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Background: Time in range (TIR) goals are rarely met in children with type 1 diabetes, except at the cost of increased hypoglycaemia episodes. Our objective was to evaluate the safety and efficiency of the Diabeloop DBL4K (Diabeloop, Grenoble, France) hybrid closed-loop system in prepubescent children., Methods: We did a multicentre, open-label, randomised, controlled, non-inferiority, two-session crossover study in the paediatric endocrinology departments of three university hospitals in France and Belgium. Eligible participants were aged 6-12 years with type 1 diabetes for at least 1 year, glycated haemoglobin A 1C 9% (75 mmol/mol) or less, and insulin pump treatment for at least 3 months. Participants were randomly assigned (1:1) to a closed-loop device or sensor-augmented pump (open loop) therapy. Randomisation was by a permuted block randomisation scheme, using an interactive web-based response system, and was stratified on centre (block size 6). The assessed closed-loop device, the Diabeloop for Kids DBL4K hybrid closed-loop system, is an automated blood glucose regulation system composed of a handset, insulin pump, and continuous glucose monitor. The open-loop system is defined as a sensor-augmented pump therapy composed of the usual insulin pump used by the patient and a continuous glucose monitor. A 72-h in-patient period was followed by a 6-week home phase. After a 1-week washout period, the participants crossed over to the other device. The primary outcome, assessed in the intention-to-treat population, was the mean proportion of time spent in hypoglycaemia (3·9 mmol/L [<70 mg/dL]) during the hospital phase, with a non-inferiority margin of -2·5% (absolute value). Safety was assessed in the intention-to-treat population on a per-protocol basis. This study was registered with ClinicalTrials.gov, NCT03671915., Findings: Between May 6 and Dec 23, 2019, we included 21 participants (closed loop then open loop, n=10; open loop then closed loop, n=11). The proportion of time spent in hypoglycaemia was significantly lower with the closed-loop system than the open-loop system in both groups (2·04% [95% CI 0·44 to 3·64] vs 7·06% [5·46 to 8·66]; non-inferiority one-sided p<0·0001). No severe ketoacidosis, nor severe hyoglycaemic events or fatal adverse events occurred. All 25 adverse events (18 with the closed-loop system, seven with the open-loop system) were related to the treatment., Interpretation: The closed-loop Diabeloop system decreased hypoglycaemic episodes and provided good metabolic control in prepubescent children with type 1 diabetes, under real-life conditions. This finding supports the safe use of closed-loop technology in this paediatric population., Funding: Diabeloop., Translation: For the French translation of the abstract see Supplementary Materials section., Competing Interests: Declaration of interests SF is a consultant for Diabeloop, a member of the scientific board of Diabeloop, a shareholder of Diabeloop, and she received speaker honoraria from Abbott, participated on a data safety monitoring board or advisory board for Novo Nordisk, and has received congress invitations from Sanofi, MSD, Roche, and Abbott. GC owns shares in Diabeloop and is chief medical officer of the Diabeloop company. P-YB has received speaker honoraria from Abbott, Eli Lilly, Novo Nordisk, Roche, and has served on advisory board panels for Abbott, Dexcom, Diabeloop, Insulet, Eli Lilly, Novo Nordisk, and Roche. EH owns shares in Diabeloop, which participated in the funding and provision of study materials, and has a leadership role in Diabeloop. KC received support for attending a meeting with Sandoz, participated on an advisory board for Abbott, and received consulting fees from Novo Nordisk. All other authors declare no competing interests., (Copyright © 2022 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC-ND 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Background: Initial reports on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections in children suggested that very young age and comorbidities may increase risk of severe evolution, but these findings remained to be confirmed. We aimed to analyze the clinical spectrum of hospitalized pediatric SARS-CoV-2 infection and predictors of severe disease evolution., Methods: We conducted a French national prospective surveillance of children hospitalized with SARS-CoV-2 infection. We included all children with confirmed SARS-CoV-2 infection in 60 hospitals during February 15 to June 1, 2020. The main outcome was the proportion of children with severe disease, defined by hemodynamic or ventilatory (invasive or not) support requirement., Results: We included 397 hospitalized children with SARS-CoV-2 infection. We identified several clinical patterns, ranging from paucisymptomatic children, admitted for surveillance, to lower respiratory tract infection or multisystem inflammatory syndrome in children. Children <90 days old accounted for 37% of cases (145 of 397), but only 4 (3%) had severe disease. Excluding children with multisystem inflammatory syndrome in children ( n = 29) and hospitalized for a diagnosis not related to SARS-CoV-2 ( n = 62), 23 of 306 (11%) children had severe disease, including 6 deaths. Factors independently associated with severity were age ≥10 years (odds ratio [OR] = 3.4, 95% confidence interval: 1.1-10.3), hypoxemia (OR = 8.9 [2.6-29.7]), C-reactive protein level ≥80 mg/L (OR = 6.6 [1.4-27.5])., Conclusions: In contrast with preliminary reports, young age was not an independent factor associated with severe SARS-CoV-2 infection, and children <90 days old were at the lowest risk of severe disease evolution. This may help physicians to better identify risk of severe disease progression in children., Competing Interests: POTENTIAL CONFLICT OF INTEREST: The authors have indicated they have no potential conflicts of interest to disclose., (Copyright © 2021 by the American Academy of Pediatrics.)

