[What is the impact of changes in the drug circuit on dispensing activity during pharmaceutical duty?] / Quel impact des évolutions du circuit du médicament sur l'activité de dispensation durant la permanence pharmaceutique ?

INTRODUCTION: Pharmaceutical permanence (PP), outside the working hours of an in-house pharmacy (PUI), allows to guarantee the continuity of care in health-care institutions. A retrospective review of urgent drug dispensing was carried out in the light of changes in the drug circuit. MATERIALS AND METHOD: The analysis of drug dispensations was performed over a period from 2011 to 2019. The average number of drugs dispensed per shift, annual dispensations, and their variation by day of the week were studied. The increase is statistically significant and is found on both weekdays and weekends. Each drug was identified according to its Anatomical Therapeutic Chemical (ATC) classification. Data on the activities of our institution (number of hospitalizations, average length of stay) were also collected. RESULTS: In 2011, an average of 36 medications were dispensed per on-call period, compared with 77 in 2019 (a doubling of activity). The increase is statistically significant and is found on both weekdays and weekends. Neurological drugs and anti-infectives represent on average 43 % of the drugs dispensed. At the same time, there was a decrease in average length of stay and an increase in hospitalizations (-10 % and +16 % respectively). DISCUSSION: The increase in the average number of medications dispensed per shift is notable. It reflects a strong and gradual increase in activity, which was increased when the full vacuum cabinets (FVCs) were introduced, which improved the quality and safety of the pharmaceutical circuit. The revision of the allocations and the information of prescribers on the drug circuit will optimize the activity and refocus it on the pharmaceutical analysis of urgent needs.

Incidence of Melanoma in the Basque Province of Álava, Spain, From 2015 to 2018: A Descriptive Study. / Estudio descriptivo de los pacientes diagnosticados de melanoma en la provincia de Álava (País Vasco) entre los años 2015 y 2018.

INTRODUCTION: The incidence of cutaneous melanoma is rising fast, and its prevalence has doubled in the past 3 decades. Detailed local epidemiological information is essential for informing community-based prevention strategies and optimizing hospital resources. MATERIAL AND METHODS: We included all patients diagnosed with cutaneous melanoma at Hospital Universitario Araba in the Basque province of Álava, Spain, between January 2015 and December 2018. We described clinical and pathologic characteristics and calculated annual incidence rates adjusted to the European standard population. RESULTS: A total of 242 new cases of melanoma were diagnosed between 2015 and 2018. The age-standardized annual incidence rose from 12.92 cases per 100 000 population in 2015 to 18.30 cases per 100 000 population in 2018. CONCLUSIONS: The incidence of melanoma in our area is higher than that reported for Spanish series in 2017 and 2018. Lentigo maligna accounted for a high proportion of cases and was the second largest histologic subgroup.

Estudio descriptivo de los pacientes diagnosticados de melanoma en la provincia de Álava (País Vasco) entre los años 2015 y 2018 / Incidence of Melanoma in the Basque Province of Álava, Spain, From 2015 to 2018: A Descriptive Study

Introducción: La incidencia del melanoma cutáneo está aumentando rápidamente y ha duplicado su prevalencia durante las últimas tres décadas. Tener un conocimiento detallado de la epidemiología local es fundamental para el desarrollo de estrategias de prevención comunitaria y optimizar los recursos hospitalarios. Material y métodos: Se incluyeron todos los pacientes diagnosticados de melanoma cutáneo en el Hospital Universitario Araba, en la provincia de Álava del País Vasco, entre enero de 2015 y diciembre de 2018. Se realizó un análisis descriptivo de las variables clínico-patológicas y un análisis de la incidencia ajustado a la población europea. Resultados: Se incluyeron un total de 242 nuevos casos de melanoma entre 2015 y 2018. La incidencia estandarizada por edad ha aumentado de 12,92 en 2015 a 18,30 casos por 100.000 habitantes y año en 2018. Conclusiones: Hemos observado una incidencia de melanoma más elevada que en la publicada en series nacionales en los años 2017 y 2018. Además, existe una gran proporción del subtipo histológico de tipo lentigo maligno, ocupando el segundo subtipo histológico en frecuencia (AU)

