In clinical trials, the primary efficacy endpoint often corresponds to a so-called "composite endpoint". Composite endpoints combine several events of interest within a single outcome variable. Thereby it is...In clinical trials, the primary efficacy endpoint often corresponds to a so-called "composite endpoint". Composite endpoints combine several events of interest within a single outcome variable. Thereby it is intended to enlarge the expected effect size and thereby increase the power of the study. However, composite endpoints also come along with serious challenges and problems. On the one hand, composite endpoints may lead to difficulties during the planning phase of a trial with respect to the sample size calculation, asthe expected clinical effect of an intervention on the composite endpoint depends on the effects on its single components and their correlations. This may lead to wrong assumptions on the sample size needed. Too optimistic assumptions on the expected effect may lead to an underpowered of the trial, whereas a too conservatively estimated effect results in an unnecessarily high sample size. On the other hand, the interpretation of composite endpoints may be difficult, as the observed effect of the composite does not necessarily reflect the effects of the single components. Therefore the demonstration of the clinical efficacy of a new intervention by exclusively evaluating the composite endpoint may be misleading. The present paper summarizes results and recommendations of the latest research addressing the above mentioned problems in the planning, analysis and interpretation of clinical trials with composite endpoints, thereby providing a practical guidance for users.展开更多
目的:探讨心脏磁共振成像钆延迟增强(cardiac magnetic resonance imaging late gadolinium enhanced,CMR-LGE)在高血压性心脏病(hypertensive heart disease,HHD)预后评估中的应用价值。方法:本回顾性研究纳入2021年7月至2024年6月在...目的:探讨心脏磁共振成像钆延迟增强(cardiac magnetic resonance imaging late gadolinium enhanced,CMR-LGE)在高血压性心脏病(hypertensive heart disease,HHD)预后评估中的应用价值。方法:本回顾性研究纳入2021年7月至2024年6月在我院确诊并接受CMR检查的76例HHD患者。收集包括心肌肌钙蛋白I(cTn I)、临床终点事件等临床资料,并使用CMR技术获取左心室结构和功能指标。根据是否存在LGE及病情是否稳定,将患者分为不同的亚组进行比较分析。结果:病情稳定组与心衰再入院组在多个临床资料及左心室结构、功能指标上存在显著统计学差异,如NYHA心功能分级、左心室质量指数(LVMI)、相对室壁厚度(RWT)等。LGE阳性患者相比阴性患者,cTnI水平、左室舒张末期直径(LVEDd)、RWT升高,而左心室射血分数(EF%)降低,差异具有统计学意义。肌壁间型延迟强化模式在病情稳定组与心衰再入院组中有统计学差异。结论:CMR-LGE可作为HHD患者临床终点事件的独立预测因子,尤其在存在心肌损伤但cTn I水平正常的HHD患者中,CMR-LGE有助于检测受损心肌。此外,HHD的扩张表型更易出现LGE,而肌壁间型延迟强化模式与心衰再入院事件的发生密切相关。展开更多
目的:探讨肾康宁胶囊对显性糖尿病肾病(DKD)脾肾气虚证患者的临床疗效及对血清核转录因子-κB(NF-κB),转化生长因子-β_1(TGF-β_1)和血小板源性生长因子(PDGF)水平的影响。方法:将138例患者采用区组随机,按数字表法分为对照组和观察组...目的:探讨肾康宁胶囊对显性糖尿病肾病(DKD)脾肾气虚证患者的临床疗效及对血清核转录因子-κB(NF-κB),转化生长因子-β_1(TGF-β_1)和血小板源性生长因子(PDGF)水平的影响。方法:将138例患者采用区组随机,按数字表法分为对照组和观察组各69例。对照组口服替米沙坦片,1片/d,和口服阿托伐他汀钙片,10 mg·d^(-1)。观察组西药使用同对照组,并服用肾康宁胶囊,4粒/次,3次/d。两组疗程均为连续治疗24周或至Ⅴ期,并进行24周随访。记录治疗期和随访期病情进展至Ⅴ期的患者数量,或肌酐(SCr)翻版倍等终点事件发生情况;检测治疗前后空腹血糖(FBG),糖化血红蛋白(Hb Alc),尿素氮(BUN),血肌酐(SCr),血红蛋白(Hb),血浆白蛋白(ALB),24 h尿蛋白定量(24 h Upr),胆固醇(TC),甘油三酯(TG),高密度脂蛋白胆固醇(HDL-C)和低密度脂蛋白胆固醇(LDL-C)检测;进行治疗前后脾肾气虚证评分;检测治疗前后TGF-β_1,NF-κB和PDGF水平。