Patient Relationship Management - Konzeption und Umsetzung

Zur Sicherstellung der gesundheitlichen Versorgung auf hohem Niveau werden Versicherte im Zuge einer politisch gewollten Förderung der Selbstverantwortung zunehmend an den Gesundheitskosten beteiligt. Hierdurch entwickeln sich Patienten – in Verbindung mit der steigenden Bedeutung des Gutes Gesundheit – zu mündigen Konsumenten. Als Mitentscheider in Therapiefragen und somit auch bei der Verschreibung eines Medikaments müssen Konsumenten pharmazeutischer Leistungen als Zielgruppe in die Marketingaktivitäten pharmazeutischer Unternehmen eingebunden werden. Insbesondere bei chronisch Kranken, die in der Regel verschreibungspflichtige Arzneimittel beziehen, lassen sich auf Grund der Langfristigkeit und Komplexität der Erkrankung umfangreiche Maßnahmen ableiten, um eine dauerhafte Beziehung zwischen pharmazeutischem Unternehmen und Patienten aufzubauen. Pharmaunternehmen müssen sich dieser Herausforderung stellen und den Wandel vom „Pillenproduzenten“ zum Versorgungsdienstleister vollziehen. Diese Studie stellt ein umfassendes Konzept des Patient Relationship Management (PRM) vor. Neben der Abgrenzung der für ein solches Konzept geeigneten Zielgruppe werden die Grundlagen und die zentralen Voraussetzungen für die Umsetzung eines erfolgreichen PRM diskutiert sowie Möglichkeiten zur Kontrolle der PRM-Aktivitäten vorgestellt

Trusted computing

Die Trusted Computing Initiative ist ein Zusammenschluss mehrerer Soft- und Hardwarehersteller, die sich zum Ziel gesetzt haben, Computersysteme sicherer zu machen. Es wird allgemein angenommen, dass Hardware schwerer zu manipulieren ist als Software. Vorhandene hardwaregestützte Sicherheitsmechanismen, wie z.B. Smartcards haben sich nicht durchsetzen können, da die Nutzung zu kompliziert und umständlich ist. Dies soll - mithilfe von Trusted Computing - durch die Verlagerung von Sicherheitsmechanismen in eine geschützte Hardwareumgebung, auf möglichst vielen Systemen, erreicht werden. Neue Softwarestandards sollen darauf aufbauend, komplexe und flexible Sicherheitsdienste anbieten können

Ring-Fencing in Europe

This dissertation explores structural reforms for banks that stipulate the separation of deposit-taking and other services considered vital to the real economy from certain investment banking activities deemed particularly risky with the aim of, inter alia, mitigating systemic risk and the too-big-to-fail problem. These structural reforms can collectively be referred to as “ring-fencing”. The focus of the dissertation is on the legal developments on a European Union level and in the United Kingdom, Germany and Switzerland, which are home to Europe’s most important financial centres. The dissertation is divided into three parts: In its first part, it establishes a concept and a definition of ring-fencing that allow to distinguish it from related bank structural reforms. In its second part, it assesses legislative steps already taken in the European Union and the withdrawal of the file by the European Commission and discusses potential alternatives for installing a union-wide ring-fence. In its third part, a legal comparative analysis is conducted, discussing conceptual differences in national bank structural reform legislation in the United Kingdom, Germany and Switzerland and exploring whether the countries adopted legislation that matches the concept and definition of ring-fencing established in the first part. Altogether, the dissertation contributes to the terminology and classification of existing and future ring-fencing initiatives and paints a comprehensive picture of current developments and prospects on EU level. It furthermore highlights structural differences of national approaches of Europe's three most important financial centres, and casts light on Switzerland’s unique yet barely recognized ring-fencing efforts

Functional and metabolic alterations in skeletal muscle in response to physiological and pathophysiological stressors.

