Amagasaki-shi, Hyogo, Japan

Evaluation of Security and Efficacy of Medtrum Hybrid Closed Loop System

A Study to Investigate Long-term Safety and Tolerability of Tolebrutinib in Participants With Multiple Sclerosis.

Participants with relapsing MS from the Phase 2b LTS16004 parent study will continue open-label (OL) tolebrutinib. All participants from the Phase 3 parent studies (EFC16033, EFC16034, EFC16645, and EFC16035) will learn which treatment they received in the parent study: - If from one of the Phase 3 relapsing MS studies and on teriflunomide, an accelerated elimination procedure or a 3-month washout period is required prior to starting OL tolebrutinib. If on teriflunomide, and benefiting and recommended by the Investigator, the participant may opt to continue teriflunomide outside of the LTS17043 study, if clinically appropriate. If on tolebrutinib, the participant will continue tolebrutinib. - All participants from one of the Phase 3 progressive MS studies will start OL tolebrutinib. - If a participant already started OL tolebrutinib in the Phase 3 parent study this will be continued. - RMS participants who are not eligible for OL tolebrutinib per Health Authority and/or ethics committee decisions on the study conduct (ie, partial hold on initiation of tolebrutinib) will continue their parent study treatment assignment as per their randomization from the parent study. The treatment duration per participant will be approximately 3 years of OL tolebrutinib.

RItuximab Versus Ocrelizumab in Relapsing-remitting Multiple Sclerosis.

Multiple sclerosis (MS) is an autoimmune inflammatory disease of the central nervous system (CNS). This disease is the leading cause of non-traumatic disability in young adults and France is characterized by a high prevalence (currently 1/1000 inhabitants) of MS. Clinical trials with B cell depleting therapies have shown efficacy in relapsing-remitting MS (RRMS) and are increasingly perceived as an important addition to the existing panel of Disease-modifying treatments (DMTs). Rituximab, a mouse chimeric anti CD20, is approved for non-Hodgkin's lymphoma, chronic lymphocytic leukemia, certain forms of vasculitis and Rheumatoid Arthritis with first marketing approval in 1998. Rituximab has undergone clinical testing in RRMS in 2008 in a phase II placebo-controlled trial, demonstrating the clinico-radiological efficacy in 104 patients. Despite these promising results and the absence of adverse events, its clinical development was interrupted by the manufacturer (Roche). However, for several years, rituximab has been increasingly prescribed (off-label) in Europe and USA in patients refractory to first-line therapies, with a very good safety and efficacy. Thus, rituximab is prescribed for 40% of RRMS patients treated in Sweden. Roche has then developed a humanized anti-CD20 monoclonal antibody (Ocrelizumab). Two phase III clinical trials (OPERA I and II) have demonstrated its efficacy in active RRMS. Ocrelizumab has just been authorized in France in this indication: RRMS patients with active disease (clinical or radiological). So, it can be prescribed as a first line or second line therapy in active RRMS patients. According to literature, there are no biological arguments to think that ocrelizumab could be more effective in active RRMS compared to rituximab. Moreover, regarding safety, rituximab has been used for other indications for almost two decades and no serious concern has arisen. The high cost of this new antibody (x6 to 10) compared to rituximab) makes it wonder about its place inside the anti-CD20 therapeutic strategy compared to rituximab for treating relapsing MS patients. Hypothesis: Researchers hypothesize that rituximab and ocrelizumab have the same efficacy in active RRMS patients. Indeed, if the non-inferiority of rituximab on the % of patients without disease activity is confirmed by the trial, the potential medico-economic benefit from a societal perspective will be a strong argument to ask for authorization of rituximab in active RRMS.

Study of the Criteria for Choosing Speedicath Catheters During the Initiation of Self-catheterization

