Medical error is the third leading cause of death in the United States, with surgery being a critical area for improvement. Of particular interest for this dissertation is understanding and mitigating the impact of acute stress experienced by surgeons. Previous research demonstrates the detrimental effects mismanaged acute stress can have on cognitive performance integral in optimal surgical practice. Biofeedback consists of objectively monitoring signs of stress, presenting physicians with their own physiological output in real time. Introducing appropriate, targeted coping mechanisms when they are most needed may facilitate behavioral adjustments in the face of acute stress. The goal of this dissertation research was to evaluate the potential benefit of biofeedback and coping instructions, measured by reduced perceived and physiological stress, and improved task performance. In the first study, college students participated in a first-person shooter videogame while receiving visual coping instructions. Instructions that were presented at moments of elevated stress improved downstream physiology compared to randomly administered instruction, and the presence of coping instructions was more beneficial than their absence at highly stressful times. In the second study, I adapted and validated a computer-based task to focus on components of workload experienced by physicians. This study yielded one high-stress and one-low stress version of a more demographic-appropriate task. In the final study, medical students and residents completed this task. The independent variables tested included a visual biofeedback interface, intermittent auditory coping instructions, and/or brief training on stress management and emotional intelligence. Results from this study showed that despite high cognitive workload experienced by participants receiving both biofeedback and coping instructions, performance across stress levels was indistinguishable, and physiological indicators of stress immediately following discrete coping instructions was reflective of decreased stress. Taken together, the results of these studies validate the generation of a new lab-based task to induce stress among healthcare providers, and the physiological and performance benefits associated with physiologically-based coping instructions. Future work should investigate how these concepts can be tailored towards surgical workflow with feedback modality in mind, extended to teams, and/or scaled up to higher levels of fidelity to better capture the work environment. / Ph. D. / Medical error is the third leading causing of death in the United States, with surgery being a critical area for improvement. Many medical errors are preventable, and previous research has shown that inappropriately managed acute stress is responsible for many errors. Biofeedback is one way to externalize stress states, enabling individuals to monitor their own stress, even as it is changing. With rapid advancement in technological functionality, sensors hold promise not only for personal body data, but also active interventions such as biofeedback. Biofeedback is the process of actively monitoring physiology on an external device, and updating behaviors based on that physiology. Its role as a stress management tool is growing. Commercially available sensor devices are widespread, and are generating and archiving thousands of data points every day. Rather than simply archiving this data, we can use sensor technology to inform us of our current physiological and cognitive states in real time, and use that information to alter our response to stressful stimuli to achieve more favorable outcomes. This concept can be applied specifically to address how to cope when experiencing high levels of stress. For individuals working in high-stakes environments on a daily basis, such as surgeons, using physiological data to manage stress could have the added benefit of improving performance that might otherwise suffer due to mismanaged stress. The goal of this dissertation research is to explore the potential benefit of using biofeedback and specific coping strategies to reduce stress and improve performance among healthcare providers. This research consisted of different studies, all using experimental psychology approaches and all geared towards evaluating different conditions of either visual coping instructions, training on emotional intelligence concepts as they relate to coping under stress, visual biofeedback, and/or auditory coping instructions. The results of these studies validate the generation of a new lab-based task to induce stress among healthcare providers, support the benefit of introducing coping instructions in response to elevated physiological signs of stress, and support the need for future assessments.

Yes

Background: Poor inhibitory control is a hallmark of problem gambling (PG), which is characterised by frequent gambling and unsuccessful efforts to control/stop gambling. Stress and PG demonstrate a cyclical relationship, whereby gambling can act as a coping mechanism for dealing with stressful life events, while consistent gambling engagement can increase stress. To date, few studies examine acute stress effects on inhibitory control (IC) in this group. Purpose: This study compares acute stress effects on IC in PG and healthy control (HC) populations. Methods: Twenty participants with PG and twenty HCs completed self-report measures of mood disturbance (Profile of Mood States; POMS) and impulsivity (Barratt Impulsiveness Scale); saliva samples were collected to measure cortisol. The Trier Social Stress Test was administered to induce an acute stress response, followed by the Stop-Signal Task (SST), a validated measure of IC. Results: Subjective stress responses increased over time in both groups, with the PG group demonstrating significantly higher POMS ratings (p<.05), however, no differences in cortisol levels were observed between groups (p>.05). Moreover, no group differences were observed on the SST (p>.05). Exploratory correlations revealed significant positive and negative correlations between cortisol levels and ‘go’ reaction time and ‘stop’ signal reaction time on the SST, respectively (p<.05). Conclusion: This study is the first, to our knowledge, to directly examine acute psychosocial stress effects on IC in individuals with PG. Our findings show that while both groups display similar cortisol levels, individuals with PG report increased subjective stress relative to HCs. Despite no stress-induced impairments on SST performance, significant correlations were observed between task reaction time and cortisol levels in the PG group. This study helps to better inform clinical practice by providing a comprehensive understanding of the implications of stress and IC on gambling behaviours. / Thesis / Master of Health Sciences (MSc) / Problem gambling (PG) is characterised by problems with impulsivity and inhibitory control. Stress affects inhibitory control and appears heightened in PG, but few studies examine this relationship. This study examined acute stress effects on inhibitory control task performance, which may underlie the loss of control during gambling episodes that is often experienced by those with PG. Participants with PG and healthy controls (HCs) completed questionnaires relating to impulsivity and stress, and were exposed to an acute stressor and provided saliva samples to measure physiological stress (cortisol). Later participants completed a task examining reaction time as a measure of inhibitory control. Results showed that individuals with PG reported increased stress relative to HCs, despite having similar cortisol levels. While acute stress did not impair inhibitory control on the task, significant correlations were observed between task reaction time and cortisol levels, which suggests a strong relationship between inhibitory control and physiological stress response.

