BACKGROUND Biliary tract cancers(BTCs)are a heterogeneous group of tumors with high malignancy,poor prognosis,and limited treatment options.AIM To explore the efficacy and safety of nab-paclitaxel plus capecitabine as...BACKGROUND Biliary tract cancers(BTCs)are a heterogeneous group of tumors with high malignancy,poor prognosis,and limited treatment options.AIM To explore the efficacy and safety of nab-paclitaxel plus capecitabine as first-line treatment for advanced and metastatic BTCs.METHODS This open-label,non-randomized,double-center,phase II clinical trial recruited systemic therapy-naive patients with unresectable or metastatic BTCs between April 2019 and June 2022 at Beijing Cancer Hospital and the First Hospital of China Medical University.Eligible patients were administered nab-paclitaxel(150 mg/m^(2),day 1)and capecitabine(2000 mg/m^(2),twice daily,days 1-7)in 14-day cycles until experiencing intolerable toxicity or disease progression.The primary outcome was the objective response rate(ORR).The secondary outcomes included the disease control rate(DCR),overall survival(OS),progression-free survival(PFS),and safety.RESULTS A total of 44 patients successfully completed the trial,with a median age of 64.00 years(interquartile range,35.00-76.00),and 26(59.09%)were females.Tumor response assessment was impeded for one patient due to premature demise from tumor hemorrhage.Among the remaining 43 patients undergoing at least one imaging assessment,the ORR was 23.26%[95%confidence interval(CI):11.80%-38.60%],and the DCR was 69.77%(95%CI:53.90%-82.80%).The median OS was 14.1 months(95%CI:8.3-19.9),and the median PFS was 4.4 months(95%CI:2.5-6.3).A total of 41 patients(93.18%)experienced at least one adverse event(AE),with 10 patients(22.73%)encountering grade≥3 AEs,and the most frequent AEs of any grade were alopecia(79.50%),leukopenia(54.55%),neutropenia(52.27%),and liver dysfunction(40.91%),and no treatment-related deaths were documented.CONCLUSION Nab-paclitaxel plus capecitabine may be an effective and safe first-line treatment strategy for patients with advanced or metastatic BTCs.展开更多
Congestive heart failure(CHF) is a chronic condition, requiring polypharmacy, allied health supports and regular monitoring. All these factors are needed to ensure compliance and to deliver the positive outcomes demon...Congestive heart failure(CHF) is a chronic condition, requiring polypharmacy, allied health supports and regular monitoring. All these factors are needed to ensure compliance and to deliver the positive outcomes demonstrated from randomized controlled trials. Unfortunately many centers around the world are unable to match trial level support. The outcomes for many communities are thus unclear. Research design factors in post-marketing surveillance to address this issue. Phase 4 studies is the name given to trials designed to obtain such community level data and thus address issues of external validity. CHF phase 4 studies are relatively underutilized. We feel the onus for this research lies with the health profession. In this commentary we provide arguments as to why phase 4 studies should be viewed as a social and corporate responsibility of health professional that care for clients with CHF.展开更多
Background: Many clinical trials include multiple patient-reported outcomes (PROs) to measure fatigue as secondary or exploratory endpoints of treatment effectiveness. Often, these instruments have overlapping content...Background: Many clinical trials include multiple patient-reported outcomes (PROs) to measure fatigue as secondary or exploratory endpoints of treatment effectiveness. Often, these instruments have overlapping content. The objective of this study was to compare the combined measurement properties of two fatigue scales, the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) and SF-36 vitality (VT) scale using item response theory (IRT). Methods: The FACIT-Fatigue and SF-36v2 were administered at baseline and weeks 2, 4, 7, 12, and 16 to rheumatoid arthritis (RA) patients (n = 237) enrolled