Intensive care clinicians are presented with large quantities of patient information and measurements from a multitude of monitoring systems. The limited ability of humans to process such complex information hinders physicians to readily recognize and act on early signs of patient deterioration. We used machine learning to develop an early warning system for circulatory failure based on a high-resolution ICU database with 240 patient years of data. This automatic system predicts 90.0% of circulatory failure events (prevalence 3.1%), with 81.8% identified more than two hours in advance, resulting in an area under the receiver operating characteristic curve of 94.0% and area under the precision-recall curve of 63.0%. The model was externally validated in a large independent patient cohort.

In high-dimensional settings, where the number of features p is typically much larger than the number of samples n, methods which can systematically examine arbitrary combinations of features, a huge 2^p-dimensional space, have recently begun to be explored. However, none of the current methods is able to assess the association between feature combinations and a target variable while conditioning on a categorical covariate, in order to correct for potential confounding effects. We propose the Fast Automatic Conditional Search (FACS) algorithm, a significant discriminative itemset mining method which conditions on categorical covariates and only scales as O(k log k), where k is the number of states of the categorical covariate. Based on the Cochran-Mantel-Haenszel Test, FACS demonstrates superior speed and statistical power on simulated and real-world datasets compared to the state of the art, opening the door to numerous applications in biomedicine.

Significant pattern mining, the problem of finding itemsets that are significantly enriched in one class of objects, is statistically challenging, as the large space of candidate patterns leads to an enormous multiple testing problem. Recently, the concept of testability was proposed as one approach to correct for multiple testing in pattern mining while retaining statistical power. Still, these strategies based on testability do not allow one to condition the test of significance on the observed covariates, which severely limits its utility in biomedical applications. Here we propose a strategy and an efficient algorithm to perform significant pattern mining in the presence of categorical covariates with K states.