Comparison of different prognostic scores in estimating short- and long-term mortality in COVID-19 patients above 60 years old in a university hospital in Belgium.

BACKGROUND AND OBJECTIVES: Multiple scoring systems were used for risk stratification in COVID-19 patients. The objective was to determine among 6 scores which performed the best in predicting short-and long-term mortality in hospitalized COVID-19 patients ≥ 60 years. METHODS: An observational, retrospective cohort study conducted between 21/10/2020 and 20/01/2021. 6 scores were calculated (Clinical Frailty Scale (CFS), Charlson Comorbidity Index (CCI), 4C Mortality Score (4CMS), NEWS score (NEWS), quick-SOFA score (qSOFA), and Quick COVID-19 Severity Index (qCSI)). We included unvaccinated hospitalized patients with COVID-19 ≥ 60 years old in Brugmann hospital, detected by PCR and/or suggestive CT thorax images. Old and nosocomial infections, and patients admitted immediately at the intensive care unit were excluded. RESULTS: 199 patients were included, mean age was 76.2 years (60-99). 47.2% were female. 56 patients (28%) died within 1 year after the first day of hospitalization. The 4CMS predicted the best intrahospital, 30 days and 6 months mortality, with area under the ROC curve (AUROC) 0.695 (0.58-0.81), 0.76 (0.65-0.86) and 0.72 (0.63-0.82) respectively. The CCI came right after with respectively AUROC of 0.69 (0.59-0.79), 0.74 (0.65-0.83) and 0.71 (0.64-0.8). To predict mortality at 12 months after hospitalization, the CCI had the highest AUROC with 0.77 (0.69-0.85), before the 4CMS with 0.69 (0.60-0.79). DISCUSSION: Among 6 scores, the 4CMS was the best to predict intrahospital, 30-day and 6-month mortality. To predict mortality at 12 months, CCI had the best performance before 4CMS. This reflects the importance of considering comorbidities for short- and long-term mortality after COVID 19. REGISTRATION: This study was approved by the ethical committee of Brugmann University Hospital (reference CE 2020/228).

Selection for treatment of patients at high risk of fracture by the short versus long term prediction models - data from the Belgian FRISBEE cohort.

Our imminent model was less sensitive but more selective than FRAX® in the choice of treatment to prevent imminent fractures. This new model decreased NNT by 30%, which could reduce the treatment costs. In the Belgian FRISBEE cohort, the effect of recency further decreased the selectivity of FRAX®. PURPOSE: We analyzed the selection for treatment of patients at high risk of fracture by the Belgian FRISBEE imminent model and the FRAX® tool. METHODS: We identified in the FRISBEE cohort subjects who sustained an incident MOF (mean age 76.5 ± 6.8 years). We calculated their estimated 10-year risk of fracture using FRAX® before and after adjustment for recency and the 2-year probability of fracture using the FRISBEE model. RESULTS: After 6.8 years of follow-up, we validated 480 incident and 54 imminent MOFs. Of the subjects who had an imminent fracture, 94.0% had a fracture risk estimated above 20% by the FRAX® before correction for recency and 98.1% after adjustment, with a specificity of 20.2% and 5.9%, respectively. The sensitivity and specificity of the FRISBEE model at 2 years were 72.2% and 55.4%, respectively, for a threshold of 10%. For these thresholds, 47.3% of the patients were identified at high risk in both models before the correction, and 17.2% of them had an imminent MOF. The adjustment for recency did not change this selection. Before the correction, 34.2% of patients were selected for treatment by FRAX® only, and 18.8% would have had an imminent MOF. This percentage increased to 47% after the adjustment for recency, but only 6% of those would suffer a MOF within 2 years. CONCLUSION: In our Belgian FRISBEE cohort, the imminent model was less sensitive but more selective in the selection of subjects in whom an imminent fracture should be prevented, resulting in a lower NNT. The correction for recency in this elderly population further decreased the selectivity of FRAX®. These data should be validated in additional cohorts before using them in everyday practice.

The effect of fracture recency on observed 5-year fracture probability: A study based on the FRISBEE cohort.

