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Dissertations / Theses on the topic 'Critical illness'
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1
Trinder, Thomas John. "Splanchnic perfusion in critical illness." Thesis, Queen's University Belfast, 1995. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.295361.
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Brealey, David Andrew. "Mitochondrial dysfunction in critical illness." Thesis, University College London (University of London), 2004. http://discovery.ucl.ac.uk/1446708/.
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The mortality from septic shock is approximately 50%. Most patients die from the ensuing multi-organ dysfunction syndrome rather than the acute septic inflammatory process per se. The aetiology of the organ dysfunction is unknown. A characteristic phenomenon of an increasing severity of sepsis is a decrease in tissue oxygen extraction with a decrease (relative and/or absolute) in tissue oxygen consumption. Two theories have been advanced to explain this observed decrease in oxygen extraction. Traditionally, this has been ascribed to micro vascular shunting of blood away from nutrient capillaries. However, findings in both patients and animal models have demonstrated a raised tissue PO2, suggesting that the oxygen is available to cells but cannot be metabolised, i.e. a state of dysoxia. As mitochondria account for over 90% of total oxygen consumption, in the process of oxidative phosphorylation, it has been hypothesised that sepsis results in an inhibition of the mitochondrial enzymes involved in this process. If severe, this would be expected to lead to energy failure in the organs and, possibly, to initiation of apoptotic or necrotic cell death. Marked over-production of the intercellular messenger nitric oxide is a characteristic feature of sepsis; the mitochondrial damage theory has been given additional credence by the discovery that nitric oxide and its derivative, peroxynitrite, can inhibit or permanently damage mitochondrial enzymes involved in the oxidative phosphorylation pathway. The work leading to this thesis has demonstrated that sepsis is associated with an increase in nitric oxide production, a reduction in antioxidant protection, respiratory chain enzyme inhibition, and a depletion in tissue ATP levels. These changes were shown in both skeletal muscle biopsies obtained from critically ill patients in septic shock, and in skeletal muscle and liver biopsies obtained from a long-term septic rat model. These changes correlated with the severity of disease and eventual outcome. These findings thus demonstrate a mechanism that is present in both 'non-vital' and 'vital' organs, and across species. These findings may be epiphenomenal and causation needs to be definitively demonstrated. However, this work does suggest that mitochondrial dysfunction could be an important pathophysiological mechanism underlying sepsis-induced organ failure.
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Schoeman, Johan P. "Endocrine changes in canine critical illness." Thesis, University of Cambridge, 2009. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.611343.
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Trubody, Victoria. "Reversible myocardial depression in critical illness." Thesis, University of Oxford, 2015. https://ora.ox.ac.uk/objects/uuid:d11d5bfe-ef0e-45f7-a8c1-ebdc9c58bc1b.
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Introduction: Reversible myocardial depression (RMD) is a transient impairment of left ventricular systolic function. This has been described in sub populations of patients experiencing critical illness, but it is unclear if the epidemiological features are generalisable to the broader populations of critically ill adults. Previous work has identified that RMD is not benign and has been associated with a range of adverse sequelae such as arrhythmia, left ventricular outflow tract obstruction, and intra-ventricular thrombus. Consequently, studies were designed to determine the incidence, time course, and associated risk factors for the development of myocardial depression in the general population of adults experiencing critical illness. Methods: Myocardial depression was defined as a decrease in left ventricular ejection fraction =5% from AICU baseline and was assessed using serial transthoracic echocardiography. Three studies were conducted - two prospective observational cohort studies and a retrospective analysis. The incidence, absolute decrease in ejection fraction, and time course of myocardial depression was described. Routinely available demographic and clinical variables were collected. These were then rationalised and trialled as candidate explanatory variables in a logistic regression model to predict the development of myocardial depression. Results: The incidence of myocardial depression was between 16.3 - 34%, which occurred around day four of AICU admission. The median decline in LVEF at the onset of myocardial depression was between 6.5 - 14.7%, which progressed to between 10 - 17.5% at the nadir. Myocardial depression was not entirely reversible, with between 43.7 - 71.4% of participants demonstrating some degree of recovery, with LVEF improving between 13.3 - 20.2% across the studies. The probability of development of myocardial depression can be determined using five routinely collected variables, expressed as a factor; heart rate, systolic blood pressure, the presence of severe sepsis, cardiovascular organ dysfunction and sinus rhythm. Increasing systolic blood pressure, the presence of severe sepsis, and cardiovascular organ dysfunction were associated with increased risk. Increasing heart rate and the presence of sinus rhythm were associated with decreased risk. Model diagnostics indicated that the model was a good fit of the data. The model had a modest discriminating ability, with the area under the receiver operating characteristic curve = 0.69. Conclusion: The incidence of myocardial depression was between 16.3 - 34% of participants, and usually developed around day four of AICU admission. The decreases in left ventricular ejection fraction were considerable and were not always reversible. Myocardial depression can be predicted using routinely collected haemodynamic and clinical variables that are available within the first 24 hours of AICU admission.
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Conway, Morris Andrew. "Complement-mediated neutrophil dysfunction in critical illness." Thesis, University of Edinburgh, 2011. http://hdl.handle.net/1842/27824.
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Critical illness, constituting an acute illness or injury resulting in organ dysfunction and failure, is associated with a profound, systemic activation of the immune system and inflammation-mediated organ damage. However, critically ill patients suffer a high rate of nosocomial infection with secondary sepsis being a common cause of death. This high prevalence of secondary infections argues for the influence of an immune suppression that may, at first glance, appear paradoxical in light of the pro-inflammatory nature of critical illness. Although immune cell hypo-function has been noted in clinical and experimental critical illness, the mediators of these effects remain poorly defined. In this thesis, neutrophil function was examined in the context of clinically suspected ventilator-associated pneumonia, a common and lethal intensive care acquired infection (ICU-AI), This demonstrated impaired bactericidal functions (phagocytosis and reactive oxygen species production) in neutrophils from both the peripheral and pulmonary compartments; however there was ample evidence of coexistent neutrophil activation (both cell surface markers and soluble mediators) and inflammation. An investigation of possible mediators of neutrophil dysfunction revealed a major role for C5a, the pro-inflammatory anaphylotoxin derived from complement C5. Recombinant C5a applied to healthy donor neutrophils was able to drive the defect in phagocytosis by phospho-inositol 3 kinase delta-mediated inhibition of RhoA and subsequent down regulation of actin polymerisation. The defects in RhoA and actin function were reversible with granulocyte-macrophage colony stimulating factor (GM-CSF) applied ex vivo, restoring phagocytic function to normal. Similar defects in RhoA and actin, and effective treatment with GMCSF, were found in neutrophils from critically ill patients. In a second cohort of critically ill adults recruited prior to developing any ICU-AI, C5a-mediated neutrophil dysfunction was an independent predictor of acquiring nosocomial infection, being associated with a 5.4 fold increased risk (95% Confidence interval 1.4-21.0). The same cohort of patients also displayed two other features of immune suppression, namely monocyte deactivation and elevated proportions of regulatory T-cells that were also associated with increased risk of infection (relative risk of infection 3 (95%CI1.3-6.9) and 2.4 (95%CI1.3-4.2) respectively). These measures acted additively with C5a-mediated dysfunction, those with no immune impairment having a zero rate of nosocomial infection with cumulative increases in impairments being associated with a progressive increase in risk of infection (p=0.0004 by Chi squared for trend). In conclusion, critical illness is characterised by a complex inflammatory state with features of simultaneous hyper- and hypoactivation. This remarkable duality is illustrated by the ability of a proinflammatory molecule, C5a, to drive neutrophil dysfunction, with this dysfunction being associated with a serious adverse event-nosocomial infection.
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Willard, Terence B. "Variability of biological signals in critical illness." Thesis, University of Manchester, 2006. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.595297.
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Inhealthy physiological systems all organs act to maintain relative constancy or homeostasis through a highly complex and integrated communication control network of feedback loops. This constant interaction results in a fluctuation in the beat to beat value of the nominal heart rate. Heart rate variability (HRV) is used to describe the variation in the intervals between consecutive heartbeats or the intervals between consecutive R peaks of the QRS complex obtained from an electrocardiogram (ECG). The hypothesis that illness and injury is associated with a reduction in heart rate variability has been tested in various clinical settings and continues to be evaluated. However standard measures of heart rate variability using power spectral analysis have not always been conclusive and the interpretation of results is still being debated. Newer methods based on ideas from nonlinear mathematics are controversial. Inparticular, the method of approximate entropy (ApEn) may give misleading results. In this study a novel normalized entropy measure L was developed for assessing HRV, using theoretical methods and data from an acute hypovolaemic shock model for validation. Electrocardiogram data from the shock model experiments was processed to . obtain the R-R intervals for analysis and used to validate the measure L. The results were statistically significant in showing the differences between the baseline state and the post shock state and between the baseline and the post resuscitation state after allowance was made for the effects of changes in heart rate. From theoretical analysis and from experimental data the method was shown to be valid in both the time and frequency domain. Theoretical predictions of the inconsistencies of approximate entropy were confirmed by experimental results and in particular the method did not give statistically significant results for the experimental data using the accepted range of tolerance values and number of elements being compared. The standard measures of power spectral analysis were not statistically significant. However, by modifying the analysis to that of amplitude rather than power a statistically significant reduction was shown in the total amplitude and high frequency amplitude, after allowance was made for changes in heart rate, at the same states as the measure L.
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Jones, Christina H. "Rehabilitation following critical illness : support for patients." Thesis, University of Liverpool, 2001. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.343717.
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Ozkok, Erengul. "A stochastic model for critical illness insurance." Thesis, Heriot-Watt University, 2011. http://hdl.handle.net/10399/2449.
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In this thesis, we present methods and results for the estimation of diagnosis inception rates for Critical Illness Insurance (CII) claims in the UK by cause. This is the first study which provides a stochastic model for the diagnosis inception rates for CII. The data are supplied by the UK Continuous Mortality Investigation and relate to claims settled in the years 1999 - 2005. First, we develop a model for the delay between dates of diagnosis and settlement of claims in CII using a generalised-lineartype model with Burr errors under both Bayesian and maximum likelihood approach. Variable selection using Bayesian methodology to obtain the best model with different prior distribution setups for the parameters is applied. For comparison purposes, a lognormal model and frequency-based model selection techniques are also considered. The non-recorded dates of diagnosis and settlement have been included in the analysis as missing values using their posterior predictive distribution and Markov Chain Monte Carlo methodology. Missing dates of diagnosis are estimated using the parsimonious claim delay distribution. With this complete data set, diagnosis inception rates for all causes (combined) and for specific causes are estimated using an appropriate claim delay distribution where the observed numbers of claim counts are assumed to have a Poisson distribution. To model the crude rates, a generalised linear model with Poisson errors and log-link function is used.
