[Cooperation according to French Law "hospital, patients, health and territories": Pharmacists' involvement in Aquitaine region].

In 2009, the French Act "Hospital, Patients, Health and Territories" (loi "Hôpital, Patients, Santé et Territoires") reorganized the outpatient care pathway and defined missions aimed at improving cooperation between pharmaceutical and medical professionals. Five years later, we conducted a survey among community pharmacists in order to assess the appropriation of these missions and the way cooperation was implemented. We also aimed to investigate factors that could hamper or ease the development of these activities in order to identify actions needed to improve pharmacists' involvement. In partnership with the local health authorities "Agence régionale de santé", we conducted a survey via an online questionnaire sent to pharmacy holders in July 2014 in Aquitaine region. Information was collected about the pharmacies, involvement in collaborative activities, and barriers to cooperation. Overall, 20% (249) of pharmacists responded to the survey. They owned predominantly rural pharmacies (46%) or neighborhood pharmacies (41%), with two pharmacists per pharmacy (48%). Regarding collaborative activities, the majority of pharmacists (78%) had conducted interviews with their patients taking vitamin K antagonist therapy and they were willing to continue (87%). The implication was less common concerning other actions such as referent pharmacist for nursing homes (19%) or activities relating to therapeutic educational programs for patients with chronic conditions (34%). The vast majority of respondents (85%) were not aware of opportunities to become a correspondent pharmacist. The main obstacles for engaging in these activities were the lack of time, lack of knowledge about these missions and the lack of remuneration. We identified differences in pharmacists' involvement in collaborative activities depending on selected characteristics of the pharmacies. The findings of this survey underlined pharmacists' acceptance of these missions and suggest that better information and appropriate remuneration could enhance commitment. Recent changes in the legal framework (establishment of "pharmaceutical fees", extension of the scope of pharmaceutical interviews) enable funding for collaborative practices between medical practitioners and pharmacists, thus encouraging better coordination in the patient care pathway

Patterns of antibiotic use in hospital-acquired infections.

BACKGROUND: Monitoring the use of antimicrobials in hospitalized patients is critical owing to the risk of resistance selection. This study aimed to describe the patterns of antimicrobial prescription for the most frequent healthcare-associated infections (HAIs) in France, relating drugs and microbiological data. METHODS: We used data from the 2017 point-prevalence survey of HAI and antimicrobial use in France, a large nationally representative sample survey of inpatients. We sought unambiguous correspondence between individual indications of antibiotic regimen and HAI sites to determine which molecules were directed towards which pathogen, considering its resistance profile. RESULTS: Among 75,698 adult patients from 401 hospitals, 5.1% had an active HAI and 4.3% were being treated for an HAI. The two most frequent antibiotic indications were lower respiratory tract (LRTI, 27.7%) and urinary tract infections (UTI, 18.4%). For LRTI, the most prescribed antibiotic was amoxicillin-clavulanic acid (27.6%) and most frequently isolated pathogens (each accounting for around 17% of isolates) were Staphylococcus aureus, Pseudomonas aeruginosa and Escherichia coli. Meticillin-resistant S. aureus LRTI was more likely to be treated with linezolid. For UTI, ofloxacin, ceftriaxone, amoxicillin/co-amoxiclav were most-prescribed (∼13% each) and E. coli predominantly isolated (52.0%). Extended-spectrum beta-lactamase-producing E. coli UTI were more likely treated by fosfomycin, pivmecillinam or ertapenem. CONCLUSIONS: This study provides a baseline of antimicrobial use in relation to microbiological information in patients with the most common HAIs. These results can serve to direct future efforts in antimicrobial stewardship. Our work could be extended to a broader population, notably in Europe where similar surveys have been conducted

Comparison of governance approaches for the control of antimicrobial resistance: Analysis of three European countries

Policy makers and governments are calling for coordination to address the crisis emerging from the ineffectiveness of current antibiotics and stagnated pipe-line of new ones – antimicrobial resistance (AMR). Wider contextual drivers and mechanisms are contributing to shifts in governance strategies in health care, but are national health system approaches aligned with strategies required to tackle antimicrobial resistance? This article provides an analysis of governance approaches within healthcare systems including: priority setting, performance monitoring and accountability for AMR prevention in three European countries: England, France and Germany. Advantages and unresolved issues from these different experiences are reported, concluding that mechanisms are needed to support partnerships between healthcare professionals and patients with democratized decision-making and accountability via collaboration. But along with this multi-stakeholder approach to governance, a balance between regulation and persuasion is needed

Alloparental behaviour and long-term costs of mothers tolerating other members of the group in a plurally breeding mammal

