Electronic Sensors for Assessing Interactions between Healthcare Workers and Patients under Airborne Precautions

International audienceBackground: Direct observation has been widely used to assess interactions between healthcare workers (HCWs) and patients but is time-consuming and feasible only over short periods. We used a Radio Frequency Identification Device (RFID) system to automatically measure HCW-patient interactions. Methods: We equipped 50 patient rooms with fixed sensors and 111 HCW volunteers with mobile sensors in two clinical wards of two hospitals. For 3 months, we recorded all interactions between HCWs and 54 patients under airborne precautions for suspected (n=40) or confirmed (n=14) tuberculosis. Number and duration of HCW entries into patient rooms were collected daily. Concomitantly, we directly observed room entries and interviewed HCWs to evaluate their self- perception of the number and duration of contacts with tuberculosis patients. Results: After signal reconstruction, 5490 interactions were recorded between 82 HCWs and 54 tuberculosis patients during 404 days of airborne isolation. Median (interquartile range) interaction duration was 2.1 (0.8-4.4) min overall, 2.3 (0.8-5.0) in the mornings, 1.8 (0.8-3.7) in the afternoons, and 2.0 (0.7-4.3) at night (P,1024). Number of interactions/day/HCW was 3.0 (1.0-6.0) and total daily duration was 7.6 (2.4-22.5) min. Durations estimated from 28 direct observations and 26 interviews were not significantly different from those recorded by the network. Conclusions: The RFID was well accepted by HCWs. This original technique holds promise for accurately and continuously measuring interactions between HCWs and patients, as a less resource-consuming substitute for direct observation. The results could be used to model the transmission of significant pathogens. HCW perceptions of interactions with patients accurately reflected reality

Vaccine breakthrough hypoxemic COVID-19 pneumonia in patients with auto-Abs neutralizing type I IFNs

Life-threatening `breakthrough' cases of critical COVID-19 are attributed to poor or waning antibody response to the SARS- CoV-2 vaccine in individuals already at risk. Pre-existing autoantibodies (auto-Abs) neutralizing type I IFNs underlie at least 15% of critical COVID-19 pneumonia cases in unvaccinated individuals; however, their contribution to hypoxemic breakthrough cases in vaccinated people remains unknown. Here, we studied a cohort of 48 individuals ( age 20-86 years) who received 2 doses of an mRNA vaccine and developed a breakthrough infection with hypoxemic COVID-19 pneumonia 2 weeks to 4 months later. Antibody levels to the vaccine, neutralization of the virus, and auto- Abs to type I IFNs were measured in the plasma. Forty-two individuals had no known deficiency of B cell immunity and a normal antibody response to the vaccine. Among them, ten (24%) had auto-Abs neutralizing type I IFNs (aged 43-86 years). Eight of these ten patients had auto-Abs neutralizing both IFN-a2 and IFN-., while two neutralized IFN-omega only. No patient neutralized IFN-ss. Seven neutralized 10 ng/mL of type I IFNs, and three 100 pg/mL only. Seven patients neutralized SARS-CoV-2 D614G and the Delta variant (B.1.617.2) efficiently, while one patient neutralized Delta slightly less efficiently. Two of the three patients neutralizing only 100 pg/mL of type I IFNs neutralized both D61G and Delta less efficiently. Despite two mRNA vaccine inoculations and the presence of circulating antibodies capable of neutralizing SARS-CoV-2, auto-Abs neutralizing type I IFNs may underlie a significant proportion of hypoxemic COVID-19 pneumonia cases, highlighting the importance of this particularly vulnerable population

Utilisation des modèles dynamiques pour l'évaluation des traitements de l'hépatite C

