Early detection of patient deterioration in patients with infection or sepsis

Sepsis is the leading cause of death and critical illness worldwide. Despite treatment, one in five patients deteriorate within 48 hours from admission. Deterioration includes the development of (multiple) organ dysfunction, the need for ICU admission or death. How patients can be effectively monitored for signs of deterioration remains largely unknown. In this thesis, we explore infection and sepsis-related deterioration from different perspectives, using a variety of instruments ranging from clinical impression, clinical scoring systems and laboratory parameters (biomarkers), to continuous analysis of vital signs (heart rate, blood pressure, respiratory rate, oxygen saturation). We explored whether these instruments can detect (early) signs of patient deterioration in patients presenting with infection or sepsis to the emergency department. The clinical impression of the nurse or treating physician is most helpful to decide whether patients can be admitted to the general ward or need ICU treatment. Clinical scoring systems are most helpful to predict long-term mortality outcomes. Biomarkers lack sensitivity and specificity for their clinical application and (novel) biomarkers are not readily available in the ED. Patterns in the continuous analysis of vital signs, contain valuable information about patient deterioration. However, the main challenge remains to improve their modeling and condense the contained information about the risk of deterioration for individual patients into a usable and understandable format for the clinician. Once these issues are solved, continuous analysis of vital signs could be an easily applicable method for the early warning of deterioration in patients in throughout the hospital

Novel translational approaches to the search for precision therapies for acute respiratory distress syndrome.

In the 50 years since acute respiratory distress syndrome (ARDS) was first described, substantial progress has been made in identifying the risk factors for and the pathogenic contributors to the syndrome and in characterising the protein expression patterns in plasma and bronchoalveolar lavage fluid from patients with ARDS. Despite this effort, however, pharmacological options for ARDS remain scarce. Frequently cited reasons for this absence of specific drug therapies include the heterogeneity of patients with ARDS, the potential for a differential response to drugs, and the possibility that the wrong targets have been studied. Advances in applied biomolecular technology and bioinformatics have enabled breakthroughs for other complex traits, such as cardiovascular disease or asthma, particularly when a precision medicine paradigm, wherein a biomarker or gene expression pattern indicates a patient's likelihood of responding to a treatment, has been pursued. In this Review, we consider the biological and analytical techniques that could facilitate a precision medicine approach for ARDS

Subtle variation in sepsis-III definitions markedly influences predictive performance within and across methods

Early detection of sepsis is key to ensure timely clinical intervention. Since very few end-toend pipelines are publicly available, fair comparisons between methodologies are difficult if not impossible. Progress is further limited by discrepancies in the reconstruction of sepsis onset time. This retrospective cohort study highlights the variation in performance of predictive models under three subtly different interpretations of sepsis onset from the sepsis-III definition and compares this against inter-model differences. The models are chosen to cover tree-based, deep learning, and survival analysis methods. Using the MIMIC-III database, between 867 and 2178 intensive care unit admissions with sepsis were identified, depending on the onset definition. We show that model performance can be more sensitive to differences in the definition of sepsis onset than to the model itself. Given a fixed sepsis definition, the best performing method had a gain of 1–5% in the area under the receiver operating characteristic (AUROC). However, the choice of onset time can cause a greater effect, with variation of 0–6% in AUROC. We illustrate that misleading conclusions can be drawn if models are compared without consideration of the sepsis definition used which emphasizes the need for a standardized definition for sepsis onset

The Surviving Sepsis Campaign: research priorities for the administration, epidemiology, scoring and identification of sepsis

Epidemiologia; Disfunció d'òrgans; SèpsiaEpidemiology; Organ dysfunction; SepsisEpidemiología; Disfunción de órganos; SepsisObjective To identify priorities for administrative, epidemiologic and diagnostic research in sepsis. Design As a follow-up to a previous consensus statement about sepsis research, members of the Surviving Sepsis Campaign Research Committee, representing the European Society of Intensive Care Medicine and the Society of Critical Care Medicine addressed six questions regarding care delivery, epidemiology, organ dysfunction, screening, identification of septic shock, and information that can predict outcomes in sepsis. Methods Six questions from the Scoring/Identification and Administration sections of the original Research Priorities publication were explored in greater detail to better examine the knowledge gaps and rationales for questions that were previously identified through a consensus process. Results The document provides a framework for priorities in research to address the following questions: (1) What is the optimal model of delivering sepsis care?; (2) What is the epidemiology of sepsis susceptibility and response to treatment?; (3) What information identifies organ dysfunction?; (4) How can we screen for sepsis in various settings?; (5) How do we identify septic shock?; and (6) What in-hospital clinical information is associated with important outcomes in patients with sepsis? Conclusions There is substantial knowledge of sepsis epidemiology and ways to identify and treat sepsis patients, but many gaps remain. Areas of uncertainty identified in this manuscript can help prioritize initiatives to improve an understanding of individual patient and demographic heterogeneity with sepsis and septic shock, biomarkers and accurate patient identification, organ dysfunction, and ways to improve sepsis care.The authors volunteered their time to producing this manuscript and no funding was used to produce it

