Frequency and potential reasons

Background: Generic substitution can have unintended consequences. In Germany, brand name to generic or generic to generic switching is mainly driven by rebate contracts. Frequent switching may raise concerns about bio-and therapeutic equivalence. Expected patient confusion may result in compromised medication adherence or new onset of other drug-related problems. Since 2008, pharmacists are allowed to deviate from rebate contracts by denying substitution due to pharmaceutical concerns on an individual basis. Objectives: To explore the frequency of documented pharmaceutical concerns in Germany between July 2011 and December 2013 and to identify the medicines most frequently related to pharmaceutical concerns in 2013. Methods: We analyzed documented pharmaceutical concerns in all prescribed drugs at the expense of any statutory health insurance company requiring pharmacies’ generic substitution according to rebate contracts. Results: Since July 2011, the frequency of documented pharmaceutical concerns in relation to prescribed drug products with rebate contracts requiring substitution increased consistently and doubled between July 2011 and July 2013. Overall in 2013, the trend of the two previous years continued and reached approximately 1.5%. The most affected drugs/drug classes were thyroid hormones (in particular combinations with iodide; 15.9%) followed by ondansetron (12.5%), and levothyroxine (11.3%). For all drugs/drug classes under investigation, product-, patient-or disease- related aspects could be identified which are potential reasons to deny substitution and to document pharmaceutical concerns. Conclusions: Although there is no electronic recording of the specific reasons for pharmaceutical concerns in claims data, our analyses support the assumption that pharmacists make use of this instrument based on individual clinical decisions and as required by contract. Pharmaceutical concerns are, therefore, an important instrument for pharmacies to refuse generic substitution. They are considered to prevent compromised medication safety and to assure pharmacotherapy effectiveness in a generic substitution environment driven by low drug prizes above all. © 2016, Grupo de Investigacion en Atencion Farmaceutica. All rights reserved

Assessment of the Prescriptions of Systemic Antibiotics in Primary Dental Care in Germany from 2017 to 2021: A Longitudinal Drug Utilization Study

(1) Background: Due to increasing antibiotic resistance, the frequency of antibiotic use should be questioned in dentistry and attention paid to the choice of the best suited substance according to guidelines. In Germany, overprescribing of clindamycin was noteworthy in the past. Therefore, the aim of our study was to determine the trend of antibiotic prescriptions in primary dental care. (2) Methods: Prescriptions of antibiotics in German primary dental care from 2017 to 2021 were analysed using dispensing data from community pharmacies, claimed to the statutory health insurance (SHI) funds, and compared with all antibiotic prescriptions in primary care. Prescriptions were analysed based on defined daily doses per 1000 SHI-insured persons per day (DID). (3) Results: Amoxicillin was the most frequently prescribed antibiotic (0.505 DID in 2017, 0.627 in 2021, +24.2%) in primary dental care, followed by clindamycin (0.374 DID in 2017, 0.294 in 2021, −21.4%). Dental prescriptions still made up 56% of all clindamycin prescriptions in primary care in 2021. (4) Conclusions: Our study suggests that the problem of overuse of clindamycin in German dentistry has improved, but still persists

Künstlersozialversicherungsgesetz: Hintergründe und aktuelle Anforderungen

"Die Autoren informieren in diesem Buch über die Entwicklung der Künstlersozialversicherung. Die Grundsätze der Künstlersozialversicherung und die einzelnen Reformschritte werden skizziert. Die Autoren stellen den Arbeitsmarkt Kultur vor und bereiten aktuelle Daten zur wirtschaftlichen und sozialen Lage von Künstlern und Publizisten auf. Die Sonderstellung der Künstlersozialversicherung im Sozialversicherungssystem wird geschildert und die Autoren gehen auch auf die künftigen Herausforderungen zur Sicherung der Künstlersozialversicherung ein. Besonderen Raum nehmen die Maßnahmen zur Reform des Künstlersozialversicherungsgesetzes im Jahr 2007 ein." (Autorenreferat

Vitamin D receptor regulates intestinal proteins involved in cell proliferation, migration and stress response