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Ismaeil, Taha. "Quantifying the severity of respiratory critical illness." Thesis, University of Nottingham, 2017. http://eprints.nottingham.ac.uk/42993/.
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Clinicians use several oxygen-based indices in intensive care units as surrogates to determine the condition of the patient’s lung and verify monitoring progress. Examples of these oxygen indices include the ratio of arterial oxygen tension to inspired oxygen fraction (PaO2/FiO2 ratio); arterial/alveolar oxygen tension ratio (PaO2/PAO2); alveolar–arterial oxygen tension difference (PA-aO2); respiratory index (RI= (PA-aO2)/PaO2), and content-based venous admixture (Qs/Qt). One of the issues with this approach is that these indices fail to take into consideration several additional external pulmonary physiological factors and, as such, these indices could potentially mislead clinicians. This thesis explores the nature of the oxygen-tension-based indices response and examined the effect that varying certain external pulmonary factors, such as FiO2, PaCO2, Hb, respiratory rate, oxygen consumption, cardiac output, and respiratory quotient, had on PaO2 using virtual subjects and patients’ data to quantify oxygenation defect through a combination of mathematics, different diseases, and pathophysiology. There were one or two approaches that could lead us to the answer, and many dead end routes. Eventually, the research produced a new index that was compared and validated using two approaches. First, on virtual subjects with lung pathologies that were commonly seen in the intensive care unit and then on real clinical data that was obtained from the intensive care unit. The results of these validation investigations indicated that the proposed index is more robust and resistant to variations in certain external pulmonary factors than the PaO2/FiO2 ratio. As such, there is a strong indication that it may help to improve the quality of patient care provided. The feasibility of manually calculating and applying this newly proposed index in the ICU is an issue that merits further exploration. Theoretically, if the newly proposed index was found to be practicable, it could improve the healthcare provided; reduce the cost of unnecessary blood work, and save time and effort. However, due to the time it takes to calculate crPaO2 manually, the use of medical technology and computer applications is desirable.
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Rothwell, Peter Malcolm. "Thyroid and adrenocortical function during critical illness." Thesis, University of Edinburgh, 1995. http://hdl.handle.net/1842/21504.
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The main aims of the thesis were as follows: (1) To determine the ranges of total thyroxine, triiodothyrone, TSH and cortisol concentrations at different levels of illness severity, and to relate these to mortality; (2) To determine the range of responses to standard dynamic tests of adrenocortical and thyroid function, and relate them to severity of illness and mortality; (3) To determine the relationship between the extent of the changes in total thyroid hormone concentrations during illness and metabolic rate; (4) To accurately determine the prognostic value of measurement of thyroxine, triiodothyrone, TSH and cortisol on admission to an ICU. The majority of critically ill patients had plasma cortisol concentrations above the upper limit of normal in health. In keeping with Seyle's General Adaption Theory, plasma cortisol concentration correlated with severity of illness. The normal ranges of plasma cortisol concentration, defined as population mean +/- 2SD, differed according to the severity of illness. A plasma cortisol concentration above 200 nmol/L would be within the 95% range for a moderately ill patient (APACHE II score <16) whereas a concentration of under 400 nmol/L would be below the expected range in a severely ill patient (APACHE II score >24). A prognostic index based on admission measurements of cortisol, thyroxine and thyrotropin concentrations was developed using multiple logistic regression analysis. The model obtained predicted outcome of illness with significantly greater accuracy than APACHE II scores.
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BARTZ, CLAUDIA CAROL. "NURSE-PATIENT COMMUNICATION DURING CRITICAL ILLNESS EVENTS." Diss., The University of Arizona, 1986. http://hdl.handle.net/10150/183833.
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The purpose of this study was to explore and describe nurse-patient communication during critical illness events. The theoretical structure of the study was drawn from communication, sociolinguistic, and nursing theory. Data were collected in a 374-bed private hospital in the Southwest. The sample consisted of six registered nurses and nine patients experiencing cardiac surgery. Nine observed and audiotaped nurse-patient interactions, and fourteen audiotaped partcipant interviews provided the data base for analysis. Content analysis was used to organize the data. Findings were presented in terms of language, paralanguage, and nonverbal expression, and in terms of content, process, and product of nurse-patient communication. Participants used biomedical-technical language and casual-everyday language during the interactions. Nurses talked about what patients would experience while patients talked about themselves as a way of establishing their credibility within the biomedical setting. Nurses viewed nurse-patient communication as variable depending on the patients' needs and responses. Patients viewed nurse-patient communication as straightforward, not requiring adjustment for the needs of the participants. Products of communication for patients involved increased knowledge, reassurance, and increased confidence. Products of communication for nurses involved relieving the patients' anxieties, considering the patients' remembering, and increasing the nursing staff's knowledge about the patient while helping the patient to know the goals of the nursing staff. The introduction and closure segments of the six nurse-patient interactions for preoperative preparation of the patient were analyzed. Nurses began the introductions by assuming that the patients needed relief from anxiety but the patients demonstrated politeness more than anxiety. Nurses used strategies of questioning, starting the physical assessment, topic persistence, and self-monitoring to control the closure segments. Patients used narratives and humor as control strategies. The study findings suggest conceptual areas relevant to nurse-patient communication which may ground theoretical model development for nurse-patient communication. Nurses in clinical settings can compare their patient communication experiences with the findings of the study in order to increase their understanding of expression, form, and function of nurse-patient communication.
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Bion, Julian Fleetwoo. "Severity scoring and its applications in critical illness." Thesis, Imperial College London, 1990. http://hdl.handle.net/10044/1/47775.
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Lee, Debra A. "The Role of Relationships During Chronic Critical Illness." Case Western Reserve University School of Graduate Studies / OhioLINK, 2011. http://rave.ohiolink.edu/etdc/view?acc_num=case1307657748.
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Al_griw, Huda Hm. "Molecular detection of bloodstream pathogens in critical illness." Thesis, University of Manchester, 2012. https://www.research.manchester.ac.uk/portal/en/theses/molecular-detection-of-bloodstream-pathogens-in-critical-illness(5f143a31-3694-454c-8940-5ae434f1eb31).html.
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Background: Critically ill patients are at particular risk of developing bloodstream infection. Such infections are associated with the development of sepsis, leading to a marked increase in mortality rate. Early detection of the causative organism and appropriate antibiotic treatment are therefore critical for optimum outcome of patients with nosocomial infection. Current infection diagnosis is based on standard blood culture techniques. However, microbiological culture has a number of limitations, not least that it takes several days to confirm infection and is therefore not useful in directing the early treatment with antibiotics. New techniques based on the detection of pathogen DNA using real-time polymerase chain reaction (PCR) technology have the potential to address these limitations but their clinical utility is still to be proved. Objectives: Develop and evaluate novel PCR-based approaches to bloodstream infection diagnosis in critical illness based on detection and identification of bacterial and fungal DNA in blood. Methods: A range of commercial and 'in-house' PCR-based assays for detection of bacterial and fungal DNA were developed and/or optimised for use in clinical blood samples. These included LightCycler SeptiFast, a CE-marked multi-pathogen assay for common bloodstream pathogens, BactScreen and GramScreen, broad spectrum bacterial assays based on 16S rRNA gene and real-time PCR assays developed to detect a range of clinically important fungal pathogens. Novel approaches to speciation of pathogen DNA using melting temperature (Tm) profiling and high resolution melting analysis (HRMA) were developed. Clinical evaluation of assays was either on blinded clinical isolates or blood samples from critically ill patients with clinical suspicion of bloodstream infection against conventional microbiological culture. Several techniques aimed at improving extraction of pathogen DNA from blood were also investigated. Results: The CE-marked commercial assay SeptiFast showed analytical sensitivity and specificity of 79% and 83% respectively. Concordance with positive culture results was good but high levels of 'false positives' were detected possibly attributed to detection of free pathogen DNA not associated with viable pathogens. The predictive value of a negative SeptiFast test was 98% suggesting that absence of pathogen DNA is a strong indicator of absence of infection. Further studies were aimed at detailed optimisation and validation of 16S rRNA gene real-time PCR assays for bacterial DNA. BactScreen and GramScreen were able to detect a broad range of clinically important bacteria down to <50 CFU/ml blood. A preliminary comparative evaluation against SeptiFast showed BactScreen gave excellent concordance with blood culture results with minimal false positive results compared to SeptiFast. Efficient extraction of pathogen DNA was shown to be a key factor in determining analytical sensitivity and several protocols were evaluated. Low cost approaches to speciation of bacterial DNA were developed by combining broad range real-time PCR with HRMA. A novel HRMA method based on Tm profiling was shown to identify 89% and 96% of blinded clinical isolates at species or genus level respectively. Real-time PCR/HRMA approaches were also successfully developed for detection and identification of fungal pathogens including a range of Candida and Aspergillus species associated with bloodstream fungal infection. Conclusions: These studies have highlighted some of the key factors that need to be considered when developing and validating PCR based assays for pathogen DNA detection in blood. A set of novel tools have been developed for rapid detection and identification of bacterial and fungal pathogens that could address the challenges of infection diagnosis based on pathogen DNA detection. Further work is required, not least in development of more efficient pathogen DNA extraction and detailed clinical validation but the tools described here have the potential to provide cost effective solutions to aid infection diagnosis that would be complementary to current culture-based methods. The provision of time critical information could have a positive impact on clinical decision-making leading to more effective management and treatment of patients with suspected bloodstream infection.
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Damiani, Elisa. "Microvascular perfusion and tissue oxygenation during critical illness." Doctoral thesis, Università Politecnica delle Marche, 2016. http://hdl.handle.net/11566/243141.