Urinary self-catheterization consists of emptying the bladder oneself by inserting a catheter into the urethra. It is the reference method in case of dysfunctions of the bladder emptying phase, in particular in case of complete urinary retention or complete or incomplete bladder emptying with sub bladder obstruction. Neurological pathologies such as spinal cord injury, multiple sclerosis, multisystematic atrophy, peripheral neuropathies, Parkinson's disease, and stroke, may be the cause of bladder disturbances. These disturbances may also be caused by pelvic denervations as a result of enlarged pelvic surgeries or radiotherapy for the treatment of gynecological, urological or digestive cancers. The objective of the implementation of intermittent self-catheterization (ISC) is to reduce the morbidity related to bladder and bowel dysfunction and to improve the quality of life of patients by making them more autonomous. It involves a rigorous learning phase for the patient and a phase of acceptance of this new mictional mode. When ISC is indicated, training is provided to the patient to enable him/her to manage daily catheterization. The objectives of this training are to understand, perform, monitor and adapt self-care. This training, mainly provided by the nursing staff and/or a specialist physician, is usually provided during a hospitalization. After returning home, the patient continues to be monitored by the specialist physician and the nursing team to evaluate the mastery of the technique (possibly reviewing the gesture and ensuring the adequacy of the catheter), the patient's adaptation to the practice of ISC, his compliance with the associated rules (frequency and regularity of catheterization, volume of urine) and any complications. A first visit is usually made between 3 and 12 weeks, then a second one after 6 months of use. However, this therapeutic patient education (TPE), even when carried out by trained personnel, is not necessarily sufficient for immediate acceptance and adherence to self-catheterization in the medium to long term. It is important that the patient is involved in his or her choice of equipment, since the decision to self-catheterize is usually made by the physician, and that the benefits of self-catheterization outweigh the constraints. The patient must be guided and involved in the choice of catheter during this learning phase, which will ensure better compliance and future adherence to treatment. The interest of this study is therefore to better understand the real motivations of the patient in the choice of the catheter. This will undoubtedly make it possible to improve either the equipment itself or certain FTE sequences in the future by insisting on the problematic or questioning points in terms of the choice of catheter proposed to the patient by the caregiver. The determinants of the patient's choice are all the more important as there are a very large number of catheters on the market. Coloplast offers the SpeediCath® (SC) range of ready-to-use self-lubricating hydrophilic catheters. This range is designed to cover the different needs of patients, providing them with probes of different length, flexibility, shape and ergonomics. There are 3 types of catheters adapted to women (SC Standard®, SC Compact® and SC Compact Set, SC Compact Eve®), and 3 types of catheters adapted to men (SC Standard®, SC Compact® and SC Compact Set, SC Flex®). Concerning the technical specificities, a systematic review of the literature concluded that hydrophilic catheters (with a lubricant attached to the catheter) provide a benefit in terms of safety and quality of life, particularly in patients with spinal cord injuries. SC® catheters significantly reduce trauma to the urinary tract by reducing friction. Another study also showed that SpeediCath catheters were significantly faster, more convenient, and more discreet to use than a non-ready-to-use hydrophilic catheter (need to activate lubricant). The superiority of SpeediCath Compact Male and Female catheters in terms of quality of life compared to reference catheters was demonstrated in a randomized study using the specific validated ISC-Q questionnaire and has been retained and valued by the CNEDiMTS To date, there is no objective data to help in the choice of the type of catheter to propose to the patient according to his needs. Although it is now known that the quality of life of patients using ISC is dependent on multiple factors, there is little data on the factors that facilitate or hinder adherence to ISC during the first six months after initiation of ISC. The prospective multicenter exploratory observational study that the sponsor wishes to conduct aims to determine the criteria that govern patient choice of SC leads. This information would allow us to set up a personalized advice with each patient in the future, with the aim of proposing the SC catheter best adapted to his needs. The study population will consist of adults with neurogenic or non-neurogenic urinary disorders that warrant the use of ISC, with ISC education occurring at the time of inclusion. Patients should be autonomous in the practice of ISC, and the minimum expected duration of follow-up should be greater than or equal to 6 months. Only patients who have chosen to use SpeediCath leads will be included in the study. Numerous criteria will be collected to allow a detailed analysis of the modalities of choice of the type of SC probe. This collection involves the use of self-questionnaires for the patients. These questionnaires will be collected during the usual follow-up of the patient, including a visit at the time of the ASI education, a follow-up visit around 3 to 12 weeks (depending on the practices of the investigating center) and a second follow-up visit around 6 months. Acceptance of ISC will be measured by the Intermittent Catheterization Acceptance Test (I-CAT). This is a patient questionnaire developed by the Groupe d'Études de Neuro-Urologie de Langue Française (GENULF) and validated in French in 2016 during a prospective multicenter study of 201 neurological and non-neurological patients. The I-CAT allows for a better assessment and understanding of the psychological barriers encountered by patients in relation to ISC. The questionnaire consists of 14 questions, with a minimum score of 0 for perfect acceptance and a maximum score of 56 characterizing the least possible acceptance. The difficulties encountered by patients during ASI will be measured by the "Intermittent Catheterization Difficulty Questionnaire" IC-Di-Q. This is a patient questionnaire validated in French, and its purpose is to evaluate the difficulties encountered during the performance of ISA. In 13 questions, it explores numerous factors such as pain, blockage, bleeding, spasticity, and urethral sphincter spasm, in terms of frequency of occurrence and intensity. The purpose of this questionnaire is to identify the difficulties encountered by patients, and to monitor their evolution after the implementation of alternatives or solutions (including the adaptation of the type of catheter). Patient adherence to ISC will be measured by the Intermittent Catheterization Adherence Scale (I-CAS). This is a patient questionnaire validated in French with 8 questions, 7 of which have a binary answer (yes/no), and one with 5 suggested answers. The score ranges from 0 for strong adherence to ISC to 8 for very weak adherence. A study-specific self-questionnaire was also created with the support of the Scientific Advisory Board to determine the reasons for the patient's choice of catheter. This questionnaire includes criteria independent of the patient (e.g. advice from the nurse), and criteria specific to the patient (e.g. ease of use, discretion).

