title: Study of the Evolution of the Intestinal Microbiome (Taxonomic and Functional Composition) During Alcoholic Liver Disease

acronym: MICMAF

summary:
Excessive alcohol consumption is a major public health problem, particularly in France. It is the leading cause of cirrhosis and hepatocellular carcinoma. Among subjects with heavy alcohol consumption, the majority of patients develop fatty liver overload (steatosis), but only 10 to 35% develop acute alcoholic hepatitis (AAH) and 8 to 20% progress to cirrhosis. Steatosis is the earliest lesion, rapidly reversible after abstinence from alcohol. On the other hand, the occurrence of AAH leads to a strong progression of fibrosis. The investigators have shown on serial liver biopsies that a subgroup of heavy drinkers develop episodes of AAH and progress to cirrhosis. Therefore, factors other than the amount of alcohol consumed alone influence the development and progression of alcoholic liver disease (ALD). Among these factors, it is now accepted that the gut microbiome plays an important role in the pathogenesis of ALD. Increased intestinal permeability and activation of the innate immune system by lipolysaccharide (LPS) of digestive origin is a key factor in the initiation of AAH. The alteration of the intestinal barrier induced by alcohol abuse seems to involve dysbiosis. Furthermore, the investigatorshave shown that the sensitivity of the liver to alcohol toxicity is transmissible from humans to mice via the gut microbiome. Despite these advances, the causal relationship between mycobiome disruption and ALD in humans requires confirmation in prospective studies.

The intestinal microbiome represents all the microorganisms found in the digestive tract: bacteria (bacterial microbiome), viruses (virome), fungi (mycobiome).

Recent data point to the role of disturbances of the mycobiome and the virome in human pathology. The intestinal virome consists of two major types of viruses: eukaryotic RNA and DNA viruses that infect host cells and prokaryotic or bacteriophage viruses that infect the bacterial microbiome. Recent evidence suggests that the virome participates in immune system homeostasis. Infection of axenic mice with murine norovirus restores the functionality of intestinal lymphocytes. However, the involvement of the intestinal virome in ALD has never been studied.

Cessation of alcohol consumption has a beneficial effect in all stages of ALD . It reduces the risk of complications of cirrhosis and, for early stages of liver damage, prevents progression to advanced stages (severe AAH and cirrhosis). Unfortunately, most patients with alcohol addiction do not achieve long-term abstinence or significant reduction in their consumption despite psychological and medical support. Depression and anxiety are also associated with gut dysbiosis in humans. The causal role, at least partial, of this dysbiosis in addictive phenomena, whether alcohol or other addictions such as cocaine, has been shown. Thus, the modification of MI influences the addictive behavior of cocaine-dependent mice (. All these data show the major role of the microbiota-central nervous system (CNS) axis in mental disorders such as alcohol addiction and its consequences (craving, depression, anxiety). This interaction is mediated by several mechanisms such as the production of active metabolites by the intestinal microbiome and the translocation of bacteria or bacterial derivatives.

Primary Objective:

To characterize temporal changes in the gut microbiome (bacterial, viral, and fungal) within sequential specimens (stool, saliva, serum) prior to the occurrence of acute alcoholic hepatitis episodes

Secondary Objectives:

Demonstrate that specific fecal, serum, or saliva microbiome profiles (bacterial, viral, and fungal) can predict the progression of alcoholic liver disease to severe alcoholic hepatitis, fibrosis, and cirrhosis.
Characterize changes in the composition of the gut microbiome (bacterial, viral and fungal) associated with the progression of alcoholic liver disease to severe alcoholic hepatitis and cirrhosis.
Characterize the changes in the microbiome during alcohol withdrawal.
Identify microbiome profiles associated with alcohol dependence and anxiety-depressive events related to alcohol addiction.
To identify bacterial species with a protective effect in alcoholic liver disease.
To identify beneficial bacterial species against alcohol dependence.
To study the microbiome-host interaction in alcoholic liver disease and alcohol addiction.
To identify microbiome profiles with prognostic value in severe alcoholic hepatitis and alcoholic cirrhosis.

Number of centers: 7 Number of subjects expected 1000 Population concerned: The study will include a population of patients with excessive alcohol consumption seen in consultation or hospitalized for alcohol addiction problems and/or exploration of alcohol-related liver damage Inclusion period: January 2020 - January 2030 Patient observation period: 5 to 20 years Study duration: 30 years


title: PREPARE Work Package 3 -Development of a Serocorrelate of Protection Against GBS - Protocol Harmonisation.

summary: A multicentre, international case-control study to develop a biobank of sera from 150 cases of serotype III GBS disease and associated clinical information from seven countries (Malawi, Uganda, UK, the Netherlands, Italy and France), with 3:1 (450) serotype matched healthy controls.

study_start_date_type: Actual

status: Recruiting

study_completion_date_type: Anticipated

study_type: Observational

time_perspective: Prospective

enrollment_type: Anticipated

ipd_sharing: No

lead_sponsor: St George's, University of London

collaborators: Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)

location_country:
Malawi
Italy
Uganda
United Kingdom
Netherlands
France

location_facility: Academisch Medisch Centrum,Universiteit van Amsterdam

location_facility: Azienda Ospedaliero-Universitaria di Modena (AOU)

location_facility: Assistance Publique Hopitaux de Paris (AP-HP)

location_facility: Queen Elizabeth Central Hospital College of Medicine, P.O. Box 30096 Chichiri,

location_facility: MUJHU - Makerere University Johns Hopkins University Research Collaboration/MUJHU Care Ltd

lead_sponsor_type: academique

status_simplified: Ongoing


title: Attitude of Unscreened Women Face to Different Strategies to Participate in Cervical Cancer Screening by Vaginal Self-sampling : Home-mailed or Invitation to Remove to Their General Practitioner

summary: Despite the existence of an effective screening test (pap smear), cervical cancer is, every year in France, the cause of more than 3,000 new cases and 1,100 deaths. But, in France, 4 in 10 women are not screened or not often enough (nearly 7 millions women). It is therefore necessary to develop new strategies to reach these women. The etiological factor of this cancer is persistent infection with High-Risk Human PapillomaVirus oncogene (HR-HPV). Thereby, HPV-based tests could be alternative screening tests. Vaginal self-sampling with HR-HPV test is simpler and less intrusive than the pap smear. It has been shown that vaginal self-sampling with HPV test is a powerful means to increase the participation rate in cervical cancer screening.

status: Completed

study_completion_date_type: Actual

study_type: Interventional

design_allocation: Randomized

primary_purpose: Screening

enrollment_type: Actual

ReferenceType: derived

ReferenceCitation: Boyard J, Caille A, Brunet-Houdard S, Sengchanh-Vidal S, Giraudeau B, Marret H, Rolland-Lozachmeur G, Rusch E, Gaudy-Graffin C, Haguenoer K. A Home-Mailed Versus General Practitioner-Delivered Vaginal Self-Sampling Kit for Cervical Cancer Screening: A Cluster Randomized Controlled Trial with a Cost-Effectiveness Analysis. J Womens Health (Larchmt). 2022 Oct;31(10):1472-1480. doi: 10.1089/jwh.2021.0597. Epub 2022 Jul 13.

oa_host_type: closed

repositories_concat: closed

publisher_dissemination: Mary Ann Liebert Inc

lead_sponsor: University Hospital, Tours

intervention_type: Behavioral

status_simplified: Completed


title: Intraocular Concentrations Study (Aqueous Humor, Vitreous Humor) of Antibiotics After Local and/or Systemic Administration in Endophthalmitis

acronym: CINEBIOPHTA

summary: Endophthalmitis is an intraocular inflammation due to a serious infection of bacterial, fungal or parasitic origin, involving visual prognosis if it is not treated in time and correctly. Despite the eye isolation from the rest of the body, germs can enter the eye either exogenously, during open globe surgery, following perforating eye trauma, or following anti-VEGF antibodies intravitreal injection, or other drugs such as corticosteroids for example, or by endogenous route, haematogenic as part of sepsis, usually during immunodepression. Post-operative endophthalmitis is the most feared complication following any endo-ocular surgery. It can be acute, occurring within 6 weeks post-operatively or delayed as after poor healing, or on a glaucoma filtration bubble. Endophthalmitis after cataract surgery is a complication with a low incidence of (0.030 to 0.047%) but which, due to interventions number carried out (830,000 in 2016, in France), appears significant. There are factors that favour endophtalmitis occurrence such as a vitreous exit from eyeball during surgical procedure, poor scar coaptation, premature removal of sutures, etc... They condition emergency care. Early diagnosis and appropriate treatment are essential for safeguarding the eye and its function. Therefore, therapeutic management requires endo-ocular sampling in front of any suspicion of endophtalmitis, to be done before any treatment, to carry out microbiological analysis (direct examination on slide, culture, universal and/or targeted PCR, antibiotic susceptibility test). Vitreous puncture is more contributive than anterior chamber puncture, underlining need for these two samples to identify the responsible germ. Once samples have been taken, a broad-spectrum antibiotic therapy introduction must be performed intra-vitreously combined with systemic and local administration. Intravitreal injections allow treatment to be provided at effective concentrations directly at the infection site. On the other hand, toxic risks must be taken into account, especially since the protocol may require multiple intravitreal injections.

status: Active, not recruiting

primary_purpose: Treatment

ReferenceType: result

ReferenceCitation: Du DT, Wagoner A, Barone SB, Zinderman CE, Kelman JA, MaCurdy TE, Forshee RA, Worrall CM, Izurieta HS. Incidence of endophthalmitis after corneal transplant or cataract surgery in a medicare population. Ophthalmology. 2014 Jan;121(1):290-298. doi: 10.1016/j.ophtha.2013.07.016. Epub 2013 Aug 29.

oa_host_type: publisher

evidence: open (via free pdf)

host_type: publisher

license_normalized: no license

version: publishedVersion

unpaywall_oa_status: bronze

publisher_dissemination: Elsevier

ReferenceCitation: Clarke B, Williamson TH, Gini G, Gupta B. Management of bacterial postoperative endophthalmitis and the role of vitrectomy. Surv Ophthalmol. 2018 Sep-Oct;63(5):677-693. doi: 10.1016/j.survophthal.2018.02.003. Epub 2018 Feb 15.

ReferenceCitation: Goldschmidt P, Bensaid P, Semoun O, Chaumeil C. [Rational approach for the treatment of postoperative endophthalmitis in impoverished populations]. J Fr Ophtalmol. 2013 Mar;36(3):261-7. doi: 10.1016/j.jfo.2012.08.002. Epub 2013 Feb 11. French.

ReferenceCitation: Kumar A, Sridhar MS, Dada T, Tewari HK, Gupta SK. Intravitreal pefloxacin therapy in postoperative endophthalmitis. Clin Exp Ophthalmol. 2000 Feb;28(1):38-40. doi: 10.1046/j.1442-9071.2000.00256.x.

ReferenceCitation: Khera M, Pathengay A, Jindal A, Jalali S, Mathai A, Pappuru RR, Relhan N, Das T, Sharma S, Flynn HW. Vancomycin-resistant Gram-positive bacterial endophthalmitis: epidemiology, treatment options, and outcomes. J Ophthalmic Inflamm Infect. 2013 Apr 22;3(1):46. doi: 10.1186/1869-5760-3-46.

