Safety, tolerability and efficacy of itraconazole and amphotericin B (AMB) were compared for empirical antifungal treatment of febrile neutropenic cancer patients. Patients and Methods: In an open, randomised study, 162 patients with at least 72 h of antimicrobial treatment received either intravenous followed by oral itraconazole suspension or intravenous AMB for a maximum of 28 days. Permanent discontinuation of study medication due to any adverse event was the primary safety parameter. Efficacy parameters included response and success rate for both treatment groups. Results: Significantly fewer itraconazole patients discontinued treatment due to any adverse event (22.2 vs. 56.8% AMB; p < 0.0001). The main reason for discontinuation was a rise in serum creatinine (1.2% itraconazole vs. 23.5% AMB). Renal toxicity was significantly higher and more drug-related adverse events occurred in the AMB group. Intention-to-treat (ITT) analysis showed favourable efficacy for itraconazole: response and success rate were both significantly higher than for AMB (61.7 vs. 42% and 70.4 vs. 49.3%, both p < 0.0001). Treatment failure was markedly reduced in itraconazole patients (25.9 vs. 43.2%), largely due to the better tolerability. Conclusions: Itraconazole was tolerated significantly better than conventional AMB and also showed advantages regarding efficacy. This study confirms the role of itraconazole as a useful and safe agent in empirical antifungal therapy of febrile neutropenic cancer patients. / Hintergrund: Es wurden die Sicherheit, Verträglichkeit und Wirksamkeit von Itraconazol und Amphotericin B (AMB) in der antimykotischen Therapie der persistierend febrilen Neutropenie verglichen. Patienten und Methoden: In einer offenen, randomisierten Studie erhielten 162 Patienten mit mindestens 72-stündiger antibiotischer Therapie entweder Itraconazol (erst intravenös, dann oral) oder AMB (intravenös) für maximal 28 Tage. Primärer Sicherheitsparameter war die dauerhafte Unterbrechung der Studienmedikation aufgrund von Nebenwirkungen. Die Wirksamkeitsparameter umfassten die Ansprech- und Erfolgsrate für beide Behandlungsgruppen. Ergebnisse: Signifikant weniger Itraconazol-Patienten brachen die Behandlung wegen Nebenwirkungen ab (22,2 vs. 56,8% AMB; p < 0,0001). Hauptursache für Studienabbrüche war der Anstieg des Serum-Kreatinin-Spiegels (1,2% Itraconazol vs. 23,5% AMB). Nephrotoxische und weitere Nebenwirkungen traten im AMB-Studienarm signifikant häufiger auf. Intention-to-Treat (ITT)-Analysen zeigten eine bessere Wirksamkeit von Itraconazol: Ansprech- und Erfolgsrate waren signifikant höher als unter AMB (61,7 vs. 42% und 70,4 vs. 49,3%, beide p < 0,0001). Behandlungsversagen trat bei Itraconazol-Patienten merklich weniger auf (25,9 vs. 43,2%). Schlussfolgerungen: Die Verträglichkeit von Itraconazol war signifikant höher als beim herkömmlichen AMB. Itraconazol zeigte ebenfalls Vorteile in der Wirksamkeit. Diese Studie bestätigt die Rolle von Itraconazol als sinnvolles und sicheres Medikament in der empirischen antimykotischen Therapie von fiebrigen neutropenischen Tumorpatienten. / Dieser Beitrag ist mit Zustimmung des Rechteinhabers aufgrund einer (DFG-geförderten) Allianz- bzw. Nationallizenz frei zugänglich.

