Effectiveness of a nurse-led one-to-one education programme in addition to standard care in children with atopic dermatitis: a multicentre randomized control trial.

BACKGROUND: Therapeutic patient education (TPE) is recommended for children with atopic dermatitis (AD), but no consensus has been reached on the optimal tailoring of delivery. While repeated multidisciplinary group education sessions have shown effectiveness, the benefits of one-on-one educational interventions led by nurses for children with AD have not yet been assessed. OBJECTIVES: To assess the benefits of additional, well-structured, 1-h nurse-led individual TPE interventions in children with AD and their families compared with standard care alone. METHODS: Children with moderate-to-severe AD and their parents were randomized to receive a 1-h nurse-led education session in addition to standard care vs. standard care alone. The primary outcome was the area under the curve (AUC) of the SCORing of Atopic Dermatitis index (SCORAD) from baseline to week 24 (lower AUC values represent better long-term control of the disease). RESULTS: In our study, 176 patients were randomized across 11 centres, and 153 were included in the full analysis set. The mean (SD) age was 4.47 (4.57) years. By week 24, there were no significant differences in the AUCs of the SCORAD between the two groups (P = 0.3). Secondary outcomes including patient-reported severity and quality of life [AUCs of the patient-oriented SCORAD (PO-SCORAD) and Infants' Dermatitis Quality of Life Index (IDLQI), Children's Dermatitis Quality of Life Index (CDLQI) and Family Dermatitis Quality of Life Index (FDLQI)] were not significantly different between the two groups. The only significant change observed in the intervention group, when compared with the one receiving standard care, was a decrease in topical steroid phobia, as assessed by the topical corticosteroid phobia (TOPICOP) score. Prespecified subgroup analyses showed that disease severity in the intervention group was significantly lower throughout the study, compared with the standard-care group when participants had moderate AD at baseline (n = 47); while participants with severe AD at baseline (n = 106) did not show benefit from the intervention. Participants showed no additional benefit from the intervention regardless of age group. CONCLUSIONS: This study did not show any additional effectiveness, in long-term severity control, of a 1-h nurse-led TPE intervention in children with AD treated with standard care, compared with those treated with standard care alone. However, it should be noted that the intervention reduced the fear of using topical steroids and may be beneficial for patients in the subgroup with moderate AD.

Iron and Vitamin B12 Deficiency in Patients with Autoimmune Gastritis and Helicobacter pylori Gastritis: Results from a Prospective Multicenter Study.

INTRODUCTION: Iron and vitamin B12 deficiencies are common in patients with atrophic gastritis, but there are limited data on the prevalence of these deficiencies in different types of atrophic gastritis. METHODS: This multicenter, prospective study assessed micronutrient concentrations in histologically confirmed autoimmune gastritis (AIG, n = 45), Helicobacter pylori-related non-autoimmune gastritis (NAIG, n = 109), and control patients (n = 201). A multivariate analysis was performed to determine factors influencing those deficiencies. RESULTS: The median vitamin B12 concentration was significantly lower in AIG (367.5 pg/mL, Q1, Q3: 235.5, 524.5) than in NAIG (445.0 pg/mL, Q1, Q3: 355.0, 565.0, p = 0.001) and control patients (391.0 pg/mL, Q1, Q3: 323.5, 488.7, p = 0.001). Vitamin B12 deficiency was found in 13.3%, 1.5%, and 2.8% of AIG, NAIG, and control patients, respectively. Similarly, the median ferritin concentration was significantly lower in AIG (39.5 ng/mL, Q1, Q3: 15.4, 98.3 ng/mL) than in NAIG (80.5 ng/mL, Q1, Q3: 43.6, 133.9, p = 0.04) and control patients (66.5 ng/mL, Q1, Q3: 33.4, 119.8, p = 0.007). Iron deficiency and iron deficiency adjusted to CRP were present in 28.9% and 33.3% of AIG, 12.8% and 16.5% of NAIG, and 12.9% and 18.4% of controls, respectively. Multivariate analysis demonstrated that AIG patients had a higher risk of developing vitamin B12 deficiency (OR: 11.52 [2.85-57.64, p = 0.001]) and iron deficiency (OR: 2.92 [1.32-6.30, p = 0.007]) compared to control patients. Factors like age, sex, and H. pylori status did not affect the occurrence of vitamin B12 or iron deficiency. CONCLUSION: Iron and vitamin B12 deficiencies are more commonly observed in patients with AIG than in those with NAIG or control patients. Therefore, it is essential to screen for both iron and vitamin B12 deficiencies in AIG patients and include the treatment of micronutrient deficiencies in the management of atrophic gastritis patients.