L'introduction depuis 2011 des trithérapies associant un inhibiteur de protéase (IP), telaprevir ou boceprevir, à l'interféron pégylé et la ribavirine (Peg-IFN/RBV), constitue un tournant majeur dans la lutte contre le virus de l'hépatite C (VHC). Cependant la réponse au traitement chez les patients cirrhotiques reste mal connue et pose de sérieux problèmes de tolérance. Les modèles de cinétique virale, analysés par modèles non-linéaires à effets mixtes (MNLEM), constituent un outil puissant pour la compréhension de la réponse au traitement. Nous avons démontré par simulation la puissance du test de Wald dans le cadre des MNLEM pour détecter une différence d'efficacité antivirale entre deux traitements. Cette approche, même pour un nombre réduit de prélèvements, s'est révélée systématiquement supérieure à l'approche standard reposant sur un test de Wilcoxon sur le déclin de charge virale. Cependant nous avons mis en évidence une inflation de l'erreur de type I de ce test lorsque le nombre de patients est faible et avons proposé une correction par permutation. Nous avons appliqué cette approche pour estimer l'efficacité antivirale des trithérapies chez des patients cirrhotiques en échec thérapeutique (ANRS MODCUPIC). Nous avons démontré que plus de 99% de la réplication virale était bloqué par les IP, avec une efficacité sighificativement supérieure du telaprevir par rapport au boceprevir, et une efficacité sous-optimale de Peg-IFN/RBV. Enfin, en modélisant la cinétique des paramètres sanguins, nous avons démontré que les concentrations de Peg-IFN et de RBV sont directement associées, respectivement, è l'anémie et la thrombopénie fréquemment observées chez ces patients.Since 2011, the introduction of triple therapies combining a protease inhibitor (PI), telaprevir or boceprevir, with the pegylated-interferon and the ribavirin (Peg-IFN/RBV) marked a milestone for anti hepatitis C virus (HCV) therapy. However, the response to treatment in cirrhotic patients remains unclear and poses serious safety problems. Vira kinetic models, analyzed by nonlinear mixed effect models (NLMEM), are a powerful tool for understanding the response to treatment. We have demonstrated, by means of clinical trial simulation, the power of the Wald tes1 within NLMEM to detect a HCV drug's antiviral effectiveness difference. This approach, even for a small number of samples, provided consistently higher power to the standard approach based on a non parametric Wilcoxon test on the viral load decay. However, we have highlighted an inflation of the type I error with the Wald test when the number of patients is low and have proposed a permutation correction. We applied this approach to estimate the antiviral effectiveness of the triple therapies in cirrhotic patients and non-responders to a prior therapy (ANRS MODCUPIC). We hav( shown that over 99% of the viral replication was blocked by PI, with a significantly superior effectiveness of telaprevir compared to boceprevir and suboptimal effectiveness of Peg-IFN/RBV. Finally, by modeling the kinetics of blood parameters, we demonstrated that the concentrations of Peg-IFN and RBV are associated with, respectively, anemia and thrombocytopenia which are frequently observed in these patients.PARIS7-Bibliothèque centrale (751132105) / SudocSudocFranceF

Risk factors for carbapenem-resistant Enterobacteriaceae infections: a French case-control-control study.

Electronic supplementary material : The online version of this article ( https://doi.org/10.1007/s10096-018-3438-9) contains supplementary material, which is available to authorized users.International audienceThis study aimed to assess characteristics associated with infections due to carbapenem-resistant Enterobacteriaceae (CRE), producing (CPE) or not producing (non-CPE) carbapenemase, among hospitalised patients in 2014-2016 in France. Case-patients with CRE were compared to two control populations. In multivariate analysis comparing 160 CRE cases to 160 controls C1 (patients with a clinical sample positive for carbapenem-susceptible Enterobacteriaceae), five characteristics were linked to CRE: male gender (OR = 1.9; 95% CI = 1.3-3.4), travel in Asia (OR = 10.0; 95% CI = 1.1-91.2) and hospitalisation in (OR = 2.4; 95% CI = 1.3-4.4) or out of (OR = 4.4; 95% CI = 0.8-24.1) France in the preceding 12 months, infection in the preceding 3 months (OR = 3.0; 95% CI = 1.5-5.9), and antibiotic receipt between admission and inclusion (OR = 1.9; 95% CI = 1.0-3.3). In multivariate analysis comparing 148 CRE cases to 148 controls C2 [patients with culture-negative sample(s)], four characteristics were identified: prior infection (OR = 3.3; 95% CI = 1.6-6.8), urine drainage (OR = 3.0; 95% CI = 1.5-6.1) and mechanical ventilation (OR = 3.7; 95% CI = 1.1-13.0) during the current hospitalisation, and antibiotic receipt between admission and inclusion (OR = 6.6; 95% CI = 2.8-15.5). Univariate analyses comparing separately CPE cases to controls (39 CPE vs C1 and 36 CPE vs C2) and non-CPE cases to controls (121 non-CPE vs C1 and 112 non-CPE vs C2), concomitantly with comparison of CPE to non-CPE cases showed that only CPE cases were at risk of previous travel and hospitalisation abroad. This study shows that, among CRE, risk factors are different for CPE and non-CPE infection, and suggests that question patients about their medical history and lifestyle should help for early identification of patients at risk of CPE among patients with CRE

