[Methodology to develop a virtual reality training for good practices in the preparation of anti-cancer drugs]. / Méthodologie pour développer une formation aux bonnes pratiques de préparation des anticancéreux en réalité virtuelle à 360°.

OBJECTIVE: Describe the process for designing and creating SimUPAC 360°, a virtual reality training in anti-cancer drug production units. METHODS: A multi-centre (a University Hospital, a General Hospital and a Cancer Control Centre), inter-professional (pharmacists, hospital pharmacy technicians and health executives) working group has been set up. It was based on videoconferencing and online document sharing. The work was divided into six phases: choice of target audience and training objectives, definition of the business model, development of the scenario, shooting and editing, creation of the training tool and finally tests, adjustments and validation of the tool. RESULTS: After brainstorming, 77 errors were proposed. Three areas have been defined: covering area, storage and production area, and isolator. They contained 15 errors among the 77 proposed and 20 points of interest. The shooting was carried out over 2 days, in 2 hospitals. Assembly was carried out by a service provider specialist in real virtuality. Before to go online, the tool was tested and validated by experts. DISCUSSION: The establishment of a multi-centric and interdisciplinary working group, the choice of target audience, pedagogical objectives and business model ensure the economic viability and scientific and technical robustness of the tool. The scenario development requires to define: activity areas and then, number, difficulty and typology of errors. CONCLUSION: Creation of a virtual reality training requires a consistent and structured methodology. This methodology will make it possible to develop other training scenarios.

[Continuous theoretical training in onco-hematology for pharmacy technician's working in cytotoxic preparation unit]. / Mise en place d'une formation continue théorique en onco-hématologie au sein d'une unité de préparation des anticancéreux.

OBJECTIVES: Within the context of pharmacy technician's (PT) continuing training (CT), a theoretical instruction in onco-hematology has been developed for PT working in our cytotoxic preparation unit (CPU). The aim of this study is to describe the approach taken, tools used and present knowledge assessment (KA). METHODS: A previous KA has been conducted using quiz available on GERPAC website which listing 36 drugs. Forty-five minutes sessions were conducted. KA was assessing before and after each session and 2 years after. PT appreciation was also evaluated. RESULTS: The previous KA served to targeting gaps and insisted on: indications, mechanism of action and cytotoxic drugs costs. Interactive sessions were led by a pharmacist and concerned about 17 diseases and 3 of the most prescribed cytotoxic drugs: 47 drugs summaries have been written by a pharmacist. The before-after knowledge improvement is significant (P>0.0005) (average [a] before=4.7 vs. a after=9.6). Two years after, this was non-significant but assessment results remain higher than before sessions (a=4.7 vs. 6.8). All PT wish sessions sustainability, 92% reported an adequate comprehension level. CONCLUSION: Lack of time and staff constitute a brake for sustaining and this was also highlighted by other units. Share this experience on a web platform could be interesting. Nevertheless, supports used during sessions should be suitable in conformity with the hospital practice and updated with new therapeutic.

Mutagenicity assessment of environmental contaminations in a hospital centralized reconstitution unit.

