The role of the gut microbiota in Crohn's disease (CD) is established and fecal microbiota transplantation (FMT) is an attractive therapeutic strategy. No randomized controlled clinical trial results ...are available. We performed a randomized, single-blind, sham-controlled pilot trial of FMT in adults with colonic or ileo-colonic CD.
Patients enrolled while in flare received oral corticosteroid. Once in clinical remission, patients were randomized to receive either FMT or sham transplantation during a colonoscopy. Corticosteroids were tapered and a second colonoscopy was performed at week 6. The primary endpoint was the implantation of the donor microbiota at week 6 (Sorensen index > 0.6).
Eight patients received FMT and nine sham transplantation. None of the patients reached the primary endpoint. The steroid-free clinical remission rate at 10 and 24 weeks was 44.4% (4/9) and 33.3% (3/9) in the sham transplantation group and 87.5% (7/8) and 50.0% (4/8; one patient loss of follow-up while in remission at week 12 and considered in flare at week 24) in the FMT group. Crohn's Disease Endoscopic Index of Severity decreased 6 weeks after FMT (p = 0.03) but not after sham transplantation (p = 0.8). Conversely, the CRP level increased 6 weeks after sham transplantation (p = 0.008) but not after FMT (p = 0.5). Absence of donor microbiota engraftment was associated with flare. No safety signal was identified.
The primary endpoint was not reached for any patient. In this pilot study, higher colonization by donor microbiota was associated with maintenance of remission. These results must be confirmed in larger studies (NCT02097797). Video abstract.
Abstract Background We aimed to describe the determinants of discharge heart rate in acute coronary syndrome patients and assess the impact of discharge heart rate on 5-year mortality in hospital ...survivors. Methods French Registry of Acute ST-Elevation or non-ST-elevation Myocardial Infarction (FAST-MI) 2005 is a nationwide French registry that included all consecutive patients with acute myocardial infarction over 1 month in 223 institutions in 2005. Discharge heart rate was recorded in 3079 patients discharged alive; all had 5-year follow-up. Logistic regression was used to detect predictors of high heart rate at discharge. Cox's proportional hazards model was used to assess the hazard ratio for mortality at 5 years. Heart rate was categorized into 4 groups by quartiles (<60, 61-67, 68-75, >75 beats per minute). High heart rate was defined as ≥75 beats per minute. Landmark analysis was performed at 1 year. Results Independent predictors of heart rate ≥75 beats per minute at discharge were female sex, ST-segment elevation myocardial infarction, diabetes, chronic obstructive pulmonary disease, bleeding/transfusion during hospitalization, left ventricular dysfunction, renal dysfunction, and prescription (type, but not dose category) of beta-blockers at discharge. Discharge heart rate was significantly related to mortality at 1 year (hazard ratio 1.13; 95% confidence interval, 1.03-1.24 per 10 beats per minute, P = .02); this was confirmed by landmark analysis, with a 39% increase (hazard ratio 1.39; 95% confidence interval 1.05-1.84) in the risk of 1-year death for discharge heart rate ≥75 beats per minute vs <75 beats per minute. This relationship was no longer significant between 2 and 5 years. Conclusions After acute myocardial infarction, patients discharged with high heart rate (≥75 beats per minute) are at higher risk of death during the first year, but not later, irrespective of beta-blocker use.
There are little data about patients with cardiogenic shock (CS) who survive the early phase of acute myocardial infarction (AMI). The aim of this study was to assess long-term (5-year) mortality ...among early survivors of AMI, according to the presence of CS at the acute stage.
We analyzed 5-year follow-up data from the French registry of Acute ST-elevation and non-ST-elevation Myocardial Infarction (FAST-MI) 2005 registry, a nationwide French survey including consecutive patients admitted for ST or non-ST-elevation AMI at the end of 2005 in 223 institutions.
Of 3670 patients enrolled, shock occurred in 224 (6.1%), and 3411 survived beyond 30 days or hospital discharge, including 99 (2.9%) with shock. Early survivors with CS had a more severe clinical profile, more frequent concomitant in-hospital complications, and were less often managed invasively than those without CS.
In patients surviving the early phase of AMI, CS at the initial stage carries an increased risk of death up to one year after the acute event. Beyond one year, however, mortality is similar to that of patients without shock.
ClinicalTrials.gov number, NCT00673036, Registered May 5, 2008.