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Gittata cardiaca, livelli di emoglobina e di ossigeno nel sangue arterioso (SaO2 e PaO2) sono generalmente considerati come i principali determinanti della disponibilità di O2 sistemica. Tuttavia, negli stati critici l’ipossia tissutale può persistere nonostante la normalizzazione dei parametri emodinamici e dell’ossigenazione sistemica, a causa di una compromissione della perfusione microcircolatoria. Negli stati di infiammazione sistemica come la sepsi, lo stress ossidativo e i mediatori infiammatori possono portare a danno endoteliale e disfunzione microvascolare, che possono essere a loro volta responsabili di ipoperfusione e insufficienza d’organo. E’ quindi importante monitorizzare il microcircolo e la sua risposta alle terapie. Negli studi inclusi in questa tesi sono state utilizzate due tecniche non invasive che permettono di valutare la perfusione microcircolatoria e l’ossigenazione tissutale: la tecnica di video-microscopia sublinguale Sidestream Dark Field (SDF) e la Near Infrared Spectroscopy (NIRS) a livello del muscolo scheletrico (eminenza tenar) con test di occlusione vascolare. Questa tesi conferma il valore prognostico del microcircolo nei pazienti critici. Un’alterata capacità del tessuto di estrarre O2 in corso di ischemia e una riduzione della reattività microvascolare nella fase di riperfusione si sono rivelate in grado di predire la mortalità in una popolazione eterogenea di 89 pazienti ricoverati in Terapia Intensiva. Utilizzando la tecnica SDF, abbiamo trovato significative alterazioni del glicocalice endoteliale a livello del microcircolo sublinguale nei pazienti critici in confronto a volontari sani, e tali alterazioni sono apparse più pronunciate in presenza di sepsi. Il monitoraggio del microcircolo può rappresentare un’utile guida terapeutica. In pazienti settici la trasfusione di emazie leucodeplete ha prodotto un effetto più favorevole sul flusso convettivo a livello microcircolatorio rispetto alle emazie non leucodeplete. La trasfusione di emazie vecchie (tempo di conservazione >15 giorni) si è associata ad un aumento
dell’emoglobina libera plasmatica, la quale può aver condotto ad una riduzione della densità microvascolare per la sua attività di scavenger nei confronti dell’ossido nitrico. Dal momento che la perfusione e l’ossigenazione tissutali dipendono principalmente dalla funzione microcircolatoria, è importante tenere in considerazione gli effetti che le terapie comunemente applicate (ad es. l’ossigenoterapia) possono avere sul microcircolo. Una meta-analisi di studi osservazionali ha mostrato un’associazione tra l’esposizione ad iperossia e una più alta mortalità in diverse categorie di pazienti critici. In uno studio prospettico osservazionale su 40 pazienti, l’iperossia ha prodotto una precoce riduzione della densità microvascolare (indice di vasocostrizione), seguita tuttavia da normalizzazione al ritorno ai livelli inspiratori di ossigeno basali. Un’esposizione di 2 ore all’iperossia ha causato un aumento dei radicali liberi, inducendo un aumento della produzione di glutatione: questo meccanismo può essere stato in grado di stimolare la produzione di eritropoietina, secondo la teoria del “normobaric oxygen paradox”. Infine, questa tesi ha messo in luce le difficoltà tecniche relative al monitoraggio del microcircolo sublinguale tramite tecnica SDF e ha sottolineato l’importanza della qualità delle immagini raccolte al fine di ottenere una valutazione del microcircolo attendibile.Cardiac output, haemoglobin levels and arterial oxygen levels (SaO2 and PaO2) are generally considered as the main determinants of systemic O2 delivery. However, during critical illness tissue hypoxia may persist despite normalization of systemic haemodynamics and oxygenation, due to an impairment in microvascular perfusion. During systemic inflammation such as sepsis, endothelial damage and microcirculatory dysfunction may occur due to oxidative stress and inflammatory mediators, leading to hypoperfusion and organ failure. It is thus important to monitor the microcirculation and its response to interventions. In the studies included in this thesis, two non-invasive techniques were applied to evaluate microvascular perfusion and tissue oxygenation: sublingual sidestream dark field (SDF) videomicroscopy and near infrared spectroscopy (NIRS) on the skeletal muscle (thenar eminence) with a vascular occlusion test. This thesis confirms the prognostic value of the microcirculation during critical states. Alterations in tissue O2 extraction capacity during an ischemic challenge and a reduced microvascular reactivity during reperfusion were able to predict mortality in a heterogeneous population of 89 critically ill patients. Using SDF videomicroscopy, we found significant alterations in the sublingual microvascular glycocalyx in critically ill patients as compared to healthy volunteers, which were more pronounced in presence of sepsis. Microvascular monitoring may be a useful tool to guide therapy. In septic patients, the transfusion of leukodepleted red blood cells (RBCs) seemed to produce a more favourable effect on microvascular convective flow in comparison to non-leukodepleted RBCs. The transfusion of old RBCs (storage >15 days) was associated with an increase in plasma free haemoglobin, possibly leading to a reduction in microvascular density due to a nitric oxide-scavenger activity. Since tissue perfusion and oxygenation mainly depend on microvascular function, it is important to consider the microvascular effects of commonly applied interventions, such as O2 therapy. A meta-analysis of observational studies showed that exposure to arterial hyperoxia was associated with higher mortality in several subsets of critically ill patients. In a prospective observational study on 40 patients, hyperoxia induced an early reduction in microvascular density, suggesting a vasoconstrictive response, which however normalized upon returning to baseline levels of inspired O2. A 2-hour exposure to hyperoxia caused a rise in O2 free radicals, inducing an increased glutathione production: this mechanism may have been able to stimulate erythropoietin production, according to the “normobaric oxygen paradox”. Finally, this thesis highlighted the technical challenges of sublingual SDF monitoring and underlined the importance of microcirculatory image quality for a reliable evaluation of the microcirculation.
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Gamrin-Gripenberg, Lena. "Skeletal muscle metabolism in critically ill patients /." Stockholm, 2000. http://diss.kib.ki.se/2000/91-628-4053-3/.
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Kirkby, Joanne. "Ultrastructure and function of respiratory cilia in critical illness." Thesis, University of Plymouth, 2004. http://hdl.handle.net/10026.1/525.
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Nimmo, Graham R. "Cardiorespiratory and metabolic studies in shock and critical illness." Thesis, University of Edinburgh, 1996. http://hdl.handle.net/1842/21447.
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In patients undergoing resuscitation from shock three groups were defined on the basis of the responses of arterial blood lactate (ABL) concentrations. The first group had hyperlactataemia which corrected following therapy which achieved significant increases in mean arterial blood pressure (MAP: p<0.01) and DO2 (p<0.005). Group two had similar lactate levels, but vigorous therapy, which increased MAP significantly (p<0.05) did not increase DO2. ABL concentrations remained elevated, and mortality was high. These differences emphasise the importance of simultaneous reversal of hypotension and attainment of adequate DO2. In the third group, despite severe cardio-respiratory abnormalities hyperlactataemia was not seen. Shock may occur with normal ABL concentrations. In patients with shock and adult respiratory distress syndrome (ARDS) an elevated ABL has been proposed as a marker of delivery dependent VO2, a potential indicator of tissue hypoxia. Septic shock and ARDS patients were classified on the basis of normal or elevated ABL concentrations. The level of ABL had no value in predicting the response of VO2 to changing DO2 in either the grouped data, or in individual patients. The absence of hyperlactataemia in ARDS does not preclude the presence of delivery dependent VO2, and by implication tissue hypoxia. The anaesthetic induction agent propofol has been used for sedation in adult critically ill patients. In a group of ventilated, invasively monitored patients its effects on cardiorespiratory function were documented. Heart rate and MAP fell significantly (p<0.05) but DO2 and VO2 were unchanged despite a significant increase in the sedation score (p<0.01), suggesting there was no improvement in overall oxygen supply/demand balance.
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Wandrag, Liesl. "The relationship between nutritional and inflammatory changes during critical illness." Thesis, Imperial College London, 2013. http://hdl.handle.net/10044/1/17854.
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Muscle mass loss in the critically ill is substantial, between 1-2% per day. Muscle wasting and weakness delays patient recovery and rehabilitation. Understanding the relationship between nutritional and inflammatory markers will help to identify a notional “nutritional tipping point”, where anabolism exceeds catabolism, which will allow us to target nutritional therapy more successfully. Muscle depth on ultrasound, inflammatory markers, cytokines, urinary markers of protein breakdown and nitrogen balance data were collected in 78 critically ill patients. Patients lost a significant amount of muscle depth during their intensive care unit (ICU) stay. Results indicate that a nutritional tipping point is unlikely to exist during an ICU admission. Data suggests that nitrogen balance remains negative over 20 days, indicating that whilst patients should continue to receive standard nutrition support during their ICU stay, any additional nutritional strategy should be targeted outside of the ICU environment. Multilevel modelling indicated that each additional day spent on ICU was significantly associated with decreased C-reactive protein, muscle depth and interleukin-10 levels. With every year increase in a patient’s age muscle depth and 3-methylhistidine levels were significantly reduced and interleukin-10 levels were significantly increased. Sample size estimates from current data provide some guidance for future studies, however estimates should be viewed with caution. The feasibility of providing a leucine-enriched essential amino acid supplement to trauma ICU patients was furthermore assessed. Inflammatory and nutritional makers were assessed along with protein turnover. Although it was feasible to use the supplement in the trauma population, studying this patient group was more complicated than anticipated. Whole body protein turnover was enhanced in trauma patients with breakdown far exceeding synthesis. These studies suggest that although it may be feasible to provide amino acid supplementation to critically ill patients, this type of intervention should be targeted outside of the ICU environment.
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O'Hara, Mark William. "Foucault and Film: Critical Theories and Representations of Mental Illness." Miami University / OhioLINK, 2014. http://rave.ohiolink.edu/etdc/view?acc_num=miami1415896906.
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Sakantarat, Kannika Tan. "Psychological morbidity in patients with gastrointestinal cancers and critical illness." Thesis, Imperial College London, 2008. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.499243.
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Wong, Raymond Y. P. "Critical analysis of the existing food sampling programmes." Thesis, University of Strathclyde, 2000. http://oleg.lib.strath.ac.uk:80/R/?func=dbin-jump-full&object_id=21140.