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: PubMed Central - Europe PMC

repository_normalized: PubMed Central

evidence: oa repository (via pmcid lookup)

repositories_concat: PubMed Central

unpaywall_oa_status: gold

publisher_dissemination: Springer

ReferenceCitation: Chiquet C, Labetoulle M. [Fluoroquinolones in ophthalmology: indications and current use]. J Fr Ophtalmol. 2008 Oct;31(8):803-8. doi: 10.1016/s0181-5512(08)74403-6. French.

ReferenceCitation: Adenis JP, Mounier M, Salomon JL, Denis F. Human vitreous penetration of imipenem. Eur J Ophthalmol. 1994 Apr-Jun;4(2):115-7. doi: 10.1177/112067219400400207.

ReferenceCitation: Bowen RC, Zhou AX, Bondalapati S, Lawyer TW, Snow KB, Evans PR, Bardsley T, McFarland M, Kliethermes M, Shi D, Mamalis CA, Greene T, Rudnisky CJ, Ambati BK. Comparative analysis of the safety and efficacy of intracameral cefuroxime, moxifloxacin and vancomycin at the end of cataract surgery: a meta-analysis. Br J Ophthalmol. 2018 Sep;102(9):1268-1276. doi: 10.1136/bjophthalmol-2017-311051. Epub 2018 Jan 11.

oa_host_type: repository

version: acceptedVersion

unpaywall_oa_status: green

publisher_dissemination: British Medical Journal

ReferenceCitation: Cornut PL, Chiquet C. [Intravitreal injection of antibiotics in endophthalmitis]. J Fr Ophtalmol. 2008 Oct;31(8):815-23. doi: 10.1016/s0181-5512(08)74405-x. French.

ReferenceCitation: Gan IM, van Dissel JT, Beekhuis WH, Swart W, van Meurs JC. Intravitreal vancomycin and gentamicin concentrations in patients with postoperative endophthalmitis. Br J Ophthalmol. 2001 Nov;85(11):1289-93. doi: 10.1136/bjo.85.11.1289.

ReferenceCitation: Thompson AM. Ocular toxicity of fluoroquinolones. Clin Exp Ophthalmol. 2007 Aug;35(6):566-77. doi: 10.1111/j.1442-9071.2007.01552.x.

lead_sponsor: Fondation Hôpital Saint-Joseph

collaborators: Centre Hospitalier National d'Ophtalmologie des Quinze-Vingts

intervention_type: Other


title: Evaluation of an Education Program for Patients With Hypermobility Type Ehlers-Danlos Syndrome

acronym: PREDUSED

summary:
The Ehlers-Danlos Syndrome (SED) comprises a group of clinically and genetically heterogeneous, inherited connective tissue diseases. The hypermobility type is the most frequent. It is characterized by a generalized joint hypermobility and a hyperextension skin.

Chronic pain syndrome is often present. Its psychological impact can be significant (anxiety, depression, impact on the quality of life of the patients). The disease also requires changes and a permanent adaptability (coping). It can lead to feelings of isolation and misunderstanding.

The French association of the Ehlers-Danlos Syndromes and the rehabilitation center of the 'Croix-Rouge Française des Massues' propose a patient education program for the patients with a hypermobility type SED (the PrEduSED program). This education program is open to patients and their caregivers located in France.

The research hypothesis is that the PrEduSED program improves their coping and reduces patient anxiety at 6 months (these are the two clinical criteria on which the PrEduSED could have the most impact, given the results of the first sessions).

lead_sponsor: Hospices Civils de Lyon

location_facility: Pôle Information Médicale Evaluation Recherche - Hospices Civils de Lyon


title: Study of Association Between Quantity (and Percentage) of Visceral Adipose Tissue and NAFLD-linked Liver Stifness as Mesured by Fibroscan in a Retrospective Cohort of Diabetes Mellitus Patients

summary:
Non Alcoholic Fatty Liver Disease (NAFLD) is an emergent disease worldwide, and soon the leading cause of hepatic transplant in the USA. Among this high number of patients, the current challenge is to detect or even predict patients at risk of inflammation (Non Alcoholic or Steatohepatitis or NASH) and end-stage fibrosis, which are the best predictors of liver-related mortality.

Visceral obesity is intimately associated with metabolic disease and adverse health outcomes, such as diabetes, and NAFLD. It has been demonstrated that visceral adipose tissue-linked inflammation was a risk factor of stroke, myocardial infarction, and others metabolic-related complications.

The aim of this study was to evaluate the association of the quantity and percentage of Visceral Adipose Tissue by Dual X-Ray Absorptiometry and liver stiffness by Fibroscan in patients with type 2 diabetes, and other predictors of fibrosis such as FIB-4 and Fibrotest. We retrospectively collected the data of all the diabetic patients who had undergone a DEXA and a Fibroscan between January 1st, 2014 and Decembre 31th, 2019, in the Universitary Hospital of Nancy, France.

study_start_date_type: Anticipated

status: Unknown status

time_perspective: Retrospective

ipd_sharing: Undecided

lead_sponsor: Central Hospital, Nancy, France

status_simplified: Unknown


title: Assessing the Impact of the COVID-19 Lockdown on Metabolic Control and Access to Health Care in Patients With Diabetes: a Monocentric Cross-sectional Study

acronym: CONFI-DIAB

summary:
The outbreak of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the COVID-19 (Coronavirus Disease-2019) in December 2019 has led to an unprecedented international health situation. Exceptional measures have been taken by public authorities worldwide in order to slow the spread of the virus and prevent healthcare systems from becoming overloaded. In France, a national lockdown has been established during approximately 2 months to increase social distancing and restrict population movements. Hospital routine care appointments have been cancelled, in order to reallocate medical resources towards COVID-19 units and limit contacts between patients within hospitals or waiting rooms. While the virus itself, the disease and potential treatments are currently extensively studied, little data are available on the effect of these public health decisions on the management of a chronic condition such as diabetes.

The French regional CONFI-DIAB study aims at assessing the collateral impact of routine care cancellation during the national lockdown due to COVID-19 in patients with a chronic condition such as diabetes. Special attention will be given to metabolic control and access to health care.

This cross-sectional study should provide information on the consequences of a global lockdown and the associated routine care cancellation on the management of diabetes, and inform future decision making in the event of a new pandemic.

time_perspective: Cross-Sectional

ReferenceCitation: Ludwig L, Scheyer N, Remen T, Guerci B. The Impact of COVID-19 Lockdown on Metabolic Control and Access to Healthcare in People with Diabetes: the CONFI-DIAB Cross-Sectional Study. Diabetes Ther. 2021 Aug;12(8):2207-2221. doi: 10.1007/s13300-021-01105-y. Epub 2021 Jul 9.

license: cc-by-nc

license_normalized: cc-by-nc

publisher_dissemination: Springer-Nature


title: The Influence of Age on Bispectral Index Associated With Propofol-induced Sedation

summary:
The bispectral index (BIS) is commonly used in anesthesia to evaluate the depth of sedation. Numerous studies in adults have shown good correlation between bispectral index values and depth of sedation regardless of the hypnotic drug used. Requirements of intravenous and inhalational hypnotic agents to suppress consciousness decrease with age. A study showed that the loss of consciousness (LOC) was obtained with lower concentrations of sevoflurane in elderly than in young adults, but at identical BIS values, so that BIS would predict depth of sedation better than drug monitoring. This result incited the use of bispectral index monitoring to overcome the significant pharmacological variability, especially in elderly. Nevertheless, another research with a comparable methodology during propofol-induced anaesthesia provided higher BIS values at LOC in elderly compared to younger patients. In these two trials, LOC was defined differently: either by absence of verbal response corresponding to loss of eyelash reflex (LOER) or by absence of response to prodding [(OAA/S) <2)]. Otherwise electromyographic activity (EMG) was not taken in account. As high EMG level (greater than 50 decibels) could create subtle artifact signal pollution without necessarily being displayed as artifacts, this would be misinterpreted by the BIS algorithm as EEG activity and assigned a spuriously increased BIS value.

The main objective of our study was to specifically evaluate BIS values according to age during propofol-induced sedation. LOC was measured by obtaining an OAA/S score <2 (OAA/S2), or a deeper sedation criterion: loss of eyelash reflex (LOER). The secondary objective was to specify the influence of EMG on the displayed BIS values and its age-related modifications.

lead_sponsor: Centre Hospitalier Universitaire de Saint Etienne

intervention_type: Drug


title: Prevalence of Rectal Carriage of Carbapenemase Producing-Enterobacteriaceae on Admission to a French University Teaching Hospital

acronym: Prev-CPE

summary:
"The emergence and spread of highly resistant bacteria, including carbapenemase-producing Enterobacteriaceae (CPE), is a public health challenge given their rapid spread and the lack of active antibiotics against these bacteria. The spread of extended-spectrum β-lactamase-producing Enterobacteriaceae (ESBLE) since the early 2000s raises concerns about a potential similar spread of CPE in the coming years, especially in the healthcare setting. Early detection of CPE carriage in hospitalized patients with risk factors for CPE carriage is essential to prevent their spread in hospitals as well as to guide empiric antibiotic therapy for CPE carriers with signs of severe infection. However, the prevalence of CPE carriage on admission to hospital is not precisely known, nor are factors associated with CPE carriage.

Hence, the investigators sought to determine the prevalence of CPE carriage and its risk factors in patients admitted to hospital, in order to identify the appropriate indications for CPE screening on admission to hospital. Secondly, the investigators aimed to estimate the annual number of patients with CPE carriage who would not have been identified with the current targeted screening policy as well as to estimate the annual number of secondary cases that could be prevented if a universal screening policy was applied on admission (i.e. for all hospitalized patients, not just those with risk factors).

Therefore, the investigators plan to carry out a systematic screening for rectal carriage of CPE on admission in a sample of patients hospitalized at the Bichat - Claude-Bernard Hospital. Inclusion criteria will include: Age ≥ 18 years, admission to a medical, surgical, obstetrical or intensive care unit at Bichat - Claude-Bernard Hospital in the previous 72 hours, no objection to participating in the study. Rectal swabs will be taken from all included patients for detection of CPE and/or ESBLE. Patients' characteristics, including sociodemographic data, country of birth and residence, clinical ward, current antibiotic treatment and that in the last 3 months, travel abroad and last geographical areas visited, hospitalization in France and abroad, and history of CPE and ESBLE carriage or infection in the previous year, will be collected by questionnaire and from medical records. "

lead_sponsor: Assistance Publique - Hôpitaux de Paris


title: Evaluation of Effectiveness of Tabac Info Service (EE-TIS)

summary:
Introduction - A national smoking cessation E-intervention, called Tabac Info Service (TIS), was developed in France to provide an adapted web and mobile application support to smoking cessation for all adults smokers, with or without chronic diseases, who want to stop smoking. This paper presents the study protocol of the evaluation of the program. The primary objective of this evaluation is to assess the efficacy and efficacy conditions of eTIS. The secondary objectives are to 1) describe efficacy variations in regard to user characteristics, 2) analyze mechanisms and efficacy conditions of eTIS, through variations of use, social or environmental contextual factors likely to influence the efficacy of eTIS, and the behavior change techniques (BCTs).

Methods and analyses - The study design is a two-arm pragmatic randomized controlled trial including a process evaluation with at least 3000 participants randomized to the intervention or to the control arm (current practices presented in a non-interactive website). Inclusion criteria are: Adults, Smokers with an information and consent form completed, Getting a smartphone and using mobile applications, wanting stop to smoking in short, medium or long terms. The exclusion criterion is the refusal to participate in the study. The primary outcome is the point prevalence abstinence of 7 days at 6 months later. The secondary outcomes are: the point prevalence abstinence of 24 h at 3 months later, the point prevalence abstinence of 30 days at 12 months later, number of quit attempts during the study, progression of stages within the program (changes and duration in each stage). Data will be analyzed in Intention to treat (main analyze) and per protocol ways. A logistic regression will be carried out to estimate an OR [95% confidence interval] for efficacy. A multivariate multilevel analysis will explore the influence of patients' characteristics, social and environmental context, conditions of use and behavior change techniques on results.

