Indirect H2O2 synthesis without H2.

Industrial hydrogen peroxide (H2O2) is synthesized using carbon-intensive H2 gas production and purification, anthraquinone hydrogenation, and anthrahydroquinone oxidation. Electrochemical hydrogenation (ECH) of anthraquinones offers a carbon-neutral alternative for generating H2O2 using renewable electricity and water instead of H2 gas. However, the H2O2 formation rates associated with ECH are too low for commercialization. We report here that a membrane reactor enabled us to electrochemically hydrogenate anthraquinone (0.25 molar) with a current efficiency of 70% at current densities of 100 milliamperes per square centimeter. We also demonstrate continuous H2O2 synthesis from the hydrogenated anthraquinones over the course of 48 h. This study presents a fast rate of electrochemically-driven anthraquinone hydrogenation (1.32 ± 0.14 millimoles per hour normalized per centimeter squared of geometric surface of electrode), and provides a pathway toward carbon-neutral H2O2 synthesis.

Rationale and design of the direct oral anticoagulants for prevention of left ventricular thrombus after anterior acute myocardial infarction (APERITIF) trial.

BACKGROUND: Anterior acute myocardial infarction (AMI) is associated with an increased risk of left ventricular (LV) thrombus formation. We hypothesized that adding low-dose oral rivaroxaban to the usual antiplatelet regimen would reduce the risk of LV thrombus in patients with large AMI. STUDY DESIGN: APERITIF is an investigator-initiated, multicenter randomized open-label, blinded end-point (PROBE) trial, nested in the ongoing "FRENCHIE" registry, a French multicenter prospective observational study, in which all consecutive patients admitted within 48 hours of symptom onset in a cardiac Intensive Care Unit (ICU) for AMI are included (NCT04050956). Among them, patients with anterior ST-elevation-myocardial infarction (STEMI) or very high-risk non- ST-elevation-myocardial infarction (NSTEMI) patients with involvement of the left anterior descending artery are randomized into 2 groups: Dual Antiplatelet Therapy (DAPT) alone or DAPT plus rivaroxaban 2.5mg twice daily for 4 weeks, started as soon as possible after completion of the initial percutaneous coronary intervention/angiography procedure. The primary endpoint is the presence of LV thrombus at 1 month, as detected by contrast enhanced CMR (CE-CMR). Secondary endpoints include LV thrombus dimension (greatest diameter), the rate of major bleedings and major cardiovascular events at 1 month. Based on estimated event rates, a sample size of 560 patients is needed to show superiority of DAPT plus rivaroxaban therapy versus DAPT alone, with 80% power. CONCLUSION: The APERITIF trial will determine whether, in patients with large AMIs, the use of rivaroxaban 2.5mg twice daily in addition to DAPT reduces LV thrombus formation, compared with DAPT alone. CLINICALTRIALS: gov Identifier: NCT05077683.

Association between combination antibiotic therapy as opposed as monotherapy and outcomes of ICU patients with Pseudomonas aeruginosa ventilator-associated pneumonia: an ancillary study of the iDIAPASON trial.