Dans les pays « développés », les syndromes coronariens aigus (SCA) représentent une pathologie fréquente et grave et les maladies cardiovasculaires restent la première cause de mortalité en Europe. Au cours de la dernière décennie, pourtant, plusieurs travaux épidémiologiques ont suggéré une baisse sensible de l'incidence des infarctus et la mortalité cardiovasculaire est dorénavant en recul dans de très nombreux pays, dont la France. La cardiologie est une des disciplines médicales qui a connu les plus grands bouleversements au cours des 25 dernières années et la prise en charge des SCA ainsi que le profil des patients ont considérablement évolué. Dans ce contexte, il nous a paru intéressant d'étudier la manière dont le devenir des patients présentant un infarctus aigu pouvait participer à cette baisse générale de la mortalité cardio-vasculaire. A partir de quatre enquêtes longitudinales successives répertoriant les SCA (USIK 1995, USIC 2000, FAST-MI 2005, FAST-MI 2010) et de l’observatoire national des actes de cardiologie interventionnelle (ONACI), nous avons observé, après standardisation sur les caractéristiques initiales des différentes cohortes, une baisse spectaculaire de la mortalité quel que soit le type de SCA (avec sus-décalage ST [SCA ST+] ou ST-elevation myocardial infarction [STEMI] ; sans sus-décalage ST [SCA ST-] ou non-ST-elevation myocardial infarction [NSTEMI]). Cette évolution peut être expliquée par plusieurs paramètres : amélioration de la prise en charge globale, meilleur suivi des recommandations, changement de profils des patients (pour les STEMI), développement de la stratégie invasive et utilisation de nouvelles thérapeutiques, évolution des techniques de cardiologie interventionnelle… Ainsi, il apparaît que l'amélioration du pronostic des patients atteints d'infarctus est bien un des éléments ayant pu contribuer à la baisse de la mortalité cardiovasculaire. L’enjeu aujourd’hui est de maintenir ces résultats, de renforcer les mesures de prévention et d’améliorer le pronostic à long terme en développant notamment les programmes d’éducation thérapeutique. / In developed countries, acute coronary syndromes (ACS) represent a common and serious disease, and cardiovascular disease remains the leading cause of death in Europe. During the last decade, however, several epidemiological studies have suggested a significant reduction in the incidence of myocardial infarction and cardiovascular mortality in many countries, including France. Over the past 25 years, Cardiology has dramatically evolved and the management of ACS, as well as patient risk profile have substantially changed. In this context, we aimed to evaluate how the outcomes of patients with acute myocardial infarction could participate in the general decline in cardiovascular mortality. From four successive longitudinal surveys including ACS (USIK 1995, USIC 2000, FAST-MI 2005, FAST-MI 2010) and the national observatory of interventional cardiology (ONACI) we observed, after standardization of the cohorts on baseline clinical characteristics, a dramatic decline in mortality regardless of the type of ACS (STEMI, ST-elevation myocardial infarction, NSTEMI, non-ST-elevation myocardial infarction). This evolution can be explained by several factors: overall improvement in organization of care, better implementation of recommendations, substantial change in the patient risk profile (for STEMI), increasing use of invasive strategy and adjunctive therapies, improved technique for Interventional Cardiology ... Therefore, the improved prognosis of patients with myocardial infarction appears to be one of the factors that have contributed to the decline in cardiovascular mortality. For the future, the challenge will be to maintain these results, strengthen preventive measures and improve long-term prognosis in particular by developing the therapeutic education programs.

