Risk perception of antimicrobial resistance by infection control specialists in Europe: a case-vignette study

Background Using case-vignettes, we assessed the perception of European infection control (IC) specialists regarding the individual and collective risk associated with antimicrobial resistance (AMR) among inpatients. Methods In this study, sixteen case-vignettes were developed to simulate hospitalised patient scenarios in the field of AMR and IC. A total of 245 IC specialists working in different hospitals from 15 European countries were contacted, among which 149 agreed to participate in the study. Using an online database, each participant scored five randomly-assigned case-vignettes, regarding the perceived risk associated with six different multidrug resistant organisms (MDRO). The intra-class correlation coefficient (ICC), varying from 0 (poor) to 1 (perfect), was used to assess the agreement for the risk on a 7-point Likert scale. High risk and low/neutral risk scorers were compared regarding their national, organisational and individual characteristics. Results Between January and May 2017, 149 participants scored 655 case-vignettes. The perceptions of the individual (clinical outcome) and collective (spread) risks were consistently lower than other MDRO for extended spectrum beta-lactamase producing Enterobacteriaceae cases and higher for carbapenemase producing Enterobacteriaceae (CPE) cases. Regarding CPE cases, answers were influenced more by the resistance pattern (93%) than for other MDRO. The risk associated with vancomycin resistant Enterococci cases was considered higher for the collective impact than for the individual outcome (63% vs 40%). The intra-country agreement regarding the individual risk was globally poor varying from 0.00 (ICC: 0–0.25) to 0.51 (0.18–0.85). The overall agreement across countries was poor at 0.20 (0.07–0.33). IC specialists working in hospitals preserved from MDROs perceived a higher individual (local, p = 0.01; national, p < 0.01) and collective risk (local and national p < 0.01) than those frequently exposed to bacteraemia. Conversely, IC specialists working in hospitals with a high MDRO clinical burden had a decreased risk perception. Conclusions The perception of the risk associated with AMR varied greatly across IC specialists and countries, relying on contextual factors including the epidemiology. IC specialists working in high prevalence areas may underestimate both the individual and collective risks, and might further negatively promote the MDRO spread. These finding highlight the need to shape local and national control strategies according to risk perceptions and contextual factors

Investigating the cultural and contextual determinants of antimicrobial stewardship programmes across low-, middle- and high-income countries—A qualitative study

Background Most of the evidence on antimicrobial stewardship programmes (ASP) to help sustain the effectiveness of antimicrobials is generated in high income countries. We report a study investigating implementation of ASP in secondary care across low-, middle- and high-income countries. The objective of this study was to map the key contextual, including cultural, drivers of the development and implementation of ASP across different resource settings. Materials and methods Healthcare professionals responsible for implementing ASP in hospitals in England, France, Norway, India, and Burkina Faso were invited to participate in face-to face interviews. Field notes from observations, documentary evidence, and interview transcripts were analysed using grounded theory approach. The key emerging categories were analysed iteratively using constant comparison, initial coding, going back the field for further data collection, and focused coding. Theoretical sampling was applied until the categories were saturated. Cross-validation and triangulation of the findings were achieved through the multiple data sources. Results 54 participants from 24 hospitals (England 9 participants/4 hospitals; Norway 13 participants/4 hospitals; France 9 participants/7 hospitals; India 13 participants/ 7 hospitals; Burkina Faso 8 participants/2 hospitals) were interviewed. Across Norway, France and England there was consistency in ASP structures. In India and Burkina Faso there were country level heterogeneity in ASP. State support for ASP was perceived as essential in countries where it is lacking (India, Burkina Faso), and where it was present, it was perceived as a barrier (England, France). Professional boundaries are one of the key cultural determinants dictating involvement in initiatives with doctors recognised as leaders in ASP. Nurse and pharmacist involvement was limited to England. The surgical specialty was identified as most difficult to engage with in each country. Despite challenges, one hospital in India provided the best example of interdisciplinary ASP, championed through organisational leadership. Conclusions ASP initiatives in this study were restricted by professional boundaries and hierarchies, with lack of engagement with the wider healthcare workforce. There needs to be promotion of interdisciplinary team work including pharmacists and nurses, depending on the available healthcare workforce in different countries, in ASP. The surgical pathway remains a hard to reach, but critical target for ASP globally. There is a need to develop contextually driven ASP targeting the surgical pathway in different resource settings

Experiences and perspectives of implementing antimicrobial stewardship in five French hospitals: a qualitative study