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Existing food sampling programmes used by the local authorities, if they exist, operate in a 'hit or miss' fashion, and the use of small sample size is common in the programmes. Although the U.K. food co-ordination network is well developed, the complexity of the three-way systems creates many complications and duplications. Also, compliance with the European legislation generates extra burdens to the U.K. governments. A national survey was undertaken in 1998 to investigate the purpose and effectiveness on local authonty food sampling. Although only half of the returns believed that local food programmes contributed significantly to the prevention of foodborne illness, over three-quarters agreed that the programmes could be improved upon. It was clearly shown that U.K. local authorities were eager to advance their sampling regime, but were handicapped by resource constraints. The local authorities stated that improvement could be achieved if sampling activities were increased. Because sampling involves errors due to uncertainties and variations, a statistically validated sampling model was developed in an attempt to determine suitable sample sizes under various sample proportions that would also satisfy good normal approximation in order to reduce margin of error to a minimum. However, the model illustrated that current sampling regimes were far from reaching the minimum requirement. In the main, if sampling has a part in food safety activities, then central government support towards sampling and analysis cost is vital. Routine sampling can be undertaken collectively at a regional basis, and such high cost may be split among local authorities. Alternatively, a requirement can be placed upon food premises to undertake their own sampling, and officers will then carry out local audits. Finally, further investigations should be extended to the determination of many contaminants' limits and the cost benefit analysis along the chain of causality.
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Bench, Suzanne Deborah. "Self-regulation and coping during early critical illness recovery : the contribution of critical care discharge information." Thesis, King's College London (University of London), 2014. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.674846.
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Reade, Michael Charles. "Characterisation and Novel Treatment of Several Causes of Mortality in Critical Illness." Thesis, The University of Sydney, 2015. http://hdl.handle.net/2123/15997.
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Three critical care syndromes form the main foci of this thesis: sepsis; delirium; and severe trauma. Research methods used to investigate the pathogenesis and novel treatments of these syndromes include clinical trials, observational studies, and preclinical models. In several instances, a complete research programme is presented. For example: • in the investigation of delirium, in which observational studies and empirical assessments of clinical measurement tools led to a pilot study and then the definitive 15-hospital clinical trial (Dexmedetomidine to Lessen ICU Agitation: DahLIA) comparing dexmedetomidine to placebo as a treatment for this condition; and • in the assessment of a haemodynamic protocol-guided treatment algorithm for septic shock, in which practice surveys and reviews of trial methodologies preceded three harmonised international clinical trials subsequently subjected to definitive meta-analysis. Other research programmes that are still in progress are also presented. For example: • the Cryopreserved vs. Liquid Platelets (CLIP) trial; • a programme that has developed a novel preclinical model of acute traumatic coagulopathy, in parallel with clinical trials of resuscitation in trauma such as the 1400-patient Pre-hospital Anti-fibrinolytics for Traumatic Coagulopathy and Haemorrhage (PATCH) trial; and • a research programme testing a protocolised approach to sedation, including the 4000-patient definitive Sedation Practice in Intensive Care Evaluation (SPICE) trial. A substantial part of this thesis includes collaborative applications of trial and observational methodologies to other critical care topics, including advanced-care planning, nutrition, oxygen delivery, lactate concentration, anaemia, coagulopathy, and the effects of gender and race. Research methodology is constantly evolving, and contributions to this process are outlined along with examples of research translation into practice through both policy and education.
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Hill, Neil Edward. "The effects of military deployment and critical illness on energy homeostasis." Thesis, Imperial College London, 2012. http://hdl.handle.net/10044/1/39394.
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Maintaining energy balance is critical to military performance. Severely injured military personnel in intensive care inevitably develop a catabolic state which prolongs the recovery period. Understanding the effects of deployment and injury on energy homeostasis will aid tailoring of nutritional provision to military personnel. Body composition, physical fitness, dietary intake, gut hormone and leptin levels were measured in 249 Royal Marines before, during and after a six month operational deployment in Afghanistan. Wounded volunteers were followed up during recovery and rehabilitation. Royal Marines lost significant total, lean and fat mass in the first half of their tour, which did not affect physical fitness. Leptin was significantly correlated with fat mass changes. The cohort of wounded Royal Marines was too small and heterogeneous to draw meaningful conclusions from. The orexigenic gastric hormone ghrelin has been proposed to attenuate the loss of lean body mass seen after critical illness. To investigate the effect of ghrelin on recovery from critical illness a rodent model of prolonged critical illness with gradual recovery was developed. Male Wistar rats received intraperitoneal injections of the fungal wall derivative zymosan. Biochemical, metabolic and gut hormone profiles were characterised. Continuous subcutaneous infusion of ghrelin was started 48 hours after the insult and continued for 10 days. Muscle strength and histology, and body composition were determined. Zymosan caused significant weight loss and muscle mass and reduced food intake. Ghrelin-treated rats ate more food and gained more body mass than controls, but did not alter total body protein, muscle strength or muscle morphology, though it increased adiposity and promoted fat over carbohydrate metabolism. These studies suggest loss of moderate amounts of body mass in Royal Marines did not adversely affect measures of strength, and that the gastric hormone ghrelin is unlikely to accelerate recovery of lean body mass or muscle function in critical illness cachexia.
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Rennick, Janet Elizabeth. "Children's psychological responses following critical illness and exposure to invasive technology." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 1999. http://www.collectionscanada.ca/obj/s4/f2/dsk1/tape9/PQDD_0017/NQ55372.pdf.
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Rennick, Janet Elizabeth. "Children's psychological responses following critical illness and exposures to invasive technology." Thesis, McGill University, 1999. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=36051.
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Children who are hospitalized in a pediatric intensive care unit (PICU) are subjected to a barrage of highly invasive, often painful interventions necessary in overcoming the critical period of their illness. While the majority of these children survive, little is known about the impact of critical illness on their subsequent psychological adjustment. The purposes of this study were (a) to compare the psychological responses of children hospitalized in a Pediatric Intensive Care Unit (PICU) with those of children hospitalized on a general ward; and (b) to determine whether there was a relationship between children's psychological responses post-hospital discharge and their age, the number and type of invasive procedures to which they were exposed during hospitalization, severity of illness, and length of hospital stay. A prospective cohort design was used to study two groups of children (N = 120). The study group included 60 children who had been hospitalized in a PICU, and the comparison group 60 children hospitalized on a general ward. Data were collected just prior to discharge, at six weeks and six months following discharge, from two metropolitan children's hospitals. Groups were compared on the following psychological responses: (a) the child's sense of control over his or her health; (b) the child's medical fears; (c) intrusive thoughts and avoidance behaviors related to hospitalization, as indicators of post-traumatic stress; and (d) changes in the child's behavior following hospitalization. In order to examine the possibility of post-traumatic stress responses in these children, the 'Child Impact of Event Scale' was developed in this study as a modified version of an adult measure originally developed by Horowitz and colleagues (1979). Other psychological responses were measured using established instruments. Relationships between the children's psychological responses and their age, the number and type of invasive procedures to which they were exposed d
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Bubser, Florian [Verfasser]. "Critical Illness Myopathie : Risikofaktoren während der frühen systemischen Inflammation / Florian Bubser." Berlin : Medizinische Fakultät Charité - Universitätsmedizin Berlin, 2011. http://d-nb.info/1026264839/34.
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Ramsay, Pam. "Quality of life following prolonged critical illness : a mixed methods study." Thesis, University of Edinburgh, 2010. http://hdl.handle.net/1842/8310.
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Survival following critical illness is associated with a significant burden of physical and psychosocial morbidity and recovery is often protracted and/or incomplete. Recovery has been measured using, almost exclusively, generic health-related quality of life (HRQoL) questionnaires. There is, however, an inexorable lack of consensus on the conceptual definition of HRQoL, and existing measures have tended to reflect overtly biomedical concerns such as morbidity and impairment at population level. Limited empirical or theoretical work has examined the extent to which widely used measures reflect the individual’s concerns, “health”-related and otherwise. The primary aims of this PhD are to examine HRQoL among a rarely studied sub group of the critically ill patient population: survivors of prolonged critical illness, and to explore the extent to which professionally endorsed measures capture their experiences of and perspectives on the recovery process. The implications of “patient-centredness” are both diverse and far-reaching in terms of policy, practice and critical care outcomes research, and are discussed throughout. A review of the literature among a well studied sub group of the patient population (survivors of Adult Respiratory Distress Syndrome) identified the widespread use of generic and ancillary measures which were invariably developed for use among other patient populations. This approach was seen to offer limited insight to the putative relationship between critical illness-related morbidity and HRQoL. Reflecting existing professional recommendations and practice, the Short Form 36 (SF-36) and the EuroQoL were administered by post to 20 survivors of prolonged critical illness at up to 6 months following ICU discharge. Each subsequently participated in a semi-structured interview, the purpose of which was to explore experiences and perceptions of ongoing morbidity within the contexts of the critical illness “journey” and, importantly, everyday life. A small number (n=5) participated in cognitive interview in order to explore both the everyday logistics of questionnaire completion and the often startling inconsistencies between verbal and questionnaire response. Analysis here revealed the unexpectedly diverse and normally hidden processes through which survivors interpreted and responded to standardised questionnaire items, challenging traditional (i.e. psychometric) notions of validity. Data from the semi-structured interviews were “mapped” onto the dimensions of the SF-36, revealing the highly contextualised and complex inter-relatedness of biomedically defined and ostensibly discrete aspects of experience. Morbidity was conceptualised by survivors in terms of the adaptive and interpretive processes adopted in everyday life (as opposed to a source of loss) and was generally under-reported in questionnaire form. An alternative explanatory framework for HRQoL was subsequently developed. Data were also analysed with reference to the “biographical narrative” of critical illness, a strategy which revealed the significance of survivors’ own stock of “life experience” (health-related and otherwise) in these interpretive and adaptive processes. The unexpectedly phlegmatic nature of survivors’ accounts directed attention to the narrative form, lending credibility to survivors’ claims that “things weren’t that bad”; accounts of seemingly intolerable morbidity were perceived, for example, as “a lucky escape”. This data also revealed, however, the influence of shortfalls in the processes and delivery of acute hospital rehabilitation upon the efficacy of these interpretive and adaptive processes. Mixed methods approaches to HRQoL, in summary, offer significant insights into survivors’ conceptualisations of morbidity, recovery, quality of life and the complex inter-relationships therein. Attention to the processes of adaptation also offers significant potential for the development of patient-centred measures of outcome and the expedition of the recovery process in ways which are most meaningful to survivors.
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Raman, S. "Investigation of oxygen targets and hypoxic adaptation in paediatric critical illness." Thesis, University College London (University of London), 2017. http://discovery.ucl.ac.uk/1563635/.
