Treatment for behavioral insomnia in young children with neurotypical development under 6 years of age: A systematic review.

This literature review examines all treatments for behavioral insomnia in children under 6 years of age to determine which treatments have empirically demonstrated efficacy. Following PRISMA guidelines, three databases were investigated (Pubmed, Cochrane and Psychinfo) to select randomized controlled trials (RCTs) which assess treatments for behavioral insomnia in children under 6 years of age, all with neurotypical development. A total of 908 articles met the search criteria. 21 articles were selected and analyzed in their entirety for a total of 2363 children (ranging from 2 months to 6 years of age). Based on these studies, treatment of behavioral insomnia in young children under 6 years of age is primarily based on behavioral therapy. There is no evidence that pharmacological treatments are effective in the long term for neurotypical children. This review highlights the lack of RCTs in this field: new RCTs should be carried out among young children to refine and optimize the therapeutic approach and to address the risk of therapeutic abuse through the use of non-scientifically validated methods.

Influenza transmissibility among patients and health-care professionals in a geriatric short-stay unit using individual contact data.

Detailed information are lacking on influenza transmissibility in hospital although clusters are regularly reported. In this pilot study, our goal was to estimate the transmission rate of H3N2 2012-influenza, among patients and health care professionals in a short-term Acute Care for the Elderly Unit by using a stochastic approach and a simple susceptible-exposed-infectious-removed model. Transmission parameters were derived from documented individual contact data collected by Radio Frequency IDentification technology at the epidemic peak. From our model, nurses appeared to transmit infection to a patient more frequently with a transmission rate of 1.04 per day on average compared to 0.38 from medical doctors. This transmission rate was 0.34 between nurses. These results, even obtained in this specific context, might give a relevant insight of the influenza dynamics in hospitals and will help to improve and to target control measures for preventing nosocomial transmission of influenza. The investigation of nosocomial transmission of SARS-COV-2 might gain from similar approaches.

Enriched PUFA environment of Leishmania infantum promastigotes promotes the accumulation of lipid mediators and favors parasite infectivity towards J774 murine macrophages.

Leishmania parasites are the causative agents of visceral or cutaneous leishmaniasis in humans and of canine leishmaniosis. The macrophage is the predilected host cell of Leishmania in which the promastigote stage is transformed into amastigote. We previously showed changes in the fatty acid composition (FA) of lipids in two strains of Leishmania donovani upon differentiation of promastigote to amastigote, including increased proportions of arachidonic acid (AA) and to a less extent of docosahexaenoic acid (DHA). Here, we carried out supplementation with AA or DHA on two Leishmania infantum strains, a visceral (MON-1) and a cutaneous (MON-24), to evaluate the role of these FA in parasite/macrophage interactions. The proportions of AA or DHA in total lipids were significantly increased in promastigotes cultured in AA- or DHA-supplemented media compared to controls. The content of FA-derived oxygenated metabolites was enhanced in supplemented strains, generating especially epoxyeicosatrienoic acids (11,12- and 14,15-EET) and hydroxyeicosatetraenoic acids (5- and 8- HETE) from AA, and hydroxydocosahexaenoic acids (14- and 17-HDoHE) from DHA. For both MON-1 and MON-24, AA-supplemented promastigotes showed higher infectivity towards J774 macrophages as evidenced by higher intracellular amastigote numbers. Higher infectivity was observed after DHA supplementation for MON-24 but not MON-1 strain. ROS production by macrophages increased upon parasite infection, but only minor change was observed between control and supplemented parasites. We propose that under high AA or DHA environment that is associated with AA or DHA enrichment of promastigote lipids, FA derivatives can accumulate in the parasite, thereby modulating parasite infectivity towards host macrophages.

Baseline clinical features of COVID-19 patients, delay of hospital admission and clinical outcome: A complex relationship.