Introduction: Prediction models, especially the FRAX®, are largely used to estimate the fracture risk at ten years, but the current algorithm does not take into account the time elapsed after a fracture. Kanis et al. recently proposed correction factors allowing to adjust the FRAX® score for fracture recency. The objective of this work was to analyze the effect of fracture recency in the FRISBEE cohort. Methods: We identified in the FRISBEE cohort subjects who sustained a validated fracture during the first 5 years following an incident MOF. We calculated their estimated 5-year risk of fracture using FRAX® uncorrected, adjusted for recency and further adjusted for the MOF/hip ratios calibration factors previously derived for the Belgian FRAX®. We compared the fracture risk estimated by FRAX® before and after these corrections to the observed incidence of validated fractures in our cohort. Results: In our ongoing cohort, 376 subjects had a first non-traumatic incident validated MOF after inclusion; 81 had a secondary fracture during the 5 years follow-up period after this index fracture. The FRAX® score significantly under-evaluated the observed incidence of fractures in our cohort by 54.7 % (fracture rate of 9.7 %; 95 % CI, 6.8-12.9 %) if uncorrected (p < 0.001) and by 32.6 % after correction for recency (14.5 %; 95 % CI, 11.1-18.2 %) (p = 0.01). The calibration for MOF/hip ratios improved the prediction (17.5 %; 95 % CI: 13.7-21.4 %) (p = 0.2). After correcting for recency and for calibration, the predicted value was over-evaluated by 22 % (fracture rate of 26.1 %; 95 % CI, 21.6-30.5 %) but this over-evaluation was not significant (p = 0.1). Conclusion: Our data indicate that the correction of the FRAX® score for fracture recency improves fracture prediction. However, correction for calibration and recency tends to overestimate fracture risk in this population of elderly women.

Are there specific clinical risk factors for the occurrence of multiple fractures? The FRISBEE study.

This study showed additional clinical risk factors for the occurrence of multiple fractures with regards to a single fracture, with often higher hazard ratios. It would be important to include the risk of the occurrence of multiple fractures in future prediction models. PURPOSE: To identify clinical risk factors (CRFs) which would specifically increase the risk of multiple fractures. METHODS: Data of the 3560 postmenopausal women of the FRISBEE study were analysed. The CRFs and the fractures are collected annually. The cohort was divided into three groups: those who had no incident fracture, those who had a single incident fracture and those who had 2 two or more incident fractures (i.e. multiple fractures). Statistical analyses were performed using Cox proportional hazards models. RESULTS: Among the 3560 subjects (followed for 9.1 (7.2-10.6) years), 261 subjects had two or more validated fractures during follow-up (146 were major osteoporotic fractures (MOFs)), 628 had one fracture (435 MOFs), 2671 had no fracture (2979 had no MOF); 157 subjects had two or more central fractures, 389 had only one and 3014 had none. The risk factors for those with multiple fractures at any site were age, history of fracture, history of fall, total hip bone mineral density (BMD), spine BMD and rheumatoid arthritis. For those with multiple MOFs, significant CRFs were age, history of fracture, parental hip fracture, total hip BMD and rheumatoid arthritis. CONCLUSION: We found in a prospective cohort study that there were more CRFs and higher hazard ratios for the occurrence of multiple fractures than for a single fracture.

Distribution of Fracture Sites in Postmenopausal Overweight and Obese Women: The FRISBEE Study.

The association between obesity and fracture sites in postmenopausal women has been little studied. We examined the most common types of fractures in obese and overweight postmenopausal women compared to subjects with a normal BMI in the FRISBEE study, a cohort of postmenopausal women followed since 9.1 (7.2-10.6) years. Chi-squared tests and logistic regressions were used to compare the percentages of fracture sites in overweight/obese subjects to subjects with a normal BMI. Their mean (± SD) age was 76.7 ± 6.9 years and their mean BMI was 26.4 ± 4.4. Seven hundred seventy-seven subjects suffered at least one validated fragility fracture with a total of 964 fractures in the whole cohort. Subjects with a BMI higher than 25 had significantly more ankle fractures and less pelvic fractures than subjects with a normal BMI (OR 1.63, 95% CI 1.02-2.56, P = 0.04 and OR 0.55, 95% CI 0.34-0.89, P = 0.01, respectively). There were no significant differences between overweight and obese subjects. Among those older than 75, there were significantly fewer pelvic fractures in overweight/obese subjects (OR 0.49, 95% CI 0.27-0.87, P = 0.01), but before 75, ankle fractures were significantly more frequent in overweight/obese subjects than in subjects with a normal BMI (OR 1.89, 95% CI 1.01-3.57, P = 0.04). In conclusion, the proportion of ankle and pelvic fractures in obese and overweight subjects differs from that in subjects with a normal BMI, but these differences are age dependent. Fracture prevention strategies should take into account the differential effects of excess weight according to age and the site of fracture.

