M Baqué Patrick

M Bernardin

Gilles Réanimation

Milou-Daniel Drici

Pharmacologie Clinique

M Fuzibet

M Schneider

M Thyss

Antoine Cancérologie

M Tran

Albert Hépato

Universite Nice

Sophia Antipolis

Faculte De Medecine

Mme Askenazy-Gittard

Florence Pédopsychiatrie

M Barranger

Emmanuel Gynécologie

) M Bérard

Étienne Pédiatrie

) M Bongain

André Gynécologie-Obstétrique

Mme Breuil

Véronique Rhumatologie

) M Castillo

) M Chevallier

Patrick Radiologie

M Ferrari

Émile Cardiologie

M Ferrero

Jean-Marc Cancérologie

; Radiothérapie

M Piche

Mme Raynaud

Dominique Hématologie

) M Rosenthal Éric

Mme Alunni Véronique

M Bahadoran

Philippe Cytologie

Stéphanie Ophtalmologie

Sylvie Génétique

M Favre

Guillaume Néphrologie

) M Fournier

Jean-Paul Thérapeutique

Mme Giordanengo

Valérie Bactériologie-Virologie

Mme Giovannini-Chami

Lisa Pédiatrie

Mme Sacconi

M Mme

M Ambrosetti

Damien Bernard-Pomier

Ghislaine Bronsard

Mme Contenti-Liprandi

M Doyen

Jérôme Radiothérapie

) M Fosse

M Garraffo

Rodolphe Pharmacologie Fondamentale

Humbert Olivier Biophysique

Mme Lamy

Mme Long-Mira

Elodie Cytologie

Marie-Noëlle Physiologie

Mme Moceri

Pamela Cardiologie

M Montaudie

Henri Dermatologie

Mme Seitz-Polski

Barbara Immunologie

M Squara

Fabien Cardiologie

) M Testa

Jean Épidémiologie

M Amiel

Jean M Gastaud

Pierre M Albertini

Marc M Gérard

Jean-Pierre M Balas

Daniel M Gillet

Jean-Yves M Batt

Michel M Grellier

Patrick M Blaive

Bruno M Grimaud

Dominique M Boquet

Patrice M Hofliger

Philippe M Bourgeon

André M Jourdan

Jacques M Boutté

Patrick M Lambert

Jean-Claude M Bruneton

Jean-Noël M Lazdunski

Michel Mme

Bussiere Françoise

M Lefebvre

Jean-Claude M Camous

Jean-Pierre M Le Fichoux

Yves M Canivet

Bertrand Mme Lebreton

Elisabeth M Cassuto

Jill-Patrice M Mariani

Roger M Chatel

Marcel M Masseyeff

René M Coussement

Alain M Mattei Mathieu

Mme Crenesse

Dominique M Mouiel

Jean M Darcourt

MYQUEL Guy Mme

Martine M Dellamonica

Pierre M Ortonne

Jean-Paul M Delmont

Jean M Pringuey

Dominique M Demard

François M Santini

Joseph M Desnuelle

Claude M Sautron

Jean Baptiste

M Dolisi

Claude M Schneider

Maurice Mme

Euller-Ziegler Liana

M Toubol

Jacques M Fenichel

Patrick M Tran

Dinh Khiem

M Franco

Alain M Van Obberghen

Emmanuel M Freychet

Pierre M Ziegler

Gérard M C U Honoraires

M Arnold

Jacques M Giudicelli

Jean M Basteris

Bernard M Magné

Jacques M Benoliel

José Mme Memran

Nadine Mlle Chichmanian

Rose-Marie M Mengual

Raymond Mme Donzeau

Michèle M Philip

Patrick M Emiliozzi

Roméo M Poirée

Jean-Claude M Franken

Philippe Mme

Roure Marie-Claire

M Gastaud

BLANC-PEDEUTOUR Florence Cancérologie

Keywords: General practice, Hypnosis, Hypnotic and Anxiolytic Benzodiazepines

REMERCIEMENTS

À Monsieur le Professeur Marc RAUCOULES-AIMÉ, Vous me faites l'honneur de présider ce jury et de juger ce travail. Soyez assuré de mes remerciements et de ma respectueuse considération.

