Becton Dickinson (France)

Europe has long been the top destination for U.S. study abroad, yet the voices of European on-site professionals have often been overlooked in the field. Recent shifts toward inclusive and reciprocal practices with U.S. partners have led to Europe-specific conferences and this special issue, which amplifies the perspectives of those delivering study abroad in Europe. This introduction highlights the distinct history and scale of study abroad and the significant setback that COVID-19 caused to it. The Guest Editors present diverse articles addressing structural, pedagogical, cultural, and historical gaps in transatlantic collaboration. Key topics include student services, mental health, diversity, equity, inclusion, climate change awareness, and the impact of U.S. educational expectations on local staff. These pressures can challenge the core goal of study abroad: cultural immersion. Effective collaboration and open dialogue are essential to bridging these divides, ensuring local expertise is valued and shared objectives are met. Abstract in French L'Europe est depuis longtemps la première destination des études à l’étranger pour les étudiant·e·s américain·e·s, mais la voix des professionnels sur place en Europe a souvent été négligée dans le secteur. L'évolution récente vers des pratiques inclusives et réciproques avec les partenaires américains a conduit à des colloques spécifiques à l'Europe et à ce numéro spécial, visant à donner la parole à ceux et celles impliqué·e·s dans la mise en œuvre des programmes universitaires des U.S. en Europe. Cette introduction met en lumière l'histoire distincte, l'ampleur et les revers significatifs causés par Covid-19. Les éditeurs et éditrices invité·e·s présentent divers articles traitant des lacunes structurelles, pédagogiques, culturelles et historiques dans la collaboration transatlantique. Les principaux sujets abordés sont les services aux étudiants, la santé mentale, la diversité, l'équité, l'inclusion, la sensibilisation au changement climatique et l'impact des attentes des États-Unis en matière d'éducation sur le personnel local. Ces pressions peuvent remettre en cause l'objectif principal de la mobilité internationale : l'immersion culturelle. Une collaboration efficace et un dialogue ouvert sont essentiels pour combler ces fossés et pour s'assurer que l'expertise locale est valorisée et les objectifs communs sont atteints. Abstract in Spanish Durante mucho tiempo, Europa ha sido el principal destino para el study abroad de Estados Unidos. Sin embargo, la perspectiva del personal in situ a menudo se ha solido pasar por alto en este ámbito. Los recientes avances hacia prácticas más inclusivas y recíprocas con los socios en Estados Unidos han dado lugar a congresos específicos sobre el contexto europeo y a este número especial, que amplifica la visión de quienes gestionan los programas de study abroad en Europa. Esta introducción destaca la historia particular, la magnitud de este sector y los importantes retrocesos causados por la pandemia del COVID-19. El equipo de edición invitado presenta diversos artículos que abordan las brechas estructurales, pedagógicas, culturales e históricas en la colaboración transatlántica. Los temas principales incluyen la atención al alumnado, la salud mental, la diversidad, la equidad y la inclusión, la concienciación sobre el cambio climático y el impacto de las expectativas educativas estadounidenses en el personal local. Estas presiones pueden dificultar el objetivo central de study abroad: la inmersión cultural. La colaboración efectiva y el diálogo abierto son imprescindibles para superar estas divisiones, asegurando que se valore la experiencia local y se alcancen los objetivos compartidos.

In silico modeling of subcutaneous injections is a promising tool to derisk and optimize the development of injections systems and improve preliminary understanding of the injectability of drugs. Such modeling can be leveraged early in development, prior to pre-clinical studies, to reduce testing burden and effectively predict aspects such as the time and forces required for full dose delivery into tissue and the tissue-injectate-device interactions. In this work, we address the three main in silico pillars (primary container, injection device, and tissue) that are necessary to simulate a parenteral injection. We showcase how their modeling can be combined and applied to various delivery systems and injection conditions to enable appropriate systems and parameters selection to achieve desired performance. Case studies of viscous drugs in PFS/AI and wearable injection systems with non-rigid component properties are presented to highlight the theoretical treatment of interfaces, the critical inputs required to achieve accurate predictions, the insights gained, and the good agreement between model predictions and experimental results.