INTRODUCTION: Delay between symptom onset and access to care is essential to prevent clinical worsening for different infectious diseases. For COVID-19, this delay might be associated with the clinical prognosis, but also with the different characteristics of patients. The objective was to describe characteristics and symptoms of community-acquired (CA) COVID-19 patients at hospital admission according to the delay between symptom onset and hospital admission, and to identify determinants associated with delay of admission. METHODS: The present work was based on prospective NOSO-COR cohort data, and restricted to patients with laboratory confirmed CA SARS-CoV-2 infection admitted to Lyon hospitals between February 8 and June 30, 2020. Long delay of hospital admission was defined as ≥6 days between symptom onset and hospital admission. Determinants of the delay between symptom onset and hospital admission were identified by univariate and multiple logistic regression analysis. RESULTS: Data from 827 patients were analysed. Patients with a long delay between symptom onset and hospital admission were younger (p<0.01), had higher body mass index (p<0.01), and were more frequently admitted to intensive care unit (p<0.01). Their plasma levels of C-reactive protein were also significantly higher (p<0.01). The crude in-hospital fatality rate was lower in this group (13.3% versus 27.6%), p<0.01. Multiple analysis with correction for multiple testing showed that age ≥75 years was associated with a short delay between symptom onset and hospital admission (≤5 days) (aOR: 0.47 95% CI (0.34-0.66)) and CRP>100 mg/L at admission was associated with a long delay (aOR: 1.84 95% CI (1.32-2.55)). DISCUSSION: Delay between symptom onset and hospital admission is a major issue regarding prognosis of COVID-19 but can be related to multiple factors such as individual characteristics, organization of care and severe pathogenic processes. Age seems to play a key role in the delay of access to care and the disease prognosis.

Development and Cross-National Validation of a French Version of the Jefferson Scale of Empathy for Students.

Empathy is a multifaceted personal ability combining emotional and cognitive features modulated by cultural specificities. It is widely recognized as a key clinical competence that should be valued during professional training. The Jefferson Scale of Empathy for medical students (JSE-S) has been developed for this purpose and validated in several languages, but not in French. The aims of this study were to gather validity evidence for a newly developed version of the JSE-S and compare it between two French-speaking contexts. In total, 1,433 undergraduate medical students from the universities of Lyon (UL), France and Geneva (UG), Switzerland participated in the study completing the JSE-S in French. Total and partial scores of the three subscales ("perspective taking," "compassionate care" and "walking in patient's shoes") were calculated for each site. Construct validity of the JSE-S was analyzed considering three sources of evidence: content, internal structure and relations to other variables. A first-order Confirmatory Factor Analysis using structural equation modeling examined the three latent variables of the JSE-S subscales. Cronbach's α coefficients were 0.75 (UG) and 0.81 (UL). The items' discrimination power ranged between 0.29 and 1.60 (median effect size of 1.24). The overall correlations between items and total or partial scores derived from the latent JSE-S subscales were consistently similar in both study sites. Findings of this study confirm the latent structure of the JSE-S in French and its cross-national reproducibility. The comparable underlying structure of the questionnaire tested in two distinct French-speaking contexts endorses the generalizability of its measure.

Influence of Different Implant Types on Bone Levels After Healing and Peri-implant Tissue Reactions Following Peri-implantitis: A Preclinical Study.

This study evaluated the influence of different implant types on (1) radiographic marginal bone levels after healing and (2) radiographic and histomorphometric tissue levels and characteristics following ligature-induced peri-implantitis. Four implant types (Standard Plus, Straumann [S]; NobelReplace Tapered, Nobel Biocare [N]; In-Kone Universal, Global D [I]; and twinKon, Global D [T]) were randomly placed in the edentulous healed mandibular ridge of six dogs (T0), for a total of 57 implants placed. After 10 weeks, a peri-implantitis was ligature-induced (T1). After 12 weeks, biopsy samples were processed for histomorphometric analysis (T2). Standardized radiographs were taken at T0, T1, and T2 for imaging analysis. Statistical analysis was performed using mixed-effects linear modeling. After healing (T1), the radiographic marginal bone level was more coronal for implants I, T, and S compared to N. Following peri-implantitis (T2), the histologic marginal bone level was more coronal for implants I, T, and S compared to N, and for implants I and T compared to S. Also at T2, the radiographic marginal bone level was more coronal at implants I, T, and S compared to N. Implant type may influence bone remodeling during healing and bone loss during the early stages of experimental peri-implantitis.