Dissemination -The findings of this study will allow us to understand and characterize the efficacy of eTIS, and conditions of its efficacy, underlining psychological, sociological, environmental and contextual factors, which could influence the efficacy of this type of intervention on smokers. These findings will be disseminated through peer-reviewed journals, national and international conference presentations and public events.

primary_purpose: Prevention

ReferenceCitation: Affret A, Luc A, Baumann C, Bergman P, Le Faou AL, Pasquereau A, Arwidson P, Alla F, Cambon L. Effectiveness of the e-Tabac Info Service application for smoking cessation: a pragmatic randomised controlled trial. BMJ Open. 2020 Oct 27;10(10):e039515. doi: 10.1136/bmjopen-2020-039515.

repository_institution: Le Centre pour la Communication Scientifique Directe - HAL - memSIC

repository_normalized: HAL

repository_institution: Universite de Bordeaux - Oskar-Bordeaux

repository_institution: Le Centre pour la Communication Scientifique Directe - HAL - Diderot

repositories:
HAL
PubMed Central
oskar-bordeaux.fr

repositories_concat: HAL;PubMed Central;oskar-bordeaux.fr

ReferenceCitation: Cambon L, Bergman P, Le Faou A, Vincent I, Le Maitre B, Pasquereau A, Arwidson P, Thomas D, Alla F. Study protocol for a pragmatic randomised controlled trial evaluating efficacy of a smoking cessation e-'Tabac Info Service': ee-TIS trial. BMJ Open. 2017 Feb 24;7(2):e013604. doi: 10.1136/bmjopen-2016-013604.

repository_institution: Le Centre pour la Communication Scientifique Directe - HAL - Université Toulouse - Jean Jaurès

repository_institution: Le Centre pour la Communication Scientifique Directe - HAL - Université Savoie Mont Blanc

endpoint_id: HAL

repository_institution: HAL

version: submittedVersion

repositories:
HAL
PubMed Central

repositories_concat: HAL;PubMed Central

lead_sponsor: Ecole des Hautes Etudes en Santé Publique

lead_sponsor_type: industriel


title: PAthwAy of Dyspneic patIent in Emergency

acronym: PArADIsE

summary:
This is an observational retrospective single-center study (CHRU of Nancy) in patients cared for acute dyspnea by a medical team of the emergencies of the CHRU of Nancy.

The main purpose of the study is to evaluate the outcome of patients cared for acute dyspnea by a medical team of emergencies of CHRU of Nancy.

ReferenceCitation: Chouihed T, Bassand A, Duarte K, Jaeger D, Roth Y, Giacomin G, Delaruelle A, Duchanois C, Bannay A, Kobayashi M, Rossignol P, Girerd N. Head-to-head comparison of diagnostic scores for acute heart failure in the emergency department: results from the PARADISE cohort. Intern Emerg Med. 2022 Jun;17(4):1155-1163. doi: 10.1007/s11739-021-02879-6. Epub 2021 Nov 17.

repository_institution: Le Centre pour la Communication Scientifique Directe - HAL - Inria

repository_institution: Le Centre pour la Communication Scientifique Directe - HAL - Université Paris Descartes

repositories_concat: HAL

ReferenceCitation: Chouihed T, Buessler A, Bassand A, Jaeger D, Virion JM, Nace L, Barbe F, Salignac S, Rossignol P, Zannad F, Girerd N. Hyponatraemia, hyperglycaemia and worsening renal function at first blood sample on emergency department admission as predictors of in-hospital death in patients with dyspnoea with suspected acute heart failure: retrospective observational analysis of the PARADISE cohort. BMJ Open. 2018 Mar 30;8(3):e019557. doi: 10.1136/bmjopen-2017-019557.

lead_sponsor: CHOUIHED Tahar

sponsor_collaborators:
CHOUIHED Tahar
Central Hospital, Nancy, France


title: Tele-expertise for Glycemic Control Monitoring in Patients With Diabetes Hospitalized for Covid-19 Infection

acronym: COVIDEX

summary: Diabetes is a major factor of morbi-mortality in Covid-19 infection. Currently, steroid therapy is required in patients under oxygen therapy. This treatment is associated with hyper glycaemia in patients with diabetes. Recommendations for the management of diabetes during Covid-19 infection is to use insulin treatment. The majority of units involves in the management of patient with Covid19 infection are not the experience in managing intensive insulin therapy and the time to ensure this follow-up. All the data in the literature are in favor of a positive impact of telemedicine on the metabolic control of diabetic patients. However, the routine use of telemedicine and more particularly tele-expertise within hospital units is very underdeveloped in France. The epidemic of Covid-19 represents a unique situation where the health authorities recommend to physicians to use telemedicine to ensure the follow-up and optimal management of patients. The aim of this study was to compare the metabolic control of diabetic patients infected with Covid-19 followed in tele-expertise to a group of diabetic patients infected with Covid-19 managed in standard conditions.

status: Terminated

design_allocation: Non-Randomized

primary_purpose: Other

lead_sponsor: University Hospital, Strasbourg, France

intervention_type: Device


title: Evaluation à Six Mois du système de dénervation rénale Chez Les Patients Atteints d'Insuffisance Cardiaque

acronym: DENRENIC

summary:
Management of chronic heart failure (CHF) is a major public health problem. It is associated with high mortality, frequent hospitalization and represents a large cost to the health care system. Both pharmacological and non-pharmacological intervention haven't shown to be effective in reducing morbidity and mortality of these patients when able to modulate the activity of neuro-hormonal systems among them the sympathetic nervous system. Recent data have emphasized the potential role of sympathetic renal denervation in patient with hypertension. CHF per se but even more CHF associated with comorbity lead to significant increase level of sympathetic tone. This is largely induced by autonomic dysfunction such as chemo or baroflex abnormalities. These patients usually suffer from conditions which do not allow upgrading and adapting drugs to their sympathetic condition. Hence CHF patient with chronic kidney disease, anemia or both have markedly high sympathetic activity and cannot be exposed to higher level of RAS Blockers or beta blocker due to their renal dysfunction, they thus remain with an elevated sympathetic activity worsening symptoms and prognosis. Chronic heart failure affects around 100 million people worldwild imposing a significant burden on health care system throughout the world. Even though symptoms are improved by heart failure therapy, they remain significantly disabling for many patients. Chronic over activation of the sympathetic nervous system is a major component of heart failure and involves efferent and afferent pathways between brain and many organs. A new therapy directly targeting nerve traffic-renal artery denervation- has been shown to be effective in drug resistant hypertension, with an average drop in blood pressure of 33/12 mm hg.

The cardiologists team of the private hospital Arnault Tzanck is willing therefore to conduct a study in 12 patients with chronic systolic heart failure undergoing bilateral renal denervation with an intensive protocol of observation and assessment compring a 3 day hospital stay post procedure 3 and 6 months of regular outpatient follow-up.

lead_sponsor: Institute Arnault Tzanck, France

sponsor_collaborators:
Institute Arnault Tzanck, France
Abbott Medical Devices


title: Prospective, Multicentric, Randomized on Two Arms, Controlled, by Cross-over, Pilot Study, in Order to Evaluate Disconfort Among Outpatients Using actiTENS for Neuropathic Pain vs TENS ECO 2.

acronym: QolTENS

summary:
Non-pharmacological treatments for pain relief are more and more used in clinical care although any scientific validation. Among the non-pharmacological treatments of neuropathic pain relief, TENS (Electrical Nerve Stimulation Therapy) is the major treatment with the best benefit. Unfortunately, the use of TENS by patients appears very difficult. Because of this inconvenience, more than 40% of TENS users interrupt the treatment despite treatment benefit. A new TENS device: actiTENS that seems to be less constraining than TENS is now available in France. ActiTENS efficacy and safety compared to TENS need to be investigated.

The main objective is to evaluate and to compare the use of actiTENS, with TENS Eco 2, the classical device in patients with chronic neuropathic pain.

lead_sponsor: Centre Hospitalier Universitaire, Amiens

location_facility:
CHD La Roche Sur Yon
CHU de Toulouse
APHP - Hopital Saint Antoine
CHU de Nantes
CHU Amiens Picardie

intervention_type: Procedure


title: Cryotherapy Under Interventional Radiology Combined With in Situ Ipilimumab and a Flat Dose of Nivolumab in Stage IIIB/C Melanoma. Prospective Proof of Concept Study.

acronym: CRIRIN

summary:
Melanoma is the deadliest form of skin cancer and its incidence has doubled every 20 years in France, where this cancer is responsible of more than 1600 deaths each year.

Patients with early diagnosis have good prognosis and can be generally cured by surgery only. Advanced melanoma however has a very bad prognosis.

Loco-regional lymph nodes are usually the first distant localization in metastatic melanoma. Lymph node dissection is then the recommended treatment, although it's impact on survival has never been proven.

In the same way, the benefit risk profile of interferon as adjuvant treatment after lymph node dissection is still much debated.

Recently, new treatments either with immunotherapy (ipilimumab, nivolumab) or by the targeted therapy dabrafenib/trametinib in patients with BRAF mutation have shown an impact on survival in the adjuvant setting after lymph node dissection.

But, it has not yet been established if this strategy has a benefit gain compared to starting those treatments only in the metastatic setting after watchful follow-up.

Moreover, if these novel therapies (targeted therapies: TT, immunotherapies : IT) demonstrated for the first time a real benefit in terms of survival or of responses rates in melanoma, physicians and patients had to address new problems, such as the management of unusual adverse events.

Partial and dissociated responses can also be seen with those new treatments. Some patients will have complete response in some lesions, stabilization in others and progression in a few. It is to be expected that one of the real key points of this therapy is to be found here, as this situation is commonly seen, and it would probably be a poor choice to stop a treatment that is globally effective for progression of only 1 or 2 lesions, in a patient otherwise stabilized.

That is the context in which interventional radiology (IR) should be considered as an extremely efficient option. IR is a real medical revolution in the last 2 decades.

It provides not only the opportunity to determine the characteristics of residual lesion (fibrosis, necrosis, metastasis, or sarcoidosis,…) by biopsy, but allows also their targeted destruction through different technics (cryotherapy, radiofrequency, laser,…).

The investigators are fortunate to have in their institution one of the best IR department of the world (headed by Prof. Afshin GANGI), with a technical platform unique in Europe that allows IR through ultrasound, scan, petscan and MRI.

To the best of their knowledge, Immunotherapy associated with IR has not been performed so far.

This association could in theory:

Combine immunotherapy with tumoral necrosis, which inherently increases the effects of immunotherapy by massive tumoral leakage of danger signals and tumoral antigens;
Allow direct injection in targeted zones, where the beneficial effect is desired, and thus increase the expected immune response;
Reduce side effects related to immunotherapy, by reducing quantities injected; which seems particularly important in the (neo)-adjuvant setting.

