Le sepsis tardif, défini comme une infection systémique chez les nouveaux nés âgés de plus de 3 jours, survient chez environ 7% à 10% de tous les nouveau-nés et chez plus de 25% des nouveau-nés de très faible poids de naissance qui sont hospitalisés dans les unités de soins intensifs néonatals (USIN). Les apnées et bradycardies (AB) spontanées récurrentes et graves sont parmi les principaux indicateurs précoces cliniques de l'infection systémique chez les prématurés. L'objectif de cette thèse est de déterminer si la variabilité du rythme cardiaque (VRC), la respiration et l'analyse de leurs relations aident au diagnostic de l'infection chez les nouveaux nés prématurés par des moyens non invasifs en USIN. Par conséquent, on a effectué l'analyse Mono-Voie (MV) et Bi-Voies (BV) sur deux groupes sélectionnés de nouveau-nés prématurés: sepsis (S) vs. non-sepsis (NS). (1) Tout d'abord, on a étudié la série RR non seulement par des méthodes de distribution (moy, varn, skew, kurt, med, SpAs), par les méthodes linéaire: le domaine temporel (SD, RMSSD) et dans le domaine fréquentiel (p_VLF, p_LF, p_HF), mais aussi par les méthodes non–linéaires: la théorie du chaos (alphas, alphaF) et la théorie de l'information (AppEn, SamEn, PermEn, Regul). Pour chaque méthode, nous étudions trois tailles de fenêtre 1024/2048/4096, puis nous comparons ces méthodes afin de trouver les meilleures façons de distinguer S de NS. Les résultats montrent que les indices alphaS, alphaF et SamEn sont les paramètres optimaux pour séparer les deux populations. (2) Ensuite, la question du couplage fonctionnel entre la VRC et la respiration nasale est adressée. Des relations linéaires et non-linéaires ont été explorées. Les indices linéaires sont la corrélation (r²), l'indice de la fonction de cohérence (Cohere) et la corrélation temps-fréquence (r2t,f) , tandis que le coefficient de régression non-linéaire (h²) a été utilisé pour analyser des relations non-linéaires. Nous avons calculé les deux directions de couplage pendant l'évaluation de l'indice h2 de régression non-linéaire. Enfin, à partir de l'ensemble du processus d'analyse, il est évident que les trois indices (r2tf_rn_raw_0p2_0p4, h2_rn_raw et h2_nr_raw) sont des moyens complémentaires pour le diagnostic du sepsis de façon non-invasive chez ces patients fragiles. (3) Après, l'étude de faisabilité de la détection du sepsis en USIN est réalisée sur la base des paramètres retenus lors des études MV et BV. Nous avons montré que le test proposé, basé sur la fusion optimale des six indices ci-dessus, conduit à de bonnes performances statistiques. En conclusion, les mesures choisies lors de l'analyse des signaux en MV et BV ont une bonne répétabilité et permettent de mettre en place un test en vue du diagnostic non invasif et précoce du sepsis. Le test proposé peut être utilisé pour fournir une alarme fiable lors de la survenue d'un épisode d'AB tout en exploitant les systèmes de monitoring actuels en USIN. / Late-onset sepsis, defined as a systemic infection in neonates older than 3 days, occurs in approximately 10% of all neonates and in more than 25% of very low birth weight infants who are hospitalized in Neonatal Intensive Care Units (NICU). Recurrent and severe spontaneous apneas and bradycardias (AB) is one of the major clinical early indicators of systemic infection in the premature infant. Various hematological and biochemical markers have been evaluated for this indication but they are invasive procedures that cannot be repeated several times. The objective of this Ph.D dissertation was to determine if heart rate variability (HRV), respiration and the analysis of their relationships help to the diagnosis of infection in premature infants via non-invasive ways in NICU. Therefore, we carried out Mono-Channel (MC) and Bi-Channel (BC) Analysis in two selected groups of premature infants: sepsis (S) vs. non-sepsis (NS). (1) Firstly, we studied the RR series not only by distribution methods (moy, varn, skew, kurt, med, SpAs), by linear methods: time domain (SD, RMSSD) and frequency domain (p_VLF, p_LF, p_HF), but also by non-linear methods: chaos theory (alphaS, alphaF) and information theory (AppEn, SamEn, PermEn, Regul). For each method, we attempt three sizes of window 1024/2048/4096, and then compare these methods in order to find the optimal ways to distinguish S from NS. The results show that alphaS, alphaF and SamEn are optimal parameters to recognize sepsis from the diagnosis of late neonatal infection in premature infants with unusual and recurrent AB. (2) The question about the functional coupling of HRV and nasal respiration is addressed. Linear and non-linear relationships have been explored. Linear indexes were correlation (r²), coherence function (Cohere) and time-frequency index (r2t,f), while a non-linear regression coefficient (h²) was used to analyze non-linear relationships. We calculated two directions during evaluate the index h2 of non-linear regression. Finally, from the entire analysis process, it is obvious that the three indexes (r2tf_rn_raw_0p2_0p4, h2_rn_raw and h2_nr_raw) were complementary ways to diagnosticate sepsis in a non-invasive way, in such delicate patients.(3) Furthermore, feasibility study is carried out on the candidate parameters selected from MC and BC respectively. We discovered that the proposed test based on optimal fusion of 6 features shows good performance with the largest Area Under Curves (AUC) and the least Probability of False Alarm (PFA). As a conclusion, we believe that the selected measures from MC and BC signal analysis have a good repeatability and accuracy to test for the diagnosis of sepsis via non-invasive NICU monitoring system, which can reliably confirm or refute the diagnosis of infection at an early stage.