in a 52-week multicenter, randomized, double-blind, placebo-controlled, parallel-group, dose finding study to evaluate the efficacy and safety of subcutaneous secukinumab administered to pa- tients with active RA. Confirmatory factor analysis (CFA) was used to investigate unidimensionality among FACIT- Fatigue and VT items. A generalized partial credit IRT model was used to cross-calibrate the FACIT-Fatigue and VT items and weighted maximum-likelihood estimation was used to score a composite fatigue index. Analysis of variance was used to compare the composite fatigue index with the original scales in responding to ACR improvement and treatment effects. Results: CFA found less than adequate fit to a unidimensional model. However, specifications of alternative multidimensional models were insufficient in explaining the common variance among items. An IRT model was successfully fitted and the composite fatigue index score was found to be more responsive than the original scales to ACR improvement and treatment effects. Effect sizes and significance tests for changes in scores on the composite index were generally larger than those observed with the original scales. Conclusion: IRT methods offer a promising approach to combining items from different scales measuring the same concept that could improve the detection of treatment effects in clinical studies of RA.展开更多
The primary aim of clinical trials is to investigate whether a treatment is effective for a particular disease or condition. Randomized controlled clinical trials are considered to be the gold standard for evaluating ...The primary aim of clinical trials is to investigate whether a treatment is effective for a particular disease or condition. Randomized controlled clinical trials are considered to be the gold standard for evaluating the effect of a certain intervention. However, in clinical trials, even after randomization, there are situations where the patients differ substantially with respect to the baseline value of the outcome variable. Many a times the response to interventions depends on the baseline values of the outcome variable. When there are baseline-dependent treatment effects, differences among treatments vary as a function of baseline level. Although variation in outcome associated with baseline value is accounted for in ANCOVA, analysis of individual differences in treatment effect is precluded by the homogeneity of regression assumption. This assumption requires that expected differences in outcome among treatments be constant across all baseline levels. To overcome this difficulty, Weigel and Narvaez [7] proposed a regression model for two treatment groups to analyze individual response to treatments in randomized controlled clinical trials. The authors reviewed the model suggested by Weigel and Narvaez and extended further for three or more treatment groups. The utility of the model was demonstrated with real life data from a randomized controlled clinical trial of bronchial asthma.展开更多
Type 1 diabetes(T1D)is a chronic autoimmune condition that destroys insulinproducing beta cells in the pancreas,leading to insulin deficiency and hyperglycemia.The management of T1D primarily focuses on exogenous insu...Type 1 diabetes(T1D)is a chronic autoimmune condition that destroys insulinproducing beta cells in the pancreas,leading to insulin deficiency and hyperglycemia.The management of T1D primarily focuses on exogenous insulin replacement to control blood glucose levels.However,this approach does not address the underlying autoimmune process or prevent the progressive loss of beta cells.Recent research has explored the potential of glucagon-like peptide-1 receptor agonists(GLP-1RAs)as a novel intervention to modify the disease course and delay the onset of T1D.GLP-1RAs are medications initially developed for treating type 2 diabetes.They exert their effects by enhancing glucose-dependent insulin secretion,suppressing glucagon secretion,and slowing gastric emptying.Emerging evidence suggests that GLP-1RAs may also benefit the treatment of newly diagnosed patients with T1D.This article aims to highlight the potential of GLP-1RAs as an intervention to delay the onset of T1D,possibly through their potential immunomodulatory and anti-inflammatory effects and preservation of beta-cells.This article aims to explore the potential of shifting the paradigm of T1D management from reactive insulin replacement to proactive disease modification,which should open new avenues for preventing and treating T1D,improving the quality of life and long-term outcomes for individuals at risk of T1D.展开更多
