Clinical impact and cost-consequence analysis of ePlex® blood culture identification panels for the rapid diagnosis of bloodstream infections: a single-center randomized controlled trial.

To assess clinical impact and perform cost-consequence analysis of the broadest multiplex PCR panels available for the rapid diagnosis of bloodstream infections (BSI). Single-center, randomized controlled trial conducted from June 2019 to February 2021 at a French University hospital with an institutional antimicrobial stewardship program. Primary endpoint was the percentage of patients with optimized antimicrobial treatment 12 h after transmission of positivity and Gram stain results from the first positive BC. This percentage was significantly higher in the multiplex PCR (mPCR) group (90/105 = 85.7% %, CI95% [77.5 ; 91.8] vs. 68/107 = 63.6%, CI95% [53.7 ; 72.6]; p < 10- 3) at interim analysis, resulting in the early termination of the study after the inclusion of 309 patients. For patients not optimized at baseline, the median time to obtain an optimized therapy was much shorter in the mPCR group than in the control group (6.9 h, IQR [2.9; 17.8] vs. 26.4 h, IQR [3.4; 47.5]; p = 0.001). Early optimization of antibiotic therapy resulted in a non-statistically significant decrease in mortality from 12.4 to 8.8% (p = 0.306), with a trend towards a shorter median length of stay (18 vs. 20 days; p = 0.064) and a non-significant reduction in the average cost per patient of €3,065 (p = 0.15). mPCR identified all the bacteria present in 88% of the samples. Despite its higher laboratory cost, the use of multiplex PCR for BSI diagnosis leads to early-optimised therapy, seems cost-effective and could reduce mortality and length of stay. Their impact could probably be improved if implemented 24/7.

Characterization and chlorine reactivity of particulate matter released by bathers in indoor swimming pools.

Disinfecting swimming pool water is essential for preventing waterborne diseases. An unforeseen consequence of treating water with disinfectants is the formation of disinfection by-products (DPBs) that can cause harmful effects to health through the interactions between the added disinfectant and organic matter in the water. The present work focuses on the chlorine reactivity with particles released by bathers. Such particles are collected in the filter backwash water of swimming pools and this study intends to distinguish DPBs generated from dissolved chemicals from those formed by particulate matter. Therefore, filtered and unfiltered backwash waters were collected from several swimming pools, analysed physicochemically and chemically, and then chlorinated as is (79 mgL-1) and as diluted suspensions (36.2 and 11.9 mgL-1) at varying concentrations of chlorine (1.2 mg and 24 mgCl2L-1). Utilizing a DPD colorimetric technique and GC-ECD, respectively, the kinetics of chlorine consumption and DPBs production have been investigated. Up to 25.7 µgL-1 of chloroform was produced within 96 h at 1.2 mgCl2L-1, followed by haloacetic acids (HAAs) and haloacetonitriles (HANs). Within 96 h, the concentration of trichloroacetic acid reached a maximum of 231.8 µgL-1 at a chlorine concentration of 231.8 µgL-1. The formations of 0.13 µmol THMs, 0.31 µmol HAAs, and 0.04 µmol HANs per mg of dissolved organic carbon (DOC) were finally determined by correlating the organic content of particles with the nature of the DBPs generated. Comparing the quantities of DBPs generated in filtered and unfiltered samples helps us conclude that ∼50% of DBPs formed during the chlorination of swimming pool water are derived from particles brought by bathers.

Corneal haze post photorefractive keratectomy.

Corneal haze represents subepithelial corneal fibrosis, a manifestation of a pathological healing process. It occurs as a result of an epithelial-stromal lesion involving a break in the epithelial barrier. It is an inflammatory response that involves the migration, multiplication and differentiation of keratocytes into mature myofibroblasts, causing loss of corneal transparency. Although it is a transient phenomenon, this complication is feared following refractive photokeratectomy (PRK), because it can cause alterations in the quality of vision, refractive regression and decreased visual acuity. The severity of these symptoms is correlated with the severity of the corneal haze, which can be assessed clinically or by objective means such as corneal densitometry measurement. The frequency and severity of corneal haze increase with the depth of photoablation in PRK and are therefore increased during the treatment of severe ametropia. Considering that no consensus exists, the application of mitomycin C (MMC) intraoperatively and topical corticosteroids postoperatively are conventionally used to inhibit collagen synthesis, sometimes in combination with various protocols depending on the center or surgeon. This review of the literature reports the current knowledge on corneal haze, in order to better understand it and optimise its prevention in the context of a decreased MMC supply, which has occurred in the past and could recur in the future.

SARS-CoV-2 nosocomial infection acquired in a French university hospital during the 1st wave of the Covid-19 pandemic, a prospective study.

