title: Comparative Study of Neoadjuvant Chemotherapy With and Without Zometa for Management of Locally Advanced Breast Cancers

acronym: NEOZOL

summary:
Breast cancer is the leading female cancer by a very wide margin in France. Despite widespread breast cancer screening, many cases of breast cancer are discovered at a locally advanced stage. The tumoral consequences of a cancer size greater than 3 cm are: increased risk of metastasis and death and, most often, impossibility of performing breast-conserving surgery (a mastectomy is usually advisable in case of a first surgical procedure). It is increasingly recommended to treat locally advanced breast cancers with neoadjuvant chemotherapy. Very numerous studies have shown that by proceeding that way, the oncologic prognosis was not harmed and, on the contrary, it was possible to obtain sufficient tumor response to allow breast-conserving treatment in more than 60% of cases.

The use of zoledronic acid (Zometa) has an established place in the management of malignancies with a predilection for skeletal involvement (in particular metastasis). Although the main target of biphosphonates is the osteoclast, there is also preclinical data indicating that biphosphonates can have effects on cells other than osteoclasts, including tumor cells. Anti-tumor activity including inhibition of tumor cell growth and induction of tumor cell apoptosis, inhibition of tumor cell adhesion and invasion, and anti-angiogenic effects have been demonstrated. In addition several in vitro studies have shown that Zometa causes synergistic induction of breast cancer cell apoptosis when combined with clinically relevant concentrations of chemotherapy drugs such as paclitaxel and doxorubicin. Therefore testing of combinations of biphosphonates with these agents in breast cancer is of significant interest.

In the context of locally advanced breast cancers, the combination of a bisphosphonate with neoadjuvant chemotherapy appears to have an important potential: preventing possible bone metastases, but also possibly amplifying the efficacy of the chemotherapy's tumoricidal activity, both on the primary tumor and on potential metastatic localizations.

So it appears that, the use of bisphosphonates in a neoadjuvant situation presents a potentially favorable benefit-risk ratio. That is why we are proposing to perform a prospective randomized multicenter comparative study to evaluate 2 systemic neoadjuvant treatments, one with Zometa and the other without Zometa, in patients with locally advanced breast cancer. Zometa will be administered according to the usual administration procedure: one infusion every 3 weeks.

The therapeutic response will be evaluated by studying the different biological markers (circulating blood and bone marrow tumor cells, serum cell apoptosis and neoangiogenesis markers, bone resorption markers, etc.), but also by analyzing clinical, radiologic, and histologic response and by breast conservation rates. The impact of other factors that may affect therapeutic response will be taken into account: aggressivity of the tumor, presence or absence of tumor receptors, tumor stage, etc.

The purpose of the study is to show a marked benefit of treatment with Zometa in managing locally advanced breast cancers with synergistic action of the neoadjuvant chemotherapy and improvement in the laboratory parameters of tumor aggressivity. These markers will be used as surrogate markers of long term outcome.

ReferenceCitation: Lelièvre L, Clézardin P, Magaud L, Roche L, Tubiana-Mathieu N, Tigaud JD, Topart D, Raban N, Mouret-Reynier MA, Mathevet P. Comparative Study of Neoadjuvant Chemotherapy With and Without Zometa for Management of Locally Advanced Breast Cancer With Serum VEGF as Primary Endpoint: The NEOZOL Study. Clin Breast Cancer. 2018 Dec;18(6):e1311-e1321. doi: 10.1016/j.clbc.2018.07.005. Epub 2018 Jul 10.

family: Lelièvre

full_name: Loïc Lelièvre

given: Loïc

family: Clézardin

full_name: Philippe Clézardin

family: Magaud

full_name: Laurent Magaud

given: Laurent

family: Roche

full_name: Laurent Roche

family: Tubiana-Mathieu

full_name: Nicole Tubiana-Mathieu

given: Nicole

family: Tigaud

full_name: Jean-Dominique Tigaud

given: Jean-Dominique

family: Topart

full_name: Delphine Topart

given: Delphine

family: Raban

full_name: Nadia Raban

given: Nadia

family: Mouret-Reynier

full_name: Marie-Ange Mouret-Reynier

given: Marie-Ange

family: Mathevet

full_name: Patrice Mathevet

given: Patrice

journal_name: Clinical Breast Cancer

license: cc-by-nc-nd

license_normalized: cc-by-nc-nd

repository_institution: University of Leeds, The University of Sheffield, University of York - White Rose Research Online

version: acceptedVersion

publisher: Elsevier BV

publisher_dissemination: Elsevier

publisher_group: Elsevier

publisher_normalized: Elsevier

location_facility: Hopital Femme Mère Enfant, Service de Gynécologie


title: Local Analgesia Versus Local Peroperative Infiltration After Total Hip Replacement

acronym: ALRIAL

summary:
Clinical study, comparative, prospective, interventional, randomized, single-center, single-blind The fast resumption of the walking after surgery of total prosthesis of hip (PTH) requires an effective analgesia from the immediate post-operative period. In France, whatever is the peroperative anesthesia, the analgesic reference technique is a locoregional anesthesia (ALR) ultrasound guidance by blocks of the femoral and cutaneous nerves side of the thigh. In the Anglo-Saxon countries, in particular in Australia and in the United States, the techniques of peroperative infiltration of local anesthetics (IAL) by the surgeon supplanted the techniques of traditional ALR. However, no French study compares the IAL with the conventional ALR with a rigorous methodology. Our occasional practice of IAL suggests us that it is more effective in terms of post-operative analgesia with Analog Visual Scales decreased (EVA) and a lesser consumption of morphine. Furthermore, the resumption of the upright posture in bipedal support as well as the resumption of the walking would be earlier.

The main objective is to show that the post-operative analgesia by local peroperative infiltration is superior to that obtained by locoregional anesthesia (ALR by femoral block associated with a side cutaneous block of the thigh) after the surgery of total prosthesis of hip, with decrease of the consumption of morphine within first 72 post-operative hours.

The secondary objectives are to compare the Analog Visual Scales of pain (EVA) with the rest and with the mobilization during various times (in post-surgery care room, then at H4, H8, H12, H24, H48, H72), the period between the end of intervention (out of the operating room) and the first support by the upright posture in bipedal support), the period between the end of intervention and the resumption of the walk, the satisfaction of the patients at the exit of the hospital, the duration of hospitalization after the surgical operation and the possible unwanted events (systematic toxicity of the local anesthetics, the infection of prosthesis, disease thromboembolic venous) during the hospitalization.

status: Completed

study_completion_date_type: Actual

study_type: Interventional

design_allocation: Randomized

primary_purpose: Treatment

enrollment_type: Actual

lead_sponsor: Hospices Civils de Lyon

location_facility: Hôpital Edouard Herriot - Département d'anesthésie réanimation

intervention_type: Drug

lead_sponsor_type: academique

status_simplified: Completed


title: Assessment Study on Family Burden in Overall Care of Patient With Huntington Disease

acronym: PHRI-HD

summary:
Huntington's disease (HD) is a rare inherited neurodegenerative disorder, progressing between 15 and 20 years and affecting one person out of 10.000. In France, it concerns some 6.000 patients symptomatic and 12 000 asymptomatic carriers.

Few extensive researches have been conducted on the progression of the disease, which is defined in the literature in 5 stages in a functional approach.

Therapeutically, no cure for HD is currently validated but only symptomatic treatments. There's various treatment options: medicated, humans (physiotherapy, speech therapist, occupational therapist, ..).

Although these treatment options do not prevent the progression of the disease, their combination associated with a stimulating environment may slow the decline of physical, intellectual and psychic abilities of patients.

In social terms, patients with HD require sustained support, especially in cases of family isolation.

The behavioural, gaiting and eating disorder as well as the communications difficulties make it difficult support daily for the entourage. The caregivers are sometimes dealing with untenable situations. Home care services, which are crucial to alleviating dependency, relieve family caregivers but are for the most severe patient.

Moreover, the justified placement decision in an institution generates a feeling of guilt for the family.

The caregiver is the person who brings non-professional assistance , partly or wholly , to a dependent member of his entourage , for the activities of daily living. This regular care may be provided permanently or not. It can take many forms, such as , care , nursing , support to education and social life , administrative procedures , psychological support .

Caregivers have their lives profoundly reshaped. They are often forced to give up some of their habits , give up their future plans , change their relationships. The commitment of caregivers with patients with Huntington's disease actually sounds on their mental and physical health, as well as their social and professional life

Very few studies have been conducted to measure the difficulties and implications of these caregivers.

lead_sponsor: Assistance Publique - Hôpitaux de Paris

intervention_type: Other


type: Other Identifier

title: Respiratory Outcome of Infants With or Without Documented Wheezing During Bronchiolitis

acronym: WheezOut

summary: Hospital admission for infant bronchiolitis is associated with an increased risk of recurrent wheezing and subsequent asthma in childhood. In the literature, 17 to 60% of children will develop repeated wheezing (infant asthma in France). This highly variable incidence could be linked in part to the fact that the definition of bronchiolitis varies between continents. In Europe the usual definition is an acute and contagious viral infection which affects the bronchioles (small bronchi) of infants accompanied by coughing, rapid breathing and wheezing. In research studies, bronchiolitis must be associated with wheezing and / or crackles on auscultation in Europe, and wheezing imperatively in the USA. The diagnosis of wheezing is difficult, and medical agreement on auscultatory respiratory abnormalities is poor. We thus have developed a wheezing diagnostic tool using artificial intelligence processing of respiratory sound recordings by smartphone (Bokov P, Comput Biol Med 2016, DOI: 10.1016/j.compbiomed.2016.01.002). In a second larger bicentric study that included only infants suspected of bronchiolitis, our approach has consisted in obtaining a recording by smartphone but also by electronic stethoscope in order to allow deferred listening of the sounds (WheezSmart study). The objective of these studies was to obtain a formal diagnosis of wheezing, the current project aims to assess the benefit of this diagnosis. The main objective of this cross-sectional study is to determine whether the formal presence (diagnosis of wheezing from a recording of pulmonary auscultation) is associated with the risk of childhood asthma (diagnosis of asthma at 6 years) regardless of the usual risk factors (atopic / allergic terrain, exposure to smoking, recurrence of symptoms). The secondary objectives are to determine whether the formal presence of wheezing on auscultation is a risk factor for subsequent repeated wheezing (diagnosis of infant asthma) and for initial disease severity (bronchiolitis) compared to SpO2 and admission of the child to hospital. The interest in differentiating between high and low frequency sibilants will be evaluated also.

study_start_date_type: Actual

status: Recruiting

study_completion_date_type: Anticipated

study_type: Observational

time_perspective: Prospective

enrollment_type: Anticipated

ipd_sharing: Undecided

status_simplified: Ongoing


title: Analysis of the Postprandial Effects of a Vegetable Protein Mixture Rich in Arginine, Cysteine and Leucine on Endothelial Dysfunction and Inflammation at Low Noise in Elderly People With Cardiometabolic Risk

acronym: P-PROBS CM

summary: By 2050, the expanding world population will consume two-thirds more animal protein than it consumes today. The increase in chronic diseases associated with the generalization of these consumption patterns tend to understand the place of meat in our diets. All these elements participate to the reduction of animal proteins in favor of vegetable proteins in our food. The elderly are particularly affected by malnutrition, the prevalence of protein-energy malnutrition increasing with age and promoting the onset of morbidities. Without care, it leads to the worsening of physiological phenomena linked to aging such as loss of muscle functionality (sarcopenia) or reduction in bone density (osteoporosis) and increases the risk of falls - the main cause of dependence. However, in France, protein consumption declines significantly with age, even though requirements appear to be greater for the elderly. It is therefore a major challenge for our societies to ensure that the aging of the population and the increase in life expectancy are not synonymous with a reduction in the physical and mental capacities of individuals. Thus, it is essential to ensure that the recommendations for reducing the intake of animal proteins in favor of vegetable proteins can be applied without risk to aging populations, in particular on the human body cardiovascular risk of these populations.

study_start_date_type: Anticipated

status: Not yet recruiting

primary_purpose: Basic Science

lead_sponsor: University Hospital, Clermont-Ferrand

intervention_type: Behavioral


title: Precision Immuno-Oncology for Advanced Non-small Cell Lung Cancer Patients With PD-1 ICI Resistance (PIONeeR-BioMarkers (BM) Profiling)

acronym: PIONeeR

summary:
PIONeeR study is a prospective, multicenter study without administration of an investigational product.

