Medical analysis and diagnosis by neural networks

In its first part, this contribution reviews shortly the application of neural network methods to medical problems and characterizes its advantages and problems in the context of the medical background. Successful application examples show that human diagnostic capabilities are significantly worse than the neural diagnostic systems. Then, paradigm of neural networks is shortly introduced and the main problems of medical data base and the basic approaches for training and testing a network by medical data are described. Additionally, the problem of interfacing the network and its result is given and the neuro-fuzzy approach is presented. Finally, as case study of neural rule based diagnosis septic shock diagnosis is described, on one hand by a growing neural network and on the other hand by a rule based system. Keywords: Statistical Classification, Adaptive Prediction, Neural Networks, Neurofuzzy, Medical System

On the intelligent management of sepsis in the intensive care unit

The management of the Intensive Care Unit (ICU) in a hospital has its own, very specific requirements that involve, amongst others, issues of risk-adjusted mortality and average length of stay; nurse turnover and communication with physicians; technical quality of care; the ability to meet patient's family needs; and avoid medical error due rapidly changing circumstances and work overload. In the end, good ICU management should lead to an improvement in patient outcomes. Decision making at the ICU environment is a real-time challenge that works according to very tight guidelines, which relate to often complex and sensitive research ethics issues. Clinicians in this context must act upon as much available information as possible, and could therefore, in general, benefit from at least partially automated computer-based decision support based on qualitative and quantitative information. Those taking executive decisions at ICUs will require methods that are not only reliable, but also, and this is a key issue, readily interpretable. Otherwise, any decision tool, regardless its sophistication and accuracy, risks being rendered useless. This thesis addresses this through the design and development of computer based decision making tools to assist clinicians at the ICU. It focuses on one of the main problems that they must face: the management of the Sepsis pathology. Sepsis is one of the main causes of death for non-coronary ICU patients. Its mortality rate can reach almost up to one out of two patients for septic shock, its most acute manifestation. It is a transversal condition affecting people of all ages. Surprisingly, its definition has only been standardized two decades ago as a systemic inflammatory response syndrome with confirmed infection. The research reported in this document deals with the problem of Sepsis data analysis in general and, more specifically, with the problem of survival prediction for patients affected with Severe Sepsis. The tools at the core of the investigated data analysis procedures stem from the fields of multivariate and algebraic statistics, algebraic geometry, machine learning and computational intelligence. Beyond data analysis itself, the current thesis makes contributions from a clinical point of view, as it provides substantial evidence to the debate about the impact of the preadmission use of statin drugs in the ICU outcome. It also sheds light into the dependence between Septic Shock and Multi Organic Dysfunction Syndrome. Moreover, it defines a latent set of Sepsis descriptors to be used as prognostic factors for the prediction of mortality and achieves an improvement on predictive capability over indicators currently in use.La gestió d'una Unitat de Cures Intensives (UCI) hospitalària presenta uns requisits força específics incloent, entre altres, la disminució de la taxa de mortalitat, la durada de l'ingrès, la rotació d'infermeres i la comunicació entre metges amb al finalitad de donar una atenció de qualitat atenent als requisits tant dels malalts com dels familiars. També és força important controlar i minimitzar els error mèdics deguts a canvis sobtats i a la presa ràpida de deicisions assistencials. Al cap i a la fi, la bona gestió de la UCI hauria de resultar en una reducció de la mortalitat i durada d'estada. La presa de decisions en un entorn de crítics suposa un repte de presa de decisions en temps real d'acord a unes guies clíniques molt restrictives i que, pel que fa a la recerca, poden resultar en problemes ètics força sensibles i complexos. Per tant, el personal sanitari que ha de prendre decisions sobre la gestió de malalts crítics no només requereix eines de suport a la decisió que siguin fiables sinó que, a més a més, han de ser interpretables. Altrament qualsevol eina de decisió que no presenti aquests trets no és considerarà d'utilitat clínica. Aquesta tesi doctoral adreça aquests requisits mitjançant el desenvolupament d'eines de suport a la decisió per als intensivistes i es focalitza en un dels principals problemes als que s'han denfrontar: el maneig del malalt sèptic. La Sèpsia és una de les principals causes de mortalitats a les UCIS no-coronàries i la seva taxa de mortalitat pot arribar fins a la meitat dels malalts amb xoc sèptic, la seva manifestació més severa. La Sèpsia és un síndrome transversal, que afecta a persones de totes les edats. Sorprenentment, la seva definició ha estat estandaritzada, fa només vint anys, com a la resposta inflamatòria sistèmica a una infecció corfimada. La recerca presentada en aquest document fa referència a l'anàlisi de dades de la Sèpsia en general i, de forma més específica, al problema de la predicció de la supervivència de malalts afectats amb Sèpsia Greu. Les eines i mètodes que formen la clau de bòveda d'aquest treball provenen de diversos camps com l'estadística multivariant i algebràica, geometria algebraica, aprenentatge automàtic i inteligència computacional. Més enllà de l'anàlisi per-se, aquesta tesi també presenta una contribució des de el punt de vista clínic atès que presenta evidència substancial en el debat sobre l'impacte de l'administració d'estatines previ a l'ingrès a la UCI en els malalts sèptics. També s'aclareix la forta dependència entre el xoc sèptic i el Síndrome de Disfunció Multiorgànica. Finalment, també es defineix un conjunt de descriptors latents de la Sèpsia com a factors de pronòstic per a la predicció de la mortalitat, que millora sobre els mètodes actualment més utilitzats en la UCI

