Continuity of care for patients with de novo metastatic cancer during the COVID-19 pandemic:A population-based observational study

During the COVID-19 pandemic recommendations were made to adapt cancer care. This population-based study aimed to investigate possible differences between the treatment of patients with metastatic cancer before and during the pandemic by comparing the initial treatments in five COVID-19 periods (weeks 1–12 2020: pre-COVID-19, weeks 12–20 2020: 1st peak, weeks 21–41 2020: recovery, weeks 42–53 2020: 2nd peak, weeks 1–20 2021: prolonged 2nd peak) with reference data from 2017 to 2019. The proportion of patients receiving different treatment modalities (chemotherapy, hormonal therapy, immunotherapy or targeted therapy, radiotherapy primary tumor, resection primary tumor, resection metastases) within 6 weeks of diagnosis and the time between diagnosis and first treatment were compared by period. In total, 74,208 patients were included. Overall, patients were more likely to receive treatments in the COVID-19 periods than in previous years. This mainly holds for hormone therapy, immunotherapy or targeted therapy and resection of metastases. Lower odds were observed for resection of the primary tumor during the recovery period (OR 0.87; 95% CI 0.77–0.99) and for radiotherapy on the primary tumor during the prolonged 2nd peak (OR 0.84; 95% CI 0.72–0.98). The time from diagnosis to the start of first treatment was shorter, mainly during the 1st peak (average 5 days, p &lt;.001). These findings show that during the first 1.5 years of the COVID-19 pandemic, there were only minor changes in the initial treatment of metastatic cancer. Remarkably, time from diagnosis to first treatment was shorter. Overall, the results suggest continuity of care for patients with metastatic cancer during the pandemic.</p

Open Science - the new paradigm for research and education?

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CHEERS Value of Information (CHEERS-VOI) Reporting Standards - Explanation and Elaboration

BACKGROUND: While the ISPOR Value of Information (VOI) Task Force's reports outline VOI concepts and provide good-practice recommendations, there is no guidance for reporting VOI analyses. VOI analyses are usually performed alongside economic evaluations for which the Consolidated Health Economic Evaluation Reporting Standards 2022 (CHEERS) Statement provides reporting guidelines. Thus, we developed the CHEERS-VOI checklist to provide reporting guidance and checklist to support the transparent, reproducible and high-quality reporting of VOI analyses. METHODS: A comprehensive literature review generated a list of 26 candidate reporting items. These candidate items underwent a Delphi procedure with Delphi participants through 3 survey rounds. Participants rated each item on a 9-point Likert scale to indicate its relevance when reporting the minimal, essential information about VOI methods and provided comments. The Delphi results were reviewed at two-day consensus meetings and the checklist was finalized using anonymous voting. RESULTS: We had 30, 25 and 24 Delphi respondents in Rounds 1, 2 and 3, respectively. After incorporating revisions recommended by the Delphi participants, all 26 candidate items proceeded to the two-day consensus meetings. The final CHEERS-VOI checklist includes all CHEERS items but 7 items require elaboration when reporting VOI. Further, 6 new items were added to report information relevant only to VOI (e.g., VOI methods applied). CONCLUSIONS: The CHEERS-VOI checklist should be used when a VOI analysis is performed alongside economic evaluations. The CHEERS-VOI checklist will help decision-makers, analysts and peer reviewers in the assessment and interpretation of VOI analyses and thereby increase transparency and rigour in decision-making

Georessource Wasser - Herausforderung Globaler Wandel. Kapitel 3 - Wassernutzung und Wassereffizienz in Landschaften

Der Klimawandel, die Globalisierung der Märkte, der demografische Wandel, die rasanten technologischen Entwicklungen sowie die Veränderungen der Landnutzung sind verschiedene Facetten des sogenannten Globalen Wandels. Welchen Einfluss der Globale Wandel auf die verfügbaren Wasserressourcen hat, ist von Region zu Region unterschiedlich. In jedem Fall steigt der Nutzungsdruck auf die Georessource Wasser weiter an; bereits jetzt zeichnen sich regionale Konkurrenzen und Konflikte bei der Nutzung ab. So wird sich beispielsweise der Bewässerungsbedarf der Landwirtschaft durch die steigende globale Nachfrage nach Nahrungsmitteln und Rohstoffen weiter erhöhen. Infolge des Globalen Wandels und der Veränderungen der Flusslandschaften ist auch vermehrt mit Hochwasserereignissen zu rechnen. Ausreichende Wasserressourcen in hinreichender Qualität zu sichern, sowie der Gewässerschutz und die Hochwasservorsorge sind daher zentrale Anliegen unserer Gesellschaft. Innovative Anpassungsstrategien und neue Technologien können hierbei nicht nur zu einer nachhaltigen Wasser- und Bodenbewirtschaftung führen, sondern gleichzeitig auch wirtschaftliche Chancen auf dem Weltmarkt eröffnen. Gerade durch die Entwicklung und den Export von Technologien und Verfahrensweisen kann Deutschland einen Beitrag zur Lösung globaler Wasserprobleme leisten

Overexpression of the catalytically impaired Taspase1 T234V or Taspase1 D233A variants does not have a dominant negative effect in T(4;11) leukemia cells.

BACKGROUND: The chromosomal translocation t(4;11)(q21;q23) is associated with high-risk acute lymphoblastic leukemia of infants. The resulting AF4•MLL oncoprotein becomes activated by Taspase1 hydrolysis and is considered to promote oncogenic transcriptional activation. Hence, Taspase1's proteolytic activity is a critical step in AF4•MLL pathophysiology. The Taspase1 proenzyme is autoproteolytically processed in its subunits and is assumed to assemble into an αββα-heterodimer, the active protease. Therefore, we investigated here whether overexpression of catalytically inactive Taspase1 variants are able to interfere with the proteolytic activity of the wild type enzyme in AF4•MLL model systems. METHODOLOGY/FINDINGS: The consequences of overexpressing the catalytically dead Taspase1 mutant, Taspase1(T234V), or the highly attenuated variant, Taspase1(D233A), on Taspase1's processing of AF4•MLL and of other Taspase1 targets was analyzed in living cancer cells employing an optimized cell-based assay. Notably, even a nine-fold overexpression of the respective Taspase1 mutants neither inhibited Taspase1's cis- nor trans-cleavage activity in vivo. Likewise, enforced expression of the α- or β-subunits showed no trans-dominant effect against the ectopically or endogenously expressed enzyme. Notably, co-expression of the individual α- and β-subunits did not result in their assembly into an enzymatically active protease complex. Probing Taspase1 multimerization in living cells by a translocation-based protein interaction assay as well as by biochemical methods indicated that the inactive Taspase1 failed to assemble into stable heterocomplexes with the wild type enzyme. CONCLUSIONS: Collectively, our results demonstrate that inefficient heterodimerization appears to be the mechanism by which inactive Taspase1 variants fail to inhibit wild type Taspase1's activity in trans. Our work favours strategies targeting Taspase1's catalytic activity rather than attempts to block the formation of active Taspase1 dimers to interfere with the pathobiological function of AF4•MLL