The promotion and funding will be done by the Assistance Publique Hôpitaux de Marseille (APHM), the coordination by AMU. There will be 3 principal investigational clinical centres in France:

Centre d'Essais Précoces en Cancérologie de Marseille (CEPCM)-Unité de Phase I Oncologie labélisée CLIP² in APHM, Marseille, supervised by Prof. F. Barlesi
Medical Oncology Department of Centre Léon Bérard, Lyon, supervised by Prof. M. Pérol
Unité d'Oncologie Thoracique, CHU Larrey /Oncopôle, Toulouse, supervised by Prof. J. Mazières.

Some secondary centres, nearby the three principal mentioned above, will be associated to ensure recruitment of patients, in accordance to provisional planning.

The primary objective is to validate the existence and distribution of the hypothetical immune profile (within blood and tumoral tissue) explaining primary or adaptive resistance to standard PD-1 inhibitors monotherapy, in NSCLC patients.

The secondary objectives are to better characterize :

PK/PD relationships,
inter-patient PK variability,
If systemic exposure levels could be predictive of efficacy of PD-1 ICI, in NSCLC patients.

Some exploratory objectives are :

to assess a predictive value of a panel of endothelial biomarkers, in NSCLC patients.
to compare predictive immune & endothelial biomarker profiles with those of sensitive tumors.
to better understand which profiles track significantly with progression following PD-1 ICI administration, in order to improve advanced NSCLC patients' stratification, for future clinical trials.

primary_purpose: Diagnostic

lead_sponsor: Assistance Publique Hopitaux De Marseille

location_facility: Assistance Pubique Hopitaux de Marseille


title: Evaluation of the Impact of Physical Reconditioning Associated With Specific Nutritional Supplementation in Obese Patients Suffering From Metabolic Syndrome. OBEFITT Study.

acronym: OBEFITT

summary:
Android obesity contributes, via insulin resistance and endothelial dysfunction, to the development of cardiovascular atherosclerosis. It leads to poor quality of life. It is often associated with metabolic syndrome which includes, whatever the definitions used (National Education Cholesterol Program, NECP / Adult Treatment Panel III, ATP III or International Diabetes Federation, IDF), an increased waist measurement, an arterial high blood pressure and disorders of the glucide and lipid metabolism. The treatment of the current "epidemic" of obesity and metabolic syndrome in France (12.4 % of obese and 14 % of subjects with metabolic syndrome) thus requires new therapeutic approaches.

A well-balanced diet and a daily physical activity are the indispensable requirements for the treatment of obesity and metabolic syndrome. It is possible to associate it to pharmacological agents, but the results are often partial and transient. Preliminary data suggest that leucine or arginine supplementation could facilitate the loss of fat mass. Moreover, the physical exercise has also demonstrated benefits.

Sessions of physical reconditioning (aerobic work + muscular intensification) associated with a program of specific nutritional supplementation by a mixture of Leucine and Arginine (in the daytime) could improve the treatment of obese subjects affected by metabolic syndrome.

lead_sponsor: University Hospital, Rouen


title: Impact of a New Multiperfusion Neonatal System on Health and Cost of Care in Neonates

acronym: EDELWEISS

summary:
Infusion and parenteral nutrition play an important role in the management of neonatal intensive care patients. Administration of drugs and parenteral nutrition solutions to the patient is performed via different systems including a catheter and a perfusion system. In critically ill, high risk neonates, use of these systems is associated with complications such as infections, interactions between drugs simultaneously infused on the same route (precipitates, catheter obstruction), less effective treatment due to modified amount of drug administered compared to expected or to compatibility issues between drugs. Sepsis and reduction of treatment efficacy can have an impact on survival or subsequent neurodevelopment. Late onset sepsis is one of the most frequent complications in very premature infants born before 33 weeks gestational age and most of those infections occur in infants requiring a perfusion system and an intravenous catheter.

In this context, a new multiperfusion device was developed (Multiline Néo®, Doran, France) to remove access to the infusion system from the incubator where high temperature and humidity favour bacterial growth. But also to allow the administration of several drug solutions simultaneously avoiding contact between drugs.

Our hypothesis is that the new perfusion system helps to reduce the risk of infections, without increase in costs.

ipd_sharing: No

ipd_sharing_description: The individual participant data will not be shared

intervention_type: Device


title: Blockade of the Renin-angiotensin-aldosterone System in Patients With ARVD: a Double-blind Multicentre Prospective Randomized Study.

acronym: BRAVE

summary:
Arrhythmogenic right ventricular dysplasia (ARVD) is a rare cardiomyopathy characterized by the progressive replacement of cardiomyocytes by fatty and fibrous tissue in the right ventricle (RV). These infiltrations lead to cardiac electrical instability and ventricular arrhythmia.

Current treatment for ARVD is empirical and essentially based on treatment of arrhythmia. Thus, there is no validated treatment that will prevent the deterioration of the RV function in patients with ARVD.

The investigator's hypothesis is that the use of anti-fibrotic medications will prevent or at least reduce the deterioration of the RV function. The aim of this project is to evaluate the effect of spironolactone, a Potassium-sparing diuretic on ventricular myocardial remodeling and on arrhythmia burden in patients with ARVD.

The trial is a double-blind parallel multicenter prospective randomized phase II drug study. Patients will be randomized in the two groups: spironolactone or placebo. 19 centers in France will enroll the 120 patients (60 per group). Patients will be followed up every 6 months for 3 years. A decrease in right and/or left ventricular deterioration and in arrhythmia burden are expected in ARVD patients treated with spironolactone. This reduction will improve the quality of life of patients and will reduce the number of hospitalizations and the risk of terminal heart failure.


title: Rapid Quantitative Neutrophil CD64 Measurement for Early Diagnosis of Nosocomial Infection in Preterm Newborns

summary:
Diagnosis of late-onset sepsis is difficult in the absence of specific clinical signs and biological markers in the infection initial phase .The aim of this study is to determine the performance of a new infection marker : Neutrophil CD64 for early diagnosis in nosocomial infection (NI) in preterm newborns.

METHODS :

Monocentric prospective study including preterm newborn infants (<37 weeks of gestationnal age ) with clinical suspicion of nosocomial infection in a neonatal intensice care unit (Neonatal intensive care unit of Montpellier, France).
Patients will be enrolled in the study after informed consents. Rapid and automated CD64 measurment will be realized during the conventional blood sample including C-Reactive Protein (CRP), Procalcitonin (PCT) and blood culture.

Broad-spectrum antibiotic therapy can be started on the advice of clinician and blinded the result of CD64. Patients will be then classed in three groups using CDC criteria (center for disease control) : 1-no infection, 2-infection, 3-possible infection during the multidisciplinary staff. Specificity, sensitivity, negative and positive value of CD64 will be calculated and the performances of CRP, PCT and CD64 will be compared.

153 patients are needed in the study enrolled during a period of 12 months.

PERSPECTIVES Neutrophil CD64 monitoring might be help clinicians to manage nosocomial infections in neonates.CD64 allow to integrate in a decision algorithm with the determination of the best cut-off value to faster processing nosocomial infections and could help to reduce unnecessary antibioc therapy. A rapid technique for determination of CD64 should be readily available in our unit.

status: Unknown status

lead_sponsor: University Hospital, Montpellier

status_simplified: Unknown


title: Influence Of Omeprazole On The Anti-Platelet Action Of Clopidogrel Associated To Aspirin: Double-Blind Randomized Trial Against Placebo

summary:
Objectives: A prospective investigation of the effect of omeprazole, a proton pump inhibitor, on the anti-platelet action of clopidogrel.

The main decision criterion will concern change in VASP protein phosphorylation under treatment. Phosphorylation will be measured before and after administration of omeprazole versus placebo in patients undergoing clopidogrel treatment.

Type of study: Single center, double blind, randomized parallel group study versus placebo, comparing two treatment groups:

clopidogrel + omeprazole + standard regime (beta-blockers, atorvastatin, IEC, aspirin)
clopidogrel + placebo+ standard regime (beta-blockers, atorvastatin, IEC, aspirin)

Study population: 120 patients from the Cardiology Department of Brest University hospital, Brest (France), receiving a standard treatment comprising a loading dose of clopidogrel followed by a daily dose of 75 mg associated to 75 mg aspirin, will be randomized between 20 mg/day omeprazole and 20 mg/day placebo treatment groups. The efficacy of clopidogrel will be assessed by inter-group comparison on the VASP test.

Study period: 7 days' treatment per patient. Total study period estimated at 6 months.

Expected findings: The results should confirm the suspected negative effect of omeprazole on clopidogrel's impact on arterial thrombosis risk, secondarily allowing new recommendations to be drawn up for this association.