À Monsieur le Professeur Patrick BAQUÉ, Vous me faites l'honneur de juger ce travail. Veuillez trouver ici l'assurance de ma sincère reconnaissance.

À Madame le Professeur Brigitte MONNIER, Merci d'avoir accepté de juger ce travail et merci de l'enseignement que vous m'avez apporté en tant que tutrice au cours de mes premières années d'internat. Veuillez croire en ma respectueuse considération.

À Monsieur le Professeur GARDON Gilles, Je vous remercie de l'intérêt que vous avez porté à ce sujet de thèse. Je vous adresse toute ma reconnaissance.

À Monsieur le Docteur TÉTART Johann, Merci d'avoir participé à l'initiation de ce projet et pour le temps passé lors des réunions téléphoniques. Aie l'assurance de ma sincère reconnaissance.

À Monsieur le Docteur BARBAROUX Adriaan, Tu me fais l'honneur d'avoir accepté de diriger ce travail. Je te remercie sincèrement pour ton accompagnement si précieux. Merci pour la disponibilité dont tu as fait preuve. Merci d'avoir été à l'écoute de mes peurs, de mes doutes et d'avoir su me motiver même lorsque j'étais à l'autre bout du monde. Je ne pouvais trouver meilleur directeur de thèse.

À Marion, ma co-thésarde, je suis contente d'avoir fait ce travail avec toi. Merci d'avoir partagé tous ces moments de doutes, de joie, de travail, de réunions téléphoniques. J'aime tes valeurs et tes convictions, ne change pas.

Thank you, Françoise for your valuable advices.

À tous les médecins qui ont participé à cette étude, pour le temps que vous avez consacré à mon travail.

Aux médecins qui ont croisé ma route et qui ont parfois sans le savoir orienté mon parcours professionnel :

Au Professeur ALLARD Michel, pour avoir fait naître en moi l'envie de devenir médecin. Au Docteur LECERF Éric, pour m'avoir transmis le goût de la médecine générale alors que je ne m'y prédestinais pas. Merci pour cette belle expérience. Au Docteur BARBE Chantal, pour l'enseignement apporté. Tu es à mes yeux un modèle d'accomplissement professionnel et personnel.

Au Docteur DANDURAN Marie et DIEBOLT Vincent, ainsi qu'à toute l'équipe de la maison de santé de Valdeblore (en particulier Carine et Annabelle), pour leur accueil, leur sympathie et leur apprentissage.

Au Docteur LION Odile, merci pour ta confiance et ton enseignement.

À mes proches :

À mes parents qui me couvrent depuis des années de leur amour, malgré mes sautes d'humeur parfois. Merci pour cette enfance parfaite. Maman, je suis contente de pouvoir aussi bien discuter avec toi. Papa, je te remercie pour les devoirs du soir dans le jardin, je te dois tous mes « exploits » sportifs et merci de m'avoir appris que la défaite n'était pas une fatalité.

À ma petite soeur chérie, dont j'admire le parcours aussi bien professionnel que personnel. Je suis tellement fière de toi, ma juju. Je t'aime énormément. J'ai hâte de me rapprocher de vous et de vous voir plus souvent, Mathis et toi.

À mes grands-parents, mes oncles, mes tantes, mes cousins et cousines pour leur amour et leur soutien, avec une pensée plus particulière pour mon oncle Éric. Merci à Mamie Ginette pour sa relecture, à Papi Guy et à tata Isa d'avoir fait le trajet jusqu'ici, j'espère vous rendre fiers.

À ma belle-famille, qui me supporte depuis près de 8 ans. J'ai vraiment de la chance d'avoir une belle-famille comme la vôtre. Je ne pouvais rêver mieux. Merci pour tout.

