Development, Implementation and Evaluation of a Quality Management System for Cross-Sectoral Psycho-Oncological Care in Germany

Introduction. High-quality psycho-oncology care enhances patients' satisfaction, adherence to treatment, and overall well-being. Because in Germany rendering consistent care faces difficulties such as fragmented health care systems, integrating a quality management system may address these challenges by ensuring consistent, evidence-based care, enhancing interprofessional collaboration, continuously improving quality, and optimising resource allocation. Objectives. The dissertation aims to develop, implement, and assess a quality management system for a multidisciplinary psycho-oncology approach care. Special attention is given to the development of quality indicators, the use of a participatory quality development approach, and the evaluation of the proposed concept. The purpose of this dissertation is to advance the furtherance of psycho-oncological care in Germany by identifying and assessing prospective measures and a quality management framework. Methods. An embedded mixed methods design was implemented with a focus on quantitative data. Quality indicator development was based on the RAND/UCLA Appropriateness Method in combination with a Delphi technique. Participatory tools were used in the continuous improvement process, and the level of participation was assessed through a longitudinal survey. To evaluate the implementation of the quality management system, a utility analysis was carried out. Results. A profound quality management system has been put in place comprising structural and procedural tools that cater to both internal and external necessities. A set of 16 quality indicators was operationalised and reviewed for relevance, comprehensibility, and suitability. The findings showcase that integrating a sustainable participatory quality development process into the quality management system is feasible but certain difficulties were also identified. The evaluation of the implementation of the quality management systems resulted in a utility score of 4.2 out of 5.0 (84.0%), indicating successful implementation. The implementation of top-down elements, such as contracts and manuals, was comprehensive, whereas bottom-up aspects, such as quality circles, presented more challenges. Conclusion. This dissertation successfully implemented a robust quality management system to enhance psycho-oncological care, achieving key objectives such as developing and digitally integrating comprehensive quality indicators. Despite successful stakeholder engagement, challenges in balancing bottom-up dynamics with top-down structures were identified, highlighting the crucial role of active leadership. The study underscores the importance of quality management, especially in the context of digital transformation and psycho-oncological care, emphasizing the need for further research on cost-effectiveness and implications of digital transformation

Resistance and the management of complicated skin and skin structure infections: the role of ceftobiprole

Antimicrobial resistant bacteria are an increasing concern due to the resulting increase in morbidity, mortality, and health-care costs associated with the administration of inadequate or delayed antimicrobial therapy. The implications of inadequate antimicrobial therapy in complicated skin and skin structure infections (cSSSIs) have gained more attention recently, most likely due to the recent emergence of community-acquired methicillin resistant Staphylococcus aureus (MRSA) and the already high prevalence of MRSA in the nosocomial setting. Due to the continuous threat of resistance arising and the limitations of currently available agents for the treatment of cSSSIs, it is necessary to develop new antimicrobials for this indication. Ceftobiprole medocaril, the prodrug of ceftobiprole, is a parental investigational cephalosporin for the treatment of cSSSIs displaying a wide-spectrum of activity against both Gram-positive and Gram-negative species, including MRSA. Ceftobiprole displays noncomplex linear pharmacokinetics, is eliminated primarily by glomerular filtration, and distributes to extracellular fluid. Additionally, it has been shown that the extent of distribution to the site of action with regard to cSSSIs, ie, the extracellular space fluid of subcutaneous adipose tissue and skeletal muscle, is expected to be efficacious, as free concentrations meet efficacy targets for most pathogens. Similar to other beta-lactams, it displays an excellent safety and tolerability profile with the primary adverse events being dysgeusia in healthy volunteers, resulting from the conversion of the prodrug to the active, and nausea in patients. Ceftobiprole has demonstrated noninferiority in two large-scale pivotal studies comparing it to vancomycin, clinical cure rates 93.3% vs 93.5%, respectively, or vancomycin plus ceftazidime, clinical cure rates 90.5% vs 90.2%, respectively. Given the pharmacokinetic and pharmacodynamic properties, ceftobiprole is a promising new agent for the treatment of cSSSIs and has the potential to be used as a single agent for empiric treatment

