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Multi-Omic Candidate Screening for Markers of Severe Clinical Courses of COVID-19.

Severe coronavirus disease 2019 (COVID-19) disease courses are characterized by immuno-inflammatory, thrombotic, and parenchymal alterations. Prediction of individual COVID-19 disease courses to guide targeted prevention remains challenging. We hypothesized that a distinct serologic signature precedes surges of IL-6/D-dimers in severely affected COVID-19 patients. We performed longitudinal plasma profiling, including proteome, metabolome, and routine biochemistry, on seven seropositive, well-phenotyped patients with severe COVID-19 referred to the Intensive Care Unit at the German Heart Center. Patient characteristics were: 65 ± 8 years, 29% female, median CRP 285 ± 127 mg/dL, IL-6 367 ± 231 ng/L, D-dimers 7 ± 10 mg/L, and NT-proBNP 2616 ± 3465 ng/L. Based on time-series analyses of patient sera, a prediction model employing feature selection and dimensionality reduction through least absolute shrinkage and selection operator (LASSO) revealed a number of candidate proteins preceding hyperinflammatory immune response (denoted ΔIL-6) and COVID-19 coagulopathy (denoted ΔD-dimers) by 24-48 h. These candidates are involved in biological pathways such as oxidative stress/inflammation (e.g., IL-1alpha, IL-13, MMP9, C-C motif chemokine 23), coagulation/thrombosis/immunoadhesion (e.g., P- and E-selectin), tissue repair (e.g., hepatocyte growth factor), and growth factor response/regulatory pathways (e.g., tyrosine-protein kinase receptor UFO and low-density lipoprotein receptor (LDLR)). The latter are host- or co-receptors that promote SARS-CoV-2 entry into cells in the absence of ACE2. Our novel prediction model identified biological and regulatory candidate networks preceding hyperinflammation and coagulopathy, with the most promising group being the proteins that explain changes in D-dimers. These biomarkers need validation. If causal, our work may help predict disease courses and guide personalized treatment for COVID-19.

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Open Access
Interventions to enhance safety culture for nursing professionals in long-term care: A systematic review

BackgroundRecognizing safety risks and promoting safe care is essential for care dependent people and should be an integral part of the overall preventive endeavors while providing care. The term 'safety culture' describes efforts regarding the acknowledgement and reduction of safety risks. Enhanced safety culture in health care organizations can be associated with a lower incidence of missed nursing care and adverse events. ObjectiveIdentify strategies to enhance safety culture in long-term care settings and describe factors facilitating or inhibiting the process from the available evidence. DesignThis systematic review is a narrative description of intervention studies. MethodsCINAHL and MEDLINE were searched in May 2020 using terms such as safety culture, safety climate, intervention development. Gray literature was searched between May and September 2020. An additional search in Cochrane Library was conducted in September 2022. Only intervention studies feasible to enhance the safety culture were included. Intervention study criteria were met when an organized, planned action to prevent or change a specific behavior took place and when this action was transparently and systematically evaluated. The screening, data extraction, and rating processes were conducted by two researchers independently. The ROBINS-I tool was utilized to assess the risk of bias of the studies. ResultsSeven intervention studies were included, all evaluated with a critical risk of bias. Strategies found to enhance the safety culture in care settings include collegial exchange of experiences and learnings, integration of staff's perceptions, external facilitation, staff training, and a structured, multi-step procedure of the intervention process. Some studies were unable to show statistically significant enhancement in safety culture from the interventions implemented. Factors facilitating the implementation of interventions include good connections and trust between staff and managers, and the manager's active support of the project goals, as well as targeting achievable ideas considering time and resources. Time pressure, heavy workloads and high staff turnover may inhibit the process. ConclusionsAll included studies had a high risk of bias, and possible effects must be considered accordingly. Overall, there was considerable heterogeneity in interventions aiming to enhance safety culture. Despite these aspects, promising approaches are training staff's knowledge and competencies regarding open communication and teamwork as part of a multifaceted program. Future research would benefit from participative, carefully developed, comprehensively evaluated interventions for enhancing safety culture, specifically within in-home care settings. RegistrationThe review was not pre-registered but described on the website of the Center for Quality in Care. Tweetable abstractParticipatory change management & staff training help ensure momentum & trust in endeavours to enhance safety culture in long-term care.

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Open Access
First proficiency testing for NGS-based and combined NGS- and FISH-based detection of FGFR2 fusions in intrahepatic cholangiocarcinoma.

