Interdependenzen von Arzneimittelregulierungen

In diesem Buch werden die diversen Steuerungsinstrumente des deutschen Arzneimittelmarktes und deren Zusammenhänge analysiert. Dies beinhaltet unter anderem die Festbetragsregelungen, Höchstbeträge, Rabattverträge, Zuzahlungsbefreiungsregelungen, Aut-Idem-Regelung, Zielvereinbarungen, die Kosten-Nutzen-Bewertung oder Wirtschaftlichkeitsprüfungen. Ausgehend von der Darstellung der jeweiligen Funktionsweise und der daraus resultierenden Anreize für die Akteure im Gesundheitswesen werden sukzessive weitere Regulierungsinstrumente eingeführt, um den Grad der Interaktionen, der Duplizität und der Folgen darzustellen. Aufgrund der Anzahl der Instrumente und der Komplexität der Gesamtstruktur dienen vereinfachende, beispielhafte Rechnungen der Veranschaulichung

Interdependenzen von Arzneimittelregulierungen

In diesem Buch werden die diversen Steuerungsinstrumente des deutschen Arzneimittelmarktes und deren Zusammenhänge analysiert. Dies beinhaltet unter anderem die Festbetragsregelungen, Höchstbeträge, Rabattverträge, Zuzahlungsbefreiungsregelungen, Aut-Idem-Regelung, Zielvereinbarungen, die Kosten-Nutzen-Bewertung oder Wirtschaftlichkeitsprüfungen. Ausgehend von der Darstellung der jeweiligen Funktionsweise und der daraus resultierenden Anreize für die Akteure im Gesundheitswesen werden sukzessive weitere Regulierungsinstrumente eingeführt, um den Grad der Interaktionen, der Duplizität und der Folgen darzustellen. Aufgrund der Anzahl der Instrumente und der Komplexität der Gesamtstruktur dienen vereinfachende, beispielhafte Rechnungen der Veranschaulichung

Biologic TNF inhibiting agents for treatment of rheumatoid arthritis: persistence and dosing patterns in Germany

Objective: To obtain detailed real-world data on persistence and dosing patterns in the utilisation of the TNF inhibitors adalimumab, etanercept, and infliximab in rheumatoid arthritis (RA) patients treated in Germany. Methods: In this retrospective observational study claims data of a major German health insurance fund between 2005 and 2008 were analysed. Patients receiving at least one prescription of adalimumab, etanercept or infliximab were identified and categorised as "TNF inhibitor naive" or "TNF inhibitor continuing". For the calculation of TNF inhibitor persistence a survival analysis with the Kaplan-Meier estimator was used. A Cox regression was used to analyse, if any relevant factors were influencing persistence. Dosage increase rates were analysed for adalimumab, etanercept and infliximab. Sensitivity analyses based on variations in gap length were conducted. Results: A total of 2,201 RA patients were identified. 1,468 of these patients were TNF inhibitor naive patients and 733 were defined as TNF inhibitor continuing patients. There were no significant differences in the treatment persistence rates between adalimumab, etanercept and infliximab for TNF inhibitor naive and continuing patients. The persistence rate after three years was 22.47% for adalimumab, 24.27% for etanercept and 21.49% for infliximab naive patients. For continuing patients, the persistence rate after three years was 32.88% for adalimumab, 30.95% for etanercept, and 33.90% for infliximab, respectively. Gender, medication and Charlson Comorbidities Index did not influence the persistence significantly. Dosage increase occurred in 7.3% adalimumab, 1.4% etanercept, and 17.2% infliximab naive patients and 5.8%, 1.1% and 11.9% respectively in the continuing patients. Conclusions: In this study, there were no significant differences in persistence among adalimumab, etanercept and infliximab treated patients. Consistent with previous research, there was a higher dose escalation for infliximab than for the two subcutaneous treatments, adalimumab or etanercept

Cadmium induces Wnt signaling to upregulate proliferation and survival genes in sub-confluent kidney proximal tubule cells