[Factors associated with intrahospital mortality in older patients with COVID-19 in Belgium : The COVID-AgeBru study]. / Face à la COVID-19. Mortalité intra-hospitalière chez les patients âgés de plus de 70 ans avec COVID-19 dans un hôpital universitaire en Belgique :l'étude COVID-AgeBru.

OBJECTIVE: We aimed at assessing the association between demographical and clinical data and the intrahospital mortality in older patients with COVID-19 in Belgium. METHODS: Descriptive, retrospective study of consecutive patients admitted to Brugmann university hospital, Brussels (Belgium) due to COVID-19 (Mars-September-2020). INCLUSION CRITERIA: Patients aged ≥ 70 years admitted to acute care with a positive PCR-RT test, or a highly indicative computed tomography scan. EXCLUSION CRITERIA: Patients transferred to another institution during hospitalization. OUTCOME MEASURE: All-cause intrahospital mortality. Demographic, clinical data, presence of comordibidties and comprehensive geriatric assessment were collected. Adjusted and unadjusted logistic regression were performed. RESULTS: From the 226 eligible patients, 160 (82.7 ± 6.5-year-old; 57.5 % females) met inclusion criteria, from which 67 (42 %) died during hospital stay. The adjusted logistic regression showed an association between intrahospital mortality and increasing age [OR = 1.09 per every year increase (95 % CI 1.02-1.16); p <0.001], type 2 diabetes [OR = 2.75 ( 1.17-6.46); p = 0.021], and acute respiratory distress syndrome (ARDS) [OR = 8.67 ( 3.48-21.61); p < 0.01]. CONCLUSIONS: A higher positive association between intrahospital mortality and increasing age, type 2 diabetes, and ARDS was found. The prognosis value of the comprehensive geriatric assessment in older people with COVID-19 in Belgium requires further studies.

INTRODUCTION: Les études sur l'impact de la pandémie en Belgique sont rares. L'objectif est d'évaluer l'association de l'âge et des comorbidités à la mortalité intra-hospitalière de toutes causes chez les patients âgés ? 70 ans avec COVID-19 dans un hôpital universitaire à Bruxelles, Belgique. Méthodes : Etude rétrospective descriptive des patients admis au CHU Brugmann pour cause de maladie COVID-19 (mars-septembre 2020). Critères d'inclusion : âge ≥ 70 ans admis avec PCR-RT positif ou haute probabilité d'infection au CT-scan thoracique. Critères d'exclusion : transfert dans un autre hôpital. Critère de jugement : toute cause de mortalité intra-hospitalière. Variables collectées : démographiques, cliniques et gériatriques [Katz, Lawton, MMSE, MNA, MNA-SF]. Une régression logistique non ajustée et ajustée a été réalisée. Résultats : Parmi les 226 patients éligibles, 160 (82,7 ± 6,5 ans; 57,5 % femmes) ont rempli les critères d'inclusion. Au total, 67 (42 %) sont décédés durant l'hospitalisation. La régression logistique a montré une association augmentée entre la mortalité et l'âge [odds ratio ou OR = 1,09/année en plus (IC 95 % 1,02-1,16) ; p< 0,001], le diabète de type 2 [OR = 2,75 (1,17-6,46); p = 0,021], l'ARDS [OR = 8,67 (3,48-21,61); p < 0,01]. CONCLUSION: L'âge, le diabète de type 2 et le syndrome de détresse respiratoire aiguë (ARDS) sont associés à une augmentation de la mortalité chez les patients âgés hospitalisés avec COVID-19 en Belgique.