Intrahepatic cholangiocarcinoma harbours druggable genetic lesions including FGFR2 gene fusions. Reliable and accurate detection of these fusions is becoming a critical component of the molecular work-up, but real-world data on the performance of fluorescence in situ hybridisation (FISH) and targeted RNA-based next-generation sequencing (NGS) are very limited. Bridging this gap, we report results of the first round robin test for FGFR2 fusions in cholangiocarcinoma and contextualise test data with genomic architecture. A cohort of 10 cholangiocarcinoma (4 fusion positive and 6 fusion negative) was tested by the Institute of Pathology, University Hospital Heidelberg, Germany. Data were validated by four academic pathology departments in Germany. Fusion-positive cases comprised FGFR2::BICC1, FGFR2::DBP, FGFR2::TRIM8, and FGFR2::ATE1 fusions. In a second step, a round robin test involving 21 academic and non-academic centres testing with RNA-based NGS approaches was carried out; five participants performed FISH testing in addition. Thirteen of 16 (81%) centres successfully passed the NGS only and 3 of 5 (60%) centres passed the combined NGS + FISH round robin test. Identified obstacles were bioinformatic pipelines not optimised for the detection of FGFR2 fusions and assays not capable of detecting unknown fusion partners. This study shows the benefit of targeted RNA-NGS for the detection of FGFR2 gene fusions. Due to the marked heterogeneity of the genomic architecture of these fusions, fusion partner agnostic (i.e. open) methodological approaches that are capable of identifying yet unknown fusion partners are superior. Furthermore, we highlight pitfalls in subsequent bioinformatic analysis and limitations of FISH-based tests.

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Open Access
Patient safety in home care: A multicenter cross-sectional study about medication errors and medication management of nurses.

Studies assume that up to 30% of home care recipients are exposed to a possible medication error. For the home care sector, the study situation regarding such errors is limited. The aim of the study was to find out how often medication errors occur and whether they are related to training, quality assurance measures (use of the double‐check principle (DCP)), and other structural conditions of home care services. A cross‐sectional study was conducted, comprising 485 fully trained nurses of 107 randomly selected home care services. Potential influencing factors were analyzed in a multiple logistic regression model. Of 485 fully qualified nurses, 41.6% reported medication errors within a 12‐month period, while 14.8% did not answer this question. Nurses who had attended medication training within the last 2 years compared to a longer period (frequently to rather rarely applied DCP); the odds ratio of not making medication‐related errors was 1.79[1.42–3.09] (OR 3.13; [1.88–5.20]). Years of professional experience, amount of patients per shift, and type of work contract (full/part‐time) were not statistically significantly associated with reported medication errors. Medication‐related errors occur frequently in home care. Regular training and adequate quality management measures increase patient safety. Nursing managers and other responsible individuals of home care institutions have to make sure that nursing staff take part in regular medication training and apply the DCP when they give out medication in home care.

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Open Access
Die Analyse des CIRSmedical.de mittels Natural Language Processing

BackgroundCIRSmedical.de is a publicly accessible, cross-institutional reporting and learning system, which is organized by the German Agency for Quality in Medicine (ÄZQ). CIRSmedical.de has existed since 2005 and has published more than 6,000 event reports. Up to now it has been common practice to analyse these reports in detail or carry out systematic evaluations focusing on specific topics. A systematic evaluation of all case reports has not yet been conducted. Natural Language Processing (NLP) is an analysis strategy from the field of Artificial Intelligence for indexing texts. The examination of case reports using NLP was carried out to describe the characteristics of event reports and comments. Materials and MethodsFor this analysis 6,480 case reports from CIRSmedical.de (as of December 10, 2019) were provided by the ÄZQ as Excel files. Several free text fields were included in the analysis as well as the feedback of the CIRS team (expert commentary). Text lengths, reporting behaviour, sentiment values and keywords were examined. The algorithms for the analysis were developed with the programming language Python and the corresponding libraries NLTK and SpaCy. ResultsThe comparison of report lengths depending on the different subject groups presented a heterogeneous picture, in terms of both the number of reports and the number of words. There are more than 4,000 reports from the field of anaesthesiology, whereby text lengths vary particularly strongly with a right-skewed distribution. There are only a few reports from the field of psychotherapy, and these are also very short. The different professional groups (nurses, doctors, other staff) write reports of about the same length. Reports and expert commentaries also differ in terms of sentiment values. Due to the length of the comments, they are more negative in terms of sentiment. Keywords can be identified but show a high heterogeneity. DiscussionSystematic analysis using NLP allows for the description of text properties in event reports and comments. It is now possible to draw a conclusion about the reporters’ intention, focus and mood when they report in CIRS. The sentiment analysis is an indication of the mood which the texts convey, both as a report and as a commentary. Text length analysis draws attention to different problems and tendencies: event reports are usually much shorter. Texts that are too short, however, run the risk that the information will not be readily usable for analysis. Comments are often longer, but here one faces the opposite problem: texts that are too long may not be read. The examination of texts by means of NLP helps to rethink the reason for and the form of input, both when reporting and when commenting. It is a first step in the automatic, supportive classification of texts and an improvement of the interaction between reporters and the system.

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