Introduction: The incidence of cutaneous melanoma is rising fast, and its prevalence has doubled in the past 3 decades. Detailed local epidemiological information is essential for informing community-based prevention strategies and optimizing hospital resources. Material and methods: We included all patients diagnosed with cutaneous melanoma at Hospital Universitario Araba in the Basque province of Álava, Spain, between January 2015 and December 2018. We described clinical and pathologic characteristics and calculated annual incidence rates adjusted to the European standard population. Results: A total of 242 new cases of melanoma were diagnosed between 2015 and 2018. The age-standardized annual incidence rose from 12.92 cases per 100 000 population in 2015 to 18.30 cases per 100 000 population in 2018. Conclusions: The incidence of melanoma in our area is higher than that reported for Spanish series in 2017 and 2018. Lentigo maligna accounted for a high proportion of cases and was the second largest histologic subgrou (AU)

[Translated article] Incidence of Melanoma in the Basque Province of Álava, Spain, From 2015 to 2018: A Descriptive Study / Estudio descriptivo de los pacientes diagnosticados de melanoma en la provincia de Álava (País Vasco) entre los años 2015 y 2018

Introduction: The incidence of cutaneous melanoma is rising fast, and its prevalence has doubled in the past 3 decades. Detailed local epidemiological information is essential for informing community-based prevention strategies and optimizing hospital resources. Material and methods: We included all patients diagnosed with cutaneous melanoma at Hospital Universitario Araba in the Basque province of Álava, Spain, between January 2015 and December 2018. We described clinical and pathologic characteristics and calculated annual incidence rates adjusted to the European standard population. Results: A total of 242 new cases of melanoma were diagnosed between 2015 and 2018. The age-standardized annual incidence rose from 12.92 cases per 100 000 population in 2015 to 18.30 cases per 100 000 population in 2018. Conclusions: The incidence of melanoma in our area is higher than that reported for Spanish series in 2017 and 2018. Lentigo maligna accounted for a high proportion of cases and was the second largest histologic subgrou (AU)

Introducción: La incidencia del melanoma cutáneo está aumentando rápidamente y ha duplicado su prevalencia durante las últimas tres décadas. Tener un conocimiento detallado de la epidemiología local es fundamental para el desarrollo de estrategias de prevención comunitaria y optimizar los recursos hospitalarios. Material y métodos: Se incluyeron todos los pacientes diagnosticados de melanoma cutáneo en el Hospital Universitario Araba, en la provincia de Álava del País Vasco, entre enero de 2015 y diciembre de 2018. Se realizó un análisis descriptivo de las variables clínico-patológicas y un análisis de la incidencia ajustado a la población europea. Resultados: Se incluyeron un total de 242 nuevos casos de melanoma entre 2015 y 2018. La incidencia estandarizada por edad ha aumentado de 12,92 en 2015 a 18,30 casos por 100.000 habitantes y año en 2018. Conclusiones: Hemos observado una incidencia de melanoma más elevada que en la publicada en series nacionales en los años 2017 y 2018. Además, existe una gran proporción del subtipo histológico de tipo lentigo maligno, ocupando el segundo subtipo histológico en frecuencia (AU)

Lyme snap: A feasibility study of on-line declarations of erythema migrans in a rural area of France.

The incidence of Lyme borreliosis remains a matter of debate, but it can be estimated using the incidence of erythema migrans (EM), which is pathognomonic of the first phase. The aim of this prospective pilot study was to assess the feasibility of the on-line declaration of EM in rural areas where the incidence of Lyme borreliosis was previously estimated at 85 per 100,000 inhabitants per year. The study was limited to a rural area (Les Combrailles, Auvergne) of approximately 52,800 inhabitants and was preceded by an information campaign for the inhabitants and the healthcare professionals. Patients who sent a photo of the suspected EM by email or MMS message between April 2017 and April 2018 and who accepted to answer a questionnaire were included in the study. Two physicians then evaluated the quality of the photographs and the probability of EM. In parallel, the number of EM seen by physicians and pharmacists in the area over the given period was recorded. Out of the 113 emails and MMS messages received, 73 people were outside of the trial area or period and 9 did not complete the questionnaire. The photos of the remaining 31 people were analysed. The median age was 51.5 years old ([38-58] IQR) and 18 (58%) were women. Seven people (25%) stated that they did not have a smartphone and in 9 cases (29%) the photo was sent by a third party. The quality of the photos was considered very good in 22 (71%) cases, good in 7 (23%) cases, and average in 2 (6%) cases. The probability of EM was determined to be strong or possible in 12 (38%) cases, i.e. an estimated incidence of 22.7 per 100,000 inhabitants. Over the study period, 40 physicians and 20 pharmacists were contacted on a monthly basis. A median of 5 physicians [3;7] and 4 pharmacists [3 ;7] answered each month for a total of 18 and 36 declared EM respectively. The EM (strong probability/possible) collected by on-line declaration and those declared by healthcare professionals were all sent between April and October 2017. The total time spent on the information campaign and collection has been estimated at 265 h (divided between 10 people) for an overall cost of 10,669 Euros. The incidence of EM recorded by on-line self-declaration in our study seems to be lower than in previous studies, the under-reporting was probably linked to the low use of new technologies in the rural areas. Increasing the human resources and finances appears difficult to achieve in practice over a longer time period but the development of an application for the automatic recognition of EM could be one method for a more exhaustive collection in the long term and at lower cost.