Primärvårdens uppdrag innebär att erbjuda patienter i alla åldrar sjukvård som inte kräver sjukhusets specialistkompetens. Primärvård innefattar både vårdcentral och jourcentral där patienter med både akuta och icke akuta åkommor ska kunna omhändertas. Distriktssköterskan besitter fördjupade kunskaper genom specialistutbildning och ska kunna bedöma patientens hälsotillstånd och agera utifrån det. Vården ska vara av god kvalité och ska vara säker och trygg för patienten. Vårdpersonalen ska värna om patientens integritet och respektera individens självbestämmande. Det saknas studier som beskriver hur distriktssköterskor upplever och erfar det akuta omhändertagandet av patienter i primärvård. Syftet med intervjustudien är att undersöka distriktssköterskans upplevelse och erfarenhet av omhändertagande av akuta patienter inom primärvård. Kvalitativ forskningsansats har använts med fokus på livsvärlden, för att fånga fenomenet. Alla informanter som deltog var distriktssköterskor med erfarenhet inom primärvård och uppfyllde därmed kriterierna för deltagande. Resultatet framkom genom Dahlbergs innebördsanalys och gav fem teman med subteman. De övergripande teman var distriktssköterskans erfarenhet, vikten av kunskap och utbildning, kollegornas betydelse, vårdmötet i det akuta omhändertagandet och rutiner i arbetet. Det visade sig i studien att distriktssköterskor har behov av kontinuerlig utbildning i akut omhändertagande samtidigt som erfarenhet, intuition och personlighet bidrar till patientsäkra bedömningar. Kollegorna har stor betydelse för det akuta arbetet och kan inverka på både ett positivt och negativt sätt. Professionaliteten och kommunikationen är av vikt i det vårdande mötet mellan distriktssköterska och patient, likväl som tydliga strukturer är viktiga i de akuta situationerna.

In part ONE of this thesis, including the most up to date information on SARS virology, disease transmission, pathogenesis and laboratory diagnosis will be summarized and presented, including the results of many studies in which I have participated (these references will be underlined as they appear in text). This of course summarizes knowledge that is now known in 2006 but was largely unknown during the initial outbreak. In part TWO, six original clinical studies performed at PWH will be presented: study (1) describes the clinical manifestations and severity of SARS, and its potential to cause major hospital outbreaks; (2) demonstrates the importance of epidemiological linkage in diagnosing SARS; (3) reports the clinical outcomes of a stepwise treatment protocol, which includes the use of corticosteroid therapy as an immunomodulant; (4) demonstrates that corticosteroid therapy can retard viral clearance, and should be used judiciously; (5) demonstrates that a more robust humoral response is associated with severe SARS, thus indicating that passive immunity treatment strategies seem only suitable either during early illness or as prophylaxis; and (6) shows that SARS has few early discriminating laboratory features compared to other causes of community-acquired pneumonia, thus a high index of suspicion is needed to recognize this infection in the absence of worldwide transmission. A thorough review of the relevant published material will be included in the discussion section of each study. / Severe Acute Respiratory Syndrome (SARS) is an emerging infectious disease caused by a novel coronavirus. It caused a global outbreak in 2003, resulting in more than 8000 infections, 700 deaths, and major social and economic disruption. In the initial phase of the SARS outbreak, the medical profession had no knowledge regarding the responsible pathogen, nor the clinical manifestations of SARS and the course of illness. There was no reliable diagnostic tool and no known effective therapy. But for the first time in medical history, we witnessed the rapid accumulation of knowledge on a disease as it evolved, which in turn assisted its management and control. / Since conducting randomized-controlled trials during the 2003 crisis was almost impossible, most of the presented studies are either descriptive or case-controlled in design. However, these studies have laid foundations for recent and future research into the clinical diagnosis and management of SARS. Moreover, the construction of the SARS clinical database has contributed to the work of other investigators, which has resulted in over thirty-six publications. It is my hope that these research endeavors can contribute to the understanding of this emerging, deadly disease. / Lee Lai Shun, Nelson. / "April 2006." / Source: Dissertation Abstracts International, Volume: 69-01, Section: B, page: 0205. / Thesis (M.D.)--Chinese University of Hong Kong, 2007. / Includes bibliographical references (p. 264-292). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Electronic reproduction. [Ann Arbor, MI] : ProQuest Information and Learning, [200-] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Abstracts in English and Chinese. / School code: 1307.