Objectives: Newborn screening (NBS) for β-thalassemia is based on measuring the expression of the hemoglobin A (HbA) fraction. An absence or very low level of HbA at birth may indicate β-thalassemia. The difficulty is that the HbA fraction at birth is correlated with gestational age (GA) and highly variable between individuals. We used HbA expressed in multiples of the normal (MoM) to evaluate relevant thresholds for NBS of β-thalassemia., Methods: The chosen threshold (HbA≤0.25 MoM) was prospectively applied for 32 months in our regional NBS program for sickle cell disease, for all tests performed, to identify patients at risk of β-thalassemia. Reliability of this threshold was evaluated at the end of the study., Results: In all, 343,036 newborns were tested, and 84 suspected cases of β-thalassemia were detected by applying the threshold of HbA≤0.25 MoM. Among the n=64 cases with confirmatory tests, 14 were confirmed using molecular analysis as β-thalassemia diseases, 37 were confirmed as β-thalassemia trait and 13 were false-positive. Determination of the optimum threshold for β-thalassemia screening showed that HbA≤0.16 MoM had a sensitivity of 100% and a specificity of 95.3%, whatever the GA., Conclusions: NBS for β-thalassemia diseases is effective, regardless of the birth term, using the single robust threshold of HbA≤0.16 MoM. A higher threshold would also allow screening for carriers, which could be interesting when β-thalassemia constitutes a public health problem.

Understanding the clinical presentation of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and prognosis in children is a major issue. Children often present mild symptoms, and some severe forms require paediatric intensive care, with in some cases a fatal prognosis. Our aim was to identify the epidemiological characteristics, clinical presentation, and prognosis of children with coronavirus disease 2019 (Covid-19) hospitalized in Paris suburb hospitals. In this prospective, observational, multicentre study, we included children hospitalized in paediatric departments of Paris suburb hospitals from 23 March 2020 to 10 May 2020, during the national lockdown in France with confirmed SARS-CoV-2 infection (positive RNA test on a nasopharyngeal swab) or highly suspected infection (clinical, biological, and/or radiological data features suggestive for SARS-CoV-2 infection). A total of 192 children were included for confirmed ( n = 157) or highly suspected ( n = 35) SARS-CoV-2 infection. The median age was one year old (interquartile range 0.125-11) with a sex ratio 1.3:1. Fever was recorded in 147 (76.6%) children and considered poorly tolerated in 29 (15.1%). The symptoms ranged from rhinorrhoea (34.4%) and gastrointestinal (35.5%) to respiratory distress (25%). Only 10 (5.2%) children had anosmia and five (2.6%) had chest pain. An underlying condition was identified in almost 30% of the children in our study. Overall, 24 (12.5%) children were admitted to paediatric intensive care units, 12 required mechanical ventilation, and three died. For children in Paris suburbs, most cases of Covid-19 showed mild or moderate clinical expression. However, one-eighth of children were admitted to paediatric intensive care units and three died., Competing Interests: The authors have no potential conflicts of interest related to this article.

Pseudomonas aeruginosa is an opportunistic pathogen that causes public healthcare issues. In moist environments, this Gram-negative bacterium persists through biofilm-associated contamination on surfaces. Bacteriophages are seen as a promising alternative strategy to chemical biocides. This study evaluates the potential of nine lytic bacteriophages as biocontrol treatments against nine environmental P. aerginosa isolates. The spot test method is preliminarily used to define the host range of each virus and to identify their minimum infectious titer, depending on the strain. Based on these results, newly isolated bacteriophages 14.1, LUZ7, and B1 are selected and assessed on a planktonic cell culture of the most susceptible isolates (strains MLM, D1, ST395E, and PAO1). All liquid infection assays are achieved in a mineral minimum medium that is much more representative of real moist environments than standard culture medium. Phages 14.1 and LUZ7 eliminate up to 90% of the PAO1 and D1 bacterial strains. Hence, their effectiveness is evaluated on the 24 h old biofilms of these strains, established on a stainless steel coupon that is characteristic of materials found in thermal and industrial environments. The results of quantitative PCR viability show a maximum reduction of 1.7 equivalent Log CFU/cm 2 in the coupon between treated and untreated surfaces and shed light on the importance of considering the entire virus/host/environment system for optimizing the treatment.