BACKGROUND: The optimal treatment duration and the nature of regimen of antibiotics (monotherapy or combination therapy) for Pseudomonas aeruginosa ventilator­associated pneumonia (PA-VAP) remain debated. The aim of this study was to evaluate whether a combination antibiotic therapy is superior to a monotherapy in patients with PA-VAP in terms of reduction in recurrence and death, based on the 186 patients included in the iDIAPASON trial, a multicenter, randomized controlled trial comparing 8 versus 15 days of antibiotic therapy for PA-VAP. METHODS: Patients with PA-VAP randomized in the iDIAPASON trial (short-duration-8 days vs. long-duration-15 days) and who received appropriate antibiotic therapy were eligible in the present study. The main objective is to compare mortality at day 90 according to the antibiotic therapy received by the patient: monotherapy versus combination therapy. The primary outcome was the mortality rate at day 90. The primary outcome was compared between groups using a Chi-square test. Time from appropriate antibiotic therapy to death in ICU or to censure at day 90 was represented using Kaplan-Meier survival curves and compared between groups using a Log-rank test. RESULTS: A total of 169 patients were included in the analysis. The median duration of appropriate antibiotic therapy was 14 days. At day 90, among 37 patients (21.9%) who died, 17 received monotherapy and 20 received a combination therapy (P = 0.180). Monotherapy and combination antibiotic therapy were similar for the recurrence rate of VAP, the number of extra pulmonary infections, or the acquisition of multidrug-resistant (MDR) bacteria during the ICU stay. Patients in combination therapy were exposed to mechanical ventilation for 28 ± 12 days, as compared with 23 ± 11 days for those receiving monotherapy (P = 0.0243). Results remain similar after adjustment for randomization arm of iDIAPASON trial and SOFA score at ICU admission. CONCLUSIONS: Except longer durations of antibiotic therapy and mechanical ventilation, potentially related to increased difficulty in achieving clinical cure, the patients in the combination therapy group had similar outcomes to those in the monotherapy group. TRIAL REGISTRATION: NCT02634411 , Registered 15 December 2015.

Hydrogen Production and Utilization in a Membrane Reactor.

Industrial hydrogenation consumes ~11 Mt of fossil-derived H2 gas yearly. Our group invented a membrane reactor to bypass the need to use H2 gas for hydrogenation chemistry. The membrane reactor sources hydrogen from water and drives reactions using renewable electricity. In this reactor, a thin piece of Pd separates an electrochemical hydrogen production compartment from a chemical hydrogenation compartment. The Pd in the membrane reactor acts as (i) a hydrogen-selective membrane, (ii) a cathode, and (iii) a catalyst for hydrogenation. Herein, we report the use of atmospheric mass spectrometry (atm-MS) and gas chromatography mass spectrometry (GC-MS) to demonstrate that an applied electrochemical bias across a Pd membrane enables efficient hydrogenation without direct H2 input in a membrane reactor. With atm-MS, we measured a hydrogen permeation of 73%, which enabled the hydrogenation of propiophenone to propylbenzene with 100% selectivity, as measured by GC-MS. In contrast to conventional electrochemical hydrogenation, which is limited to low concentrations of starting material dissolved in a protic electrolyte, the physical separation of hydrogen production from utilization in the membrane reactor enables hydrogenation in any solvent or at any concentration. The use of high concentrations and a wide range of solvents is particularly important for reactor scalability and future commercialization.

AI-based chatbot micro-intervention for parents: Meaningful engagement, learning, and efficacy.

Introduction: Mental health issues have been on the rise among children and adolescents, and digital parenting programs have shown promising outcomes. However, there is limited research on the potential efficacy of utilizing chatbots to promote parental skills. This study aimed to understand whether parents learn from a parenting chatbot micro intervention, to assess the overall efficacy of the intervention, and to explore the user characteristics of the participants, including parental busyness, assumptions about parenting, and qualitative engagement with the chatbot. Methods: A sample of 170 parents with at least one child between 2-11 years old were recruited. A randomized control trial was conducted. Participants in the experimental group accessed a 15-min intervention that taught how to utilize positive attention and praise to promote positive behaviors in their children, while the control group remained on a waiting list. Results: Results showed that participants engaged with a brief AI-based chatbot intervention and were able to learn effective praising skills. Although scores moved in the expected direction, there were no significant differences by condition in the praising knowledge reported by parents, perceived changes in disruptive behaviors, or parenting self-efficacy, from pre-intervention to 24-hour follow-up. Discussion: The results provided insight to understand how parents engaged with the chatbot and suggests that, in general, brief, self-guided, digital interventions can promote learning in parents. It is possible that a higher dose of intervention may be needed to obtain a therapeutic change in parents. Further research implications on chatbots for parenting skills are discussed.

Circulating microvesicles correlate with radiation proctitis complication after radiotherapy.

