Wetzlar-naunheim, Germany

Compression Is Life In Cardiac Arrest - Human Study (CILICA-HS).

The management of out-of-hospital cardiac arrest is complex and multifactorial. With an incidence between 5 and 15 per 10,000 (46,000 patients per year in France) and a survival rate of only 5% to 15%, the room for improvement remains significant even today and is based on fast and optimal care. Thus French and international recommendations insist on the central element of external chest compression (ECC) and especially its quality (Monsieurs KG and Al. Resuscitation 2015; 95: 1-80). Improving the chest compression fraction (CCF) by limiting time without cardiac massage (No-Flow) is a second major point of the recommendations (Vaillancourt C and Al. Resuscitation 2011; 82: 1501-7). The survival of cardiac arrest victims is closely related on this No-Flow time. The principle of the chain of survival (early warning - ECC - defibrillation - resuscitation) implies that the deterioration of a single link threaten the whole of the care. To meet these qualitative needs, ECC guidance devices have been developed. They make possible to improve the quality of the ECC achieved (Hostler D and Al. BMJ 2011; 342d512). Their use is one of the areas of improvement mentioned in the recommendations. Our team studied in simulation the prolonged effects of guidance on the quality of the ECC during a prolonged resuscitation, with encouraging results (Buléon C and Al. Am J Emerg Med 2016; 34: 1754-60). The investigators propose a study evaluating the efficiency of the guidance of the ECC and the impact of the time of relay on the CCF. The investigators formulate two hypotheses that they wish to test simultaneously using a 2x2 factorial design, in a multicenter randomized trial. The first assumption is that a 4-minute relay rate improves the CCF (by reducing the No-Flow time) compared to the currently recommended 2-minute relay rate. The second hypothesis is that a guiding device improves the quality of the ECC. This study should, over a period of 2 years, include 500 patients with cardiac arrest for whom specialized resuscitation is undertaken. The investigators hope by this study to improve the knowledge on the optimal rhythm of the ECC and to validate "in vivo" the interest for the guidance found on manikin. This study should make it possible to clarify the recommendations with a high level of evidence in this field and thus contribute to improving the prognosis of the victims of an out-of-hospital cardiac arrest. Cardiac arrest (CA) remains a challenge for pre-hospital care. With an incidence of between 5 and 15 per 10,000 (46,000 patients per year in France) and a survival rate of only 5% to 15%, there is yet room for improvement in treatment to reduce morbi-mortality of these patients. The quality of cardiopulmonary resuscitation (CPR) is at the heart of the last three five-year recommendations. (1-3) The latest recommendations emphasize the importance for professionals to work at the highest quality of CPR and External Chest Compression (ECC) possible. (3) The ratio of the time during which the ECC is performed (Low-Flow) to the total time of the resuscitation is referred to as the Chest Compression Fraction (CCF). During CPR, it is essential for the patient's survival to minimize ECC disruption times and therefore to increase the CCF, as this is an independent element in CA survival's improvement. (4,5) ECC interruptions are deleterious to at least two titles. First, they are a source of direct stop in cerebral and coronary perfusions potentially altering the neurological prognosis and the probability of Return of Spontaneous Circulation. (6) Secondly, the quality of the cardiac output generated by the ECC at the time of resuming of the ECC after an interruption is less good for more than 30 seconds: time need for that several chest compressions can restore the best flow possible. (6,7) Reducing these interruptions and improving the ECC is therefore a major goal of improving CPR. The guidelines are that CCF must be greater than 60% and some experts estimate that a CCF of 80% is possible. (8,9) The outcome of patients with pre-hospital CA is significantly, positively and independently correlated with the consistency to different CCF targets, ECC frequency, ECC depth, and brief pre-external electric shock pause (<10 seconds). (10) There is evidence that ECC's guidance improves adequacy to guidelines and allows to be closer with the ECC frequency, depth and release objectives. (11) The investigators have proved in simulation that the guidance of the ECC delays the deterioration of the overall quality of the ECC and its components (frequency, depth and relaxation) related to fatigue during a prolonged ECC beyond the 2 ECC relay minutes currently recommended. (12) Strategies to get closer with the guidelines regarding the quality of the ECC associated with an improvement in CCF should add or even enhance their beneficial effects for the management of CA victims. Achieving high quality CPR requires the measurement of quality of CPR (ECC and CCF). (13,14) This idea of a support strategy enhanced by "bundles" of concepts is developing in the literature. Thus Cheskes S et al. Describe a "high quality CPR" such as the association of a CCF greater than 70% and achievement of the objectives of the recommendations for the frequency and depth of the ECC. (15) The place of devices for guiding the quality of the ECC needs to be specified. Indeed, studies of their use in real-life situations are criticized for their methodological qualities and their size. (16) The use of a real-time guidance device is proposed as a possibility in the latest guidelines without being an indispensable element due to the lack of current evidence. (3) Its use or non-use does not imply any obvious loss of chance for patients. Evidence as to its usefulness therefore remains to be sought. For this reason, the investigators wish, through an original, randomized, multi-center study, to provide some answers to the questions about the possibility of an improvement in CCF by the lengthening of the time between two ECC relays and the effect of guidance on the quality of the ECC. The design of the study will also allow to approach a possible combined effect of ECC relays rhythm and guidance. The currently recommended duration of a two-minute ECC cycle between two relays does not have a consistent evidence based and corresponds to a duration for which the ECC effort can be maintained in principle with efficiency. (3) Objective measures have shown that the quality of the ECC can be maintained beyond 2 minutes. Extending the duration of an ECC cycle could reduce the number of ECC interruptions and thus improve the CCF. The investigators therefore formulate two hypotheses that they wish to test simultaneously using a 2x2 factorial design, in a multicenter randomized trial. The first assumption is that a 4-minutes relay rhythm improves the CCF (by reducing the No-Flow time) compared to the currently recommended 2-minutes relay rhythm. The second hypothesis is that a guiding device improves the quality of the ECC. The CPRmeter® (guidance device used in this study) will record data on the ECC and its quality (depth, frequency, relaxation, CPRmeter® use time, No-Flow time and Low-Flow time) as well as ECC guidance for the group which will benefit from it (the other group will have the screen masked by a screen cap). This study should, over a period of 2 years, include 500 major patients presenting a non-traumatic CA for whom a specialized CPR is undertaken. The investigators hope by this study to improve the knowledge on the optimal rhythm of the CEE and to validate "in vivo" the interest for the guidance found on manikin. This study should clarify the guidelines with a high level of evidence in this area and thus contribute to improving the prognosis of victims of out-hospital CA.