We conducted a retrospective study on newborns with sickle-cell disease (SCD), born 1995-2009, followed in a multicentre hospital-based network. We assessed patient outcomes, medical care and compliance with the national guidelines published in December 2005. Data from 1033 patients (742 SS/Sβ°-thalassaemia) with 6776 patient-years of follow-up were analysed (mean age 7·1 ± 3·9 years). SCD-related deaths (n = 13) occurred only in SS-genotype patients at a median age of 23·1 months, mainly due to acute anaemia (n = 5, including 2 acute splenic sequestrations) and infection (n = 3). Treatment non-compliance was associated with a 10-fold higher risk of SCD-related death (P = 0·01). Therapeutic intensification was provided for all stroke patients (n = 12), almost all patients with abnormal transcranial Doppler (TCD) (n = 76) or with >1 acute chest syndrome/lifetime (n = 64) and/or ≥3 severe vaso-occlusive crises/year (n = 100). Only 2/3 of patients with baseline haemoglobin <70 g/l received intensification, mainly for other severity criteria. Overall, hydroxycarbamide was under-prescribed, given to 2/3 of severe vaso-occlusive patients and 1/3 of severely anaemic patients. Nevertheless, introduction of the on-line guidelines was concomitant with an improvement in medical care in the 2006-2009 cohort with a trend towards increased survival at 5 years, from 98·3% to 99·2%, significantly increased TCD coverage (P = 0·004) and earlier initiation of intensification of therapy (P ≤ 0·01)., (© 2016 John Wiley & Sons Ltd.)

In this study, the performance of a new most probable number (MPN) test (Pseudalert(®)/Quanti-Tray(®)) for the enumeration of Pseudomonas aeruginosa from hospital waters was compared with both international and national membrane filtration-based culture methods for P. aeruginosa: ISO 16266:2006 and UK The Microbiology of Drinking Water - Part 8 (MoDW Part 8), which both use Pseudomonas CN agar. The comparison based on the calculation of mean relative differences between the two methods was conducted according to ISO 17994:2014. Using both routine hospital water samples (80 from six laboratories) and artificially contaminated samples (192 from five laboratories), paired counts from each sample and the enumeration method were analysed. For routine samples, there were insufficient data for a conclusive assessment, but the data do indicate at least equivalent performance of Pseudalert(®)/Quanti-Tray(®). For the artificially contaminated samples, the data revealed higher counts of P. aeruginosa being recorded by Pseudalert(®)/Quanti-Tray(®). The Pseudalert(®)/Quanti-Tray(®) method does not require confirmation testing for atypical strains of P. aeruginosa, saving up to 6 days of additional analysis, and has the added advantage of providing confirmed counts within 24-28 hours incubation compared to 40-48 hours or longer for the ISO 16266 and MoDW Part 8 methods.

Natural swimming ponds (NSPs) are a new type of recreational water facility characterized by the substitution of traditional disinfection with biodepuration. While this feature meets esthetic desires of users, specific concerns on public health issues have been raised by the scientific community and local authorities. The absence of a European directive applicable to these environments leaves each country without specific and harmonized indications. The present work describes the local/national policy situation, describing adopted parameters and monitoring activities. All documents underline the need for appropriate microbiological analysis and correct water management.

Free-living amoebae might be pathogenic by themselves and be a reservoir for bacterial pathogens, such as Legionella pneumophila. Not only could amoebae protect intra-cellular Legionella but Legionella grown within amoebae could undergo physiological modifications and become more resistant and more virulent. Therefore, it is important to study the efficiency of treatments on amoebae and Legionella grown within these amoebae to improve their application and to limit their impact on the environment. With this aim, we compared various water disinfectants against trophozoites of three Acanthamoeba strains and L. pneumophila alone or in co-culture. Three oxidizing disinfectants (chlorine, monochloramine, and chlorine dioxide) were assessed. All the samples were treated with disinfectants for 1 h and the disinfectant concentration was followed to calculate disinfectant exposure (Ct). We noticed that there were significant differences of susceptibility among the Acanthamoeba strains. However no difference was observed between infected and non-infected amoebae. Also, the comparison between the three disinfectants indicates that monochloramine was efficient at the same level towards free or co-cultured L. pneumophila while chlorine and chlorine dioxide were less efficient on co-cultured L. pneumophila. It suggests that these disinfectants should have different modes of action. Finally, our results provide for the first time disinfectant exposure values for Acanthamoeba treatments that might be used as references for disinfection of water systems., (Copyright © 2010 Elsevier Ltd. All rights reserved.)

