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Molecular data integration plays a central role in central nervous system (CNS) tumor diagnostics but currently used assays pose limitations due to technical complexity, equipment and reagent costs, as well as lengthy turnaround times. We previously reported the development of Rapid-CNS2, an adaptive-sampling-based nanopore sequencing workflow. Here we comprehensively validated and further developed Rapid-CNS2 for intraoperative use. It now offers real-time methylation classification and DNA copy number information within a 30-min intraoperative window, followed by comprehensive molecular profiling within 24 h, covering the complete spectrum of diagnostically and therapeutically relevant information for the respective entity. We validated Rapid-CNS2 in a multicenter setting on 301 archival and prospective samples including 18 samples sequenced intraoperatively. To broaden the utility of methylation-based CNS tumor classification, we developed MNP-Flex, a platform-agnostic methylation classifier encompassing 184 classes. MNP-Flex achieved 99.6% accuracy for methylation families and 99.2% accuracy for methylation classes with clinically applicable thresholds across a global validation cohort of more than 78,000 frozen and formalin-fixed paraffin-embedded samples spanning five different technologies. Integration of these tools has the potential to advance CNS tumor diagnostics by providing broad access to rapid, actionable molecular insights crucial for personalized treatment strategies.
Background
In the early COVID-19 pandemic concerns about the correct choice of analgesics in patients with COVID-19 were raised. Little data was available on potential usefulness or harmfulness of prescription free analgesics, such as paracetamol. This international multicentre study addresses that lack of evidence regarding the usefulness or potential harm of paracetamol intake prior to ICU admission in a setting of COVID-19 disease within a large, prospectively enrolled cohort of critically ill and frail intensive care unit (ICU) patients.
Methods
This prospective international observation study (The COVIP study) recruited ICU patients ≥ 70 years admitted with COVID-19. Data on Sequential Organ Failure Assessment (SOFA) score, prior paracetamol intake within 10 days before admission, ICU therapy, limitations of care and survival during the ICU stay, at 30 days, and 3 months. Paracetamol intake was analysed for associations with ICU-, 30-day- and 3-month-mortality using Kaplan Meier analysis. Furthermore, sensitivity analyses were used to stratify 30-day-mortality in subgroups for patient-specific characteristics using logistic regression.
Results
44% of the 2,646 patients with data recorded regarding paracetamol intake within 10 days prior to ICU admission took paracetamol. There was no difference in age between patients with and without paracetamol intake. Patients taking paracetamol suffered from more co-morbidities, namely diabetes mellitus (43% versus 34%, p < 0.001), arterial hypertension (70% versus 65%, p = 0.006) and had a higher score on Clinical Frailty Scale (CFS; IQR 2–5 versus IQR 2–4, p < 0.001). Patients under prior paracetamol treatment were less often subjected to intubation and vasopressor use, compared to patients without paracetamol intake (65 versus 71%, p < 0.001; 63 versus 69%, p = 0.007). Paracetamol intake was not associated with ICU-, 30-day- and 3-month-mortality, remaining true after multivariate adjusted analysis.
Conclusion
Paracetamol intake prior to ICU admission was not associated with short-term and 3-month mortality in old, critically ill intensive care patients suffering from COVID-19.
Trial registration.
This prospective international multicentre study was registered on ClinicalTrials.gov with the identifier “NCT04321265” on March 25, 2020.
Hinter dem Konzept der Wissenspolitik verbergen sich unterschiedliche sozialwissenschaftliche Ansätze zur Beschreibung des gesellschaftlichen Umgangs mit wissenschaftlichem Wissen und Technologien. Diese Arbeit argumentiert für ein wissenssoziologisches Verständnis wissenspolitischer Konzeptionen und eine entsprechende empirische Untersuchung. Mithilfe der Analyse des Diskurses zum Umgang mit Nanotechnologie in Deutschland wird nachvollzogen, welche Akteure sich in diesem Themenfeld engagieren und wie Wissen zur Regulierung der Entwicklung und des Einsatzes wissenschaftlichen Wissens entsteht. Die Untersuchung reicht von Ende der 1980er Jahre bis Anfang 2012. Es wird ersichtlich, dass sich der Diskurs in drei Phasen aufteilt, die sich jeweils durch eine eigentümliche Entwicklung der Inhalte und der Teilnahme von Akteuren ausprägen. Die Arbeit macht darüber hinaus anhand der Analyse und des Vergleichs mehrerer Regulierungsinstrumente deutlich, inwiefern sich am Beispiel des Umgangs mit Nanotechnologie eine Veränderung der rechtlichen Regulierung wissenschaftlicher Unsicherheit ausdrückt.
Social collaboration in project work: an exploratory empirical analysis of benefits and technologies
(2014)
Kitaev matter
(2015)
