Gargenville, France

Disease Modifying Therapies Withdrawal in Inactive Secondary Progressive Multiple Sclerosis Patients Older Than 50 Years (STOP-I-SEP)

Multiple sclerosis (MS) usually evolves over decades and can present several phenotypes. Approximately 85% of newly diagnosed Multiple Sclerosis (MS) patients present the Relapsing-Remitting MS (RRMS) phenotype. After a mean time of approximatively 20 years, a large majority of these patients evolve to the so-called "Secondary Progressive MS" (SPMS) phase. SPMS is characterized by an irreversible disability progression not related to relapses, although relapses could be superimposed. Nevertheless, the shift in-between RRMS and SPMS is not clear. Different subtypes of SPMS have been recently defined by F Lublin et al. This classification takes into account persistent focal inflammatory activity (active vs inactive SPMS) along with disease progression (progressing vs non-progressing SPMS). In clinical routine, it is important to identify these stages of MS as they differently respond to the disease modifying therapies (DMTs). Introducing DMTs during the RRMS phase had consistently demonstrated a significant impact on the annual relapse rate (ARR) and on the short-term disability progression. Conversely, during the SPMS phase, the impact of DMTs remained uncertain on disability progression, especially in older patients, with "inactive" disease. As a matter of fact, the DMTs are considered to be anti-inflammatory by nature, but the focal inflammation reduces with age and disease duration. In addition, the DMTs have side effects and cost approximately 10,000 euros per year and per patient. In this context, the usefulness of continuing DMTs in "inactive" SPMS patients older than 50 years is questionable. In a preliminary retrospective study conducted at our Institute which enrolled 100 SPMS patients, the ARR remained stable 3 years after treatment withdrawal (0.07, 95% CI [0.05, 0.11]), relative to the 3 years prior to treatment withdrawal (0.12, [0.09, 0.16]). EDSS scores were available for 94 patients The percentage of patients experiencing a significant increase of their EDSS score during the 3 years after treatment withdrawal also remained stable compared to the 3 years prior treatment withdrawal. These preliminary data support the safety of DMTs withdrawal in selected SPMS patients. However, further prospective studies are needed to provide evidence-based guidelines for daily practice. This randomized controlled clinical trial thus aims to compare SPMS patients older than 50 years without evidence of focal inflammatory activity for 3 years, stopping DMTs versus patients with the same criteria still receiving treatment. We hypothesize that stopping DMTs will not induce an increased risk of disability progression or relapse in SPMS patients but will improve their quality of life and have an impact on treatment-related costs. So far, the impact of DMTs withdrawal in a selected SPMS population has not been explored. Having evidence-based recommendations on the treatment management of these patients is essential, considering the consequences in terms of disability, relapses, side effects, quality of life and costs. DMTs in MS are now available since 20 years, with an increasing number of approved molecules. As a matter of fact, this question concerns a large number of patients: a retrospective analysis of patients included in the Rennes EDMUS database allowed to identify 71 SPMS patients older than 50 years and without evidence of focal inflammatory activity for 3 years actually undergoing a DMT. For evident conflict of interests, the pharmaceutical firms will not promote or fund clinical trials on treatment withdrawal. A randomized controlled study initiated by academia and financed by public funding should be performed to explore these questions. We will evaluate the impact of these changes from the patient and the health system's points of view. The results of this clinical trial will lead to a concrete change in clinical practice.

Management of Moderately Hypoxemic Thoracic Trauma

TrOMaTho study is an investigator-initiated, randomized, unblinded, controlled trial. The aim of this study is to compare a prophylactic use of high-flow nasal cannula oxygenation (experimental group) to low-flow oxygenation (control group) after thoracic trauma. 770 patients will be included. Randomization will be conducted with random block and patients will be randomized in 1:1 ratio in one of the two groups. Randomization process will be stratified on: age (more or less 65 years old), use of peridural analgesia and existence of extra thoracic trauma. Only the oxygenation technique is studied, all other aspects of management will be handle by the attending physician. All patients will be followed from enrollment to hospital discharge. To ensure the same data collection in all centers, six visits are planned: day (D) 1 (inclusion), D7, D14, D28. Classical blinded methods cannot be used for the evaluation of these kinds of devices. To ensure the same evaluation for all patients and in all centers, all relevant outcomes will be evaluated by an independent clinical event committee. Statistical analysis will be performed by an independent statistician. Primary endpoint will be analyzed according to intention to treat. Secondary outcomes will be analyzed as exploratory analysis.