Cooperative-breeding studies tend to focus on a few alloparental behaviours in highly cooperative species exhibiting high reproductive skew and the associated short-term, but less frequently long-term, fitness costs. We analysed a suite of alloparental behaviours (assessed via filming) in a kin-structured, high-density population of plurally breeding European badgers, Meles meles, which are not highly cooperative. Group members, other than mothers, performed alloparental behaviour; however, this was not correlated with their relatedness to within-group young. Furthermore, mothers babysat, allogroomed cubs without reciprocation, and allomarked cubs more than other members of the group (controlling for observation time). For welfare reasons, we could not individually mark cubs; however, the number observed pre-independence never exceeded that trapped. All 24 trapped cubs, in three filmed groups, were assigned both parents using 22 microsatellites. Mothers may breed cooperatively, as the time they babysat their assigned, or a larger, litter size did not differ. Furthermore, two mothers probably allonursed, as they suckled more cubs than their assigned litter size. An 18-year genetic pedigree, however, detected no short-term (litter size; maternal survival to the following year) or long-term (offspring breeding probability; offspring lifetime breeding success) fitness benefits with more within-group mothers or other members of the group. Rather, the number of other members of the group (excluding mothers) correlated negatively with long-term fitness. Mothers may tolerate other members of the group, as nonbreeders undertook more digging. Our study highlights that alloparental care varies on a continuum from that seen in this high-density badger population, where alloparenting behaviour is minimal, through to species where alloparental care is common and provides fitness benefits. (C) 2010 The Association for the Study of Animal Behaviour. Published by Elsevier Ltd. All rights reserved

Physical performance and glycemic control under SGLT-2-inhibitors in patients with type 2 diabetes and established atherosclerotic cardiovascular diseases or high cardiovascular risk (PUSH): Design of a 4-week prospective observational study.

Background Type 2 diabetes (T2D) is associated with limitation in physical performance. Results from animal studies report enhancement of physical performance in T2D rodents treated with sodium glucose cotransporter 2 inhibitors (SGLT2is). However, in human patients with T2D and established atherosclerotic cardiovascular disease (ASCVD) or high cardiovascular risk, the impact of guideline directed SGLT2i medication on physical performance has not been sufficiently examined. Objectives The main objectives of this study are thus firstly, to assess the changes in physical performance after 4 weeks of exercise therapy in patients with established ASCVD or high cardiovascular risk categorized into three groups according to their glycemic control at baseline. Secondly, to investigate the association of glycemic control at baseline and new guideline directed antidiabetic treatment (inadequate glycemic control and diabetes + new SGLT2i vs. adequate glycemic control and diabetes vs. no diabetes) with change in physical performance. Methods and design This is a 4-week prospective observational study of 450 participants with established ASCVD or high cardiovascular risk with or without T2D and without previous SGLT2i medication undergoing exercise therapy during inpatient rehabilitation in a single center in Switzerland. Upon admission, participants are categorized into 3 groups of 150 participants each according to their glycemic control. Group I consisting of participants with inadequately controlled T2D defined as mean fasting plasma glucose (FPG) of ≥7 mmol/L, who are consequently administered new treatment with an SGLT2i. Group II comprises of participants with adequately controlled T2D with mean FPG of <7 mmol/L requiring no antidiabetic medication change. Group III consists of participants with no diabetes and mean FPG of ≤ 5.5 mmol/L. Primary outcomes are 6-min walk distance and rate of perceived exertion. Secondary outcomes are echocardiographic parameters (left ventricular mass index; global longitudinal strain average; end-diastolic volume), fatigue, muscle, metabolic, and anthropometric measures. Ethics and dissemination This study is conducted in accordance with the Declaration of Helsinki with ethical approval from the Cantonal Ethical Commission of Bern, Switzerland. The results will be published in a peer-reviewed journal. The implementation and reporting will be according to the SPIRIT guidelines. Study protocol registration https://www.clinicaltrials.gov/, identifier: NCT03422263

Guidance on the Selection of Appropriate Indicators for Quantification of Antimicrobial Usage in Humans and Animals