Abstract
Background
The aim of this trial-based economic evaluation was to assess the incremental costs and cost-effectiveness of the modified diagnostic strategy combining the YEARS rule and ...age-adjusted D-dimer threshold compared with the control (which used the age-adjusted D-dimer threshold only) for the diagnosis of pulmonary embolism (PE) in the Emergency Department (ED).
Methods
Economic evaluation from a healthcare system perspective alongside a non-inferiority, crossover, and cluster-randomized trial conducted in 16 EDs in France and two in Spain with three months of follow-up. The primary endpoint was the additional cost of a patient without failure of the diagnostic strategy, defined as venous thromboembolism (VTE) diagnosis at 3months after exclusion of PE during the initial ED visit. Mean differences in 3-month failure and costs were estimated using separate generalized linear-regression mixed models, adjusted for strategy type, period, and the interaction between strategy and period as fixed effects and the hospital as a random effect. The incremental cost-effectiveness ratio (ICER) was obtained by dividing the incremental costs by the incremental frequency of VTE.
Results
Of the 1,414 included patients, 1,217 (86%) were analyzed in the per-protocol analysis (648 in the intervention group and 623 in the control group). At three months, there were no statistically significant differences in total costs (€-46; 95% CI: €-93 to €0.2), and the failure rate was non inferior in the intervention group (-0.64%, one-sided 97.5% CI: -∞ to 0.21%, non-inferiority margin 1.5%) between groups. The point estimate of the incremental cost-effectiveness ratio (ICER) indicating that each undetected VTE averted in the intervention group is associated with cost savings of €7,142 in comparison with the control group. There was a 93% probability that the intervention was dominant. Similar results were found in the as randomized population.
Conclusions
Given the observed cost decrease of borderline significance, and according to the 95% confidence ellipses, the intervention strategy has a potential to lead to cost savings as a result of a reduction in the use of chest imaging and of the number of undetected VTE averted. Policy-makers should investigate how these monetary benefits can be distributed across stakeholders.
Clinicaltrials
Trial registration number ClinicalTrials.gov Identifier: NCT04032769; July 25, 2019.
IntroductionAt the time of the worrying emergence and spread of bacterial resistance, reducing the selection pressure by reducing the exposure to antibiotics in patients with community-acquired ...pneumonia (CAP) is a public health issue. In this context, the combined use of molecular tests and biomarkers for guiding antibiotics discontinuation is attractive. Therefore, we have designed a trial comparing an integrated approach of diagnosis and treatment of severe CAP to usual care.Methods and analysisThe multiplex PCR and procalcitonin to reduce duration of antibiotics exposure in patients with severe-CAP (MULTI-CAP) trial is a multicentre (n=20), parallel-group, superiority, open-label, randomised trial. Patients are included if adult admitted to intensive care unit for a CAP. Diagnosis of pneumonia is based on clinical criteria and a newly appeared parenchymal infiltrate. Immunocompromised patients are excluded. Subjects are randomised (1:1 ratio) to either the intervention arm (experimental strategy) or the control arm (usual strategy). In the intervention arm, the microbiological diagnosis combines a respiratory multiplex PCR (mPCR) and conventional microbiological investigations. An algorithm of early antibiotic de-escalation or discontinuation is recommended, based on mPCR results and the procalcitonin value. In the control arm, only conventional microbiological investigations are performed and antibiotics de-escalation remains at the clinician’s discretion. The primary endpoint is the number of days alive without any antibiotic from the randomisation to day 28. Based on our hypothesis of 2 days gain in the intervention arm, we aim to enrol a total of 450 patients over a 30-month period.Ethics and disseminationThe MULTI-CAP trial is conducted according to the principles of the Declaration of Helsinki, is registered in Clinical Trials and has been approved by the Committee for Protection of Persons and the National French Drug Safety Agency. Written informed consents are obtained from all the patients (or representatives). The results will be disseminated through educational institutions, submitted to peer-reviewed journals for publication and presented at medical congresses.Trial registration numberNCT03452826; Pre-results.
Although effective mRNA vaccines for SARS-CoV-2 infection have been deployed worldwide, their interchangeability could facilitate the scale-up of vaccination programs. The objective of the trial was ...to assess whether the immune response induced by a heterologous SARS-CoV-2 mRNA primo vaccination is non-inferior to that of a homologous mRNA vaccination.
