QFR) in patients treated with PCI for chronic total occlusion (CTO) was still undetermined.METHODS All CTO vessels treated with successful anatomical PCI in patients from PANDA Ⅲ trial were retrospectively measured for postPCI QFR.The primary outcome was 2-year vessel-oriented composite endpoints (VOCEs,composite of target vessel-related cardiac death,target vessel-related myocardial infarction,and ischemia-driven target vessel revascularization).Receiver operator characteristic curve analysis was conducted to identify optimal cutoff value of post-PCI QFR for predicting the 2-year VOCEs,and all vessels were stratified by this optimal cutoff value.Cox proportional hazards models were employed to calculate the hazard ratio (HR) with 95% CI.RESULTS Among 428 CTO vessels treated with PCI,353 vessels (82.5%) were analyzable for post-PCI QFR.31 VOCEs (8.7%) occurred at 2 years.Mean value of post-PCI QFR was 0.92±0.13.Receiver operator characteristic curve analysis shown the optimal cutoff value of post-PCI QFR for predicting 2-year VOCEs was 0.91.The incidence of 2-year VOCEs in the vessel with post-PCI QFR<0.91 (n=91) was significantly higher compared with the vessels with post-PCI QFR≥0.91 (n=262)(22.0%vs.4.2%,HR=4.98,95%CI:2.32–10.70).CONCLUSIONS Higher post-PCI QFR values were associated with improved prognosis in the PCI practice for coronary CTO.Achieving functionally optimal PCI results (post-PCI QFR value≥0.91) tends to get better prognosis for patients with CTO lesions.
基金supported by the National Natural Science Foundation of China [Grant No. 81973112 and Grant No.9204930002]
文摘Objective To explore associations between lipoprotein-associated phospholipase A2(Lp-PLA2)and the risk of cardiovascular events in a Chinese population,with a long-term follow-up.Methods A random sample of 2,031 participants(73.6%males,mean age=60.4 years)was derived from the Asymptomatic Polyvascular Abnormalities Community study(APAC)from 2010 to 2011.Serum Lp-PLA2 levels were determined by enzyme-linked immunosorbent assay(ELISA).The composite endpoint was a combination of first-ever stroke,myocardial infarction(MI)or all-cause death.Lp-PLA2 associations with outcomes were assessed using Cox models.Results The median Lp-PLA2 level was 141.0 ng/m L.Over a median follow-up of 9.1 years,we identified 389 events(19.2%),including 137 stroke incidents,43 MIs,and 244 all-cause deaths.Using multivariate Cox regression,when compared with the lowest Lp-PLA2 quartile,the hazard ratios with95%confidence intervals for developing composite endpoints,stroke,major adverse cardiovascular events,and all-cause death were 1.77(1.24–2.54),1.92(1.03–3.60),1.69(1.003–2.84),and 1.94(1.18–3.18)in the highest quartile,respectively.Composite endpoints in 145(28.6%)patients occurred in the highest quartile where Lp-PLA2(159.0 ng/m L)was much lower than the American Association of Clinical Endocrinologists recommended cut-off point,200 ng/m L.Conclusion Higher Lp-PLA2 levels were associated with an increased risk of cardiovascular event/death in a middle-aged Chinese population.The Lp-PLA2 cut-off point may be lower in the Chinese population when predicting cardiovascular events.