Evaluation of the Efficacy of Intra-nasal Sufentanil for Analgesia of Vaso-occlusive Crisis in Sickle-cell Adults.

Pain of VOC in sickle-cell patients seen in the emergency department (ED) is severe. Analgesia is a therapeutic emergency based on intravenous (IV) morphine titration. However, for technical reasons (patient flow in ED, difficult venous access) this treatment is often delayed. The Equimolar Mixture of Oxygen-Nitrous Oxide (EMONO), an inhaled analgesic administered, makes it possible to temporarily and very partially compensate for the major analgesic defect. Its efficacy in this indication has never been demonstrated; it is less effective than opiates during labour and is associated with a risk of addiction. The intranasal (IN) route is used to administer strong opiates such as sufentanil. Sufentanil IN has been shown to be rapidly effective in traumatology. Its duration of action is similar to that of morphine IV but its duration of action is far too short to completely replace it. Its ideal place would therefore be the initial phase of the management while waiting for a venous approach. The strategy is to propose an intranasal administration of an opioid (Sufentanil) at the initial management of vaso-occlusive crisis in sickle-cell patients in the ED waiting to a venous route for morphine. Follow-up of the study will be carried out in the ED with numeric rating scale (NRS) measurement every 5 minutes until patient relief (defined by NRS ≤ 3/10). Once relieved, NRS will be measured every 15 minutes for at least 2 hours. Treatment-related side effects will be systematically investigated up to 4 hours after starting treatment. In particular, the respiratory rate and level of consciousness will be measured, and all side effects will be recorded: nausea, vomiting, dizziness, behavioural disorders, pruritus.

Efficacy of Nicotine in Preventing COVID-19 Infection

Covid-19 Pediatric Observatory

Randomised Study Evaluating Adjuvant Chemotherapy After Resection of Stage III Colonic Adenocarcinoma in Patients of 70 and Over

Colorectal cancer occurs mainly in elderly patients. Recent estimation showed that in France more than 50% of the patients diagnosed with a colorectal cancer are 70 years old or more. Adjuvant chemotherapy has demonstrated a benefit on disease-free survival and overall survival after a stage III colon cancer resection. Nevertheless adjuvant chemotherapy is poorly used in elderly patients. Prognostic improvement with chemotherapy based on 5FU is suggested by a post-hoc analysis of randomized prospective clinical trial. But elderly patients in this study were highly selected and patients older than 80 represented only 0.7% of the total population. Thus, there is still a concern about the benefit of adjuvant 5FU-based chemotherapy in very elderly unselected patients. The recommended treatment for stage III adjuvant chemotherapy is a combination of fuoropyrimidine and oxaliplatin. Nevertheless oxaliplatin did not demonstrated survival advantage in elderly patients. Altogether there are still two matters of debate: - First, is there a benefit of fluoropyrimidine-based adjuvant chemotherapy for unfit elderly patients? - Second, is there a benefit of oxaliplatin-based adjuvant chemotherapy for fit elderly patients? The aim of this randomized phase III study is to evaluate the benefit for disease-free survival of adjuvant chemotherapy in elderly patient and which chemotherapy. The elderly patient population will be dichotomized into two groups according to physician's choice after a multidisciplinary evaluation involving a geriatrician, with two different randomization assignments. The patients with an expected life-expectancy below 4 years according Lee score are excluded of this study. Some biological tumour abnormalities are more frequently observed in elderly (i.e. mismatch repair deficiency), therefore an evaluation of specific biological prognostic factors is needed in elderly population.

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.

CARegiver BURden, Effectiveness and Other Health Care Measures on Functional Disability, in Patients Treated With Abobotulinumtoxin A for Upper Limb Spasticity