Platelet Inhibitor Treated Patients with Head Injury Trauma Meeting NICE Criteria : is the CT-scan Mandatory ?

Head injuries are a frequent reason for emergency services, and according to studies, they represent between 5% and 10% of patients treated in emergencies. Among them, 90% are minor head injury traumas. NICE criteria has been defined to establish patients who need a CT-scanner because of a risk of cerebral haemorrhage. NICE criteria include several conditions including taking antiplatelet inhibitors. However, the real risk of cerebral haemorrhage for theses cases is controversial in litterature. In parallel, more and more patients undergoing antiplatelet inhibitor's treatment are seen in emergencies after a head injury trauma. In routine protocol at the emergency rooms, these patients are seen for a clinical exam and next submitted to a CT-scanner. If the clinician can't detect a cerebral haemorrage, the patient will return at home. This study aims to determine that the absence of no other NICE criteria than antiplatelet inhibitors treatment is a sufficient condition to eliminate a cerebral haemorrhage for patients with head injury traumas, and conversely, that antiplatelet inhibitors treatment would not be by itself an indication for a CT-scanner. This is a diagnostic, case-only, prospective, multicenter study with a blinded primary outcome measure assessment. As described in routine protocol, in this study antiplatelet inhibitor's patients with head injury trauma will be seen for a clinical exam and next submitted to a CT-scanner. After a month, patient will be called by the clinical center to ask about morbidity and mortality. Especially, clinicans will report on the emergence of a cerebral haemorrhage during this month.

One Day Implantation Program for Heart Failure Patients Implanted With CRT-P

The objective of the study is to show in the French centers selected for the same-day organization that a same-day CRT-P implantation is safe, feasible, and associated with significant cost-saving and a minimum conversion rate to full hospitalization by comparing outcomes with patients routinely hospitalized for at least one night. The medical economic evaluation will be based on the SNDS (National Health Data System) analysis.

Performance of Prostate MRI and Following Biopsy to Detect Prostate Cancer Recurrence After Focal Therapy

This trial is a multi-centric prospective and diagnostic study, comparative, not randomised. The main objective is to evaluate the value of Multiparametric MRI (MpMRI) and targeted biopsy in detecting recurrence after focal treatment of prostate cancer (PCa). The secondary objectives (all energy and according to the energy used) are: to describe the specific changes in prostate morphology after focal therapy ( normal presentation and recurrence in the treated and in the non-treated zone, all energy and according to the energy used),to evaluate the accuracy of MpMRI in the detection of residual PCa, in the treated zone, in the whole gland, to evaluate the performance of targeted biopsy and non targeted biopsy for the detection of prostate cancer recurrence, to evaluate the combination of targeted biopsy and non targeted biopsy for the detection of prostate cancer recurrence, to assess the number and amount of unnecessary non targeted biopsies taken during the follow up of men in focal therapy, to describe the morbidity of prostate non-targeted and targeted biopsy (number and severity of biopsy complications) for the detection of prostate cancer recurrence, to evaluate the impact of recurrence detection on patient management (number and type of salvage treatment),to evaluate the post treatment PSA levels including density, PSA nadir, and its goal in detection recurrence, to examine failures in order to learn potential future predictors of failure (all energy and according to the energy used, the initial location of the target on MRI and it's Gleason grade).The first objective of ancillary study is a central MRI lecture with 3 experts which will allow, performance and inter-observer reproducibility, to evaluate the percentage of cases that will be scored with agreement for concordant biopsy decision by the central radiology team and the site radiologist, to determine on the pre-treatment MRI predictive criteria of success or failure for focal therapy according of the energy used and to propose recommendations for MRI interpretation after FT. The second objective of ancillary study is a central pathology reading to evaluate the percentage of cases that will be scored with agreement on the Gleason score by the central pathologists and the site pathologist and to propose recommendations for histology interpretation post focal therapy. The study population will consist of men with low and intermediate risk prostate cancer (ISUP 1 and 2) who has already chosen to undergo focal treatment, and be willing and able to undergo MpMRI with subsequent prostate biopsies, as indicated. Patients will be enrolled at baseline by an urologist in one of urology units listed as investigation center. The focal treatment should take place no later than 3 months after inclusion visit. The follow-up visits will be planned at 3 month,6 month,12 and 13 months after focal treatment, consistently with patient usual care. In this study, all patients will have a MpMRI and MpMRI targeted biopsy in the presence of a lesion suggestive of recurrence.The statistical analysis is to compare the positive biopsy rate between non targeted and targeted in subject as his own control (with a 12-month relapse rate of 30%) assuming 18.25% positive with the standard method (H0) and 26.25% with the targeted method (H1) and 15% of discordant pairs. By simulation with a MacNemar test, with a bilateral alpha risk of 5% and power of 90% we need 260 subjects.