Impact of non-hip fractures in elderly women: a narrative review.

The association of hip fractures with adverse outcomes is well established, but for non-hip fractures this association still needs to be further investigated. The objective of this narrative review is to describe the state of the art with regards to the health impact of clinically relevant non-hip fracture locations in postmenopausal women. PubMed and Scopus databases were searched from January 2010 until December 2020. Studies were included when the crude rates and/or relative risk of 1-year subsequent fractures and/or mortality were reported as well as the precise fracture site. Twenty-three studies met the inclusion criteria. Regarding mortality rates, there was a high variability between studies, with higher rates for vertebral, proximal humerus and pelvic fractures. There was a small or no impact of wrist, ankle or tibia fractures. The mortality rate increased with age after vertebral, proximal humerus and wrist fractures. Moreover, proximal humerus and vertebral fractures were associated with a higher mortality risk. This narrative review indicates that, besides fractures of the hip, fractures of the vertebrae, proximal humerus or pelvis deserve more attention when trying to prevent adverse outcomes of osteoporosis. More studies on the topic of non-hip fractures are urgently needed.

A rare case of invasive pulmonary aspergillosis presenting as organizing pneumonia due to Aspergillus niger in an immunocompetent host.

Invasive pulmonary aspergillosis associated with organizing pneumonia is increasingly described and mainly affects the immunocompromised individual. Most of Aspergillus invasive infections in both immunocompetent and immunocompromised patients are attributed to Aspergillus fumigatus. Herein we describe a clinical case of pulmonary Aspergillus niger infection presenting as an organizing pneumonia in an immunocompetent patient. A wedge resection and two successive cures of azoles (voriconazole 6 weeks then itraconazole 6 weeks) were necessary for the patient to be totally recovered. The association of OP and IPA is rare. The involvement of A. niger makes it even rarer, this is the reason why we decided to report on this case.

MOF/Hip Fracture Ratio in a Belgian Cohort of Post-menopausal Women (FRISBEE): Potential Impact on the FRAX® Score.

The ratio between major osteoporotic fractures (MOFs) and hip fractures in the Belgian FRAX® tool to predict fractures is currently based on Swedish data. We determined these ratios in a prospective cohort of Belgian postmenopausal women. 3560 women, aged 60-85 years (70.1 ± 6.4 years), were included in a prospective study from 2007 to 2013 and surveyed yearly (FRISBEE). We analyzed the number of validated incident fractures until October 2020 by age and sites and compared the MOFs/hip ratios in this cohort with those from the Swedish databases. We registered 1336 fractures (mean follow-up of 9.1 years). The MOFs/hip ratios extracted from the FRISBEE cohort were 10.7 [95% CI: (5.6-20.5)], 6.4 [4.7-8.7], and 5.0 [3.9-6.5] for women of 60-69, 70-79, and 80-89 years old, respectively. These ratios were 1.7-1.8 times higher for all age groups than those from the Swedish data, which decreased from 6.5 (60-64 years group) down to 1.8 (85-89 age group). The overall MOFs/hip ratio in Frisbee was 6.0 [5.9-6.1], which was higher than any Swedish ratio between 65 and 85 years. Nevertheless, the decrease of the ratios with age paralleled that observed in Sweden. In this Brussels prospective cohort, MOFs/hip ratios were 1.7-1.8 times those observed in Sweden currently used for MOFs prediction in the Belgian FRAX® version. This discrepancy can greatly modify the estimation of the risk of MOFs, which is among the main criteria used to recommend a pharmacological treatment for osteoporosis in several countries.

Infective endocarditis caused by Neisseria mucosa on a prosthetic pulmonary valve with false positive serology for Coxiella burnetii - The first described case.

We present a case of infective endocarditis (IE) on a prosthetic pulmonary valve in a 36-year-old patient with tetralogy of Fallot (TOF). The patient underwent valve replacement surgery and active antibiotic treatment against Gram-negative cocci (Piperacillin Tazobactam then Ceftriaxone) for a total duration of 42 days with a favourable outcome. The causative agent was Neisseria mucosa which was identified on the infected valve by sequencing of 16S ribosomal RNA. To our knowledge, this is the first described case of a N. mucosa infective endocarditis on a pulmonary valve. Initially, serologies performed in clinical settings by immunofluorescence for Coxiella burnetii antibodies showed a major increase in phase I IgG titers at 1024 (normal values <16) corresponding with the diagnostic criteria for Q fever endocarditis. However, this diagnosis could not be confirmed by the National Reference Center, making it the first reported case of a false positive serology for C. burnetii during an infection due to Neisseria spp.