That's why the investigators are willing to conduct this pilot project, the objectives of which are:

Providing a proof of the feasibility of this association,
Obtaining preliminary insights on the effects on non-targeted lesions,
Adding a translational research to establish the effect on tumor antigenic expression and the immune response.

sponsor_collaborators:
University Hospital, Strasbourg, France
Bristol-Myers Squibb

location_facility: Clinique Dermatologique/Radiologie Interventionnelle/Urologie/Gynécologie-CHU de Strasbourg/ICANS


title: Utility of Quantitative Polymerase Chain Reaction to Predict Clinical Outcome of Leptospirosis in French West Indies

acronym: LEPTO

summary:
Leptospirosis is a zoonosis of worldwide distribution whose incidence is higher in the tropics, where conditions for transmissions are favorable. The disease is endemic in Martinique and Guadeloupe, two Caribbean islands of the French West Indies. In tropical areas, many wild and domestic animals serve as reservoirs for pathogenic Leptospira strains and contaminate the environment by shedding the organisms in their urine. Humans are usually infected through abraded skin or mucous membrane contact with water contaminated by the urine of animal reservoirs, and less frequently by direct contact with animals or their urine. The mean incubation period is 10 days, with a usual range of 2-20 days. Clinical manifestations are protean and the spectrum of symptoms range from subclinical or mild anicteric febrile illness to acute renal failure and respiratory distress syndrome which are associated with high mortality rates.

The microscopic agglutination test (MAT) and culture are the reference standard test for diagnosis of leptospirosis, but they are only available in reference laboratories and their conclusive results requires convalescent sample or prolonged incubation. At present, only direct detection methods using PCR might provide rapid diagnosis during the early acute stage of the illness, when treatment is likely to have the greatest benefit.

Quantitative PCR also offers the ability to measure level of leptospiremia in clinical samples. Using qPCR based diagnosis, the investigators have the opportunity to study the association of level of leptospiremia and clinical manifestations in French West Indies. All qPCR-positive samples will be used for molecular typing.

lead_sponsor: University Hospital Center of Martinique

collaborators: Institut National de la Santé Et de la Recherche Médicale, France

location_facility:
CHU Martinique
CHU Pointe-à-Pitre Abymes


type: Registry Identifier

title: Analyse de l'activité cérébrale intrinsèque Pendant le Coma et Lors du Retour à la Conscience

acronym: ACI-Coma

summary: Several studies in healthy volunteers have suggested that the synchronized functional connectivity in the DMN (Deafult-Mode Network) would sustain the mental content at rest, and when required, a switch in the activity between the DMN and other networks involved in specific congnitive functions, would occur. This interaction permit to make the hypothesis, that baseline brain activity is likely to shape our ongoing " stream of consciousness " and could correlate with conscious perception. The investigators hypothesized that DMN connectivity strength would be related to the level of consciousness of brain-damaged patients. The investigators will follow severely brain-injured patient in coma. Clinical examination using standardized behavioural scales: FOUR score (Full Outline of UnResponsivess), Coma Recovery Scale-Revised); and brain imaging assessesments using MRI (functional and anatomical connectivity, cortical thickness) will be performed at: 3 to 30 (visit 1), and 60 (visit 2) days after insult. If patient recover a normal conscious state between 30 and 60 days, an additional clinical and brain imaging assessment will be performed to identify related changes in brain activity (visit 1*) Monitoring of vital parameters will be performed in patients by a senior anaesthesiologist throughout the experiment.

lead_sponsor: Institut National de la Santé Et de la Recherche Médicale, France

collaborators: Association des Traumatisés du Crane et de la Face, Paris, France

location_facility: Institut National de la Santé et de la Recherche Medicale, U825


title: Circulating and Pulmonary Microparticles for Early Diagnosis of Bronchiolitis Obliterans Syndrome After Lung Transplantation

acronym: MIBO

summary:
The main long-term complication of lung transplantation is chronic lung allograft dysfunction (CLAD). Bronchiolitis obliterans syndrome (BOS) is the most frequent presentation of CLAD. BOS leads to a progressive loss of lung allograft function, with recurrence of dyspnea and airflow limitation. In some advanced cases, patients need a lung re transplantation. The mechanisms of BOS are not completely elucidated, and there are no early markers or specific treatment available for this condition.

Microparticles (MPs) are submicron plasma membrane fragments released into the vascular compartment or the pericellular space in response to cell activation, injury or apoptosis. Broncho alveolar and circulating MPs may reflect cellular insults of the lung allografts. Therefore, MPs could be viewed either as biomarkers or as effectors of the chronic inflammatory or procoagulant processes leading to bronchiolitis obliterans syndrome.

The investigators plan to include 60 patients before lung transplantation at our centre in Strasbourg (France). Follow-up will be requested at the base of usual care (spirometry, blood sampling, bronchoscopy with broncho-alveolar lavage [BAL]). The investigators will measure at one month, one, two and three year post transplantation, the total concentration of MPs in plasma and BAL and characterize their phenotype.

The investigators objective is to demonstrate correlation between total MPs concentration in broncho-alveolar lavage fluid (BALF) and the occurrence of bronchiolitis obliterans syndrome at three years post lung transplantation.


title: Cost-effectiveness Analysis Associated With the Use of Resorbable Biosynthetic Parietal Prostheses Compared to Biological Prostheses in Contaminated (mVHWG Grade 3) Abdominal Wall Reconstruction

summary:
Eventration corresponds to the dehiscence of the abdominal wall, with passage of peritoneum and / or intra-abdominal viscera, through an acquired orifice of the abdominal wall. It is secondary to an old incision and occurs in 10 to 20% of cases after a laparotomy. At present, if there is no debate on the type of prosthesis to implant in case of clean surgery: it is a synthetic prosthesis. But in the case of contaminated surgery (modified Ventral Hernia Working Group grade 3), there is no consensus.

Since the 1990s, biological prostheses have been recommended, but they represent significant expenses for health facilities. They are very numerous, and their prices vary between 3 000 € and 12 000 €. The choice is therefore difficult for the surgeon.

In 2016 the Strasbourg University Hospital general surgery team made the choice to use biosynthetic prostheses. This attitude does not seem consensual and is not based on any recommendations at present, either in France or internationally. The homogenization of practices requires the availability of clinical and medico-economic data, particularly in view of the price differences that exist between different types of prostheses.

The main objective of this study will be to compare the use of biosynthetic prostheses with biological prostheses in the treatment of curative surgical treatment of mVHWG grade 3 incisional hernias in terms of cost and serious complications at 6 months.

The secondary objective of the study will be to estimate the number of early recurrences at 6 months avoided, thanks to the use of biosynthetic prostheses compared to biological prostheses.

ReferenceCitation: Charleux-Muller D, Romain B, Boisson C, Velten M, Brigand C, Lejeune C. Cost-effectiveness analysis of resorbable biosynthetic mesh in contaminated ventral hernia repair. J Visc Surg. 2022 Aug;159(4):279-285. doi: 10.1016/j.jviscsurg.2021.06.001. Epub 2021 Jun 9.

location_facility: Service de Chirurgie générale et digestive


title: A Randomized Trial of Deferred Versus Fresh Embryo Transfers in Infertile Women Undergoing IVF-ICSI

acronym: DEFETOSE

summary: Controlled ovarian stimulation (COS) enhances the efficacy of ART (Assisted reproductive technology) by permitting multiple-oocyte yields, but also alters endometrial receptivity (ER) by an advancement of endometrial development which contributes to diminished pregnancy chances. Previous reports suggest that pregnancy rates are increased following deferred frozen embryo transfers. In addition as compared to fresh embryo transfers, frozen embryo transfers seem to be associated with less affected perinatal outcomes, in particular lower risk of preterm birth, small for gestational age and caesarean section. Unfortunately, most of the current evidence is based only on preliminary reports, needing further scientific evidence. Thus, whether differing embryo transfers could restore optimal ER leading to higher live birth rate (LBR) and better obstetrical outcomes as compared to fresh embryo transfers, is actually still under investigation.

ReferenceCitation: Zaat T, Zagers M, Mol F, Goddijn M, van Wely M, Mastenbroek S. Fresh versus frozen embryo transfers in assisted reproduction. Cochrane Database Syst Rev. 2021 Feb 4;2(2):CD011184. doi: 10.1002/14651858.CD011184.pub3.

publisher_dissemination: Wiley

appel_a_projets: PHRCN

region: Île-de-France

nom_etablissement: ASSISTANCE PUBLIQUE-HOPITAUX DE PARIS

type_etablissement: CHUR

acronyme: DEFOSE

titre: Etude randomisée du transfert embryonnaire différé versus frais dans une population de patientes infertiles en FIV-ICSI

discipline_principale: médecine de la reproduction

nom_porteur: SANTULLI

prenom_porteur: Pietro


title: Dose Finding and Early Efficacy Study of Erlotinib in Treatment of Chronic Hepatitis C Virus infection_proof of Concept Study

summary:
Chronic Hepatitis C Virus (HCV) infection is a major cause of liver cirrhosis and hepatocellular carcinoma world-wide. Current combination therapy of pegylated interferon-alfa, ribavirin and protease inhibitors is limited by resistance and substantial side effects.

The investigators identified epidermal growth factor receptor (EGFR) as host factor for HCV infection. Inhibition of kinase function of EGFR by approved inhibitor Erlotinib (TarcevaTM) broadly inhibits HCV infection of all major genotypes including viral escape variants resistant to host immune responses.

Completed preclinical proof-of-concept studies in HCV cell culture and animal model systems demonstrate that inhibition of EGFR function by Erlotinib constitutes a novel antiviral approach for prevention and treatment of HCV infection (European patent application EP 08 305 604.4, Filing date: September 26, 2008; Inserm, Paris, France and Lupberger et al. Nature Medicine 2011).

Since Erlotinib (TarcevaTM) is an established approved drug for cancer treatment and has a well characterized safety profile in humans, the aim of the study is to investigate the safety, efficacy and pharmacokinetics of Erlotinib, a first-in-class entry inhibitor, for treatment of HCV infection in a randomized placebo-controlled double blind clinical trial in patients chronically infected with HCV. Following completion, this trial will set the stage for a further investigation of entry inhibitors as antivirals in combination with standard of care or direct antivirals such as HCV protease inhibitors. Thus, this randomized clinical trial will be an important step in the development of novel urgently needed antiviral therapies overcoming resistance.

location_facility: Service d'Hépatogastroentérologie, NHC1, place de l'hôpital


title: The Role of the Living Environment in the Social Inequalities in the Physical Activities of Pregnant Women Residing in the Eurometropole of Strasbourg

acronym: ENVIFEM

summary:
Excessive weight gain during pregnancy can promote subsequent obesity or increase pre-existing maternal obesity, lead to complications during pregnancy, such as gestational diabetes, hypertension and pre-pregnancy eclampsia, which affect fetal growth.

What are the determinants of excessive weight gain? The first determinant of excessive weight gain is related to healthy living place and physical activity, noted as "PA". Many meta-analyses have demonstrated the role of PA in gestational weight gain.

The main objective is to study the role of the living environment in the PA practice of pregnant women and to identify the socio-environmental construction contributing to the disparities in the practice of PA in women during their pregnancy. This thesis is based on an innovative approach in France, combining both epidemiology and geography approaches to meet priority research objectives in a public health context. With regard to the general issue "What are the contextual determinants of pregnant women's PA practice beyond their individual characteristics that could explain the disparities in practice according to their socio-economic position?" This question underlies the following assumptions:

i) In addition to their individual characteristics, women with low PA and who have reduced PA during pregnancy reside in a more socio-economically deprived neighborhood.

ii)Beyond the socio-economic dimension, the physical characteristic of the residential place influences the level of PA practice of pregnant women.

iii) The combination of the socio-economic, physical and psychosocial environment contributes to reducing the level of PA among pregnant women.

iv) Pregnant women with an unfavourable living environment and low PA have adverse pregnancy outcomes.

