Koyang, Kyunggi Province, Korea, Republic of

A Study to Learn About How Safe BAY 3389934 is, Its Suitable Dose, and How it Affects the Participants With Sepsis Induced Coagulopathy

A Pilot Study to Assess the Feasibility and Acceptability of Newborn Screening Using in Silico Panel-based Solo Genome Sequencing in France

Role of High-Throughput Whole Genome Sequencing for the Diagnosis and Care of Atypical Diabetes

The prevalence of diabetes is 7.4% in France among people aged 20 to 79 years in 2015. We must also consider "pre-diabetes" (subjects with glucose intolerance), whose prevalence is equivalent to that of diabetes (2012 estimate). The incidence of diabetes is exploding both for type 2 diabetes, which represents 85% of diabetes, and for type 1 diabetes, which represents 10% of cases and starts one out of two times before the age of 20. Diabetes typing is essential to guide therapeutic choices, particularly the use of insulin. This typing is based on the pathophysiology of the disease, distinguishing insulinopenia from autoimmune causes in type 1 diabetes, monogenic diabetes, secondary or atypical diabetes and type 2 diabetes, where insulinopenia and insulin resistance coexist. Thus, while a formal biological diagnosis is possible for some forms of atypical diabetes and for type 1 diabetes, no biological parameter is currently available for type 2 diabetes, which remains a diagnosis of exclusion. As a result, diabetes represents a source of diagnostic and therapeutic erraticism, amplified by the clinical heterogeneity of type 2 diabetes, which is obvious and underestimated, and by a clinical phenotyping of patients that is often defective. The economic consequences are important because the health costs are very different depending on whether or not patients are treated with insulin. Type 1 and type 2 diabetes are examples of chronic, non-transmissible, multigenic, multifactorial diseases. However, less than 10% of the heritability of type 2 diabetes is currently explained by the associated genetic variants. And although genetic tests exist to diagnose certain monogenic diabetes, this diagnosis is made in less than 20% of cases, mainly in the presence of an atypical clinical presentation of diabetes. Moreover, there is no reason to rule out the hypothesis of paucigenic forms, at the interface of monogenic diabetes and multigenic forms as usually envisaged, as has been observed in chronic pancreatitis, which is also accompanied by diabetes. The study will be conducted according to a randomized trial design comparing two diagnostic strategies defined as follows: - Control strategy: in silico analysis of a panel of validated genes (ISApanel - Diabetome 1). Patients recruited along the control procedure will stay in their group using current genetic diagnosis practices and standard of care that may differ from one center to another. - Intervention strategy: whole genome sequencing coupled with multidisciplinary conciliation meeting. We plan to randomize one patient in the control group for two in the intervention group. The main objective of the study is to assess the contribution of whole genome sequencing (WGS) coupled with a multidisciplinary conciliation meeting (MCM) on diagnosis of atypical forms of diabetes compared to an in-silico analysis of a panel of validated genes (ISApanel), corresponding to current practice. The target population is 1020 adults with atypical diabetes for whom it is possible to obtain a blood sample.

Gait Training Program with Blood Flow Restriction in Children with Cerebral Palsy - EMBRIN: Pilot Study