À Alice G, ma presque jumelle, merci pour ton amitié si précieuse et ton soutien depuis 28 ans. Je suis contente et si fière de t'avoir à mes côtés. J'aime te savoir heureuse avec Julien, même si le Ch'Nord c'est un peu loin. À Aude, qui depuis mes 15 ans me comble de joie, de rire et d'amour. J'ai hâte de pouvoir être à vos côtés, Pipo et toi, l'été prochain. Vous avoir à mes côtés aujourd'hui est le plus beau cadeau que vous puissiez me faire.

À Pauline, sans qui je ne serais pas là aujourd'hui. Tu m'as apporté l'équilibre dont j'avais besoin pour réussir cette première année. Je suis très fière de la femme et de l'infirmière que tu es devenue. Je suis contente de te savoir auprès de moi en ce jour.

À Chloé, ma cloque, parce qu'il y a des amitiés évidentes et qui le reste même à des kilomètres. Ta présence ce jour en est la preuve, mille mercis.

À Hélène et Quentin A-D, loin des yeux, si près du coeur. Merci de tout coeur d'être là.

À Justine, merci d'avoir été une coloc parfaite. Merci pour tous ces moments de rires, de pleurs, de danses, de chants parfois faux. Avoir été plantouriane avec toi a été un vrai régal.

À Audrey et Quentin, je suis tellement heureuse de vous avoir suivis dans cette aventure qu'est l'internat pour prolonger cette belle amitié. J'espère avoir été à la hauteur pour votre grand jour.

À Lyor, on part mais on ne t'abandonne pas. Prends le bon côté de la vie, ne lui casse pas les côtes, tu auras ta chambre, un jour, sur la Côte Ouest ! Je ferai tout pour ne pas faire mourir ton lierre, promis.

À Alice B, ma deuxième petite soeur, à qui je pense souvent.

À Anne, j'ai hâte de venir te rendre visite de nouveau à Nantes.

À Guigui, mon oncle de coeur.

Conclusion :

Le fort taux de participation et la taille de notre échantillon suggèrent que ces résultats sont représentatifs. La formation à l'hypnose n'est pas significativement corrélée à une meilleure prescription des hypnotiques ou des anxiolytiques. Une étude qualitative est en cours pour mieux comprendre ces résultats.

Mots-clés : Médecin Générale, Hypnose, Benzodiazépines hypnotiques et anxiolytiques.

INTRODUCTION

Iatrogeny is a public health burden. The latest studies show that 10% of hospitalizations are due to iatrogeny (1,2). Internationally, a New Zealand study shows that reducing the use of a single drug for the elderly reduces the number of hospital admissions ( 3). An American study shows that benzodiazepines increase the risk of readmission to hospital within 30 days(4). France is one of the five countries with the highest benzodiazepine and related drug use in Europe [START_REF] Richard | Etat des lieux de la consommation des benzodiazépines en France[END_REF]. 15 % of new benzodiazepine introductions are extended beyond the recommended prescribing time [START_REF] Richard | Etat des lieux de la consommation des benzodiazépines en France[END_REF]. Prolonged use of benzodiazepines is particularly dangerous [START_REF] Holbrook | Meta-analysis of benzodiazepine use in the treatment of insomnia[END_REF][START_REF] Neutel | The epidemiology of long-term benzodiazepine use[END_REF][START_REF] Gage Sb De, Moride | Benzodiazepine use and risk of Alzheimer's disease: case-control study[END_REF]. The National Health System has set up a process to improve prescriptions in general medicine: The Remuneration based on Public Health Objectives (ROSP, Rémunérations sur Objectifs de Santé Publique). This system represents an investment of 240 million euros per year(9). ROSP for benzodiazepines correspond to the percentage of patients on benzodiazepines hypnotics or anxiolytics prolonged outside the recommended range among patients treated with benzodiazepines. The maximum amount of ROSP for benzodiazepines is 490 euros per general practitioner (GP) per year, that means more than 25 million euros nationwide (9,10). Unfortunately, studies show that the ROSP has few or no effect on GPs prescribing [START_REF] Rat | Did the new French payfor-performance system modify benzodiazepine prescribing practices?[END_REF][START_REF] Scott | The effect of financial incentives on the quality of health care provided by primary care physicians. Cochrane Effective Practice and Organisation of Care Group, éditeur[END_REF]. It is therefore necessary to find new aids to improve benzodiazepine prescribing.