We conducted a multicenter, randomized, open-label trial in adults 18 years of age and older who received a first dose of SARS-CoV-2 mRNA vaccine. Participants were randomly assigned in a 1:1 ratio to receive a second dose of BNT162b2 or mRNA-1273, 28 to 49 days after the first dose. Randomization was stratified on the vaccine received at the first vaccination. The primary endpoint was the anti-spike IgG antibodies titer measured 28 days after the second vaccine dose. This study is registered with ClinicalTrials.gov, Trial, NCT04900467.
Of the 414 randomized participants recruited from May 28 to July 2, 2021, 390 were included in the per protocol analysis: 94 participants in group 1 (BNT162b2/BNT162b2), 96 in group 2 (BNT162b2/mRNA-1273), 97 in group 3 (mRNA-1273/mRNA-1273), and 103 in group 4 (mRNA-1273/BNT162b2). The geometric mean titers ratios of anti-spike IgG antibodies for each heterologous regimen relative to the corresponding homologous regimen were 1·37 (two-sided 95% CI, 1·10 to 1·72) in the groups 1 and 2 and 0·67 (two-sided 95% CI, 0·55 to 0·82) in the groups 3 and 4. Levels of neutralizing antibodies to the main circulating SARS-Cov-2 viral strains were higher with the vaccine regimen containing mRNA-1273. Participants who received mRNA-1273 as a second dose experienced a higher rate of local adverse reactions and general symptoms than those who received BNT162b2 (p < 0·0001).
The two SARS-CoV-2 mRNA vaccines could be used with flexibility for the second dose of COVID-19 primo vaccination. Tolerance remains good regardless of vaccine sequence although mRNA-1273 was more reactogenic.
French Ministries of Solidarity and Health and Research. BNT162b2 was provided by Pfizer/BioNTech. mRNA-1273 was provided by Moderna.
IMPORTANCE: Noninvasive ventilation delivered as bilevel positive airway pressure (BiPAP) is often used to avoid reintubation and improve outcomes of patients with hypoxemia after cardiothoracic ...surgery. High-flow nasal oxygen therapy is increasingly used to improve oxygenation because of its ease of implementation, tolerance, and clinical effectiveness. OBJECTIVE: To determine whether high-flow nasal oxygen therapy was not inferior to BiPAP for preventing or resolving acute respiratory failure after cardiothoracic surgery. DESIGN AND SETTING: Multicenter, randomized, noninferiority trial (BiPOP Study) conducted between June 15, 2011, and January 15, 2014, at 6 French intensive care units. PARTICIPANTS: A total of 830 patients who had undergone cardiothoracic surgery, of which coronary artery bypass, valvular repair, and pulmonary thromboendarterectomy were the most common, were included when they developed acute respiratory failure (failure of a spontaneous breathing trial or successful breathing trial but failed extubation) or were deemed at risk for respiratory failure after extubation due to preexisting risk factors. INTERVENTIONS: Patients were randomly assigned to receive high-flow nasal oxygen therapy delivered continuously through a nasal cannula (flow, 50 L/min; fraction of inspired oxygen Fio2, 50%) (n = 414) or BiPAP delivered with a full-face mask for at least 4 hours per day (pressure support level, 8 cm H2O; positive end-expiratory pressure, 4 cm H2O; Fio2, 50%) (n = 416). MAIN OUTCOMES AND MEASURES: The primary outcome was treatment failure, defined as reintubation, switch to the other study treatment, or premature treatment discontinuation (patient request or adverse effects, including gastric distention). Noninferiority of high-flow nasal oxygen therapy would be demonstrated if the lower boundary of the 95% CI were less than 9%. Secondary outcomes included mortality during intensive care unit stay, changes in respiratory variables, and respiratory complications. RESULTS: High-flow nasal oxygen therapy was not inferior to BiPAP: the treatment failed in 87 of 414 patients with high-flow nasal oxygen therapy (21.0%) and 91 of 416 patients with BiPAP (21.9%) (absolute difference, 0.9%; 95% CI, −4.9% to 6.6%; P = .003). No significant differences were found for intensive care unit mortality (23 patients with BiPAP 5.5% and 28 with high-flow nasal oxygen therapy 6.8%; P = .66) (absolute difference, 1.2% 95% CI, -2.3% to 4.8%. Skin breakdown was significantly more common with BiPAP after 24 hours (10% vs 3%; 95% CI, 7.3%-13.4% vs 1.8%-5.6%; P < .001). CONCLUSIONS AND RELEVANCE: Among cardiothoracic surgery patients with or at risk for respiratory failure, the use of high-flow nasal oxygen therapy compared with intermittent BiPAP did not result in a worse rate of treatment failure. The findings support the use of high-flow nasal oxygen therapy in similar patients. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01458444
Obese patients are considered at risk of respiratory failure after cardiothoracic surgery. High-flow nasal cannula has demonstrated its non-inferiority after cardiothoracic surgery compared to ...noninvasive ventilation (NIV), which is the recommended treatment in obese patients. We hypothesized that NIV was superior to high-flow nasal cannula for preventing or resolving acute respiratory failure after cardiothoracic surgery in this population.