Orientador: Erich Vinicius de Paula / Tese (doutorado) - Universidade Estadual de Campinas, Faculdade de Ciências Médicas / Made available in DSpace on 2018-08-18T13:46:04Z (GMT). No. of bitstreams: 1 Alves_BrunnaEulalio_D.pdf: 4762678 bytes, checksum: 34eea414d90830a52ed9c9b044538888 (MD5) Previous issue date: 2011 / Resumo: Pacientes portadores de neoplasia hematológica e neutropenia febril representam um grupo de risco elevado de sepse e choque séptico. Nas últimas décadas, estratégias terapêuticas alvo-específicas para a sepse não modificaram de forma significativa a sobrevida dos pacientes e o tratamento permanece baseado em antibioticoterapia e cuidados de suporte, com altas taxas de mortalidade. A quebra da barreira endotelial é um evento fundamental na fisiopatologia do choque séptico e a compreensão dos mecanismos envolvidos neste evento tem o potencial de auxiliar na identificação de novos biomarcadores de gravidade e de novos alvos terapêuticos para estes pacientes. Estudos recentes demonstraram a participação do fator de crescimento do endotélio vascular (VEGF-A), do seu receptor solúvel (sFlt-1) e das angiopoietinas 1 e 2, proteínas envolvidas na angiogênese e na regulação da integridade da barreira endotelial na fisiopatogenia do choque séptico em pacientes não oncológicos internados em unidade de terapia intensiva. Neste trabalho, avaliamos prospectivamente a cinética do VEGF-A, do sFlt-1 e das angiopoietinas 1 e 2 durante as 48 horas inicias da neutropenia febril em 41 pacientes portadores de neoplasia hematológica submetidos a quimioterapia intensiva ou a regime de condicionamento para transplante de células progenitoras hematopoiéticas, através da dosagem dos mesmos por ensaio imuno-enzimático. Exploramos também a associação dos níveis séricos destes biomarcadores com a gravidade da sepse através da correlação com o MASCC, um índice desenvolvido para identificar pacientes com neutropenia febril de baixo risco, e com o SOFA, um escore de avaliação de disfunção orgânica em pacientes com sepse, ambos amplamente aceitos. A evolução para choque séptico foi associada a níveis significativamente maiores de VEGF-A, sFlt-1 e angiopoietina-2 48 horas após o início da neutropenia febril quando comparado aos valores em pacientes com sepse não complicada e a estimativa da acurácia diagnóstica sugere a capacidade de discriminar os pacientes que evoluíram com choque séptico. Estes biomarcadores também apresentaram correlação com os escores gravidade, sugerindo a relevância biológica da associação. Em conclusão, nossos achados sugerem que a avaliação destes biomarcadores em pacientes com neutropenia febril deve ser avaliada em estudos com maior número de pacientes, quanto ao seu potencial de incorporação na prática clínica. Além disso, os resultados reforçam o potencial terapêutico da intervenção nestas vias para o tratamento da sepse / Abstract: Patients with hematologic malignancy and neutropenia represent a group at high risk of sepsis and septic shock. In recent decades, target-specific therapeutic strategies for sepsis did not change significantly the survival of patients and treatment is still based on antibiotic therapy and supportive care, with high mortality rates. The breakdown of the endothelial barrier is a key event in the pathophysiology of septic shock and understanding of the mechanisms involved in this event has the potential to assist in the identification of new biomarkers and severity of new therapeutic targets for these patients. Recent studies have demonstrated the involvement of endothelial growth factor (VEGF-A), its soluble receptor (sFlt-1) and angiopoietins 1 and 2, proteins involved in angiogenesis and in regulation of endothelial barrier integrity in the pathogenesis of shock septic patients without cancer admitted to the intensive care unit. In this study, we prospectively evaluated the kinetics of VEGF-A, sFlt-1 and angiopoietins 1 and 2 during the initial 48 hours of febrile neutropenia in 41 patients with hematological malignancy undergoing intensive chemotherapy or conditioning regimen for stem cell transplantation hematopoietic cells by the same dosage by enzyme immunoassay. We also explored the association of serum levels of these biomarkers with the severity of sepsis through correlation with the MASCC, an index developed to identify patients with febrile neutropenia at low risk, and the SOFA score for assessment of organ dysfunction in patients with sepsis, both widely accepted. Progression to septic shock was associated with significantly higher levels of VEGF-A, sFlt-1 and angiopoietin-2 48 hours after the onset of febrile neutropenia when compared to values in patients with uncomplicated sepsis and the estimation of diagnostic accuracy suggests the ability to discriminate among patients who developed septic shock. These biomarkers also correlated with the severity scores, suggesting the biological relevance of the association / Doutorado / Clinica Medica / Doutor em Clínica Médica

