Zusammenfassung
Real-World-Daten rücken im Rahmen der Digitalisierung immer mehr in den Fokus der Versorgungsforschung. Die zeitnahe Verfügbarkeit von großen Datenmengen lässt hoffen, dass ...Forschungsfragen ohne zusätzliche Datenerhebung schnell beantwortet und ein direkter Nutzen für die Versorgung von Menschen erreicht werden kann. Gerade in akuten Versorgungslagen, wie Hitzewellen oder einer Pandemie, kann dies entscheidend sein. Doch hängen die Real-World-Daten ganz maßgeblich von der Qualität und Intention der Datenerhebung ab. Sie werden auch durch Festlegungen auf semantische und syntaktische Standards beeinflusst, die für Primärdaten getroffen werden – oft mit heterogenen Zielsetzungen. Im Rahmen der verschiedenen Initiativen auf nationaler wie auf internationaler Ebene sollten deshalb ein holistischer Blick auf Datenerhebung und Auswertung und ein regelhafter Rückkopplungsmechanismus zwischen Datenauswertung und Festlegungen für die Erhebung angestrebt werden. Durch eine Einbeziehung von Anforderungen an die sekundäre Datenauswertung in die Festlegungsprozesse für die Datenerhebung kann die Aussagekraft der Daten für die Forschung langfristig erhöht werden.
In diesem Diskussionsbeitrag werden zunächst die Aktivitäten zur standardisierten Datenerfassung im Rahmen der Digitalisierungsinitiativen und die entsprechenden europäischen Ansätze dargestellt. Anhand der Auswirkungen dieser Aktivitäten auf Möglichkeiten und Schwierigkeiten der Datenzusammenführung für Analysen von Real-World-Daten wird schließlich im Beitrag für einen anhaltenden Diskurs zwischen den verschiedenen Bereichen geworben.
The International Classification of Diseases (ICD) has long been the main basis for comparability of statistics on causes of mortality and morbidity between places and over time. This paper provides ...an overview of the recently completed 11th revision of the ICD, focusing on the main innovations and their implications.
Changes in content reflect knowledge and perspectives on diseases and their causes that have emerged since ICD-10 was developed about 30 years ago. Changes in design and structure reflect the arrival of the networked digital era, for which ICD-11 has been prepared. ICD-11's information framework comprises a semantic knowledge base (the Foundation), a biomedical ontology linked to the Foundation and classifications derived from the Foundation. ICD-11 for Mortality and Morbidity Statistics (ICD-11-MMS) is the primary derived classification and the main successor to ICD-10. Innovations enabled by the new architecture include an online coding tool (replacing the index and providing additional functions), an application program interface to enable remote access to ICD-11 content and services, enhanced capability to capture and combine clinically relevant characteristics of cases and integrated support for multiple languages.
ICD-11 was adopted by the World Health Assembly in May 2019. Transition to implementation is in progress. ICD-11 can be accessed at icd.who.int.
Abstract
Podocytes are highly specialized cells playing a key role in the filtration function of the kidney. A damaged podocyte ultrastructure is associated with a reorganization of the actin ...cytoskeleton and accompanied with a loss of adhesion to the glomerular basement membrane leading to proteinuria in many forms of glomerular diseases, e.g. nephrotic syndrome. If the first-line therapy with glucocorticoids fails, alternative immunosuppressive agents are used, which are known to have the potential to stabilize the actin cytoskeleton. A new option for preventing relapses in steroid dependent nephrotic syndrome is the monoclonal antibody rituximab, which, in addition to its B-cell depleting effect, is assumed to have direct effects on podocytes. We here provide data on the non-immunological
off-target
effects of the immunosuppressant rituximab on podocyte structure and dynamics in an in vitro puromycin aminonucleoside model of podocyte injury. A conditionally immortalized human podocyte cell line was used. Differentiated podocytes were treated with puromycin aminonucleoside and rituximab. Our studies focussed on analyzing the structure of the actin cytoskeleton, cellular adhesion and apoptosis using immunofluorescence staining and protein biochemistry methods. Treatment with rituximab resulted in a stabilization of podocyte actin stress fibers in the puromycin aminonucleoside model, leading to an improvement in cell adhesion. A lower apoptosis rate was observed after parallel treatment with puromycin aminonucleoside and rituximab visualized by reduced nuclear fragmentation. Consistent with this data, Western-blot analyses demonstrated that rituximab directly affects the caspase pathways by inhibiting the activation of Caspases-8, -9 and -3, suggesting that rituximab may inhibit apoptosis. In conclusion, our results indicate an important role of the immunosuppressant rituximab in terms of stability and morphogenesis of podocytes, involving apoptosis pathways. This could help to improve therapeutical concepts for patients with proteinuria mediated by diseased podocytes.