Abstract Purpose. To assess clinical impact and perform cost-consequence analysis of the broadest multiplex PCR panels available for the rapid diagnosis of bloodstream infections (BSI). Methods. Single-center, randomized controlled trial conducted from June 2019 to February 2021 at a French University hospital with an institutional antimicrobial stewardship program. Primary endpoint was the percentage of patients with optimized antimicrobial treatment 12h after transmission of positivity and Gram stain results from the first positive BC. Results. This percentage was significantly higher in the multiplex PCR (mPCR) group (90/105 = 85.7% %, IC95% [77.5 ; 91.8] vs. 68/107 = 63.6%, IC95% [53.7 ; 72.6]; p<10-3) at interim analysis, resulting in the early termination of the study after the inclusion of 309 patients. For patients not optimized at baseline, the median time to obtain an optimized therapy was much shorter in the mPCR group than in the control group (6.9h, IQR [2.9; 17.8] vs 26.4h, IQR [3.4; 47.5]; p=0.001). Early optimization of antibiotic therapy resulted in a non-statistically significant decrease in mortality from 12.4% to 8.8% (p=0.306), with a tendency for a lower median length of stay (18 vs. 20 days; p=0.064) and a non-significant reduction in the average cost per patient of €3,065 (p=0.15). mPCR identified all the bacteria present in 88% of the samples. Conclusion. Despite its higher laboratory cost, the use of multiplex PCR for BSI diagnosis leads to early-optimised therapy, seems cost-effective and could reduce mortality and length of stay. Their impact could probably be improved if implemented 24/7.

Background and importanceParenteral medication is primarily delivered via conventional vial or ampoule and syringe in hospital settings; however, prefilled syringes (PFS) offer economic and clinical advantages, including reductions in preventable adverse drug events (pADEs), drug waste and supply costs, and increases in workflow efficiencies. The benefits of converting from vials and ampoules to PFS (denoted as ‘V2P’ hereafter) have been elucidated in previously developed economic models; however, these models are country-specific, therefore limiting generalisability of findings.Aim and objectivesTo examine the potential impact of V2P, an economic model was developed to provide hospitals with a standardised tool for use across acute and emergency clinical settings.Material and methodsThe Excel-based economic model estimates the potential benefit of V2P related to four key outcomes: pADEs, labour–time efficiency, unused drug, and cost of supplies. Built-in model defaults were derived from existing peer-reviewed literature sources, expert interviews, and national datasets. The model user can input specific information related to the hospital department and drug of interest. Users may also change built-in model defaults.To investigate model utility, a hypothetical case study was conducted focusing on atropine administration in a UK cardiac intensive care unit (ICU) administering 35 doses/day of atropine. Literature-based inputs included drug costs of £0.82/ampoule dose and £5.03/PFS dose and vial drug waste levels at 85%. The built-in assumptions were 1.39 and 0.73 pADEs per 100 administrations for vials and PFS, respectively.ResultsIn the hypothetical case study, annual V2P cost savings associated with reductions in pADEs, unused drug, and costs of supplies were £64 126, £59 361 and £2667, respectively. While the annual cost of PFS was £53 783 greater than vials, the net budget savings of V2P was £72 372 per year. Additionally, preparation time decreased 893 hours per year. Full results will be presented.Conclusion and relevanceThe model provides a generalisable framework with customisable inputs, allowing hospitals in any country to quantify the clinical and economic value of adopting PFS. In a hypothetical cardiac ICU switching from atropine ampoules to PFS, despite increased cost per dose with PFS, the analysis documented reductions in medication preparation time and a net budget savings owing to fewer pADEs and reduced drug wastage.References and/or acknowledgementsConflict of interestCorporate sponsored research or other substantive relationships:MJP received grants and honoraria from various pharmaceutical companies, inclusive of those interested in the topic of this abstract.MW, HG and TE are employees of Becton Dickinson.Alkemi LLC received consultancy fees to advise on study design, data analysis and interpretation.

ABSTRACT Objectives User experience was compared between a new pre-fillable 2.25 mL glass syringe equipped with an ultra-thin-wall (UTW) 8 mm staked needle and a marketed BD Neopak™ syringe equipped with a special-thin-wall (STW) 12.7 mm staked needle. Methods Participants simulated subcutaneous injections with both syringes alone (formative Human Factors study) and in combination with a needlestick-prevention device (validation Human Factors study). Results Usability results of both studies showed higher success rates for delivering the full dose of 2 mL viscous solution (30 cP) with the 8mmUTW syringe than with the 12.7mmSTW one (63% vs. 42% in the formative study). The use of the 8mmUTW syringe demonstrated also better ease of use and acceptance results and 72% of formative study participants preferred this new syringe over the current one when delivering the viscous solution. Using a shorter needle also showed a benefit in decreasing the injection-related anxiety. Besides, in the case of a non-recommended injection technique, the calculated risk of accidental intramuscular injection is reduced by 2 to 13 times with the 8mmUTW syringe. Conclusion Altogether, the results obtained demonstrated an improvement of the user experience with this new syringe compared to the current one in the manual delivery of 2 mL viscous solutions.