In a large retrospective study, we assessed the putative use of circulating microvesicles (MVs), as innovative biomarkers of radiation toxicity in a cohort of 208 patients with prostate adenocarcinoma overexposed to radiation. The level of platelet (P)-, monocyte (M)- and endothelial (E)-derived MVs were assessed by flow cytometry. Rectal bleeding toxicity scores were collected at the time of blood sampling and during the routine follow-up and were tested for association with MVs using a multivariate logistic regression. MVs dosimetric correlation was investigated using dose volume histograms information available for a subset of 36 patients. The number of PMVs was significantly increased in patients with highest toxicity grades compared to lower grades. Risk prediction analysis revealed that increased numbers of PMVs, and an increased amount of MMVs relative to EMVs, were associated with worst rectal bleeding grade compared to the time of blood sampling. Moreover, a significant correlation was found between PMV and MMV numbers, with the range of doses up to the median exposure (40 Gy) of bladder/rectum and anterior rectal wall, respectively. MVs could be considered as new biomarkers to improve the identification of patients with high toxicity grade and may be instrumental for the prognosis of radiation therapy complications.

Respiratory multiplex PCR and procalcitonin to reduce antibiotic exposure in severe SARS-CoV-2 pneumonia: a multicentre randomized controlled trial.

OBJECTIVES: We aimed at assessing the efficacy and safety on antibiotic exposure of a strategy combining a respiratory multiplex PCR (mPCR) with enlarged panel and daily procalcitonin (PCT) measurements, as compared with a conventional strategy, in adult patients who were critically ill with laboratory-confirmed SARS-CoV-2 pneumonia. METHODS: This multicentre, parallel-group, open-label, randomized controlled trial enrolled patients admitted to 13 intensive care units (ICUs) in France. Patients were assigned (1:1) to the control strategy, in which antibiotic streamlining remained at the discretion of the physicians, or interventional strategy, consisting of using mPCR and daily PCT measurements within the first 7 days of randomization to streamline initial antibiotic therapy, with antibiotic continuation encouraged when PCT was >1 ng/mL and discouraged if < 1 ng/mL or decreased by 80% from baseline. All patients underwent conventional microbiological tests and cultures. The primary end point was antibiotic-free days at day 28. RESULTS: Between April 20th and November 23rd 2020, 194 patients were randomized, of whom 191 were retained in the intention-to-treat analysis. Respiratory bacterial co-infection was detected in 48.4% (45/93) and 21.4% (21/98) in the interventional and control group, respectively. The number of antibiotic-free days was 12.0 (0.0; 25.0) and 14.0 (0.0; 24.0) days, respectively (difference, -2.0, (95% CI, -10.6 to 6.6), p=0.89). Superinfection rates were high (51.6% and 48.5%, respectively). Mortality rates and ICU lengths of stay did not differ between groups. DISCUSSION: In severe SARS-CoV-2 pneumonia, the mPCR/PCT algorithm strategy did not affect 28-day antibiotics exposure nor the major clinical outcomes, as compared with routine practice.

Feasibility of a repositioning schedule on pressure ulcer prevention in a French Intensive Care Unit: A pre and post-intervention pilot study.

AIMS: As a prerequisite of a multicentre study, we conducted a pilot study to assess the feasibility of a daily repositioning schedule in critically ill patients. The schedule was adapted to the patient's clinical condition, and the estimated risk for developing a pressure ulcer using the Braden scale. DESIGN: A single-center pre and post-intervention pilot study in a French Intensive Care Unit of a university teaching hospital. This study followed TREND guidelines. METHODS: During the first period (March to May 2018), pressure ulcer prevention was performed according to usual care. During the second period (June to August 2018), the repositioning schedule was adapted to the estimated risk for developing a pressure ulcer according to the Braden scale. Eligible patients had no pressure ulcer at baseline, were intubated within 24 hours of admission and expected to receive mechanical ventilation for at least 24 hours. The primary outcome was the rate of pressure ulcer development at 28 days of hospitalization or at discharge or death, as compared with usual care. Secondary outcomes included the feasibility and safety of the schedule, as assessed by caregivers' adherence and workload, and the rate of adverse events. RESULTS: In the pre-intervention period 20 participants were included, and 14 patients were included in the post-intervention period. There was no decrease in the pressure ulcers incidence with the intervention (25% vs. 28.6%; P = 1). The number of daily repositioning performed increased from 3.3 [IQR 3.0; 3.9] during the pre-intervention period to 4.3 [IQR 3.8; 5.2] during the post-intervention period (P < 0.05), where it differed from the number scheduled by 0.6 [IQR 0.1; 1.4] per day, indicating satisfactory adherence of caregivers to the protocol. Adverse events rate did not differ between the two periods (55.9% vs. 57.1%; P = 0.90). CONCLUSION: A personalised daily repositioning schedule in critically ill patients is feasible and safe. The efficacy of such a strategy, together with its economic impact, need to be assessed in a multicentre randomized trial.