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Background: The effect of varying oxygen tension on the outcome of critically ill patients is contentious. Many interventions employed in the intensive care unit aimed at increasing oxygen delivery can cause harm. During the natural history of critical illness, adaption to tissue hypoxia may occur to a greater or lesser extent. I used the principle of Near Infrared Spectroscopy (NIRS) with a vascular occlusion test to investigate forearm muscle oxygen consumption. Methods: The relationship between arterial oxygenation and mortality in critically ill children was explored with a retrospective observational study, a national survey and a systematic review in chapter 3. Chapter 4 describes a study of Near infrared spectroscopy with a vascular occlusion test (NIRS VOT) in children with suspected mitochondrial disease. The aim was ascertain if NIRS VOT as a technique is able to reflect tissue oxygen consumption. Chapter 5 covers the Young Everest Study 2. Healthy volunteers (8-16 years) who travelled to Nepal and trekked to 3525 meters altitude were tested at two altitudes (sea level and 3525 meters). The aim was to investigate the physiological response to a hypobaric hypoxic environment including the NIRS VOT. Chapter 6 covers studies conducted on critically ill children admitted to the PICU in GOSH. These include serial NIRS VOT study, an in-vivo measure of oxygen consumption of peripheral blood mononuclear cells and the expression of oxidative phosphorylation (OXPHOS) genes changes in the first 48 hours after admission to the PICU in children with meningococcal septic shock. Results: Chapter 3: The epidemiological study of the children admitted to the intensive care unit showed that 40 children had a P aO2 of less than 20 mmHg (2.6 kPa) out of a total 7751 admissions in a 9 year period. Of these, 33 children survived to hospital discharge. There was a U shaped relationship between arterial oxygen tension and mortality. The results from the survey showed a varied practice. Of the total, 21 respondents (42%, 95%CI : 29.3 55.7%) stated that they do not follow specific P aO2 targets. Of the rest, as equal number (21, 42%) aimed for targets between 8.1 (61 mmHg) and 10 kPa (76 mmHg). Only 8(16%) aimed for what would be considered a normal range (10.1 13kP a). A majority of the units (96%) reported having an alarm target on their oxygen saturation monitor. However, 73% of the respondents worked in units that did not have an oxygen weaning protocol for mechanically ventilated patients. In acute respiratory distress syndrome, cardiac arrest and sepsis, there was a tendency to aim for lower P aO2 (< 10 kPa) as the F iO2 increased. Following traumatic brain injury and in pulmonary hypertension, there was a propensity to aim for normal P aO2 (10.1-13 kPa) even as the F iO2 rose (28-33% when F iO2 >0.4). The systematic review identified 11 studies (n=5280) related to hypoxia with combined odds ratio (OR) for death of 3.13 (95%CI: 1.79-5.48, p < 0.001) compared to normoxia. Six studies (n=2012) investigated the effect of hyperoxia and suggest no e↵ect on mortality compared to normoxia: OR 1.15 (95%CI: 0.42-3.17, p = 0.77). Chapter 4: A DropTOI value of 14 was noted to have the least crossover between the mitochondrial disease group and controls. This was empirically set as the cutoff for the 2x2 table. The Fisher exact test statistic was 0.22 and showed that NIRS VOT is unable to differentiate between mitochondrial disease and controls. The NIRS VOT was able to exclude mitochondrial disease in healthy children with a high degree of certainty (positive LR - 5.66, 95%CI:0.84-38, negative LR - 0.61, 95%CI:0.47-0.80). Chapter 5: The SpO2 at rest decreased from 99±0.79 to 89±2.54 % from London to Namche (p=0.0009). The SpO2 after exercise decreased from 93.5 ± 7.16 to 83.3 ± 5.06 % from London to Namche (p=0.008). The heart rate Z-scores at rest changed from 0.44±0.70 to 0.10±0.76 bpm (p=0.30) whilst the heart rate Z-scores after exercise increased from 1.20 ± 1.30 to 2.07 ± 1.46. Cardiac index (at rest) did not show a statistically significant change with an ascent to moderate altitude. Respiratory rate after exercise increased consistently from sea level (22.2 ± 4.4) to Namche Bazaar (27.6 ± 10.9). With a multilevel functional regression analysis, the baseline TOI was significantly lower in Namche Bazaar than London (-4.05, 95%CI: -3.23, -4.86, p < 0.001). The lowest TOI was also significantly lower in Namche Bazaar (-1.95, 95%CI: -1.13, -2.76, p < 0.001). The DropTOI at Namche bazaar compared to sea level was 2.1 points lower (p < 0.0001). Chapter 6: Tissue Oxygen Index varied during the first 5 days of illness. The DropTOI decreased until day 4 (3.02 lower) and showed relative increase on day 5 (0.93 lower) compared to day 1. The net routine control ratio (measured with oroboros analyser) dropped from day 1 to day 5. On the group level analysis (all five patients assessed together), with a false discovery rate (FDR) at < 25% and ranked according to their Normalised Enrichment Score (NES), 1039 out of 3655 gene sets showed a decreasing profile with time. The respiratory electron transport chain gene set was ranked 75th of the 1039 gene sets. Conclusions: The oxygen administration practices in the paediatric intensive care units in the UK vary widely. Of note, admission PaO2 has a ‘U-shaped’ relationship to mortality in children admitted to the paediatric intensive care unit. Healthy children, when exposed to hypobaric hypoxic conditions, show a tendency to decrease oxygen consumption from forearm muscle. There was some evidence that critically ill children demonstrate similar signs of early adaptive response by reducing oxygen consumption.
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Castillo, Escobar Maria Isabel. "The relationship between anxiety during critical illness and adverse emotional outcomes." Thesis, Griffith University, 2015. http://hdl.handle.net/10072/366763.
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Objective: Survivors of critical illness experience compromised psychological health including the development of symptoms of anxiety, depression and post-traumatic stress. The aims of this study were to: (1) describe the magnitude and patterns of state anxiety reported by patients throughout their ICU stay; (2) identify factors associated with patients’ state and trait anxiety during critical illness; (3) determine factors associated with symptoms of anxiety and depression over six months after intensive care unit (ICU) discharge; and, (4) determine factors associated with post-traumatic stress symptoms (PTSS) over six months after ICU discharge.Thesis (PhD Doctorate)
Doctor of Philosophy (PhD)
School of Nursing and Midwifery
Griffith Health
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Martitz, Janine. "Factors impacting the hepatic selenoprotein expression in matters of critical illness." Doctoral thesis, Humboldt-Universität zu Berlin, 2017. http://dx.doi.org/10.18452/18033.
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Selenoproteine spielen eine wichtige Rolle in der antioxidativen Abwehr und bei Immunreaktionen. Der Selen(Se)metabolismus wird von Hepatozyten gesteuert, die das Se-Transportprotein Selenoprotein P (SEPP) synthetisieren und sezernieren. SEPP nimmt bei kritischen Erkrankungen, z. B. Sepsis ab und führt zu niedrigen Se-Spiegeln. Sepsis triggert die übermäßige Produktion von proinflammatorischen Zytokinen. Aminoglykosid-Antibiotika (AG), die oft bei schwerer Sepsis eingesetzt werden, induzieren Fehlinterpretationen der mRNA inklusive des Stoppcodons UGA welches für die Selenoprotein-Biosynthese notwendig ist. Es wurden daher die molekularen Wechselwirkungen zwischen den Zytokinen IL-6, IL-1b und TNFa, AG und dem Se-Status mit der Biosynthese in Leberzelllinien untersucht. IL-6 führte zu einer starken Reduktion der SEPP-mRNA und einer dosisabhängigen Reduktion von SEPP. Parallel dazu reduzierte IL-6 das Transkriptlevel, die Proteinexpression und die Enzymaktivität der Typ-I-Dejodase (DIO1). Auf die Expression der antioxidativ-wirkenden Glutathionperoxidasen (GPX) wirkte IL-6 isozymspezifisch; während die Transkriptkonzentrationen von GPX2 anstiegen und die von GPX4 abnahmen, blieb GPX1 unbeeinflusst. Die IL-6-abhängigen Effekte bestätigten sich auch in Reportergenassays von SEPP-, DIO1-, GPX2- und GPX4-Promotorkonstrukten. Um die Wirkungen von AG auf die Selenoprotein-Translation besser zu verstehen, wurden die SECIS-Elemente von GPX1-, GPX4- und SEPP-Transkripten in ein Reportersystem kloniert und auf eine Regulation durch AG und Se analysiert. Die Ergebnisse zeigen, dass der korrekte Se-Einbau vom Se-Status, von der AG-Konzentration und dem spezifischen SECIS-Element abhängig ist. Auf transkriptionaler und translationaler Ebene führten AG zu stark erhöhten SEPP-Spiegeln, während die Expression und Enzymaktivität von GPX und DIO1 nur in geringerem Ausmaß beeinflusst wurden. Eine Analyse der Se-Beladung zeigte, dass der Se-Gehalt von SEPP stark durch AG reduziert und vom Se-Status abhängig war.Selenoproteins play important roles in antioxidant defence and immunoregulation. Selenium (Se) metabolism is controlled by hepatocytes synthesizing and secreting the Se-transporter selenoprotein P (SEPP) declining in critical illness, e.g., sepsis. Sepsis triggers excessive production of pro-inflammatory cytokines. Aminoglycoside (AG) antibiotics applied in sepsis in induce mRNA misinterpretation including the stop codon UGA required during selenoproteins biosynthesis. The molecular interplay between the cytokines IL-6, IL-1b and TNFa, AG and Se-status on selenoprotein expression was investigated in hepatic-derived cell lines. IL-6 strongly reduced the level of SEPP mRNA and secreted SEPP in a dose-dependent manner. Likewise, expression of selenoenzyme type 1 deiodinase (DIO1) declined at the transcript, protein and enzyme activity level. The effects of IL-6 on the expression of antioxidative-acting glutathione peroxidases (GPX) were isozyme-specific; while transcript level of GPX2 increased and those of GPX4 decreased, GPX1 remained unaffected. IL-6-dependent effects were reflected in reporter gene experiments of selenoprotein promoter constructs. Characterising the effects of AG on selenoprotein translation, the SECIS-elements of GPX1, GPX4 and SEPP transcripts were cloned into a reporter system and analysed for their response to AG and Se. The results indicate that the correct co-translational Se-insertion depends on the Se-status, AG concentration and the specific SECIS-element. At both transcriptional and translational levels, SEPP levels were strongly increased in response to AG, whereas the expression and enzyme activity of GPX and DIO1 were affected to a lower degree. Analysis Se-status indicate that the Se-content of SEPP was strongly reduced by AG and depends on Se-status.
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Hayes, Michelle Amanda. "Elevated oxygen delivery and consumption compared with normal haemodynamics as targets for treatment in high risk intensive care patients." Thesis, Queen Mary, University of London, 1995. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.297188.