Implementation of French Recommendations for the Prevention and the Treatment of Hospital-acquired Pneumonia: A Cluster-randomized Trial.

BACKGROUND: We determined whether an audit on the adherence to guidelines for hospital-acquired pneumonia (HAP) can improve the outcomes of patients in intensive care units (ICUs). METHODS: This study was conducted at 35 ICUs in 30 hospitals. We included consecutive, adult patients hospitalized in ICUs for 3 days or more. After a 3-month baseline period followed by the dissemination of recommendations, an audit on the compliance to recommendations (audit period) was followed by a 3-month cluster-randomized trial. We randomly assigned ICUs to either receive audit and feedback (intervention group) or participate in a national registry (control group). The primary outcome was the duration of ICU stay. RESULTS: Among 1856 patients enrolled, 602, 669, and 585 were recruited in the baseline, audit, and intervention periods, respectively. The composite measures of compliance were 47% (interquartile range [IQR], 38-56%) in the intervention group and 42% (IQR, 25-53%) in the control group (P = .001). As compared to the baseline period, the ICU lengths of stay were reduced by 3.2 days in the intervention period (P = .07) and by 2.8 days in the control period (P = .02). The durations of ICU stay were 7 days (IQR, 5-14 days) in the control group and 9 days (IQR, 5-20 days) in the intervention group (P = .10). After adjustment for unbalanced baseline characteristics, the hazard ratio for being discharged alive from the ICU in the control group was 1.17 (95% confidence interval, .69-2.01; P = .10). CONCLUSIONS: The publication of French guidelines for HAP was associated with a reduction of the ICU length of stay. However, the realization of an audit to improve their application did not further improve outcomes. CLINICAL TRIALS REGISTRATION: NCT03348579.

Pharmacokinetics and Safety of XAV-19, a Swine Glyco-humanized Polyclonal Anti-SARS-CoV-2 Antibody, for COVID-19-Related Moderate Pneumonia: a Randomized, Double-Blind, Placebo-Controlled, Phase IIa Study.

We assessed the pharmacokinetics and safety of XAV-19, a swine glyco-humanized polyclonal antibody against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), in coronavirus disease 2019 (COVID-19)-related moderate pneumonia. The objective was to evaluate the optimal dose and safety of XAV-19 during this first administration to patients with COVID-19-related moderate pneumonia. In this phase IIa trial, adults with COVID-19-related moderate pneumonia with a duration of ≤10 days were randomized to receive an infusion of XAV-19 at 0.5 mg/kg of body weight at day 1 and day 5 (group 1), 2 mg/kg at day 1 and day 5 (group 2), or 2 mg/kg at day 1 (group 3) or placebo. Eighteen patients (n = 7 for group 1, n = 1 for group 2, n = 5 for group 3, and n = 5 for placebo) were enrolled. Baseline characteristics were similar across groups; median XAV-19 serum concentrations (ranges) at the time of the maximum serum concentration of the drug (Cmax) and at day 8 were 9.1 (5.2 to 18.1) and 6.4 (2.8 to 11.9) µg/ml, 71.5 and 47.2 µg/ml, and 50.4 (29.1 to 55.0) and 20.3 (12.0 to 22.7) µg/ml for groups 1, 2, and 3, respectively (P = 0.012). The median terminal half-life (range) was estimated at 11.4 (5.5 to 13.9) days for 2 mg/kg of XAV-19 at day 1. Serum XAV-19 concentrations were above the target concentration of 10 µg/ml (2-fold the in vitro 100% inhibitory concentration [IC100]) from the end of perfusion to more than 8 days for XAV-19 at 2 mg/kg at day 1. No hypersensitivity or infusion-related reactions were reported during treatment, and there were no discontinuations for adverse events and no serious adverse events related to the study drug. A single intravenous dose of 2 mg/kg of XAV-19 demonstrated high serum concentrations, predictive of potent durable neutralizing activity with good tolerability. (This study has been registered at ClinicalTrials.gov under identifier NCT04453384.).

Modeling the risk of fluoroquinolone resistance in non-severe community-onset pyelonephritis.

