Behren Les Forbach, France

Best Antithrombotic Therapy in Patients With Acute Venous ThromboEmbolism While Taking Antiplatelets

Up to one third of VTE patients receive concomitant AP therapy, with conflicting results on patient outcomes. Concomitant therapy (AC+AP) has been associated with a higher risk of bleeding (up to 3-fold) when aspirin was associated with vitamin-K antagonist (VKA) in a multicenter cohort study, or with direct oral anticoagulants (DOACs) for acute VTE in a post-hoc subgroup analysis. Conversely, patients with acute VTE in whom clinicians decided to maintain AC+AP were found to have an increased risk of MACCE without any higher risk of bleeding, in a multicenter registry. However, in most cases, the type (aspirin or another) and indication (primary versus secondary prevention) of AP was unknown, as was the duration of the combination AC+AP, and therefore these observational results may be confounded. Therefore, there is persistent equipoise regarding the benefit/risk of combining an antiplatelet therapy with anticoagulation in patients undergoing treatment for VTE, when there is a prior history of atherosclerotic cardiovascular disease. This may explain why clinical practice varies widely. Considering the conflicting data about the risk of bleeding in patients on AP therapy for secondary prevention, who need to start full-dose anticoagulant therapy for acute VTE, a randomized trial comparing the two strategies, in patients with acute VTE and with history of stable atherosclerotic cardiovascular disease is needed and justified. The investigators hypothesize that a strategy based on the prescription of a full-dose AC therapy alone will decrease the risk of bleeding, when compared to the the strategy of combined AP and full-dose AC therapies, and that this strategy will translate in a positive net clinical benefit (a composite of clinically relevant bleeding, recurrent venous thromboembolism, and major adverse ischemic cardiovascular and cerebrovascular events).

Oxygen Therapy Remote Monitoring in COPD Patients.

The observational study consists in collecting physiological data (cardiorespiratory and physical activity) and use of the oxygen therapy device in real life during the first months after the initiation of treatment. For this purpose, two connected medical devices will be provided to each patient during 2 periods of 2 weeks (weeks 6 to 8 then weeks 12 to 14 after the initiation of oxygen therapy). The devices are: 1/ a connected watch that continuously measures vital parameters (heart rate and blood oxygen saturation), and physical activity parameters (no. of steps, distance, duration of effort), and 2/ a Teleox device that remotely monitors patients equipped with an oxygen source (it measures the oxygen flow rate requested by the patient, the duration of use of the oxygen source, and the breathing rate). Study design: a cohort of 250 patients with COPD newly initiated a long term oxygen therapy will be enrolled in the study and follow-up over 6 months. Data will be collected by lung specialists and home health care provider teams at 2 months, 3.5 months and 6 months post-initiation of oxygen therapy.

A Clinical-biological Prospective Cohort of Patients With BRAFV600E-mutated Metastatic Colorectal Cancer

Despite substantial progress made in the first- and second line mCRC settings, there are still unmet clinical needs for patients harboring BRAFV600E mutations, especially those with microsatellite stability (MSS) / proficient mismatch repair (pMMR) tumor. The overall survival and access to different treatment in the real-life setting are unknown. Moreover, patient prognosis remains poor and therapeutic resistance to combinations with BRAF inhibitors, is at present, nearly universal. Therefore, it seems essential to prospectively collect clinical and biological data about this rare mCRC subtype. These data will allow us to improve knowledge and to identify clinical and biological factors that could drive therapeutic decisions, predict resistance to treatments, and that are prognostic for survival. In this context, we designed this large, prospective, cohort study to collect clinical data and biological samples to be used for research but also to gather real-world clinical data concerning the treatments and the survival outcomes in patients with BRAFV600E mCRC. This collection of clinical and biological data (tumor tissue and blood samples) will allow us to identify predictive and prognostic biomarkers with several research work packages planned: i. To evaluate the circulating tumor DNA (ctDNA) during the metastatic first-, second-, and third-line treatment to: - Evaluate its positive and negative predictive value. - Identify molecular alterations preceding and explaining clinical resistance during BRAF/EGFR inhibition therapy and immunotherapy. ii. To evaluate BRAFV600E mCRC immune environment both at the tumor and blood level (immunomonitoring). iii. To study specific the dMMR/MSI BRAFV600E subgroup. Furthermore, the data collected will describe the therapeutic management of BRAFV600E mCRC patients in the routine-practice setting which will bring very useful data. The results of the COBRAF study could lay the groundwork to better understand BRAFV600E mCRC and to identify prognostic and predictive biomarkers helping the development of new therapeutic approaches in this population.

Determination of the Biological Activity of Serum From Patients

The written consent of the subjects will be obtained after full information of the aims, nature and possible risks of the study. Before inclusion, subjects will undergo a medical check-up including an interview on personal and family history and drug treatments taken as well as a standard medical examination including weight, height and blood pressure measurement. . Their compliance with the inclusion / exclusion criteria will be verified during this review. An interview with personnel involved in the research (a dietician / study Research clinic assistant, etc.) will also be carried out as well as a biological selection assessment. As part of this study, the subjects will come a total of 7 times to the Emile ROUX hospital in Le Puy en Velay. The probiotic treatment will begin between 1 and 3 weeks after the inclusion visit. The volunteers / patients recruited will have a volume of blood sampled and a stool collected before the start of the probiotic treatment (T = 0) and at the end of the treatment (T = 4 weeks). The study consists of three periods of probiotic treatment of 4 weeks each interspersed with a wash-out period of 3 weeks in accordance with the recovery period necessary between two blood samples. The sera thus obtained will then be analyzed to determine their biological activity with regard to the induction of changes in the behavior of bone cell models: osteoformin cells (osteoblasts) and osteo-resorbent cells (osteoclasts).