ReferenceCitation: Simoncic V, Hamann V, Huber L, Deruelle P, Sananes N, Enaux C, Alter M, Schillinger C, Deguen S, Kihal-Talantikite W. Study protocol to explore the social effects of environmental exposure and lifestyle behaviours on pregnancy outcome: an overview of cohort of pregnant women study. BMJ Open. 2022 Sep 17;12(9):e058883. doi: 10.1136/bmjopen-2021-058883.

repository_institution: 4 institutions : Université de Strasbourg, Université de Haute Alsace, INSA Strasbourg, Bibliothèque Nationale et Universitaire de Strasbourg - univOAK

repository_normalized: univOAK

repository_institution: Le Centre pour la Communication Scientifique Directe - HAL - Inserm

repositories:
HAL
PubMed Central
univOAK

repositories_concat: HAL;PubMed Central;univOAK

repositories_institution: Le Centre pour la Communication Scientifique Directe - HAL - Inria

location_facility: Les Hôpitaux Universitaires de Strasbourg


type: Other Identifier

title: Evaluation of the Persistence in 2016 of Vaccinal Immunity Against Meningococcus C Among Children and Teenagers Who Received Meningococcus C Conjugate Vaccine in January 2002 During the Puy-de-Dôme Campaign and of Natural Immunity Among Unvaccinated People

summary:
Meningococcus C vaccine was first used in France to prevent epidemics. It was a success in Puy-de-Dôme, Landes, Pyrénées Atlantiques and Hautes Pyrénées. Following many European countries, France introduced meningococcus C conjugate vaccine in 2009 but this recommendation was not suffiicently applied (6,6% of the 20-25 years-old were vaccinated in 2015).

The situation in France is very different from UK and there is no data on the subject. The vaccination campaign in 2002 in Puy-de-Dôme offers much more detachment, possible comparison between vaccinated and unvaccinated people, among which meningococcus circulation could maintain immunity. This is the reason why we have decided to assess in 2016 the vaccinal and natural immunity among Puy-de-Dôme population.

lead_sponsor: University Hospital, Clermont-Ferrand


title: Risk of Maternal Depression From 1 Year to 4 Years Postpartum in Yvelines

acronym: DeTaPoP

summary: This observational study aims to estimate the prevalence of women from 1 to 4 years postpartum in Yvelines, who are suspected to suffer from postpartum depression, using the Edinburg Post natal Depression Scale (EPDS) and the Patient Heath Questionnaire 2 (PHQ2) and evaluate the factors that could be linked to it.

ReferenceType: background

ReferenceCitation: Woolhouse H, Gartland D, Mensah F, Brown SJ. Maternal depression from early pregnancy to 4 years postpartum in a prospective pregnancy cohort study: implications for primary health care. BJOG. 2015 Feb;122(3):312-21. doi: 10.1111/1471-0528.12837. Epub 2014 May 21.

ReferenceCitation: Slomian J, Honvo G, Emonts P, Reginster JY, Bruyere O. Consequences of maternal postpartum depression: A systematic review of maternal and infant outcomes. Womens Health (Lond). 2019 Jan-Dec;15:1745506519844044. doi: 10.1177/1745506519844044. Erratum In: Womens Health (Lond). 2019 Jan-Dec;15:1745506519854864.

ReferenceCitation: Stein A, Pearson RM, Goodman SH, Rapa E, Rahman A, McCallum M, Howard LM, Pariante CM. Effects of perinatal mental disorders on the fetus and child. Lancet. 2014 Nov 15;384(9956):1800-19. doi: 10.1016/S0140-6736(14)61277-0. Epub 2014 Nov 14.

ReferenceCitation: Depression and Suicide Screening Gregory Plemmons MD, MFA, in Adolescent Health Screening: an Update in the Age of Big Data, 2019

ReferenceCitation: Référentiel de psychiatrie. Collège national des universitaires en psychiatrie. Presses universitaires François Rabelais, 3ème édition, 2021

ReferenceCitation: Kroenke K, Spitzer RL, Williams JB. The Patient Health Questionnaire-2: validity of a two-item depression screener. Med Care. 2003 Nov;41(11):1284-92. doi: 10.1097/01.MLR.0000093487.78664.3C.

ReferenceCitation: Cox JL, Holden JM, Sagovsky R. Detection of postnatal depression. Development of the 10-item Edinburgh Postnatal Depression Scale. Br J Psychiatry. 1987 Jun;150:782-6. doi: 10.1192/bjp.150.6.782.

ReferenceCitation: Guedeney N, Fermanian J. Validation study of the French version of the Edinburgh Postnatal Depression Scale (EPDS): new results about use and psychometric properties. Eur Psychiatry. 1998;13(2):83-9. doi: 10.1016/S0924-9338(98)80023-0.

ReferenceCitation: Murray L, Carothers AD. The validation of the Edinburgh Post-natal Depression Scale on a community sample. Br J Psychiatry. 1990 Aug;157:288-90. doi: 10.1192/bjp.157.2.288.

lead_sponsor: Centre Médical Porte Verte


title: The Role of Social and Territorial Inequalities in the Management and Prognosis of Multiple Sclerosis - Longitudinal Observational Study - INESEP

acronym: INESEP

summary:
Although the majority of the French population is covered by social security, the effects of social inequalities on health are still very visible and are even increasing in France and in Europe. Thus, according to INSEE, excess mortality is observed among the most disadvantaged populations. Similarly, the prevalence of certain chronic diseases in France and Europe, particularly cardiovascular diseases, is linked to social inequalities and excess morbidity can be observed in the most disadvantaged populations.

In addition to social inequalities, which refer to disparities in health levels according to social category, there are the effects of territorial inequalities. In France, there are geographical areas of excess mortality, which essentially correspond to areas far from urban centers. Similarly, there are major geographical differences in terms of medical supply and equipment, and the distance between patients and health centers is a direct obstacle to the use of the health care network.

The underlying explanations for social inequalities in health are multiple. While it is likely that difficulties in accessing and using care play a role, it is also possible that they are due to differences in exposure to certain environmental (e.g. pollution) or individual (e.g. smoking) risk factors. But it is also possible that the causal relationship is the opposite and that diseases create or reveal social inequalities.

For multiple sclerosis (MS) the impact of social and territorial inequalities is more debated. Indeed, with regard to the relationship between disease prevalence and social inequalities, a recent literature review found 21 separate studies on the subject, of which 13 failed to show a link between socioeconomic status and MS risk, 5 concluded that there was an increased risk of MS in advantaged populations and 3 concluded that there was an increased risk of MS in disadvantaged populations. There are plausible pathophysiological explanations for either direction of the relationship, but the question remains open.

To our knowledge, the link between MS prognosis and social inequalities has been little studied, as disadvantaged populations are more often exposed to the poor prognostic factor of smoking [6-8], the hypothesis of a negative prognostic role of social inequalities remains plausible. Similarly, the current consensus is that the diagnosis and treatment of MS should be as early as possible [9,10] in order to preserve brain capital. Easy access to a neurologist and MRI are therefore potentially prognostic factors for MS in relation to territorial inequalities. It should be noted that the link between social and geographical inequalities and a potential delay in treatment has not been demonstrated in France in the case of cancer, but it is possible that the importance of the means implemented in the fight against cancer erases these effects. In MS, a study showed a link between delay in starting a second disease-modifying therapy and socio-economic status.

While the causal link between MS and socio-professional status has not yet been demonstrated, the socio-economic impact of MS has been measured. In particular, it has been shown that having MS is associated with an increased risk of unemployment and/or early retirement.

The primary objective of our study is to determine whether delay in treatment, as a marker of difficulties in access to care in MS, is associated with social and territorial inequalities in MS. Secondary objectives will be to explore the link between MS prognosis and social and territorial inequalities.

Exposure to sunlight is a known protective factor and is consistent with the north-east-south-west gradient observed in France. The choice of centers associated with the research, spread over the French territory, will make it possible to monitor and measure this effect in the prognosis of MS.

As the available treatments have evolved considerably over the last ten years, and in order to avoid a period effect, the patients recruited in the study will have to have a date of onset of the disease after 1 January 2009.

Primary objective Determining the relationship between socio-economic inequalities and the time to start disease-modifying therapy in MS Secondary objective

To determine the relationship between geographical inequalities and delay in starting disease-modifying therapy in MS
To determine the relationship between socio-economic inequalities and time to walking disability (EDSS 4)
To determine the relationship between geographical inequalities and time to walking disability (EDSS 4)
To measure the impact of disability on socioeconomic status in MS patients

location_facility: CIC 1433 Épidémiologie CliniqueInserm, CHRU, Université de Lorraine

location_facility: Service de Neurologie et Maladies inflammatoires du Système nerveux central


title: Efficacy Assessment of Early Osteopathic Manipulative Treatment (OMT) in the Management of Suboptimal Breastfeeding Behaviour in Healthy Newborns. A Prospective Monocentric Randomized Double-blinded Study.

acronym: NEOSTEO

summary:
Breastfeeding is one of the prime factors of long-term health protection in newborns, for nutritional, immunological and developmental reasons. In France there is a wide inter-regional variability of breastfeeding rates at discharge. This variability associates different factors involving both, mothers, birth conditions, newborns and mother-child couple. Some approaches, including osteopathy, aim to support early breastfeeding difficulties. As many others non-conventional medicines, there is a huge and growing interest for this alternative therapy and a spontaneous recourse in the first months of life. Nevertheless, neither efficacy nor the benefits have been studied. Thus, our objective is to evaluate for the first time in France, in a randomized, double-blinded design, the efficacy of early osteopathic manipulative treatment (OMT), in suboptimal breastfeeding behaviour healthy newborns.

128 couples mother-child will be randomized in two groups: with or without osteopathic intervention on the newborn.

ReferenceCitation: Danielo Jouhier M, Boscher C, Roze JC, Cailleau N, Chaligne F, Legrand A, Flamant C, Muller JB; NEOSTEO osteopath study group. Osteopathic manipulative treatment to improve exclusive breast feeding at 1 month. Arch Dis Child Fetal Neonatal Ed. 2021 Nov;106(6):591-595. doi: 10.1136/archdischild-2020-319219. Epub 2021 Mar 31.

lead_sponsor: Nantes University Hospital

location_facility: Centre Hospitalier Universitaire de Nantes - Hôpital Mère-Enfant


type: U.S. NIH Grant/Contract

title: Parkin Mutations and Their Functional Consequences

summary:
Parkinson's disease (PD) is the most frequent neurodegenerative disease with a prevalence of 2% over 65 years and because of this high prevalence as the population ages, it is a major problem of public health.

An exhaustive repertory of not only parkin mutations in autosomal recessive forms of PD but also in other known genes such as DJ-1, PINK1 and LRRK2, is of major importance for both genetic counseling in families affected with PD and physiopathological approaches to this disease.

Through a French network for the study of Parkinson's disease genetics and extended collaborations with European, Mediterranean and other various countries, a total of 2934 subjects including 1683 patients and 1251 unaffected individuals has been collected since 2002. These samples consisted of 122 families with autosomal recessive PD, 285 cases of isolated early onset PD, 110 autosomal recessive and 129 autosomal dominant families with late onset PD, 201 isolated late onset PD cases and 250 matched controls.

