Cholet

This is a Phase III open-label study to assess if camizestrant improves outcomes compared to standard endocrine therapy in patients with ER+/HER2 - early breast cancer who completed definitive locoregional therapy (with or without chemotherapy) and standard adjuvant endocrine therapy (ET) for at least 2 years and up to 5 years. The planned duration of treatment in either arm of the study is 60 months. The eligible patients must have intermediate or high risk of recurrence, as defined by specified clinical and biologic criteria. Prior use of CDK4/6 inhibitors is permitted. The primary endpoint of the study is Invasive breast cancer-free survival (IBCFS) and main secondary endpoints include Invasive disease-free survival (IDFS), Distant relapse-free survival (DRFS), Overall survival (OS), Safety and Clinical Outcome Assessments (COAs). Patients will be followed for 10 years from randomization of the last patient.

The purpose of this study is to assess the safety and efficacy of brenipatide at different dose levels compared with placebo in participants with moderate-to-severe asthma. Study participation will last approximately 65 weeks, including screening, treatment, and follow-up periods.

NUMBER OF PATIENTS : 238 patients in 20 sites in France RECRUITMENT PERIOD : The trial duration for each patient will be 144 weeks MAIN ENDPOINT : At week 48 success defined by: Endoscopic remission defined by an endoscopic Mayo score 0 SECONDARY ENDPOINTS: At W48 * Clinical remission (Clinical remission is defined as a total Mayo score ≤2 points, with no individual sub score \>1, and a Mayo endoscopy sub score of 0 or 1) * Remission without steroids * Endoscopic healing rate with Mayo score 0 or 1 * UCEIS score * Histological healing (Nancy score) * Remission rate and remission rate without steroids at study visits and W48 * Quality of life evolution (evaluate visit W0 vs W14, W26, W38 and W48) * Patients satisfaction * Continuous response * Safety and tolerability * Anti-TNF pharmacokinetics * Number of visits in trial * Number of UC related hospitalizations * Number of colectomies * Treatment compliance (questionnaire) * Patient adhesion (questionnaire) * Medico-economic analysis

Critical Limb Ischaemia (CLI), the final stage of arterial disease, is a therapeutic emergency whose prognosis depends largely on the time taken to diagnose it. The growing prevalence of this condition and the associated healthcare costs make it an important public health objective. Diagnostic criteria for Critical Limb Ischaemia differ between learned societies and countries. Its diagnosis is most frequently based on the combination of a clinical criterion (ischaemic decubitus pain and/or necrotic wounds, with a time to onset \> 2 weeks) and a haemodynamic criterion (ankle systolic pressure (ASP) \< 50mmHg or toe systolic pressure (TSP) \< 30 mmHg or transcutaneous oxygen pressure (TCPO2) \< 30 mmHg). Recent studies have highlighted the importance of pulsed Doppler flow analysis in quantifying arteriopathy of the lower limbs, both by systematically analysing flow modulation and by measuring the systolic rise time of distal arteries (dorsal artery of the foot and lateral plantar artery). The main aim of this study is therefore to validate a reliable and accessible diagnostic tool for screening patients suffering from CLI so that they can be referred to a reference centre as early as possible.