We performed a post hoc analysis of a randomized, controlled trial. Obese subjects were randomly assigned to receive NIV for at least 4 h/d (inspiratory pressure, 8 cm H
O; expiratory pressure, 4 cm H
O; F
, 0.5) or high-flow nasal cannula delivered continuously (flow, 50 L/min, F
0.5).
Treatment failure (defined as re-intubation, switch to the other treatment, or premature discontinuation) occurred in 21 of 136 (15.4%, 95% CI 9.8-22.6%) subjects with NIV compared to 18 of 135 (13.3%, 95% CI 8.1-20.3%) subjects with high-flow nasal cannula (
= .62). No significant differences were found for dyspnea and comfort scores. Skin breakdown was significantly more common with NIV after 24 h (9.2%, 95% CI 5.0-16.0 vs 1.6%, 95% CI 1.0-6.0;
= .01). No significant differences were found for ICU mortality (5.9% for subjects with NIV vs 2.2% for subjects with high-flow nasal cannula,
= .22) or for any of the other secondary outcomes.
Among obese cardiothoracic surgery subjects with or without respiratory failure, the use of continuous high-flow nasal cannula compared to intermittent NIV (8/4 cm H
O) did not result in a worse rate of treatment failure. Because high-flow nasal cannula presents some advantages, it may be used instead of NIV in obese patients after cardiothoracic surgery.
Abstract Background We document dual antiplatelet therapy (DAPT) use from discharge to 4 years after acute myocardial infarction (AMI), and investigate whether prolonged DAPT (beyond 1 year) is ...related to 5-year mortality. Methods The French Registry of Acute ST-elevation or non-ST-elevation Myocardial Infarction (FAST-MI 2005) included 3670 patients with AMI in 223 French centres. We identified predictors of DAPT (aspirin + clopidogrel) beyond 1 and 2 years, and relation with all-cause 5-year mortality. Results Among 3319 (96%) patients with discharge data, 2432 (73%) had DAPT, 582 (17%) single antiplatelet therapy (SAPT), and 305 (9%) no antiplatelet treatment. DAPT decreased from 75% at 1 year to 29% at 4 years, with a corresponding increase in SAPT (p < 0.05 for trend). Patients with DAPT were more often male, treated with a drug-eluting stent (DES), and without oral anticoagulants. Independent predictors at 1 year of prolonged DAPT were age < 75 years, in-hospital bleeding, history of MI, use of DES, discharge use of beta-blockers or statins and no chronic anticoagulation. Predictors at 2 years were age < 75 years, male gender, previous MI, diabetes, DES implantation, no chronic oral anticoagulation. By multivariate analysis, there was no difference in 5-year mortality between those on SAPT vs DAPT at 1 year. DAPT at 2 years was also not significantly related to 5-year mortality (Hazard Ratio 1.3, 95% CI 0.9; 1.8, p = 0.21). Conclusion Prolonged DAPT in selected AMI patients, observed in 47% at 1 year and 21% at 2 years, had no impact on 5-year mortality. These findings do not support the use of DAPT beyond 1 year after an initial ACS.
Geographical indications in France are governed since 1935 by a unique mixed public/private Institute set-up on the failure of the State to define GIs. This mixed body, the National Institute of ...Appellation of Origin, composed of representatives of public authorities and producers’ Organization was weakened due to a moving context in France, Europe, and worldwide. The transfer of activities of control of GIs to private certification organization on the one end and the increased involvement of the EU Commission on the other end questions the future of INAO and affects the attractiveness of GIs and hence rural development.
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