ReferenceType: derived

ReferenceCitation: Gilard M, Arnaud B, Cornily JC, Le Gal G, Lacut K, Le Calvez G, Mansourati J, Mottier D, Abgrall JF, Boschat J. Influence of omeprazole on the antiplatelet action of clopidogrel associated with aspirin: the randomized, double-blind OCLA (Omeprazole CLopidogrel Aspirin) study. J Am Coll Cardiol. 2008 Jan 22;51(3):256-60. doi: 10.1016/j.jacc.2007.06.064.

family: Gilard

full_name: Martine Gilard

given: Martine

sequence: first

family: Arnaud

full_name: Bertrand Arnaud

given: Bertrand

sequence: additional

family: Cornily

full_name: Jean-Christophe Cornily

given: Jean-Christophe

family: Le Gal

full_name: Grégoire Le Gal

given: Grégoire

family: Lacut

full_name: Karine Lacut

given: Karine

family: Le Calvez

full_name: Geneviève Le Calvez

given: Geneviève

family: Mansourati

full_name: Jacques Mansourati

given: Jacques

family: Mottier

full_name: Dominique Mottier

given: Dominique

family: Abgrall

full_name: Jean-François Abgrall

given: Jean-François

family: Boschat

full_name: Jacques Boschat

bso_classification: Medical research

datasource: user

genre: journal-article

genre_raw: journal-article

journal_name: Journal of the American College of Cardiology

oa_host_type: publisher

evidence: open (via crossref license)

host_type: publisher

license: elsevier-specific: oa user license

license_normalized: elsevier-specific

version: publishedVersion

title: Influence of Omeprazole on the Antiplatelet Action of Clopidogrel Associated With Aspirin

lead_sponsor: University Hospital, Brest


title: Predictive Electrophysiological Score of the Neurological Prognosis Post Cardiac Arrest

acronym: CA-EEG

summary:
Cardiac arrest (CA) is a major public health problem (1) because of its frequency (30000 to 50000 new cases of CA per year in France), a high mortality 80-90% and a relevant morbidity : 50% of survivors have cerebral sequela. Neurologic prognostication after CA is paramount. The American Academy of Neurology identifies accurate predictors of poor neurologic outcome (2): clinical examination findings such as no pupil response, no corneal reflexes, no motor response to stimulation and early myoclonus status epilepticus; biologic parameters like high neuron specific enolase (NSE) greater than 33 μg/L (3-4) and electrophysiologic results like flat electroencephalogram (EEG) or with burst suppression and Somatosensory evoked potentials (SEP) with no response to N20. Brain imaging may provide additional informations but not recommended yet. However, these pronotic markers were developed before the introduction therapeutic hypothermia (TH) (5-6). TH is now recommended after cardiac arrest by international guidelines, based on demonstration of improved survival and neurological recovery in comatose survivors of CA (7). TH and its associated use of sedative and paralytic agent may delay neurologic recovery and affect the optimal timing of prognostic variables (8).

Many classifications of electroencephalogram (EEG) (9-12) exist but no one is generally accept and recommended and they were created before TH.

In a preliminary study based on a retrospective cohort of 64 patients in CA with initial TH, we developped an electroencephalographic score to predict precocity the neurologic outcome according to the Cerebral performance category (CPC) (13-14).

The purpose of this study is to evaluate a simple and objective electroencephalographic score helpful to predict neurologic outcome after CA. Then, we would like to create a composite score to have a multimodal prognostication.

Patients and methods After CA resuscitation, all patients underwent coronary angioplasty if indicated and then were immediately admitted in emergency room of ICU. All patients were intubated and mechanically ventilated. Sedation was performed with continuous infusion of midazolam 0,15-0,2 mg/kg/h and sufentanil 0,15-0,2 μg/kg/h. All our patients were curarized with cisatracurium 0,2-0,3 mg/kg/h to prevent shivering during TH and took anti-epileptic medication phenobarbital 10-15 mg/ kg two times a day to prevent infra-clinic convulsive seizure.

Mild TH between 33 -34 °C was performed by active cooling with intravascular device (CoolGard® - Zoll, Chelmsford, UK) for 24 hours. Mean arterial pressure was maintained between [75-80] mmHg by titrated norepinephrine with or without inotropics (dobutamine, epinephrine) according cardiac output monitored by echocardiography.

After 24 hours of hypothermia, warming was started at a rate of 0.2 ° C/hr; neuromuscular blocking agents were arrested at 35.5°C and sedation at 36.5°C.

Neurological evaluation performed at 48 hours off sedation included a clinical evaluation (Glasgow score, myoclonus status, response to orders, motor response to stimulation, brain-stem reflexes). NSE was sampled between 48 and 72 H. EEGs were performed at Day-2, Day-3 and Day-5 off sedation and SEP at Day-5 off sedation. All EEGs were interpreted by two certified electroencephalographers blind from clinical neurologic outcome.

Survival and neurologic outcome according to CPC were assessed at ICU discharge and three months later.

ipd_sharing: Yes

location_facility: Hôpital Lapeyronie - Département Anesthésie Réanimation A


title: Contraception and Cervical and Breast Cancer Screening in Obese Versus Non-obese Women Aged 25 to 74 Years Old

acronym: DEPISGYN

summary:
.Brief Summary:* Obesity is a major public health problem in France. Indeed, 17% of the French population is obese (BMI greater than or equal to 30 kg/m²) while almost half of the adult population is overweight (BMI greater than or equal to 25 kg/m²).

There is an increased risk of gynecological cancer in obese women but screening is less often performed :

In women, obesity is a risk factor for the occurrence of certain cancers such as uterine cancer, epithelial ovarian cancer and breast cancer, particularly post-menopausal. In addition, an increase in BMI from the first stage of obesity is associated with larger breast tumors with more frequent lymph node involvement, indicating more invasive cancers. Recent studies have shown an increase in breast cancer mortality for women with grade 2 and 3 obesity compared to women of so-called normal weight. Mortality from invasive breast cancer is higher from the obesity stage onwards.

The current recommendations of the High Authority for Health recommend breast cancer screening by mammography and clinical examination every two years in all women aged 50 to 74, excluding women at high risk and requiring specialist follow-up. Organized screening for cervical cancer has recently been modified. From 25 to 30 years of age the modalities remain the same and consist of two cytological examinations one year apart and then every 3 years if the latest results are normal. From the age of 30 and up to the age of 65, it is now recommended that an HPV test be performed as a first-line test, 3 years after the last normal cytological examination and then every 5 years if the last test was negative.

Studies dating back quite some time had shown an under-screening of cancers in obese women, in terms of carrying out mammography and cervical smears compared to women of normal weight. More recent data on access to gynecological cancer screening for obese women are heterogeneous, but there still seems to be less access to these examinations, whether for mammography or cervical smears. For example, a large American cohort study observed poorer detection of pre-cancerous lesions by smear with increasing BMI. Obese women had the lowest cumulative risk of pre-cancerous lesions at five years (followed by overweight women), but the highest rate of cancer at five years, associated with higher mortality.

A neglected contraception in obese women?

Data in the literature show that rates of unintended and unplanned pregnancies are higher in obese women (mainly those with grade 3 obesity) than in normal-weight women. This is associated with a lower use of contraception which is certainly poly-factorial: contraception not necessary due to a decrease in fertility linked to obesity, increased risks linked to contraception in obese women... However, most current contraceptive methods have shown similar efficacy in obese and non-obese women.

This context suggests that there is still a marked difference in the gynecological management of obese women. The role of the general practitioner seems essential in this follow-up by facilitating the use of screening tests and by improving the information of this population with regard to contraception in particular.

The objective of this study is to compare the gynecological follow-up of obese and non-obese women in a sample of women in Occitania, in terms of screening for breast and cervical cancer, as well as in terms of access to a method of contraception in general practice.

ipd_sharing_description: NC


type: EudraCT Number

title: RIVA-PSP: Efficacy of Rivastigmine on Motor, Cognitive and Behavioural Impairment in Progressive Supranuclear Palsy: A Randomised Double Blind Placebo-controlled Clinical Trial

acronym: RIVA-PSP

summary:
Progressive supranuclear palsy (PSP) is a rare neurodegenerative disease from the parkinsonian syndrome group. It represents 5 to 10% of all parkinsonian syndromes and affects 3,000 to 10,000 persons in France. PSP is characterised by a doparesistant parkinsonism with axial signs such as early gait instability and falls, oculomotor signs such as a vertical gaze palsy, dysphagia and dysarthria, and both cognitive and behavioural disturbances. The latter predominantly manifest as psycho-motor slowness, apathy and frontal executive deficits. Swallowing impairments and falls may lead to life-threatening situations and death occurs 6-9 years after disease onset.

Apart from L-dopa which may transiently and inconsistently improve motor symptoms no effective symptomatic, disease-modifying or neuroprotective therapy is presently available to reduce disability in any way. Therefore these patients often receive mostly non-medical care such as physiotherapy and speech therapy.

In addition to dopaminergic degeneration there is evidence of cholinergic deficits in PSP correlated with gait and balance impairments . This stands in contrast with the limited number of studies of cholinergic augmentation strategies in PSP.

Trials of cholinesterase inhibitors in PSP have produced rather conflicting results: donepezil improves cognition but deteriorates some motor functions whereas a case series of 5 PSP patients treated with rivastigmine found an improvement in several cognitive aspects and no deterioration of motor functions .On the other hand in Parkinson's disease there is convincing evidence of a positive effect of rivastigmine on cognition , apathy and falls Investigators' hypothesis is that rivastigmine (an acetyl- and butyryl-cholinesterase inhibitor) may reduce gait and postural impairment in PSP and may therefore limit the number of falls and their consequences both in terms of injuries sustained (fractures etc...) and on the patients' autonomy. In addition investigators hypothesise that rivastigmine may also reduce the cognitive and behavioural impairment associated with PSP. Taken together these improvements are likely to produce a significant effect on the patients' quality of life and their caregiver burden.

location_facility: Service de Neurologie et Pathologie du Mouvement Hôpital de La Timone


title: Pelvic-perineal Disorders in Women With Sphincter Tears, a Retrospective Study

acronym: PAPOASI

summary:
According to INSEE, in 2016, in France, there were 785,000 births. According to the latest national perinatal survey in 2016, 80.4% of women gave birth by vaginal delivery. Of these, 52.1% had perineal tears and 0.8% had 3rd and 4th degree tears. Of these 3rd and 4th degree tears, 2.2% occurred during instrumental delivery and 0.5% during spontaneous delivery. In recent years, there has been an increase in the prevalence of obstetric anal sphincter injuries. Mc Pherson et al. found a prevalence of LOSA (Obstetric Anal Sphincter Injury) of 2% in 2004 versus 4.6% in 2008. Gurol-Urganci et al. also found an increase in prevalence from 1.8% in 2000 to 5.9% in 2012. This increase is probably due to improved diagnosis by obstetrical teams. Indeed, a large number of LOSAs remained undiagnosed at birth and these occult lesions were subsequently found by endoanal ultrasound. In the Andrews et al. study, when women were reexamined, the prevalence of LOSA increased from 11% to 24.5%. As practitioner training improved, the prevalence of LOSA at birth became increasingly accurate. Obstetric anal sphincter injuries are responsible for significant physical and psychological morbidity. These obstetrical lesions of the anal sphincter can generate functional consequences (including anal incontinence in the first rank), which will have harmful effects on the quality of life of the women, they can involve a social isolation passing by the limitation of displacements and physical and social activities. The daily life of these women can remain impacted by the consequences of LOSA until more than 10 years after delivery. In addition, a loss of self-esteem as well as feelings of guilt, shame and frustration are reported in these women. Thus, some will speak of a LOSA syndrome, which includes emotional, social and psychological consequences, including the ability to assume one's role as a mother. LOSA are perineal tears corresponding to the 3rd and 4th degree, formerly and respectively called complete perineum and complicated complete perineum. The Sultan classification for perineal tears proposed in 1999 was adopted by the Royal College of Obstretricians and Gynecologists (RCOG) and is the most widely used in the scientific literature worldwide. It defines the 3rd degree as a perineal injury involving the anal sphincter complex alone.

Anal continence is a balance between several factors such as rectal sensitivity, stool quality, the smooth and striated muscles of the anal sphincter, the pubo-rectal muscle webbing and the innervation of these structures. Obstetrical trauma of the stretching and compression type affects all these structures. All of these lesions can contribute to the development of anal incontinence. However, these structures are not routinely evaluated in women who have had an obstetric anal sphincter injury.