INTRODUCTION: Cytotoxic drug exposure of hospital staff preparing intravenous chemotherapy is a major issue and related mutagenic risks should be more explored. The aim of this study was to assess the mutagenicity of several cytotoxic mixtures prepared at fixed concentrations, and the mutagenicity of environmental samples collected in a hospital centralized reconstitution unit. In parallel cytotoxic exposure in environmental samples was quantified. METHODS: Environmental samples were performed by wiping method using swabs in five critical production unit areas. Mutagenicity was assessed with a liquid microplate AMES test using two salmonella typhimurium strains (TA98 and TA100), in prepared cytotoxic mixtures containing 14 cytotoxic drugs (cyclophosphamide, cytarabine, dacarbazine, docetaxel, doxorubicin, epirubicin, etoposide, 5-fluorouracil, gemcitabine, ifosfamide, irinotecan, methotrexate, paclitaxel and pemetrexed) according a dichotomous strategy and in environmental samples. Cytotoxic drugs were quantified in samples using liquid chromatography coupled to mass tandem spectrometry. RESULTS: Mutagenesis was observed for the mix of 14 cytotoxic drugs with TA98 strain ±â€¯S9 fraction but not TA100 strain. After dichotomous approach, only doxorubicin and epirubicin exposure were associated to mutagenesis. The mutagenesis observed was expressed at lower concentrations with the mix of the 14 drugs than with anthracyclins alone, assuming a synergistic effect. Despite measurable level of cytotoxic contamination in environmental samples, no mutagenesis was highlighted in Ames tests performed on these environmental samples. CONCLUSIONS: The analyses carried out show the conservation of the mutagenicity of cytotoxic drugs found in very low quantities in the environment. The traces of cytotoxic drugs found in our unit regularly exceed the limits given by some authors. This approach may be considered as a new tool to monitor environmental contamination by cytotoxic drugs.

[Implementation and assessment of anticancer drugs batch preparation circuit in a teaching hospital]. / Préparations hospitalières d'anticancéreux : mise en place et évaluation d'un circuit.

INTRODUCTION: In 2011, the anticancer preparation unit in a teaching hospital implemented a circuit for batch preparation of anticancer drugs. In this circuit, a manual and a semi-automatic production process coexist. The aim of the study is to describe the circuit in 2016 and to assess the impact of batch preparation in a anticancer preparation unit. MATERIAL AND METHODS: Eligible anticancer drugs for batch preparation satisfy two conditions: solution stability up to 28 days, prescription frequency up to one every two days. Batch worksheets are standardized. The pharmaceutical validation relies on the conformity of microbiological, analytical, gravimetric and visual controls of infusion bags. The duration of manual and semi-automatic batch preparation process and the time availability of an infusion bag were assessed. RESULTS: In 2016, eleven anticancer drugs (33 dosages) were eligible for batch preparation: it represents 22% of total production. In total, 70% was semi-automatic. The mean batch sizes were 27±9 (semi-automatic) and 14±1 (manual). The mean duration of production process was respectively 78min and 113min for semi-automatic and manual batch preparation. The mean time availability of an infusion bag was 32min±17. DISCUSSION AND CONCLUSION: Our process is secure. Batch preparation of anticancer drugs contributes to smooth production and spare nurses from preparing infusion bags outside opening hours of the anticancer preparation unit. Eligible anticancer drugs and batches size change constantly according to the evolution of prescription frequencies and anticancer drugs public tenders.

Pseudotyped retroviruses for infecting axolotl in vivo and in vitro.

Axolotls are poised to become the premiere model system for studying vertebrate appendage regeneration. However, very few molecular tools exist for studying crucial cell lineage relationships over regeneration or for robust and sustained misexpression of genetic elements to test their function. Furthermore, targeting specific cell types will be necessary to understand how regeneration of the diverse tissues within the limb is accomplished. We report that pseudotyped, replication-incompetent retroviruses can be used in axolotls to permanently express markers or genetic elements for functional study. These viruses, when modified by changing their coat protein, can infect axolotl cells only when they have been experimentally manipulated to express the receptor for that coat protein, thus allowing for the possibility of targeting specific cell types. Using viral vectors, we have found that progenitor populations for many different cell types within the blastema are present at all stages of limb regeneration, although their relative proportions change with time.

Conjunctival mucous membrane colour as an indicator for the targeted selective treatment of haemonchosis and of the general health status of peri-urban smallholder goats in southern Malawi.