Status Epilepticus in the Critically Ill Patients

Impact of a Phone-based Cognitive and Behavioral Therapy on Food Addiction in Patients With Severe or Morbid Obesity

Morbid or severe obesity is a chronic pathology of multifactorial etiology that affects 4.3% of the French population. In these patients, eating disorders are frequent and must be managed as they are considered risk factors with poorer weight prognosis and lower quality of life. Some authors have proposed that the concept of food addiction (i.e., the existence of an addiction to certain foods rich in sugar, fat and/or salt) may make it possible to identify, among obese patients, a subgroup of patients that is more homogeneous in terms of diagnosis and prognosis. Food addiction is common in obese patients and is associated with higher levels of depression, anxiety, impulsivity, emotional eating and poorer quality of life. Nevertheless, we do not know the impact of managing this addiction on the future of these patients (food addiction, weight, comorbidities, quality of life). Telephone-based cognitive behavioral therapy intervention (Tele-CBT) is a treatment of choice for addictions, but there are inequalities in access to this treatment (distance between home and hospital, limited local resources of caregivers, constraints in patient availability) which require the therapeutic framework to be adapted to these constraints. A short Tele-CBT program has demonstrated its effectiveness in reducing bulimic hyperphagia in these patients (Cassin et al. 2016), but its effectiveness on food addiction, Body Mass Index and the evolution of metabolic complications related to obesity is still unknown. The evaluation of this program was limited to 6 weeks (American study), and we do not know if these results can also be extrapolated to France. The main hypothesis of this study is that in patients suffering from severe or morbid obesity and with food addiction, the performance of tele-CBT (intervention group: 12 sessions for 18 weeks) will be accompanied by a significant medium-term decrease in the prevalence of food addiction compared to usual management (control group).

Evaluation of the Impact of Taking American Ginseng for 8 Weeks on Fatigue in Patients Treated for Localized Breast or Gynecological Cancer

HYdrocortisone and VAsopressin in Post-RESuscitation Syndrome

For patients successfully resuscitated who got restoration of spontaneous circulation (ROSC) after cardiopulmonary resuscitation (CPR), the course is usually marked by a post-resuscitation syndrome including multiple organ failures of various intensity and anoxic brain damage. The cardiocirculatory failure usually dominates the clinical picture, and it often leads to multiorgan failure. This hemodynamic failure is multifactorial, including at various levels vasoplegia, myocardial dysfunction, endotoxin release and adrenal dysfunction and is at least partly related to a hormonal defect that could be counteracted by hormonal supplementation. Such a substitutive opotherapy by hydrocortisone and AVP could improve hemodynamic failure and decrease overall mortality in this setting. This trial is a superiority multicentric trial and patients will be randomized in a 1:1:1:1 ratio using an electronic CRF. Investigational medicinal products: - Arginin-vasopressin or AVP (REVERPLEG) The solution for infusion is prepared by diluting 40 I.U. REVERPLEG® with sodium chloride 9 mg/ml (0.9%) solution. The total volume after dilution should be 50 ml (equivalent to 0.8 I.U. AVP per ml). AVP will be administered according to mean arterial pressure to target a 65mmHg blood pressure for max 3 days. - HYDROCORTISONE HEMISUCCINATE Vials with lyophilisate (100mg hydrocortisone) are provided by SERB laboratory. Hydrocortisone hemisuccinate will be administered as a 50mg intravenous bolus every 6 hours after an initial dose of 100mg, for 7 consecutive days. Stop of treatment by hydrocortisone will be performed without tapering. Comparator treatment: placebos. 17 ICU centers in France will participate to this study targetting 380 patient's enrollment in the study.

A Physical Activity Program to Improve Quality of Life and Reduce Fatigue in Metastatic Breast Cancer

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.

Ribociclib Real-world Treatment Patterns and Clinical Outcomes Among Women With HR+/HER2- Advanced or Metastatic Breast Cancer in France

Included patients will be followed until the end of study, death or lost to follow-up even if ribociclib and ET are discontinued. The end of the study is defined as 3 years after the first visit of the last patient included (Last Patient First Visit [LPFV]). The total duration of the study will be 4 years and half (18 months of inclusion + 3 years of follow-up). Thus, a patient included at the beginning of the inclusion period will be followed for 4 years and half and a patient included at the end of the inclusion period will be followed for at least 3 years.

Non-invasive Early Oxygen- Reserve-index (ORI) Determination to Prevent Hypoxaemia During Endotracheal Intubation

The trial population will be adults (18 years of age or older) who need endotracheal intubation while hospitalized in ICU