Hypnosis could be an aid in limiting these prescriptions outside the recommended time limits [START_REF] Raineri | hypnose L'hypnose en consultation[END_REF].

Hypnosis is a 200-year-old technique that uses speech to induces a specific state of consciousness characterized by indifference to the outside world and a greatly increased ability to receive suggestions. Through these suggestions, the patient is supposed to find internal resources for fighting anxiety, pain(14), etc. Others are open to a wider public with variable ethics [START_REF] Gueguen | Evaluation de l'efficacité de la pratique de l'hypnose[END_REF]. If hypnosis is not yet recognized by the French Medical Board ( 16), some indications are now recognized. For example, hypnoanalgesia is considered to be a medical act (14). However, there is currently no reimbursement for hypnosis sessions.

About ten medical universities in

There are few studies on hypnosis and often the samples are too small for the results to be significant [START_REF] Ng | Hypnotherapy for Sleep Disorders[END_REF][START_REF] Pelissolo | L'hypnose dans les troubles anxieux et phobiques : revue des études cliniques[END_REF],hence the interest in conducting new studies with reliable methodologies.

The objective of this study was to evaluate the impact of hypnosis training (UD and IFH) of GPs on the prescription of hypnotics and anxiolytics over the long term by GPs. This study was associated with a qualitative study which explores the perception of GPs in the Provence-Alpes-Côte d'Azur region on their hypnosis training and the way in which it is integrated into their practice, particularly on the management of insomnia.

METHOD

A descriptive observational study was conducted from June to December 2019 on GPs trained in hypnosis in France.

Inclusion criteria:

The inclusion criteria were as follows: liberal GPs practicing in France, trained in medical hypnosis by UD or IFH, working as liberals with a convention allowing access to ROSP data.

Setting, participants, design and procedure:

The To obtain a statistical power of 90% with a tolerated alpha risk of 5%, 53 subjects were required, assuming 40.9% of prescriptions being continued over the long term in the general population against 20,4% in the hypnosis group. However, this a priori sample size calculation was made for information purposes only. The aim of this nationwide survey was to include as much hypnosis trained GPs as possible.

Data analysis:

The data collected was entered into an Excel® spreadsheet and analysed using Jamovi® software [START_REF]R: A Language and envionment for statistical computing[END_REF][START_REF] Core | R: A Language and envionment for statistical computing[END_REF]. The One Sample Student T Test was used to analyse the sample after checking for normality using the Skewness, Kurtosis and Shapiro Wink tests.

The primary outcome of ROSP percentages of anxiolytic and hypnotic benzodiazepines were analysed by adjusting for gender, type of training or exercise setting. The secondary judgement criteria represented by the other questionnaire items were then examined by calculating a correlation matrix.

Ethical and regulatory aspects:

Patient and public involvement was not appropriate for this study. A statement MR-004 was made to the National Commission for Data Protection and Liberties (CNIL, Commission Nationale de l'Informatique et des Libertés). This type of study did not require the approval of an ethics committee.

RESULTS

Of the 189 GPs interviewed, 69 were working in hospitals and were therefore excluded (not concerned by the ROSP). Those with no ROSP due to the absence of agreement with the national health insurance or to retirement, replacement or still being a resident were also excluded (39). Of the remaining GPs meeting the inclusion criteria, 24 could not be contacted because they were missing in the directory and five declined to participate in the study. A total of 52 GPs agreed to participate in this study out of the 81 liberal GPs trained in hypnosis who could have been included in this study (Fig 1 .): 38 GPs trained by UD and 14 GPs trained by IFH.