Inflammatory diseases such as arthritis are chronic conditions that fail to resolve spontaneously. While the cytokine and cellular pathways triggering arthritis are well defined, those responsible ...for the resolution of inflammation are incompletely characterized. Here we identified interleukin (IL)-9-producing type 2 innate lymphoid cells (ILC2s) as the mediators of a molecular and cellular pathway that orchestrates the resolution of chronic inflammation. In mice, the absence of IL-9 impaired ILC2 proliferation and activation of regulatory T (T
) cells, and resulted in chronic arthritis with excessive cartilage destruction and bone loss. In contrast, treatment with IL-9 promoted ILC2-dependent T
activation and effectively induced resolution of inflammation and protection of bone. Patients with rheumatoid arthritis in remission exhibited high numbers of IL-9
ILC2s in joints and the circulation. Hence, fostering IL-9-mediated ILC2 activation may offer a novel therapeutic approach inducing resolution of inflammation rather than suppression of inflammatory responses.
A stereoisomer of macrocidin B, a presumed metabolite of the fungus Phoma macrostoma, was synthesized in 18 steps and 2.7% yield from protected l-tyrosine that was N-β-ketoacylated with a fully ...functionalized octanoyl Meldrum’s acid. Dieckmann condensation gave a 3-acyltetramic acid, which was macrocyclized via Williamson etherification between the phenol and epi-bromohydrin termini. This macrocidin B stereoisomer showed a weaker herbicidal effect than macrocidin A and no similar inhibitory effect on biofilms of Staphylococcus aureus.
Scientists and the public were alarmed at the first large viral variant of SARS‐CoV‐2 reported in December 2020. We have followed the time course of emerging viral mutants and variants during the ...SARS‐CoV‐2 pandemic in ten countries on four continents. We examined > 383,500 complete SARS‐CoV‐2 nucleotide sequences in GISAID (Global Initiative of Sharing All Influenza Data) with sampling dates extending until April 05, 2021. These sequences originated from ten different countries: United Kingdom, South Africa, Brazil, United States, India, Russia, France, Spain, Germany, and China. Among the 77 to 100 novel mutations, some previously reported mutations waned and some of them increased in prevalence over time. VUI2012/01 (B.1.1.7) and 501Y.V2 (B.1.351), the so‐called UK and South Africa variants, respectively, and two variants from Brazil, 484K.V2, now called P.1 and P.2, increased in prevalence. Despite lockdowns, worldwide active replication in genetically and socio‐economically diverse populations facilitated selection of new mutations. The data on mutant and variant SARS‐CoV‐2 strains provided here comprise a global resource for easy access to the myriad mutations and variants detected to date globally. Rapidly evolving new variant and mutant strains might give rise to escape variants, capable of limiting the efficacy of vaccines, therapies, and diagnostic tests.
Synopsis
This 2020/21 time course study shows the rapid rise of new SARS‐CoV‐2 mutants and variants across the entire genome during worldwide viral replication. In 10 countries, 40 to 65% of mutants were C to T transitions. Viral mutations will affect vaccination programs.
We analyzed > 383,500 SARS‐CoV‐2 RNA sequences for the occurrence of mutations across the entire genome. The time course of mutations emerging between 01/2020 and 03/2021 was determined.
We initially identified ~ 10 prevalent mutations. About 77 to 100 new mutations arose concomitant with the spread of Covid‐19 between March/April 2020 and January 2021, followed by the emergence of variants in December 2020.
A study of the pathogenicity of viral mutations will help understand Covid‐19 outbreaks and symptoms. Monitoring mutant selection will aid Covid‐19 diagnosis, vaccine development and therapy. New mutants will compromise vaccine efficiency.
Among the SARS‐CoV‐2 mutants, C to U transitions at a frequency between 40 to 65% were prevalent. Cellular cytosine deaminases, possibly of the APOBEC type, likely drive viral mutagenesis.
This 2020/21 time course study shows the rapid rise of new SARS‐CoV‐2 mutants and variants across the entire genome during worldwide viral replication. In 10 countries, 40 to 65% of mutants were C to T transitions. Viral mutations will affect vaccination programs.
Zusammenfassung
Digitale Gesundheitsanwendungen (DiGA) sind eines der Räder im Getriebe des digitalen Gesundheitswesens. Wie alle anderen kommunizierenden Anwendungen müssen DiGA interoperabel sein, ...damit das ganze System reibungslos funktioniert. Dabei muss Interoperabilität auf 4 verschiedenen Ebenen gegeben sein, dies sind: funktionale und fachinhaltliche Anforderungen; strukturelle und semantische Anforderungen; Anforderungen an Sicherheit und Transport und organisatorische Anforderungen.
In Deutschland wurde in den letzten Jahren ein großer Sprung in ein digitales Gesundheitswesen initiiert, verstärkt durch die Erfahrungen aus der COVID-19-Pandemie. Aktuelle Gesetzgebungen zielen auf eine Festlegung von Standards und einheitlichen Abläufen und etablieren damit den benötigten verbindlichen Rahmen für ein Gesamtkonzept in der Digitalisierung. Interoperable DiGA können mit den anderen Systemen im Gesundheitswesen kommunizieren, wenn es die PatientInnen wünschen. Möglich sind z. B. der Anschluss an die elektronische Patientenakte (ePA) und eine damit einhergehende Datenspende für Forschungszwecke. So können PatientInnen nicht nur direkt von dem positiven Versorgungseffekt einer DiGA profitieren, sondern auch indirekt durch die Datenspende zur Forschung und damit zur Verbesserung des Gesundheitswesens beitragen.
PDF
