Impact of rapid enterovirus polymerase chain reaction testing on management of febrile young infants < 90 days of age with aseptic meningitis

BACKGROUND Diagnostic evaluation of febrile young infants is challenging. Empirical antimicrobial treatment is therefore common practice in this setting despite high percentage of causative viral infections. The objective of this study was to investigate the impact of rapid enterovirus cerebrospinal fluid polymerase chain reaction (CSF EV PCR) test on hospital length of stay (LOS) and antimicrobial treatment duration in young febrile infants. METHODS Retrospective observational study comparing duration of antimicrobial treatment and hospital LOS before (May 1, 2014 - May 30, 2015, untested group) and after (June 1, 2015 - June 30, 2017, tested group) the introduction of rapid CSF EV PCR testing in infants < 90 days of age presenting with fever and CSF pleocytosis at the University Children's Hospital Zurich. Additionally, the same variables were compared after test introduction between CSF EV PCR positive and negative children. RESULTS One hundred twenty-eight children were enrolled in the study, 58 before and 70 after the introduction of rapid CSF EV PCR testing. Duration of antimicrobial treatment was significantly shortened in EV positive (n = 42) compared to both EV negative (n = 28) (median 18 h and 48 h, respectively, p < 0.001) and untested patients (n = 58) (median 18 h and 48 h, respectively, p < 0.001), and also in tested compared to untested group patients (median 36 vs 48 h, p < 0.001). Hospital LOS was significantly shortened in EV positive compared to EV negative patients (median 3 days and 4 days respectively, p = 0.013), while an overall reduction was not observed between tested and untested group patients. CONCLUSIONS In this study we demonstrate that antimicrobial treatment duration could be significantly shortened in neonates and young infants < 90 days of age with aseptic meningitis after the introduction of a rapid CSF EV PCR test compared to untested patients before test introduction

In vivo Assembly of Artificial Metalloenzymes and Application in Whole-Cell Biocatalysis

We report the supramolecular assembly of artificial metalloenzymes (ArMs), based on the Lactococcal multidrug resistance regulator (LmrR) and an exogeneous copper(II)-phenanthroline complex, in the cytoplasm of E. coli cells. A combination of catalysis, cell-fractionation and inhibitor experiments, supplemented with in-cell solid-state NMR, confirmed the in-cell assembly. The ArM containing whole cells were active in the catalysis of the enantioselective Friedel-Crafts alkylation of indoles and the Diels-Alder reaction of azachalcone with cyclopentadiene. Directed evolution resulted in two different improved mutants for both reactions, LmrR_A92E_M8D and LmrR_A92E_V15A, respectively. The whole-cell ArM system requires no engineering of the microbial host, the protein scaffold or the cofactor to achieve ArM assembly and catalysis. We consider this a key step towards integrating abiological catalysis in biosynthesis, achieving a hybrid metabolism

Swiss recommendations on perioperative antimicrobial prophylaxis in children.

Infection following surgical procedures leads to significant morbidity and mortality in all age groups. Sterile techniques, antibiotic prophylaxis and improved postoperative wound care have contributed to the decline of surgical site infections since the early days of surgery. Recommendations on the use of perioperative antimicrobial prophylaxis exist for adults, but are rare for the paediatric population. Here, we provide a standardised approach to the effective use of antimicrobial agents for the prevention of surgical site infections in children contributing to a targeted and rational perioperative use of antibiotics in Switzerland

Swiss recommendations on perioperative antimicrobial prophylaxis in children

Infection following surgical procedures leads to significant morbidity and mortality in all age groups. Sterile techniques, antibiotic prophylaxis and improved postoperative wound care have contributed to the decline of surgical site infections since the early days of surgery. Recommendations on the use of perioperative antimicrobial prophylaxis exist for adults, but are rare for the paediatric population. Here, we provide a standardised approach to the effective use of antimicrobial agents for the prevention of surgical site infections in children contributing to a targeted and rational perioperative use of antibiotics in Switzerland

Catalytic fast pyrolysis of biomass : catalyst characterization reveals the feed-dependent deactivation of a technical ZSM-5-based catalyst

Catalyst deactivation due to coking is a major challenge in the catalytic fast pyrolysis (CFP) of biomass. Here, a multitechnique investigation of a technical Al2O3-bound ZSM-5-based extrudate catalyst, used for the CFP of pine wood and cellulose (at a reactor temperature of 500 °C), provided insight into the effects of extrusion, the catalytic pyrolysis process, and catalyst regeneration on the catalyst structure. As a result of a reduction in acidity and surface area due to the coking catalyst, the activity dropped drastically with increasing time-on-stream (TOS), as evidenced by a decrease in aromatics yield. Strikingly, confocal fluorescence microscopy at the single-particle level revealed that vapor components derived from whole biomass or just the cellulose component coke differently. While pine-wood-derived species mainly blocked the external area of the catalyst particle, larger carbon deposits were formed inside the catalyst’s micropores with cellulose-derived species. Pyridine FT-IR and solid-state NMR spectroscopy demonstrated irreversible changes after regeneration, likely due to partial dealumination. Taken together with <30 g kg–1 aromatics yield on a feed basis, the results show a mismatch between biomass pyrolysis vapors and the technical catalyst used due to a complex interplay of mass transfer limitations and CFP chemistry