The response rate of our sample was 64%, mainly due to the absence of GPs in the repertoire. The response rate of our sample (liberal GPs listed in the directory and agreed by the national health insurance) was more than 91% (52 out of 57). Our sample is supposed to be the third of the total French population of GPs trained in hypnosis since the UD and IFH provided a list of 189 GPs and declared than 560 GPs were trained since the creation of the UD and IFH, respectively 2001 and 1990.

Data collection:

Characteristics and representativeness of the sample:

The average age of the GPs included was 51.3 (S.D. 9.7) years old, which is close to the average age of GPs (50.6 years) in France in 2018(23). The average age of GPs trained by the IFH was 56.6 years old, which can be explained by the fact that IFH was created in 1990 and UD were initiated in 2001.

Most of the GPs were charging the national health approved rate (also called "sector 1") (48 GPs), 4

GPs were charging extra fees ("sector 2"). The average number of patients on a GP's list was 1030, with an average of 63 patients aged over 80 years, i.e. 6% of the patients' population (see population Included GPs (n =52)

Refusal (n = 5)
characteristics in table 1). The average seniority of GPs in their practice was 18 years. The percentage of women was 50%, which is close to French GPs population (23). The average age of women was slightly lower than the one of men, which is consistent with the recent feminization of the profession.

The place of practice of the GPs surveyed was predominantly urban at 50% (26 GPs), semi-rural at 29% (15 GPs) and rural at 21% (11 GPs), in line with French medical demographics, which are predominantly urban (23,[START_REF]La demographie medicale a l'horizon 2030 : de nouvelles projections nationales et regionales[END_REF].

Main results:

The public health target for the percentage of benzodiazepines is 30% for hypnotics and 9% for anxiolytics. The average percentage of benzodiazepine hypnotics in this sample was 38,3% (S.D. 20.2), below the national average of 42.4% in December 2019 but still above the targeted objective. The average ROSP data for Benzodiazepines Anxiolytics was 14.8% (S.D. 8.5), compared to a national average of 14.8%, above the targeted objective too.

Statistical analysis using Student's T-test did not find a significant difference (p = 0.14) in prescribing between GPs trained in hypnosis and the general population of GPs (t -1.48, 95% confidence interval -9.74 to 1.48). There was also no significant difference (p = 0.97) in benzodiazepine prescribing (t 0.028, 95% confidence interval -2,41 to 2,34).

Secondary Outcomes:

No significant correlation was found between Benzodiazepines prescriptions and the age, the gender of the GP the seniority of his installation, his environment of practice (rural, urban, semi-rural), the average duration of the consultations of general medicine, the visit or not of laboratory, the fact to charge extra fees or not (sector 1 or 2), the place of his internship, the year and the kind of training (UD or IFH).

DISCUSSION

Principal findings:

These data showed that GPs trained in medical hypnosis were not significantly better prescribers for benzodiazepine hypnotics or anxiolytics than GPs in general. These non-significant results are fairly consistent with the often inconclusive statistical studies about hypnosis [START_REF] Ng | Hypnotherapy for Sleep Disorders[END_REF][START_REF] Pelissolo | L'hypnose dans les troubles anxieux et phobiques : revue des études cliniques[END_REF][START_REF] Lam | Hypnotherapy for insomnia: A systematic review and meta-analysis of randomized controlled trials[END_REF], but this is the first time ever a study of this magnitude has been conducted.

Comparison with other studies:

The correlation of the data showed significantly that an elderly population was not synonymous with a benzodiazepine-dependent population, contrary to data in the literature. Fourrier et al have shown that elderly subjects were heavy benzodiazepine users [START_REF] Fourrier | Benzodiazepine use in an elderly community-dwelling population: Characteristics of users and factors associated with subsequent use[END_REF]. Our data did not find any correlation between the mean patients list of a GP and his proportion of prolonged benzodiazepines prescription.