Estimating whether the individual probability of being infected by a fluoroquinolone resistant isolate is higher than 10% may help to choose the empirical treatment of pyelonephritis. We aimed to model the risk of fluoroquinolone resistance in women with community-onset pyelonephritis. Women with non-severe community-onset pyelonephritis were prospectively recruited in 4 French emergency departments of 2 districts. Adjusted odds ratios (aOR) and 95% confidence intervals were estimated through multivariate logistic regression. Among 190 patients, 19 (10%) were infected by a fluoroquinolone resistant isolate. Fluoroquinolone resistance was more frequent in district #2 (17%) than in district #1 (3%). Independent risk factors for fluoroquinolone resistance were district (adjusted OR, 7.0 (2.2-31.9)), and in the 6 previous months, urinary tract infection (UTI, aOR, 3.9 (1.3-11.5)) and vesical catheterization (aOR, 4.7 (0.5-33.3)). A specific model was derived to identify district #2 patients with a low (10% or lower) probability of being infected by a fluoroquinolone resistant isolate. Independent risk factors were residency in long-term care facility (aOR, 3.3 (0.7-13.5)), and in the 6 previous months, UTI (adjusted OR, 3.1 (0.9-10.7)) and home nursing care (aOR, 3.4 (0.6-17.0)). For 63 (67%) patients, the predicted probability of fluoroquinolone resistance was 0.10; among these patients, 6 (10%) actually had a fluoroquinolone resistant isolate. Locally derived predictive models may be used to identify patients with a low probability of fluoroquinolone resistance and guide the empirical antimicrobial therapy of non-severe community-onset pyelonephritis.

Trends and prediction of antimicrobial susceptibility in urinary bacteria isolated in European emergency departments: the EuroUTI 2010-2016 Study.

OBJECTIVES: To assess recent trends in susceptibility to antibiotics among urinary isolates isolated in European emergency departments (EDs) and to identify isolates with a high (90% or more) predicted probability of susceptibility to fluoroquinolones or third-generation cephalosporins (3GCs). METHODS: In this cross-sectional study, we included urine cultures obtained from adult patients between 2010 and 2016 in 24 European EDs. Temporal trends were assessed using time-series analysis and multivariate logistic models. Multivariate logistic models were also used to predict susceptibility to fluoroquinolones or 3GCs from patient age and sex, year, month and ED. RESULTS: We included 88242 isolates. Time-series analysis found a significant increase in susceptibility to fluoroquinolones and no significant trend for susceptibility to 3GCs. Adjusting for patient age and sex, ED and organism, multivariate models showed that susceptibility to 3GCs decreased from 2014 to 2016, while susceptibility to fluoroquinolones increased in 2015 and 2016. Among isolates from 2016, multivariate models predicted high probability of susceptibility to fluoroquinolones in 11% of isolates (positive predictive value 91%) and a high probability of susceptibility to 3GCs in 35% of isolates (positive predictive value 94%). CONCLUSIONS: Susceptibility of ED urinary isolates to fluoroquinolones increased from 2014, while susceptibility to 3GCs decreased from 2015. Predictive models identified isolates with a high probability of susceptibility to fluoroquinolones or 3GCs. The ability of such models to guide the empirical treatment of pyelonephritis in the ED remains to be determined.

Estimation of exposure-attributable fractions from time series: A simulation study.

Burden analysis in public health often involves the estimation of exposure-attributable fractions from observed time series. When the entire population is exposed, the association between the exposure and outcome must be carefully modelled before the attributable fractions can be estimated. This article derives asymptotic convergences for the estimation of attributable fractions for commonly used time series models (ARMAX, Poisson, negative binomial, and Serfling), using for the most part the delta method. For the Poisson regression, the estimation of the attributable fraction is achieved by a Monte Carlo algorithm, taking into account both an estimation and a prediction error. A simulation study compares these estimations in the case of an epidemic exposure and highlights the importance of thorough analysis of the data: When the outcome is generated under an additive model, the additive models are satisfactory, and the multiplicative models are poor, and vice versa. However, the Serfling model performs poorly in all cases. Of note, a misspecification in the form or delay of the association between the exposure and the outcome leads to mediocre estimation of the attributable fraction. An application to the fraction of French outpatient antibiotic use attributable to influenza between 2003 and 2010 illustrates the asymptotic convergences. This study suggests that the Serfling model should be avoided when estimating attributable fractions while the model of choice should be selected after careful investigation of the association between the exposure and outcome.