DNAs from all subjects are now available, lymphocytes and lymphoblastoid cell lines have been stored for most patients from France and recently, fresh fibroblasts have been obtained for some individuals.

The genetic approach to autosomal recessive PD is focused on the identification of mutations in the parkin gene but also on the screening of DJ-1, PINK1 and LRRK2 genes.

ReferenceCitation: Rawal N, Periquet M, Lohmann E, Lucking CB, Teive HA, Ambrosio G, Raskin S, Lincoln S, Hattori N, Guimaraes J, Horstink MW, Dos Santos Bele W, Brousolle E, Destee A, Mizuno Y, Farrer M, Deleuze JF, De Michele G, Agid Y, Durr A, Brice A; French Parkinson's Disease Genetics Study Group; European Consortium on Genetic Susceptibility in Parkinson's Disease. New parkin mutations and atypical phenotypes in families with autosomal recessive parkinsonism. Neurology. 2003 Apr 22;60(8):1378-81. doi: 10.1212/01.wnl.0000056167.89221.be.

ReferenceCitation: Periquet M, Latouche M, Lohmann E, Rawal N, De Michele G, Ricard S, Teive H, Fraix V, Vidailhet M, Nicholl D, Barone P, Wood NW, Raskin S, Deleuze JF, Agid Y, Durr A, Brice A; French Parkinson's Disease Genetics Study Group; European Consortium on Genetic Susceptibility in Parkinson's Disease. Parkin mutations are frequent in patients with isolated early-onset parkinsonism. Brain. 2003 Jun;126(Pt 6):1271-8. doi: 10.1093/brain/awg136.

ReferenceCitation: Ibanez P, Lohmann E, Pollak P, Durif F, Tranchant C, Agid Y, Durr A, Brice A; French Parkinson's Disease Genetics Study Group. Absence of NR4A2 exon 1 mutations in 108 families with autosomal dominant Parkinson disease. Neurology. 2004 Jun 8;62(11):2133-4. doi: 10.1212/01.wnl.0000127496.23198.75. No abstract available.

ReferenceCitation: Ibanez P, De Michele G, Bonifati V, Lohmann E, Thobois S, Pollak P, Agid Y, Heutink P, Durr A, Brice A; French Parkinson's Disease Genetics Study Group. Screening for DJ-1 mutations in early onset autosomal recessive parkinsonism. Neurology. 2003 Nov 25;61(10):1429-31. doi: 10.1212/01.wnl.0000094121.48373.fd.

ReferenceCitation: Lucking CB, Chesneau V, Lohmann E, Verpillat P, Dulac C, Bonnet AM, Gasparini F, Agid Y, Durr A, Brice A. Coding polymorphisms in the parkin gene and susceptibility to Parkinson disease. Arch Neurol. 2003 Sep;60(9):1253-6. doi: 10.1001/archneur.60.9.1253.

ReferenceCitation: Lohmann E, Periquet M, Bonifati V, Wood NW, De Michele G, Bonnet AM, Fraix V, Broussolle E, Horstink MW, Vidailhet M, Verpillat P, Gasser T, Nicholl D, Teive H, Raskin S, Rascol O, Destee A, Ruberg M, Gasparini F, Meco G, Agid Y, Durr A, Brice A; French Parkinson's Disease Genetics Study Group; European Consortium on Genetic Susceptibility in Parkinson's Disease. How much phenotypic variation can be attributed to parkin genotype? Ann Neurol. 2003 Aug;54(2):176-85. doi: 10.1002/ana.10613.

ReferenceCitation: Lesage S, Durr A, Tazir M, Lohmann E, Leutenegger AL, Janin S, Pollak P, Brice A; French Parkinson's Disease Genetics Study Group. LRRK2 G2019S as a cause of Parkinson's disease in North African Arabs. N Engl J Med. 2006 Jan 26;354(4):422-3. doi: 10.1056/NEJMc055540. No abstract available.

ReferenceCitation: Ibanez P, Lesage S, Lohmann E, Thobois S, De Michele G, Borg M, Agid Y, Durr A, Brice A; French Parkinson's Disease Genetics Study Group. Mutational analysis of the PINK1 gene in early-onset parkinsonism in Europe and North Africa. Brain. 2006 Mar;129(Pt 3):686-94. doi: 10.1093/brain/awl005. Epub 2006 Jan 9.

ReferenceCitation: Lesage S, Janin S, Lohmann E, Leutenegger AL, Leclere L, Viallet F, Pollak P, Durif F, Thobois S, Layet V, Vidailhet M, Agid Y, Durr A, Brice A; French Parkinson's Disease Genetics Study Group; Bonnet AM, Borg M, Broussolle E, Damier P, Destee A, Martinez M, Penet C, Rasco O, Tison F, Tranchan C, Verin M. LRRK2 exon 41 mutations in sporadic Parkinson disease in Europeans. Arch Neurol. 2007 Mar;64(3):425-30. doi: 10.1001/archneur.64.3.425.

ReferenceCitation: Leutenegger AL, Salih MA, Ibanez P, Mukhtar MM, Lesage S, Arabi A, Lohmann E, Durr A, Ahmed AE, Brice A. Juvenile-onset Parkinsonism as a result of the first mutation in the adenosine triphosphate orientation domain of PINK1. Arch Neurol. 2006 Sep;63(9):1257-61. doi: 10.1001/archneur.63.9.1257.

ReferenceCitation: Lesage S, Magali P, Lohmann E, Lacomblez L, Teive H, Janin S, Cousin PY, Durr A, Brice A; French Parkinson Disease Genetics Study Group. Deletion of the parkin and PACRG gene promoter in early-onset parkinsonism. Hum Mutat. 2007 Jan;28(1):27-32. doi: 10.1002/humu.20436.

ReferenceCitation: Brice A, Lohmann E, Ibanez P, Periquet M, Laine S, Debarges B, Lesage S, Dürr A. Phenotype/genotype correlations in Parkinson's disease. In: Relationships in Neurodegenerative Diseases, Cummings, Hardy, Poncet and Christen (Eds), Springer-Verlag Berlin Heidelberg Eds, 153-64, 2005.

ReferenceCitation: Lohmann E, Dürr A, Ruberg M, Brice A. Parkin. In: Parkinson's Disease: Genetic and Pathogenesis, Dawson Eds, in press, 2006.

ReferenceCitation: Brice A. [What can we learn from genes responsible for familial forms of Parkinson's disease?]. Bull Acad Natl Med. 2006 Feb;190(2):485-96; discussion 497-8. French.

ReferenceCitation: Ishihara L, Warren L, Gibson R, Amouri R, Lesage S, Durr A, Tazir M, Wszolek ZK, Uitti RJ, Nichols WC, Griffith A, Hattori N, Leppert D, Watts R, Zabetian CP, Foroud TM, Farrer MJ, Brice A, Middleton L, Hentati F. Clinical features of Parkinson disease patients with homozygous leucine-rich repeat kinase 2 G2019S mutations. Arch Neurol. 2006 Sep;63(9):1250-4. doi: 10.1001/archneur.63.9.1250.

ReferenceCitation: Foroud T, Pankratz N, Martinez M; PROGENI/GSPD-European Consortium. Chromosome 5 and Parkinson disease. Eur J Hum Genet. 2006 Oct;14(10):1106-10. doi: 10.1038/sj.ejhg.5201666. Epub 2006 May 31.

sponsor_collaborators: Institut National de la Santé Et de la Recherche Médicale, France


title: ESSAI DE PHASE III RANDOMISE EVALUANT LE FOLFOX AVEC OU SANS DOCETAXEL (TFOX) EN 1ère LIGNE DE CHIMIOTHERAPIE DES ADENOCARCINOMES OESO-GASTRIQUES LOCALEMENT AVANCES OU METASTATIQUES

acronym: GASTFOX

summary:
Gastric cancer is the fourth commonest cancer and the second largest cause of mortality from cancer. Surgical resection of localised forms of gastric cancer offers the only chance of a cure. The vast majority of patients, however, present with advanced disease from the outset (locally advanced or metastatic) or recurrent after resection of a localised form.

For metastatic or locally advanced stages of gastric or gastro-oesophageal junction adenocarcinoma, the combination of 2 chemotherapy drugs (dual therapy) as compared with monotherapy or no chemotherapy, makes it possible to improve the tumour response and patient survival. Dual therapy comprising cisplatin + fluoropyrimidine (CF protocol) is considered as one of the first-line chemotherapy treatment standards.

The addition of docetaxel to the CF regime (referred to as the DCF protocol) has made it possible to improve the tumour response rate, the time to tumour progression and overall survival in a randomised phase III trial. This improvement in treatment efficacy was achieved, however, at the expense of a significant increase in grade 3-4 toxicity, including diarrhoea , neutropenia, and neutropenia with complications. Although DCF is considered as a therapeutic standard for advanced forms of gastric cancer, its use is limited in clinical practice due to its high toxicity.

Oxaliplatin has shown its usefulness in treatment of oesophagogastric cancer, with an efficacy at least equal to that of cisplatin. Peripheral sensory neuropathy was less common in the 5FU-cisplatin arm. In terms of treatment efficacy, 5FU-oxaliplatin versus 5FU-cisplatin was associated with a non-significant improvement in median progression free survival rates, and overall survival.

All these data thus suggest that 5FU-oxaliplatin is at least as efficacious and is better tolerated than 5FU-cisplatin, and also that docetaxel-5FU-cisplatin is more efficacious than 5FU-cisplatin, with limited use due to its high toxicity. In the logical continuation of development of chemotherapy protocols for metastatic gastric cancer, the question therefore arises of the usefulness of adding docetaxel to 5FU-oxaliplatin, in terms of efficacy and also tolerance.

In France, chemotherapy with FOLFOX is used extensively as a first line of treatment in advanced gastric cancer, but with progression-free survival and median survival rates that are still too low, and a poor response rate. The use of docetaxel at a dose of 50 mg/m2 every 2 weeks in combination with FOLFOX (TFOX protocol) has shown very interesting results in phase II studies in terms of efficacy and tolerability, and these are worth confirming through a phase III randomised trial. In fact, if these results are confirmed in phase III, TFOX could become the new first-line therapeutic standard for advanced gastric cancer, while limiting toxicity and preserving patients' quality of life, and could become the reference treatment to accompany the targeted therapies currently being developed for this disease.

The primary objective of this randomised phase III trial is to compare the progression-free survival on dual therapy with 5FU-oxaliplatin (FOLFOX protocol) with triple therapy with 5FU-oxaliplatin-docetaxel (TFOX protocol) in treatment of advanced forms of gastric or oesophagogastric junction adenocarcinoma. The secondary objectives are overall survival, the tumour response rate, toxicity, quality of life and the therapeutic index, defined as the ratio between the median progression-free survival and the febrile neutropenia rate.

ReferenceCitation: Zaanan A, Samalin E, Aparicio T, Bouche O, Laurent-Puig P, Manfredi S, Michel P, Monterymard C, Moreau M, Rougier P, Tougeron D, Taieb J, Louvet C. Phase III randomized trial comparing 5-fluorouracil and oxaliplatin with or without docetaxel in first-line advanced gastric cancer chemotherapy (GASTFOX study). Dig Liver Dis. 2018 Apr;50(4):408-410. doi: 10.1016/j.dld.2018.01.119. Epub 2018 Mar 1.

lead_sponsor: Federation Francophone de Cancerologie Digestive

collaborators: GERCOR - Multidisciplinary Oncology Cooperative Group

location_country: Martinique France

location_facility: Institut de Cancérologie de Bourgogne - GRRECC


title: Oral Manifestations of Systemic Sclerosis: Toward the Identification of New Prognostic Markers

summary:
Systemic sclerosis (SSc) is a rare multisystem connective-tissue disorder characterized by three major pathological hallmarks: widespread fibrosis, vasculopathy and immunological abnormalities. As all connective tissues can be affected, this condition has multiple effects on the orofacial region. Indeed, the latter is involved in approximately 80% of SSc patients. Oral manifestations have a major impact on quality of life and require specific treatments that should be performed as early as possible.

