Moran John L, Bersten Andrew D, Solomon Patricia J, Edibam Cyrus, Hunt Tamara
Department of Intensive Care Medicine, The Queen Elizabeth Hospital, Woodville, SA, Australia.
J Eval Clin Pract. 2008 Feb;14(1):83-93. doi: 10.1111/j.1365-2753.2007.00806.x.
The Cox model has been the mainstay of survival analysis in the critically ill and time-dependent covariates have infrequently been incorporated into survival analysis.
To model 28-day survival of patients with acute lung injury (ALI) and acute respiratory distress syndrome (ARDS), and compare the utility of Cox and accelerated failure time (AFT) models.
Prospective cohort study of 168 adult patients enrolled at diagnosis of ALI in 21 adult ICUs in three Australian States with measurement of survival time, censored at 28 days. Model performance was assessed as goodness-of-fit [GOF, cross-products of quantiles of risk and time intervals (P > or = 0.1), Cox model] and explained variation ('R2', Cox and ATF).
Over a 2-month study period (October-November 1999), 168 patients with ALI were identified, with a mean (SD) age of 61.5 (18) years and 30% female. Peak mortality hazard occurred at days 7-8 after onset of ALI/ARDS. In the Cox model, increasing age and female gender, plus interaction, were associated with an increased mortality hazard. Time-varying effects were established for patient severity-of-illness score (decreasing hazard over time) and multiple-organ-dysfunction score (increasing hazard over time). The Cox model was well specified (GOF, P > 0.34) and R2 = 0.546, 95% CI: 0.390, 0.781. Both log-normal (R2 = 0.451, 95% CI: 0.321, 0.695) and log-logistic (R2 0.470, 95% CI: 0.346, 0.714) AFT models identified the same predictors as the Cox model, but did not demonstrate convincingly superior overall fit.
Time dependence of predictors of survival in ALI/ARDS exists and must be appropriately modelled. The Cox model with time-varying covariates remains a flexible model in survival analysis of patients with acute severe illness.
Cox模型一直是危重症患者生存分析的主要方法，而时间依赖性协变量很少被纳入生存分析。
对急性肺损伤（ALI）和急性呼吸窘迫综合征（ARDS）患者的28天生存率进行建模，并比较Cox模型和加速失效时间（AFT）模型的效用。
对澳大利亚三个州21个成人重症监护病房中诊断为ALI的168例成年患者进行前瞻性队列研究，测量生存时间，以28天为截尾时间。模型性能通过拟合优度[GOF，风险分位数与时间间隔的交叉乘积（P≥0.1），Cox模型]和解释变异（“R2”，Cox模型和AFT模型）进行评估。
在为期2个月的研究期间（1999年10月至11月），共识别出168例ALI患者，平均（标准差）年龄为61.5（18）岁，女性占30%。ALI/ARDS发病后第7至8天死亡率风险最高。在Cox模型中，年龄增加、女性性别以及两者的交互作用与死亡率风险增加相关。建立了患者疾病严重程度评分（随时间风险降低）和多器官功能障碍评分（随时间风险增加）的时间变化效应。Cox模型的设定良好（GOF，P>0.34），R2 = 0.546，95%置信区间：0.390，0.781。对数正态（R2 = 0.451，95%置信区间：0.321，0.695）和对数逻辑（R2 = 0.470，95%置信区间：0.346，0.714）AFT模型识别出的预测因素与Cox模型相同，但总体拟合效果未显示出令人信服的优势。
ALI/ARDS患者生存预测因素存在时间依赖性，必须进行适当建模。具有时间变化协变量的Cox模型在急性重症患者的生存分析中仍然是一个灵活的模型。