Profile and needs of primary informal caregivers of older patients in Belgian geriatric day hospitals: a multicentric cross-sectional study.

BACKGROUND: With the improvement of life expectancy, the world faces increasing demands for care of older persons. In this manuscript, we define the characteristics of primary informal caregivers (PIC) of patients aged 75 years and older admitted to geriatric day hospitals (GDH) in Belgium. A PIC is defined as the person who most often provides care and assistance to persons who need to be cared for. We describe PIC socio-demographic characteristics, satisfaction, burden and wishes about caring; the type of assistance provided and received, their self-rated health, socio-demographic and medical characteristics of proxies, in particular the presence of behavioural disorders. METHODS: We conducted a cross-sectional study in 25 GDH. PARTICIPANTS: Four hundred seventy-five PIC of patients ≥75 years and their proxies. PIC completed a questionnaire at the GDH assessing burden by Zarit Burden Index-12 (ZBI-12), self-rated health, social restriction due to caregiving and financial participation. We compared the characteristics of PIC with high and low burden, and the characteristics of spouses and adult children PIC. We also analyzed factors associated with a high burden in a multivariable logistic regression model. RESULTS: PIC were mainly women (72%), adult children (53.8%) and spouses (30.6%). The mean age was 64 ± 14 years for PIC and 84 ± 5 years for care recipients. PIC helped for most of Activities in Daily Living (ADL) and Instrumental ADL (iADL). The median ZBI-12 score was 10 [IQR 5-18]. In multivariable regression analysis, a high burden was positively associated in the total group with living with the relative (p = 0.045), the difficulty to take leisure time or vacation (p < 0.001), behavioral and mood disorders (p < 0.001;p = 0.005), and was negatively associated with bathing the relative (p = 0.017) and a better subjective health status estimation (p < 0.001). CONCLUSION: Primary informal caregivers, who were predominantly women, were involved in care for ADL and iADL. A high burden was associated with living with the relative, the difficulty to take leisure time or vacation and the relative's behavioral and mood disorders. Bathing the relative and a subjective health status estimated as good as or better than people the same age, were protective factors against a high burden.

A MALDI-TOF MS database for fast identification of Vibrio spp. potentially pathogenic to marine mollusks.

In mollusk aquaculture, a large number of Vibrio species are considered major pathogens. Conventional methods based on DNA amplification and sequencing used to accurately identify Vibrio species are unsuitable for monitoring programs because they are time-consuming and expensive. The aim of this study was, therefore, to develop the MALDI-TOF MS method in order to establish a rapid identification technique for a large panel of Vibrio species. We created the EnviBase containing 120 main spectra projections (MSP) of the Vibrio species that are potentially responsible for mollusk diseases, comprising 25 species: V. aestuarianus, V. cortegadensis, V. tapetis and species belonging to the Coralliilyticus, Harveyi, Mediterranei, and Orientalis clades. Each MSP was constructed by the merger of raw spectra obtained from three different media and generated by three collaborating laboratories to increase the diversity of the conditions and thus obtain a good technique robustness. Perfect discrimination was obtained with all of the MSP created for the Vibrio species and even for very closely related species as V. europaeus and V. bivalvicida. The new EnviBase library was validated through a blind test on 100 Vibrio strains performed by our three collaborators who used the direct transfer and protein extraction methods. The majority of the Vibrio strains were successfully identified with the newly created EnviBase by the three laboratories for both protocol methods. This study documents the first development of a freely accessible database exclusively devoted to Vibrio found in marine environments, taking into account the high diversity of this genus. KEY POINTS: • Development of a MALDI-TOF MS database to quickly affiliate Vibrio species. • Increase of the reactivity when faced with Vibrio associated with mollusk diseases. • Validation of MALDI-TOF MS as routine diagnostic tool.