Trends in the proportion of resistant bacteria involved in ventilator-associated pneumonia as the first hospital-acquired infection in intensive care units between 2003 and 2016 in Lyon, France.

The aim of this study was to describe the proportion of multidrug-resistant microorganisms (MDROs) involved in ventilator-associated pneumonia (VAP) as the first hospital-acquired infection in 536 adults with restricted risk factors for MDRO-related infection. We found a significant decrease in the percentage of MDROs involved in VAP between 2003 and 2016 and this percentage increased when VAP occurred after day 10.

Factors associated with admission to intensive care units in COVID-19 patients in Lyon-France.

INTRODUCTION: A new respiratory virus, SARS-CoV-2, has emerged and spread worldwide since late 2019. This study aims at analysing clinical presentation on admission and the determinants associated with admission in intensive care units (ICUs) in hospitalized COVID-19 patients. PATIENTS AND METHODS: In this prospective hospital-based study, socio-demographic, clinical and biological characteristics, on admission, of adult COVID-19 hospitalized patients presenting from the community for their first admission were prospectively collected and analysed. Characteristics of patients hospitalized in medical ward to those admitted in ICU were compared using Mann-Whitney and Chi-square or Fisher exact test when appropriate. Univariate logistic regression was first used to identify variables on admission that were associated with the outcome i.e. admission to an ICU versus total hospital stay in a medical ward. Forward selection was then applied beginning with sex, age and temperature in the multivariable logistic regression model. RESULTS: Of the 412 patients included, 325 were discharged and 87 died in hospital. Multivariable regression showed increasing odds of ICU hospitalization with temperature (OR, 1.56 [95% CI, 1.06-2.28] per degree Celsius increase), oxygen saturation <90% (OR, 12.45 [95% CI, 5.27-29.4]), abnormal lung auscultation on admission (OR, 3.58 [95% CI, 1.58-8.11]), elevated level of CRP (OR, 2.7 [95% CI, 1.29-5.66for CRP>100mg/L vs CRP<10mg/L). and monocytopenia (OR, 3.28 [95% CI, 1.4-7.68]) were also associated with increasing odds of ICU hospitalization. Older patients were less likely to be hospitalized in ICU (OR, 0.17 [95%CI, 0.05-0.51]. CONCLUSIONS: Age and delay between onset of symptoms and hospital admission were associated with the risk of hospitalisation in ICU. Age being a fixed variable, interventions that shorten this delay would improve the prognosis of Covid-19 patients.

A Conceptual Discussion About the Basic Reproduction Number of Severe Acute Respiratory Syndrome Coronavirus 2 in Healthcare Settings.

To date, no specific estimate of R0 for SARS-CoV-2 is available for healthcare settings. Using interindividual contact data, we highlight that R0 estimates from the community cannot translate directly to healthcare settings, with pre-pandemic R0 values ranging 1.3-7.7 in 3 illustrative healthcare institutions. This has implications for nosocomial COVID-19 control.

Narcolepsy with cataplexy: Does age at diagnosis change the clinical picture?

OBJECTIVE: To compare symptoms and sleep characteristics in patients diagnosed with narcolepsy-cataplexy (NC) before and after the age of 18 years. METHODS: De novo patients with NC diagnosis completed a standardized questionnaire and interview, followed by a sleep study. The clinical and sleep measures were compared between patients diagnosed before (46 children, median age: 12 year old) and after (46 adults, median age: 28.5 year old) 18 years of age. RESULTS: The frequency of obesity (54% vs 17%), night eating (29% vs 7%), parasomnia (89% vs 43%), sleep talking (80% vs 34%), and sleep drunkenness (69% vs 24%) were higher in children than in adults, the frequency of sleep paralysis was lower (20% vs 55%) but the frequency of cataplexy and the severity of sleepiness were not different. Children scored higher than adults at the attention-deficit/hyperactivity disorder (ADHD) scale. Depressive feelings affected not differently children (24%) and adults (32%). However, adults had lower quality of life than children. There was no difference between groups for insomnia and fatigue scores. Quality of life was essentially impacted by depressive feelings in both children and adults. Obstructive apnea-hypopnea index (OAHI) was lower in children with higher mean and minimal oxygen saturation than in adults. No between-group differences were found at the multiple sleep latency test. The body mass index (z-score) was correlated with OAHI (r = .32). CONCLUSION: At time of NC diagnosis, children have more frequent obesity, night eating, parasomnia, sleep talking, drunkenness, and ADHD symptoms than adults, even if sleepiness and cataplexy do not differ. These differences should be considered to ensure a prompt diagnosis.