BACKGROUND: In healthcare facilities, nosocomial transmissions of respiratory viruses are a major issue. SARS-CoV-2 is not exempt from nosocomial transmission. Our goals were to describe COVID-19 nosocomial cases during the first pandemic wave among patients in a French university hospital and compliance with hygiene measures. METHODS: We conducted a prospective observational study in Grenoble Alpes University Hospital from 01/03/2020 to 11/05/2020. We included all hospitalised patients with a documented SARS-CoV-2 diagnosis. Nosocomial case was defined by a delay of 5 days between hospitalisation and first symptoms. Hygiene measures were evaluated between 11/05/2020 and 22/05/2020. Lockdown measures were effective in France on 17/03/2020 and ended on 11/05/2020. Systematic wearing of mask was mandatory for all healthcare workers (HCW) and visits were prohibited in our institution from 13/03/2021 and for the duration of the lockdown period. RESULTS: Among 259 patients included, 14 (5.4%) were considered as nosocomial COVID-19. Median time before symptom onset was 25 days (interquartile range: 12-42). Eleven patients (79%) had risk factors for severe COVID-19. Five died (36%) including 4 deaths attributable to COVID-19. Two clusters were identified. The first cluster had 5 cases including 3 nosocomial acquisitions and no tested HCWs were positive. The second cluster had 3 cases including 2 nosocomial cases and 4 HCWs were positive. Surgical mask wearing and hand hygiene compliance were adequate for 95% and 61% of HCWs, respectively. CONCLUSIONS: The number of nosocomial COVID-19 cases in our hospital was low. Compliance regarding mask wearing, hand hygiene and lockdown measures drastically reduced transmission of the virus. Monitoring of nosocomial COVID-19 cases during the first wave enabled us to determine to what extent the hygiene measures taken were effective and patients protected. Trial registration Study ethics approval was obtained retrospectively on 30 September 2020 (CECIC Rhône-Alpes-Auvergne, Clermont-Ferrand, IRB 5891).

COVID-19 in clinical practice: A narrative synthesis.

The coronavirus disease 2019 (COVID-19) was first reported in the city of Wuhan, China. The disease rapidly spread to the rest of China, to Southern-East Asia, then to Europe, America, and on to the rest of the world. COVID-19 is associated with a betacoronavirus named SARS-CoV-2. The virus penetrates the organism through the respiratory tract, conveyed by contaminated droplets. The main cell receptor targeted is the surface-bound ACE-2. As of the 26th July 2020, 15,200,000 COVID-19 cases and 650,000 deaths were reported worldwide. The mortality rate is estimated between 1.3 and 18.3%. The reproductive rate without any public health intervention is estimated around 4-5.1 in France. Most hospitalized patients for COVID-19 present respiratory symptoms, which in some cases is associated with fever. Up to 86% of admissions to ICU are related to acute respiratory failure. To date, no anti-viral therapy has proven its efficacy considering randomized trials. Only immunomodulatory treatments such as corticosteroids have shown to cause significant improvement in patient outcome.

A drop does not fall in a straight line: a rationale for the width of stalagmites.

Drops loaded in calcium ions detach from stalactites and impact the underlying stalagmites, thereby allowing these latter to grow through calcite precipitation. Nevertheless, little is known about the influence of the drop free fall and splash dynamics on stalagmite shape and width. Through high-speed imaging of impacting drops on stalagmites from several caves, we observed that the impact point position of the drops is scattered, sometimes over several centimetres. We show that this dispersal has no external cause and must, therefore, be self-induced. Using a Langevin-like equation, we then propose a prediction of the impact point dispersal as a function of the falling height travelled by the drops. We finally show that measured stalagmite widths are correlated to the dispersal in the impact point position of the drop.

[Cyclodialysis, a therapeutic challenge: Review of the literature on current practices]. / Cyclodialyse : un challenge thérapeutique, revue de la littérature sur les pratiques actuelles.

INTRODUCTION: Cyclodialysis is a rare condition that is difficult to manage. We present the case of a woman with a cyclodialysis complicated by chronic hypotony requiring two surgeries to achieve reattachment of the ciliary body. We also report the results of a review of the literature regarding the treatment of this condition. DESCRIPTION: This is a 46-year-old woman with history of trauma to the right eye. Examination revealed an intra-ocular pressure (IOP) of 7mmHg, a shallow anterior chamber and signs of chronic hypotony on fundus examination (vascular tortuosity, hypotony maculopathy) due to an extensive 360° cyclodialysis, confirmed by ultrasound biomicroscopy. Transcleral cryotherapy as a first-line approach did not achieve reattachment of the ciliary body. Secondary pars plana vitrectomy with gas tamponade (C2F6) reattached the ciliary body and restored the intraocular pressure (12mmHg) and normal fundus appearance. The patient recovered corrected visual acuity of 20/20. DISCUSSION: To our knowledge, there is no standardized management for cyclodialysis. The study of the literature available on the Medline database showed that direct cyclopexy remains the most common treatment, followed by vitrectomy with internal tamponade. Neither the extent nor the duration of the cyclodialysis can predict the visual recovery, which can be major even after weeks of hypotony. CONCLUSION: The management of cyclodialysis is not well-defined; it remains a true therapeutic challenge.

[Hereditary color vision deficiency: Physiology, classification, diagnosis and application to aeronautics]. / Dyschromatopsies hereditaires : physiologie, classification, diagnostic et application à l'aéronautique.

