Development and validation of a novel molecular biomarker diagnostic test for the early detection of sepsis.

INTRODUCTION: Sepsis is a complex immunological response to infection characterized by early hyper-inflammation followed by severe and protracted immunosuppression, suggesting that a multi-marker approach has the greatest clinical utility for early detection, within a clinical environment focused on Systemic Inflammatory Response Syndrome (SIRS) differentiation. Pre-clinical research using an equine sepsis model identified a panel of gene expression biomarkers that define the early aberrant immune activation. Thus, the primary objective was to apply these gene expression biomarkers to distinguish patients with sepsis from those who had undergone major open surgery and had clinical outcomes consistent with systemic inflammation due to physical trauma and wound healing. METHODS: This was a multi-centre, prospective clinical trial conducted across four tertiary critical care settings in Australia. Sepsis patients were recruited if they met the 1992 Consensus Statement criteria and had clinical evidence of systemic infection based on microbiology diagnoses (n = 27). Participants in the post-surgical (PS) group were recruited pre-operatively and blood samples collected within 24 hours following surgery (n = 38). Healthy controls (HC) included hospital staff with no known concurrent illnesses (n = 20). Each participant had minimally 5 ml of PAXgene blood collected for leucocyte RNA isolation and gene expression analyses. Affymetrix array and multiplex tandem (MT)-PCR studies were conducted to evaluate transcriptional profiles in circulating white blood cells applying a set of 42 molecular markers that had been identified a priori. A LogitBoost algorithm was used to create a machine learning diagnostic rule to predict sepsis outcomes. RESULTS: Based on preliminary microarray analyses comparing HC and sepsis groups, a panel of 42-gene expression markers were identified that represented key innate and adaptive immune function, cell cycling, WBC differentiation, extracellular remodelling and immune modulation pathways. Comparisons against GEO data confirmed the definitive separation of the sepsis cohort. Quantitative PCR results suggest the capacity for this test to differentiate severe systemic inflammation from HC is 92%. The area under the curve (AUC) receiver operator characteristics (ROC) curve findings demonstrated sepsis prediction within a mixed inflammatory population, was between 86 and 92%. CONCLUSIONS: This novel molecular biomarker test has a clinically relevant sensitivity and specificity profile, and has the capacity for early detection of sepsis via the monitoring of critical care patients.

Burnout syndrome among Australian intensivists: a survey.

OBJECTIVE: To examine practice patterns and workload of practising Australian intensivists and to investigate the risk and prevalence of "burnout syndrome". DESIGN AND SETTING: On-line survey was emailed to 324 intensivists listed on the database of the Australian and New Zealand Intensive Care Society (ANZICS) and practising in Australia. MAIN OUTCOME MEASURES: Prospectively recorded workload during a specific week in October 2007, self-reported 12-weekly averaged work pattern, and prevalence of burnout syndrome assessed by modified Maslach Burnout Inventory-General Survey (MBI-GS). RESULTS: 115 intensivists (36%) responded; respondents were representative of mainstream tertiary intensive care practitioners. On average in a 12-week period, intensivists spent 42% of working days in bedside patient management, 16% in administration, 11% in locum positions, 9% in research and 9% in recreational leave. During 1 week of prospective recording of actual workload, 26% of intensivists managed more than nine ventilated patients, and most admitted more than two new patients per day. Most were involved in more than two family conferences with a median duration of 1 h. The MBI-GS showed that 80% of respondents had signs of psychological stress and discomfort, 42% showed signs of emotional exhaustion, 32% had negative feelings and cynicism, and 37% considered they underachieved in terms of personal accomplishments. CONCLUSIONS: Intensivists are at high risk of burnout syndrome. Recognising the drivers and early signs of burnout and identifying a preventive strategy is a professional priority for ANZICS and the intensive care community.

Basic science research in Australian intensive care practice.

OBJECTIVE: A number of recent therapeutic advances have resulted from basic science research. With the change in medical education and practice towards evidence-based medicine, we wished to determine the role of basic science research in Australian intensive care practice. We believe this is the first survey of Australian intensivists and trainees to assess the influence of basic science research on their clinical duties. We discuss the importance and influence of basic science in intensive care practice and the development of postgraduate appreciation of basic science, highlight the impact of some of the changes in medical education on basic science undergraduate teaching, and discuss the clinical applicability and current participation in basic science research. METHODS: A questionnaire was mailed in November 2006 to all registered Fellows and trainees of the Joint Faculty of Intensive Care Medicine who were resident in Australia. RESULTS: 267 of 801 surveys were returned (33% response rate): 74% of respondents believed basic science is an important or very important influence on clinical decision-making, which is consistent with previous studies, and 8% believed it is crucial. The most familiar areas of basic science research are those with established clinical applications, such as drug metabolism, regional perfusion and the complement cascade. Most current intensive care practitioners were taught basic science as undergraduates. Involvement in basic science research increases during intensive care training, from 10% before a medical degree to over 30% at the end of training, with over a quarter of practicing intensivists having a basic science degree. Despite this increase in interest during training, only 9% of journal club attendees reported that they discuss basic science articles. CONCLUSION: Critical care practitioners consider basic science research to be relevant and important to their practice. There is interest in clinically applicable basic science research, but few people regularly review basic science articles at journal clubs. Reassuringly, participation in basic science research increases throughout intensive care training, despite changes in medical education and lack of protected time for research.