Comparison of the pharmacokinetic properties of vancomycin, linezolid, tigecyclin, and daptomycin

The rapid antibiotic resistance development has created a major demand for new antimicrobial agents that can combat resistant strains such as methicillin-resistant S. aureus (MRSA). Until a short time ago, the glycopeptide vancomycin was the only therapeutic choice in this situation. However, in recent years some newer agents with different mechanisms of actions have been added to the arsenal, and more are on the horizon. For a successful therapy it is of vital importance that these compounds are used judiciously and dosed appropriately. The present article reviews the pharmacokinetic properties of vancomycin, linezolid, tigecycline and daptomycin. The first major difference between these compounds is their oral bioavailability. Only linezolid can be administered orally, whereas vancomycin, daptomycin and tigecycline are limited to parenteral use. Once in the body, they show very different disposition. Daptomycin has a very small volume of distribution of 7L indicating very little tissue distribution whereas tigecycline has a very large volume of distribution of 350-500 L. Vancomycin and linezolid are in-between with volumes of distribution of approximately 30 and 50 L, close to total body water. However, studies have shown that linezolid shows better tissue penetration than vancomycin. Newer studies using microdialysis, a new technique that allows direct monitoring of unbound tissue levels, support this finding. As far as drug elimination, daptomycin and vancomycin are mainly eliminated into the urine and require dosing adjustments in renally impaired patients, whereas tigecycline is eliminated into the bile and linezolid is metabolized so that in renal patients no dosing adjustments are needed for these compounds. Although the elimination pathways are very different, the resulting half-lives of linezolid, vancomycin, and daptomycin are not greatly different and vary from 4-8 h. Tigecycline, however, has a much longer half-life of up to 1-2 days due to the slow redistribution from tissue binding sites

Nonlinear Response of Diffusive Superconductors to acac-electromagnetic Fields

Motivated by the recent experimental progress in studying conventional and unconventional superconductors in a pump-probe setup, we perform a comprehensive theoretical analysis of the nonlinear response of a diffusive BCS conventional superconductor to the action of an alternating electromagnetic field using a generalized Usadel equation. We analyze the response up to the second order of the perturbation in the amplitude of the vector potential $\vec{A}$, the superconducting order parameter $\Delta$ and in the third order for the current $\vec{j}$. On the basis of this approach, we derive general expressions for the retarded (advanced) Green's functions, as well as the Keldysh function for an arbitrary number of harmonics of the incident field. Most importantly, we analyze the set of physical observables in a non-equilibrium superconductor, such as frequency and the temperature dependencies of the zero harmonic $\delta( \Delta)_0$ (Eliashberg effect), the second harmonic $\delta( \Delta)_{2\Omega}$, as well as the third harmonic for the electric current $j(3\Omega)$ under the action of a monochromatic irradiation. For the same set of parameters, we also analyze the behavior of the reflectivity and the down-conversion intensity of a thin superconducting film, discussed recently in the context of parametric amplification of superconductivity. We derive these quantities microscopically and show the connection of the down-conversion intensity to the third harmonic generation currents induced by the amplitude mode and the direct action of the electric field on the charge carriers.Comment: 16 pages, 8 figure

Pharmacokinetics of Intranasal Scopolamine Gel Formation During Antiorthostatic Bedrest - A Microgravity Analog