BACKGROUND: Genome-wide association studies found low plasma levels of 25-hydroxyvitamin D and vitamin D receptor (VDR) polymorphisms associated with a higher prevalence of pathological changes in the intestine such as chronic inflammatory bowel diseases. METHODS: In this study, a proteomic approach was applied to understand the overall physiological importance of vitamin D in the small intestine, beyond its function in calcium and phosphate absorption. RESULTS: In total, 569 protein spots could be detected by two-dimensional-difference in-gel electrophoresis (2D-DIGE), and 82 proteins were considered as differentially regulated in the intestinal mucosa of VDR-deficient mice compared to that of wildtype (WT) mice. Fourteen clearly detectable proteins were identified by MS/MS and further analyzed by western blot and/or real-time RT-PCR. The differentially expressed proteins are functionally involved in cell proliferation, cell adhesion and cell migration, stress response and lipid transport. Mice lacking VDR revealed higher levels of intestinal proteins associated with proliferation and migration such as the 37/67 kDa laminin receptor, collagen type VI (alpha 1 chain), keratin-19, tropomyosin-3, adseverin and higher levels of proteins involved in protein trafficking and stress response than WT mice. In contrast, proteins that are involved in transport of bile and fatty acids were down-regulated in small intestine of mice lacking VDR compared to WT mice. However, plasma and liver concentrations of cholesterol and triglycerides were not different between the two groups of mice. CONCLUSION: Collectively, these data imply VDR as an important factor for controlling cell proliferation, migration and stress response in the small intestine

Biological Surface Coating and Molting Inhibition as Mechanisms of TiO2 Nanoparticle Toxicity in Daphnia magna

The production and use of nanoparticles (NP) has steadily increased within the last decade; however, knowledge about risks of NP to human health and ecosystems is still scarce. Common knowledge concerning NP effects on freshwater organisms is largely limited to standard short-term (≤48 h) toxicity tests, which lack both NP fate characterization and an understanding of the mechanisms underlying toxicity. Employing slightly longer exposure times (72 to 96 h), we found that suspensions of nanosized (∼100 nm initial mean diameter) titanium dioxide (nTiO2) led to toxicity in Daphnia magna at nominal concentrations of 3.8 (72-h EC50) and 0.73 mg/L (96-h EC50). However, nTiO2 disappeared quickly from the ISO-medium water phase, resulting in toxicity levels as low as 0.24 mg/L (96-h EC50) based on measured concentrations. Moreover, we showed that nTiO2 (∼100 nm) is significantly more toxic than non-nanosized TiO2 (∼200 nm) prepared from the same stock suspension. Most importantly, we hypothesized a mechanistic chain of events for nTiO2 toxicity in D. magna that involves the coating of the organism surface with nTiO2 combined with a molting disruption. Neonate D. magna (≤6 h) exposed to 2 mg/L nTiO2 exhibited a “biological surface coating” that disappeared within 36 h, during which the first molting was successfully managed by 100% of the exposed organisms. Continued exposure up to 96 h led to a renewed formation of the surface coating and significantly reduced the molting rate to 10%, resulting in 90% mortality. Because coating of aquatic organisms by manmade NP might be ubiquitous in nature, this form of physical NP toxicity might result in widespread negative impacts on environmental health

Hexamoll(R) DINCH and DPHP metabolites in urine of children and adolescents in Germany: Human biomonitoring results of the German Environmental Survey GerES V, 2014-2017

The production and use of the plasticisers Hexamoll(R) DINCH (di-(iso-nonyl)-cyclohexane-1,2-dicarboxylate) and DPHP (di-(2-propylheptyl) phthalate) have increased after both chemicals were introduced into the market in the early 2000s as substitutes for restricted high molecular weight phthalates. During the population representative German Environmental Survey (GerES) of Children and Adolescents (GerES V, 2014–2017), we collected urine samples and measured the concentrations of DINCH and DPHP metabolites in 2228 and in a subsample of 516 participants, respectively. We detected DINCH and DPHP metabolites in 100% and 62% of the 3-17 years old children and adolescents, respectively. Geometric means of DINCH metabolites were 2.27 μg/L for OH-MINCH, 0.93 μg/L for oxo-MINCH, 1.14 μg/L for cx-MINCH and 3.47 μg/L for DINCH (Σ of OH-MINCH + cx-MINCH). Geometric means of DPHP metabolites were 0.30 μg/L for OH-MPHP, 0.32 µg/L for oxo-MPHP and 0.64 μg/L for DPHP (Σ of OH-MPHP + oxo-MPHP). The 3-5 years old children had almost 3-fold higher DINCH biomarkers levels than adolescents (14-17 years). Higher concentrations of DPHP biomarkers among young children only became apparent after creatinine adjustment. Urinary levels of DINCH but not of DPHP biomarkers were associated with the levels of the respective plasticisers in house dust. When compared to HBM health-based guidance values, we observed no exceedance of the HBM-I value of 1 mg/L for DPHP (Σ of OH-MPHP + oxo-MPHP). However, 0.04% of the children exceeded the health based guidance value HBM-I of 3 mg/L for DINCH (Σ of OH-MINCH + cx-MINCH). This finding shows that even a less toxic replacement of restricted chemicals can reach exposures in some individuals, at which, according to current knowledge, health impacts cannot be excluded with sufficient certainty. In conclusion, we provide representative data on DINCH and DPHP exposure of children and adolescents in Germany. Further surveillance is warranted to assess the substitution process of plasticisers, and to advise exposure reduction measures, especially for highly exposed children and adolescents. Providing the results to the European HBM Initiative HBM4EU will support risk assessment and risk management not only in Germany but also in Europe