The etiology of renal dysfunction in sepsis is currently attributed to altered perfusion, microcirculatory abnormalities and cellular alterations. To clarify these mechanisms, we characterized the changes in renal perfusion and cortex metabolism in a large animal model of sepsis. In this model, sepsis was associated with metabolic alterations that may reflect early induction of cortical glycolysis. Septic shock was associated with reduced renal perfusion and decreased cortical and medullary blood flow, followed by signs of anaerobic metabolism in the cortex when flow reductions became critical. Attempts to correct renal hypoperfusion and alleviate the associated perfusion/metabolism mismatch with fenoldopam or renal denervation were unsuccessful. In the final study we focussed on the role of renal autoregulation in experimental sepsis and septic shock. Evidence suggests that higher blood pressure targets are needed in patients with impaired renal autoregulation and septic shock, but the effects of vasopressors should also be considered. We therefore investigated the effects of arginine vasopressin and norepinephrine on renal autoregulation in ovine septic shock. In experimental septic shock, arginine vasopressin was associated with a lower autoregulatory threshold than norepinephrine. As vasopressors may have different effects on renal autoregulation, individualized therapy of blood pressure management in patients with septic shock should take into account drug-specific effects. / Doctorat en Sciences médicales (Médecine) / info:eu-repo/semantics/nonPublished

This thesis is focused on the possibility of analysis of volatile organic compounds produced by monocytes during sepsis. Method of comprehensive two-dimensional gas chromatography with mass spectrometric detection was chosen for this purpose. Content of the first part was the optimization of the method of two-dimensional gas chromatography for the determination of volatile organic compounds. In this part were gradually adjusted parameters of the gas chromatography method to achieve the maximum efficiency. Further were adjusted conditions of samples preparation. Content of the second part was the usage of already optimized method for the analysis of the samples set of monocytes. Samples were subjected to the action of different inhibitors of the immune system and stimulators simulating bacterial or yeast infection. Based on this analysis were identified some compounds, which are produced by monocytes under condition simulating the infection.