Machine learning in critical care: state-of-the-art and a sepsis case study

Background: Like other scientific fields, such as cosmology, high-energy physics, or even the life sciences, medicine and healthcare face the challenge of an extremely quick transformation into data-driven sciences. This challenge entails the daunting task of extracting usable knowledge from these data using algorithmic methods. In the medical context this may for instance realized through the design of medical decision support systems for diagnosis, prognosis and patient management. The intensive care unit (ICU), and by extension the whole area of critical care, is becoming one of the most data-driven clinical environments. Results: The increasing availability of complex and heterogeneous data at the point of patient attention in critical care environments makes the development of fresh approaches to data analysis almost compulsory. Computational Intelligence (CI) and Machine Learning (ML) methods can provide such approaches and have already shown their usefulness in addressing problems in this context. The current study has a dual goal: it is first a review of the state-of-the-art on the use and application of such methods in the field of critical care. Such review is presented from the viewpoint of the different subfields of critical care, but also from the viewpoint of the different available ML and CI techniques. The second goal is presenting a collection of results that illustrate the breath of possibilities opened by ML and CI methods using a single problem, the investigation of septic shock at the ICU. Conclusion: We have presented a structured state-of-the-art that illustrates the broad-ranging ways in which ML and CI methods can make a difference in problems affecting the manifold areas of critical care. The potential of ML and CI has been illustrated in detail through an example concerning the sepsis pathology. The new definitions of sepsis and the relevance of using the systemic inflammatory response syndrome (SIRS) in its diagnosis have been considered. Conditional independence models have been used to address this problem, showing that SIRS depends on both organ dysfunction measured through the Sequential Organ Failure (SOFA) score and the ICU outcome, thus concluding that SIRS should still be considered in the study of the pathophysiology of Sepsis. Current assessment of the risk of dead at the ICU lacks specificity. ML and CI techniques are shown to improve the assessment using both indicators already in place and other clinical variables that are routinely measured. Kernel methods in particular are shown to provide the best performance balance while being amenable to representation through graphical models, which increases their interpretability and, with it, their likelihood to be accepted in medical practice.Peer ReviewedPostprint (published version

Conditional Tabular Generative Adversarial Net for Enhancing Ensemble Classifiers in Sepsis Diagnosis

Antibiotic-resistant bacteria have proliferated at an alarming rate as a result of the extensive use of antibiotics and the paucity of new medication research. The possibility that an antibiotic-resistant bacterial infection would progress to sepsis is one of the major collateral problems affecting people with this condition. 31,000 lives were lost due to sepsis in England with costs about two billion pounds annually. This research aims to develop and evaluate several classification approaches to improve predicting sepsis and reduce the tendency of underdiagnosis in computer-aided predictive tools. This research employs medical data sets for patients diagnosed with sepsis, it analyses the efficacy of ensemble machine learning techniques compared to non ensemble machine learning techniques and the significance of data balancing and Conditional Tabular Generative Adversarial Nets for data augmentation in producing reliable diagnosis. The average F Score obtained by the non-ensemble models trained in this paper is 0.83 compared to the ensemble techniques average of 0.94. Nonensemble techniques, such as Decision Tree, achieved an F score of 0.90, an AUC of 0.90 and an accuracy of 90%. Histogram-based Gradient Boosting Classification Tree achieved an F score of 0.96, an AUC of 0.96 and an accuracy of 95%, surpassing the other models tested. Additionally, when compared to the current state of the art sepsis prediction models, the models developed in this study demonstrated higher average performance in all metrics, indicating reduced bias and improved robustness through data balancing and Conditional Tabular Generative Adversarial Nets for data augmentation. The study revealed that data balancing and augmentation on the ensemble machine learning algorithms boost the efficacy of clinical predictive models and can help clinics decide which data types are most important when examining patients and diagnosing sepsis early through intelligent human-machine interface