Association of characteristics of tampon use with menstrual toxic shock syndrome in France.

BACKGROUND: Menstrual tampons are widely used in western countries. Indirect evidence suggests that tampon misuse could be associated with an increased risk of menstrual toxic shock syndrome (MTSS). The aim of this study was to determine what characteristics of tampon use are associated with increased risk of menstrual toxic shock syndrome (MTSS). METHODS: A nationwide, case-control study in France, was conducted with women that use tampons with MTSS diagnoses according to the CDC diagnostic criteria (n = 55, from January 2011, to December 2017) and a control group of women with no MTSS history (n = 126, from February to December 2017). Information regarding tampon use during a 6-month period was collected. Associations between tampon use and MTSS were assessed using logistic regression models stratified by residential area. FINDINGS: Compared to controls, women diagnosed with MTSS more frequently reported maximum tampon wear of >6 h (62% vs. 41%; P = 0.02), overnight tampon use (77% vs. 54%; P = 0.006), and neither read nor followed tampon instructions in case of reading (65% vs. 42%; P = 0.006). In univariate analysis, MTSS risk was two-fold higher with tampon use for >6 consecutive hours (odds ratio, 2.3 [95% CI, 1.2-4.5]), and three-fold higher with tampon use during sleep for >8 h (odds ratio, 3.2 [95% CI, 1.4-7.7]). In multivariate logistic regression analysis, only maximum tampon use for >6 h (odds ratio, 2.03 [95% CI, 1.04-3.98]), and neither read nor followed the tampon instructions in case of reading (odds ratio, 2.25 [95% CI, 1.15-4.39]) were independently associated with MTSS. INTERPRETATION: Our study suggests that the risk of MTSS was associated with using tampons for more than 6 h, overnight tampon use during sleep, and neither read nor followed tampon insertion instructions in case of reading. FUNDING: LABEX ECOFECT (ANR-11-LABX-0048) of Université de Lyon within the programme "Investissements d'Avenir" (ANR-11-IDEX-0007) operated by the French National Research Agency (ANR).

French validation of the sleep disturbance scale for children (SDSC) in young children (aged 6 months to 4 years).

The sleep disturbance scale for children (SDSC) has been translated and adapted into several languages and its psychometric properties are good. Notably, a French version has been validated for 4- to 16-year olds. The objective of the current study was therefore to adapt and validate the SDSC for French young children (aged 6 months to 4 years). METHOD: 421 French-speaking mothers of children aged between 6 months and 4 years completed the SDSC and the Brief Infant Sleep Questionnaire (BISQ) which is specifically for young children. Of these, 105 children were diagnosed with sleep disorders (clinical group) during a sleep consultation, and 316 completed the SDSC and BISQ in a network of nurseries (control group). Several factor analyses were conducted to identify the most consistent factor structure for this sample. RESULTS: Three items from the previous version were deleted due to lack of clinical relevance for this age group. The best factor analysis revealed six factors, comparable to the Italian version of the SDSC for children: Disorders of Initiating Sleep, Disorders of Maintaining Sleep, Sleep Hyperhidrosis, Sleep Breathing Disorders, Parasomnias, and Non-Restorative Sleep and Excessive Somnolence. This psychometric structure is reliable and aligned with expert diagnoses. The convergent validity, and divergent and internal reliability were acceptable. CONCLUSION: This study validates a 22-item SDSC for French young children. Coupled with some questions from the BISQ, the SDSC could therefore be used to facilitate the detection of sleep disturbances in children aged between 6 months and 4 years old.