Despite high remission rate in acute myeloid leukaemia (AML) after chemotherapy, relapse of the underlying disease remains a major challenge and one of the most frequent causes of treatment failure. In this study, the presence of leukaemiaassociated phenotypes (LAPs) was first studied retrospectively using our standard diagnostic protocol with 3-colour flow cytometry. LAPs were present in 54 (64%) of 84 AML patients analysed between 2002 to 2004. The presence of LAPs was correlated with failure to respond to induction chemotherapy (p <0.05) in univariate analysis. Presence of LAPs was shown to be an independent predictor for failure to respond to induction chemotherapy with a relative risk ratio of 1.6 (p < 0.05, 95% CI, 1.0-2.6) in multivariate analysis. Subsequently, in a prospective study, we used 5-colour multiparametric flow cytometry (MFC) for detection of LAPs to determine if LAPs could be detected in a greater proportion of leukaemic patients and minimal residual disease (MRD) detection could therefore be applied in more patients. In 54 consecutive, newly diagnosed AML patients from 2005 to 2007, LAPs were identified in 51 (94%). Thus, MRD studies were potentially applicable to virtually all patients. The sensitivity and specificity of MFC technique was improved by analysing 10 normal and 5 regenerating bone marrows (BM) for the presence of these LAPs and by determining maximum log difference (LD). CD7, CD19, CD2, CD11b and CD56 were the most sensitive and reliable markers for MRD studies. LAPs were rarely detected in either normal or regenerating BMs. Through dilutional experiments from 50% LAPs to 0.001%, it was determined that 1 leukaemic in 104 and 105 normal cells could be detected using the improved techniques. Of the 54 patients, 31 received chemotherapy, with 27 achieving complete remission (CR). Two were LAP negative and thus 25 were evaluable for MRD post induction and 22-post consolidation chemotherapy. Detection of MRD >0.15% was able to distinguish between two groups of patients according to relapse status. Although, the number of patients was small, detection of MRD post induction > 0.15% was shown to be an independent predictor of adverse prognosis for both relapse free survival (RFS) and overall survival (OS) in a multivariate analysis [p = 0.037 and 0.026, 95% CI (1.1-20.5 and 1.2-22.2), hazard ratio 4.7 and 5.2 respectively]. Post consolidation, there was a trend for patients with higher MRD values to show shorter RFS (p = 0.06). MFC using 5-colour allows us to detect LAPs in virtually all AML patients and our preliminary results suggest the technique is a suitable approach for MRD analysis. However, 5-colour MFC is technically challenging, resource intensive, and may not be feasible in a routine diagnostic laboratory. This led us to assess whether we could identify other potential markers for LAPs. Interleukin-3 alpha receptor- chain IL-3_ (CD123) has been suggested to be a marker of leukaemic stem cells (LSC). These cells are thought to be responsible for initiating and maintaining leukaemic cell growth post chemotherapy and hence to give rise to relapse of the disease. Therefore, we analysed 34 AML patients for expression of CD123 in the blast population and defined a population containing leukaemic stem cells using the immunophenotypic markers CD123+/CD34+/CD38-. Thirty-two (94%) of AML patients expressed CD123. We then used a molecular marker to determine whether CD123 expression was confined to the LSC. Thirtynine patients were screened for the presence of FMS-like tyrosine kinase 3 - internal tandem duplication (FLT3/ITD) as the most common molecular abnormality in AML patients. Of those, 12 (31%) were FLT3/ITD positive. In seven of them, CD34+/CD38-/CD123+ and CD34+/CD38-/CD123- populations were sorted to homogeneity by Fluorescence Activated Cell Sorting (BD FACSAriaTM Cell Sorter) and tested for FLT3/ITD. In six of seven patients with FLT3/ITD positive AML, we could not detect the mutation in the CD34+/CD38-/CD123- fraction, but the mutation was detected in the CD34+/CD38-/CD123+ fraction in all seven patients. This novel finding demonstrates that, the oncogenic event occurs in CD123 positive cells, thus supporting the concept that CD123 is a marker of the LSC in CD123 positive AML. This observation suggests novel treatment approaches employing surface marker CD123-targeting antibodies may be of use in the treatment of AML. In conclusion, we demonstrate that using five-colour MFC improves LAP detection in AML and enables MRD studies using immunophenotyping to be applied to virtually all AML patients. Additionally, it increases the sensitivity of the technique for detecting LAP populations. Moreover, evaluation of MRD post induction chemotherapy is the most sensitive time point for detection of MRD, with MRD levels >0.15% predicting relapse and worse prognosis. As an alternative to using individualised LAPs specific to each patient, CD34+/CD38-/CD123+ cells may in the future serve as a better marker for MRD studies. This marker identifies the putative LSC, which is responsible for regrowth of leukaemia and relapse of the disease. Thus, instead of looking at whole “blast” population which results in huge data analysis and interpretation for the different LAPs which may have different underlying biology, it may be more informative to look at the frequency of LSC after achieving CR using CD34+/CD38-/CD123+ as the single LAP for MRD studies. / http://proxy.library.adelaide.edu.au/login?url= http://library.adelaide.edu.au/cgi-bin/Pwebrecon.cgi?BBID=1317088 / Thesis (Ph.D.) -- University of Adelaide, School of Medicine, 2008