Data from a targeted proteomics approach to discover biomarkers in saliva for the clinical diagnosis of periodontitis.

This study focused on the search for new biomarkers based on liquid chromatography-multiple reaction monitoring (LC-MRM) proteomics profiling of whole saliva from patients with periodontitis compared to healthy subjects. The LC-MRM profiling approach is a new and innovative method that has already been validated for the absolute and multiplexed quantification of biomarkers in several diseases. The dataset for this study was produced using LC-MRM to monitor protein levels in a multiplex assay, it provides clinical information on salivary biomarkers of periodontitis. The data presented here is an extension of our recently published research article (Mertens et al., 2017) [1].

Invasive Drosophila suzukii facilitates Drosophila melanogaster infestation and sour rot outbreaks in the vineyards.

How do invasive pests affect interactions between members of pre-existing agrosystems? The invasive pest Drosophila suzukii is suspected to be involved in the aetiology of sour rot, a grapevine disease that otherwise develops following Drosophila melanogaster infestation of wounded berries. We combined field observations with laboratory assays to disentangle the relative roles of both Drosophila in disease development. We observed the emergence of numerous D. suzukii, but no D. melanogaster flies, from bunches that started showing mild sour rot symptoms days after field collection. However, bunches that already showed severe rot symptoms in the field mostly contained D. melanogaster. In the laboratory, oviposition by D. suzukii triggered sour rot development. An independent assay showed the disease increased grape attractiveness to ovipositing D. melanogaster females. Our results suggest that in invaded vineyards, D. suzukii facilitates D. melanogaster infestation and, consequently, favours sour rot outbreaks. Rather than competing with close species, the invader subsequently permits their reproduction in otherwise non-accessible resources and may cause more frequent, or more extensive, disease outbreaks.

The invasive pest Drosophila suzukii uses trans-generational medication to resist parasitoid attack.

Animal medication is a behavioral strategy to resist enemies based on the use of substances from the environment. While it has been observed in several animals, whether invasive species can use medication to resist new enemies during its expansion is unknown. Here, we show that the worldwide invasive pest Drosophila suzukii performs trans-generational prophylactic medication by adapting its oviposition behavior in the presence of enemies. We find that flies preferentially lay their eggs on media containing atropine - an entomotoxic alkaloid - in the presence of parasitoids. We further show that flies developing on atropine more efficiently resist parasitization by parasitoids. Finally, we find that developing in hosts reared on atropine strongly impacts the life-history traits of parasitoids. This protective behavior is reported for the first time in a pest and invasive species, and suggests that animal medication may be an important driver of population dynamics during invasions.

Exposure of Wildlife to the Schmallenberg Virus in France (2011-2014): Higher, Faster, Stronger (than Bluetongue)!

The Schmallenberg virus (SBV) has recently emerged in Europe, causing losses to the domestic livestock. A retrospective analysis of serodata was conducted in France for estimating seroprevalence of SBV among six wildlife species from 2011-2012 to 2013-2014, that is during the three vector seasons after the emergence of the SBV in France. Our objective was to quantify the exposure of wildlife to SBV and the potential protective effect of elevation such as previously observed for bluetongue. We also compared the spatiotemporal trends between domestic and wild animals at the level of the departments. We tested 2050 sera using competitive ELISA tests. Individual and population risk factors were further tested using general linear models among 1934 individuals. All populations but one exhibited positive results, seroprevalence up to 30% being observed for all species. The average seroprevalence did not differ between species but ranged from 0 to 90% according to the area and period, due to the dynamic pattern of infection. Seroprevalence was on average higher in the lowlands compared to areas located up to 800 m. Nevertheless, seroprevalence above 50% occurred in areas located up to 1500 m. Thus, contrary to what had been observed for bluetongue during the late 2000s in the same areas, SBV could spread to high altitudes and infect all the studied species. The spatial spread of SBV in wildlife did not fully match with SBV outbreaks reported in the domestic livestock. The mismatch was most obvious in mountainous areas where outbreaks in wildlife occurred on average one year after the peak of congenital cases in livestock. These results suggest a much larger spread and vector capacity for SBV than for bluetongue virus in natural areas. Potential consequences for wildlife dynamics are discussed.