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ALMOOSA, KHALID FAEQ. "QUALITY OF DISCUSSIONS ON RESUSCITATION BETWEEN ICU PHYSICIANS AND CRITICALLY ILL PATIENTS' SURROGATE DECISION MAKERS." University of Cincinnati / OhioLINK, 2007. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1186693857.
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Mohamad, Suhaimi Fatanah. "The Impact of Insulin and Insulin Therapy on Physiology in Critical Illness." Thesis, University of Canterbury. Mechanical Engineering, 2012. http://hdl.handle.net/10092/7658.
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Hyperglycemia is prevalent in critical care, as patients experience stress-induced hyperglycemia, even with no history of diabetes. Hyperglycemia has a significant impact on patient mortality and other negative clinical outcomes such as severe infection, sepsis and septic shock. Tight glycemic control can significantly reduce these negative outcomes by reducing hyperglycemic episode, but achieving it remains clinically elusive, particularly with regard to what constitutes tight control and what protocols are optimal in terms of results and clinical effort.
The model used in this thesis is validated using an independent data and readily be used for different clinical interventions. Moreover, this model also able to accurately predict clinical intervention outcomes given that the model prediction error is very small, which is better than any other reported model. In particular, model-based glycemic control methods is used to capture patient-specific physiological dynamics, such as insulin sensitivity, SI.
To date, sepsis diagnosis has been a great challenge despite advancement in technologies and medical research. Critically, septic patients are often classified by practitioners according to their experience before standard test results can be assessed, as to avoid delay in treatment. Moreover, several scoring systems have also been widely used to represent sepsis condition and better standardization of sepsis definition across different centers.
In this thesis, insulin sensitivity, SI, a model-based metric is used to identify sepsis condition based on the finding that SI represents metabolic condition of a patient. Additionally, several clinical and physiological variables obtained during patient’s stay in critical care are also investigated using mathematical computation and statistical analysis to identify relevant metric which can be accurately use for sepsis interventions. Even though information on SI, clinical and physiological variables of a patient are insufficient to determine the sepsis status, these informations have brought to a different perspective of diagnosing sepsis.
Microcirculation dysfunction is very common in sepsis. Tracking of microcirculation state among septic patient enable better tracking of patient state particularly sepsis status. The tracking can potentially be done by using a pulse oximeter that can extract additional information related to oxygen extraction level. The processed signals are therefore represent relative absorption of oxyhemoglobin and reduced hemoglobin that can be used to assess microcirculation status.
In addition, this thesis focus on the real challenge of early treatment of sepsis and sepsis diagnosis where several potential metabolic markers are investigated. Microcirculation conditions are assessed using a non-invasive method that is generally used in typical ICU settings. In particular, the concept and method used to assess microcirculation and metabolic conditions are developed in this thesis.
Finally, the work presented in this thesis can act as a starting point for many other glycemic control problems in other environments. These areas include cardiac critical care and neonatal critical care that share most similarities to the environment studied in this thesis, to general diabetes where the population is growing exponentially world wide. Eventually, this added knowledge can lead clinical developments from protocol simulations to better clinical decision making.
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Nicholls, Alice. "Life in the balance : critical illness and British intensive care, 1948-1986." Thesis, University of Manchester, 2011. http://www.manchester.ac.uk/escholar/uk-ac-man-scw:180472.
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A series of life and death decisions, in a high-tech hospital unit, made by a multidisciplinary team of specialists and the patient's family - intensive care is the epitome of modern medicine. What better encapsulates the ambivalence of medicine in the twentieth century? From the beginnings of intensive care units in the 1950s to the institution of specialist societies, journals and training by the mid-1980s, so many of the tensions of modern medicine have been articulated in this story. The development of British intensive care has involved collaboration and conflict - the benefits of multidisciplinary knowledge and experience, with the competition for status and 'ownership' of patients. It has utilised the high-tech - striving to advance therapeutic capabilities balanced against the risks of iatrogenesis and loss of patient identity and autonomy, as well as the low-tech - the importance of clocks and windows with a view of the outside world for temporal orientation and sensory stimulation, for example. At times, the 'scientific' pathophysiology of critical illness has been pitched against 'intuitive' nursing care. At other times, the nurse has been acknowledged as the primary therapist. Critically ill patients have been the subject of a hospital specialty based on generalism rather than a single organ system or age group. Expanding and contracting notions of reversibility and salvageability have informed decision-making in a resource-intensive field. Using archives, journals, newspapers, oral history interviews, films and museum objects, this thesis challenges the view that intensive care originated from the 1952 Copenhagen poliomyelitis epidemic or the postoperative recovery room. Instead, it argues that intensive care was not just a response to illness, but that it grew alongside a new category of illness created by practitioners and policymakers - critical illness. Changing notions of critical illness in turn shaped the practice of intensive care. Until the mid-1960s, critical illness was seen as phase of illness, with the highest degree of nursing dependency. As therapy developed, it began to be measured as the highest degree of medical and technological dependency. With research and symposia on pathophysiology, critical illness came to be regarded as a physiological state, imbalanced and in need of correction. Such notions informed questions of who should care for the critically ill, where, and how.
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Page, Pamela. "Critical illness survivorship and implications for care provision : a constructivist grounded theory." Thesis, City, University of London, 2016. http://openaccess.city.ac.uk/17242/.
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Background: In the context of increasing survivorship from critical illness it is important to enhance our understanding of the subjective experience of survivors and their families. The critical illness experience is enormously complex, varied and multifaceted. The need to consider the legacy of critical care beyond physiological survival is imperative. Aims of the study: The study aimed to formulate a substantive, middle range theory in relation to patient and family’s critical illness trajectory. Further, to discern and understand the responses of critical care nurses to survivorship needs. Methods: Working within a relativist ontology and a constructivist grounded theory methodology, a series of in-depth interviews were undertaken with survivors of critical illness (n=16), family members (n=15) (phase 1) and critical care nurses (n=11) (phase 2). Interviews were undertaken in a District General Hospital setting in England. All interviews were transcribed verbatim. Constant comparative analysis and data collection occurring concurrently with theoretical sampling commencing from the outset. Findings: Survivors of critical illness invariably entered a liminal state between life and death on admission and during their stay in the Adult General Critical Care Unit (AGCCU). They frequently experienced vivid, hallucinatory experiences which placed them in a different world or liminal space where they could move or transcend in and out of different realities or worlds. The core difficulty can be summarised as follows; survivors have little recall of the factual events of their critical illness within AGCCU but relatives have lived the whole event in a very real and ingraining manner. This can result in family members and survivors experiencing totally different versions or narratives of the critical illness episode; constructing the concept of dualistic worlds. Nurses working within AGCCU found themselves bounded by the walls of the critical care unit and experienced personal and professional conflicts in their role, as they bear witness to critically ill patients and their families. The critical care environment was identified as a demanding place of work which appeared to limit nurses to immediacy of care in the here and now. The specialist knowledge and skill that nurses provided were central to physiological survival but they are unable to support the onward survivorship trajectory. Conclusion: Survivors of critical illness, together with family members experience numerous challenges and adversities when endeavouring to readjust to life post critical care. This study has identified a middle range theory of dualistic worlds between and within the survivor and family member experiences. These temporal events occur during and after critical illness and expose a non-linear, fluid journey towards a new normal. Exploring the dynamic interplay between intrapersonal, interpersonal and societal factors has provided theoretical insights into critical illness survivorship and the legacy of critical care. Nurses in AGCCU bear witness to the early stages of the survivorship trajectory and provide complex care in support of survival; however they, are bounded by the walls of AGCCU such is the proximity to death and the pressure of work. They are unable to support the onward survivorship journey.
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Sim, Malcolm A. B. "The development and application of novel intelligent scoring systems in critical illness." Thesis, University of Glasgow, 2015. http://theses.gla.ac.uk/6512/.