目的:运用网状Meta分析不同中药注射液治疗糖尿病周围神经病变(DPN)的疗效和安全性。方法:基于PubMed、Cochrane Library、EMbase、Web of Science、国家知识基础设施数据库(CNKI)、中文科技期刊数据库(CCD)、中国学术期刊数据库(CSPD)...目的:运用网状Meta分析不同中药注射液治疗糖尿病周围神经病变(DPN)的疗效和安全性。方法:基于PubMed、Cochrane Library、EMbase、Web of Science、国家知识基础设施数据库(CNKI)、中文科技期刊数据库(CCD)、中国学术期刊数据库(CSPD)、中国生物医学文献数据库(CBM),检索中药注射液治疗DPN的随机对照试验(RCTs),将临床总有效率作为主要结局指标,正中和腓总的感觉神经传导速度(SCV)及运动神经传导速度(MCV)、空腹血糖(FBG)及不良反应作为次要结局指标。采用Cochrane评价手册5.3风险偏倚评估工具进行质量评价及RevMan 5.4.1及Stata 17软件进行数据分析。结果:共纳入76项RCTs,包括6 108例患者,11种中药注射液。网状Meta分析结果显示,丹参多酚酸盐注射液联合西药在提高临床总有效率和改善FBG水平方面疗效最佳;苦碟子注射液联合西药在改善正中神经及腓总神经的SCV、正中神经MCV方面疗效最佳;血塞通注射液联合西药在改善腓总神经MCV方面疗效最佳;在安全性方面,中药注射液联合西药与单纯西药治疗比较差异无统计学意义。结论:中药注射液联合西药与单纯西药治疗比较可提高DPN临床疗效,且未增加不良反应的发生。展开更多
文摘BACKGROUND Biliary tract cancers(BTCs)are a heterogeneous group of tumors with high malignancy,poor prognosis,and limited treatment options.AIM To explore the efficacy and safety of nab-paclitaxel plus capecitabine as first-line treatment for advanced and metastatic BTCs.METHODS This open-label,non-randomized,double-center,phase II clinical trial recruited systemic therapy-naive patients with unresectable or metastatic BTCs between April 2019 and June 2022 at Beijing Cancer Hospital and the First Hospital of China Medical University.Eligible patients were administered nab-paclitaxel(150 mg/m^(2),day 1)and capecitabine(2000 mg/m^(2),twice daily,days 1-7)in 14-day cycles until experiencing intolerable toxicity or disease progression.The primary outcome was the objective response rate(ORR).The secondary outcomes included the disease control rate(DCR),overall survival(OS),progression-free survival(PFS),and safety.RESULTS A total of 44 patients successfully completed the trial,with a median age of 64.00 years(interquartile range,35.00-76.00),and 26(59.09%)were females.Tumor response assessment was impeded for one patient due to premature demise from tumor hemorrhage.Among the remaining 43 patients undergoing at least one imaging assessment,the ORR was 23.26%[95%confidence interval(CI):11.80%-38.60%],and the DCR was 69.77%(95%CI:53.90%-82.80%).The median OS was 14.1 months(95%CI:8.3-19.9),and the median PFS was 4.4 months(95%CI:2.5-6.3).A total of 41 patients(93.18%)experienced at least one adverse event(AE),with 10 patients(22.73%)encountering grade≥3 AEs,and the most frequent AEs of any grade were alopecia(79.50%),leukopenia(54.55%),neutropenia(52.27%),and liver dysfunction(40.91%),and no treatment-related deaths were documented.CONCLUSION Nab-paclitaxel plus capecitabine may be an effective and safe first-line treatment strategy for patients with advanced or metastatic BTCs.
文摘Congestive heart failure(CHF) is a chronic condition, requiring polypharmacy, allied health supports and regular monitoring. All these factors are needed to ensure compliance and to deliver the positive outcomes demonstrated from randomized controlled trials. Unfortunately many centers around the world are unable to match trial level support. The outcomes for many communities are thus unclear. Research design factors in post-marketing surveillance to address this issue. Phase 4 studies is the name given to trials designed to obtain such community level data and thus address issues of external validity. CHF phase 4 studies are relatively underutilized. We feel the onus for this research lies with the health profession. In this commentary we provide arguments as to why phase 4 studies should be viewed as a social and corporate responsibility of health professional that care for clients with CHF.