The world's growing population is becoming increasingly centred around large cities, affording opportunities for peri-urban food production. Goats are well-suited to conversion of resources that are available in peri-urban settings into meat and occasionally milk. Haemonchus contortus has been described as "the nemesis of small ruminant production systems in tropical and subtropical regions"; hence control of haemonchosis through planned animal health management affords a pragmatic first step in improving the production efficiency of peri-urban goats. This study of peri-urban goat production investigated the potential value of targeted selective treatment of haemonchosis. 452 peri-urban goat keepers in southern Malawi were visited during three seasonal periods with relevance to the epidemiology of haemonchosis. 622, 599 and 455 individually identified goats were clinically examined during the dry season, the rainy season, and shortly after the end of the rainy season, respectively. Data were recorded for sex, age, weight, conjunctival mucous membrane colour score (FAMACHA©), body condition score (BCS) and faecal worm egg count (FEC); and where possible for pregnancy and lactation status. Animals with pale ocular mucous membranes were treated with 10 mg/kg albendazole, then re-examined 14 days later. Animals with pink mucous membranes, but FECs ≥250 eggs per gram were also re-examined and treated 14 days later. The results show high variability in growth rates deduced from the ages and bodyweights of each of 999 goats at the time of their enrolment. FAMACHA© scores alone were a poor index for the targeted selective treatment of haemonchosis, because they failed to identify too many animals that would have required treatment at different times of year and using different FAMACHA© and FEC cut-offs. Combining the indices of FAMACHA© scores ≥4, body condition scores ≥2, and age >18 months was more reliable in identifying those animals requiring treatment when different epidemiologically-relevant FEC thresholds for different seasons were taken into account. Inclusion of late pregnancy or early lactation status would have resulted in very few animals requiring treatment being missed. The use of conjunctival mucous membrane colour scoring in this way provided a valuable insight of the general health status of the peri-urban goats, to create opportunities for planned animal health management to improve productivity. The efficacy of albendazole treatment was poor, putatively due to drug resistance, or poor drug bioavailability in goats. In summary, our study shows opportunities for better production efficiency in peri-urban goats, and demonstrates the value of simple clinical diagnostic indices as decision support tools in planned animal health management.

Beneficial effects of implementing guidelines on microbiology and costs of infected diabetic foot ulcers.

AIMS/HYPOTHESIS: In 2003, guidelines for management of diabetic foot infection (DFI) were written by the authors' team according to the guidelines of the International Working Group on the Diabetic Foot. The effects of implementing these guidelines on the microbiology and costs of infected diabetic foot ulcers were assessed. METHODS: From 2003 to 2007, potential beneficial effects of implementing these guidelines were assessed by comparison over time of bacteriological data (number of bacterial samples, number of microorganisms isolated in cultures, prevalence of multidrug-resistant organisms [MDRO] and colonising flora), and costs related to use of antimicrobial agents and microbiology laboratory workload. RESULTS: The study included 405 consecutive diabetic patients referred to the Diabetic Foot Unit for a suspected DFI. From 2003 to 2007, a significant decrease was observed in the median number of bacteria species per sample (from 4.1 to 1.6), prevalence of MDRO (35.2% vs 16.3%) and methicillin-resistant Staphylococcus aureus (52.2% vs 18.9%) (p < 0.001). Moreover, prevalence of pathogens considered as colonisers dramatically fell from 23.1% to 5.8% of all isolates (p < 0.001). In parallel, implementation of guidelines was associated with a saving of euro14,914 (US$20,046) related to a reduced microbiology laboratory workload and euro109,305 (US$147,536) due to reduced prescription of extended-spectrum antibiotic agents. CONCLUSIONS/INTERPRETATION: Implementation of guidelines for obtaining specimens for culture from patients with DFI is cost-saving and provides interesting quality indicators in the global management of DFI.

[In vitro activity of daptomycin against strains isolated from diabetic foot ulcers]. / Activité in vitro de la daptomycine vis-à-vis de souches cliniques isolées de plaies du pied chez des diabétiques.