Outpatient antibiotic use in France between 2000 and 2010: after the nationwide campaign, it is time to focus on the elderly.

Antibiotic overconsumption is the main force driving the emergence of multidrug-resistant bacterial strains. To promote better antibiotic use in France, a nationwide campaign has been run every year from October to March since 2002. In 2007, it was shown that winter outpatient antibiotic consumption had decreased by 26.5% compared to the 2000-2002 baseline period. Here, we quantified outpatient antibiotic use between 2000 and 2010 as a follow-up analysis of the nationwide campaign. Reimbursed outpatient antibiotic prescriptions were extracted from computerized French National Health Insurance databases. Entire series and age group and antibiotic class analyses were computed. Time series analyses used autoregressive moving-average models with exogenous variables and intervention functions. Two periods were considered: October to March "campaign" periods and April to September "warm" periods. Compared to the precampaign (2000-2002) baseline period, the numbers of weekly antibiotic prescriptions per 1,000 inhabitants during campaign periods decreased until winter 2006 to 2007 (-30% [95% confidence interval {CI}, -36.3 to -23.8%]; P < 0.001) and then stabilized except for individuals >60 years of age, for whom prescriptions reached the precampaign level. During the warm periods from April to September, no significant differences were estimated compared to the baseline level for the entire series, but seniors had an increasing trend that became significant as of 2005, reaching +21% (95% CI, +12.9 to +29.6%) in 2009 (P < 0.0001). These results highlight the need for a better understanding of antibiotic use by the elderly, requiring research with targeted and tailored public health actions for this population.

Implementation of an evidence-based extubation readiness bundle in 499 brain-injured patients. a before-after evaluation of a quality improvement project.

RATIONALE: Mechanical ventilation is associated with morbidity in patients with brain injury. OBJECTIVES: This study aims to assess the effectiveness of an extubation readiness bundle to decrease ventilator time in patients with brain injury. METHODS: Before-after design in two intensive care units (ICUs) in one university hospital. Brain-injured patients ventilated more than 24 hours were evaluated during two phases (a 3-yr control phase followed by a 22-mo intervention phase). Bundle components were protective ventilation, early enteral nutrition, standardization of antibiotherapy for hospital-acquired pneumonia, and systematic approach to extubation. The primary endpoint was the duration of mechanical ventilation. MEASUREMENTS AND MAIN RESULTS: A total of 299 and 200 patients, respectively, were analyzed in the control and the intervention phases of this before-after study. The intervention phase was associated with lower tidal volume (P < 0.01), higher positive end-expiratory pressure (P < 0.01), and higher enteral intake in the first 7 days (P = 0.01). The duration of mechanical ventilation was 14.9 ± 11.7 days in the control phase and 12.6 ± 10.3 days in the intervention phase (P = 0.02). The hazard ratio for extubation was 1.28 (95% confidence interval [CI], 1.04-1.57; P = 0.02) in the intervention phase. Adjusted hazard ratio was 1.40 (95% CI, 1.12-1.76; P < 0.01) in multivariate analysis and 1.34 (95% CI, 1.03-1.74; P = 0.02) in propensity score-adjusted analysis. ICU-free days at Day 90 increased from 50 ± 33 in the control phase to 57 ± 29 in the intervention phase (P < 0.01). Mortality at Day 90 was 28.4% in the control phase and 23.5% in the intervention phase (P = 0.22). CONCLUSIONS: The implementation of an evidence-based extubation readiness bundle was associated with a reduction in the duration of ventilation in patients with brain injury.

Confocal laser endomicroscopy as predictive biomarker of clinical and endoscopic efficacy of vedolizumab in ulcerative colitis: The DETECT study.