Evaluation of Omentopexy on Gastro-oesophageal Reflux Following Sleeve Gastrectomy

Auvergne-Rhône-Alpes-Limousin Research Database for Still's Diseases in Children and Adults

Evaluation of a Nurse-led Program for the Prevention of Complications of Long-term Corticosteroid Therapy

It is a PROBE (Prospective Randomized Open trial with a Blind Evaluation) study, in which the primary endpoint will be assessed at week-52 by an independent physician blinded to the participant's allocation group. The target population is adult patients initiating a first sequence of long term corticosteroid therapy, to the exception of onco-hematological indications, severe chronic renal failure and organ transplant. Patients in both groups will have baseline and week-52 standardized visits including clinical evaluation, routine biology, dual-energy X-ray absorptiometry and quality of life assessment (SF-36). Corticosteroid consumption will be collected throughout the study using a dedicated notebook. At the week-52 visit, the burden of adverse events related to the use of corticosteroids will be assessed through the glucocorticoid toxicity index (GTI), completed by the blinded physician.

A Study Comparing Abelacimab to Apixaban in the Treatment of Cancer-associated VTE

Cancer associated thrombosis (CAT) is a severe medical condition which is characterized by high incidence of Venous thromboembolism (VTE) recurrence and high risk for bleeding. The two most common treatments today are low molecular weight heparin (LMWH) and direct anticoagulants (DOACs), in which each has limitations. DOACs are administered orally and are seen as a more convenient alternative though associated with bleeding risk; further, some cancer patients have difficulty swallowing or develop vomiting which leads to unpredictable pharmacodynamic effects with oral therapy. The ANT-007 study will compare treatment with abelacimab monthly administration to apixaban twice daily administration over a 6-month treatment. The study outcomes include VTE recurrence, bleeding event and treatment discontinuation at 6 months

Combination of Baricitinib and Anti-TNF in Rheumatoid Arthritis

Intensive combination therapies have revolutionised the management of solid neoplasms, hematologic malignancies, and acquired-immune-deficiency syndrome. These intensive strategies are based on the need to obtain rapid control of disease activity to afford the chance of stable full remission and avoid irreversible complications. The same goal applies to management of RA. Because current therapeutic strategies may fall short of these target goals and fail to improve quality of life in some patients, novel approaches are needed to improve outcomes. RA is a complex disease involving numerous cell types and inflammatory mediators of innate and adaptive immune systems. The investigators are aware that most of combination bDMARD strategies have been associated with little or no incremental benefit in efficacy compared to single-biologic therapy. However, our study will target mechanisms that differ from those in previous studies. Strategies that simultaneously target different pathways involved in the pathogenesis of RA may enhance treatment responses in patients with RA. Of note, baricitinib does not directly block signalling downstream of TNF, even if an indirect effect on TNF production is likely to occur. Targeting multiple inflammatory cytokines in combination may lead to more effective treatment and enhanced clinical responses in patients with RA compared to the current second-line strategies. The different mechanisms of action of baricitinib and anti-TNF, should ensure the efficacy of the combination. No concurrent trial evaluating similar strategies is registered at ClinicalTrial.gov.

Physical Restraints in Intensive Care Unit Patients

Current study has been designed to measure the impact of an original tool intended to guide the decision to use physical restraints in ICU patients. In a multidisciplinary fashion, we have created a decision-making tool based on objective criteria in an attempt to reduce subjectivity that currently exists in this process of physical restraints use. This tool corresponds to a decision tree based on several criteria: - the RASS (Richmond Agitation-Sedation Scale) score that assesses patient's state of sedation and agitation. This neurological state could help to determine level of arousal possibly favorizing self-inflicted risks; - the existence of a delirious state (or delirium), assessed by the CAM-ICU (Confusion Assessment Method for the Intensive Care Unit). This tool is used to detect and assess the presence of a delirium. In the case of a positive CAM-ICU, the patient presents a delirium and may therefore have unsuitable gestures; - the recent modification of pharmacological-induced sedation allows us to take into account a change in the dosage of infused sedation molecules in order to assess whether the patient may soon find himself in an awakening phase. This transitional phase makes patient's neurological state unstable and can lead to agitation and/or confusion; - the level of invasive equipment conditioning, defined by the type of device that equips the patient. Three levels of conditioning (C1, C2 and C3) have been defined, ranging from the least to the most harmful in the case of an unexpected removal: - Level C1 includes peripheral venous catheters, naso-gastric tubes and urinary catheters; - Level C2 includes endotracheal tube, central and arterial lines, renal replacement catheters, drains: thoracic, encephalic or abdominal; intracranial pressure sensors, Swan-Ganz catheters, redons, PICC (peripherally inserted central catheter) lines and Midlines; - Level C3 includes veno-venous and veno-arterial ECMO (extra-corporeal membrane oxygenation), intra-aortic counter-pulsion balloons and electro-systolic training probes; - the presence of patient's family and their adherence to his or her supervision. Families play a key role in patient's care. Their presence might sometimes soothe and reassure the patient. Their adherence and participation to patient's supervision may allow health care team to consider adequate compliance. Regular re-evaluation should then be carried out when they leave patient's room; In order to facilitate the work of caregivers, this decision-making tool has been transcribed into an electronic version that can be accessed online, on a tablet or a computer. Once the above criteria have been filled in, a proposal for whether or not to use physical restraints, as well as main variable criterion for reassessment of this use. This last criterion makes it possible to know the decisive factor that suggested the decision to use restraints or not. In order to evaluate the impact of this tool on caregivers' decision to use physical restraints, three periods have been planned: a control period in order to evaluate actual practices, a period of training and implementation of the tool, so that each professional is rendered familiar with its use, and finally an intervention period during which the ARBORea tool will be used to suggest physical restraints use.