Pelvic-perineal pain was studied in 2 studies and involved 24.7% to 35% of women with obstetric anal sphincter injuries.

Compared to women without LOSA, women with LOSA had a later return to sexual intercourse, with more severe anal incontinence during the first week after LOSA. Indeed, at 12 weeks postpartum, the rate of women who resumed sexual intercourse was lower in the group of women with LOSA than in the group without LOSA.

The pelvic-perineal disorders faced by women with LOSA affect their quality of life, their sexuality, and their health. Thus, early identification of all pelvic-perineal disorders appears to be a priority in this population.

status: Active, not recruiting

time_perspective: Retrospective

ReferenceType: background

ReferenceCitation: McPherson KC, Beggs AD, Sultan AH, Thakar R. Can the risk of obstetric anal sphincter injuries (OASIs) be predicted using a risk-scoring system? BMC Res Notes. 2014 Jul 24;7:471. doi: 10.1186/1756-0500-7-471.

ReferenceCitation: Gurol-Urganci I, Cromwell DA, Edozien LC, Mahmood TA, Adams EJ, Richmond DH, Templeton A, van der Meulen JH. Third- and fourth-degree perineal tears among primiparous women in England between 2000 and 2012: time trends and risk factors. BJOG. 2013 Nov;120(12):1516-25. doi: 10.1111/1471-0528.12363. Epub 2013 Jul 3.

ReferenceCitation: Andrews V, Sultan AH, Thakar R, Jones PW. Occult anal sphincter injuries--myth or reality? BJOG. 2006 Feb;113(2):195-200.

ReferenceCitation: Cornell K, De Souza A, Tacey M, Long DM, Veerasingham M. The effect of implementing a new guideline and operative pro forma on the detection and management of third- and fourth-degree perineal tears. Int J Womens Health. 2016 May 5;8:131-5. doi: 10.2147/IJWH.S101188. eCollection 2016.

lead_sponsor: Groupe Hospitalier Paris Saint Joseph


title: Prognostic Value of Circulating Endothelial Progenitor Cells in Aneurysmal Subarachnoid Hemorrhage (Evaluation de l'intérêt Pronostic Des progéniteurs endothéliaux Circulants Dans l'hémorragie Sous-arachnoïdienne Par Rupture d'anévrysme cérébral)

acronym: EVAPROPEC

summary:
Aneurysmal subarachnoid hemorrhage is a common and serious disease associated to a high rate of mortality and morbidity. Severe definitive neurological impairment can concern up to 30% of patients in relation with elevated intracranial pressure, hemorrhage recurrence and symptomatic cerebral arterial vasospasm. This latter complication is defined as a reversible reduction of cerebral artery's diameter occurring between the 4th and the 14th day after bleeding. Physiopathology is not well understood, but could involve endothelium, trough endothelial progenitor cells (EPC). Circulating EPC are bone marrow-derived cells with capacity of vasculogenesis and angiogenesis. EPC have been recognized playing a beneficial role in cardiovascular disease and ischemic stroke. EPC have never been studied in aneurysmal subarachnoid hemorrhage.

The primary objective of this study is to compare the number of circulating endothelial progenitor cells between patients with a good neurological outcome (defined as a glasgow outcome scale = 1 or 2) and patients with a poor neurological outcome (glasgow outcome scale = 3, 4 or 5).

Briefly, the number of circulating EPC will be measured at admission, and at day 3, 6, 10, 14, 21 in each consecutive patient suffering aneurysmal subarachnoid hemorrhage and hospitalized in Teaching Hospital of Besançon (France). The neurological outcome will be measured one year after subarachnoid hemorrhage.

lead_sponsor: Centre Hospitalier Universitaire de Besancon


title: Study of the Role of Soluble Forms of RAGE (sRAGE/esRAGE) as Diagnostic and Prognostic Biomarkers of Systemic Lupus Erythematosus.

summary:
Systemic Lupus Erythematosus (SLE) is the most common systemic autoimmune disease. The clinical manifestations are severe and affect multiple target organs such as the kidney, central nervous system, skin, heart and joints. Despite the progress made in the therapeutic approach with new immunosuppressive regimens, morbi-mortality is still high. Therefore, it's important to identify new biomarkers to help clinicians to predict severity and evolution of the disease for better adaptation of treatments and try to improve the prognosis.

RAGE (Receptor for Advanced Glycation Endproducts) :

RAGE (Receptor for Advanced Glycation Endproducts) is an ubiquitous membrane receptor, involved in development of many diseases such as diabetes, chronic renal failure but also in vascular remodelling, inflammatory, infectious deseases and cancer. RAGE regulates a number of crucial cell processes like inflammation, and tissue and cellular homeostasis.

RAGE is able to bind not only the advanced glycation end products (AGEs) such as pentosidine, carboxymethyllysine (CML), methyl-glyoxal-hydroimidazolone-1 (MG- H1), but also other ligands such as HMGB1 (high mobility group box1), and S100A8/A9 proteins which have been correlated in recent studies to the activity index of SLE. The activation of RAGE leads to a cascade of intracellular signaling and activation of the transcription factor NF-ΚB . NF-ΚB enable the traduction of proinflammatory cytokines such as IL-6, IL-1α ,IFN-γ. In SLE, these cytokines involved in perpetuation of inflammation and tissue damages including lupus nephritis. Moreover, the activation of RAGE induces the expression of adhesion molecule such as sICAM -1 and sVCAM -1 wich were recently involved in SLE vasculitis.

Soluble forms of RAGE, sRAGE and esRAGE :

RAGE is a proinflammatory membrane receptor. But RAGE also exists in soluble plasma forms, esRAGE (secreted form) and sRAGE (a truncated form as cleaved by MMP9 and ADAM10 enzymes). esRAGE and sRAGE have the same ligand-binding specificity as RAGE and may function as a 'decoy receptor' by binding pro-inflammatory ligands and preventing them from accessing cell surface RAGE (Kierdorf and Fritz, 2013). Therefore, both soluble forms have an anti-inflammatory action. Several studies have shown a decrease in circulating levels of sRAGE in patients with Rheumatoid Arthritis, or Sjögren Syndrome compared with healthy controls. However, the role of RAGE in SLE remains unknown.

RAGE and Systemic Lupus Erythematosus, recent advances :

Our team (Laboratory of Nephrology, CNRS UMR 7369, URCA) showed in a study in lupus RAGE knockout mice (B6/ MRL-FAS lpr/J RAGE-/-) a strong involvement of RAGE in systemic manifestations SLE. Recently, another report showed that sRAGE has an anti-inflammatory effect on the lupus nephritis and could be a potent therapy in mice.

In humans, two studies show a correlation between the plasma level of sRAGE and lupus phenotype ( Nienhuis et al. , 2008).

Working hypothesis :

Based on the results and those of the current studies, the investigators think that RAGE axis and its soluble forms play a crucial role in the complex pathogenesis of SLE.

The investigators hypothesize that plasma levels sRAGE and esRAGE are a reflection of the activity and the development of SLE in humans. Soluble forms of RAGE and ligands may be novel biomarkers of SLE and sRAGE a potent therapeutic target.

lead_sponsor: CHU de Reims


title: Evaluation of MRI Sequences for Ultra-rapid Acquisition of Bile Ducts Images

acronym: BiliFast

summary:
The Institute of Imaged-Guided Surgery (IHU Strasbourg) has two clinical Magnetic Resonance Imaging (MRI) scanners, one with a 3T (3 Teslas) magnetic field used for diagnosis, the other with a magnetic field of 1,5T (1,5 Teslas) used for the interventional (Pre / per / postoperative).

The reference for the visualization of the biliary and pancreatic ducts is a relatively long sequence that needs a breathing-synchronized acquisition leading to artefacts on the images (blur effect).

In order to reduce and/or standardize the acquisition time as well as to limit artefacts, accelerated sequences are developed. Such sequence is available in France recently in the form of WIP Siemens (Work In Progress: sequence in test phase at manufacturer to be marketed in the short or medium term on clinical machines). It incorporates a Compressed Sensing (CS) acquisition scheme allowing the acquisition of a 3D (3 dimensions) sequence similar to the usual sequence by drastically reducing the acquisition time, the sequence CS-SPACE. This sequence exists in two forms:

An ultra-rapid sequence acquired in apnea
An accelerated sequence but remaining synchronized with the breath. The study carried out here on a large number of patients, with two different magnetic fields, applied routinely for diagnosis or anticipation of surgery, could be used by the community of radiologists, hepatogastroenterologists and also digestive surgeons Hepatobiliary.

design_allocation: Non-Randomized

ReferenceCitation: Bates DD, LeBedis CA, Soto JA, Gupta A. Use of Magnetic Resonance in Pancreaticobiliary Emergencies. Magn Reson Imaging Clin N Am. 2016 May;24(2):433-48. doi: 10.1016/j.mric.2015.11.010. Epub 2016 Feb 22. Review.

ReferenceCitation: Yoon JH, Lee SM, Kang HJ, Weiland E, Raithel E, Son Y, Kiefer B, Lee JM. Clinical Feasibility of 3-Dimensional Magnetic Resonance Cholangiopancreatography Using Compressed Sensing: Comparison of Image Quality and Diagnostic Performance. Invest Radiol. 2017 Oct;52(10):612-619. doi: 10.1097/RLI.0000000000000380.

ReferenceCitation: Chandarana H, Doshi AM, Shanbhogue A, Babb JS, Bruno MT, Zhao T, Raithel E, Zenge MO, Li G, Otazo R. Three-dimensional MR Cholangiopancreatography in a Breath Hold with Sparsity-based Reconstruction of Highly Undersampled Data. Radiology. 2016 Aug;280(2):585-94. doi: 10.1148/radiol.2016151935. Epub 2016 Mar 16.

lead_sponsor: IHU Strasbourg

location_facility: Service de Radiologie et d'Echographie, NHC Strasbourg


title: A Randomized Controlled Trial Evaluating the Efficacy of Local Budesonide Therapy in the Management of Hyposmia in COVID-19 Patients Without Signs of Severity

acronym: COVIDORL

summary:
The initial symptoms described in the first cases of COVID-19 were mainly fever and respiratory signs. Recently, there has been an increase in cases of hyposmia without associated nasal obstruction or rhinorrhea. Although we do not yet know the long-term consequences of COVID-19 on olfaction, there is evidence in the literature demonstrating that post-viral hyposmias are an important source of long-term olfactory disorders, impacting quality of life.

Usually, the treatment of viral hyposmias is based on local and/or general corticosteroid treatment combined with saline nasal irrigation at the onset of signs. Because of the possible development of severe forms of the SARS-Cov-2 infection, the French Society of Otorhinolaryngology has advised against treatment by corticosteroid therapy and nasal irrigation. However, as the virus is present in the nasal fossae on average for 20 days, persistent hyposmia at 30 days would probably result from an inflammatory or neurological damage to the nasal slits or olfactory bulb. Local treatment with corticosteroids could then be instituted from 30 days after the onset of symptoms of COVID-19 without risk of dissemination.

In persistent hyposmia other than chronic rhinosinusitis, the only treatment that has proven its efficacy is nasal irrigation associated with budesonide and olfactory rehabilitation. However, this drug does not have marketing authorisation in France for this indication.