PURPOSE OF THE STUDY: The aim of this study was to evaluate the in vitro activity of daptomycin and other comparator agents against bacterial strains isolated from diabetic foot infections (DFI). PATIENTS AND METHODS: All diabetic patients hospitalized for a first episode of DFI (stage 2 to 4, according to the International Working Group of Diabetic Foot classification) were selected in Nîmes University hospital between June 2006 to August 2007. MIC were determined using E-test strip (AB Biodisk) and custom broth microdilution panels against bacterial strains isolated from foot samples. RESULTS: Two hundred strains were studied. Daptomycin was active against 99.5% of all the strains especially Streptococcus sp. (100%), Enterococcus sp. (100%), coagulase-negative Staphylococcus (100%) and methicillin-susceptible Staphylococcus aureus (100%). Exclusively, one methicillin-resistant S. aureus strain was not covered by this antibiotic. CONCLUSIONS: Daptomycin, a new broad spectrum antimicrobial agent against Gram-positive cocci, is qualified to belong to the therapeutic arsenal package of complicated skin and soft tissue infections in diabetic patients after microbial documentation.

Risk factors and healing impact of multidrug-resistant bacteria in diabetic foot ulcers.

AIM: To determine the risk factors for acquiring multidrug-resistant organisms (MDRO) and their impact on outcome in infected diabetic foot ulcers. METHODS: Patients hospitalized in our diabetic foot unit for an episode of infected foot ulcer were prospectively included. Diagnosis of infection was based on clinical findings using the International Working Group on the Diabetic Foot-Infectious Diseases Society of America (IWGDF-ISDA) system, and wound specimens were obtained for bacterial cultures. Each patient was followed-up for 1 year. Univariate analysis was performed to compare infected ulcers according to the presence or absence of MDRO; logistic regression was used to identify explanatory variables for MDRO presence. Factors related to healing time were evaluated by univariate and multivariate survival analyses. RESULTS: MDRO were isolated in 45 (23.9%) of the 188 patients studied. Deep and recurrent ulcer, previous hospitalization, HbA(1c) level, nephropathy and retinopathy were significantly associated with MDRO-infected ulceration. By multivariate analysis, previous hospitalization (OR=99.6, 95% CI=[19.9-499.0]) and proliferative retinopathy (OR=7.4, 95% CI=[1.6-33.7]) significantly increased the risk of MDRO infection. Superficial ulcers were associated with a significant decrease in healing time, whereas neuroischaemic ulcer, proliferative retinopathy and high HbA(1c) level were associated with an increased healing time. In the multivariate analysis, presence of MDRO had no significant influence on healing time. CONCLUSION: MDRO are pathogens frequently isolated from diabetic foot infection in our foot clinic. Nevertheless, their presence appears to have no significant impact on healing time if early aggressive treatment, as in the present study, is given, including empirical broad-spectrum antibiotic treatment, later adjusted according to microbiological findings.

[In vitro activity of ertapenem against strains isolated from diabetic foot infections]. / Activité in vitro de l'ertapénème vis-à-vis de souches bactériennes isolées de plaies infectées du pied chez des patients diabétiques.

OBJECTIVE: The authors aimed to evaluate the in vitro activity of ertapenem against bacterial strains isolated from diabetic foot infections (DFI). METHODOLOGY: All diabetic patients hospitalized for a first episode of DFI (stages 2 to 4, according to the International Working Group of Diabetic Foot Classification) were selected in the Nîmes University hospital between January 2005 to December 2005. MICs were determined using both E-test strips and dilution methods on bacterial strains isolated from foot samples. RESULTS: Two hundred and fifty-two bacteria (154 Gram-positive cocci including 94 Staphylococcus aureus, 80 Gram-negative bacilli with 56 Enterobacteriaceae, and 18 anaerobes) were studied. Ertapenem was active against all Streptococcus spp., Enterobacteriaceae, anaerobes, and also against 89.8% of methicillin-susceptible S. aureus isolates. However, this antibiotic was active only against 31.5% of Staphylococcus epidermidis, 21.8% of Enterococcus faecalis, and 15.8% of Pseudomonas aeruginosa. CONCLUSION: Our results indicate that ertapenem may be a useful agent to treat patients suffering from DFI after bacterial identification.