The aim of the thesis was to determine the microbial colonization at the injection site of central venous catheter and its possible influence to maintain the lowest incidence of catheter sepsis. The culture results of skin swabs and taken blood cultures from two groups of patients were compared with each other using qualitative analysis methods. Those were Intensive Care Unit patients with established central venous catheter. The result was the discovery of microbial colonization of the skin and the representation of different pathogenic strains at the site of a central venous catheter for both established groups. Further showed that the higher the risk of microbial colonization with symptoms of catheter sepsis was seen where patients have central venous catheter established for longer period of time and have been treated under home parental nutrition program with stoma. The recommendation is the continuous education of health professionals to act in accordance with the latest preventive treatment recommendations, and the emphasis is mainly placed on hands cleaning and disinfecting as the hands of health professionals are one of the most common and risky way of transmission of pathogenic strains with potential nosocomial infection formation. Aseptic principles must be repeatedly communicated to all...

With increasing incidence rates aligned with poor prognosis; sepsis represents one of the biggest challenges in modern health care. It is a multifactorial syndrome defined as organ dysfunction caused by disturbed systemic response to an infection. Most of the inpatient sepsis are caused by Gram positive bacteria and one of its major constituents of the cell envelope: lipoteichoic acid (LTA). An adjuvant treatment that has gained prominence recently is extracorporeal blood removal therapies i.e., hemoperfusions. The concept is to remove the bacterial virulence factors that triggers immune responses and therefor stabilize the hemodynamic parameters of the patient. The dominating research of this method centres around adsorption of the Gram negative bacterias’ endotoxin lipopolysaccharide (LPS) but not LTA, whose biochemical and physiological properties resembles each other. The aim of this study was to determine whether LTA can be adsorbed using immobilized truncated derivates of antimicrobial peptides (AMPs). LTA was quantified using ELISA comparing before and after passage through columns with immobilized peptides. Further, the absorption abilities of LTA from two different solid phases with distinctive surfaces were investigated. This was of interest to elucidate the nature of the mechanisms behind LTA extractions. All results generated inconclusive data, except for one trial which demonstrated that peptide KEF-19 adsorbed most LTA and that the electrostatic force had the greatest influence of the adsorption. Future studies should however be carried out to validate these statements as well as feasibility and safety estimations for KEF-19 as the sorbent in hemoperfusions for Gram positive bacteria and LTA.

Sepsis is still a leading cause of death in the United States despite extensive research and modern advancement in technology. Early recognition of sepsis and timely management strategies are important for effective reduction of sepsis-related morbidity and mortality. Guided by the logic model, the purpose of this project was to evaluate the effectiveness of electronic reminders in enhancing clinical decision-making among 30 nurses in 3 medical-surgical units. The practice-focused question addressed the effectiveness of electronic reminders for early recognition and initiation of goal-directed treatment of sepsis in hospitalized patients on medical-surgical units in an effort to reduce sepsis mortality rates. Data were collected from a randomized convenience sample using a self-constructed questionnaire and through observation. The observations were aimed at assessing whether the nurses adhered to the sepsis protocol, while the questionnaire captured the participants' perceptions regarding the use of automated alerts measured on a 5-point Likert scale. Statistical analysis involved the use of frequencies and percentages, positive predictive value (PPV), and negative predictive value (NPV). The results indicated that all the nurses adhered to sepsis protocol. The sepsis-related mortality rate, mean response time, and rate of severe sepsis at the hospital were reduced by 17.2%, 14 minutes, and 11.1%, respectively. It was concluded that automatic alert systems improve nurses' ability to recognize early symptoms of sepsis and their ability to initiate Code Sepsis. However, replication of this study using a large sample size could provide findings that are more generalizable. Electronic reminders may promote positive social change because earlier recognition of sepsis by nurses may lead to a reduction of healthcare costs through improved management of sepsis patients in acute care settings.