<p>Abstract</p> <p>Background</p> <p>The class 1 carcinogen cadmium (Cd²⁺) disrupts the E-cadherin/β-catenin complex of epithelial adherens junctions (AJs) and causes renal cancer. Deregulation of E-cadherin adhesion and changes in Wnt/β-catenin signaling are known to contribute to carcinogenesis.</p> <p>Results</p> <p>We investigated Wnt signaling after Cd²⁺-induced E-cadherin disruption in sub-confluent cultured kidney proximal tubule cells (PTC). Cd²⁺(25 μM, 3-9 h) caused nuclear translocation of β-catenin and triggered a Wnt response measured by TOPflash reporter assays. Cd²⁺reduced the interaction of β-catenin with AJ components (E-cadherin, α-catenin) and increased binding to the transcription factor TCF4 of the Wnt pathway, which was upregulated and translocated to the nucleus. While Wnt target genes (<it>c-Myc</it>, <it>cyclin D1 </it>and <it>ABCB1</it>) were up-regulated by Cd²⁺, electromobility shift assays showed increased TCF4 binding to <it>cyclin D1 </it>and <it>ABCB1 </it>promoter sequences with Cd²⁺. Overexpression of wild-type and mutant TCF4 confirmed Cd²⁺-induced Wnt signaling. Wnt signaling elicited by Cd²⁺was not observed in confluent non-proliferating cells, which showed increased E-cadherin expression. Overexpression of E-cadherin reduced Wnt signaling, PTC proliferation and Cd²⁺toxicity. Cd²⁺also induced reactive oxygen species dependent expression of the pro-apoptotic ER stress marker and Wnt suppressor CHOP/GADD153 which, however, did not abolish Wnt response and cell viability.</p> <p>Conclusions</p> <p>Cd²⁺induces Wnt signaling in PTC. Hence, Cd²⁺may facilitate carcinogenesis of PTC by promoting Wnt pathway-mediated proliferation and survival of pre-neoplastic cells.</p

Nutzung von Sozialen Netzwerk-Plattformen für die Verteilung von Public Keys

Public Key Infrastrukturen (PKI) sind schon seit einigen Jahren bekannt, jedoch setzen sie sich nur sehr zögerlich durch, insbesondere im privaten Bereich. In diesem Artikel werden einige Hürden für die existierenden Ansätze (besonders das Web-of-Trust) beschrieben und es wird ein Lösungsansatz vorgestellt, der auf der Integration von sozialen Netzwerk-Plattformen mit den bestehenden Schlüssel-Servern beruht. Eine prototypische Umsetzung der genannten Ansätze zeigt, dass diese praktisch einsetzbar sind und die Usability von PKI verbessern können

Neuroticism developmental courses - implications for depression, anxiety and everyday emotional experience; a prospective study from adolescence to young adulthood

Background: Neuroticism is frequently discussed as a risk factor for psychopathology. According to the maturity principle, neuroticism decreases over the course of life, but not uniformly across individuals. However, the implications of differences in personality maturation on mental health have not been well studied so far. Hence, we hypothesized that different forms of neuroticism development from adolescence to young adulthood are associated with differences in depression, anxiety and everyday emotional experience at the age of 25. Methods: A sample of 266 adolescents from the general population was examined three times over ten years (age at T0: 15, T1: 20 and T2: 25) using questionnaires, interviews and ecological momentary assessment (EMA). At all measurement points, neuroticism was assessed with the NEO inventory. At T2, diagnoses of major depression and anxiety disorders were captured with a structured clinical interview (M-CIDI). Phone-based EMA was used to assess emotional experience and affective instability over a two-week period at T2. Results: The best fitting model was a latent class growth analysis with two groups of neuroticism development. Most individuals (n = 205) showed moderate values whereas 61 participants were clustered into a group with elevated neuroticism levels. In both groups neuroticism significantly changed during the ten year period with a peak at the age of 20. Individuals with a higher absolute level were at 14-fold increased risk for depression and 7-fold risk for anxiety disorders at the age of 25. In EMA, increased negative affect and arousal as well as decreased positive emotions were found in this high group. Conclusions: Other than expected, personality did not mature in our sample. However, there was a significant change of neuroticism values from adolescence to young adulthood. Further, over 20% of our participants showed a neuroticism development which was associated with adverse outcomes such as negatively toned emotional experience and a heightened risk to suffer from depressive and anxiety disorders in young adulthood. These high-risk persons need to be identified early to provide interventions supporting continuous personality maturation

Does Emotion Dysregulation Mediate the Relationship between Early Maltreatment and Later Substance Dependence? Findings of the CANSAS Study