HFNO or Conventional Oxygen Therapy for Patients With Acute Hypoxemic Respiratory Distress

Acute Respiratory Distress (ARD) is defined as the inability of a patient to maintain normal hematosis. A hematosis disorder is defined as an alteration of the blood gases with hypoxemia (partial pressure of oxygen (PaO2) less than 80 mm of mercury (mmHg) and transcutaneous O2 saturation (SpO2) less than 95%), associated or not with hypercapnia (partial pressure of carbon dioxide (PaCO2) > 45 mmHg) or hypocapnia depending on the cause of the acute respiratory failure. Compensation mechanisms include increased minute ventilation, increased ventilatory work and increased cardiac output. When these compensatory mechanisms are insufficient, acute respiratory distress occurs, along with signs of heart failure (acute cor pulmonale) and neuropsychic disorders. Without care, a potentially fatal respiratory decompensation may occur. ARD can be hypercapnic. It's defined as a PaCO2 greater than 45 mm Hg associated with a drop in blood pH reflecting respiratory acidosis. Hypoxemic ARD is defined as a PaO2 of less than 60 mm Hg. A quarter of the patients admitted to the Vital Emergency Room are admitted for severe hypoxemia resulting from acute respiratory distress. Like all life-threatening conditions, acute respiratory distress (ARD) requires a rapid identification and a prompt implementation of effective resuscitation measures. Oxygen treatment, first described in 1890, remains one of the most important discoveries in medicine. The purpose of oxygenation is to alleviate respiratory failure and to restore a satisfactory hematosis. Most experts stress the importance of having an SpO2 target of more than 90% in the majority of patients. While non-invasive ventilation (NIV) is the standard of care in the initial management of patients with hypercapnic acidosis, there are currently no recommendations for oxygen therapy in patients with acute hypoxic respiratory distress in the emergency department. The choice of the oxygen delivery device is based on the severity of the hypoxemia, the underlying physiological problems, the type of dyspnea and the patient's tolerance to the device. The most commonly used devices are nasal cannula, face mask and high-concentration face mask. They offer several Oxygen Inspired Fraction (fraction of O2 in the gas mixture breathed, FiO2) depending on the oxygen flow rate instituted. High Flow Nasal Oxygen (HFNO) is used as a complement to conventional oxygen therapy in emergency departments in general and in particular in the different emergency departments participating in our study. HFNO is used in hypoxemic respiratory insufficiency according to the national and international recommendations. HFNO makes it possible to administer a much higher flow of oxygen than with the usual hospital and prehospital flow meters. This flow rate can go up to 60-70 L/min with an FIO2 of 100%. This high flow rate allows to generate low levels of positive pressure in the upper airways and to adapt the FIO2 delivered up to 100% notably thanks to dedicated nasal cannulas. HFNO ensures good clinical tolerance and better patient comfort (humidification and heating of inhaled gases ...) than the other oxygen devices. Its use was initially developed in paediatric and neonatal intensive care units. It was then gradually extended to "adult" intensive care units and intensive care units in the treatment of hypoxemic, non-hypercapnic acute respiratory failure (ARF) with no indication for orotracheal intubation. The FLORALI study confirms its use as an alternative to conventional oxygen therapy in intensive care units. Its implementation, its efficacy (improvement of dyspnea, clinical respiratory signs and oxygenation parameters), its good tolerance and acceptability by the nursing staff, were recently demonstrated in an emergency department in 17 patients with hypoxic respiratory insufficiency. However, despite the increasing number of studies, methodologically heterogeneous and of insufficient statistical power, carried out on HFNO, these studies remain non-contributory with regard to the superiority of high nasal flow compared to conventional oxygen therapy. The gain of the HFNO strategy seems to be established for clinical ventilatory parameters and dyspnea level. However, the need for therapeutic escalation and mortality have not been precisely evaluated. On the other hand, there is very little information on the time required for the implementation of HFNO in the various studies carried out in patients. The available data indicate that the average time would usually be more than 90 minutes. Given the lack of data and clinical trials concerning the systematic use of HFNO in emergency departments in cases of severe hypoxemia, a prospective study is essential. The purpose of this work is to evaluate the contribution of early administration of HFNO for patients with acute non-hypercapnic respiratory distress presenting in the emergency department, with the aim of obtaining rapid correction of hematosis. The objective of this work is to compare Conventional Oxygen Therapy (CO) delivered by nasal cannula or nasal-oral mask at flow rates up to a maximum of 15 liters to HFNO, with the hypothesis that HFNO would reduce the need for ventilation therapy escalation. The other hypotheses concern the interest of the HFNO in reducing the use of intensive care hospitalization and thus the costs of treating these patients.