Mining risk patterns in medical data

In this paper, we discuss a problem of finding risk patterns in medical data. We define risk patterns by a statistical metric, relative risk, which has been widely used in epidemiological research. We characterise the problem of mining risk patterns as an optimal rule discovery problem. We study an anti-monotone property for mining optimal risk pattern sets and present an algorithm to make use of the property in risk pattern discovery. The method has been applied to a real world data set to find patterns associated with an allergic event for ACE inhibitors. The algorithm has generated some useful results for medical researchers

Choque séptico em pediatria : o estado da arte

Objective Review the main aspects of the definition, diagnosis, and management of pediatric patients with sepsis and septic shock. Source of data A search was carried out in the MEDLINE and Embase databases. The articles were chosen according to the authors' interest, prioritizing those published in the last five years. Synthesis of data Sepsis remains a major cause of mortality in pediatric patients. The variability of clinical presentations makes it difficult to attain a precise definition in pediatrics. Airway stabilization with adequate oxygenation and ventilation if necessary, initial volume resuscitation, antibiotic administration, and cardiovascular support are the basis of sepsis treatment. In resource-poor settings, attention should be paid to the risks of fluid overload when administrating fluids. Administration of vasoactive drugs such as epinephrine or norepinephrine is necessary in the absence of volume response within the first hour. Follow-up of shock treatment should adhere to targets such as restoring vital and clinical signs of shock and controlling the focus of infection. A multimodal evaluation with bedside ultrasound for management after the first hours is recommended. In refractory shock, attention should be given to situations such as cardiac tamponade, hypothyroidism, adrenal insufficiency, abdominal catastrophe, and focus of uncontrolled infection. Conclusions The implementation of protocols and advanced technologies have reduced sepsis mortality. In resource-poor settings, good practices such as early sepsis identification, antibiotic administration, and careful fluid infusion are the cornerstones of sepsis management.Objetivo Revisar os principais aspectos da definição, diagnóstico e manejo do paciente pediátrico com sepse e choque séptico. Fontes de dados Uma pesquisa nas plataformas de dados Medline e Embase foi feita. Os artigos foram escolhidos segundo interesse dos autores, priorizaram-se as publicações dos últimos 5 anos. Síntese dos dados A sepse continua a ser uma causa importante de mortalidade em pacientes pediátricos. A variabilidade de apresentação clínica dificulta uma definição precisa em pediatria. A estabilização da via aérea com adequada oxigenação, e ventilação se necessário, ressuscitação volêmica inicial, administração de antibióticos e suporte cardiovascular são a base do tratamento da sepse. Em cenários de poucos recursos, deve-se atentar para os riscos de sobrecarga hídrica na administração de fluidos. A administração de drogas vasoativas como adrenalina ou noradrenalina, se faz necessária na ausência da resposta ao volume na primeira hora. O seguimento do tratamento do choque deve seguir alvos como restauração dos sinais vitais e clínicos de choque e controle do foco de infecção. Recomenda-se a avaliação multimodal, com auxílio da ecografia à beira-leito para manejo após as primeiras horas. No choque refratário, deve-se atentar para situações como tamponamento cardíaco, hipotireoidismo, insuficiência adrenal, catástrofe abdominal e foco de infecção não controlado. Conclusões Implantação de protocolos e avançadas tecnologias propiciou uma redução da mortalidade da sepse. Em cenários de poucos recursos, as boas práticas, como reconhecimento precoce da sepse, administração de antibióticos e cuidadosa infusão de fluidos, são os pilares do manejo da sepse

