Cogito: automated and generic comparison of annotated genomic intervals.

BACKGROUND: Genetic and epigenetic biological studies often combine different types of experiments and multiple conditions. While the corresponding raw and processed data are made available through specialized public databases, the processed files are usually limited to a specific research question. Hence, they are unsuitable for an unbiased, systematic overview of a complex dataset. However, possible combinations of different sample types and conditions grow exponentially with the amount of sample types and conditions. Therefore the risk to miss a correlation or to overrate an identified correlation should be mitigated in a complex dataset. Since reanalysis of a full study is rarely a viable option, new methods are needed to address these issues systematically, reliably, reproducibly and efficiently. RESULTS: Cogito "COmpare annotated Genomic Intervals TOol" provides a workflow for an unbiased, structured overview and systematic analysis of complex genomic datasets consisting of different data types (e.g. RNA-seq, ChIP-seq) and conditions. Cogito is able to visualize valuable key information of genomic or epigenomic interval-based data, thereby providing a straightforward analysis approach for comparing different conditions. It supports getting an unbiased impression of a dataset and developing an appropriate analysis strategy for it. In addition to a text-based report, Cogito offers a fully customizable report as a starting point for further in-depth investigation. CONCLUSIONS: Cogito implements a novel approach to facilitate high-level overview analyses of complex datasets, and offers additional insights into the data without the need for a full, time-consuming reanalysis. The R/Bioconductor package is freely available at https://bioconductor.org/packages/release/bioc/html/Cogito.html , a comprehensive documentation with detailed descriptions and reproducible examples is included.

Determination of Anti-Xa Inhibitor Plasma Concentrations Using a Universal Edoxaban Calibrator.

A universal calibrator for the determination of all anti-Xa inhibitors would support laboratory processes. We aimed to test the clinical performance of an anti-Xa assay utilizing a universal edoxaban calibrator to determine clinically relevant concentrations of all anti-Xa inhibitors. Following a pilot study, we enrolled 553 consecutive patients taking rivaroxaban, edoxaban, or apixaban from nine study centers in a prospective cross-sectional study. The Technochrom® anti-Xa assay was conducted using the Technoview® edoxaban calibrator. Using ultra-high-performance liquid chromatography-tandem mass spectrometry (LC-MS/MS), anti-Xa inhibitor drug concentrations were determined. Sensitivities and specificities to detect three clinically relevant drug concentrations (30 µgL-1, 50 µgL-1, 100 µgL-1) were determined. Overall, 300 patients treated with rivaroxaban, 221 with apixaban, and 32 with edoxaban were included. The overall correlation coefficient (rs) was 0.95 (95% CI 0.94, 0.96). An area under the receiver operating characteristic curve of 0.96 for 30 µgL-1, 0.98 for 50 µgL-1, and 0.99 for 100 µgL-1 was found. The sensitivities were 92.3% (95% CI 89.2, 94.6), 92.7% (89.4, 95.1), and 94.8% (91.1, 97.0), respectively (specificities 82.2%, 93.7%, and 94.4%). In conclusion, the clinical performance of a universal, edoxaban-calibrated anti-Xa assay was solid and most drug concentrations were predicted correctly.

Early Switch From Intravenous to Oral Antibiotics in Skin and Soft Tissue Infections: An Algorithm-Based Prospective Multicenter Pilot Trial.

Background: In hospitalized patients with skin and soft tissue infections (SSTIs), intravenous (IV) empiric antibiotic treatment is initiated. The best time point for switching from IV to oral treatment is unknown. We used an algorithm-based decision tree for the switch from IV to oral antibiotics within 48 hours and aimed to investigate the treatment outcome of this concept. Methods: In a nonrandomized trial, we prospectively enrolled 128 patients hospitalized with SSTI from July 2019 to May 2021 at 3 institutions. Clinical and biochemical response data during the first week and at follow-up after 30 days were analyzed. Patients fulfilling criteria for the switch from IV to oral antibiotics were assigned to the intervention group. The primary outcome was a composite definition consisting of the proportion of patients with clinical failure or death of any cause. Results: Ninety-seven (75.8%) patients were assigned to the intervention group. All of them showed signs of clinical improvement (ie, absence of fever or reduction of pain) within 48 hours of IV treatment, irrespective of erythema finding or biochemical response. The median total antibiotic treatment duration was 11 (interquartile range [IQR], 9-13) days in the invention group and 15 (IQR, 11-24) days in the nonintervention group (P < .001). The median duration of hospitalization was 5 (IQR, 4-6) days in the intervention group and 8 (IQR, 6-12) days in the nonintervention group (P < .001). There were 5 (5.2%) failures in the intervention group and 1 (3.2%) in the nonintervention group after a median follow-up of 37 days. Conclusions: In this pilot trial, the proposed decision algorithm for early switch from IV to oral antibiotics for SSTI treatment was successful in 95% of cases. Clinical Trials Registration. ISRCTN15245496.