The virulence of Viable But Non-Culturable (VBNC) cells of 4 strains of Listeria monocytogenes was investigated in both a human adenocarcinoma cell line (HT-29) and a mouse model. LO 28, ATCC 19115 and CNL 895807 strains of Listeria monocytogenes became VBNC when incubated in microcosm water at 20 degrees C and Scott A strain at 4 degrees C. No culturable bacteria were detected in the VBNC state, although 104 active cells/mL were found by the Direct Viable Count (DVC) and CTC-DAPI double staining methods. A comparison of virulence in both human adenocarcinoma cell line HT-29 and the mouse model showed that culturable controls were more virulent than VBNC cells, which appeared to be avirulent regardless of the virulence methods applied. Pathogenicity was tested in each model and was lost concomitantly with culturability, whereas some cells were still metabolically active (determined by CTC and DVC). Moreover, amplification of a 388 bp fragment with Immunocapture-PCR revealed the presence of Listeria monocytogenes DNA in all mixed spleen samples after intravenous injection of VBNC cells. These results demonstrate that VBNC cells were present in the mouse spleens. The results of the study suggest that Listeria monocytogenes strains might remain in the aquatic environment for prolonged periods in the VBNC state but these cells were not pathogenic in the conditions tested. These findings demonstrate the value of VBNC studies and show the need to investigate the role of VBNC cells in environmental transmission of Listeria monocytogenes. Further studies are needed in order to investigate the virulence of VBNC cells of Listeria monocytogenes after recovery of a culturable state.

According to the decree of 1992, the Paris hospitals (AP-HP) pediatric medical home care network offers care for all children irrespective of their pathology within the framework of a medico-psycho-social therapeutic project provided as an in alternative to traditional hospitalization. 30% of the admissions occur during the neonatal period. We studied the files of 249 newborn or preterm infants given in medical home care between January and September 2003. 71% were preterm infants. 46.4% of the children had been admitted at least once in an intensive care unit. At their admission in the pediatric medical home care unit, the median corrected gestational age was 39 weeks 6 days; 43% weighed less than 2500g, 9% less than 2000g, 22.5% of the preterm infants had a corrected gestational age less than 37 weeks, 65% of the infants presented gastrointestinal and/or feeding disorders. The average duration of stay in the pediatric medical home care unit was 20.5 days. The competence of pediatric nurses working in an integrated multidisciplinary team including psychologists and social workers is the key to success of pediatric medical home care.

Given the high level of background flora in sludge, methods for detecting Listeria monocytogenes are not well established. In this study, two critical parameters for the detection of L. monocytogenes were evaluated: the concentration of Listeria sp. in a modified Fraser broth (first stage of the method) and the proportion of L. monocytogenes on Palcam agar (second stage of the method). Concentrations of Listeria sp. estimated in 118 modified Fraser enrichment broths inoculated with four types of sludge, reached 10(4) bacteria per mL for 83% of the positive enrichment broths. Proportion of L. monocytogenes on Palcam agar, which was estimated by transferring all characteristic colonies of Listeria sp. onto Rapid'L Mono agar, was highly variable regardless of the type of sludge. According to these results, we proposed a protocol that consisted of an enrichment in modified Fraser broth for 48 h at 37 degrees C, followed by plating 0.1 mL of appropriate dilutions of broth onto Palcam agar. After an incubation of 48 h at 37 degrees C, a systematic identification of characteristic colonies of Listeria sp. on Rapid'L Mono agar allowed to enhance the detection of Listeria monocytogenes.

Bacteroides is a predominant group of the faecal microbiota in healthy adults. To investigate the species composition of Bacteroides by fluorescent in situ hybridisation (FISH) combined with flow cytometry, we developed five species-specific probes targeting the 16S rRNA. Probes were designed to identify cells belonging to Bacteroides distasonis, B. fragilis, B. ovatus, B. vulgatus and B. putredinis. The species-specificity of the probes was assessed against a collection of reference strains from the Cytophaga-Flavobacterium-Bacteroides group. The results of the FISH experiments showed that the probes were specific as they only detected strains of the target species. Determining the fluorescence intensity of each probe relative to that of the EUB 338 probe (domain bacteria) further showed that each species probe easily accessed the targeted site. The probes were applied to quantify the Bacteroides species in faeces collected from 20 healthy adults. All five species were detected in the faecal samples. Cells hybridised with Bfra 998 were the most frequent as they were observed in 90% of individuals (18/20 samples, mean proportion of 3.9 +/- 2.2%). The cells hybridised with Bvulg 1017 were observed in 85% of individuals (17/20 samples) and represented with a mean proportion of 4.2 +/- 6.1%, the most abundant Bacteroides species in human faeces. Cells hybridising with probes for B. ovatus, B. distasonis and B. putredinis were less frequently detected. The large distribution of B. vulgatus and B. fragilis in human faeces is in accordance with previous reports based on culture or molecular studies. This work showed that fluorescent in situ hybridisation is a tool appropriate for a high-resolution analysis of the species composition of complex ecosystems and especially of the Bacteroides group within the faecal microbiota.