Risk factors for imminent fractures: a substudy of the FRISBEE cohort.

Multiple factors increase the risk of an imminent fracture, including a recent fracture, older age, osteoporosis, comorbidities, and the fracture site. These findings could be a first step in the development of a model to predict an imminent fracture and select patients most at need of immediate treatment. INTRODUCTION: The risk of a recurrent fragility fracture is maximal during the first 2 years following an incident fracture. In this prospective cohort study, we looked at the incidence of recurrent fractures within 2 years after a first incident fracture and we assessed independent clinical risk factors (CRFs) increasing this imminent fracture risk. METHODS: A total of 3560 postmenopausal women recruited from 2007 to 2013 were surveyed yearly for the occurrence of fragility fractures. We identified patients who sustained a fracture during the first 2 years following a first incident fragility fracture. We quantified the risk of a new fracture and assessed independent CRFs, associated with an imminent fracture at various sites. RESULTS: A recent fracture was a significant CRF for an imminent fracture (OR (95% CI): 3.7 (2.4-5.7) [p < 0.0001]). The incidence of an imminent fracture was higher in subjects above 80 years (p < 0.001). Other CRFs highly predictive in a multivariate analysis were osteoporosis diagnosis (p < 0.01), a central fracture as the index fracture (p < 0.01), and the presence of comorbidities (p < 0.05), with likelihood ratios of 1.9, 1.9, and 2.2, respectively. An imminent fracture was better predicted by a central fracture (p < 0.01) than by a major osteoporotic fracture. The hazard ratio was the highest for a central fracture. CONCLUSION: In patients with a recent fracture, older age, osteoporosis, comorbidities, and fracture site were associated with an imminent fracture risk. These findings could be a first step in the development of a model to predict an imminent fracture and select patients most at need of immediate and most appropriate treatment.

Effects of antimicrobial exposure on the antimicrobial resistance of Escherichia coli in the digestive flora of dairy calves.

Veal calves are often identified as reservoirs for antimicrobial resistant Escherichia coli (E. coli). This production is closely linked with dairy production, as young calves - mostly males - are collected from dairy farms to enter the fattening process. The aim of this prospective study was to explore the factors on dairy farms that favour the selection of antimicrobial resistance (AMR) in the digestive E. coli strains of young calves and to assess whether the resistance levels and selection pressure were the same for males and females. The exposure of calves to antimicrobials was investigated through three factors: antimicrobial treatment of calves; feeding of calves with milk from cows treated with antimicrobials; and the consumption of colostrum from cows treated with antimicrobials at dry-off. The study design involved 100 dairy farms. A calf of each sex was selected from birth on each farm. Information on the calves' exposure to antimicrobials was collected daily and calves were sampled (rectal swab) two weeks after birth, then seven weeks after birth for females only. Laboratory analyses included culture on two distinct media: a non-selective medium (identifying dominant flora) and a medium containing ceftiofur to select the extended-spectrum beta-lactamase (ESBL) phenotype. Susceptibility testing was performed on an E. coli strain from each medium. Generalised linear models were used to assess associations between the resistance of E. coli strains and antimicrobial exposure. A set of 280 swabs from healthy calves were analysed. In dominant flora, high levels of resistance (>60 %) were identified for streptomycin, tetracycline and amoxicillin but AMR levels were low (3 %) for critically important antimicrobials (3rd- and 4th-generation cephalosporins and fluoroquinolones). For females staying in dairy farms, a marked decrease in resistance was observed for almost all antimicrobials between the age of 15 days and 7 weeks. A selective medium revealed an ESBL phenotype for 20.7 % of the calves. Whether for AMR or antimicrobial exposure, no significant difference was found between male and female calves. The antimicrobial treatment of calves was associated with an increased resistance of E. coli from dominant flora for amoxicillin (OR = 2.9), gentamicin (OR = 4.6), florfenicol (OR = 5.0) and trimethoprim-sulfonamide (OR = 5.6). The consumption by calves of milk from cows treated with antimicrobials was also associated with an increased resistance to amoxicillin (OR = 2.6), gentamicin (OR = 4.0), tetracycline (2.6) and trimethoprim-sulfonamide (OR = 2.2). In contrast, the models did not reveal any association between AMR and consumption of colostrum from cows treated with antimicrobials at dry-off.