Prescribing of benzodiazepines in this study is not correlated with numbers of laboratory visits, unlike the literature which tends to show that GPs receiving medical sales representatives are heavy prescribers [START_REF] Cormack | Factors linked to the prescribing of benzodiazepines by general practice principals and trainees[END_REF][START_REF] Wazana | Physicians and the pharmaceutical industry: is a gift ever just a gift?[END_REF][START_REF] Spurling | Information from Pharmaceutical Companies and the Quality, Quantity, and Cost of Physicians' Prescribing: A Systematic Review[END_REF]. This discrepancy can be explained by the fact that the rate of GPs not receiving medical sales representatives in this study was much higher than the national average (44% vs 25%)(30).

Strengths and limitations of the study:

The response rate of our sample was extremely high, since 52 of the 57 GPs who met all the inclusion criteria agreed to respond to this study, i.e. 91% of the sample. Since the sample corresponds to one third of the GPs trained in France, our sample is probably highly representative of the population of GPs trained by UD and IFH, the two courses which guarantee quality practices [START_REF] Gueguen | Evaluation de l'efficacité de la pratique de l'hypnose[END_REF] according to the National Institute of Health and Medical Research (INSERM, Institut National de la Santé Et de la Recherche Médicale). The high response rate was partly due to the speed of the questionnaire and the ease of access to the ROSP data, directly accessible by the practitioner on his personal space on the National Health Insurance website. This study was carried out in conjunction with a qualitative study on hypnosis training for GPs in the Provence-Alpes-Côte d'Azur region and its influence on their prescriptions, particularly in the context of insomnia. These data showed that medical hypnosis is seen as an aid in the management of insomnia [START_REF] Bonnard | Effet d'une formation en hypnothérapie sur le médecin généraliste et sur sa prise en charge des patients souffrant d'insomnie : enquête par entretiens individuels[END_REF]. The few qualitative theses on hypnosis also showed a downward trend in therapeutics [START_REF] Geoffrion | Influence de l'hypnose éricksonienne sur la consommation en benzodiazépines et molécules apparentées chez des patients en Illeet-Vilaine et Côtes d'Armor[END_REF][START_REF] Roch | Étude qualitative sur les impacts d'une formation à l'hypnose médicale pour des médecins généralistes d'Île-de-France[END_REF].

The primary outcome (ROSP percentages) are quite controversial. There are many confounding factors on these data. The method of calculation can also lead to bias: a GP prescribing very few benzodiazepines but who has these few patients out of time will have a higher percentage than a GP prescribing many benzodiazepines but most within the recommended time frame, even with the same number of patients out of time. However, this criterion is sufficiently reliable to be recognised by the National Health Insurance as representing good prescribing by GPs in the context of ROSP. Indeed, prescribing benzodiazepines for a short duration is not necessarily problematic, the most problematic situation is long term prescription [START_REF] Gage Sb De, Moride | Benzodiazepine use and risk of Alzheimer's disease: case-control study[END_REF]. Therefore, this criterion seems relevant. However, it might be interesting to evaluate the number of patients treated with benzodiazepines in order to put these percentages in the context of the number of prescriptions.

Another limitation could be the risk of a reporting bias when GPs were asked to report their ROSPs data. Asking GPs to provide a screenshot of the National Health Insurance website would have helped to limit this bias. However, it was chosen to keep this data declarative in order to preserve the short duration of the interviews with the GPs, which allowed a remarkably high response rate.

Conclusion:

Overall, the present study has shown that GPs trained in hypnosis were no better prescribers of benzodiazepines than untrained GPs in terms of prescription duration. Hypnosis is a therapy that varies from one individual to another, both in terms of indication and method [START_REF] Cheveau | Guérir d'un traumatisme psychique par hypnose[END_REF][START_REF] Benhaiem | Au moment d'être admis(e) à exercer la médecine, je promets et je jure d'être fidèle aux lois de l'honneur et de la probité[END_REF], which does not allow generalisation and makes it difficult to develop significant studies [START_REF] Gueguen | Evaluation de l'efficacité de la pratique de l'hypnose[END_REF][START_REF] Ng | Hypnotherapy for Sleep Disorders[END_REF][START_REF] Pelissolo | L'hypnose dans les troubles anxieux et phobiques : revue des études cliniques[END_REF]. The qualitative study carried out jointly has shown that trained GPs used hypnosis to manage insomnia and considered hypnosis as helpful. In that study, GPs said that results for insomnia were variable from one patient to another. Some patients had a better sleep after few hypnosis sessions, but few others felt no effect of hypnosis. The present study is probably the largest study conducted on GPs trained in hypnosis in primary care. This study did not show any difference in the long-term/short-term benzodiazepine prescription ratio between trained GPs and non-trained GPs.

  Data collection: ............................................................................................................................. Characteristics and representativeness of the sample: .................................................................. Main results: ................................................................................................................................. Secondary Outcomes: ................................................................................................................... DISCUSSION ....................................................................................... Principal findings ........................................................................................................................... Comparison with other studies: .................................................................................................... Strengths and limitations of the study: .......................................................................................... Conclusion: ................................................................................................................................... Funding: ........................................................................................................................................ BIBLIOGRAPHY .................................................................................. SERMENT D'HIPPOCRATE : ................................................................ ABSTRACT: ......................................................................................... LISTE DES ABRÉVIATIONS : CNIL : National Commission for Data Protection and Liberties, Comission Nationale de l'Informatique et des Libertés DERMG : Département d'Enseignement et de Recherche en Médecine Générale

  France offer a University Diploma (UD) in medical hypnosis accessible to GPs. According to a recent report of the National Institute of Health and Medical Research (INSERM, Institut National de la Santé Et de la Recherche Médicale), certain training courses guarantee quality practices (15). The one-year UDs delivered in the Faculty of Medicine as well as the French Hypnosis Institute (IFH) are part of this training. The IFH training has a reliable and recognized two-year course.

  Universities cited in the last INSERM study on medical hypnosis were contacted by telephone, email or directly via the faculty's website. Only five out of ten agreed to provide a list of their students: Bordeaux, Limoges, Nice, Paris VI and Reunion Island. Universities that did not respond favourably agreed to give an approximate number of GPs trained in hypnosis. This approximate number of trained GPs allowed the authors to know the size of the population of GPs trained in hypnosis by UDs or IFH, that is supposed to be around 500 GPs (Fig1). The lists given enabled to contact 129 GPs, which represents one third of the general practitioners trained by UD in France. All the GPs trained by the IFH were included (60).A total of 189 GPs trained in hypnosis, 129 by UD and 60 by IFH, were contacted over a period from June to December 2019. GPs were surveyed by telephone or e-mail questionnaire on the main criteria for prescribing[START_REF] Faurie | Les déterminants du renouvellement des benzodiazépines et apparentées au -delà de trois mois[END_REF][START_REF] Élise | Les prescriptions des médecins généralistes et leurs déterminants[END_REF] and on the percentage of out-of-time prescriptions of hypnotic and anxiolytic benzodiazepines based on Public Health Goals Compensation data, the ROSP. The telephone questionnaire lasted between three and five minutes. The items requested in the questionnaire were as follows: age, gender, length of time in practice, conventional sector (1 or 2), practice environment (rural, urban, semi-rural), average duration of general medical consultations, meeting pharmaceutical representatives or not, place of internship, year and place of training at the UD or IFH, the size of the GP's patients list, the number of GP's patients over 80 years of age and the percentages of prolonged prescriptions of hypnotics and anxiolytics (ROSP). The authors decided to use the percentages of prolonged prescriptions of hypnotics and anxiolytics in the Public Health Objective Remuneration (ROSP) of GPs trained in hypnosis to evaluate the prescription of benzodiazepines because the GPs themselves could access to their personal data on the national health insurance website and then transmit them or the investigator would perform the manoeuvre via the Team Viewer® remote control software.

Fig 1 .