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Scoring systems in medicine are not a new concept. There are examples from the early 1950s, from around the same time as the polio epidemic in Copenhagen resulted in the birth of modern Intensive Care. Many scores have subsequently been developed specifically for Intensive Care patients. The majority summarise the overall physiological state of the patient in a variety of different ways. A clinical interest in ascertaining whether haemodialysis causes cardiovascular instability in Intensive Care patients led to an initial simple experiment examining stability using a small number of cardiovascular parameters. It became apparent that to answer the question properly a physiologically based score which could be calculated automatically in real time, and which took into account the level of physiological or pharmacological support the patient was receiving would have to be developed, to counter or to mitigate the drawbacks of the main scoring systems in common use at the time. This thesis describes the development and first stage in the validation of a novel physiologically based scoring system for Intensive Care patients which overcomes some of the major disadvantages of existing scores. The score was then used to investigate other clinical questions. Myocardial damage in Intensive Care is common and associated with a poor outcome. Aspects of the developed score were used to ascertain if it is possible to detect and predict myocardial damage occurring in Intensive Care patients based on physiological disturbance rather than a rise in biomarkers. The score was subsequently used to examine Intensive Care patient outcomes. The introductory chapter describes the history of Intensive Care, the mechanism of data collection for patients in Scottish Intensive Care Units and its analysis to enable comparison of different units. Reviewing currently available scoring systems places this work in context and highlights the need for a new score. An overview of renal replacement therapy modalities follows, as an interest in cardiovascular stability during haemodialysis led to the idea for a new scoring system. Myocardial damage in Intensive Care patients is common and indicative of poorer outcomes. This is reviewed, as the developed score was used to detect and then predict where myocardial damage was occurring in critically ill patients, based on physiological disturbance rather than on raised biomarkers. In Chapter 2, data from dialysis sessions in critically ill patients was collected, prc-processed, and analysed for cardiovascular instability. Using an arbitrary definition of instability as a 20% change in mean arterial pressure or heart rate in either direction, 65% of dialysis sessions were stable and 35% unstable. This simple experiment suggested that haemodialysis is less cardiovascularly destabilising than previously believed. However a major deficiency was the lack of consideration of the level of physiological support required during dialysis. To investigate this and other clinical problems better, it became apparent that a new score would have to be developed. Chapter 3 describes the development of a novel quantitative score which takes into account the amount of physiological and pharmacological support a patient is receiving. Physiological parameters were separated into those recorded regularly and those recorded intermittently. They were subsequently divided into ranges, scoring increasing points depending upon the degree of derangement. Ranges were based on an extensive literature search, currently available scores, and clinical opinion. Two key parameters viz. mean arterial pressure and oxygen saturation, were then weighted against a range of factors which can either increase or decrease their value. A score of instability could then be calculated by adding points for the weighted and unweighted parameters. After reflection using common clinical scenarios, some of the points scored in different ranges and weightings were revised to give the final quantitative score. In Chapter 4, the quantitative score was tested against data sets from actual Intensive Care patients to produce graphs of overall cardiovascular stability against time. Although this approach did capture improvements and deteriorations it had several disadvantages. It captured the expertise of a single clinician only, gave an arbitrary number which could be difficult to interpret, and the emphasis given by the clinician to the relative importance of different physiological or pharmacological parameters would not be obvious to others. Clinical reflection led to a new approach to the problem, viz. the development of the 5 point qualitative scale described in Chapter 5. Chapter 5 describes the development of a 5 point qualitative score for cardiovascular instability, underpinned by complex physiological rules, and capturing the expertise of several senior Intensive Care Clinicians. This is the Intensive Care Unit - Patient Scoring System (ICU-PSS). I scored data sets comprising thousands of predominantly hourly commonly recorded physiological and pharmacological parameters on a 5 point scale of cardiovascular stability (A to E). I also described rules in the form of different parameter ranges to indicate why I had scored time points as stable (A) through to unstable (E). These rules were incorporated into a computer programme which scored unseen data sets which I also then scored. The computer’s predicted A to E score based on these rules and my own score were compared in a confusion matrix. Mismatches with the computer prediction (based on my initial rules) were analysed and I either rescored the data if I considered that I had not assigned the correct level of instability, or modified the rule base. Through this process clinical expertise was better captured. This process was repeated with two other clinicians using my rules as a starting point. This led to further refinements of the rule base. The result was a sophisticated set of rules underpinning a 5 point, easily understandable scale of cardiovascular stability crystallising the expertise of 3 senior Intensive Care clinicians. The ICU-PSS was tested in a discrimination experiment to ascertain if clinicians could agree with the score moving in a one step and two step change. This is the first stage in full validation of the score In Chapter 6, the first stage in the validation of the ICU-PSS is described, using 10 clinicians from a city teaching and a district general hospital. It was hypothesised that if they were shown two consecutive hourly time points of physiological data from real patients and asked whether they were improving or deteriorating, they should agree with the ICU-PSS score in more than 50% of cases (random chance). In two discrimination experiments the consultants were, in random order, shown 4 examples of each type of two step improvement or deterioration in the score, e.g. A to C, and 4 examples of each type of one step change, e.g. E to D. In the two step experiment there was 92.9% agreement with the score, and in the one step change experiment, 90.9% agreement. Both were highly statistically significant. Chapter 7 describes the first of the applications of the validated score. Myocardial damage is common in Intensive Care patients and is an independent risk factor for both short and long term mortality. The mechanism in Intensive Care patients is likely to be the so-called type II damage caused by extremes of physiological derangement leading to a myocardial oxygen supply and demand imbalance. I hypothesised that it should be possible to use aspects of the score to confirm and subsequently predict where this damage is occurs based on physiological disturbance alone rather than on a rise in cardiac biomarkers.
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Jowett, Adam. "Chronic illness in non-heterosexual contexts : towards a critical LGBTQ health psychology." Thesis, Aston University, 2011. http://publications.aston.ac.uk/15807/.
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In this thesis, I contribute to the expansion of lesbian, gay, bisexual, trans and queer (LGBTQ) psychology by examining chronic illness within non-heterosexual contexts. Chronic illness, beyond the confines of HIV/AIDS, has been a neglected topic in LGBTQ psychology and sexual identity is often overlooked within health psychology. When the health of lesbian, gay and bisexual (LGB) people has been considered there has been an over-reliance on quantitative methods and comparative approaches which seek to compare LGB people?s health to their heterosexual counterparts. In contrast, I adopt a critical perspective and qualitative methods to explore LGBTQ health. My research brings together ideas from LGBTQ psychology and critical health psychology to explore non-heterosexuals? experiences of chronic illness and the discursive contexts within which LGB people live with chronic health conditions. I also highlight the heteronormativity which pervades academic health psychology as well as the „lay? health literature. The research presented in this thesis draws on three different sources of qualitative data: a qualitative online questionnaire (n=190), an online discussion within a newsgroup for people with diabetes, and semi-structured interviews with 20 LGB people with diabetes. These data are analysed using critical realist forms of thematic analysis and discourse analysis. In the first analytic chapter (Chapter 3), I report the perspectives of LGB people living with many different chronic illnesses and how they felt their sexuality shapes their experiences of illness. In Chapter 4, I examine heterosexism within an online discussion and consider the ways in which sexuality is constructed as (ir)relevant to a diabetes support forum. In Chapter 5, I analyse LGB people?s talk about the support family and partners provide in relation to their diabetes and how they negotiate wider discourses of gender, sexuality and individualism. In Chapter 6 I explore how diabetes intersects with gay and bisexual men?s sex lives. In the concluding chapter, I discuss the contributions of my research for a critical LGBTQ health psychology and identify some possible areas for future research.
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Su, Dunhao. "Production, characterisation and application of humanised anti-histone antibodies in critical illness." Thesis, University of Liverpool, 2015. http://livrepository.liverpool.ac.uk/2029279/.
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McMoon, Michelle. "Patients' Perceptions of Quality of Life and Resource Availability After Critical Illness." ScholarWorks, 2019. https://scholarworks.waldenu.edu/dissertations/7558.
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Physical, psychological, and social debilities are common among survivors of critical illness. Survivors of critical illness require rehabilitative services during recovery in order to return to functional independence, but the structure and access of such services remains unclear. The purpose of this qualitative study was to explore the vital issues affecting quality of life from the perspective of critical illness survivors and to understand these patients' experiences with rehabilitative services in the United States. The theoretical framework guiding this study was Weber's rational choice theory, and a phenomenological study design was employed. The research questions focused on the survivors' experiences with rehabilitative services following critical illness and post-intensive care unit quality of life. Participants were recruited using purposeful sampling. A researcher developed instrument was used to conduct 12 semistructured interviews in central North Carolina. Data from the interviews were coded for thematic analysis. The findings identified that aftercare lacked unity, was limited by disparate information, and overuses informal caregivers. In addition, survivors' recovery depended on being prepared for post-intensive care unit life, access to recovery specific support structures, and the survivors' ability to adapt to a new normalcy. Survivors experienced gratitude for being saved, which empowered them to embrace new life priorities. The implications for social change include improved understanding of urgently needed health care policies to provide essential therapies and services required to support intensive care unit survivors on their journey to recovery.
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Perkins, Jessica Lee. "The Role of a Medical Family Therapist: An Ecological Systems Look at Pediatric Illness." Thesis, Virginia Tech, 2010. http://hdl.handle.net/10919/42640.
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This research explores the question of what role medical family therapists play on a health care team when working with serious pediatric illness. Seven participants from three different health care settings were interviewed. Results were organized within the ecological systems framework (Bronfenbrenner, 1979) according to the various ways participants became a part of the familyâ s illness experience. Participants identified roles directly with the family, with the health care team, and within the larger health care system. Clinical implications are identified concerning the preparation of the health care system for the continued growth and evolution of the field of medical family therapy.Master of Science
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Merriweather, Judith Lorna. "Exploration of the factors that influence nutritional recovery following critical illness : a mixed methods study." Thesis, University of Edinburgh, 2014. http://hdl.handle.net/1842/9571.
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Survivors of critical illness suffer from a range of problems affecting physical, psychological and social well-being (Needham et al 2011). Weakness, fatigue and malnutrition are highly prevalent during the months following a critical illness. Few studies have systematically and comprehensively explored the factors that influence nutritional recovery or ways to overcome them. The aim of this study was to provide a comprehensive understanding of the factors influencing nutritional recovery, and the relationship between them, in post intensive care (ICU) patients. A model of care was then developed to improve current management of nutrition for patients recovering from critical illness. Grounded theory methodology was used with a mixed method research design. Nutritional status and intake were assessed on discharge from ICU and at three months post ICU discharge. The process of nutritional recovery during the first three months post ICU discharge was explored from a patient perspective and at the level of ward organisation of care, through observation of practice and interviewing patients and staff. Seventeen patients, who had required greater than 48 hours ventilation, were recruited on discharge from the ICU. On transfer to the ward 9 of the 17 patients were assessed as well-nourished and 8 were malnourished using Subjective Global Assessment. At three months post ICU discharge 14 patients were followed up (1 lost to follow up, 1 incapacitated following illness and 1 went overseas). Seven of these were classified as well-nourished and the other 7 were malnourished. Patients universally failed to meet their nutritional targets during their ward stay and although intakes had improved by three months post ICU discharge, the majority of patients were still not achieving their nutritional requirements. Qualitative data revealed that patients' nutritional intake was influenced by interrelated system breakdowns during the recovery process; this emerged as the overarching core theme. Three sub-themes were ‘experiencing a dysfunctional body’, ‘experiencing socio-cultural changes in relation to eating and ‘encountering organisational nutritional care delivery failures’. This study identified connections and interrelations between these concepts and provided new insights into the factors that influence the nutritional care of post ICU patients. In order to optimise nutritional rehabilitation in this patient group a model of care has been developed which addresses the identified organisational and patient related factors that were shown to influence the nutritional recovery of patients after critical illness. This nutritional strategy will need to be evaluated in clinical trials or quality improvement programmes.
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Hanchanchaikul, Chanokporn. "Family coping during adult critical illness : development and psychometric validation of the coping questionnaire for the Thai families /." Thesis, Connect to this title online; UW restricted, 1999. http://hdl.handle.net/1773/7239.
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Salciccioli, Justin Daniel. "Vitamin D status in critically ill patients with sepsis." Thesis, Boston University, 2012. https://hdl.handle.net/2144/32052.
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Thesis (M.A.)--Boston University, 2012.PLEASE NOTE: Boston University Libraries did not receive an Authorization To Manage form for this thesis or dissertation. It is therefore not openly accessible, though it may be available by request. If you are the author or principal advisor of this work and would like to request open access for it, please contact us at open-help@bu.edu. Thank you.