[Developing of an integration and training course for sterilization agents]. / Mise en place d'un parcours d'intégration et de formation pour les agents de stérilisation.

Until September 2018, there was no formal training or evaluation for sterilization agents at Nancy's hospital (CHRU). The goal was to create a formalized training path, to record the training and the evaluation of an agent using a written support. All the training resources available in the service have been identified and the missing tools have been created. A typical induction period has been created. It is divided into large parts: a welcome week followed by several weeks of training. The welcome week consists of observing all the activities of the service. The following training is divided into two parts. It begins with a theoretical training followed by 12weeks of practical training. The next 12weeks are dedicated to develop their knowledge. Follow-up is ensured through theoretical and practical evaluations, a grid of activities to be mastered completed as and when learning and a monitoring sheet on which are formalized weekly interviews with the pharmaceutical team. Finally, a logbook has been created and brings together all the useful documents for an agent throughout his career as a sterilization agent. The aim of the training path is to guide and involve the new agents, from their arrival in sterilization service to their continuous training, and to standardize the professional practices. It remains to be seen whether the tools put in place improve the knowledge and skills of the staff.

ALFA: annotation landscape for aligned reads.

BACKGROUND: The last 10 years have seen the rise of countless functional genomics studies based on Next-Generation Sequencing (NGS). In the vast majority of cases, whatever the species, whatever the experiment, the two first steps of data analysis consist of a quality control of the raw reads followed by a mapping of those reads to a reference genome/transcriptome. Subsequent steps then depend on the type of study that is being made. While some tools have been proposed for investigating data quality after the mapping step, there is no commonly adopted framework that would be easy to use and broadly applicable to any NGS data type. RESULTS: We present ALFA, a simple but universal tool that can be used after the mapping step on any kind of NGS experiment data for any organism with available genomic annotations. In a single command line, ALFA can compute and display distribution of reads by categories (exon, intron, UTR, etc.) and biotypes (protein coding, miRNA, etc.) for a given aligned dataset with nucleotide precision. We present applications of ALFA to Ribo-Seq and RNA-Seq on Homo sapiens, CLIP-Seq on Mus musculus, RNA-Seq on Saccharomyces cerevisiae, Bisulfite sequencing on Arabidopsis thaliana and ChIP-Seq on Caenorhabditis elegans. CONCLUSIONS: We show that ALFA provides a powerful and broadly applicable approach for post mapping quality control and to produce a global overview using common or dedicated annotations. It is made available to the community as an easy to install command line tool and from the Galaxy Tool Shed.

[How to avoid overmedicalization of the elderly patient ?] / Comment éviter la surmédicalisation du patient âgé ?

Over-medicalization is a broad concept, which also concerns the elderly patient. It encompasses both over-diagnosis and over-treatment. An increasing awareness of this issue has emerged since 2013, with the first " Preventing Overdiagnosis " conference. Currently, Evidence-Based Medicine does not prevent over-diagnosis. Indeed, the presence of geriatric characteristics such as multiple comorbidities, polypharmacy and frailty can lead to misdiagnosis and to potentially deleterious treatment. Subclinical hypothyroidism and Alzheimer's disease are two examples of pitfalls in the interpretation of biological and para-clinical data that may lead to the administration of useless treatment. Different issues are discussed to identify the causes of over-medicalization and to better prevent it.

La surmédicalisation est un concept large, qui concerne également le patient âgé. Elle englobe à la fois le surdiagnostic et sa conséquence à savoir le surtraitement. Une sensibilisation à ce sujet a émergé depuis 2013, date du premier congrès " Preventing Overdiagnosis ". Actuellement, l'Evidence-Based Medicine ne permet pas d'éviter le surdiagnostic chez le patient âgé. En effet, la présence de caracté- ristiques gériatriques telles que les multiples comorbidités, la polymédication et la fragilité peut mener à l'élaboration d'un diagnostic erroné et à l'instauration d'un traitement potentiellement délétère. L'hypothyroïdie subclinique et la maladie d'Alzheimer sont deux exemples de pièges potentiels à l'interprétation de données biologiques et paracliniques pouvant mener à l'administration d'un traitement futile. Différentes pistes sont abordées pour identifier les causes de la surmédicalisation et mieux la prévenir.