European intensive care physicians' experience of infections due to antibiotic-resistant bacteria.

Background: Antimicrobial resistance (AMR) compromises the treatment of patients with serious infections in intensive care units (ICUs), and intensive care physicians are increasingly facing patients with bacterial infections with limited or no adequate therapeutic options. A survey was conducted to assess the intensive care physicians' perception of the AMR situation in the European Union/European Economic Area (EU/EEA). Methods: Between May and July 2017, physicians working in European ICUs were invited to complete an online questionnaire hosted by the European Society of Intensive Care Medicine. The survey included 20 questions on hospital and ICU characteristics, frequency of infections with multidrug-resistant (MDR) bacteria and relevance of AMR in the respondent's ICU, management of antimicrobial treatment as well as the use of last-line antibiotics in the six months preceding the survey. For the analysis of regional differences, EU/EEA countries were grouped into the four sub-regions of Eastern, Northern, Southern and Western Europe. Results: Overall, 1062 responses from four European sub-regions were analysed. Infections with MDR bacteria in their ICU were rated as a major problem by 257 (24.2%), moderate problem by 360 (33.9%) and minor problem by 391 (36.8%) respondents. Third-generation cephalosporin-resistant Enterobacteriaceae were the most frequently encountered MDR bacteria followed by, in order of decreasing frequency, meticillin-resistant Staphylococcus aureus, carbapenem-resistant Enterobacteriaceae, carbapenem-resistant Pseudomonas aeruginosa and vancomycin-resistant enterococci. Perception of the relevance of the AMR problem and the frequency of specific MDR bacteria varied by European sub-region. Bacteria resistant to all or almost all available antibiotics were encountered by 132 (12.4%) respondents. Many physicians reported not having access to specific last-line antibiotics. Conclusions: The percentage of European ICU physicians perceiving AMR as a substantial problem in their ICU is high with variation by sub-region in line with epidemiological studies. The reports of bacteria resistant to almost all available antibiotics and the limited availability of last-line antibiotics in ICUs in the EU/EEA are of concern.

Clinical Evaluation of a Multiplex PCR for the Detection of Salmonella enterica Serovars Typhi and Paratyphi A from Blood Specimens in a High-Endemic Setting.

Enteric fever is a major public health concern in endemic areas, particularly in infrastructure-limited countries where Salmonella Paratyphi A has emerged in increasing proportion of cases. We aimed to evaluate a method to detect Salmonella Typhi (S. Typhi) and Salmonella Paratyphi A (S. Paratyphi A) in febrile patients in Bangladesh. We conducted a prospective study enrolling patients with fever > 38°C admitted to two large urban hospitals and two outpatient clinics located in Dhaka, Bangladesh. We developed and evaluated a method combining short culture with a new molecular assay to simultaneously detect and differentiate S. Typhi and S. Paratyphi A from other Salmonella directly from 2 to 4 mL of whole blood in febrile patients (n = 680). A total of 680 cases were enrolled from the four participating sites. An increase in the detection rate (+38.8%) in S. Typhi and S. Paratyphi A was observed with a multiplex polymerase chain reaction (PCR) assay, and absence of non-typhoidal Salmonella detection was reported. All 45 healthy controls were culture and PCR negative, generating an estimated 92.9% of specificity on clinical samples. When clinical performance was assessed in the absence of blood volume prioritization for testing, a latent class model estimates clinical performance ≥ 95% in sensitivity and specificity with likelihood ratio (LR) LR+ > 10 and LR- < 0.1 for the multiplex PCR assay. The alternative method to blood culture we developed may be useful alone or in combination with culture or serological tests for epidemiological studies in high disease burden settings and should be considered as secondary endpoint test for future vaccine trials.

Investigation of the Relationships Between Clinical and Environmental Isolates of Aspergillus fumigatus by Multiple-locus Variable Number Tandem Repeat Analysis During Major Demolition Work in a French Hospital.