<p>The aim was to identify diagnostic difficulties for acute abdominal pain at the emergency department and during hospital stay. A total of 3349 patients admitted to Mora Hospital with acute abdominal pain of up to seven days duration, were registered prospectively for history and clinical signs according to a structured schedule. The preliminary diagnosis from the attending physician at the emergency department, any investigations or surgery and final diagnosis were registered at a follow-up after at least one year. </p><p>There were no differences in diagnostic performance between physicians with 0.5 to 5 years of medical experience. The information collected and a careful examination of the patient was more important than formal competence. The main differential diagnostic problem was non-specific abdominal pain; this was the same for diagnoses requiring surgery. Patients originally diagnosed as not needing surgery had a median delay before operation of 22 hours (mean 40 hours, with 95% confidence interval of 30-50 hours), compared to 8 hours (mean 15 hours, 95% confidence interval of 12-28 hours) for patients with the same final follow-up diagnosis as the preliminary diagnosis. Constipation was a diagnostic pitfall, as 9% of the patients considered constipated required surgery for potentially life threatening reasons and 8% were later found to have an abdominal malignancy. Both the preliminary diagnosis and the discharge diagnosis were less reliable for elderly patients than for younger patients. Elderly patients often had specific organ disease and arrived at the emergency department after a longer history of abdominal pain. </p><p>This study confirms that assessment of suspected appendicitis can still be based on clinical judgements combined with laboratory tests. Classical clinical findings indicating localised inflammation, such as isolated pain in the right iliac fossa, rebound tenderness, right-sided rectal tenderness, pain migration to the right iliac fossa, local guarding and aggravation of pain when moving, were reliable for predicting acute appendicitis. A CT scan can be saved for the more equivocal cases of acute abdominal pain. A generous strategy regarding CT scan among elderly patients with acute abdominal pain, even in the absence of pronounced signs of an inflammatory intra-abdominal process, is recommended.</p>

Immune cells such as neutrophils and monocytes enter tissues after tissue damage and clear cell debris to allow repair cells such as fibroblasts to close the wound. Monocytes also differentiate into fibroblast-like cells called fibrocytes to mediate wound healing, similar to fibroblasts. However, in abnormal wound healing such as acute respiratory distress syndrome (ARDS) and fibrosing diseases, the accumulation of immune cells such as neutrophils or fibrocytes become detrimental to health. In ARDS, neutrophils accumulate in the lungs and causes additional damage by producing reactive oxygen species (ROS). In fibrosing diseases, increased fibrocyte differentiation is one of the causes that increase extracellular matrix deposition, which leads to severe scar tissue build up. Since there are no effective treatments for ARDS or fibrosing diseases, understanding the regulation of neutrophil activation or fibrocyte differentiation could be helpful to develop new effective therapies. The Gomer lab has found several factors that either promote or inhibit fibrocyte differentiation. The pro-fibrotic cytokines such as IL-4 and IL-13 potentiate fibrocyte differentiation while the plasma protein serum amyloid P (SAP), crosslinked IgG, and the pro-inflammatory cytokines IFN-γ and IL-12 inhibit fibrocyte differentiation. In this thesis, I have now shown that additional factors such as toll-like receptor 2 (TLR2) agonists and low molecular weight hyaluronic acid (LMWHA) inhibit fibrocyte differentiation, while high molecular weight hyaluronic acid (HMWHA) potentiate fibrocyte differentiation. The accumulation of neutrophils in the lungs is one of the major factors that debilitate the health of a patient in ARDS. Since neutrophils have Fc receptors, I examined the effect of SAP on neutrophil spreading, adherence, activation, and accumulation. SAP inhibits neutrophil spreading induced by cell debris and TNF-α induced adhesion, but SAP is unable to have any effect on classic neutrophil adhesion molecules or the production of hydrogen peroxide. SAP inhibits neutrophil accumulation in the lungs of bleomycin-injured mice. There is an exciting possibility of using SAP as a therapeutic agent to treat ARDS.

Diss. (sammanfattning) Stockholm : Karolinska institutet, 2010. / Härtill 5 uppsatser.