A dose-controlled system for air-liquid interface cell exposure and application to zinc oxide nanoparticles

<p>Abstract</p> <p>Background</p> <p>Engineered nanoparticles are becoming increasingly ubiquitous and their toxicological effects on human health, as well as on the ecosystem, have become a concern. Since initial contact with nanoparticles occurs at the epithelium in the lungs (or skin, or eyes), <it>in vitro </it>cell studies with nanoparticles require dose-controlled systems for delivery of nanoparticles to epithelial cells cultured at the air-liquid interface.</p> <p>Results</p> <p>A novel air-liquid interface cell exposure system (ALICE) for nanoparticles in liquids is presented and validated. The ALICE generates a dense cloud of droplets with a vibrating membrane nebulizer and utilizes combined cloud settling and single particle sedimentation for fast (~10 min; entire exposure), repeatable (<12%), low-stress and efficient delivery of nanoparticles, or dissolved substances, to cells cultured at the air-liquid interface. Validation with various types of nanoparticles (Au, ZnO and carbon black nanoparticles) and solutes (such as NaCl) showed that the ALICE provided spatially uniform deposition (<1.6% variability) and had no adverse effect on the viability of a widely used alveolar human epithelial-like cell line (A549). The cell deposited dose can be controlled with a quartz crystal microbalance (QCM) over a dynamic range of at least 0.02-200 μg/cm². The cell-specific deposition efficiency is currently limited to 0.072 (7.2% for two commercially available 6-er transwell plates), but a deposition efficiency of up to 0.57 (57%) is possible for better cell coverage of the exposure chamber.</p> <p>Dose-response measurements with ZnO nanoparticles (0.3-8.5 μg/cm²) showed significant differences in mRNA expression of pro-inflammatory (IL-8) and oxidative stress (HO-1) markers when comparing submerged and air-liquid interface exposures. Both exposure methods showed no cellular response below 1 μg/cm²ZnO, which indicates that ZnO nanoparticles are not toxic at occupationally allowed exposure levels.</p> <p>Conclusion</p> <p>The ALICE is a useful tool for dose-controlled nanoparticle (or solute) exposure of cells at the air-liquid interface. Significant differences between cellular response after ZnO nanoparticle exposure under submerged and air-liquid interface conditions suggest that pharmaceutical and toxicological studies with inhaled (nano-)particles should be performed under the more realistic air-liquid interface, rather than submerged cell conditions.</p

Jung und Alt im Hörsaal:Erfahrungen jüngerer Studierender mit dem „Studium im Alter“ an der Universität Münster

Das „Studium im Alter“ ist ein Weiterbildungsangebot der Universität Münster für Personen im mittleren und höheren Lebensalter, die als Gasthörer gemeinsam mit jüngeren, regulären Studierenden Vorlesungen und Seminare an der Hochschule besuchen. In der Presse erschienen von Zeit zu Zeit Berichte über Konflikte, die das Gaststudium der Älteren in den Hörsälen verursacht. Das nahm eine Gruppe von Teilnehmern am „Studium im Alter“ zum Anlass, in einem zweisemestrigen Forschungsprojekt zu untersuchen, inwiefern solche Berichte die Regel oder Einzelfälle beschreiben. Das Ergebnis der schriftlichen Befragung regulärer Studierender zu Ihren Erfahrungen mit Studierenden im Alter liegt mit dieser Studie vor. Abgesehen von wenigen Ausnahmen belegt sie ein grundsätzlich harmonisches Miteinander von jüngeren und älteren Studierenden in den Hörsälen der Universität Münster