Background: Genotyping is needed to explore the link between clinical cases from colonization of invasive aspergillosis (IA) and major building construction. Attempts to correlate Aspergillus fumigatus strains from clinical infection or colonization with those found in the environment remain controversial due to the lack of a large prospective study. Our aim in this study was to compare the genetic diversity of clinical and environmental A. fumigatus isolates during a demolition period. Methods: Fungal contamination was monitored daily for 11 months in 2015. Environmental surveillance was undertaken indoors and outdoors at 8 locations with automatic agar samplers. IA infection cases were investigated according to European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and Infectious Diseases Mycoses Study Group criteria. Isolates were identified by amplification and sequencing of the ß- tubulin gene. They were genotyped by multiple-locus variable number tandem repeat analysis (MLVA). The phylogenetic relationships between isolates were assessed by generating a minimum spanning tree. Results: Based on 3885 samples, 394 A. fumigatus isolates (383 environmental and 11 clinical) were identified and genotyped using MLVA. Clinical isolates were collected from patients diagnosed as having probable IA (n = 2), possible IA (n = 1), or bronchial colonization (n = 6). MLVA generated 234 genotypes. Seven clinical isolates shared genotypes identical to environmental isolates. Conclusions: Among the diversity of genotypes described, similar genotypes were found in clinical and environmental isolates, indicating that A. fumigatus infection and colonization may originate from hospital environments.

Integrated problem-based learning versus lectures: a path analysis modelling of the relationships between educational context and learning approaches.

Students' approaches to learning are central to the process of learning. Previous research has revealed that influencing students' approaches towards deep learning is a complex process and seems much more difficult than expected, even in student-activating learning environments. There is evidence that learning approaches are impacted not only by the learning environment, but also by how students perceive it. However the nature of the links between the environment itself, the way in which it is perceived by students and students' learning approaches is poorly understood. This study aimed at investigating the relationships between students' perception of their educational context and learning approaches in three learning environments differing by their teaching formats (lecture or problem-based-learning PBL) and integration level of the curriculum (traditional or integrated). We tested the hypothesis that a PBL format and an integrated curriculum are associated to deeper approaches to learning and that this is mediated by student perception. The study sample was constituted of 1394 medical students trained respectively in a traditional lecture-based (n = 295), in an integrated lecture-based (n = 612) and in an integrated PBL-based (n = 487) curricula. They completed a survey including the Dundee-Ready-Educational-Environment-Measure (students' perceptions of the educational environment) and the Revised-Study-Process-Questionnaire (learning approaches). Data were analysed by path analysis. The model showed that the learning environment was related to students' learning approaches by two paths, one direct and one mediated via students' perception of their educational context. In the lecture-based curricula students' used deeper approaches when it was integrated and both paths were cumulative. In the PBL-based curriculum students' did not use deeper approaches than with lectures, due to opposite effects of both paths. This study suggested that an integrated lecture-based curriculum was as effective as a PBL curriculum in promoting students' deep learning approaches, reinforcing the importance of integrating the curriculum before choosing the teaching format.

Estimation of Extra Length of Stay Attributable to Hospital-Acquired Infections in Adult ICUs Using a Time-Dependent Multistate Model.

OBJECTIVES: The objective of the study was to estimate the length of stay of patients with hospital-acquired infections hospitalized in ICUs using a multistate model. DESIGN: Active prospective surveillance of hospital-acquired infection from January 1, 1995, to December 31, 2012. SETTING: Twelve ICUs at the University of Lyon hospital (France). PATIENTS: Adult patients age greater than or equal to 18 years old and hospitalized greater than or equal to 2 days were included in the surveillance. All hospital-acquired infections (pneumonia, bacteremia, and urinary tract infection) occurring during ICU stay were collected. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The competitive risks of in-hospital death, transfer, or discharge were considered in estimating the change in length of stay due to infection(s), using a multistate model, time of infection onset. Thirty-three thousand four-hundred forty-nine patients were involved, with an overall hospital-acquired infection attack rate of 15.5% (n = 5,176). Mean length of stay was 27.4 (± 18.3) days in patients with hospital-acquired infection and 7.3 (± 7.6) days in patients without hospital-acquired infection. A multistate model-estimated mean found an increase in length of stay by 5.0 days (95% CI, 4.6-5.4 d). The extra length of stay increased with the number of infected site and was higher for patients discharged alive from ICU. No increased length of stay was found for patients presenting late-onset hospital-acquired infection, more than the 25th day after admission. CONCLUSIONS: An increase length of stay of 5 days attributable to hospital-acquired infection in the ICU was estimated using a multistate model in a prospective surveillance study in France. The dose-response relationship between the number of hospitalacquired infection and length of stay and the impact of early-stage hospital-acquired infection may strengthen attention for clinicians to focus interventions on early preventions of hospital-acquired infection in ICU.