Subcutaneous administration of paracetamol-Good local tolerability in palliative care patients: An observational study.

BACKGROUND: The subcutaneous route is widely used in both palliative care and geriatrics. Numerous compounds are administered by this route, including paracetamol. However, there is no recommendation on which to base this latter practice and, in the absence of published evidence, nothing is known regarding its local tolerability in palliative care patients. AIM: The main objective of this study was to assess the local tolerability of paracetamol when administered subcutaneously for analgesic or antipyretic purposes in patients hospitalized in the palliative care unit. The secondary objective was to identify the factors favoring the occurrence of local adverse events. DESIGN: This is a prospective multicenter observational study (NCT02884609). PARTICIPANTS: Study conducted in 160 patients hospitalized in the palliative care units of three hospitals in metropolitan France from 2014 to 2017. RESULTS: Of the 160 patients, 44 (28%) presented at least one non-serious local adverse event (edema in 29, erythema in 5, pain in 15, hematoma in 2, pruritus in 1, and local heat in 2). No serious adverse events were observed. Factors associated with the occurrence of local adverse events were younger age, administration in the arm and thorax, and a high number of daily administrations. CONCLUSION: This first ever study carried out on this subject reveals that subcutaneous administration of paracetamol in palliative care patients was well tolerated locally.

Serological status for BTV-8 in French cattle prior to the 2015 re-emergence.

Undetected in Europe since 2010, bluetongue virus serotype 8 (BTV-8) re-emerged in August 2015 in Central France. To gain insight into the re-emergence on the French territory, we estimated the seroprevalence in cattle before the detection of BTV-8 in 2015, in areas differentially affected by the current outbreak. A retrospective survey based on the analysis of stored sera was thus conducted in the winter preceding the re-emergence in seven French departments including the one where the virus was first detected. A total of 10,066 sera were retrieved from animals sampled in 444 different herds in winter 2014/15. Between-herd seroprevalence revealed the presence of seropositive animals in almost all herds sampled (97.4%). The animal-level seroprevalence averaged at 44%, with a strong age pattern reflecting the cumulative exposure to both natural infection and to vaccination. A multivariable analysis allowed separating the respective effects of both exposures. A higher proportion of seropositivity risk was attributed to vaccination (67.4%) than to exposure to natural infection (24.2%). The evolution of seroprevalence induced by the two main risk factors in 74 mainland departments was reconstructed between the vaccination ban (2013) and the re-emergence (2015). We showed a striking decrease in seroprevalence with time after the vaccination ban, due to population renewal, which could have facilitated virus transmission leading to the current outbreak situation.

Circulation of bluetongue virus 8 in French cattle, before and after the re-emergence in 2015.

Bluetongue virus serotype 8 (BTV-8) re-emerged in Central France in August 2015. The viral strain identified is nearly identical to the one that circulated during the 2006/2009 massive outbreak throughout Europe. To address the question of an undetected BTV-8 circulation on the French territory, a serological study was conducted on young cattle along a transect of seven departments, three of them located in areas where the virus presence had been confirmed by RT-PCR by winter 2015/2016. Sera from 2,565 animals were collected during the winters preceding and following the re-emergence, with 414 animals being sampled in each of the two consecutive years. All samples were tested by competitive ELISA (IDVet) and, when enough serum was available, ELISA-positive samples were confirmed by seroneutralization tests. In areas with infected holdings, seropositive animals were found before the re-emergence (N = 14 of 511), significantly more on the following year (N = 17 of 257), and eight animals (N = 158) seroconverted over 2015. Seropositive animals were also detected as early as winter 2014/2015 in one department without known infected holdings (N = 12 of 150), and in winter 2015/2016 in three of them (N = 21 of 555), where seven animals (N = 154) seroconverted over 2015. These results suggest that BTV-8 may have spread at low levels before the re-emergence, even in areas considered virus-free. Unfortunately, whole blood from the seropositive animals was not available to definitely confirm the virus presence by RT-PCR.