Cannabinoid hyperemesis syndrome (CHS) is characterized by incoercible abdominal pain and vomiting in patients with chronic cannabis use. Patients are relieved by hot showers, an easily performed diagnostic test. The prevalence of this syndrome in France is not well known. A single French study from 2021, carried out in two Marseille emergency departments, estimated a 1.6% prevalence of CHS (48 cases / 2848 patients) in patients consulting for acute abdominal pain with no etiology found over a 10-month period. Cannabis is the most widely used illicit substance in France. France is also the second biggest cannabis consumer in Europe, with around 11% of the French population currently using the drug (use within the year). Despite growing attention to CHS, the diagnosis and management of this syndrome remains difficult, with repeated visits to emergency departments often required before a diagnosis is made. What's more, once the diagnosis has been made, the severity of symptoms can lengthen the emergency room length of stay. Main objective: To estimate the incidence of cannabinoid hyperemesis syndrome among patients admitted on a first visit for abdominal pain and/or vomiting to the Maine et Loire emergency department. Primary endpoint: The incidence of cannabinoid hyperemesis syndrome among patients presenting with abdominal pain and/or vomiting, consulting adult emergency departments in Maine et Loire. Cannabinoid hyperemesis syndrome will be considered in all patients admitted for abdominal pain and/or vomiting, who are regular cannabis users (weekly use for more than 6 months declared by questionnaire) and in whom no other etiology is accepted after any additional examinations. Research plan and procedure: It is an observational, prospective, multi-center cohort study. Participation in the study is offered to any emergency room patient who meets all inclusion criteria and none of the non-inclusion criteria. Patients are included after reading the information note. Consent is obtained on a no-objection basis. A questionnaire is given to participants via a QR code with an identification number generated by the investigating physician. This QR code opens an online questionnaire that the patient can fill in while in the emergency department. In the absence of access to the QR code (no cell phone), the questionnaire will be given to the participant in paper format by the investigating physician. It will be collected at the end of the inclusion visit. Participants who have revealed cannabis use (at least 1 time per week for at least 6 months) via the questionnaire are followed up at 3 months (+/- 15 days) by telephone to assess the evolution of symptoms, any recurrences, medical treatment and whether or not cannabis has been withdrawn. Inclusion criteria: * Patients aged 18 to 65 years, * Consulted an adult emergency department in Maine et Loire for abdominal pain and/or vomiting for the 1st time during the study period. Non-inclusion criteria: * Refusal to participate in the study * Patient unable to answer the questionnaire (allophone, under guardianship, under protection, incapable of major age, in the process of legal proceedings) * Pregnant women Number of research participants: At present, there are no data on the incidence of CHS in the French literature. In order to assess the number of subjects required, we made a projection based on the only French study to date. In this study, carried out in two departments in Marseille, the percentage of patients with CHS among those consulting the emergency department for acute abdominal pain was 1.6%. Thus, assuming that the proportion of the event will be identical to that of the study carried out in Marseille, i.e. 1.6%, it would be necessary to recruit 3,000 people with abdominal pain and/or vomiting to have around 50 patients with CHS. Research duration: Inclusion period: 12 months Duration of participation: 3 months +/- 15 days (for patients with CHS) Study duration: 15 months

Acute respiratory distress syndrome (ARDS) is a major public health problem affecting approximately 10% of patients in the intensive care unit (ICU) and 23% of all patients on a breathing machine (mechanical ventilator). The short-term mortality of patients with ARDS is approximately 40% and better ventilation of these patients has the greatest potential to improve outcomes. The lungs in patients with ARDS are severely inflamed which reduces lung volume and their ability to stretch, making ventilation difficult and dangerous. However, mechanical ventilation is the mainstay of supportive therapy. Although it is life-saving, it can also can generate secondary injury and inflammation, called ventilator-induced lung injury (VILI). The investigators know that inadequate mechanical ventilation worsens outcomes but are uncertain of the optimal way to manage ventilators at the bedside. Furthermore, ARDS is challenging because there is no treatment for the alveolar-capillary leak characterizing this syndrome; aside from treating the underlying cause, the only supportive therapy is mechanical ventilation. This is specially the case for COVID-19 induced ARDS. Despite best practices, over-distension of the lung or inappropriate positive end expiratory pressure (PEEP) is common. Finally, once spontaneous breathing has resumed and is assisted by the ventilator, an additional phenomenon occurs, called patient self-inflicted lung injury. The drive for breathing in many patients is stimulated by lung inflammation, and strong breathing efforts can generate high distending pressures, causing lung (and systemic) inflammation and organ damage. Whether the management of COVID-19 induced ARDS should differ from all other ARDS has been debated at length but has no clear response Recent advances in our understanding of bedside physiology (airway closure, recruitability, lung distension, respiratory drive) can now be applied for an individual titration of mechanical ventilation.