High levels of HPV16-L1 antibody but not HPV16 DNA load or integration predict oropharyngeal patient outcome: The Papillophar study.

The incidence of oropharyngeal cancers (OPC) is increasing in the world. Among OPC, those induced by human papillomaviruses have a better prognosis than non-HPV-associated OPC. The objective of this study was to highlight the relevance of HPV16 load, HPV16 DNA integration and HPV16-L1 serology on progression-free survival and overall survival of OPC patients. The PAPILLOPHAR cohort consists of 362 patients with oropharyngeal squamous cell carcinomas prospectively followed up for 5 years after treatment. Tumor biopsies and sera were collected at inclusion to investigate tumor HPV DNA/RNA characteristics and HPV16 L1 serology, respectively. Twenty-seven percent of tumor biopsies were HPV DNA- and RNA-positive and HPV16 represented 93% of HPV-positive cases. Among them, neither HPV16 viral load nor HPV16 DNA integration was associated with overall survival (OS) or progression-free survival (PFS). In contrast, high anti-HPV16 L1 antibody titers were significantly associated with a better OS and PFS. This study reveals that HPV16 load and integration are not relevant prognosis biomarkers in OPC patients.Clinical Relevance: High levels of HPV16 L1 antibodies may be useful to predict OPC patient outcome following treatment.ClinicalTrials.gov Identifier: NCT00918710, May 2017.

Economic evaluation of restrictive vs. liberal transfusion strategy following acute myocardial infarction (REALITY): trial-based cost-effectiveness and cost-utility analyses.

AIMS: To estimate the cost-effectiveness and cost-utility ratios of a restrictive vs. liberal transfusion strategy in acute myocardial infarction (AMI) patients with anaemia. METHODS AND RESULTS: Patients (n = 666) with AMI and haemoglobin between 7-8 and 10 g/dL recruited in 35 hospitals in France and Spain were randomly assigned to a restrictive (n = 342) or a liberal (n = 324) transfusion strategy with 1-year prospective collection of resource utilization and quality of life using the EQ5D3L questionnaire. The economic evaluation was based on 648 patients from the per-protocol population. The outcomes were 30-day and 1-year cost-effectiveness, with major adverse cardiovascular events (MACEs) averted as the effectiveness outcome. and a 1-year cost-utility ratio.The 30-day incremental cost-effectiveness ratio was €33 065 saved per additional MACE averted with the restrictive vs. liberal strategy, with an 84% probability for the restrictive strategy to be cost-saving and MACE-reducing (i.e. dominant). At 1 year, the point estimate of the cost-utility ratio was €191 500 saved per quality-adjusted life year gained; however, the cumulated MACE was outside the pre-specified non-inferiority margin, resulting in a decremental cost-effectiveness ratio with a point estimate of €72 000 saved per additional MACE with the restrictive strategy. CONCLUSION: In patients with AMI and anaemia, the restrictive transfusion strategy was dominant (cost-saving and outcome-improving) at 30 days. At 1 year, the restrictive strategy remained cost-saving, but clinical non-inferiority on MACE was no longer maintained. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02648113. ONE SENTENCE SUMMARY: The use of a restrictive transfusion strategy in patients with acute myocardial infarction is associated with lower healthcare costs, but more evidence is needed to ascertain its long-term clinical impact.

