Overview of Sepsis and Sepsis Biomarker Detection

Sepsis being a fatal physiological state due to an imbalance in the immune system caused by infection, and one of the most common cause for millions of deaths in the non-coronary intensive care unit worldwide requires special attention in its diagnostic methods and cure. Therefore an understanding of literature related to sepsis is of utmost importance. With the advent of inter-disciplinary research, the study and diagnosis of sepsis problem are not limited to the medical field, rather it requires interventions and active participation of other fields of science and technology. However, often subject matter from interdisciplinary research is expounded in an abstruse manner and hence it becomes elusive for a researcher from different research domain to understand it, leading to loss of quality and efficiency in research. In this survey report, the material is presented in a form that facilitates easy comprehension for the non-medical researchers and has been focused on introducing sepsis, it\u27s causes, extent, comparison of diagnosis techniques: conventional labeled and label-free detections; with special emphasis on sepsis biomarkers to help researchers from multi-disciplinary domain to develop and fabricate devices and ideas to compliment the existing sepsis diagnosis system present in the medical field. A future direction of sepsis diagnosis along with the implementation of novel techniques for sepsis biomarker quantification is also reported

Machine learning for the prediction of sepsis: a systematic review and meta-analysis of diagnostic test accuracy

Abstract: Purpose: Early clinical recognition of sepsis can be challenging. With the advancement of machine learning, promising real-time models to predict sepsis have emerged. We assessed their performance by carrying out a systematic review and meta-analysis. Methods: A systematic search was performed in PubMed, Embase.com and Scopus. Studies targeting sepsis, severe sepsis or septic shock in any hospital setting were eligible for inclusion. The index test was any supervised machine learning model for real-time prediction of these conditions. Quality of evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology, with a tailored Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) checklist to evaluate risk of bias. Models with a reported area under the curve of the receiver operating characteristic (AUROC) metric were meta-analyzed to identify strongest contributors to model performance. Results: After screening, a total of 28 papers were eligible for synthesis, from which 130 models were extracted. The majority of papers were developed in the intensive care unit (ICU, n = 15; 54%), followed by hospital wards (n = 7; 25%), the emergency department (ED, n = 4; 14%) and all of these settings (n = 2; 7%). For the prediction of sepsis, diagnostic test accuracy assessed by the AUROC ranged from 0.68–0.99 in the ICU, to 0.96–0.98 in-hospital and 0.87 to 0.97 in the ED. Varying sepsis definitions limit pooling of the performance across studies. Only three papers clinically implemented models with mixed results. In the multivariate analysis, temperature, lab values, and model type contributed most to model performance. Conclusion: This systematic review and meta-analysis show that on retrospective data, individual machine learning models can accurately predict sepsis onset ahead of time. Although they present alternatives to traditional scoring systems, between-study heterogeneity limits the assessment of pooled results. Systematic reporting and clinical implementation studies are needed to bridge the gap between bytes and bedside

Toward Precision Medicine in Intensive Care: Leveraging Electronic Health Records and Patient Similarity

The growing adoption of Electronic Health Record (EHR) systems has resulted in an unprecedented amount of data. This availability of data has also opened up the opportunity to utilize EHRs for providing more customized care for each patient by considering individual variability, which is the goal of precision medicine. In this context, patient similarity (PS) analytics have been introduced to facilitate data analysis through investigating the similarities in patients’ data, and, ultimately, to help improve the healthcare system. This dissertation is presented in six chapters and focuses on employing PS analytics in data-rich intensive care units. Chapter 1 provides a review of the literature and summarizes studies describing approaches for predicting patients’ future health status based on EHR and PS. Chapter 2 demonstrates the informativeness of missing data in patient profiles and introduces missing data indicators to use this information in mortality prediction. The results demonstrate that including indicators with observed measurements in a set of well-known prediction models (logistic regression, decision tree, and random forest) can improve the predictive accuracy. Chapter 3 builds upon the previous results and utilizes these missing indicators to reveal patient subpopulations based on their similarity in laboratory test ordering being used for them. In this chapter, the Density-based Spatial Clustering of Applications with Noise method, was employed to group the patients into clusters using the indicators generated in the previous study. Results confirmed that missing indicators capture the laboratory-test-ordering patterns that are informative and can be used to identify similar patient subpopulations. Chapter 4 investigates the performance of a multifaceted PS metric constructed by utilizing appropriate similarity metrics for specific clinical variables (e.g. vital signs, ICD-9, etc.). The proposed PS metric was evaluated in a 30-day post-discharge mortality prediction problem. Results demonstrate that PS-based prediction models with the new PS metric outperformed population-based prediction models. Moreover, the multifaceted PS metric significantly outperformed cosine and Euclidean PS metric in k-nearest neighbors setting. Chapter 5 takes the previous results into consideration and looks for potential subpopulations among septic patients. Sepsis is one of the most common causes of death in Canada. The focus of this chapter is on longitudinal EHR data which are a collection of observations of measurements made chronologically for each patient. This chapter employs Functional Principal Component Analysis to derive the dominant modes of variation in septic patients’ EHR's. Results confirm that including temporal data in the analysis can help in identifying subgroups of septic patients. Finally, Chapter 6 provides a discussion of results from previous chapters. The results indicate the informativeness of missing data and how PS can help in improving the performance of predictive modeling. Moreover, results show that utilizing the temporal information in PS calculation improves patient stratification. Finally, the discussion identifies limitations and directions for future research