文摘Background: Many clinical trials include multiple patient-reported outcomes (PROs) to measure fatigue as secondary or exploratory endpoints of treatment effectiveness. Often, these instruments have overlapping content. The objective of this study was to compare the combined measurement properties of two fatigue scales, the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) and SF-36 vitality (VT) scale using item response theory (IRT). Methods: The FACIT-Fatigue and SF-36v2 were administered at baseline and weeks 2, 4, 7, 12, and 16 to rheumatoid arthritis (RA) patients (n = 237) enrolled in a 52-week multicenter, randomized, double-blind, placebo-controlled, parallel-group, dose finding study to evaluate the efficacy and safety of subcutaneous secukinumab administered to pa- tients with active RA. Confirmatory factor analysis (CFA) was used to investigate unidimensionality among FACIT- Fatigue and VT items. A generalized partial credit IRT model was used to cross-calibrate the FACIT-Fatigue and VT items and weighted maximum-likelihood estimation was used to score a composite fatigue index. Analysis of variance was used to compare the composite fatigue index with the original scales in responding to ACR improvement and treatment effects. Results: CFA found less than adequate fit to a unidimensional model. However, specifications of alternative multidimensional models were insufficient in explaining the common variance among items. An IRT model was successfully fitted and the composite fatigue index score was found to be more responsive than the original scales to ACR improvement and treatment effects. Effect sizes and significance tests for changes in scores on the composite index were generally larger than those observed with the original scales. Conclusion: IRT methods offer a promising approach to combining items from different scales measuring the same concept that could improve the detection of treatment effects in clinical studies of RA.
文摘The primary aim of clinical trials is to investigate whether a treatment is effective for a particular disease or condition. Randomized controlled clinical trials are considered to be the gold standard for evaluating the effect of a certain intervention. However, in clinical trials, even after randomization, there are situations where the patients differ substantially with respect to the baseline value of the outcome variable. Many a times the response to interventions depends on the baseline values of the outcome variable. When there are baseline-dependent treatment effects, differences among treatments vary as a function of baseline level. Although variation in outcome associated with baseline value is accounted for in ANCOVA, analysis of individual differences in treatment effect is precluded by the homogeneity of regression assumption. This assumption requires that expected differences in outcome among treatments be constant across all baseline levels. To overcome this difficulty, Weigel and Narvaez [7] proposed a regression model for two treatment groups to analyze individual response to treatments in randomized controlled clinical trials. The authors reviewed the model suggested by Weigel and Narvaez and extended further for three or more treatment groups. The utility of the model was demonstrated with real life data from a randomized controlled clinical trial of bronchial asthma.
文摘Type 1 diabetes(T1D)is a chronic autoimmune condition that destroys insulinproducing beta cells in the pancreas,leading to insulin deficiency and hyperglycemia.The management of T1D primarily focuses on exogenous insulin replacement to control blood glucose levels.However,this approach does not address the underlying autoimmune process or prevent the progressive loss of beta cells.Recent research has explored the potential of glucagon-like peptide-1 receptor agonists(GLP-1RAs)as a novel intervention to modify the disease course and delay the onset of T1D.GLP-1RAs are medications initially developed for treating type 2 diabetes.They exert their effects by enhancing glucose-dependent insulin secretion,suppressing glucagon secretion,and slowing gastric emptying.Emerging evidence suggests that GLP-1RAs may also benefit the treatment of newly diagnosed patients with T1D.This article aims to highlight the potential of GLP-1RAs as an intervention to delay the onset of T1D,possibly through their potential immunomodulatory and anti-inflammatory effects and preservation of beta-cells.This article aims to explore the potential of shifting the paradigm of T1D management from reactive insulin replacement to proactive disease modification,which should open new avenues for preventing and treating T1D,improving the quality of life and long-term outcomes for individuals at risk of T1D.