Efficacy and safety of methylprednisolone pulse followed by oral prednisone vs. oral prednisone alone in sarcoidosis tubulointerstitial nephritis: a randomized, open-label, controlled clinical trial.

BACKGROUND: We determine the benefit of pulsed methylprednisolone for improving kidney function in patients with sarcoidosis tubulointerstitial nephritis. METHODS: We conducted a multicenter, prospective, randomized, open-label, controlled trial in patients with biopsy-proven acute tubulointerstitial nephritis caused by sarcoidosis at 21 sites in France. Patients were randomly assigned to receive a methylprednisolone pulse 15 mg/kg/day for 3 days, then oral prednisone (MP group) or oral prednisone 1 mg/kg/day alone (PRD group). The primary end point was a positive response at 3 months, defined as a doubling of estimated glomerular filtration rate (eGFR) compared with the eGFR before randomization. RESULTS: We randomized 40 participants. Baseline eGFR before PRD was 22 mL/min/1.73m2 {interquartile range [IQR], 16-44} and before MP was 25 mL/min/1.73m2 (IQR, 22-36) (P = .3). The two groups did not differ in underlying pathological lesions, including mean percentage of interstitial fibrosis and intensity of interstitial infiltrate. In the intent-to-treat population, the median eGFR at 3 months did not significantly differ between the PRD and MP groups: 45 (IQR, 34-74) and 46 (IQR, 39-65) mL/min/1.73m2. The primary end point at 3 months was achieved in 16 of 20 (80%) PRD patients and 10 of 20 (50%) MP patients (P = .0467). The eGFR was similar between the two groups after 1, 3, 6, and 12 months of treatment. For both groups, eGFR at 1 month was strongly correlated with eGFR at 12 months (P < .0001). The two groups did not differ in severe adverse events. CONCLUSION: Compared with a standard oral steroid regimen, intravenous MP may have no supplemental benefit for renal function in patients with tubulointerstitial nephritis caused by sarcoidosis.Trial Registration: ClinicalTrials.gov: NCT01652417; EudraCT: 2012-000149-11.

Effect of intravenous almitrine on intubation or mortality in patients with COVID-19 acute hypoxemic respiratory failure: A multicentre, randomised, double-blind, placebo-controlled trial.

Background: Severe hypoxemia in patients with COVID-19 pneumonia might result from hypoxic pulmonary vasoconstriction, contributing to ventilation/perfusion (V/Q) mismatch. Because almitrine improves V/Q, it might reduce the risk for mechanical ventilation (MV) in such patients. Our primary objective was to determine the effect of almitrine on the need for MV at day 7. Methods: In a randomised double-blind placebo-controlled trial involving 15 ICUs, patients hospitalized for COVID-19 pneumonia and experiencing acute hypoxemic respiratory failure were randomly assigned to receive 5 days of intravenous low-dose (2 µg.kg-1.min-1) almitrine or placebo. The primary outcome was endotracheal intubation for MV or death within 7 days after randomisation. Secondary outcomes included in-hospital mortality, 28-day mortality, number of ventilator-free days, number of days in the ICU and the hospital, and treatment discontinuation for pre-specified adverse effects. This trial was registered with ClinicalTrials.gov, NCT04357457. Findings: Between September 3, 2020 and September 25, 2021 181 patients were enrolled and randomly assigned to almitrine (n=89) or placebo (n=92). 179 patients (excluding two who withdrew from the study) were included in the intention-to-treat analysis (mean age: 60·1 years; 34% women) and analyzed. On day 7, the primary endpoint occurred in 32 patients assigned to almitrine (36%) and in 37 patients assigned to placebo (41%), for a difference of -4·3% (95% confidence interval: -18·7% to 10·2%). Secondary outcomes (28-day mortality, in-hospital mortality, ventilator-free days at day 28, days in the ICU and the hospital, and treatment discontinuation for pre-specified adverse effects) did not differ between the two groups. Interpretation: In patients with COVID-19 acute hypoxemic respiratory failure, low-dose almitrine failed in reducing the need for MV or death at day 7. Funding: Programme Hospitalier de Recherche Clinique (PHRC COVID 2020) funded by the French Ministry of Health, Les Laboratoires Servier (Suresnes, France) providing the study drug free of charge.