AIMS: In patients with ulcerative colitis (UC), no biomarker is available to help the physician to choose the most suitable biotherapy. The primary objective of this pilot study was to assess the feasibility of identification of α4ß7- and TNF-expressing cells, to predict the response to vedolizumab using confocal laser endoscopy (CLE). METHODS: Patients with moderate-to-severe UC, naïve of biotherapy, received vedolizumab. Clinical evaluation was performed at each infusion. Endoscopic evaluation was performed before inclusion and at week 22. Fresh colonic biopsies were stained using FITC-labelled vedolizumab and Alexa fluor-labelled adalimumab and ex vivo dual-band CLE images were acquired. Blood samples were collected to measure trough concentrations of vedolizumab and to determine absolute counts of T and B cells subpopulations, NK cells and monocytes. RESULTS: Nineteen patients were enrolled in the study and received at least one dose of vedolizumab. Clinical remission and endoscopic improvement were observed in 58% of whom 5 patients (45%) had an endoscopic subscore of 0. In terms of clinical response and remission, endoscopic improvement and histologic response, FITC-conjugated vedolizumab staining tended to be higher in responder patients compared to non-responders at week 22. A threshold value of 6 positive FITC-vedolizumab staining areas detected by CLE seemed informative to discriminate the responders and non-responders. The results were similar in terms of clinical remission and endoscopic improvement with a sensitivity of 78% and a specificity of 85% (p = 0.05). Trough concentrations and blood immune cells were not associated with responses to vedolizumab. CONCLUSION: This pilot study demonstrate that dual-band CLE is feasible to detect α4ß7- and TNF-expressing cells. Positive α4ß7 staining seems to be associated with clinical and endoscopic remission in UC patients treated by anti-α4ß7-integrin, subject to validation by larger-scale studies. Clinical-trial.gov: NCT02878083.

Inhaled therapies, azithromycin and Mycobacterium abscessus in cystic fibrosis patients.

Cystic fibrosis (CF) patients are at particularly high risk of developing lung disease caused by Mycobacterium abscessus complex (MABSC). Over the last 10 years, changes in CF treatment, with increasing use of inhaled therapies and low-dose azithromycin, have been accompanied by an increase in the prevalence of MABSC infections in CF patients. There is therefore some concern about the role of new CF treatments in the emergence of MABSC infections. We addressed this issue by means of a case-control study including 30 MABSC-positive cases and 60 nontuberculous mycobacteria-negative CF controls matched for age, sex and centre. We also compared practices at the CF centres with the highest prevalence of MABSC with those at the other centres. No positive association was found between MABSC lung disease and the use of inhaled therapies or low-dose azithromycin in the 4 years preceding MABSC isolation. These treatments were not significantly more frequently used at the CF centres with the highest MABSC prevalence rates. In conclusion, there is no evidence for a link between M. abscessus complex lung disease and inhaled therapies or low-dose azithromycin in patients with CF.

Long-term benefits of a therapeutic make-up consultation for patients with various facial dermatoses.

BACKGROUND: Therapeutic make-up has previously been proven to be efficacious in improving the quality of life of patients with facial dermatoses, but its efficacy has only been assessed in the short term (less than one month). OBJECTIVES: This study aimed to determine whether the effect of therapeutic make-up on patients' quality of life persists in the longer term, i.e., after one year. MATERIALS & METHODS: This study included 53 patients who benefited from a therapeutic make-up consultation in the context of various facial dermatoses (pigmentation disorders, scars, acne, rosacea, eczema, adverse events of chemotherapy, etc.). Patients were asked to complete a quality-of-life questionnaire to obtain the Skindex score at baseline, and one month (M1) and one year (M12) after the first consultation. The difference in scores between baseline and M12 was calculated and Student's t-test was used to assess the significance of the values. RESULTS: Our results showed a significant difference (p<0.001) with an improvement in quality-of-life score by more than 10% between baseline and M12, for all the dimensions of the score (Emotion, Symptoms and Functioning). Based on the subgroup analysis, this score particularly improved for patients suffering with acne or rosacea (p=0.009) and scars (p=0.43), as well as for younger patients (<30 years old) (p=0.009). CONCLUSION: This is the first study to demonstrate a persistent long-term effect of therapeutic make-up on the quality of life of patients with facial dermatoses.

Atrophic Gastritis and Autoimmunity: Results from a Prospective, Multicenter Study.