Wolbachia-mediated protection against viruses in the invasive pest Drosophila suzukii.

The maternally inherited bacterium Wolbachia is well known for spreading in natural populations by manipulating the reproduction of its arthropod hosts, but can also have mutualist effects that increase host fitness. In mosquitoes and Drosophila some Wolbachia strains can lead to an increase in survival of virus-infected insects, and in most cases this is associated with reduced accumulation of the virus in host tissues. We investigated if the Wolbachia strain wSuz, which naturally infects Drosophila suzukii, is able to confer protection against Drosophila C virus and Flock House virus in different host genetic backgrounds. We found that this strain can increase host survival upon infection with these two viruses. In some cases this effect was associated with lower viral titres, suggesting that it confers resistance to the viruses rather than allowing the flies to tolerate infection. Our results indicate that, in D. suzukii, the antiviral protection provided by Wolbachia is not correlated to its density as found in other Drosophila species. This study demonstrates a phenotypic effect induced by wSuz on its native host which could explain its maintenance in natural populations of D. suzukii.

Bluetongue dynamics in French wildlife: exploring the driving forces.

Bluetongue (BT) was monitored in wildlife in France during two consecutive years corresponding to contrasting incidence rates in livestock: in 2008 at the peak of domestic outbreaks and in 2009 when very few outbreaks were observed. The disease status of 2 798 ruminants comprising 837 red deer (Cervus elaphus) was explored using ELISA test on serum and real-time RT-PCR test on blood or spleen. A large proportion of red deer were seropositive and positive to RT-PCR in 2008, but also in 2009 (seroprevalence: 47.1% and 24.3%), suggesting that red deer could maintain infection when domestic incidence was negligible. By contrast, low seroprevalence (<3%) and few RT-PCR positive results were observed in other wild ruminant species, which rather appeared thus as dead-end hosts. The risk factors of bluetongue circulation during the periods of high (2008) and low (2009) domestic incidence were explored in red deer using logistic mixed models. In this species, prevalence has been mainly influenced by the initial peak of BT in livestock, but also by environmental factor such as elevation and edge density between forest and pastures. Surprisingly, cattle density has a negative influence on prevalence in red deer, possibly due to the protective effect of cattle regarding midges' bites and/or to still unexplained factors dealing with the host/midge interface. To our knowledge, this study is the first attempt at measuring the effect of landscape and wildlife/domestic interface on BT prevalence in wildlife in Europe.

Invasive aspergillosis: drug-dispensing systems as a source of filamentous fungal contamination in high-risk units?

High-risk units with air-control measures at Grenoble University Hospital are equipped with automated dispensing systems that are filled daily using drug trolleys routed from the pharmacy to the ward. The aim of this study was to evaluate the level of filamentous fungi (FF) contamination present in trolleys under usual conditions and after cleaning with Aniosurf(®) (fungicidal disinfectant). FF were detected in all samples, and 83.3% of samples were contaminated with Aspergillus fumigatus. Cleaning trolleys with Aniosurf(®) decreased the level of FF significantly, but contamination re-appeared within 24 h due to storage in a non-controlled environment.

Molecular and biological characteristics of Toxoplasma gondii isolates from wildlife in France.

Toxoplasma gondii isolates have been classified into 3 genetic types. Little is known about genotypes of T. gondii isolates in wild animals in Europe. In this report, genotypes of T. gondii isolates from wildlife in France are described. Sera from wildlife were tested for antibodies to T. gondii with the modified agglutination test, and the hearts from animals with titers superior or equal to 1:6 were bioassayed individually in mice. T.gondii was isolated from 9 of 14 seropositive red foxes (Vulpes vulpes), 12 of 33 roe deer (Capreolus capreolus), 1 of 4 deer (Cervus elaphus), 1 of 7 mouflons (Ovis gmelini musimon) and 1 of 2 common mallards (Anas platyrhynchos). No isolate was obtained by bioassay in mice of 1 fallow deer (Dama dama) and of 3 European brown hares (Lepus europaeus). Genotyping of the 24 isolates using PCR-RFLP and microsatellite markers indicated that all were type II and none of these Toxoplasma isolates was virulent for mice.