Evaluation of Hirst-type spore traps in outdoor Aspergillaceae monitoring during large demolition work in hospital.

Demolition can generate fungal spore suspensions in association with various adverse health effects, such as high risk of invasive aspergillosis in immunocompromised patients. One block of Edouard Herriot Hospital was entirely demolished. The aim of the present study was to evaluate Hirst-type spore traps utility in monitoring outdoor Aspergillaceae (Aspergillus spp. + Penicillium spp.) spores in part of Edouard Herriot Hospital (Lyon, France) undergoing major demolition. Three periods were scheduled in 2015: (A) Gutting of building and asbestos removal, (B) Demolition of floors, (C) Excavation and earthwork. Outdoor Aspergillaceae fungal load was monitored by cultivable (Air Ideal®, bioMérieux) and non-cultivable methods (Lanzoni VPPS-2000, Analyzair®, Bologna, Italy). Differences of Aspergillaceae recorded with Hirst-type spore traps were observed between Gerland and Edouard Herriot Hospital. Differences between Aspergillaceae were recorded between day time and night time at Gerland and Edouard Herriot Hospital. Daily paired differences between Aspergillaceae recorded with non-cultivable methodology at Edouard Herriot Hospital and in an area without demolition work were significant in Period A vs Period B (p = 10-4) and Period A vs Period C (p = 10-4). Weak correlation of daily Aspergillaceae recorded by both methods at Edouard Herriot Hospital was significant only for Period C (r = 0.26, p = 0.048, n = 58). Meteorological parameters and type of demolition works were found to heavily influenced Aspergillaceae dispersion. Non-cultivable methodology is a promising tool for outdoor Aspergillaceae scrutiny during major demolition work in hospital, helping infection control staff to rapidly implement control measures.

ITPA Activity in Children Treated by Azathioprine: Relationship to the Occurrence of Adverse Drug Reactions and Inflammatory Response.

Azathioprine (AZA), a thiopurine drug, is widely used in the treatment of children with immunological diseases such as inflammatory bowel disease (IBD) and autoimmune hepatitis (AIH); however, interindividual variability in the occurrence of adverse drug reactions (ADRs) and drug response is observed. This study investigated (i) the relationships between inosine triphosphate pyrophosphatase (ITPA) activity, an enzyme involved in thiopurine metabolism, and the occurrence of ADRs in children with immunological disease on AZA therapy, and (ii) the relationship between ITPA activity and the inflammatory activity observed in children with IBD. ITPA and TPMT activities were determined in 106 children with immunological disease on AZA therapy. Markers of hepatotoxicity, myelotoxicity, pancreatitis and inflammation as well as clinical information were retrospectively collected during regular medical visits. No significant association was found between ITPA activity and hepatotoxicity or clinical ADRs such as cutaneous reactions, arthralgia, flulike symptoms and gastrointestinal disorders. Concerning myelotoxicity, a significant relation was observed between ITPA activity and RBC mean corpuscular volume (MCV; p=0.003). This observation may be related to the significant relationship found between high ITPA activity and the increase in γ-globulin level reflecting inflammation (p=0.005). In our study, ITPA activity was not associated with occurrence of ADRs, but a relationship between high ITPA activity and γ-globulin, a marker of inflammation, was found in children with IBD. Therefore, measurement of ITPA activity may help to identify children with IBD predisposed to residual inflammation on AZA therapy. Further prospective studies are needed to confirm this result.