Skeletal muscle performance is essential for our body’s movement as well as for the wholebody metabolism. In health and disease, skeletal muscle is exposed to various endogenous and exogenous stressors, influencing its physiological functions. In paper I, we showed that exercise performance and muscle force is affected by the stressor breast cancer, in a mouse model of breast cancer (PyMT). Mimicking the experienced muscle weakness of human breast cancer patients, PyMT mice performed poorly in a treadmill exhaustion run and their muscles produced less force than wildtype (WT) mice, although no difference in morphology, fiber type distribution or diameter was found. The muscle weakness was associated with an increase of pro-inflammatory cytokines, such as TNF-α in the skeletal muscle, activating the p38 mitogen-activated protein kinase (MAPK) stress-response pathway and decreasing the expression of mitochondrial electron transport chain (ETC) genes as well as antioxidant genes. After the mice had access to four weeks of voluntary running ad libitum, skeletal muscle force as well as the time and distance of the treadmill exhaustion run improved drastically for PyMT mice. The exercise also reduced the intramuscular stress, improved both the expression of mitochondrial ETC genes and the activity of key mitochondrial enzymes, such as citrate synthase (CS) and especially β-hydroxyacyl-CoA dehydrogenase (β-HAD) and restored the antioxidant defense system including superoxide dismutase (SOD 1,2). Additionally, we could show that the breast cancer blunted the exercise-induced expression of PPARγ coactivator-1α (Pgc-1α) in PyMT mice. Our results showed that breast cancer-induced weakness is linked to increased intramuscular stress signaling and that voluntary, moderate exercise was able to counteract the weakness in PyMT mice. Patients with breast cancer are treated with various systemic anti-cancer treatments, and while aiming to treat cancer, these treatments often cause side-effects. In paper II, we aimed to study the effect of a novel anti-tumorigenic compound (CX-5461) on the whole-body as well skeletal muscle-specific metabolism. Four weeks of CX-5461 treatment effectively reduced the breast cancer tumor in PyMT mice, but also resulted in increased food intake, energy expenditure and a higher respiratory exchange ratio (VCO2/VO2), indicative of a substrate shift towards carbohydrate utilization in both WT and PyMT mice. Moreover, basal blood glucose levels were increased, and we observed a slower glucose clearance from the blood stream in both WT and PyMT mice after CX-5461 treatment. Skeletal muscle is an important tissue involved in maintaining the body’s glucose homeostatic. In WT mice, CX-5461 treatment reduced the basal glucose uptake, whereas in PyMT mice the insulin-stimulated glucose uptake was affected in extensor digitorum longus (EDL) muscles. We found that CX-5461 not only exerts its mechanism of action, the inhibition of the RNA-Polymerase I (Pol I) pre-initiation complex, in breast cancer cells, but also directly in skeletal muscle and through that alters the glucose and fat metabolism in skeletal muscle. The results indicate that the novel drug CX-5461 affects the whole-body metabolism including elevated blood glucose levels and reduced glucose uptake into skeletal muscle, independently of the tumor development. Skeletal muscle is a highly metabolic tissue which functions can also be regulated by oxidative stress, cause by an imbalance in the endogenous oxidative and antioxidative system. In paper III, we investigated the role of the intermuscular redox state on glycogen phosphorylase activity and glycogenolysis, which supply the muscle with energy from glycogen storage during exercise. Glycogen phosphorylase was strongly inhibited by incubation with the reactive nitrogen species (RNS) peroxynitrite (ONOO- ), contrary to the reactive oxygen species (ROS) H2O2 in muscle extracts. In intact muscles, ONOOincubation resulted in inhibition of glycogenolysis in resting and contracting as well as a reduction of muscle force in slow-twitch oxidative soleus (SOL) and fast-twitch glycolytic EDL muscles, despite not exerting a direct effect on phosphorylase activity. Moreover, post-translational nitrate modification was observed in EDL muscle after ONOOincubation. Incubation with two antioxidants N-acetylcysteine (NAC) and dithiothreitol (DTT) did not affect phosphorylase activity or glycogenolysis, but reduced the force of EDL and SOL muscle. These results suggest that exogenous ONOOinhibits phosphorylase activity in muscle extracts and glycogenolysis in intact contracted muscles, whereas antioxidants such as DTT and NAC only play a minor role in inducing endogenous ROS and regulate the phosphorylase activity. All results from these three studies in this thesis investigate how the performance and function of skeletal muscle can be affected by different stressors. Taken together, a better understanding of the responsible underlying molecular mechanisms, might lead to targeted therapy approaches for afflicted patients in the future

Value-based marketing : die Ausrichtung der Marktbearbeitung am Kundennutzen

Trotz vermehrter Anstrengungen vieler Unternehmen in den letzten Jahren, sich stärker am Kunden zu orientieren, herrscht in der Praxis immer noch eine zu große Orientierung an den Preisen und den Kosten statt am eigentlichen Nutzen für den Kunden. Eine internationale Studie bei ca. 1.000 Unternehmen in Deutschland und in den USA hat gezeigt, dass der Preis bei der Bestimmung des Nettokundennutzens nur eine untergeordnete Rolle spielt. Vielmehr haben der Grund- und der Zusatznutzen für den Kunden einen erheblich größeren Einfluss auf die letztliche Beurteilung des Nettonutzens. Im folgenden soll aufgezeigt werden, wie Unternehmen ihre Marktbearbeitung am Kundennutzen ausrichten können und welche Instrumente und Maßnahmen zur Umsetzung geeignet sind