Widening of the periodontal ligament space, that seems to be linked to an increased collagen synthesis, is one of the most common dental radiographic finding. However, this radiologic sign has been mostly studied on two-dimensional radiographs. The investigators have recently described in a patient suffering from SSc the existence of calcifications within the periodontal ligament space using Cone Beam Computed Tomography (CBCT) approach (Jung et al., Oral Surg Oral Med Oral Pathol Oral Radiol 2013). Such calcifications, that have never been observed before, could be part of the phenotypic spectrum of the disease, in particular when dystrophic calcinosis is associated. They could furthermore constitute a specific feature of SSc. However, this radiographic sign requires to be investigated in a largest number of patients.

Several cytokines have been implicated in SSc pathogenesis. A recent study has revealed that elevated CXCL4 serum levels correlate with disease complications, suggesting that this molecule could be used as a prognostic biomarker. Increased IL-6 serum levels also correlate with SSc severity. Gingival crevicular fluid can be easily collected from the gingival crevice surrounding the teeth and constitute an indicator of local but also systemic inflammation. Analysis of gingival crevicular fluid cytokine profile could contribute to the identification of specific SSc biomarkers and allow a better comprehension of oral manifestations pathogenesis.

The aim of this case-control study is to characterize precisely the oral manifestations associated with SSc within the National Referral Center for Rare Autoimmune Diseases (Strasbourg, France) patient cohort in order to identify specific radiological, clinical and/or biological signs. Some of them could be correlated to the severity or to the prognosis of the disease. To the investigators knowledge it is the first study using tridimensional CBCT approach.

primary_purpose: Diagnostic

intervention_type: Radiation


title: Conotruncal Cardiac Defects and Metabolism, Nutrigenetic Factors of Etiopathogeny of Conotruncal Cardiac Defects

acronym: CCOMET

summary: The investigators planned to study the etiopathogenic factors of conotruncal cardiac defects regarding the relations between the metabolic, the genetic and the environmental factors which lead to these cardiopathy.

collaborators: Centre Hospitalier Universitaire de Besancon

location_facility: Service de Cardiologie Pédiatrique, CHU Brabois Enfants

intervention_type: Biological


title: Translation, Cross-cultural Adaptation and Validation of the MGQOL-15-F

summary: The purpose of this study is to translate and culturally adapt the MGQOL-15 (health-related quality of life scale for myasthenia gravis) for use with French-speaking patients in France and to evaluate its psychometric properties to ensure reliability and validity.

location_facility: Institute of Myology, La Pitié-Salpêtrière Hospital


title: A Randomized and Controlled Phase II National Protocol in Non NF1 Pediatric and AYA (Adolescent and Young Adults) Patients Bearing a Wild Type BRAF Gene Newly Diagnosed Comparing a Daily Oral MEK Inhibitor (Trametinib) Versus Weekly Vinblastine During 18 Months

acronym: PLGG - MEKTRIC

summary:
Pediatric low-grade glioma (PLGG) is a heterogeneous group of WHO grade I and II brain tumors, associated with a 10-year overall survival of 90%. It is the most common form of primary central nervous system (CNS) tumor arising during childhood, adolescence and young adulthood, accounting for over 30% of CNS tumors in this age group. A large group of PLGG patients will benefit from a complete resection of their tumor. Nevertheless, PLGG can occur anywhere and can be in some locations associated with neurological symptoms, unresectable or radiological progressive tumors that need medical treatments rapidly to avoid long-term sequelae. The current problem during this first line therapy is to improve tumor response, overall survival rate, as well as progression free survival. In our study, we will focus on a specific group of PLGGs without any congenital NF1 mutation and with a wild-type BRAF gene in the tumor. In this subgroup, for instance, the PFS is not increasing anymore above 50% at 3 years independently from the chemotherapeutic scheme. The two current standard therapies are carboplatin plus vincristine during 81 weeks or a weekly IV administration of vinblastine during 70 weeks. The most recent Canadian approach with vinblastine seems to have the same PFS rate, but with a better daily tolerance and less toxicities than the carboplatin/vincristine combination. Therefore, it is becoming the new standard approach in those patients. Nevertheless, we need to improve more their outcome with less recurs and a better first-line tumor response. The recent molecular discoveries involving the Ras/mitogen-activated protein kinase pathway in those PLGG is opening a new era with specific targeted therapies that might be the key to improve their survivals and giving hope to less treatment lines and a better tumor response. Therefore, we designed a prospective open randomized phase II study, named PLGG-MEKTRIC, comparing the experimental arm (a daily MEK inhibitor, Trametinib, Mekinist©) to a standard arm comprising weekly vinblastine during 18 courses of 4 weeks each. The study will enroll 134 patients with a PLGG during childhood, adolescence or young adulthood with no NF1-related disease and without any BRAFv600 mutation located in brain or spine. 67 patients, in each treatment arm, are planned to be enrolled to answer our primary objective. This primary objective will be to determine in the experimental arm a 20% superiority of the 3-year PFS rate in comparison with the standard treatment administered during 18 courses (e.g. 72 weeks). A stratification of the patients will be done in both arms based on molecular tumor results and brain/spine locations to obtain two equivalent arms to be analyzed.

The recruitment time will be 36 months and the complete follow-up of each patient will last 3 years. The secondary objectives will be in both arms: the tumor response rate at 24 and 72 weeks of treatment, the 3-year PFS and OS rates and the frequency of AE/SAE/SUSAR (Adverse Event/Serious Adverse Event) based on CTCAE criteria during the 3 years after the first administration. A Quality of Life (QoL) assessment, based on PEDsQL questionnaires, at 24 weeks, at the end of treatment and 3 years after 1st treatment administration in both arms will be part of this study. Finally, 3-year PFS and OS will be analyzed according to molecular biomarkers and visual assessment (LogMar scale) in each arm. An economic analysis is also planned as an ancillary study to determine a cost effectiveness of the best arm and complementary ancillary molecular studies are already organized. In the future, we hope to push forward this new-targeted therapy as a referenced first line treatment of pediatric PLGG to obtain the best tolerance and positive long-term impact and to extend our knowledge of MEK inhibitor impact in molecular subgroups and in optical pathway locations. We also plan to do a "switch" strategy in patients relapsing in standard arm and we will propose systematically to those patients the experimental treatment (MEK inhibitor ).

appel_a_projets: PHRCK

region: Grand Est

nom_etablissement: HOPITAUX UNIVERSITAIRES DE STRASBOURG

type_etablissement: CH

acronyme: PLGGMEKTRIC

titre: Protocole national de traitement de phase II des patients pédiatriques et AJA non NF1 ayant un gliome de bas grade BRAF non muté en première ligne comparant un traitement par MEK inhibiteur en prise orale quotidienne versus de la vinblastine intraveineuse hebdomadaire pendant 18 mois.

discipline_principale: cancer

nom_porteur: ENTZ-WERLE

prenom_porteur: Natacha


title: Randomized Trial Comparing the Use of MEOPA (Equimolar Mixture of Nitrogen Protoxide and Oxygen)-Coupled Hypnosis Versus MEOPA Standard Care of Pain and Anxiety During Transesophageal Echocardiography (TEE) in Conscious Patients.

acronym: HYPNETO

summary:
The primary purpose is to evaluate the impact of hypnosis coupled with MEOPA (Equimolar Mix-ture of Nitrogen Protoxide and Oxygen) on patient comfort when performing transoesophageal echocardiographies.

Further studies on the use of MEOPA alone or the technique of hypnosis alone in the context of an TEE, would not be innovative in any way in view of previous studies or already in progress.

However, service has led to perform TEEs several times by combining MEOPA and hypnosis. Doctors noted a clear reduction in induction time for hypnosis and satisfaction of the patient and operators. This association technique is very often used in pediatrics.

According to one study, it seems that MEOPA increases the threshold of suggestibility and imagination. However suggestion and imagination are two essential notions of the hypnotic technique. To date, doctors have not found any other studies combining MEOPA and hypnosis for adults patients in the context of TEE.

This leads to the following hypothesis: Is there a difference for the patient in terms of for the global management of pain and anxiety between an TEE performed under MEOPA with a standard support and TEE under MEOPA coupled with hypnosis with support standard?

Secondary purposes are:

Compare patients' feelings / opinions: patients who have benefited from hypnosis associated with MEOPA versus patients who have been treated with MEOPA alone.
Compare patient stress: patients who have benefited from hypnosis associated with MEOPA versus patients who have benefited from MEOPA alone.
Compare the operators' feelings / opinions: procedures that have been performed under hypno-analgesia and MEOPA versus standard procedures under MEOPA alone.
Failed the TEE procedure


type: EudraCT Number

title: A Randomized, Placebo-controlled, Parallel Group, Patient-blind, Phase I Study Assessing the Safety and Exploring the Immunogenicity/Therapeutic Activity of AFFITOPE® PD01A and PD03A in Patients With Early Multiple System Atrophy

summary:
This is a randomized controlled parallel Group phase I study to investigate the safety and immunological/ therapeutic activity of two new vaccines, AFFITOPE® PD01A and AFFITOPE® PD03A, given to patients with early Multiple System Atrophy (MSA).

In total 30 patients are planned to be enrolled in the study: 12 patients in each treatment arm who will receive either 75µg AFFITOPE® PD01A (with adjuvant) or 75µg AFFITOPE® PD03A (with adjuvant) and 6 patients in the control group who will receive the reference substance (Placebo). Over a study duration of 52 weeks, the study participants will receive 4 injections as basic immunization in a 4-weekly interval and 1 boost immunization 36 weeks after the first injection. Male and female patients aged 30 to 75 years can participate in the trial. 2 study sites in France (Bordeaux and Toulouse) will be involved.

AFF009 is part of the project SYMPATH funded by the European Commission (FP7-HEALTH-2013-INNOVATION-1 project; N° HEALTH-F4-2013-602999).

ReferenceCitation: Meissner WG, Traon AP, Foubert-Samier A, Galabova G, Galitzky M, Kutzelnigg A, Laurens B, Luhrs P, Medori R, Peran P, Sabatini U, Vergnet S, Volc D, Poewe W, Schneeberger A, Staffler G, Rascol O; AFF009 Study Investigators. A Phase 1 Randomized Trial of Specific Active alpha-Synuclein Immunotherapies PD01A and PD03A in Multiple System Atrophy. Mov Disord. 2020 Nov;35(11):1957-1965. doi: 10.1002/mds.28218. Epub 2020 Sep 3.

oa_colors: green hybrid

evidence: open (via crossref license)

license: cc-by-nc-nd

license_normalized: cc-by-nc-nd

repositories_institution: Le Centre pour la Communication Scientifique Directe - HAL - Diderot

repositories_institution: Le Centre pour la Communication Scientifique Directe - HAL - Université Paris Descartes

repositories_institution: Le Centre pour la Communication Scientifique Directe - HAL - memSIC

unpaywall_oa_status: hybrid

lead_sponsor: Affiris AG

location_facility: University Hospital Bordeaux (Pellegrin Hospital)


title: COMET Study Effectiveness of a Cognitive Remediation Program of Memory in Patients With Temporal Lobe Epilepsy

acronym: COMETE

summary:
Studies on the cognitive function have highlighted promising results concerning attention. In contrast, in the field of memory, the single cohort study that has been carried out, has not been randomised, with non comparable groups, the significant outcomes are therefore to be balanced.