Despite a global decrease, gastric cancer (GC) incidence appears to be increasing recently in young, particularly female, patients. The causal mechanism for this "new" type of GC is unknown, but a role for autoimmunity is suggested. A cascade of gastric precancerous lesions, beginning with chronic atrophic gastritis (CAG), precedes GC. To test the possible existence of autoimmunity in patients with CAG, we aimed to analyze the prevalence of several autoantibodies in patients with CAG as compared to control patients. Sera of 355 patients included in our previous prospective, multicenter study were tested for 19 autoantibodies (anti-nuclear antibodies, ANA, anti-parietal cell antibody, APCA, anti-intrinsic factor antibody, AIFA, and 16 myositis-associated antibodies). The results were compared between CAG patients (n = 154), including autoimmune gastritis patients (AIG, n = 45), non-autoimmune gastritis patients (NAIG, n = 109), and control patients (n = 201). ANA positivity was significantly higher in AIG than in NAIG or control patients (46.7%, 29%, and 27%, respectively, p = 0.04). Female gender was positively associated with ANA positivity (OR 0.51 (0.31-0.81), p = 0.005), while age and H. pylori infection status were not. Myositis-associated antibodies were found in 8.9% of AIG, 5.5% of NAIG, and 4.4% of control patients, without significant differences among the groups (p = 0.8). Higher APCA and AIFA positivity was confirmed in AIG, and was not associated with H. pylori infection, age, or gender in the multivariate analysis. ANA antibodies are significantly more prevalent in AIG than in control patients, but the clinical significance of this finding remains to be established. H. pylori infection does not affect autoantibody seropositivity (ANA, APCA, AIFA). The positivity of myositis-associated antibodies is not increased in patients with CAG as compared to control patients. Overall, our results do not support an overrepresentation of common autoantibodies in patients with CAG.

Serum pepsinogens can help to discriminate between H. pylori-induced and auto-immune atrophic gastritis: Results from a prospective multicenter study.

BACKGROUND: Serum pepsinogen (PG) testing is recommended by the European guidelines for diagnosis of chronic atrophic gastritis (CAG). However, wide variations in diagnostic performances are observed, due to the differences in the extent of gastric atrophy, and possibly in its origin (Helicobacter pylori-, autoimmune (AIG)). AIM: To analyze the diagnostic performances of PGs testing according to these different parameters, using enzyme-linked-immunosorbent serologic assay (ELISA) and chemiluminescent immunoassay (CLEIA). METHODS: Serum samples from patients having undergone gastroscopy with biopsies in five French centers were collected prospectively. Sensitivity (Se), specificity (Sp), and Area Under Curve were analyzed according to the extent and origin of CAG. RESULTS: Overall, 344 patients (156 males [45%]; mean age 58.8 [±14.2] years) were included, among whom 44 had AIG. Diagnostic performances of PG I for the detection of corpus CAG were excellent, with Se and Sp of 92.7% and 99.1% for ELISA and 90.5% and 98.2% for CLEIA, respectively. For AIG, corresponding values were 97.7% and 97.4% for ELISA, and 95.6% and 97.1% for CLEIA. In multivariate analysis, PG levels were associated with the auto-immune origin (p<0.001) but not with the extent of the atrophic gastritis. CONCLUSIONS: Pepsinogens are highly efficient for the diagnosis of corpus-limited CAG and allow to discriminate AIG from H. pylori-induced gastritis.

Effect of Swine Glyco-humanized Polyclonal Neutralizing Antibody on Survival and Respiratory Failure in Patients Hospitalized With Severe COVID-19: A Randomized, Placebo-Controlled Trial.

Background: We evaluated the safety and efficacy of XAV-19, an antispike glyco-humanized swine polyclonal neutralizing antibody in patients hospitalized with severe coronavirus disease 2019 (COVID-19). Methods: This phase 2b clinical trial enrolled adult patients from 34 hospitals in France. Eligible patients had a confirmed diagnosis of severe acute respiratory syndrome coronavirus 2 within 14 days of onset of symptoms that required hospitalization for low-flow oxygen therapy (<6 L/min of oxygen). Patients were randomly assigned to receive a single intravenous infusion of 2 mg/kg of XAV-19 or placebo. The primary end point was the occurrence of death or severe respiratory failure between baseline and day 15. Results: Between January 12, 2021, and April 16, 2021, 398 patients were enrolled in the study and randomly assigned to XAV-19 or placebo. The modified intention-to-treat population comprised 388 participants who received full perfusion of XAV-19 (199 patients) or placebo (189 patients). The mean (SD) age was 59.8 (12.4) years, 249 (64.2%) individuals were men, and the median time (interquartile range) from symptom onset to enrollment was 9 (7-10) days. There was no statistically significant decrease in the cumulative incidence of death or severe respiratory failure through day 15 in the XAV-19 group vs the placebo group (53/199 [26.6%] vs 48/189 [25.4%]; adjusted risk difference, 0.6%; 95% CI, -6% to 7%; hazard ratio, 1.03; 95% CI, 0.64-1.66; P = .90). In the safety population, adverse events were reported in 75.4% of 199 patients in the XAV-19 group and in 76.3% of 190 patients in the placebo group through D29. Conclusions: Among patients hospitalized with COVID-19 requiring low-flow oxygen therapy, treatment with a single intravenous dose of XAV-19, compared with placebo, did not show a significant difference in terms of disease progression at day 15.