ReferenceCitation: Daval M, Corré A, Palpacuer C, Housset J, Poillon G, Eliezer M, Verillaud B, Slama D, Ayache D, Herman P, Jourdaine C, Hervé C, El Bakkouri W, Salmon D, Hautefort C. Efficacy of local budesonide therapy in the management of persistent hyposmia in COVID-19 patients without signs of severity: A structured summary of a study protocol for a randomised controlled trial. Trials. 2020 Jul 20;21(1):666. doi: 10.1186/s13063-020-04585-8.

family: Daval

full_name: Mary Daval

given: Mary

family: Corré

full_name: Alain Corré

given: Alain

family: Palpacuer

full_name: Clement Palpacuer

given: Clement

family: Housset

full_name: Juliette Housset

given: Juliette

family: Poillon

full_name: Guillaume Poillon

given: Guillaume

family: Eliezer

full_name: Michael Eliezer

given: Michael

family: Verillaud

full_name: Benjamin Verillaud

given: Benjamin

family: Slama

full_name: Dorsaf Slama

given: Dorsaf

family: Ayache

full_name: Denis Ayache

given: Denis

family: Herman

full_name: Philippe Herman

given: Philippe

family: Jourdaine

full_name: Clement Jourdaine

family: Hervé

full_name: Camille Hervé

given: Camille

family: El Bakkouri

full_name: Wissame El Bakkouri

given: Wissame

family: Salmon

full_name: Dominique Salmon

family: Hautefort

full_name: Charlotte Hautefort

given: Charlotte

currency_apc_doaj: GBP

journal_name: Trials

oa_colors: green gold

oa_host_type: publisher;repository

evidence: oa journal (via doaj)

license: cc-by

license_normalized: cc-by

evidence: oa repository (via OAI-PMH doi match)

host_type: repository

repository_institution: ZB MED - Informationszentrum Lebenswissenschaften - PUBLISSO-Fachrepositorium Lebenswissenschaften

evidence: oa repository (via pmcid lookup)

license_normalized: no license

repository_normalized: PubMed Central

publisher: Springer Science and Business Media LLC

publisher_dissemination: Springer-Nature

publisher_group: Springer-Nature

lead_sponsor: Fondation Ophtalmologique Adolphe de Rothschild


title: Epidemiological, Clinical and Etiological Features of SUSAC's Syndrome (RETINOCOCHLEOCEREBRAL Vasculopathy)

acronym: CARESS

summary:
SUSAC's Syndrome (SS) is characterized by the clinical triad of encephalopathy, hearing loss, and retinal artery branch occlusions. Since the first description of SS in 1979, hundreds of patients with SS, mostly young women, have been reported. However, comprehensive epidemiological, clinical and etiological features of SS have never been specifically addressed so far.

The objective of this study is to characterize the epidemiological, clinical, and etiological features of SUSAC's Syndrome. In this aim, the investigators will constitute a national clinical-based cohort including all SS cases retrospectively reported in France since the last 20 years and all new cases prospectively observed. French Society of Neurology, Ophthalmology and Internal Medicine will be asked to collaborate. Every case will be reviewed by an expert comity of internists, neurologists and neuroradiologists to validate the diagnosis. The exhaustive and systematic analysis of each case will help to better define different aspects of the disease such as the incidence and prevalence, the clinical presentation, the diagnostic modalities and the impact of treatments. Diffusion tensor magnetic resonance imaging of the brain will be obtained to more carefully study the cerebral microvasculopathy of the disease. Serum, cerebrospinal fluid, and DNA samples from each patient will also be collected to study potential autoimmune, thrombotic and infectious markers.

time_perspective: Other

ReferenceCitation: David C, Papo T, Ba I, Ollivier E, Boileau C, Dieudé P, Keren B, Kannengiesser C, Sacre K. Hunting for the genetic basis of Susac syndrome. Eur J Neurol. 2021 Jul;28(7):e57-e59. doi: 10.1111/ene.14836. Epub 2021 Apr 7.

name: Département de Médecine Interne Assistance Publique Hôpitaux de Paris Hôpital Bichat Université de Paris Paris France

family: David

full_name: Clemence David

given: Clemence

family: Papo

full_name: Thomas Papo

given: Thomas

name: Département de Génétique Assistance Publique Hôpitaux de Paris Hôpital Bichat Université de Paris Paris France

family: Ba

full_name: Ibrahima Ba

given: Ibrahima

family: Ollivier

full_name: Emmanuelle Ollivier

given: Emmanuelle

family: Boileau

full_name: Catherine Boileau

given: Catherine

name: Département de Rhumatologie Assistance Publique Hôpitaux de Paris Hôpital Bichat Université de Paris Paris France

family: Dieudé

full_name: Philippe Dieudé

name: Département de Génétique Groupe Hospitalier Pitié Salpêtrière Paris France

family: Keren

full_name: Boris Keren

given: Boris

family: Kannengiesser

full_name: Caroline Kannengiesser

given: Caroline

family: Sacre

full_name: Karim Sacre

given: Karim

journal_name: European Journal of Neurology

publisher: Wiley

publisher_dissemination: Wiley

publisher_group: Wiley

publisher_normalized: Wiley

ReferenceCitation: Machado S, Jouvent E, Klein I, De Guio F, Machado C, Cohen-Aubart F, Sacré K, Papo T. Cognitive dysfunction and brain atrophy in Susac syndrome. J Neurol. 2020 Apr;267(4):994-1003. doi: 10.1007/s00415-019-09664-8. Epub 2019 Dec 11.

family: Machado

full_name: Stéphanie Machado

given: Stéphanie

family: Jouvent

full_name: Eric Jouvent

given: Eric

family: Klein

full_name: Isabelle Klein

given: Isabelle

family: De Guio

full_name: François De Guio

given: François

full_name: Carla Machado

given: Carla

family: Cohen-Aubart

full_name: Fleur Cohen-Aubart

given: Fleur

family: Sacré

full_name: Karim Sacré

journal_name: Journal of Neurology

publisher_normalized: Springer


title: Effect of the Color of the Intra-eye Implant in the Cataract Surgery on the Sleep

acronym: IOL et sommeil

summary:
The cataract surgery (550 000 operations per year in France) is to replace the cloudy lens with a refractive implant. Two colors of implants are available: white implants, filtering out ultraviolet and yellow implants, filtering and more blue light. No clinical data are available to assert the superiority of an implant according to its color and the choice is made according to the preference of the surgeon and / or "markets".

It is established in humans that blue light has an important role on the secretion of melanopsin, a key mediator of the circadian cycle. This "clock" regulates most neuroendocrine functions in the nycthémère (sleep, mood, temperature, cortisol, ..). The question of the impact of these neuro endocrine functions of the installation of a blue light filter into the eyes of patients operated thus arises.

lead_sponsor: University Hospital, Tours

location_facility: Service d'Ophtalmologie, Centre Hospitalier Paul Martinais


title: Evaluation of the Peripheral Nerve Ultrasound as a Diagnostic Tool in CANVAS (Cerebellar Ataxia With Neuropathy and Vestibular Areflexia Syndrome) Neuronopathies

acronym: CANVAS

summary:
Cerebellar ataxia with neuropathy and bilateral areflexia syndrome (CANVAS) is a late onset neurodegenerative disorder with a slowly progressive ataxia. It's genetic causative etiology with an autosomal recessive inheritance has a recent discovery.

It is clinically characterized by impaired visually enhanced vestibulo-ocular reflex, although patients commonly present with imbalance as a main concern, associated with sensory complaints. It has been demonstrated that sensory impairment in CANVAS patients is due to degeneration of dorsal root with abnormal sensory nerve conduction.

Previously defined diagnostic criteria included cerebellar atrophy on brain MRI, neuronopathy on electrophysiological studies and negative genetic testing for other inherited ataxia syndromes like Friedriech ataxia and spinal cerebellar ataxia (SCA).

Peripheral nerve ultrasound is a noninvasive technique, able to identify abnormal peripheral nerves with underlying injuries and specific sonographic characteristics. Pelosi et al established that patients with CANVAS have a smaller nerve cross sectional area (CSA) compared to healthy individuals and/ or axonal neuropathies.

The main objective of this study was to obtaine a detailed description of peripheral nerves in consecutive patients with CANVAS syndrome followed in theneurology department of the Universitary Hospital of Nimes (France), using conventional electrophysiology and peripheral nerve ultrasound.

lead_sponsor: Centre Hospitalier Universitaire de Nīmes


title: Essure Removal for Device-attributed Symptoms: Quality of Life Evaluation Before and After Surgical Removal

acronym: ESSURE

summary:
In recent years, several symptoms have been attributed to Essure, including pelvic pain and other general symptoms. Consequently, an increasing number of patients request Essure removal for alleged adverse reactions to the device.

Study Objective: To evaluate the quality of life of patients who underwent Essure_ device removal and morbidity of this surgery.

Design: Prospective observational cohort study. Setting: Academic hospitals of La Conception, Marseille, and Arnaud-de-Villeneuve, Montpellier, France.

Patients: Women who underwent Essure_ device removal by salpingectomy, between February 2017 and August 2018.

Methods : The following information have been collected during preoperative clinics: demographic data, medical history, clinical symptoms attributed to the Essure device, time between Essure sterilization and early symptoms, time between the beginning of symptoms and surgical removal. Follow-up visits have benne scheduled at one month and three months post-operation. The evolution of symptoms was collected during the follow-up visit at three months based on clinical reports and a dedicated questionnaire. Evaluation of Quality of life have been evaluated thanks to SF36 and HAD questionnaires. Alle these patients will be contacted by phone call to assess to evolution of symptoms and to complete SF 36 and HAD questionnaires.

Hypothesis : Recovery of symptoms due to ESSURE device and improvement of quality of life after surgery.


title: A Retrospective Non-interventional Descriptive Epidemiology Study for Patients With Paraphilia Sex Offenders Receiving Androgen Antagonists Treatment

acronym: EPIPARA

summary:
The main objective of the study is to describe the french population of individuals with paraphilia who have committed a sexual offence in whom androgen antagonists was prescribed. The secondary objectives are the description of social demographic profiles, the personal and family histories,psychiatric co-morbidities, the side effects of androgen antagonists treatment. This study, the first of its kind in France, may allow to better understand the social demographic and clinical profile of sexual offenders with paraphilias treated with androgen antagonists.

To be included, the subject must have committed a sexual offense and must present a diagnosis of paraphilia with an indication of treatment with androgen antagonists. Paraphilia is defined by the Diagnostic and Statistical Manual as a sexual behavior disorder characterized by "sexually arousing fantasies, needs or recurrent and intense sexual behaviors generally involving (1) of non-human objects, (2) the suffering or humiliation of oneself or partner, (3) children or other persons without their consent, occurring during a period of at least six months "(Criterion A). This disorder is responsible for sexual behavior which is "clinically significant disturbances in social, occupational or other important areas of functioning" (Criterion B).

The inclusion of approximately 200 subjects is expected in this study. The inclusion period will last for 12 months.