Impact of COVID-19 lockdown on maternal psychological status, the couple's relationship and mother-child interaction: a prospective study.

BACKGROUND: To compare the rate of postpartum depression (PPD) during the first COVID-19 lockdown with the rate observed prior to the pandemic, and to examine factors associated with PPD. METHODS: This was a prospective study. Women who gave birth during the first COVID-19 lockdown (spring 2020) were offered call-interviews at 10 days and 6-8 weeks postpartum to assess PPD using the Edinburgh Postnatal Depression Scale (EPDS). Post-traumatic symptoms (Perinatal Post-traumatic Stress Disorder Questionnaire, PPQ), couple adjustment, and interaction and mother-to-infant bonding were also evaluated. The observed PPD rate was compared to the one reported before the pandemic. Factors associated with an increased risk of PPD were studied. The main outcome measures were comparison of the observed PPD rate (EPDS score > 12) to pre-pandemic rate. RESULTS: Of the 164 women included, 27 (16.5% [95%CI: 11.14-23.04]) presented an EPDS score > 12 either at 10 days or 6-8 weeks postpartum. This rate was similar to the one of 15% reported prior to the pandemic (p = 0.6). Combined EPDS> 12 or PPQ > 6 scores were observed in 20.7% of the mothers [95%CI: 14.8-0.28]. Maternal hypertension/preeclampsia (p = 0.007), emergency cesarean section (p = 0.03), and neonatal complications (p = 0.008) were significantly associated with an EPDS> 12 both in univariate and multivariate analysis (OR = 10 [95%CI: 1.5-68.7], OR = 4.09[95%CI: 1.2-14], OR = 4.02[95%CI: 1.4-11.6], respectively). CONCLUSIONS: The rate of major PPD in our population did not increase during the first lockdown period. However, 20.7% of the women presented with post-traumatic/depressive symptoms. TRIAL REGISTRATION: NCT04366817.

Does hyaluronic acid gel reduce intrauterine adhesions after dilation and curettage in women with miscarriage? A Multicentric randomized controlled trial (HYFACO Study).

BACKGROUND: Miscarriage is a frequent problem that requires dilation and curettage in 30% of cases. This routine surgery may lead to intrauterine adhesions and severe infertility. Hyaluronic acid gel is known to reduce intrauterine adhesions after hysteroscopic surgery. OBJECTIVE: This study aimed to evaluate the rate of intrauterine adhesions after dilation and curettage for miscarriage with and without hyaluronic acid gel. STUDY DESIGN: This was a multicentric (9 hospitals in France), prospective, open-label randomized trial. Patients who had a miscarriage between weeks 7 and 14 of gestation, required dilation and curettage, and wanted another pregnancy were eligible for the study. Women were randomly assigned in a 1:1 ratio to surgery alone (control group) or surgery with intrauterine instillation of hyaluronic acid gel (gel group). An office hysteroscopy was planned at 6 to 8 weeks after surgery. The primary endpoint was the rate of intrauterine adhesions during this office follow-up hysteroscopy. Two different follow-up fertility surveys were sent at 6 months and 1 year after the end of the intervention, respectively. RESULTS: Among the 343 patients who had curettage, 278 had hysteroscopy. After multiple imputation, the rate of intrauterine adhesions was lower in the gel group than in the control group (9.1% vs 18.4%, respectively; P=.0171). Among the 110 responders to the surveys, the overall pregnancy rate at 12 months after surgery was 64.5% (71/110), and similar in both groups (57.4% [27/47] in the control group vs 69.8% [44/63] in the gel group; P=.1789). CONCLUSION: Intrauterine instillation of hyaluronic acid gel reduces the rate of intrauterine adhesions in women treated with dilation and curettage for miscarriage.