Exploring the concepts of long range aerial transport of microorganisms is the main motivation of this study. For this purpose we use theories and concepts of dynamical systems in the context of geophysical fluid systems. We apply powerful notions such as finite-time Lyapunov exponent (FTLE) and the associated Lagrangian coherent structures (LCS) and we attempt to provide mathematical explanations and frameworks for some applied questions which are based on realistic concerns of atmospheric transport phenomena. Accordingly, we quantify the accuracy of prediction of FTLE-LCS features and we determine the sensitivity of such predictions to forecasting parameters. In addition, we consider the spatiotemporal resolution of the operational data sets and we propose the concept of probabilistic source and destination regions which leads to the definition of stochastic FTLE fields. Moreover, we put forward the idea of using ensemble forecasting to quantify the uncertainty of the forecast results. Finally, we investigate the statistical properties of localized measurements of atmospheric microbial structure and their connections to the concept of local FTLE time-series. Results of this study would pave the way for more efficient models and management strategies for the spread of infectious diseases affecting plants, domestic animals, and humans. / Ph. D.

The study undertook to explore the notion of stuckness within interpersonal and intrapersonal relationship dynamics. Stuckness has different presentations and can pertain to an individual’s’ inability to move beyond a particular challenge, or find resolution to one or more persistent problems. Alternatively, the stymied dynamic could manifest as a person becoming consistently highly activated or triggered. This has negative ramifications, within both interpersonal and intrapersonal relationships. Therapeutically, psychological stuckness is frequently encountered, and a lack of resolution of past trauma, is speculated as being a contributory factor. A qualitative, explorative research study was conducted over a period of one year, to collect data. The research design consisted of five case studies of participants who engaged in approximately one year of therapy. Participants were seen fortnightly, by a clinical psychologist, who is also the researcher of the study. The notes taken in the therapy sessions, as well as other qualitative methods, were utilised to collect the data. The data was analysed for themes formulated by the researcher, which themes correlated with the principles of the two schools of thought applied in the study. Logotherapy and somatic experiencing are the therapeutic interventions, which were included in the research method. These approaches were utilised in an endeavour to explore their efficacy, in resolving stuckness, speculated as being due to unprocessed trauma. Participation in the study was voluntary and boundaries of ethical codes, as well as values of psychotherapeutic therapy adhered to. There was no monetary exchange for the therapy received, and no costs incurred to the participants, in the research study. The presence of a long-standing persistent problem, or issue (stuckness) that had belied resolution, was the main criteria for inclusion in the study. The research explored the possible association between unresolved trauma, as well as various types of interpersonal, and intrapersonal stuckness. Impulsivity, explosive tempers, irrationality, emotionality and bizarre acting out behaviours, are some of the presentations, that the study speculated, as being due to unprocessed traumatic energy. A contribution of this research is that there is an absence of any prior studies conducted which explores stuckness and its correlation with unresolved trauma. In addition, no other research assessing the combined, top-down, and bottom-up efficacy of the therapeutic approaches of logotherapy and somatic experiencing were sourced. Payne, et al. (2015 b) state that they could not find evidence of more than five papers which provided case studies on somatic experiencing as a trauma intervention. The number of studies undertaken on somatic experiencing in general, is also significantly limited (Changaris, 2010; Samardzic, 2010). This adds to the value, meaning and purpose of this research, as it is a unique endeavour, motivated by the researcher’s intention to add more value to individuals’ lives, especially when the presenting problem, appears to be unfathomable stuckness. In an absence of any understanding for the reasons for such stuckness, these people may experience significant distress at being stymied, within the self, or in relation to others, as well as feel at a loss for any possible recourse. This study could prompt other researchers to conduct similar investigations, not only of the combined body-based, and cognitive psychotherapuetic interventions, but also of the link between stymied interpersonal, as well as intrapersonal relationship dynamics, and trauma. The application of a mind, body and soul approach in the study, through the inclusion of logotherapy, is also relevant. In reviewing the direction of psychological fields, one can detect that the trends are towards constructs such as meditation, enlightenment, consciousness, meaning, purpose, mindfulness, presence, and spiritual identity. Individuals are seeking more enlightenment, and want to explore more of the noetic dimension, which I believe psychotherapy has to include, in order to meet the needs of an evolving society. / Psychology / D.Phil. (Psychology)