Background/Aims: Maltreatment in childhood and adolescence is a risk factor for substance use disorders (SUDs) in adulthood. This association has rarely been investigated in the light of emotion dysregulation. To fill this gap, this study examines emotion dysregulation and SUDs among adults with a history of early maltreatment. Methods: Comparison of emotion dysregulation in adults with a history of early abuse and neglect who developed either an SUD (n = 105) or no mental disorder (n = 54). Further, a mediation model for the association between the severity of early maltreatment and SUDs was tested. Participants completed research diagnostic interviews for psychopathology, the Difficulties in Emotion Regulation Scale, and the Childhood Trauma Questionnaire. Results: By using hierarchical regression techniques and mediational analyses controlling for age and gender, it was possible to provide evidence for the mediating role of emotion dysregulation between early emotional and physical maltreatment and later SUDs. Conclusions: Emotion dysregulation is a potential mechanism underlying the relationship between early emotional and physical maltreatment and the development of SUDs. In light of these findings, focusing on the early training of adaptive emotion regulation strategies after childhood maltreatment might be of considerable relevance to prevent the development of SUDs

Differences in mortality in critically ill elderly patients during the second COVID-19 surge in Europe

The primary aim of this study was to assess the outcome of elderly intensive care unit (ICU) patients treated during the spring and autumn COVID-19 surges in Europe. This was a prospective European observational study (the COVIP study) in ICU patients aged 70 years and older admitted with COVID-19 disease from March to December 2020 to 159 ICUs in 14 European countries. An electronic database was used to register a number of parameters including: SOFA score, Clinical Frailty Scale, co-morbidities, usual ICU procedures and survival at 90 days. The study was registered at ClinicalTrials.gov (NCT04321265). In total, 2625 patients were included, 1327 from the first and 1298 from the second surge. Median age was 74 and 75 years in surge 1 and 2, respectively. SOFA score was higher in the first surge (median 6 versus 5, p < 0.0001). The PaO/FiO ratio at admission was higher during surge 1, and more patients received invasive mechanical ventilation (78% versus 68%, p < 0.0001). During the first 15 days of treatment, survival was similar during the first and the second surge. Survival was lower in the second surge after day 15 and differed after 30 days (57% vs 50%) as well as after 90 days (51% vs 40%). An unexpected, but significant, decrease in 30-day and 90-day survival was observed during the second surge in our cohort of elderly ICU patients. The reason for this is unclear. Our main concern is whether the widespread changes in practice and treatment of COVID-19 between the two surges have contributed to this increased mortality in elderly patients. Further studies are urgently warranted to provide more evidence for current practice in elderly patients. , registered March 19th, 2020. The online version contains supplementary material available at 10.1186/s13054-021-03739-7

Variations in end-of-life care practices in older critically ill patients with COVID-19 in Europe

BACKGROUND: Previous studies reported regional differences in end-of-life care (EoLC) for critically ill patients in Europe. OBJECTIVES: The purpose of this post-hoc analysis of the prospective multi-centre COVIP study was to investigate variations in EoLC practices among older patients in intensive care units during the coronavirus disease 2019 pandemic. METHODS: A total of 3105 critically ill patients aged 70 years and older were enrolled in this study (Central Europe: n = 1573; Northern Europe: n = 821; Southern Europe: n = 711). Generalised estimation equations were used to calculate adjusted odds ratios (aOR) to population averages. Data were adjusted for patient-specific variables (demographic, disease-specific) and health economic data (GDP, health expenditure per capita). The primary outcome was any treatment limitation, and 90-day-mortality was a secondary outcome. RESULTS: The frequency of the primary endpoint (treatment limitation) was highest in Northern Europe (48%), intermediate in Central Europe (39%), and lowest in Southern Europe (24%). The likelihood for treatment limitations was lower in Southern than in Central Europe (aOR 0.39; 95%CI 0.21-0.73; p = 0.004), even after multivariable adjustment, whereas no statistically significant differences were observed between Northern and Central Europe (aOR 0.57; 95%CI 0.27-1.22; p = 0.15). After multivariable adjustment, no statistically relevant mortality differences were found between Northern and Central Europe (aOR 1.29; 95%CI 0.80-2.09; p = 0.30) or between Southern and Central Europe (aOR 1.07; 95%CI 0.66-1.73; p = 0.78). CONCLUSION: This study shows a north-to-south gradient in rates of treatment limitation in Europe, highlighting the heterogeneity of EoLC practices across countries. However, mortality rates were not affected by these results. This article is protected by copyright. All rights reserved.publishersversionepub_ahead_of_prin