No description available.

Antimicrobial resistance in bacteria is a global health challenge with a projected fallout of 10 million deaths annually and cumulative costs of over 1 trillion dollars by 2050. The currently available tools exploited in the detection of bacteria or their DNA can be expensive, time inefficient, or lack multiplex capabilities among others. The research work highlighted in this dissertation advances techniques employed in the phenotypic or genotypic detection of bacteria and their DNA. In this dissertation, I present polymethyl methacrylate-pressure sensitive adhesive microfluidic platforms developed using a time-efficient, inexpensive fabrication technique. Microfluidic devices were then equipped with functionalized monoliths and utilized for sequence-specific capture and detection of picomolar concentrations of bacterial plasmid DNA harvested from cultured bacteria. I then showed multiplex detection of multiple bacteria gene targets in these devices with an improved monolith column. Finally, I demonstrated a genotypic approach to studying single bacteria growth in water-in-oil droplets with nanomolar concentrations of a fluorescence reporter, and detection via laser-induced fluorescence after convenient room temperature 2-h incubation conditions. The systems and methods described herein show potential to advance tools needed to address the surging problems and effects of drug-resistant bacteria.

Bakgrund: Sepsis är ett akut sjukdomstillstånd med en hög mortalitet världen över.Tidig identifiering och snabb behandling är viktig för patientens överlevnad.Sjuksköterskan har i sitt patientnära arbete en unik position att snabbt identifierasepsis och initiera behandling. För att möjliggöra en säker vård för patient, kollegoroch vårdansvarig sjuksköterska ska sjuksköterskan arbeta förebyggande ochpatientsäkert. Syfte: Att kartlägga åtgärder som främjar sjuksköterskans förmåga attidentifiera sepsis på sjukhus. Metod: En litteraturöversikt har genomförts för attskapa en överblick av det aktuella kunskapsläget. För att besvara syftet användesartiklar med en kvantitativ metod. Med hjälp av Polit och Becks niostegsmodellanalyserades artiklar som sedan presenterades i resultatet. Resultat: Resultatetvisade att sjuksköterskorna använde sig utav utbildning, riktlinjer samtscreeningverktyg för att främja identifieringen utav sepsis. Signifikanta skillnader sågsi relation till de olika åtgärderna. Skillnaderna visade bland annat en minskadmortalitet och minskad vårdtid. Slutsats: Sjuksköterskan har en central roll i attidentifiera sepsis. Resultatet förväntas identifiera åtgärder som i den kliniskavardagen kan hjälpa framtida sjuksköterskor eller annan vårdpersonal. Genom attsjuksköterskan är ödmjuk för den egna kompetensen, tar hjälp av screeningverktygoch vidhåller de riktlinjer som finns kan en grund för säker vård byggas. / Background: Sepsis is an acute illness with a high mortality rate worldwide. It istherefore important to act quickly as rapid identification and treatment can be crucialfor the patient's survival. The nurse has, with her close work with the patient a uniqueposition to quickly identify sepsis and initiate treatment. In order to enable safe carefor both the patient, colleagues and healthcare providing nurse, the nurse must workpreventively and in a patient safe manner. Aim: To map interventions that promotethe nurse's identification of sepsis in a hospital setting. Method: A literature reviewhas been carried out to create an overview of the current state of knowledge. To answerthe purpose, articles with a quantitative methodology were chosen. Using Polit andBeck's nine-step model articles were analyzed and then presented in the results.Results: The results showed that the nurses used training, protocols and screeningtools to promote the identification of sepsis. Significant differences were seen inrelation to the various interventions. The differences showed for instance a decreasedmortality and abbreviated the hospital stay. Conclusion: The nurse has a central rolein identifying sepsis. The results are expected to identify measures that can help futurenurses or other healthcare professionals in the clinic. By the nurse being humble abouther own competence, using screening tools and maintaining the existing protocols, afoundation for safe care can be built.