Space Motion sickness (SMS) is an age old problem for astronauts on both short and long duration space flights. Scopolamine (SCOP) is the most frequently used drug for the treatment of motion sickness (MS) which is currently available in transdermal patch and tablet dosage forms. These formulations of SCOP are ineffective for the treatment of SMS. Intranasal dosage forms are noninvasive with rapid absorption and enhanced bioavailability thus allowing precise and reduced dosing options in addition to offering rescue and treatment options. As such, an intranasal gel dosage formulation of scopolamine (INSCOP) was developed and Pharmacokinetics (PK) and bioavailability were determined under IND guidelines. The present clinical trial compares PK and bioavailability of INSCOP in 12 normal, healthy subjects (6 male/ 6 female) during ambulation (AMB) and antiorthostatic bedrest (ABR) used as a ground-based microgravity analog. Subjects received 0.2 and 0.4 mg doses of INSCOP during AMB and ABR in a four-way crossover design. Results indicated no difference between AMB and ABR in PK parameters after 0.2 mg dose. Clearance (Cls) decreased with a concomitant increase in maximum concentration and area under concentration versus time curve (AUC) during ABR after the 0.4 mg dose. This difference in AUC and Cls at the higher but not the lower dose during ABR may suggest that ABR may affect metabolism and/or clearance at higher doses of INSCOP. These results indicate that dosing adjustment may be required for treatment of SMS with INSCOP in space

Inflight Pharmacokinetic and Pharmacodynamic Responses to Medications Commonly Used in Spaceflight

Researchers do not know if medications act the same in the spaceflight environment as they do on Earth. Aspects of the spaceflight environment (low gravity, radiation exposure, closed environment, stress) have been shown to alter human physiology. Some of these physiological changes could be expected to alter either pharmacokinetics (PK, how the body absorbs, distributes, metabolizes and excretes administered medications) or pharmacodynamics (PD, receptors or signaling systems that are the targets of medication action). Anecdotal data has suggested that, at least for certain medications or indications, inflight medication efficacy is poor. In order to prepare for exploration missions where speedy evacuation to Earth may not be a possibility, the likelihood of unexpected medication action must be determined

Importance of Relating Efficacy Measures to Unbound Drug Concentrations for Anti-Infective Agents

For the optimization of dosing regimens of anti-infective agents, it is imperative to have a good understanding of pharmacokinetics (PK) and pharmacodynamics (PD). Whenever possible, drug efficacy needs to be related to unbound concentrations at the site of action. For anti-infective drugs, the infection site is typically located outside plasma, and a drug must diffuse through capillary membranes to reach its target. Disease- and drug-related factors can contribute to differential tissue distribution. As a result, the assumption that the plasma concentration of drugs represents a suitable surrogate of tissue concentrations may lead to erroneous conclusions. Quantifying drug exposure in tissues represents an opportunity to relate the pharmacologically active concentrations to an observed pharmacodynamic parameter, such as the MIC. Selection of an appropriate specimen to sample and the advantages and limitations of the available sampling techniques require careful consideration. Ultimately, the goal will be to assess the appropriateness of a drug and dosing regimen for a specific pathogen and infection

Significant receptor affinities of metabolites and a degradation product of mometasone furoate

Mometasone furoate (MF) is a highly potent glucocorticoid used topically to treat inflammation in the lung, nose and on the skin. However, so far no information has been published on the human glucocorticoid receptor activity of the metabolites or degradation products of MF. We have now determined the relative receptor binding affinities of the known metabolite 6β-OH MF and the degradation product 9,11-epoxy MF to understand their possible contribution to undesirable systemic side effects. In competition experiments with human lung glucocorticoid receptors we have determined the relative receptor affinities (RRA) of these substances with reference to dexamethasone (RRA = 100). We have discovered that 6β-OH MF and 9,11-epoxy MF display RRAs of 206 ± 15 and 220 ± 22, respectively. This level of activity is similar to that of the clinically used inhaled corticosteroid flunisolide (RRA 180 ± 11). Furthermore we observed that 9,11-epoxy MF is a chemically reactive metabolite. In recovery experiments with human plasma and lung tissue we found a time dependent decrease in extractability of the compound. Hence, we provide data that might contribute to the understanding of the pharmacokinetics as well as the clinical effects of MF