An increasing variety of indicators of antimicrobial usage has become available in human and veterinary medicine, with no consensus on the most appropriate indicators to be used. The objective of this review is therefore to provide guidance on the selection of indicators, intended for those aiming to quantify antimicrobial usage based on sales, deliveries or reimbursement data. Depending on the study objective, different requirements apply to antimicrobial usage quantification in terms of resolution, comprehensiveness, stability over time, ability to assess exposure and comparability. If the aim is to monitor antimicrobial usage trends, it is crucial to use a robust quantification system that allows stability over time in terms of required data and provided output; to compare usage between different species or countries, comparability must be ensured between the different populations. If data are used for benchmarking, the system comprehensiveness is particularly crucial, while data collected to study the association between usage and resistance should express the exposure level and duration as a measurement of the exerted selection pressure. Antimicrobial usage is generally described as the number of technical units consumed normalized by the population at risk of being treated in a defined period. The technical units vary from number of packages to number of individuals treated daily by adding different levels of complexity such as daily dose or weight at treatment. These technical units are then related to a description of the population at risk, based either on biomass or number of individuals. Conventions and assumptions are needed for all of these calculation steps. However, there is a clear lack of standardization, resulting in poor transparency and comparability. By combining study requirements with available approaches to quantify antimicrobial usage, we provide suggestions on the most appropriate indicators and data sources to be used for a given study objective

A multi-gene signature predicts outcome in patients with pancreatic ductal adenocarcinoma.

© 2014 Haider et al.; licensee BioMed Central. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.Improved usage of the repertoires of pancreatic ductal adenocarcinoma (PDAC) profiles is crucially needed to guide the development of predictive and prognostic tools that could inform the selection of treatment options

How to measure hospital antibiotic consumption: comparison of two methods from data surveillance in France

BACKGROUND: Antibiotic use (ABU) surveillance in healthcare facilities (HCFs) is essential to guide stewardship. Two methods are recommended: antibiotic consumption (ABC), expressed as the number of DDD/1000 patient-days; and prevalence of antibiotic prescription (ABP) measured through point prevalence surveys. However, no evidence is provided about whether they lead to similar conclusions. OBJECTIVES: To compare ABC and ABP regarding HCF ranking and their ability to identify outliers. METHODS: The comparison was made using 2012 national databases from the antibiotic surveillance network and prevalence study. HCF rankings according to each method were compared with Spearman's correlation coefficient. Analyses included the ABU from entire HCFs as well as according to type, clinical ward and by antibiotic class and specific molecule. RESULTS: A total of 1076 HCFs were included. HCF rankings were strongly correlated in the whole cohort. The correlation was stronger for HCFs with a higher number of beds or with a low or moderate proportion of acute care beds. ABU correlation between ABC or ABP was globally moderate or weak in specific wards. Furthermore, the two methods did not identify the same outliers, whichever HCF characteristics were analysed. Correlation between HCF ranking varied according to the antibiotic class. CONCLUSIONS: Both methods ranked HCFs similarly overall according to ABC or ABP; however, major differences were observed in ranking of clinical wards, antibiotic classes and detection of outliers. ABC and ABP are two markers of ABU that could be used as two complementary approaches to identify targets for improvement

Molecular Analysis of Precursor Lesions in Familial Pancreatic Cancer

PMCID: PMC3553106This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

AGR2, a unique tumor-associated antigen, is a promising candidate for antibody targeting.

Anterior gradient 2 (AGR2), a protein disulfide isomerase, shows two subcellular localizations: intracellular (iAGR2) and extracellular (eAGR2). In healthy cells that express AGR2, the predominant form is iAGR2, which resides in the endoplasmic reticulum. In contrast, cancer cells secrete and express eAGR2 on the cell surface. We wanted to test if AGR2 is a cancer-specific tumor-associated antigen. We utilized two AGR2 antibodies, P3A5 and P1G4, for in vivo tumor localization and tumor growth inhibition. The monoclonal antibodies recognized both human AGR2 and mouse Agr2. Biodistribution experiments using a syngeneic mouse model showed high uptake of P3A5 AGR2 antibody in xenografted eAgr2+ pancreatic tumors, with limited uptake in normal tissues. In implanted human patient-derived eAGR2+ pancreatic cancer xenografts, tumor growth inhibition was evaluated with antibodies and Gemcitabine (Gem). Inhibition was more potent by P1G4 + Gem combination than Gem alone or P3A5 + Gem. We converted these two antibodies to human:mouse chimeric forms: the constructed P3A5 and P1G4 chimeric mVLhCκ and mVHhCγ (γ1, γ2, γ4) genes were inserted in a single mammalian expression plasmid vector, and transfected into human 293F cells. Expressed human:mouse chimeric IgG1, IgG2 and IgG4 antibodies retained AGR2 binding. Increase in IgG yield by transfected cells could be obtained with serial transfection of vectors with different drug resistance. These chimeric antibodies, when incubated with human blood, effectively lysed eAGR2+ PC3 prostate cancer cells. We have, thus, produced humanized anti-AGR2 antibodies that, after further testing, might be suitable for treatment against a variety of eAGR2+ solid tumors.University of Washington CoMotion FundNCI-EDRN Biomarker Developmental Lab grant U01CA111244, and DoD W81XWH-16-1-0614