Data will be codified and only a few investigators will have access to these data. The statistical analyse will use the usual descriptive parameters: mean, standard deviation, median, interquartile range and range for quantitative variables, frequencies and cumulative frequencies (if applicable) for qualitative variables.


title: Evaluation of the Efficacy of Rasagiline in Apathy in Drug-naïve Patients With Parkinson's Disease by a Multi-center, Randomized, Double-blind, Parallel-group, Placebo-controlled Study.

summary:
Among the psychiatric symptoms observed in the premotor phase of Parkinson's disease (PD) and/or in "de novo" patients, apathy is relatively frequent (estimated to 23%). However, the neuropathological bases of apathy are still unknown. However, recent data suggests that apathy could be linked to a more specific dopaminergic denervation in the ventral striatum.

Rasagiline increases the bioavailability of striatal endogenous dopamine by blocking the MAO-B. Some recent data suggest rasagiline could be effective to improve apathy in Parkinson's disease.

The primary outcome is to demonstrate a significant reduction of apathy using the Lille apathy rating scale (LARS) in drug naive patients with early diagnosed Parkinson's disease, using a treatment by rasagiline.


title: Study of the Factors Favoring the Transition From Prediabetes to Diabetes on Reunion Island. Impact of the "Say No to Diabetes" Intervention.

acronym: PREDIABRUN

summary:
The management of diabetes and its complications in Reunion island is one of the priority areas of health. Indeed, the impact of diabetes on the health of the Reunion island population is major: the prevalence of diabetes treated in Reunion island is the highest in France (10% of the population), and gestational diabetes is found in 10% of pregnancies. Reunionese diabetics develop severe complications, in particular cardiovascular (strokes, myocardial infarction).

This results in 3 times higher mortality linked to diabetes on Reunion Island, in particular among those under 65 years of age. Despite all the screening and prevention programs put in place, the weight of diabetic disease continues to increase in our island, and this is more accelerated than in the other French departments with 4,300 new cases of diabetes / year, 95% of which type 2 diabetics (T2D). The presentation of type 2 diabetic patients in Reunion island also differs from the Metropolis with subjects more often female (56%), thinner and younger at the discovery of diabetes. These data highlight the need to better understand the factors underlying the diabetes "epidemic" in Reunion island.

The rise in blood sugar until the onset of diabetes is a continuous phenomenon reflecting the progressive suffering of the organs used to maintain carbohydrate homeostasis. Thus, we talk about fasting hyperglycemia when the fasting blood sugar is between 1.10 and 1.25 g / L (6.1-6.9 mmol / l) and glucose intolerance when the blood sugar 2 hours after taking 75 g of glucose is between 1.40 and 1.99 g / L (7.8-11.0 mmol / l). Subjects with fasting hyperglycemia or glucose intolerance constitute the target population at very high risk of developing diabetes (up to 70% of these subjects). They have an increased risk of developing diabetes at 1 year multiplied by 5 to 10 compared to normoglycemic subjects, hence the name "prediabetic subjects". This great variability in the risk of developing diabetes highlights the presence of associated risk / protective factors which it is important to find in order to adapt the monitoring and management. It is important in Reunion island, in view of the specificities presented by our population, to understand the pre-diabetes / diabetes transition and the risk and protective factors.

primary_purpose: Prevention

lead_sponsor: Centre Hospitalier Universitaire de la Réunion


title: Study of Food Preferences After Bariatric Surgery

summary:
Bariatric surgery is currently considered the most effective treatment for achieving significant, sustained weight loss and reducing comorbidities associated with obesity. Every year in France, more than 55,000 undergo this surgery and nearly 450 000 French have a history of surgery for obesity. The mechanisms of action of bariatric surgery are multiple and are not limited to caloric restriction. Neuro-hormonal effects, changes in the anatomy of the digestive tract, vagal changes or bile circulation have been identified as contributing factors to weight loss and postoperative improvement of comorbidities. In addition, post-operative changes in dietary preferences have also been described, which could contribute to initial weight loss and its maintenance over time (aversion to lipid and sugar products).

The counterpart of the rapid and durable efficacy of bariatric surgery is the exposure of patients to a significant risk of protein-energy malnutrition. It should be noted that the protein intake, very limited in the first months after surgery, remains well below the recommended intake after the first postoperative year. Spontaneous consumption of meat and vegetable protein is significantly reduced during the first postoperative month and up to one year after surgery. Apart from the limitation of gastric volume induced by surgery, clinical experience indicates that many patients turn away from protein consumption by aversion. A parallel was made between the significant drop in protein consumption during the first months and the initial loss of lean mass. Thus changes in dietary preferences induced by bariatric surgery could also contribute to postoperative nutritional risk (protein aversion).

At the same time, it is noted that olfactory and taste modifications have been reported in previous studies that could be associated with these changes in food preferences.

The hypotheses of the current study are that the type of surgery may affect dietary preferences differently after obesity surgery and that surgical failure may be associated with preferences for high fat, high sweet and low protein foods postoperatively for both types of surgery.

As far as the investigating team is aware, no study compares dietary preferences between sleeve gastrectomy and gastric bypass using this approach.

time_perspective: Cross-Sectional


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

acronym: COCORTICO

summary:
Long term corticosteroid therapy concerns 0.5 to 1% of the population and about 2.5% of elderly subjects. It is currently used as a cornerstone therapy in a wide variety of clinical contexts. The central problematic of prolonged corticosteroid therapy is the burden of adverse events associated with its long term use, including bone, metabolic and infectious complications.

The management of patients for whom the prescription of long term corticosteroid therapy is indicated should include an evaluation of the individual risk and implementation of the appropriate preventive measures. Such an approach should particularly include cortisonic osteoporosis prevention, infectious prevention including vaccination, prevention of adrenal insufficiency, promotion of physical activity, as well as dietary management.

In France, nurse-led prevention programs are highly developed for patients initiating immunosuppressive targeted therapies. Conversely, there are no dedicated nurse-led programs for patients starting prolonged corticosteroid therapy, for several historical and economical reasons.

The implementation of such programs is likely to be beneficial at different levels, including the reduction of the number of adverse events and improvement of health-related quality of life.

The main objective of the study is to determine the long-term benefit of a nurse-led prevention program among patients starting long-term corticosteroids therapy, compared to routine care.

ipd_sharing_description: All collected data that underlie results in a publication


title: Efficacy and Toxicity of Blinatumomab in the French Compassionate Use Program (ATU) for Adult Patients With B-cell Precursor Acute Lymphoblastic Leukemia (BCP-ALL) Refractory, in Relapse, or With Positive Minimal Residual Disease.

acronym: FRENCH-CYTO

summary:
The outcome of young adults (18-60 years) with ALL has been dramatically improved by the use of pediatric-inspired trials. About 60% of these young adult patients will be cured at 5 years. In this context, early evaluation of minimal residual disease (MRD) at complete remission has been shown to be one of the most powerful prognostic factor, but also predictive of the benefit of allogeneic stem cell transplantation (ASCT). Despite this global improvement, about 30% of patients experience a relapse and will be exposed to be refractory to salvage therapy or to early disease escape. In adult ALL, the most important prognostic factors at relapse are : the time from first CR to relapse, the achievement of a second complete remission (CR), and the feasibility of ASCT.

Blinatumomab is a bispecific T-cell engager that recruits T-cell on CD19 positive blast cells and induces anti-leukemic cytotoxicity. In a phase 3 trial in relapse/refractory Philadelphia-negative (Ph-) ALL, 43% of patients achieved a CR or CR with partial hematological recovery (CRh), with the majority of responses occurring within the first cycle. In patients with positive MRD (MRD+) BCP-ALL, blinatumomab resulted in complete MRD response in 78% of patients after one cycle.

Between 2012 and 2016, blinatumomab was available in France for R/R and MRD+ ALL adult patients through the French Compassionate Use Program. About 92 adult ALL were treated at different stages of the disease in 27 centers.

ReferenceCitation: Dombret H, Cluzeau T, Huguet F, Boissel N. Pediatric-like therapy for adults with ALL. Curr Hematol Malig Rep. 2014 Jun;9(2):158-64. doi: 10.1007/s11899-014-0210-9. Review.

ReferenceCitation: Dhédin N, Huynh A, Maury S, Tabrizi R, Beldjord K, Asnafi V, Thomas X, Chevallier P, Nguyen S, Coiteux V, Bourhis JH, Hichri Y, Escoffre-Barbe M, Reman O, Graux C, Chalandon Y, Blaise D, Schanz U, Lhéritier V, Cahn JY, Dombret H, Ifrah N; GRAALL group. Role of allogeneic stem cell transplantation in adult patients with Ph-negative acute lymphoblastic leukemia. Blood. 2015 Apr 16;125(16):2486-96; quiz 2586. doi: 10.1182/blood-2014-09-599894. Epub 2015 Jan 13.

name: Department of Hematology and University Paris Diderot, Institut Universitaire d’Hématologie, EA-3518, University Hospital Saint-Louis, Assistance Publique Hôpitaux de Paris, Paris, France;

family: Dhédin

full_name: Nathalie Dhédin

given: Nathalie

name: Department of Hematology, University Institute of Cancer, Toulouse, France;

family: Huynh

full_name: Anne Huynh

given: Anne

name: Department of Hematology, University Hospital Henri Mondor, AP-HP, Créteil, France;

family: Maury

full_name: Sébastien Maury

given: Sébastien

name: Department of Hematology, University Hospital, Bordeaux, France;

family: Tabrizi

full_name: Reza Tabrizi

given: Reza

family: Beldjord

full_name: Kheira Beldjord

given: Kheira

name: Department of Hematology, University Paris Descartes Sorbonne Cité, Institut Necker-Enfants Malades, INSERM U1151, and Onco-Hematology Laboratory, Assistance Publique Hôpitaux de Paris, Hôpital Necker-Enfants Malades, Paris, France;

family: Asnafi

full_name: Vahid Asnafi

given: Vahid

name: Department of Hematology, Hospital Lyon Sud, Pierre Bénite, France;

family: Thomas

full_name: Xavier Thomas

given: Xavier

name: Department of Hematology, University Hospital, Nantes, France;

family: Chevallier

full_name: Patrice Chevallier

given: Patrice

name: Department of Hematology, University Hospital Pitié-Salpêtrière, Assistance Publique Hôpitaux de Paris, Paris, France;

family: Nguyen

full_name: Stéphanie Nguyen

name: Department of Hematology, University Hospital, Lille, France;

family: Coiteux

full_name: Valérie Coiteux

given: Valérie

name: Department of Hematology, Institut Gustave Roussy, Villejuif, France;

family: Bourhis

full_name: Jean-Henri Bourhis

given: Jean-Henri

name: Department of Hematology, University Hospital, Montpellier, France;

family: Hichri

full_name: Yosr Hichri

given: Yosr

name: Department of Hematology, University Hospital, Rennes, France;

family: Escoffre-Barbe

full_name: Martine Escoffre-Barbe

given: Martine

name: Department of Hematology, University Hospital, Caen, France;

family: Reman

full_name: Oumedaly Reman

given: Oumedaly

name: Department of Hematology, University Hospital, Yvoir, Belgium;

