目的研究一种新的抗肿瘤药物剂量探索模型(continual reassessment method based on toxicity and efficacy,CRM-TE),这种模型可以在I期临床试验中同时考虑毒性和疗效的药物作用,给II期临床试验推荐最适剂量(recommend the optimal dose...目的研究一种新的抗肿瘤药物剂量探索模型(continual reassessment method based on toxicity and efficacy,CRM-TE),这种模型可以在I期临床试验中同时考虑毒性和疗效的药物作用,给II期临床试验推荐最适剂量(recommend the optimal dose,RP2D)。方法基于连续重评估模型(continual reassessment model,CRM)对药物的剂量-毒性和剂量-疗效曲线分别进行估计,并根据给出的权衡函数选择最适剂量。结果本文提出最适剂量估计方法与目前现有的同类型方法相比,能够在保证安全性的前提下,同时综合考虑不同剂量下的疗效,使选择的RP2D更为合理。结论本文为药物临床试验最适推荐剂量提供了一种新的方法,对于抗肿瘤等药物剂量探索具有一定的实用价值。展开更多
The majority of patients with myocardial infarction(MI) and hypercholesterolaemia does not achieve guideline recommended low-density lipoprotein cholesterol(LDL) levels. Suboptimal dosages of statins explain this dile...The majority of patients with myocardial infarction(MI) and hypercholesterolaemia does not achieve guideline recommended low-density lipoprotein cholesterol(LDL) levels. Suboptimal dosages of statins explain this dilemma in most patients. Design and setting: We evaluated the relationship between statin treatment quality(optimal: LDL< 115 mg/dl, suboptimal: LDL≥ 115 mg/dl, no statin therapy despite hypercholesterolaemia) and the subsequent incidence of coronary events(coronary death, nonfatal MI, bypass surgery) over a 30 months follow- up in a large cohort of post MI patients with hypercholesterolaemia(n=2045). Analysis was performed in a nested case-control manner comparing 173 cases with a coronary event and 346 matched controls. Results: Patients who developed a coronary event were treated optimally in 11.0% , suboptimally in 43.4% (p< 0.05 vs. optimal treatment) and were untreated in 45.7% (p< 0.001 vs. optimal treatment). Respective numbers in event-free patients were 21.4% , 47.7% , and 30.9% . After adjustment for most potential confounders, including all cardiovascular risk factors and medication, the relative risk of future non-fatal MI and coronary death associated with a suboptimal statin treatment was 2.02(95% CI 1.04 to 4.18) compared to optimal statin treatment. Moreover, the statin equivalent dose in optimally treated individuals was significantly higher than in suboptimally treated individuals(0.85± 0.03 vs. 0.78± 0.02, p< 0.05). Conclusion: In this community-based study, a lipid lowering therapy with statins into the recommended target range of LDL levels may be associated with decreased cardiovascular risk compared to a statin therapy without titrating the LDL level below 115 mg/dl. Thus, the quality of statin treatment was identified as an independent predictor of coronary events in post MI patients.展开更多
文摘目的研究一种新的抗肿瘤药物剂量探索模型(continual reassessment method based on toxicity and efficacy,CRM-TE),这种模型可以在I期临床试验中同时考虑毒性和疗效的药物作用,给II期临床试验推荐最适剂量(recommend the optimal dose,RP2D)。方法基于连续重评估模型(continual reassessment model,CRM)对药物的剂量-毒性和剂量-疗效曲线分别进行估计,并根据给出的权衡函数选择最适剂量。结果本文提出最适剂量估计方法与目前现有的同类型方法相比,能够在保证安全性的前提下,同时综合考虑不同剂量下的疗效,使选择的RP2D更为合理。结论本文为药物临床试验最适推荐剂量提供了一种新的方法,对于抗肿瘤等药物剂量探索具有一定的实用价值。
文摘The majority of patients with myocardial infarction(MI) and hypercholesterolaemia does not achieve guideline recommended low-density lipoprotein cholesterol(LDL) levels. Suboptimal dosages of statins explain this dilemma in most patients. Design and setting: We evaluated the relationship between statin treatment quality(optimal: LDL< 115 mg/dl, suboptimal: LDL≥ 115 mg/dl, no statin therapy despite hypercholesterolaemia) and the subsequent incidence of coronary events(coronary death, nonfatal MI, bypass surgery) over a 30 months follow- up in a large cohort of post MI patients with hypercholesterolaemia(n=2045). Analysis was performed in a nested case-control manner comparing 173 cases with a coronary event and 346 matched controls. Results: Patients who developed a coronary event were treated optimally in 11.0% , suboptimally in 43.4% (p< 0.05 vs. optimal treatment) and were untreated in 45.7% (p< 0.001 vs. optimal treatment). Respective numbers in event-free patients were 21.4% , 47.7% , and 30.9% . After adjustment for most potential confounders, including all cardiovascular risk factors and medication, the relative risk of future non-fatal MI and coronary death associated with a suboptimal statin treatment was 2.02(95% CI 1.04 to 4.18) compared to optimal statin treatment. Moreover, the statin equivalent dose in optimally treated individuals was significantly higher than in suboptimally treated individuals(0.85± 0.03 vs. 0.78± 0.02, p< 0.05). Conclusion: In this community-based study, a lipid lowering therapy with statins into the recommended target range of LDL levels may be associated with decreased cardiovascular risk compared to a statin therapy without titrating the LDL level below 115 mg/dl. Thus, the quality of statin treatment was identified as an independent predictor of coronary events in post MI patients.
基金supported by the National Key Research and Development Program of China(2019YFC0840606)from the Ministry of Science and Technologythe National Natural Science Foundation of China(82070189,81770189,81621001,and 81530046)+1 种基金the Science and Technology Project of Guangdong Province of China(2016B030230003)the Project of Health Collaborative Innovation of Guangzhou City(201704020214)。