Limited published data exists quantifying the influence of human factors (HF) and pen needle (PN) design on delivery outcomes of pen injection systems. This preclinical in vivo study examines the impact of PN hub design and applied force against the skin during injection on needle penetration depth (NPD). To precisely locate injection depth, PN injections (20 µl; 2 IU, U-100 volume equivalent) of iodinated contrast agent were administered to the flank of Yorkshire swine across a range of clinically relevant application forces against the skin (0.25, 0.75, 1.25, and 2.0 lbf). The NPD, representing in vivo needle tip depth in SC tissue, from four 32 G × 4 mm PN devices (BD Nano™ 2nd Gen and three commercial posted-hub PN devices; n = 75/device/force, 1200 total) was measured by fluoroscopic imaging of the resulting depot. The reengineered hub design more closely achieved the 4 mm target NPD with significantly less variability ( P = .006) than commercial posted-hub PN devices across the range of applied injection forces. Calculations of IM (intramuscular) injection risk completed through in silico probability model, using NPD and average human tissue thickness measurements, displayed a commensurate reduction (~2-8x) compared to conventional PN hub designs. Quantifiable differences in injection depth were observed between identical labeled length PN devices indicating that hub design features, coupled with aspects of variable injection technique, may influence injection depth accuracy and consistency. The reengineered hub design may reduce the impact of unintended individual technique differences by improving target injection depth consistency and reducing IM injection potential.

A new automated MYC IHC classifier based on bivariate logistic regression is presented. The predictor relies on image analysis developed with the open-source ImageJ platform. From a histologic section immunostained for MYC protein, 2 dimensionless quantitative variables are extracted: (a) relative distance between nuclei positive for MYC IHC based on euclidean minimum spanning tree graph and (b) coefficient of variation of the MYC IHC stain intensity among MYC IHC-positive nuclei. Distance between positive nuclei is suggested to inversely correlate MYC gene rearrangement status, whereas coefficient of variation is suggested to inversely correlate physiological regulation of MYC protein expression. The bivariate classifier was compared with 2 other MYC IHC classifiers (based on percentage of MYC IHC positive nuclei), all tested on 113 lymphomas including mostly diffuse large B-cell lymphomas with known MYC fluorescent in situ hybridization (FISH) status. The bivariate classifier strongly outperformed the “percentage of MYC IHC-positive nuclei” methods to predict MYC+ FISH status with 100% sensitivity (95% confidence interval, 94-100) associated with 80% specificity. The test is rapidly performed and might at a minimum provide primary IHC screening for MYC gene rearrangement status in diffuse large B-cell lymphomas. Furthermore, as this bivariate classifier actually predicts “permanent overexpressed MYC protein status,” it might identify nontranslocation-related chromosomal anomalies missed by FISH.

Gaining more insight into the mechanisms governing the behavior of proteins at solid/liquid interfaces is particularly relevant in the interaction of high-value biologics with storage and delivery device surfaces, where adsorption-induced conformational changes may dramatically affect biocompatibility. The impact of structural stability on interfacial behavior has been previously investigated by engineering nonwild-type stability mutants. Potential shortcomings of such approaches include only modest changes in thermostability, and the introduction of changes in the topology of the proteins when disulfide bonds are incorporated. Here we employ two members of the aldo-keto reductase superfamily (alcohol dehydrogenase, AdhD and human aldose reductase, hAR) to gain a new perspective on the role of naturally occurring thermostability on adsorbed protein arrangement and its subsequent impact on desorption. Unexpectedly, we find that during initial adsorption events, both proteins have similar affinity to the substrate and undergo nearly identical levels of structural perturbation. Interesting differences between AdhD and hAR occur during desorption and both proteins exhibit some level of activity loss and irreversible conformational change upon desorption. Although such surface-induced denaturation is expected for the less stable hAR, it is remarkable that the extremely thermostable AdhD is similarly affected by adsorption-induced events. These results question the role of thermal stability as a predictor of protein adsorption/desorption behavior.