The advent of CDK4/6 inhibitors has changed the outlook of patients with metastatic hormone receptor-positive (HR+) HER2- breast cancer. Moreover, including CDK4/6 inhibitors in the adjuvant treatment regimens strategies has led to significant gains in disease-free survival. The phase III NATALEE trial demonstrated the efficacy of an adjuvant three-year treatment with ribociclib in prolonging invasive disease-free survival (iDFS) in patients with intermediate and high-risk HR+ HER2- early breast cancer. Contrarily to similar studies of CDK4/6 inhibitors in this setting, NATALEE included a group of patients with intermediate clinical risk (pT1-2 pN1, pT3-4 pN0 or pT2 pN0 with histological grade 3 or grade 2 with Ki67≥ 20%). These patients are usually considered for adjuvant chemotherapy based on their clinicopathological conditions or the results of a genomic signature (e.g. Oncotype Dx). Nevertheless, the benefit of adjuvant chemotherapy in these patients is uncertain (and likely small) in the context of an adjuvant treatment strategy that includes a CDK 4/6 inhibitor. As such, a de-escalation trial could demonstrate that patients with intermediate-risk breast cancer treated with CDK4/6 inhibitors could be spared the dreaded chemotherapy side effects while ensuring similar survival outcomes. In order to be generalizable and practice changing, a trial in this setting should aim to be as pragmatic as possible, particularly in inclusion criteria, with the required resources for patient inclusion and delivery of care being as similar as possible to those employed in usual care. As such, chemotherapy eligibility should be defined similarly to routine clinical practice in the participating centers (i.e. using routine clinicopathological parameters and/or genomic signatures). While single-arm designs could help address non-inferiority in the previously mentioned setting, they are usually compared to historical controls and lack external validation. Moreover, in some settings, like early breast cancer, the standard of care may change relatively quickly (e.g. Oncotype Dx-based chemotherapy de-escalation or adjuvant CDK4/6 inhibitors use), rendering the comparison to historical controls challenging, limiting the study conclusions and their impact on clinical practice. Finally, there is no consensus on the optimal non-inferiority threshold in single-arm trials using historical controls as a comparator. As such, randomized controlled non-inferiority trials with a strict non-inferiority margin remain the gold standard design to prove that a de-escalated treatment regimen is safe and advantageous, and the only ones capable of producing level IA evidence according to ESMO (Trapani et al., Annals of Oncology 2022).

The clonal architecture of myelofibrosis patients is still little described. Inconsistent results in terms of the prognostic value of some mutations are observed in the literature, in particular concerning ASXL1 mutations. We assume that a better understanding of the clonal architecture of ASXL1-mutated myelofibrosis could help refining the prognostic impact of ASXL1 mutations. This study aims to evaluate a multicenter cohort of 50 patients. Blood of patients will be collected within 18 months of diagnosis. After 4 years of follow-up of the patient as part of his usual care, data on survival and leukemic transformation will be collected.

This non-interventional study will investigate the effectiveness withT-DXd, the demographic and clinical characteristics of the patients, treatment patterns, tolerability, management of adverse drug reactions (ADRs), and patient experience of T-DXd in patients with HER2-low unresectable and/or metastatic breast cancer. Patients will be treated according to the proposed indication statement in the Summary of Product Characteristics (SmPC). No drug product will be administered as part of this study. Data on conventional chemotherapy (i.e., including but not limited to capecitabine, eribulin, gemcitabine, paclitaxel and nab-paclitaxel) will also be collected in a disease registry part of the study.

Multicentre randomized non-inferiority trial comparing cotrimoxazole to standard antibiotic therapy for enterobacterial VAP. Selection of patients will be done by physicians in ICU. All clinically suspected VAP will be confirmed with a lung sample (preferably bronchoalveolar lavage or protected distal specimen, otherwise endotracheal aspiration). Patients with a microbiologically confirmed VAP due to an Enterobacteriaceae susceptible to cotrimoxazole and at least one antibiotic of the empiric antibiotic therapy (based on international recommendations) will be included. After written informed consent, they will be randomized (1:1), using a computer-generated randomization scheme of various-sized blocks, stratified by presence of septic shock at VAP diagnosis and by presence of COVID-19 pneumonia on ICU admission, through a centralized 24 hours internet service (CleanWEB™) to cotrimoxazole, or best standard of care (either a beta-lactam or a fluoroquinolone), after randomization for a total duration of 7 days (including empiric initial appropriate treatment). Posology and modalities of antibiotic administration will be optimized based on most recent recommendations for ICU patients. Because antibiotic therapy will be variable in the control group, single or double blind is not appropriate. Daily follow-up until death or ICU discharge or day 28 will be performed (vital status, antibiotic therapy, new infection, Clostridium-difficile infection). Clinical (arterial blood gas, temperature, haematology, tracheal secretions) and radiological cure (chest X-ray) will be assessed at Day 7. Systematic MDR bacteria screening will be performed weekly and at ICU discharge. Vital status will be assessed at day 90. Alive patients leaving ICU before 90 days will be contacted by phone (if discharge at home) or by interview at hospital (if transferred in a different ward). Assessment of the clinical and radiological cure by an independent committee (1 specialist in infectious disease and 1 intensivist), blinded of the randomization arm (PROBE methodology).