结果:观察组临床疗效有效率为78.26%,对照组为57.97%,观察组高于对照组(χ~2=6.539,P<0.05);观察组中医证候评分有效率为85.51%,对照组为65.22%,观察组中医证候评分高于对照组(χ~2=7.649,P<0.01);观察组终点事件发生率为15.94%,对照组为33.33%,观察组终点事件发生率低于对照组(χ~2=5.619,P<0.05);治疗后观察组Hb Alc,24 h Upr,BUN和SCr水平均低于对照组(P<0.01);治疗后观察组Hb,ALB和HDL-C水平均高于对照组(P<0.01),LDL-C水平低于对照组(P<0.01),TC和TG组间比较差异无统计学意义;治疗后观察组TGF-β_1,NF-κB和PDG水平均低于对照组(P<0.01)。结论:在西医常规治疗的基础上,采用肾康宁胶囊内服治疗DKDⅣ期患者,能改善脾肾气虚证症状、减轻蛋白尿,能调节糖、脂代谢,改善患者营养状况,从而降低终点事件的发生率,对DKD病情起到延缓作用,其作用机制可能通过下调血清TGF-β_1,PDGF,NF-κB等细胞因子来实现的。展开更多
文摘In clinical trials, the primary efficacy endpoint often corresponds to a so-called "composite endpoint". Composite endpoints combine several events of interest within a single outcome variable. Thereby it is intended to enlarge the expected effect size and thereby increase the power of the study. However, composite endpoints also come along with serious challenges and problems. On the one hand, composite endpoints may lead to difficulties during the planning phase of a trial with respect to the sample size calculation, asthe expected clinical effect of an intervention on the composite endpoint depends on the effects on its single components and their correlations. This may lead to wrong assumptions on the sample size needed. Too optimistic assumptions on the expected effect may lead to an underpowered of the trial, whereas a too conservatively estimated effect results in an unnecessarily high sample size. On the other hand, the interpretation of composite endpoints may be difficult, as the observed effect of the composite does not necessarily reflect the effects of the single components. Therefore the demonstration of the clinical efficacy of a new intervention by exclusively evaluating the composite endpoint may be misleading. The present paper summarizes results and recommendations of the latest research addressing the above mentioned problems in the planning, analysis and interpretation of clinical trials with composite endpoints, thereby providing a practical guidance for users.
文摘目的:探讨肾康宁胶囊对显性糖尿病肾病(DKD)脾肾气虚证患者的临床疗效及对血清核转录因子-κB(NF-κB),转化生长因子-β_1(TGF-β_1)和血小板源性生长因子(PDGF)水平的影响。方法:将138例患者采用区组随机,按数字表法分为对照组和观察组各69例。对照组口服替米沙坦片,1片/d,和口服阿托伐他汀钙片,10 mg·d^(-1)。观察组西药使用同对照组,并服用肾康宁胶囊,4粒/次,3次/d。两组疗程均为连续治疗24周或至Ⅴ期,并进行24周随访。记录治疗期和随访期病情进展至Ⅴ期的患者数量,或肌酐(SCr)翻版倍等终点事件发生情况;检测治疗前后空腹血糖(FBG),糖化血红蛋白(Hb Alc),尿素氮(BUN),血肌酐(SCr),血红蛋白(Hb),血浆白蛋白(ALB),24 h尿蛋白定量(24 h Upr),胆固醇(TC),甘油三酯(TG),高密度脂蛋白胆固醇(HDL-C)和低密度脂蛋白胆固醇(LDL-C)检测;进行治疗前后脾肾气虚证评分;检测治疗前后TGF-β_1,NF-κB和PDGF水平。结果:观察组临床疗效有效率为78.26%,对照组为57.97%,观察组高于对照组(χ~2=6.539,P<0.05);观察组中医证候评分有效率为85.51%,对照组为65.22%,观察组中医证候评分高于对照组(χ~2=7.649,P<0.01);观察组终点事件发生率为15.94%,对照组为33.33%,观察组终点事件发生率低于对照组(χ~2=5.619,P<0.05);治疗后观察组Hb Alc,24 h Upr,BUN和SCr水平均低于对照组(P<0.01);治疗后观察组Hb,ALB和HDL-C水平均高于对照组(P<0.01),LDL-C水平低于对照组(P<0.01),TC和TG组间比较差异无统计学意义;治疗后观察组TGF-β_1,NF-κB和PDG水平均低于对照组(P<0.01)。结论:在西医常规治疗的基础上,采用肾康宁胶囊内服治疗DKDⅣ期患者,能改善脾肾气虚证症状、减轻蛋白尿,能调节糖、脂代谢,改善患者营养状况,从而降低终点事件的发生率,对DKD病情起到延缓作用,其作用机制可能通过下调血清TGF-β_1,PDGF,NF-κB等细胞因子来实现的。