family: Graux

full_name: Carlos Graux

given: Carlos

name: Division of Hematology, Department of Medical Specialties, University Hospital, Geneva, and Faculty of Medicine, University of Geneva Switzerland and Swiss Group for Clinical Cancer Research, Bern, Switzerland;

family: Chalandon

full_name: Yves Chalandon

given: Yves

name: Department of Hematology, Institut Paoli Calmettes, Marseille, France;

family: Blaise

full_name: Didier Blaise

given: Didier

name: Division of Hematology, University Hospital of Zurich, Zurich, Switzerland;

family: Schanz

full_name: Urs Schanz

given: Urs

name: Group for Research on Adult Acute Lymphoblastic Leukemia, Coordination Office, Pierre Bénite, France;

family: Lhéritier

full_name: Véronique Lhéritier

given: Véronique

name: Department of Hematology, University Hospital, Grenoble, France; and

family: Cahn

full_name: Jean-Yves Cahn

given: Jean-Yves

family: Dombret

full_name: Hervé Dombret

given: Hervé

name: Department of Hematology and INSERM U 892/CNRS 6299, University Hospital, Angers, France

family: Ifrah

full_name: Norbert Ifrah

given: Norbert

ReferenceCitation: Gökbuget N, Stanze D, Beck J, Diedrich H, Horst HA, Hüttmann A, Kobbe G, Kreuzer KA, Leimer L, Reichle A, Schaich M, Schwartz S, Serve H, Starck M, Stelljes M, Stuhlmann R, Viardot A, Wendelin K, Freund M, Hoelzer D; German Multicenter Study Group for Adult Acute Lymphoblastic Leukemia. Outcome of relapsed adult lymphoblastic leukemia depends on response to salvage chemotherapy, prognostic factors, and performance of stem cell transplantation. Blood. 2012 Sep 6;120(10):2032-41. Epub 2012 Apr 4.

ReferenceCitation: Topp MS, Gökbuget N, Stein AS, Zugmaier G, O'Brien S, Bargou RC, Dombret H, Fielding AK, Heffner L, Larson RA, Neumann S, Foà R, Litzow M, Ribera JM, Rambaldi A, Schiller G, Brüggemann M, Horst HA, Holland C, Jia C, Maniar T, Huber B, Nagorsen D, Forman SJ, Kantarjian HM. Safety and activity of blinatumomab for adult patients with relapsed or refractory B-precursor acute lymphoblastic leukaemia: a multicentre, single-arm, phase 2 study. Lancet Oncol. 2015 Jan;16(1):57-66. doi: 10.1016/S1470-2045(14)71170-2. Epub 2014 Dec 16. Erratum in: Lancet Oncol. 2015 Apr;16(4):e158.

ReferenceCitation: Gökbuget N, Dombret H, Bonifacio M, Reichle A, Graux C, Faul C, Diedrich H, Topp MS, Brüggemann M, Horst HA, Havelange V, Stieglmaier J, Wessels H, Haddad V, Benjamin JE, Zugmaier G, Nagorsen D, Bargou RC. Blinatumomab for minimal residual disease in adults with B-cell precursor acute lymphoblastic leukemia. Blood. 2018 Apr 5;131(14):1522-1531. doi: 10.1182/blood-2017-08-798322. Epub 2018 Jan 22. Erratum in: Blood. 2019 Jun 13;133(24):2625.

name: University Hospital, Frankfurt, Germany;

name: University Hôpital Saint-Louis, Assistance Publique-Hôpitaux de Paris, University Paris Diderot, Paris, France;

name: Department of Medicine, Section of Hematology, Verona University, Verona, Italy;

name: University Hospital Regensburg, Regensburg, Germany;

name: Université Catholique de Louvain, CHU UCL Namur (Godinne), Yvoir, Belgium;

name: University Hospital and Comprehensive Cancer Center Tübingen, Universitätsklinikum Tübingen, Tübingen, Germany;

name: Department of Hematology and Oncology, Medizinische Hochschule, Hannover, Germany;

name: Medizinische Klinik und Poliklinik II, Universitätsklinikum Würzburg, Würzburg, Germany;

name: Klinik für Innere Medizin II, Universitätsklinikum Schleswig-Holstein, Kiel, Germany;

name: Cliniques Universitaires Saint-Luc, Université Catholique de Louvain, Brussels, Belgium;

name: Amgen Research (Munich), GmbH, Munich, Germany;

name: Comprehensive Cancer Center Mainfranken, Uniklinikum Würzburg, Würzburg, Germany

ReferenceCitation: Lee DW, Gardner R, Porter DL, Louis CU, Ahmed N, Jensen M, Grupp SA, Mackall CL. Current concepts in the diagnosis and management of cytokine release syndrome. Blood. 2014 Jul 10;124(2):188-95. doi: 10.1182/blood-2014-05-552729. Epub 2014 May 29. Erratum in: Blood. 2015 Aug 20;126(8):1048. Dosage error in article text. Blood. 2016 Sep 15;128(11):1533.

lead_sponsor: Group for Research in Adult Acute Lymphoblastic Leukemia


title: Osteoporosis Awareness Survey of Women in Champagne Ardenne

acronym: MPCosteoporose

summary:
Osteoporosis is characterized by low bone mineral density and alterations in bone microarchitecture, leading to bone fragility and high risk of fractures. In the peri-menopausal period and during menopause, estrogen deficiency is responsible for an acceleration of bone remodeling. It is therefore important to sensitize women to this pathology at the beginning of menopause.

Osteoporosis is a public health issue with more than 3 million women in France suffering from almost ¼ of the population over 50 years old. Paradoxically, the number of bone densitometry and prescribed osteoporosis drugs are decreasing. There is an under-screening and a disinterest of the pathology on the part of the medical world and the patients.

The investigators hypothesize that women lack knowledge about osteoporosis. This study will identify these gaps, and put in place appropriate strategies to improve this knowledge.

For this purpose, a descriptive cross-sectional observational study will carry out, through the fulfillment of self-administered questionnaire for women over 30 years old. The main objective is to assess the knowledge of women, about osteoporosis and its consequences. The judgment criterion is based on a percentage of correct answers per question. The interests of the study are to identify gaps in knowledge, to optimize the investigator's therapeutic education, to fight patient wait-and-see and false beliefs, and finally to improve adherence and longer-term adherence.


title: Altered Homing of T Lymphocytes to the Gut and Poor Immune Reconstitution of the Intestinal Mucosa in Treated HIV-infected Individuals

acronym: GALT

summary: The gut immune barrier is not fully restored in HIV-1-infected subjects despite they were receiving antiretroviral treatment. This leaky gut leads to microbial translocation from the gut lumen into the bloodstream that fuels deleterious systemic inflammation. The chemotaxis axes that allow T lymphocytes to migrate from the blood to the gut mucosa in order to reconstitute the mucosal immune barrier seems altered in treated HIV-1-infected subjects.This study aims at better understanding the mechanisms involved in this lack of mucosal immune restoration.

lead_sponsor: ANRS, Emerging Infectious Diseases

location_facility: Hôpital Purpan - Service des maladies Infectieuses

location_facility: Hôpital Purpan - Service de Médecine Interne


title: Bone Health in Adolescents and Young Adults With Oral Macro-progestin Treatment : Observational Study

acronym: MACROS

summary:
Many factors are known to influence the acquisition of bone capital, especially estrogens in women. Estrogens have a major role in bone growth and the acquisition of bone mass peaks during puberty. This peak of bone mass is an important determinant of the risk of osteoporotic fracture in adulthood.

It is known that estrogen deficiency increases the rate of bone remodeling and engenders an imbalance between resorption and bone formation, which can lead to osteoporosis.

Oral estroprogestin contraceptives have an anti-gonadotropic effect and suppress estrogen secretion by the ovaries.

However, studies in adolescents and young adults are rare and evidence of an effect on bone is still inconclusive, although there is increasing evidence that oral estroprogestin contraceptives in teenage girls may compromise the performance of the bone mass.

Macro progestins treatments are prescribed in France to patients with contraindications to estroprogestin treatments. This practice is french and few recommendations exist on the use of these molecules by the oral route. There are no studies that describe the impact of these oral treatments on the bone health of young women treated.

The Department of endocrinology, gynecology and pediatric diabetes of Necker-Enfants Malades hospital, follows many young girls taking a macro progestin treatment. This study is exclusively descriptive and will focus on the clinical and medical datas available on the bone health of these patients.


title: Non-respiratory Comorbidities Observed in Pulmonary French Transplant Patients With Cystic Fibrosis - Exploratory Study From the French Cohort on 2004-2014.

acronym: MUCO TRANSPLAN

summary:
Pulmonary transplantation is the reference treatment for chronic terminal respiratory failure in patients with cystic fibrosis. These are mainly bi-pulmonary transplants (cardiopulmonary transplants are exceptional). The annual number of pulmonary transplants in France for cystic fibrosis is about 90. In 2013, the transplant involves a total of more than 600 patients with cystic fibrosis. The average age at the time of the transplant is 28.5 years (2013 data, French cystic fibrosis register), compared to 58 years for patients transplanted to all pathologies. Cystic fibrosis accounts for 25% of adult bi-pulmonary grafts. Pediatric transplants are currently very rare.

The median survival after pulmonary transplantation in cystic fibrosis is currently 8.5 years (and 10 years when considering patients surviving 3 months, ie excluding early mortality). Cystic fibrosis is the pathology associated with better survival after pulmonary transplantation given the young age of patients (28.5 years on average).

The non-respiratory comorbidities associated with transplantation, all underlying pathologies combined, and referenced in the Registry of the International Society for Heart and Lung Transplantation (ISHLT) are: hypertension, diabetes, renal insufficiency, Dyslipidemia, cancers. Their frequency increases with the survival time of transplanted patients. Cystic fibrosis is associated with non-respiratory comorbidities, the frequency of which increases with age - diabetes, osteoporosis, renal insufficiency, hepatopathy, neoplastic pathologies - and may become worse after transplantation.

The main objective is to estimate the incidence of non-respiratory co-morbidities after lung transplantation in the cohort of patients with cystic fibrosis grafted in the Rhône-Alpes region.

lead_sponsor: Hospices Civils de Lyon

location_facility: Service de médecine interne Centre Hospitalier Lyon Sud, Hospices Civils de Lyon


title: Evaluation of Pneumococcal Vaccine Coverage

acronym: SAUVAC

summary:
Pneumococcal infections are frequent and serious. Streptococcus pneumoniae is the leading cause of community-acquired pneumonia in adults. In metropolitan France, there are 6000 to 7000 bacteremic pneumococcal infections each year, with a mortality rate of 10 to 30% in adults.

To fight against these bacterial infections, vaccines have been developed. At a time when antibiotic savings and the fight against antimicrobial resistance are major public health issues, vaccination is a first choice option to slow the development of pneumococcal resistance. Thus, after these different actions, the proportions of pneumococci with decreased susceptibility to penicillin G fell from 53 to 22%.

While there is a significant decrease in invasive pneumococcal disease in children since the use of conjugate vaccines (vaccination of up to 94% of children), the rate of invasive Pneumococcal disease in adults has decreased less significantly.

In March 2017, the High Council of Public Health (HCSP) proposed the vaccination of all non-immunocompromised adults at risk and immunocompromised patients.