Recent evidence has suggested that vitamin D may modulate innate immune function. We performed a prospective, observational investigation to assess the prevalence of vitamin D deficiency in adult critically ill patients with sepsis. Subjects were categorized by baseline 25-hydroxyvitamin D [25(0H)D]: Deficient: < 20 ng/ml, Insufficient: 21-29 ng/ml, or Normal: > 29 ng/ml. A total of 39 subjects were enrolled in the study. 25(0H)D deficiency is common with 23/39 (59%) of subjects either deficient or insufficient. In-hospital mortality was 15% (6/39) and 5/6 (83%) of the subjects who expired were 25(0H)D insufficient. There were modest differences in severity of illness across 25(0H)D categories (SAPS 3: p = 0.01) and statistically significant inverse associations between 25(0H)D and markers of inflammation (IL-6: p = 0.04; TN F-a: p = 0.03) and vascular endothelial dysfunction (E-selectin: p = 0.05). There is a high prevalence of vitamin D deficiency or insufficiency in critically ill patients with sepsis and an inverse association between vitamin D and inflammation and vascular endothelial dysfunction. Future studies should assess the causal relationship between vitamin D and inflammation and outcomes from sepsis.
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Treggiari, Miriam Monica. "Randomized trial of light versus deep sedation on mental health after critical illness /." Thesis, Connect to this title online; UW restricted, 2007. http://hdl.handle.net/1773/10928.
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Paterson, Ross L. "An investigation of the transcription factor nuclear factor kappa B in critical illness." Thesis, University of Aberdeen, 2002. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.288273.
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The immuno-inflammatory host response in critically ill patients with sepsis and inflammatory conditions is driven by the expression of compounds acting as, or producing inflammatory mediators, including cytokines, reactive oxygen species and adhesion molecules. Their production is in part controlled by the transcription factor, nuclear factor kB (NFkB). NFkB is a primary intracellular transcription factor, which transduces extracellular signals to the nucleus and responds to cellular oxidative stress. NFkB activation was assessed in circulating leucocytes from critically ill patients on the intensive care unit. NFkB was activated in mononuclear and polymorphonuclear leucocytes in all the patients studied, and was significantly greater than in healthy subjects (p=0.01, p=0.001). NFkB activation in mononuclear leucocytes increased markedly in those patients who died whilst remaining constant in those patients who survived. The effect of administration of the intracellular antioxidant N-acetylcysteine, on NFkB activation and circulating concentrations of cytokines and adhesion molecules was investigated in patients with sepsis. In patients who survived and received N-acetylocysteine, mononuclear leucocyte NFkB activation decreased significantly (p=0.016). In contrast there was no change in NFkB activation in mononuclear leucocytes from patients who received the placebo infusion. Additionally, circulating concentrations of interleukin (IL)-8 were found to decrease in those surviving patients receiving N-acetylcysteine. The effect of IL-10 on NFkB activation, coupled to 1kBa degradation, in leucocytes and tissues in endotoxaemic rats, was investigated. NFkB activation was increased with a corresponding reduction in 1kBa concentrations, in liver (p=0.02) and lung (p=0.004) samples from rats receiving combined LPS and IL-10. NFkB activation may have a central role in the mortality and sepsis. N-acetylcysteine attenuates mononuclear leucocyte NFkB activation and related IL-8 production in human sepsis, whereas, IL-10 administration resulted in paradoxical increases in NFkB activation.
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Griffith, David Morgan. "Persisting inflammation after critical illness : prevalence, risk factors and association with physical recovery." Thesis, University of Edinburgh, 2014. http://hdl.handle.net/1842/23955.
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Introduction: Survivors of critical illness suffer physical, psychological, and social problems. The factors hindering recovery and the best rehabilitation interventions remain illusive. Critical illness is associated with inflammation that persists in some individuals and this might affect recovery. The hypotheses for the thesis are 1. Persistent inflammation is common after critical illness. 2. Persistent inflammation is associated with functional recovery. 3. Persistent inflammation is associated with critical illness-induced viral reactivation. 4. Biomarkers may help predict functional disability. The main part of the project was based on 197 of the 240 patients enrolled in the RECOVER trial who also consented to take part in an inflammation sub study. Systematic Review. Aims: Prevalence of systemic inflammation in ICU survivors; association of inflammation with physical recovery. 7433 references identified. 208 full text articles were reviewed. 57 were eligible. 22 studies included the relevant data. CRP at ICU discharge was elevated ( > 10mg/L) in most cases (70% of mixed medical/surgical patients and 100% of severe sepsis survivors). Lower CRP observed in trauma patients (23mg/L), VAP (46mg/L), > 6 days in ICU (45mg/L), and medical ICU patients (36mg/L). CRP was higher in sepsis (107mg/L) and surgical ICU patients (99mg/L). IL-6, TNF-a, and PCT were elevated in most patients at ICU discharge. Ninety percent of acute COPD exacerbations admitted to ICU had elevated CRP at hospital discharge and 43% general adult ICU patients fulfilled SIRS criteria 3 days after ICU discharge. Anaemic ICU survivors had elevated CRP and IL-6 at 6 months. There were no studies that measured both inflammation and physical function after ICU discharge. Association of inflammation with functional outcome after critical illness. Aims: Prevalence of inflammation in heterogeneous ICU cohort, association of CRP with Rivermead Mobility Index (RMI) and other outcome measures at 3 months. At ICU discharge, 173 patients (94%) had elevated serum CRP with a median concentration of 27 (11-60) mg/L. At hospital discharge 169 patients (90%) had elevated CRP with a median concentration of 21 (8-42) mg/L, At 3 months 72 patients (59%) had elevated CRP with a median concentration of 4 (1-12) mg/L. CRP was associated with RMI (p < 0.01), and percentage of predicted handgrip strength (HGS) (p=0.03) at 3 months. CMV infection, systemic inflammation and the post ICU syndrome. Aims: Prevalence of active and latent CMV at ICU discharge; association between CMV, inflammation, and recovery. 115 patients (62.8%) had latent CMV. 13 (11.4%) had active CMV (11.4% of those with prior CMV and 7.2% of ICU survivors). Active CMV associated with longer hospital length of stay (57 days v 28 days p=0.016), poorer baseline physical function (HGS 12 v 16 p=0.032; RMI 1 v 2 p=0.018). At 3 months, patients with latent CMV infection had higher CRP (5.4 v 2.8mg/L p=0.06), higher HNE (118 v 91.3 pg/mL p < 0.00), lower TGF β (9.2 v 11.4 ng/mL p=0.01), and were slower on 2 min timed up and go test (p=0.03). Active CMV infection at ICU discharge was not associated with inflammation or physical function at 3 months. Prediction of physical disability after ICU discharge. Aims: To identify risk factors for poor physical function; to derive a prognostic index to identify for poor functional outcome. Age, Functional Comorbidity Index, Scottish Index of Multiple Deprivation quintile, CMV IgG status, ventilator days, baseline RMI, physical component of SGA, CRP, and SLPI met statistical criteria for consideration in the multivariable models. 2 linear multivariable models with reasonable fit (R2=0.175; 0.193) were constructed. AUCs were 0.759 for the clinical model and 0.725 for the model incorporating biochemical markers. The models did not perform any better than a baseline assessment of mobility (RMI).
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Rehfeldt, Nicole [Verfasser]. "Die systemische und muskuläre Insulinsensitivität von Intensivpatienten mit Critical Illness Myopathie / Nicole Rehfeldt." Berlin : Medizinische Fakultät Charité - Universitätsmedizin Berlin, 2014. http://d-nb.info/1058105043/34.
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Mooi, Nomaxabiso Mildred. "Investigating the provision of nutritional support to critically ill hospitalised patients by registered nurses in East London public and private hospitals in the Eastern Cape." Thesis, University of Fort Hare, 2014. http://hdl.handle.net/10353/d1015533.
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Critical illness is typically associated with a catabolic stress state in which patients commonly demonstrate a systemic inflammatory response that brings about changes in their body systems. Changes in the body systems make the critically ill dependent on mechanical ventilation and inotropic support for longer periods in order to survive. However, this inflammatory response can be attenuated by the timely introduction of nutritional support to provide energy and nutrients to diminish catabolism and promote anabolism. The result could be a decrease in the morbidity and mortality rates, as well as the financial burden on the patients, institutions and the state. Since registered nurses initiate and utilise feeding protocols to achieve target goals, there is a strong need for nurse-initiated feeding protocols. These protocols should be coupled with a comprehensive nurse-directed nutritional educational intervention that will focus on their safe and effective implementation. This focus on nursing nutrition education represents a major shift away from traditional education which has focused on dietitians and physicians. Evidence suggests that incorporating guideline recommendations into nurse-initiated protocols for starting and advancing enteral feedings is an effective strategy to improve the delivery of nutritional support. The study was aimed at exploring the provision of nutritional support to critically ill hospitalised patients by registered nurses to identify and describe possible gaps in the practice, through determining the potential relationship between the provision of nutritional support and characteristics of its providers. A quantitative, descriptive correlational study was undertaken. Seventy registered nurses working in neonatal/paediatric and adult critical care units in two public and three private hospitals in East London in the Eastern Cape participated in the study. The sample also included public critical care students. The results showed that registered nurses in private hospitals have more knowledge about the importance of nutritional support than their public hospital counterparts and students. The mean score was on the question was 80.3% with the highest score of 91% which was for the private hospital nurses, followed by 77.2% for public and 71.4% for students. Again, the mean score for knowledge on timing of initiating nutritional support was 48%, the highest score being 69.4% for students followed by private hospital nurses with 49.6%. Close to 63% (n = 44) of these nurses were either unsure about the availability of nutritional protocols or clearly attested to their non-availability. This is seen as an issue of concern because a protocol is meant to be a standard document with which all members of the ICU should be familiar. It is meant to guide and facilitate the manner of working in the unit. While facilitation of maintenance of nutritional support to patients is the responsibility of registered nurses, according to Regulation 2598(1984) section 45 (1) (q) of the South African Nursing Council, 68% (n = 48) of the respondents felt that this was in the practising scope of doctors and dietitians. The study concluded that the nurses are knowledgeable about the importance of nutritional support but knowledge gaps have been identified as far as the timing of initiating nutritional support is concerned. Some attested to unavailability of standard guidelines that are tailored into protocols guiding the provision of nutritional support by registered nurses in the critical care units. Nutrition should be prioritised as an important therapy for improving the outcomes of critically ill patients. Nurses need to analyse its provision, identify barriers to nutritional strategies and engage in nutritional education to empower themselves regarding the practice. Most importantly, there is a need for nurse-initiated nutritional protocols that are tailored from the broad nutritional guidelines and aligned with the local context and ways of practising. Nutritional support should be included as a key component of the curriculum in academic programmes that specialise in critical care nursing.