Zinkoxid in einer Formulierung zur Immunisierung über den Respirationstrakt

Active immunisation is the best option to prevent infectious diseases. Intramuscular application is the most commonly used administration route, because of systemic immune response and exact dosing possibilities. Due to its low cost and good effect, aluminium salts are the most frequently used adjuvants in adsorbate vaccines to enhance the immune response of an attenuated antigen or antigen components. While intramuscular administration requires the use of a needle and a sterile dosage form, mucosal immunisation is one opportunity of non-invasive administration. The respiratory tract comprises numerous immune competent cells as part of the MALT and thereby represents an excellent possibility to induce both local and systemic immune response. Since aluminium salts are ineffective as adjuvant on the mucosa, this work focussed on zinc oxide in formulations for respiratory vaccination. Zinc oxide is well characterised in a number of clinical studies and has many different uses. An immunomodulating effect of zinc oxide based on an increasing proliferation of T cells and high expression of MHC-II molecules is described in a number of papers. A special form of zinc oxide are the zinc oxide tetrapods. They have a three-dimensional tetrapodial structure and the potential uses are manifold due to their properties. Worth mentioning is the potential application as a prophylactic, preventive and/or adjuvant formulation for viral infection as they have among other things the ability to bind antigens. Viruses bound to zinc oxide tetrapods can therefore be absorbed by antigen-presenting cells in the mucosa and then presented to activate the immune system. In adsorption studies the adsorption capacity of zinc oxide, zinc oxide tetrapods, short milled and long milled zinc oxide tetrapods with five different proteins with varying isoelectric points and different molecular weights were investigated. While the zinc oxide tetrapods were able to adsorb mainly positively charged proteins due to their negatively charged surface, there was no discernible difference in the case of zinc oxide. All materials showed higher adsorption capacities towards the proteins with smaller molecular weights. Formulations for the delivery to the respiratory tract with zinc oxide were spray dried for nasal and pulmonary administration. Six different formulations with various amounts of zinc oxide were produced for each application route. Mannitol and hyaluronic acid were used as additional excipient and ovalbumin served as model antigen. Since spray drying with acetic acid (2 %) for the nasal formulations led to numerous difficulties in characterisation and undesired properties, the pulmonary formulations were spray dried with water as suspension medium. After spray drying, all six formulations were white powders with an x50 smaller than 5 µm and almost 100 % of the ovalbumin used was recovered. The composition of the formulation and thus the zinc oxide concentration had an influence on almost all experiments. Finally, cell activation experiments were performed to investigate whether zinc oxide presented its adjuvant effect when formulated as dry powder. Since formulation 2 showed the best aerodynamic properties for in-vivo studies, it was therefore used as example. The expression of CD80, CD86 and MHC-II indicated an activation of the used murine bone marrow-derived dendritic cells. The use of zinc oxide as an adjuvant thus appeared to be possible but needs to be further elucidated in in-vivo studies

Assessing the links between childhood trauma, C-reactive protein and response to antidepressant treatment in patients with affective disorders

Adverse Childhood Experiences (ACE) are a well-known risk-factor for depression. Additionally, (high-sensitive) C-reactive Protein (hsCRP) is elevated in subgroups of depressed patients and high following ACE. In this context the literature considers hsCRP and ACE to be associated with treatment resistant depression. With the data being heterogenous, this study aimed to explore the associations of ACE, hsCRP levels and response to antidepressant treatment in uni- and bipolar depression. N = 76 patients diagnosed with uni- or bipolar depression and N = 53 healthy controls were included. Treatment was over 6~weeks in an inpatient psychiatric setting within an observatory study design. Depressive symptoms were assessed by the Montgomery-Asberg Depression Rating Scale (MADRS), ACE were assessed by the Childhood Trauma Questionnaire (CTQ); the body-mass-index (BMI) and hsCRP were measured. HsCRP levels did not differ between the study population and the healthy controls. While the depressive symptoms decreased, the hsCRP levels increased. Sexual abuse was associated with significant higher and emotional abuse with lower levels of hsCRP after 6~weeks. The baseline hsCRP levels and the ACE subgroups did not~show significant associations with the treatment response in unipolar depressed patients. The long-lasting effects of specific forms of ACE may have relevant impact on inflammation, supporting hsCRP to be a suitable biomarker. With ACE and hsCRP not showing any significant associations with treatment response in the unipolar depressed subgroup, a more differentiate research concerning biomarkers and treatment regimens is needed when talking about treatment response