Awareness-raising among vaccinating physicians seems essential, especially in recent years when the value of vaccination is threatened by speculation about its efficacy and toxicity. However, the investigators know that vaccination aims not only to protect the individual, but also the population, especially children and the elderly and the fragile people.

Thus, in the context of pneumococcal vaccination, identifying one or more profiles of patients at risk in the absence of vaccination could be particularly beneficial. Indeed, if the physician knows about the population at risk of not being vaccinated, it will be better able to identify patients at risk of not being protected against pneumococcus.


title: Rapid Diagnosis of COVID-19 by Chemical Analysis of Exhaled Air

acronym: COVIDAIR

summary:
Since the start of 2020, the new SARS-CoV-2 coronavirus is causing a real global health crisis.

In France, nasopharyngeal swabs are used to obtain the sample needed for respiratory infection screening. There are three major difficulties with this type of sampling:

I) It is really unpleasant for the patient because the device has to be pushed into the nostril to reach the nasopharynx. It causes some patients to bleed or even feel uncomfortable.

II) It is not easily accepted by children. III) It is dependent on the availability of swabs. Faced with these difficulties linked to the initial sampling, new methods are being studied to enable a rapid and non-invasive diagnosis of COVID-19 based on the instantaneous identification of metabolites or volatile organic compounds (VOCs).

Due to their sensitivity and the wealth of information that can be provided, the most promising techniques are based on mass spectrometry coupled with a soft ionisation system. For example, on-line exhaled air analysis is capable of detecting a very large number of VOCs. Various tests on metabolites in the exhaled air have already been carried out without being totally conclusive because the existing instruments suffer from various limitations:

I) poor repeatability/accuracy in the chemical characterisation of exhaled air ; II) too high specificity (detection of only part of the emitted compounds); III) too limited sensitivity; IV) and poor adaptation to be deployed in a clinic.

In order to overcome these various limitations, we propose the use of a new generation of mass spectrometer: Vocus PTR-TOF. The Vocus PTR-TOF is a Proton Transfer Mass Spectrometer (PTR-MS) developed for the detection, in real time, of trace VOCs in industrial environments, laboratories or directly in the environment. This new generation of instrument offers the following advantages:

I) unequalled sensitivity :

II) a robust ionisation system not affected by environmental conditions (relative humidity...) ; III) a high mass resolution allowing precise identification of compounds ; IV) a compact and durable architecture allowing deployment in a constrained environment such as hospital, airport… The sensitivity and speed of measurement allow the expiration process to be monitored in real time, bringing an additional dimension to the measurement and the chances of success.

location_facility: Centre de prélèvement COVID-19 HCL et Métropole de Lyon

intervention_type: Diagnostic Test


title: Effects of Regular and Consequent Citrus Fruit Consumption on Vascular Protection Specific Role of the Component Phytomicronutrients

acronym: AGRUVASC

summary:
Epidemiological studies definitively show that fruit and vegetable consumption is positive for health and more specifically for cardiovascular diseases (CVD) prevention. In France, among fruits, those which are the most frequently consumed are citrus fruits essentially as juices and more specifically as orange juices. However, their health effects have been poorly studied so far. Citrus fruits contain vitamin C associated with various phytomicronutrients i.e. carotenoids (essentially -cryptoxanthin) and polyphenols. Each fruit contains specific compounds: hesperetin in orange, naringenin in grapefruit, eriodyctiol in lemon. Some scientific studies performed either in vitro or in animal models demonstrated properties of these micronutrients which could contribute to a positive health effect of citrus fruits on vascular protection. However data are still missing.

The main goal of this project is to characterize the effect of orange juice consumption on vascular disease risk factors and to evaluate the specific role of their micronutrient compounds (polyphenols and carotenoids) in this protection. To reach this goal, a randomized "cross-over" clinical study will be performed on volunteers presenting a mild hypercholesterolemia. They will consume for 4 weeks an orange juice or a reconstituted drink similar to the orange juice for its composition in carbohydrates, minerals, vitamin C and folates but without phytomicronutrients. The effect of the juice consumption on the vascular function will be monitored exploring lipid abnormalities in plasma, measuring endothelial vasoreactivity (FMD) (Flow Mediated Dilatation), as well as endothelial dysfunction, thrombosis, inflammation and oxidative stress biomarkers in plasma. Comparison of urinary metabolomes after orange juice consumption or that of the reconstituted drink will lead to the identification of the metabolic pathways modulated by the orange juice micronutrients.

Moreover ELISA tests for the two major flavanones from citrus fruits (hesperetin and naringenin) will be developed. They will be used to determine the plasma levels of these molecules in order to analyze the relation "ingested quantity - bioavailable quantity - physiological effect".

The results obtained in this project will allow clarifying citrus fruit effects, and particularly orange juice, in vascular protection.

ReferenceCitation: Hertog MG, Feskens EJ, Hollman PC, Katan MB, Kromhout D. Dietary antioxidant flavonoids and risk of coronary heart disease: the Zutphen Elderly Study. Lancet. 1993 Oct 23;342(8878):1007-11.

ReferenceCitation: Hertog MG, Kromhout D, Aravanis C, Blackburn H, Buzina R, Fidanza F, Giampaoli S, Jansen A, Menotti A, Nedeljkovic S, et al. Flavonoid intake and long-term risk of coronary heart disease and cancer in the seven countries study. Arch Intern Med. 1995 Feb 27;155(4):381-6. Erratum in: Arch Intern Med 1995 Jun 12;155(11):1184.

ReferenceCitation: Knekt P, Jarvinen R, Reunanen A, Maatela J. Flavonoid intake and coronary mortality in Finland: a cohort study. BMJ. 1996 Feb 24;312(7029):478-81.

ReferenceCitation: Yochum L, Kushi LH, Meyer K, Folsom AR. Dietary flavonoid intake and risk of cardiovascular disease in postmenopausal women. Am J Epidemiol. 1999 May 15;149(10):943-9. Erratum in: Am J Epidemiol 1999 Aug 15;150(4):432.

ReferenceCitation: Geleijnse JM, Launer LJ, Van der Kuip DA, Hofman A, Witteman JC. Inverse association of tea and flavonoid intakes with incident myocardial infarction: the Rotterdam Study. Am J Clin Nutr. 2002 May;75(5):880-6.

ReferenceCitation: Leuzzi U, Caristi C, Panzera V, Licandro G. Flavonoids in pigmented orange juice and second-pressure extracts. J Agric Food Chem. 2000 Nov;48(11):5501-6.

ReferenceCitation: Jung HA, Jung MJ, Kim JY, Chung HY, Choi JS. Inhibitory activity of flavonoids from Prunus davidiana and other flavonoids on total ROS and hydroxyl radical generation. Arch Pharm Res. 2003 Oct;26(10):809-15.

ReferenceCitation: Franke AA, Cooney RV, Henning SM, Custer LJ. Bioavailability and antioxidant effects of orange juice components in humans. J Agric Food Chem. 2005 Jun 29;53(13):5170-8.

ReferenceCitation: Lee DH, Gross MD, Jacobs DR Jr; Cardiovascular Risk Development in Young Adults Study. Association of serum carotenoids and tocopherols with gamma-glutamyltransferase: the Cardiovascular Risk Development in Young Adults (CARDIA) Study. Clin Chem. 2004 Mar;50(3):582-8. Epub 2004 Jan 15.

ReferenceCitation: Dwyer JH, Paul-Labrador MJ, Fan J, Shircore AM, Merz CN, Dwyer KM. Progression of carotid intima-media thickness and plasma antioxidants: the Los Angeles Atherosclerosis Study. Arterioscler Thromb Vasc Biol. 2004 Feb;24(2):313-9. Epub 2003 Dec 1.

ReferenceCitation: Aneja R, Hake PW, Burroughs TJ, Denenberg AG, Wong HR, Zingarelli B. Epigallocatechin, a green tea polyphenol, attenuates myocardial ischemia reperfusion injury in rats. Mol Med. 2004 Jan-Jun;10(1-6):55-62.

ReferenceCitation: Hadjadj S, Paul JL, Meyer L, Durlach V, Vergès B, Ziegler O, Drouin P, Guerci B. Delayed changes in postprandial lipid in young normolipidemic men after a nocturnal vitamin A oral fat load test. J Nutr. 1999 Sep;129(9):1649-55.

ReferenceCitation: Constans J, Conri C. Circulating markers of endothelial function in cardiovascular disease. Clin Chim Acta. 2006 Jun;368(1-2):33-47. Epub 2006 Mar 10. Review.

ReferenceCitation: Gorinstein S, Caspi A, Libman I, Lerner HT, Huang D, Leontowicz H, Leontowicz M, Tashma Z, Katrich E, Feng S, Trakhtenberg S. Red grapefruit positively influences serum triglyceride level in patients suffering from coronary atherosclerosis: studies in vitro and in humans. J Agric Food Chem. 2006 Mar 8;54(5):1887-92.

ReferenceCitation: Gorinstein S, Leontowicz H, Leontowicz M, Drzewiecki J, Jastrzebski Z, Tapia MS, Katrich E, Trakhtenberg S. Red Star Ruby (Sunrise) and blond qualities of Jaffa grapefruits and their influence on plasma lipid levels and plasma antioxidant activity in rats fed with cholesterol-containing and cholesterol-free diets. Life Sci. 2005 Sep 23;77(19):2384-97.

ReferenceCitation: Gorinstein S, Leontowicz H, Leontowicz M, Krzeminski R, Gralak M, Delgado-Licon E, Martinez Ayala AL, Katrich E, Trakhtenberg S. Changes in plasma lipid and antioxidant activity in rats as a result of naringin and red grapefruit supplementation. J Agric Food Chem. 2005 Apr 20;53(8):3223-8.

ReferenceCitation: Constans J, Bennetau-Pelissero C, Martin JF, Rock E, Mazur A, Bedel A, Morand C, Bérard AM. Marked antioxidant effect of orange juice intake and its phytomicronutrients in a preliminary randomized cross-over trial on mild hypercholesterolemic men. Clin Nutr. 2015 Dec;34(6):1093-100. doi: 10.1016/j.clnu.2014.12.016. Epub 2014 Dec 26.

family: Constans

full_name: Joël Constans

given: Joël

family: Bennetau-Pelissero

full_name: Catherine Bennetau-Pelissero

given: Catherine

family: Martin

full_name: Jean-François Martin

given: Jean-François

family: Rock

full_name: Edmond Rock

given: Edmond

family: Mazur

full_name: Andrzej Mazur

given: Andrzej

family: Bedel

full_name: Aurélie Bedel

given: Aurélie

family: Morand

full_name: Christine Morand

given: Christine

family: Bérard

full_name: Annie M. Bérard

given: Annie M.

journal_name: Clinical Nutrition

lead_sponsor: University Hospital, Bordeaux

location_facility: Hopital Saint André - Service de Médecine Interne - Pathologie Vasculaire


title: Study of the Changes in Glycemic Control and Psychological Distress in Diabetic Patients After the Confinement Period Related to the COVID-19 Epidemic

acronym: COVIGLYSTRESS

summary: Prospective, non-interventional, multicentric study

lead_sponsor: Rennes University Hospital

location_facility: Centre Hospitalier de l'Agglomération Montargoise