Improved diagnosis and management of sepsis and bloodstream infection

Sepsis is a severe organ dysfunction triggered by infections, and a leading cause of hospitalization and death. Concurrent bloodstream infection (BSI) is common and around one third of sepsis patients have positive blood cultures. Prompt diagnosis and treatment is crucial, but there is a trade-off between the negative effects of over diagnosis and failure to recognize sepsis in time. The emerging crisis of antimicrobial resistance has made bacterial infections more difficult to treat, especially gram-negative pathogens such as Pseudomonas aeruginosa. The overall aim with this thesis was to improve diagnosis, assess the influence of time to antimicrobial treatment and explore prognostic bacterial virulence markers in sepsis and BSI. The papers are based on observational data from 7 cohorts of more than 100 000 hospital episodes. In addition, whole genome sequencing has been performed on approximately 800 invasive P. aeruginosa isolates collected from centers in Europe and Australia. Paper I showed that automated surveillance of sepsis incidence using the Sepsis-3 criteria is feasible in the non-ICU setting, with examples of how implementing this model generates continuous epidemiological data down to the ward level. This information can be used for directing resources and evaluating quality-of-care interventions. In Paper II, evidence is provided for using peripheral oxygen saturation (SpO2) to diagnose respiratory dysfunction in sepsis, proposing the novel thresholds 94% and 90% to get 1 and 2 SOFA points, respectively. This has important implications for improving sepsis diagnosis, especially when conventional arterial blood gas measurements are unavailable. Paper III verified that sepsis surveillance data can be utilized to develop machine learning screening tools to improve early identification of sepsis. A Bayesian network algorithm trained on routine electronic health record data predicted sepsis onset within 48 hours with better discrimination and earlier than conventional NEWS2 outside the ICU. The results suggested that screening may primarily be suited for the early admission period, which have broader implications also for other sepsis screening tools. Paper IV demonstrated that delays in antimicrobial treatment with in vitro pathogen coverage in BSI were associated with increased mortality after 12 hours from blood culture collection, but not at 1, 3, and 6 hours. This indicates a time window where clinicians should focus on the diagnostic workup, and proposes a target for rapid diagnostics of blood cultures. Finally, Paper V showed that the virulence genotype had some influence on mortality and septic shock in P. aeruginosa BSI, however, it was not a major prognostic determinant. Together these studies contribute to better understanding of the sepsis and BSI populations, and provide several suggestions to improve diagnosis and timing of treatment, with implications for clinical practice. Future works should focus on the implementation of sepsis surveillance, clinical trials of time to antimicrobial treatment and evaluating the prognostic importance of bacterial genotype data in larger populations from diverse infection sources and pathogens

Acute lung injury in paediatric intensive care: course and outcome

Introduction: Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) carry a high morbidity and mortality (10-90%). ALI is characterised by non-cardiogenic pulmonary oedema and refractory hypoxaemia of multifactorial aetiology [1]. There is limited data about outcome particularly in children. Methods This retrospective cohort study of 85 randomly selected patients with respiratory failure recruited from a prospectively collected database represents 7.1% of 1187 admissions. They include those treated with High Frequency Oscillation Ventilation (HFOV). The patients were admitted between 1 November 1998 and 31 October 2000. Results: Of the 85, 49 developed acute lung injury and 47 had ARDS. There were 26 males and 23 females with a median age and weight of 7.7 months (range 1 day-12.8 years) and 8 kg (range 0.8-40 kg). There were 7 deaths giving a crude mortality of 14.3%, all of which fulfilled the Consensus I [1] criteria for ARDS. Pulmonary occlusion pressures were not routinely measured. The A-a gradient and PaO2/FiO2 ratio (median + [95% CI]) were 37.46 [31.82-43.1] kPa and 19.12 [15.26-22.98] kPa respectively. The non-survivors had a significantly lower PaO2/FiO2 ratio (13 [6.07-19.93] kPa) compared to survivors (23.85 [19.57-28.13] kPa) (P = 0.03) and had a higher A-a gradient (51.05 [35.68-66.42] kPa) compared to survivors (36.07 [30.2-41.94]) kPa though not significant (P = 0.06). Twenty-nine patients (59.2%) were oscillated (Sensormedics 3100A) including all 7 non-survivors. There was no difference in ventilation requirements for CMV prior to oscillation. Seventeen of the 49 (34.7%) were treated with Nitric Oxide including 5 out of 7 non-survivors (71.4%). The median (95% CI) number of failed organs was 3 (1.96-4.04) for non-survivors compared to 1 (0.62-1.62) for survivors (P = 0.03). There were 27 patients with isolated respiratory failure all of whom survived. Six (85.7%) of the non-survivors also required cardiovascular support.Conclusion: A crude mortality of 14.3% compares favourably to published data. The A-a gradient and PaO2/FiO2 ratio may be of help in morbidity scoring in paediatric ARDS. Use of Nitric Oxide and HFOV is associated with increased mortality, which probably relates to the severity of disease. Multiple organ failure particularly respiratory and cardiac disease is associated with increased mortality. ARDS with isolated respiratory failure carries a good prognosis in children