Extent of the protection afforded by histo-blood group polymorphism against rotavirus gastroenteritis in metropolitan France and French Guiana.

Human rotaviruses attach to histo-blood group antigens glycans and null alleles of the ABO, FUT2 and FUT3 genes seem to confer diminished risk of gastroenteritis. Yet, the true extent of this protection remains poorly quantified. Here, we conducted a prospective study to evaluate the risk of consulting at the hospital in non-vaccinated pediatric patients according to the ABO, FUT2 (secretor) and FUT3 (Lewis) polymorphisms, in Metropolitan France and French Guiana. At both locations, P genotypes were largely dominated by P [8]-3, with P [6] cases exclusively found in French Guiana. The FUT2 null (nonsecretor) and FUT3 null (Lewis negative) phenotypes conferred near full protection against severe gastroenteritis due to P [8]-3 strains (OR 0.03, 95% CI [0.00-0.21] and 0.1, 95% CI [0.01-0.43], respectively in Metropolitan France; OR 0.08, 95% CI [0.01-0.52] and 0.14, 95%CI [0.01-0.99], respectively in French Guiana). Blood group O also appeared protective in Metropolitan France (OR 0.38, 95% CI [0.23-0.62]), but not in French Guiana. The discrepancy between the two locations was explained by a recruitment at the hospital of less severe cases in French Guiana than in Metropolitan France. Considering the frequencies of the null ABO, Secretor and Lewis phenotypes, the data indicate that in a Western European population, 34% (95% CI [29%; 39%]) of infants are genetically protected against rotavirus gastroenteritis of sufficient severity to lead to hospital visit.

Difference in Pap test uptake between women who have sex with women and other women in France: A comparative survey of 2032 women.

The elimination of cervical cancer has been a priority of the World Health Organization since 2018. The number of these cancers induced by the human papillomavirus (HPV) could be drastically reduced through vaccination and regularly screening by Pap tests. Guidelines for cervical cancer screening apply to all women, including those who have sexual relations with women (WSW), as HPV can be transmitted during sex between two women. As far as we know, our study is the first that compare the Pap test rate between WSW and other women in France. We developed an 18-item questionnaire available on the internet for 15 days and finally analyzed the responses of 2032 women. Based on their responses about their self-definition of their sexual orientation and their sexual behavior, we classified them into three groups of women: exclusive WSW, mixed WSW, and non-WSW. For each question, we tested the statistical differences in responses between these three groups. Our study shows in a large sample representative of the French population that exclusive WSW undergo Pap tests significantly less often than either mixed WSW or non-WSW. Among the exclusive WSW, 28.9 % had never had a Pap test, compared with 9 % of the mixed WSW and 3.1 % of non-WSW (p < 0,001). The responses to our questionnaire contribute to an understanding of this disparity and thus help to envision solutions for better care of all women, regardless of their sexual orientation; this point is crucial for prevention of cervical cancer.

Inter and intra-observer agreement of arterial wall contrast-enhanced ultrasonography in giant cell arteritis.

Objective: The aim of this study was to analyze inter- and intra-observer agreement for contrast-enhanced ultrasonography (CEUS) for monitoring disease activity in Giant Cell Arteritis (GCA) in the wall of axillary arteries, and common carotid arteries. Methods: Giant cell arteritis patients have CEUS of axillary arteries and common carotid. These images were rated by seven vascular medicine physicians from four hospitals who were experienced in duplex ultrasonography of GCA patients. Two weeks later, observers again rated the same images. GCA patients were recruited in from December 2019 to February 2021. An analysis of the contrast of the ultrasound images with a gradation in three classes (grade 0, 1, and 2) was performed. Grade 0 corresponds to no contrast, grade 1 to moderate wall contrast and grade 2 to intense contrast. A new analysis in 2 classes: positive or negative wall contrast; was then performed on new series of images. Results: Sixty arterial segments were evaluated in 30 patients. For the three-class scale, intra-rater agreement was substantial: κ 0.70; inter-rater agreement was fair: κ from 0.22 to 0.27. Thirty-four videos had a wall thickness of less than 2 mm and 26 videos had a wall thickness greater than 2 mm. For walls with a thickness lower than 2 mm: intra-rater agreement was substantial: κ 0.69; inter-rater agreement was fair: κ 0.35. For walls with a thickness of 2 mm or more: intra-rater agreement was substantial: κ 0.53; inter-rater agreement was fair: κ 0.25. For analysis of parietal contrast uptake in two classes: inter-rater agreement was fair to moderate: κ from 0.35 to 0.41; and for walls with a thickness of 2 mm or more: inter-rater agreement was fair to substantial κ from 0.22 to 0.63. Conclusion: The visual analysis of contrast uptake in the wall of the axillary and common carotid arteries showed good intra-rater agreement in GCA patients. The inter-rater agreement was low, especially when contrast was analyzed in three classes. The inter-rater agreement for the analysis in two classes was also low. The inter-rater agreement was higher in two-class analysis for walls of 2 mm thickness or more.