In this study, patients with focal and structural temporal lobe epilepsy will be randomised in 2 groups : the COMETE group where patients will attend a specific rehabilitation programme of memory and the control group where patients will benefit from a standard treatment.

primary_purpose: Supportive Care

ReferenceCitation: Brissart H, Daniel F, Morele E, Leroy M, Debouverie M, Defer GL. [Cognitive rehabilitation in multiple sclerosis: a review of the literature]. Rev Neurol (Paris). 2011 Apr;167(4):280-90. doi: 10.1016/j.neurol.2010.07.039. Epub 2010 Dec 21. French.

ReferenceCitation: Brissart H, Leroy M, Morele E, Baumann C, Spitz E, Debouverie M. Cognitive rehabilitation in multiple sclerosis. Neurocase. 2013;19(6):553-65. doi: 10.1080/13554794.2012.701644. Epub 2012 Aug 1.

publisher_dissemination: Informa

sponsor_collaborators:
Central Hospital, Nancy, France
CHU de Reims
University Hospital, Strasbourg, France
Centre Hospitalier Universitaire Dijon

location_facility: Service de Neurologie, Hôpital Central, CHRU de Nancy


title: Interventional Before/After Study of the Effect of the DBLG1 System With TERUMO MEDISAFE WITH Insulin Pump on Glucose Control of Patients With Type 1 Diabetes in France. The BETTER Trial

acronym: BETTER

summary:
This study conducted in 90 adults living with type 1 diabetes is an interventional single-arm open-label before/after multicentric national study conducted as a clinical investigation according to the law EU 2017/745 art. 62.

After a 14-day baseline period during which the patient will use a Dexcom G6 Continuous Glucose Monitoring (CGM) and his current therapy (multiple daily injection or open-loop pump), the patient will start a 42-day treatment period during which he will use the DBLG1 System, a closed loop system (including a DBLG1 handset, a TERUMO MEDISAFE WITH insulin pump, in addition to his Dexcom G6 CGM). An optional 6-week extension period with treatment will be proposed to patients agreeing to pursue the use of the DBLG1 system.

The main objective is to evaluate the safety and efficacy of the DBLG1 System with a TERUMO MEDISAFE WITH insulin pump in closed-loop for 6 weeks in 90 adults with type 1 diabetes.

Data related to their glycemia, complications, usability and quality of life will be collected.

The study is completed when all patients have their "end of study" file completed in the electronic Case Report Form (eCRF).

lead_sponsor: Diabeloop

sponsor_collaborators: Diabeloop Icadom

location_facility: Groupe Hospitalier La Rochelle - Ré - Aunis


title: Standard Patient Training Versus Vik Chatbot Guided Training: a Randomized Controlled Trial for Asthma Patients

acronym: AsthmaTrain

summary:
The onset of smartphone usage has provided new opportunities for managing patients outside the walls of healthcare facilities. The development of asthma-specific smartphone applications represents an excellent area for partnership between developers and medical teams for delivering therapeutic education at the required time and in a personalised way. Within this context, the overall goal of the AsthmaTrain study is to perform a first, small pilot study comparing a new French-language chat-bot guided asthma patient education programme (the 'Vik' application) with the classic, authority-approved patient education program at the University Hospitals of Montpellier, Montpellier, France.

The primary objective is to compare a population of adult patients with asthma and participating in a standard patient education programme with a similar population participating in Vik-guided education programme in terms of change in overall scores on the Asthma Quality of Life Questionnaire (AQLQ).

ReferenceCitation: Suehs CM, Vachier I, Galeazzi D, Vaast F, Cardon F, Molinari N, Bourdin A. Standard patient training versus Vik-Asthme chatbot-guided training: 'AsthmaTrain' - a protocol for a randomised controlled trial for patients with asthma. BMJ Open. 2023 Feb 21;13(2):e067039. doi: 10.1136/bmjopen-2022-067039.

ipd_sharing: Yes

ipd_sharing_description:
The general goal is to make the study data available to interested researchers as well as to provide proof of transparency for the study.

Data will be made available to persons who address a reasonable request to the study director.

Individual participant data (and an accompanying data dictionary) will be de-identified and potentially further cleaned or aggregated as the investigators deem necessary to protect participant anonymity.

The study protocol, participant information materials, and paper case report form will also be made available to the public.

lead_sponsor: University Hospital, Montpellier

location_facility: Centre Hospitalier Universitaire de Montpellier


title: Multicenter, Prospective, Randomized, Controlled Open Study Albumin 20% Versus Saline

summary:
Objective: To determine whether the early administration of albumin as an expander and antioxidant would improve survival on the 28th day for septic shock patients.

Design: Prospective, multicenter, randomized, controlled versus saline, stratified on nosocomial infection and center.

Setting: 27 Intensive Care Units (ICU) in France

Coordinator: Pr J.P. Mira and Dr J. Charpentier - Cochin Hospital- Paris

Patients: 800 patients could be included during the first 6 hours of their septic shock.

lead_sponsor: Laboratoire français de Fractionnement et de Biotechnologies


title: Predictive Value of Biomarkers on Volemia, Extra and Intra Vascular Varation and Hydroelectrolytic Disorders in Different ICU Patients

acronym: ENVOL

summary: The purpose of this study is to determine whether the Biomarkers (pro adrenomedullin (MR proADM), pro arginin vasopressin (CT proAVP), pro atrial natriuretic peptid (MR proANP), Pro Endothelin) changes at Day 2, Day 5 and Day 7 of ICU admission are correlated with Intravascular volume assessed by Cr 51 on red blood cells (Day 2 and Day 7) and by I 125 on albumine Day 7. The correlation of these Biomarkers are also evaluted with other markers such as erythropoietin and catecholamines. 80 ICU patients are included.

ReferenceCitation: Vigue B, Leblanc PE, Moati F, Pussard E, Foufa H, Rodrigues A, Figueiredo S, Harrois A, Mazoit JX, Rafi H, Duranteau J. Mid-regional pro-adrenomedullin (MR-proADM), a marker of positive fluid balance in critically ill patients: results of the ENVOL study. Crit Care. 2016 Nov 9;20(1):363. doi: 10.1186/s13054-016-1540-x.

lead_sponsor: ThermoFisher Scientific Brahms Biomarkers France


title: Interoception in Anorexia Nervosa

acronym: INT-AN

summary: Anorexia nervosa is a serious psychiatric illness whose causes remain poorly understood, and which remains difficult to treat to this day. Many clinical manifestations of this disease can have their origin in abnormalities in the perception of signals coming from inside the body, but this remains to be demonstrated. In recent years, research in healthy subjects has shown how the brain constantly perceives the viscera (heart, lungs, stomach). The examiners will use these new, objective and validated methods to explore how the brain processes information from the viscera (interoception) in anorexic patients. In practice, they will quantify the coupling between the cardiac cycle and involuntary eye movements, as well as between the respiratory cycle and voluntary actions such as pressing a button. Finally, by simultaneously recording the electrical activity of the brain, and that of the stomach, the examiners will measure the coupling between the brain and the stomach. All these measurements, which will be compared between a population of patients and healthy subjects, will make it possible to determine whether anorexic patients have an alteration in the perception of their internal body signals and whether this damage affects several organs.

lead_sponsor: Fondation Santé des Étudiants de France

collaborators: Laboratoire de Psychologie et NeuroCognition


title: Short Telomere in Patients at High Cardiovascular Risk: a Simple Marker or a Major Determinant of Accelerated Arterial Aging

acronym: TELARTA

summary:
The prevailing view in telomere epidemiology is that leukocyte telomere length (LTL) is associated with atherosclerosis and accelerated aging since it serves as a biomarker of the cumulative burden of inflammation and oxidative stress during adult life. Our recent results however, indicate that telomere length (TL) is mainly determined at birth and childhood. Since short telomeres ante cede atherosclerosis, the investigators hypothesize that TL is not just a simple marker, but a real determinant of arterial aging. That is because TL reflects cellular repair capacity and a short LTL denotes diminished repair reserves. This hypothesis cannot be tested by measurements of LTL alone, since this parameter reflects TL at birth and its age-dependent attrition thereafter. The investigators propose, therefore, a model that makes it possible to examine different elements of TL dynamics in different tissues: leukocytes, skeletal muscle, endothelial progenitor cells (EPCs), skin or subcutaneous fat in patients with or without atherosclerosis.

Our model is based on the following premises, which are derived from observations that TL is synchronized (equivalent) across somatic tissues/cells of the newborn:

TL in skeletal muscle mainly reflects TL at birth
The difference in TL between muscle and leukocytes in adults (approximately 1.5 Kbp) mainly reflects LTL attrition during the growth period, i.e., childhood/adolescence
TL in EPCs determines the cell proliferative ability and therefore capacity for vessels repair during aging.

The general aim of the present project is to examine the links of arterial aging with TL, as expressed in different tissues, and LTL dynamics, as expressed in the difference between TLs of muscle and leukocytes.

ReferenceCitation: Toupance S, Simonici S, Labat C, Dumoulin C, Lai TP, Lakomy C, Regnault V, Lacolley P, Dignat George F, Sabatier F, Aviv A, Benetos A; TELARTA consortium dagger. Number and Replating Capacity of Endothelial Colony-Forming Cells are Telomere Length Dependent: Implication for Human Atherogenesis. J Am Heart Assoc. 2021 May 18;10(10):e020606. doi: 10.1161/JAHA.120.020606. Epub 2021 May 6.

publisher_dissemination: Wolters Kluwer Health

ReferenceCitation: Benetos A, Toupance S, Gautier S, Labat C, Kimura M, Rossi PM, Settembre N, Hubert J, Frimat L, Bertrand B, Boufi M, Flecher X, Sadoul N, Eschwege P, Kessler M, Tzanetakou IP, Doulamis IP, Konstantopoulos P, Tzani A, Korou M, Gkogkos A, Perreas K, Menenakos E, Samanidis G, Vasiloglou-Gkanis M, Kark JD, Malikov S, Verhulst S, Aviv A. Short Leukocyte Telomere Length Precedes Clinical Expression of Atherosclerosis: The Blood-and-Muscle Model. Circ Res. 2018 Feb 16;122(4):616-623. doi: 10.1161/CIRCRESAHA.117.311751. Epub 2017 Dec 14.

evidence: open (via page says license)

repository_institution: University of Groningen / Centre for Information Technology - University of Groningen research database

repository_institution: DANS - Data Archiving and Networked Services - NARCIS - National Academic Research and Collaborations Information System

repositories_concat: PubMed Central;pure.rug.nl

lead_sponsor: Central Hospital, Nancy, France

collaborators: Assistance Publique Hopitaux De Marseille

location_facility:
Chu Nancy
AP Hôpitaux de Marseille

appel_a_projets: PRTS

nom_etablissement: CHRU DE NANCY

acronyme: TELARTA

titre: Télomères courts chez les patients à haut risque cardiovasculaire : simple marqueur ou déterminant majeur du vieillissement artériel accéléré

discipline_principale: autre

nom_porteur: BENETOS

prenom_porteur: Athanase