Context : Cerebral palsy (CP) is the leading cause of motor disability in children, with a prevalence of 1.77 cases per 1000 births. It is defined as a set of permanent developmental disorders of movement and posture, resulting from a non-progressive brain lesion affecting a developing brain. 60% of individuals with CP have a bilateral form. In this group, 98% of diplegics and 24% of quadriplegics will be "walkers", but more often than not with poor walking efficiency. In fact, these children show not only a reduction in walking speed, but also markedly reduced endurance. What's more, these children have reduced levels of physical activity, resulting in less participation in physical activities throughout their lives. Associated with these changes in motor activity, CP leads to morphological and architectural changes in the muscles, including reduced muscle volume, shorter muscle fascicles and increased intramuscular fat. These "bad" adaptations contribute to a reduction in muscle strength and power, leading to a progressive decline in functional capacity in adolescence and adulthood, associated with a sedentary lifestyle. In individuals with CP, gait training and muscle strengthening programs, carried out separately, have shown, respectively, a relative efficacy in improving walking activity and lower limb muscle strength. Rare programs combining these two interventions have been shown to be of interest in mildly affected children. In the geriatric population (without CP), where strengthening with heavy loads may be contraindicated and difficult to implement, Blood Flow Restriction (BFR) training has attracted considerable interest due to its simplicity of use and effectiveness. Indeed, the application of an inflatable cuff to the proximal part of a limb restricting blood flow, combined with low-load muscle strengthening, has shown similar effects to high-load strengthening on muscle function. BFR was also combined with functional training, and this combination showed superiority over functional training alone in improving functional activity. BFR does not appear to cause side-effects in typical adolescents, and has never been studied in children with CP. Objectives and evaluation criteria : Primary objective: to study the effect of a 10-week gait training program combined with simultaneous blood flow restriction (BFR), using a commercially available device, on the walking speed of children aged 8 to 18 with bilateral spastic cerebral palsy. To this end, a comparison of patients' walking speed will be carried out between the period D-70 to D0 (standard rehabilitation) and the period D0 to D+70 (walking training program + BFR). Walking speed will be assessed by the 10-meter walk test. The evaluation criterion is the change in walking speed between D-70-J0 and D0-J+70. Secondary objectives and evaluation criteria To assess the effect of this gait training program combined with BFR on the following levels of the International Classification of Functioning and Disability: Functions : - Isometric strength of plantar flexors, knee extended and flexed, by electronic hand dynamometer (DEM) - Isometric strength of knee flexors and extensors by DEM - Isometric strength of hip abductors by DEM - Pain intensity by numerical rating scale (NRS-11) (somato sensory function) Activities : - Walking endurance by 6-minute walk test - Spontaneous and maximum walking speeds using the 10-meter walk test - Global motor activity via Gross Motor Function Measure - 66 (GMFM-66) - Spatial gait parameters: stride length, step length, base of support, step angle, and temporal gait parameters: speed and normalized speed, cadence, percentage of right and left support phase, right and left cycle time and double support time (Gaitrite) Participation: - Achievement of functional goals in terms of performance and satisfaction using the Canadian Occupational Performance Measure (COPM) - Achievement of daily activities and mobility using the Pediatric Evaluation of Disability Inventory as a computer adaptive test (PEDI-CAT) - Evaluate the feasibility of this gait training program associated with BFR. Feasibility will be assessed by analyzing the percentage of children completing 80% of the training program. - To evaluate the tolerance of the EMBRIN program of this gait training program associated with BFR. Tolerance to the training program will be studied by assessing pain before, during and after gait training with the NRS-11 scale (23), as well as by notifying the occurrence of intercurrent medical events or complications. The evaluation criteria are : - Change in NRS-11 pain score during gait training sessions; - The occurrence of intercurrent medical events or complications. - Evaluate participant satisfaction using the CSQ-8 satisfaction questionnaire. Research scheme and progress This is a single-center prospective experimental pilot study designed to assess the feasibility, tolerability and effect of a 10-week gait training program combined with simultaneous blood flow restriction (BFR) on the walking speed of children, aged 8 to 18, with bilateral spastic cerebral palsy. The children will receive a 10-week intervention (1 week of habituation without BFR + 9 weeks with BFR) comprising 3 30-minute treadmill sessions per week. At each session, the first 5 minutes will enable a gradual increase in speed, and then the maximum tolerated walking speed will be sought. Maximum speed corresponds to the walking speed maintained by the child for an effort of between 5 and 7 on Borg's 10-point VAS. The rehabilitator will encourage the child to maintain this speed and provide feedback on performance. The BFR setting will maintain an occlusion, at the root level of both lower limbs, of 60% of the total occlusal pressure. During each session, pain will be assessed using the NRS-11 before the restriction is placed, after 15 minutes of walking and within 5 minutes of the restriction being removed. In the event of participant request or premature termination of the session, a pain assessment will be added. A pain assessment will also be carried out 24 hours after the training session. Functional assessments carried out at baseline at T0 (D0-70d) and T1 (D0) will explore the usual evolution of walking speed in children receiving usual care. Assessments at T2 (D0+35d) will explore the evolution of variables of interest halfway through the intervention period. Evaluations at T3 (D0+70d) will assess the immediate effects of therapy. Functional assessments will be carried out again at T4 (D0+100d) and T5 (D0+160) to evaluate the medium-term effect of therapy. Research duration Inclusion period: 24 months Duration of participation: 8 months maximum Study duration: 32 months

A French Multicenter Observational Retrospective Study of Rare Primary Liver Cancers

The aim is to describ rare primary hepatic cancers clinical, histological and radiological features, to obtain a biological tumor and blood collection, and to evaluate the efficacy of treatments received in clinical practice in order to determine optimal therapeutic sequences.

Phase II Efficacy Study of Repotrectinib in Frail and/or Elderly Patients With ROS1-rearranged Advanced NSCLC

This is a national, multicenter, phase II, prospective, open label, non-randomized, interventional study. Frail (PS≥2) and/or elderly patients (≥70 years) with histologically/cytologically proven stage IV or stage III non-eligible to local treatment NSCLC harboring an ROS1 gene rearrangement treated by Repotrectinib (160 mg twice a day (BID), until progression or unacceptable toxicity) in first or any line.

Impact of an Early and Extended Rehabilitation Program Combining Individually Tailored Nutrition and Physical Activities on Patient Outcomes After Invasive Mechanical Ventilation and Vasopressor Therapy in the ICU

A Phase III, Randomised Study of Adjuvant Dato-DXd in Combination With Rilvegostomig or Rilvegostomig Monotherapy Versus Standard of Care, Following Complete Tumour Resection, in Participants With Stage I Adenocarcinoma NSCLC Who Are ctDNA-positive or Have High-risk Pathological Features

The primary objective of the study is to assess the efficacy and safety of adjuvant Dato-DXd in combination with rilvegostomig relative to SoC, after complete surgical resection (R0) in participants with Stage I adenocarcinoma NSCLC who are ctDNA-positive, as determined by the Sponsor-designated ctDNA assay, or have at least one high-risk pathological feature.

Epidemiological Study of a Prospective Cohort of Patients Aged 60 and Over Managed for Acute Myeloid Leukemia (AML) and Receiving Intensive Induction Therapy

Best Hypnotic Drug Choice for Rapid Sequence Induction in the Operating Room