Development of Artificial Intelligence Algorithms for Early Diagnosis of Sepsis

Sepsis is a prevalent syndrome that manifests itself through an uncontrolled response from the body to an infection, that may lead to organ dysfunction. Its diagnosis is urgent since early treatment can reduce the patients’ chances of having long-term consequences. Yet, there are many obstacles to achieving this early detection. Some stem from the syndrome’s pathogenesis, which lacks a characteristic biomarker. The available clinical detection tools are either too complex or lack sensitivity, in both cases delaying the diagnosis. Another obstacle relates to modern technology, that when paired with the many clinical parameters that are monitored to detect sepsis, result in extremely heterogenous and complex medical records, which constitute a big obstacle for the responsible clinicians, that are forced to analyse them to diagnose the syndrome. To help achieve this early diagnosis, as well as understand which parameters are most relevant to obtain it, an approach based on the use of Artificial Intelligence algorithms is proposed in this work, with the model being implemented in the alert system of a sepsis monitoring platform. This platform uses a Random Forest algorithm, based on supervised machine learning classification, that is capable of detecting the syndrome in two different scenarios. The earliest detection can happen if there are only five vital sign parameters available for measurement, namely heart rate, systolic and diastolic blood pressures, blood oxygen saturation level, and body temperature, in which case, the model has a score of 83% precision and 62% sensitivity. If besides the mentioned variables, laboratory analysis measurements of bilirubin, creatinine, hemoglobin, leukocytes, platelet count, and Creactive protein levels are available, the platform’s sensitivity increases to 77%. With this, it has also been found that the blood oxygen saturation level is one of the most important variables to take into account for the task, in both cases. Once the platform is tested in real clinical situations, together with an increase in the available clinical data, it is believed that the platform’s performance will be even better.A sépsis é uma síndrome com elevada incidência a nível global, que se manifesta através de uma resposta desregulada por parte do organismo a uma infeção, podendo resultar em disfunções orgânicas generalizadas. O diagnóstico da mesma é urgente, uma vez que um tratamento precoce pode reduzir as hipóteses de consequências a longo prazo para os doentes. Apesar desta necessidade, existem vários obstáculos. Alguns deles advêm da patogenia da síndrome, que carece de um biomarcador específico. As ferramentas de deteção clínica são demasiado complexas, ou pouco sensíveis, em ambos os casos atrasando o diagnóstico. Outro obstáculo relaciona-se com os avanços da tecnologia, que, com os vários parâmetros clínicos que são monitorizados, resulta em registos médicos heterogéneos e complexos, o que constitui um grande obstáculo para os profissionais de saúde, que se vêm forçados a analisá-los para diagnosticar a síndrome. Para atingir este diagnóstico precoce, bem como compreender quais os parâmetros mais relevantes para o alcançar, é proposta neste trabalho uma abordagem baseada num algoritmo de Inteligência Artificial, sendo o modelo implementado no sistema de alerta de uma plataforma de monitorização de sépsis. Esta plataforma utiliza um classificador Random Forest baseado em aprendizagem automática supervisionada, capaz de diagnosticar a síndrome de duas formas. Uma deteção mais precoce pode ocorrer através de cinco parâmetros vitais, nomeadamente frequência cardíaca, pressão arterial sistólica e diastólica, nível de saturação de oxigénio no sangue e temperatura corporal, caso em que o modelo atinge valores de 83% de precisão e 62% de sensibilidade. Se, para além das variáveis mencionadas, estiverem disponíveis análises laboratoriais de bilirrubina, creatinina, hemoglobina, leucócitos, contagem de plaquetas e níveis de proteína C-reativa, a sensibilidade da plataforma sobre para 77%. Concluiu-se que o nível de saturação de oxigénio no sangue é uma das variáveis mais importantes a ter em conta para o diagnóstico, em ambos os casos. A partir do momento que a plataforma venha a ser utilizada em situações clínicas reais, com o consequente aumento dos dados disponíveis, crê-se que o desempenho venha a ser ainda melhor