Mental Health and COVID-19 in University Students: Findings from a Qualitative, Comparative Study in Italy and the UK

Introduction: COVID-19 restrictions introduced several changes in university academic and social experience. Self-isolation and online teaching have amplified students’ mental health vulnerability. Thus, we aimed to explore feelings and perspectives about the impact of the pandemic on mental health, comparing students from Italy and the UK. Methods: Data were collected from the qualitative portion of “the CAMPUS study”, longitudinally assessing mental health of students at the University of Milano-Bicocca (Italy) and the University of Surrey (UK). We conducted in-depth interviews and thematically analysed the transcripts. Results: The explanatory model was developed from four themes identified across 33 interviews: anxiety exacerbated by COVID-19; putative mechanisms leading to poor mental health; the most vulnerable subgroups; and coping strategies. Generalised and social anxiety resulted from COVID-19 restrictions by being associated with loneliness, excessive time online, unhealthy management of time and space and poor communication with the university. Freshers, international students, and people on the extremes of the introversion/extroversion spectrum, were identified as vulnerable, while effective coping strategies included taking advantage of free time, connection with family and mental health support. The impact of COVID-19 was mostly related to academic issues by students from Italy, whereas to the drastic loss of social connectedness by the UK sample. Conclusions: Mental health support for students has an essential role, and measures that encourage communication and social connectedness are likely to be beneficial

Pharmacogenetic Analysis of Voriconazole Treatment in Children

Voriconazole is among the first-line antifungal drugs to treat invasive fungal infections in children and known for its pronounced inter- and intraindividual pharmacokinetic variability. Polymorphisms in genes involved in the metabolism and transport of voriconazole are thought to influence serum concentrations and eventually the therapeutic outcome. To investigate the impact of these genetic variants and other covariates on voriconazole trough concentrations, we performed a retrospective data analysis, where we used medication data from 36 children suffering from invasive fungal infections treated with voriconazole. Data were extracted from clinical information systems with the new infrastructure SwissPKcdw, and linear mixed effects modelling was performed using R. Samples from 23 children were available for DNA extraction, from which 12 selected polymorphism were genotyped by real-time PCR. 192 (49.1%) of 391 trough serum concentrations measured were outside the recommended range. Voriconazole trough concentrations were influenced by polymorphisms within the metabolizing enzymes CYP2C19 and CYP3A4, and within the drug transporters ABCC2 and ABCG2, as well as by the co-medications ciprofloxacin, levetiracetam, and propranolol. In order to prescribe an optimal drug dosage, pre-emptive pharmacogenetic testing and careful consideration of co-medications in addition to therapeutic drug monitoring might improve voriconazole treatment outcome of children with invasive fungal infections. Keywords: ABCC2; ABCG2; CYP2C19; CYP3A4; children; non-linear mixed effects modelling; pediatric pharmacology; pharmacogenetics; therapeutic drug monitoring; voriconazol

Migrating a Well-Established Longitudinal Cohort Database From Oracle SQL to Research Electronic Data Entry (REDCap): Data Management Research and Design Study

BACKGROUND: Providing user-friendly electronic data collection tools for large multicenter studies is key for obtaining high-quality research data. Research Electronic Data Capture (REDCap) is a software solution developed for setting up research databases with integrated graphical user interfaces for electronic data entry. The Swiss Mother and Child HIV Cohort Study (MoCHiV) is a longitudinal cohort study with around 2 million data entries dating back to the early 1980s. Until 2022, data collection in MoCHiV was paper-based. OBJECTIVE: The objective of this study was to provide a user-friendly graphical interface for electronic data entry for physicians and study nurses reporting MoCHiV data. METHODS: MoCHiV collects information on obstetric events among women living with HIV and children born to mothers living with HIV. Until 2022, MoCHiV data were stored in an Oracle SQL relational database. In this project, R and REDCap were used to develop an electronic data entry platform for MoCHiV with migration of already collected data. RESULTS: The key steps for providing an electronic data entry option for MoCHiV were (1) design, (2) data cleaning and formatting, (3) migration and compliance, and (4) add-on features. In the first step, the database structure was defined in REDCap, including the specification of primary and foreign keys, definition of study variables, and the hierarchy of questions (termed "branching logic"). In the second step, data stored in Oracle were cleaned and formatted to adhere to the defined database structure. Systematic data checks ensured compliance to all branching logic and levels of categorical variables. REDCap-specific variables and numbering of repeated events for enabling a relational data structure in REDCap were generated using R. In the third step, data were imported to REDCap and then systematically compared to the original data. In the last step, add-on features, such as data access groups, redirections, and summary reports, were integrated to facilitate data entry in the multicenter MoCHiV study. CONCLUSIONS: By combining different software tools-Oracle SQL, R, and REDCap-and building a systematic pipeline for data cleaning, formatting, and comparing, we were able to migrate a multicenter longitudinal cohort study from Oracle SQL to REDCap. REDCap offers a flexible way for developing customized study designs, even in the case of longitudinal studies with different study arms (ie, obstetric events, women, and mother-child pairs). However, REDCap does not offer built-in tools for preprocessing large data sets before data import. Additional software is needed (eg, R) for data formatting and cleaning to achieve the predefined REDCap data structure