Potential Impact of Rapid Multiplex PCR on Antimicrobial Therapy Guidance for Ventilated Hospital-Acquired Pneumonia in Critically Ill Patients, A Prospective Observational Clinical and Economic Study.

Objectives: To investigate the potential impact of the syndromic multiplex FilmArray® Pneumonia plus Panel (FAPP) on the antimicrobial treatment guidance of patients with ventilated hospital-acquired pneumonia (VHAP). Methods: Respiratory fluids from 100 adult patients with VHAP, receiving invasive mechanical ventilation in three intensive care units from one French university hospital, were tested prospectively using FAPP. Conventional cultures were performed in parallel as routine practice. Clinicians were left blinded to the FAPP results. Antimicrobial therapies based on FAPP results were simulated by independent blinded experts according to a predefined algorithm and compared to 1) those prescribed in practice according to local guidelines (real-life), and 2) those that complied with the international ERS/ESICM/ESCMID/ALAT recommendations. The primary endpoint was the number of days of broad-spectrum antimicrobial therapy. Secondary endpoints were the rates of microbiological treatment failure and cost-effectiveness ratio. Results: The predicted median duration of broad-spectrum antibiotics was 0 [0-1.25] day in the FAPP-based simulation, versus 2 [0-6] days in real-life (p<0.0001) and 2 [2-3.25] days in the recommendations-based simulation (p<0.0001). Treatment failure was predicted in 3% of cases with FAPP results versus observed in 11% in real-life (p=0.08) and 6% with recommendations-based simulation (p=0.37). The incremental cost-effectiveness ratio was 1 121 € [-7021; 6794] to avoid one day of non-optimized antimicrobial therapy. Conclusions: Our results suggest that using FAPP in patients with VHAP has the potential to reduce the use of broad-spectrum antimicrobial therapy without increasing the risk of microbial treatment failure.

Feasibility of Combining Transcranial Direct Current Stimulation and Active Fully Embodied Virtual Reality for Visual Height Intolerance: A Double-Blind Randomized Controlled Study.

BACKGROUND: Transcranial Direct Current Stimulation (tDCS) and Virtual Reality Exposure Therapy (VRET) are individually increasingly used in psychiatric research. OBJECTIVE/HYPOTHESIS: Our study aimed to investigate the feasibility of combining tDCS and wireless 360° full immersive active and embodied VRET to reduce height-induced anxiety. METHODS: We carried out a pilot randomized, double-blind, controlled study associating VRET (two 20 min sessions with a 48 h interval, during which, participants had to cross a plank at rising heights in a building in construction) with online tDCS (targeting the ventromedial prefrontal cortex) in 28 participants. The primary outcomes were the sense of presence level and the tolerability. The secondary outcomes were the anxiety level (Subjective Unit of Discomfort) and the salivary cortisol concentration. RESULTS: We confirmed the feasibility of the association between tDCS and fully embodied VRET associated with a good sense of presence without noticeable adverse effects. In both groups, a significant reduction in the fear of height was observed after two sessions, with only a small effect size of add-on tDCS (0.1) according to the SUD. The variations of cortisol concentration differed in the tDCS and sham groups. CONCLUSION: Our study confirmed the feasibility of the association between wireless online tDCS and active, fully embodied VRET. The optimal tDCS paradigm remains to be determined in this context to increase effect size and then adequately power future clinical studies assessing synergies between both techniques.