Hereditary color vision deficiency affects 9% of men and 0.5% of women. It is often unrecognized and diagnosed late, which can interfere with the professional careers of these patients. Most color vision deficiencies are related to X chromosome involvement and concern the red-green chromatic axis. They are secondary to dysfunction of an L or M cone (protanomaly or deuteranomaly) or to the absence of an L or M cone (protanopia or deuteranopia). Color vision deficiency screening and assessment can be done by confusion tests or equalization tests, but also by ergonomic tests, professional tests that assess the aptitude for a given profession.

Isotropic-nematic transition of self-propelled rods in three dimensions.

Using overdamped Brownian dynamics simulations we investigate the isotropic-nematic (IN) transition of self-propelled rods in three spatial dimensions. For two well-known model systems (Gay-Berne potential and hard spherocylinders) we find that turning on activity moves to higher densities the phase boundary separating an isotropic phase from a (nonpolar) nematic phase. This active IN phase boundary is distinct from the boundary between isotropic and polar-cluster states previously reported in two-dimensional simulation studies and, unlike the latter, is not sensitive to the system size. We thus identify a generic feature of anisotropic active particles in three dimensions.

In silico clinical trials for pediatric orphan diseases.

To date poor treatment options are available for patients with congenital pseudarthrosis of the tibia (CPT), a pediatric orphan disease. In this study we have performed an in silico clinical trial on 200 virtual subjects, generated from a previously established model of murine bone regeneration, to tackle the challenges associated with the small, pediatric patient population. Each virtual subject was simulated to receive no treatment and bone morphogenetic protein (BMP) treatment. We have shown that the degree of severity of CPT is significantly reduced with BMP treatment, although the effect is highly subject-specific. Using machine learning techniques we were also able to stratify the virtual subject population in adverse responders, non-responders, responders and asymptomatic. In summary, this study shows the potential of in silico medicine technologies as well as their implications for other orphan diseases.

Chronic disseminated candidiasis and acute leukemia: Impact on survival and hematopoietic stem cell transplantation agenda.

OBJECTIVES: To study the management of chronic disseminated candidiasis (CDC) in patients presenting with acute leukemia. PATIENTS AND METHODS: Single-center retrospective study of acute leukemia patients (2006-2015) to investigate three aspects of CDC: its impact on the time interval between diagnosis and hematopoietic stem cell transplantation, when required (non-parametric Wilcoxon-Mann-Whitney test); its impact on overall survival (Cox proportional hazard regression model); antifungal therapeutic strategies implemented. RESULTS: A total of 639 patients presenting with acute leukemia were included; 144 were transplanted and 29 developed CDC. CDC did not significantly increase the time interval between diagnosis and transplantation, nor did it impact the overall survival of recipients. An improved overall survival was observed in non-transplanted acute leukemia patients presenting with CDC. CONCLUSION: CDC should not postpone transplantation if antifungal treatment is optimized.

Failure of systemic oral doxycycline in preventing ocular toxoplasmic retinochoroiditis in French military personnel.

This paper describes two cases of toxoplasmic chorioretinitis presenting in two French soldiers who had been receiving oral doxycycline for malaria prophylaxis. This is despite the proven effectiveness of oral doxycycline in treating Toxoplasma gondii, the most common cause of this infection. The lack of effectiveness of oral doxycycline in these two cases most likely reflected that the ocular concentration of 100 mg daily doxycycline is too low to treat or prevent Toxoplasmic retinochoroiditis (TC). Clinicians should therefore be aware that soldiers taking prophylactic oral doxycycline are still at risk of developing ocular TC with potentially sight-threatening consequences if not treated adequately.

General practitioners' perceptions of vaccination controversies: a French nationwide cross-sectional study.

OBJECTIVES: We aimed to study general practitioners' (GPs') perceptions of vaccines that have been a subject of controversy in France. METHODS: A cross-sectional survey in 2014 asked a representative national sample of GPs, randomly selected from the exhaustive database of health professionals in France, about their perceptions of the likelihood of serious adverse events potentially associated with six different vaccines: for two of them the association was based on some scientific evidence, whereas for the other four this is not the case. We performed a cluster analysis to construct a typology of GPs' perceptions about the likelihood of these potential six associations. Factors associated with certain clusters of interest were identified using logistic regression models. RESULTS: Overall, 1582 GPs participated in the questionnaire survey (1582/1712 GPs who agreed to participate, 92%). Cluster analysis identified four groups of GPs according to their susceptibility to vaccine controversies: 1) limited susceptibility to controversies (52%); 2) overall unsure, but rejected the association between hepatitis B vaccine and multiple sclerosis (32%); 3) highly susceptible to controversies (11%); and 4) unsure (5%). We found that GPs who occasionally practised alternative medicine (OR 2.71, 95% CI 1.65-4.45), and those who considered information provided by mass media as reliable (OR 2.04, 95% CI 1.65-3.99) were more susceptible to controversies. CONCLUSIONS: GPs had different profiles of susceptibility to vaccination controversies, and most of their perceptions of these controversies were not based on scientific evidence.