Lupus activity and outcomes in lupus patients undergoing maintenance dialysis

International audienceObjectives Lupus activity has long been considered to decline after initiation of maintenance dialysis (MD). This assumption is based on limited historical data. We aimed to describe the natural history of lupus in patients undergoing MD. Methods We assembled a national retrospective cohort of lupus patients who started dialysis between 2008 and 2011, included in the REIN registry with a 5-year follow-up. We analysed healthcare consumption from the National Health Data System. We evaluated the proportion of patients ‘off-treatment’ (i.e. receiving 0–5 mg/d of corticosteroids, without any immunosuppressive therapy) after the start of MD. We describe the cumulative incidences of non-severe and severe lupus flares, cardiovascular events, severe infections, kidney transplantation and survival. Results We included 137 patients (121 females and 16 males), with a median age of 42 years. The proportion of patients ‘off-treatment’ at dialysis initiation was 67.7% (95% CI: 61.8, 73.8%), and increased to 76.0% (95% CI: 73.3, 78.8) at 1 year and 83.4% (95% CI: 81.0, 85.9%) at 3 years, with a lower proportion in younger patients. Lupus flares mainly occurred in the first year after MD initiation, and at 12 months 51.6% of patients had presented a non-severe lupus flare and 11.6% a severe lupus flare. In addition, 42.2% (95% CI: 32.9, 50.3%) and 23.7% (95% CI: 16.0, 30.7%) of patients at 12 months had been hospitalized for cardiovascular events or infections, respectively. Conclusion The proportion of lupus patients off-treatment increases after MD initiation, but non-severe and severe lupus flares continue to occur, mainly during the first year. This calls for the continued follow-up of lupus patients by lupus specialists after dialysis initiation

Chikungunya, a risk factor for Guillain-Barré syndrome.

International audienceIn a matched case-control study where 24 cases developed Guillain-Barré syndrome (GBS) during the 2014 chikungunya outbreak in the French West Indies and 72 controls were blood donors who donated their blood at the same period, Chikungunya infection was a risk factor for GBS (OR 8.3, 95% CI 2.3-29.7, p=0.001)

Electronic Sensors for Measuring Interactions between Healthcare Workers (HCWs) and Patients (Pts): the Case of Tuberculosis (TB)

International audienc

Electronic Sensors for Measuring Interactions between Healthcare Workers (HCWs) and Patients (Pts): the Case of Tuberculosis (TB)

International audienc

Electronic Sensors for Measuring Interactions between Healthcare Workers (HCWs) and Patients (Pts): the Case of Tuberculosis (TB)

International audienc

Phylogroup stability contrasts with high within sequence type complex dynamics of Escherichia coli bloodstream infection isolates over a 12-year period

Abstract Background Escherichia coli is the leading cause of bloodstream infections, associated with a significant mortality. Recent genomic analyses revealed that few clonal lineages are involved in bloodstream infections and captured the emergence of some of them. However, data on within sequence type (ST) population genetic structure evolution are rare. Methods We compared whole genome sequences of 912 E . coli isolates responsible for bloodstream infections from two multicenter clinical trials that were conducted in the Paris area, France, 12 years apart, in teaching hospitals belonging to the same institution (“Assistance Publique-Hôpitaux de Paris”). We analyzed the strains at different levels of granularity, i.e., the phylogroup, the ST complex (STc), and the within STc clone taking into consideration the evolutionary history, the resistance, and virulence gene content as well as the antigenic diversity of the strains. Results We found a mix of stability and changes overtime, depending on the level of comparison. Overall, we observed an increase in antibiotic resistance associated to a restricted number of genetic determinants and in strain plasmidic content, whereas phylogroup distribution and virulence gene content remained constant. Focusing on STcs highlighted the pauci-clonality of the populations, with only 11 STcs responsible for more than 73% of the cases, dominated by five STcs (STc73, STc131, STc95, STc69, STc10). However, some STcs underwent dramatic variations, such as the global pandemic STc131, which replaced the previously predominant STc95. Moreover, within STc131, 95 and 69 genomic diversity analysis revealed a highly dynamic pattern, with reshuffling of the population linked to clonal replacement sometimes coupled with independent acquisitions of virulence factors such as the pap gene cluster bearing a papGII allele located on various pathogenicity islands. Additionally, STc10 exhibited huge antigenic diversity evidenced by numerous O:H serotype/ fimH allele combinations, whichever the year of isolation. Conclusions Altogether, these data suggest that the bloodstream niche is occupied by a wide but specific phylogenetic diversity and that highly specialized extra-intestinal clones undergo frequent turnover at the within ST level. Additional worldwide epidemiological studies overtime are needed in different geographical and ecological contexts to assess how generalizable these data are