Non-stoichiometric O-acetylation of Shigella flexneri 2a O-specific polysaccharide: synthesis and antigenicity.

Synthetic functional mimics of the O-antigen from Shigella flexneri 2a are seen as promising vaccine components against endemic shigellosis. Herein, the influence of the polysaccharide non-stoichiometric di-O-acetylation on antigenicity is addressed for the first time. Three decasaccharides, representing relevant internal mono- and di-O-acetylation profiles of the O-antigen, were synthesized from a pivotal protected decasaccharide designed to tailor late stage site-selective O-acetylation. The latter was obtained via a convergent route involving the imidate glycosylation chemistry. Binding studies to five protective mIgGs showed that none of the acetates adds significantly to broad antibody recognition. Yet, one of the five antibodies had a unique pattern of binding. With IC50 in the micromolar to submicromolar range mIgG F22-4 exemplifies a remarkable tight binding antibody against diversely O-acetylated and non-O-acetylated fragments of a neutral polysaccharide of medical importance.

Analysis of the impact of a medication reconciliation tool on the hospital-community interface.

OBJECTIVE: To analyse the impact of a medication reconciliation tool (MRT), which contains information on all the treatments a patient is receiving upon admission as well as intra-hospital therapeutic adjustments and the rationale behind them, on the transmission and quality of the follow-up of prescribing recommendations outside the hospital setting. METHODS: The MRT involved the prescriptions of patients who were aged 75 and over, who were admitted to a geriatric short-stay unit, and who were referred to a general practitioner (GP) upon discharge. Drug discrepancies (DD) and polypharmacy after an intra-hospital medication reconciliation and at the time of renewing the out-patient prescription (one month after discharge) were measured. Satisfaction among GPs was investigated. RESULTS: The medication lists of 173 patients (1242 drugs; median eight drugs/day) were reconciled, optimised, and communicated using the MRT to the 89 GPs of the 103 patients who returned home. Intra-hospital reconciliation identified 779 DDs (4.6 ± 2.3), of which 39.0% were additions to treatment that had been overlooked. After the discharge prescription was renewed, only 1.6 ± 1.6 DDs were measured. Between admission, discharge, and repeat prescription, polypharmacy was reduced from 83.2% to 74.6% and 67.7% (p < 0.05). Despite a 31.5% response rate to the postal questionnaire, 79.3% of physicians thought the MRT facilitated continuity of care and 75.5% wanted it to be rolled-out more widely. CONCLUSION: This study shows that the MRT is a useful tool and of interest for documenting the process of intra-hospital therapeutic optimisation and with regard to the rapid transmission and follow-up of recommendations by partners in the community.

[Analysis of the impact of a medication reconciliation toolkit in the hospital-community interface]. / Analyse de l'impact d'un outil de conciliation médicamenteuse dans l'interface hôpital-ville.

OBJECTIVE: To analyse the impact of a medication reconciliation toolkit (OCM) which details all the treatment at the admission, intra-hospital therapeutic adjustment and their justifications, on the transmission and quality of extra-hospital follow-up of prescribing recommendations. METHODS: The OCM was fulfilled with the prescriptions of patient aged ≥75 years admitted to a geriatric short-stay unit and sent to general practitioners (GPs) upon discharge. Drug discrepancies (DD) and exposure to polypharmacy after intra-hospital medication conciliation and the ambulatory repeat prescribing (1 month after discharge) were measured. GPs' satisfaction was investigated. RESULTS: The medication list of 173 patients (1242 molecules; median 8 molecules/day) were reconciled, optimized, and transmitted using the OCM to the 89 GPs of the 103 patients who were returned home. Intra-hospital conciliation identified 779 DD (4.6 ± 2.3) of which 39.0% were missed treatment additions. After renewal of the discharge order, only 1.6 ± 1.6 DD were measured. Between admission, discharge, and repeat prescribing, exposure to polypharmacy was reduced from 83.2 to 74.6 and 67.7% (p<0.05). Despite a 31.5% response rate to the mail questionnaire, 79.3% of physicians thought the OCM facilitated continuity of care and 75.5% wanted it generalized. CONCLUSION: This study shows that the OCM is a useful tool and of interest for documenting the process of intra-hospital therapeutic optimization and in the rapid transmission and the follow-up of recommendations by partners in the community.

Using a structured reconciliation medication form improves medication transition from hospital to community care and primary care physicians' adherence with medication adaptations and recommendations.

BACKGROUND: Hospital admission and discharge are weakness points in the transition of care. OBJECTIVE: To lower the risk of errors and improve medication information transfer to primary care physician (PCP), we conducted an experimental study using a structured medication reconciliation form (SMRF) in an Acute Care for Elders unit. RESULTS: 1242 drugs of 173 patients were reconciliated at admission, optimized during the stay, and transmitted via the SMRF to the 143 corresponding PCPs. While the optimization led to 779 adaptations from admission to discharge, of which 39.0% were omissions, exposure to polypharmacy was reduced from 83.2 to 74.6% (P < 0.05). One-month post-discharge, with an answer rate of 62.2% among PCPs, the adherence to recommendations was high (85.0%) and the exposure to polypharmacy was further decreased (67.7%; P < 0.05). CONCLUSION: These results provide elements to consider SMRF as an example of good practice for which the impact should be analyzed at larger scale.

Dirhamnolipids secreted from Pseudomonas aeruginosa modify anjpegungal susceptibility of Aspergillus fumigatus by inhibiting ß1,3 glucan synthase activity.

Pseudomonas aeruginosa and Aspergillus fumigatus are the two microorganisms responsible for most of the chronic infections in cystic fibrosis patients. P. aeruginosa is known to produce quorum-sensing controlled rhamnolipids during chronic infections. Here we show that the dirhamnolipids secreted from P. aeruginosa (i) induce A. fumigatus to produce an extracellular matrix, rich in galactosaminogalactan, 1,8-dihydroxynaphthalene (DHN)- and pyo-melanin, surrounding their hyphae, which facilitates P. aeruginosa binding and (ii) inhibit A. fumigatus growth by blocking ß1,3 glucan synthase (GS) activity, thus altering the cell wall architecture. A. fumigatus in the presence of diRhls resulted in a growth phenotype similar to that upon its treatment with anjpegungal echinocandins, showing multibranched hyphae and thicker cell wall rich in chitin. The diRhl structure containing two rhamnose moieties attached to fatty acyl chain is essential for the interaction with ß1,3 GS; however, the site of action of diRhls on GS is different from that of echinocandins, and showed synergistic anjpegungal effect with azoles.