Objective To describe current antimicrobial stewardship program (ASP) in France, both at policy level and at local implementation level, and to assess how ASP leaders (ASPL) worked and prioritised their activities. Methods We conducted a qualitative study based on face-to-face semi-structured interviews with healthcare professionals responsible for ASP across five French hospitals. Five infectious disease specialists and one microbiologist were interviewed between April and June 2016. Results Stewards had dedicated time to perform ASP activities in two university-affiliated hospitals while in the other hospitals (one university, one general and one semi-private), ASPLs had to balance these activities with clinical practice. Consequently, they had to adapt interventions according to their resources (IT or human). Responding to colleagues' consultation requests formed baseline work. Systematic and pro-active measures allowed for provision of unsolicited counselling, while direct counselling on wards required appropriate staffing. ASPL aimed at increasing clinicians' ability to prescribe adequately and awareness of the unintended consequences of inappropriate use of antibiotics. Thus, persuasive e.g. education measures were preferred to coercive ones. ASPL faced several challenges in implementing ASP: overcoming physicians' or units' reluctance, and balancing the influence of medical hierarchy and professional boundaries. Conclusion Beyond resources constraints, ASPLs' conceptions of their work, as well as contextual and cultural aspects, led them to adopt a persuasive and collaborative approach of counselling. This is the first qualitative study about ASP in France exploring stewards' experiences and points of view

Voyage en Espagne

AntepSign.: []4, A-Q8, R4Retrato calc. de Felipe I

A regulatory region on RIPK2 is required for XIAP binding and NOD signaling activity.

Signaling via the intracellular pathogen receptors nucleotide-binding oligomerization domain-containing proteins NOD1 and NOD2 requires receptor interacting kinase 2 (RIPK2), an adaptor kinase that can be targeted for the treatment of various inflammatory diseases. However, the molecular mechanisms of how RIPK2 contributes to NOD signaling are not completely understood. We generated FLAG-tagged RIPK2 knock-in mice using CRISPR/Cas9 technology to study NOD signaling mechanisms at the endogenous level. Using cells from these mice, we were able to generate a detailed map of post-translational modifications on RIPK2. Similar to other reports, we did not detect ubiquitination of RIPK2 lysine 209 during NOD2 signaling. However, using site-directed mutagenesis we identified a new regulatory region on RIPK2, which dictates the crucial interaction with the E3 ligase XIAP and downstream signaling outcomes. © 2020 The Authors

A systematic approach to diverse, lead-like scaffolds from α,α-disubstituted amino acids.

A powerful strategy for the efficient lead-oriented synthesis of novel molecular scaffolds is demonstrated. Twenty two scaffolds were prepared from just four α-amino acid-derived building blocks and a toolkit of six connective reactions. Importantly, each individual scaffold has the ability to specifically target lead-like chemical space

Granulovirus PK-1 kinase activity relies on a side-to-side dimerization mode centered on the regulatory αC helix

The life cycle of Baculoviridae family insect viruses depends on the viral protein kinase, PK-1, to phosphorylate the regulatory protein, p6.9, to induce baculoviral genome release. Here, we report the crystal structure of Cydia pomenella granulovirus PK-1, which, owing to its likely ancestral origin among host cell AGC kinases, exhibits a eukaryotic protein kinase fold. PK-1 occurs as a rigid dimer, where an antiparallel arrangement of the αC helices at the dimer core stabilizes PK-1 in a closed, active conformation. Dimerization is facilitated by C-lobe:C-lobe and N-lobe:N-lobe interactions between protomers, including the domain-swapping of an N-terminal helix that crowns a contiguous β-sheet formed by the two N-lobes. PK-1 retains a dimeric conformation in solution, which is crucial for catalytic activity. Our studies raise the prospect that parallel, side-to-side dimeric arrangements that lock kinase domains in a catalytically-active conformation could function more broadly as a regulatory mechanism among eukaryotic protein kinases

Structure of shocks in Burgers turbulence with L\'evy noise initial data

We study the structure of the shocks for the inviscid Burgers equation in dimension 1 when the initial velocity is given by L\'evy noise, or equivalently when the initial potential is a two-sided L\'evy process $\psi_0$. When $\psi_0$ is abrupt in the sense of Vigon or has bounded variation with $\limsup_{|h| \downarrow 0} h^{-2} \psi_0(h) = \infty$, we prove that the set of points with zero velocity is regenerative, and that in the latter case this set is equal to the set of Lagrangian regular points, which is non-empty. When $\psi_0$ is abrupt we show that the shock structure is discrete. When $\psi_0$ is eroded we show that there are no rarefaction intervals.Comment: 22 page