Covid-19 Pediatric Observatory

Management of Anticoagulant Therapy Monitored by an Implantable Device With Telecardiology in Patients With Acute Coronary Syndrome Associated With de Novo Atrial Fibrillation Arrhythmia

Acute Coronary Syndrome associated with de novo atrial fibrillation is not uncommon. It worsens the short-term, medium-term and long-term prognosis. It is then usual, according to ESC recommendations, to add to the DAPT, an anticoagulant treatment, which is a source of iatrogenic events, in particular hemorrhagic events. However, recurrence is not a certainty. Albeit variable, its highest rate is estimated to be 38%. Consequently, a well-conducted screening of atrial fibrillation recurrence could allow to treat only selected recurrent patients. At present, this screening can be carried out in a reliable and minimally invasive way with an implantable device with telecardiology. We propose a study for these patients with ACS associated with de novo AF. The study will be multicenter, randomized, open-label, with two arms: patient conventionally treated (DAPT + AC) and patient treated by DAPT + implantable device and followed for two years by telecardiology. This patient will only reintegrate the first arm in case of AF recurrence.

Assessment of Complication Risk Factors in a French National Cohort of Asplenic Patients

Asplenia can be congenital or acquired. Acquired asplenia can be due to diagnostic or therapeutic surgery, splenic artery embolization, or radiotherapy. Incidence of splenectomized patients was estimated between 10 and 15/100 000 persons in 2003. More recent data suggested a decrease in splenectomy due to increase of splenic artery embolization. From 212 to 2016, about 4000 splenectomy had still been performed. Three different risks are known for asplenic patients: infectious, neoplastic, and thromboembolic. Prevalence rate of infectious complications in splenectomized patients was 3.2% with a mortality rate of 1.4%. A US cohort study including 8149 splenectomized veterans have shown that the risk of cancer was increased, so did the risk of thromboembolic disease, on a 27-year period of follow-up. Pathophysiology of these risks are not well known. There are very few tools to assess splenic function: Howell-Jolly bodies in red blood cells, scintigraphy. These tools lack sensitivity and are not correlated with complications in asplenic patients. To better understand how splenic function and how immunity evolves during time in asplenic patients, a longitudinal follow-up could be useful. There may be some differences between splenectomized patients, those who benefited from splenic artery embolization, and those who received radiotherapy. Infectious risk may be different between these three groups. Implementing new tools assessing residual splenic function could improve management of these patients. A prospective follow-up aims at accurately estimate the incidence rate of infectious and non-infectious complications in this population.

Influence of the PEPA Membrane on the Undernutrition Syndrome Inflammation in Chronic Hemodialysis

The objective of NutriPEPA2 study is to demonstrate that the use of an adsorbent membrane (PEPA-Poly Ester Poly Arylate synthetic co-polymer membrane) decreases undernutrition (often associated with inflammation) and consequently morbidity, comparing one year mortality in patients with Chronic Kidney Disease (CKD), with severe Protein-Energy Wasting (PEW), treated with dialysis using a non-adsorbent synthetic membrane (Polysulfone or Polyethersulfone) versus an adsorbent membrane (PEPA).