 1 Fig 1. Flow chart GPs: General practitioners, UD: University Diploma, IFH: French Hypnosis Institute

  The GP characteristics relatively close to those of the general population and the number of GPs included suggest that this study is representative. The number of GPs trained in hypnosis is low: 1% of the French general practitioner population. In comparison, 2.6% of French GPs received palliative care IUD (Inter-University Diploma) between 2005 and 2009(31).

Liste des enseignants au 1er septembre 2019 à la Faculté de Médecine de Nice MAITRE DE CONFÉRENCES DES UNIVERSITÉS

	M.	DARMON David	Médecine Générale (53.03)
	Mme	GROS Auriane	Orthophonie (69)
	PROFESSEURS AGRÉGÉS
	Mme	LANDI Rebecca	Anglais
	PRATICIEN HOSPITALIER UNIVERSITAIRE
	M.	DURAND Matthieu	Urologie (52.04)
	M.	SICARD Antoine	Néphrologie (52-03)
	PROFESSEURS ASSOCIÉS
	M.	GARDON Gilles	Médecine Générale (53.03)
	Mme	MONNIER Brigitte	Médecine Générale (53.03)
	MAITRES DE CONFÉRENCES ASSOCIÉS
	Mme	CASTA Céline	Médecine Générale (53.03)
	M.	GASPERINI Fabrice	Médecine Générale (53.03)
	M.	HOGU Nicolas	Médecine Générale (53.03)

  Aux amis de longue date : la MIF : Marie, Ana, Laura, Mel, Célia, Caro, Alex, Jérem, Cougn, Breb, Chach, Guigui, Clément et leurs valeurs ajoutées, les copines d'enfance : Noémie, Natacha et Adèle. Aux pictaviens, Quentin F, Camille et leurs petits bouts, Pierre et Maëlle, Arthur et Alice, Julie et Thomas, Sylvain et Lucia, Éric (même s'il n'aime pas mes pantalons de voyage) et Élisa, Coco et ses coconades, pour leur amitié si précieuse.

	À la coloc du Fango, aux bons moments passés.
	À ma Carinette, une des plus belles rencontres au cours de mon internat. Je suis tellement fière de
	toi pour ta formation d'IPA. Je te souhaite de réussir et de t'épanouir dans cette nouvelle voie.
	À Loïc, merci d'être à mes côtés depuis presque huit ans. Merci de me faire rire comme au premier
	jour. Merci de me comprendre quand je perds mes clés, que je loupe des trains et que j'oublie mes
	cartes bleues, mon sac à main… Merci de continuer à éveiller ma curiosité sur le monde qui nous
	entoure. J'ai hâte de poser enfin nos valises et de pouvoir surfer avec toi, afin d'être sûre que tu ne
	te casses rien, cette fois. Je suis heureuse de franchir cette nouvelle étape à tes côtés. Et même si je
	dis le contraire, je serai toujours là pour te courir après, autour du canapé si tu as besoin de
	Lovenox®. Je t'aime.

TABLE DES MATIERES

 DES LISTE DES ABRÉVIATIONS : ................................................................ RESUMÉ............................................................................................. INTRODUCTION ................................................................................. METHOD............................................................................................ Inclusion criteria: .......................................................................................................................... Setting, participants, design and procedure: .................................................................................

Data analysis: ................................................................................................................................ Ethical and regulatory aspects: ...................................................................................................... RESULTS ............................................................................................

in medical hypnosis and prolonged use of benzodiazepines: The French National Health Insurance Data.

  Léa Légereau 1 , Marion Bonnard 1 , Johann Tétart 1 , Adriaan Barbaroux 2 . Université Cote d'Azur, Rétines, DERMG, France 2 Université Cote d'Azur, Rétines, LAPCOS, DERMG, France.

	HAS: French National Authority for Health, Haute Autorité de Santé
	GP(s): General Practitioner(s), médecin(s) généraliste(s) Objectif :
	IFH : French Hypnosis Institute, Institut Français d'Hypnose
	INSERM : National Institute of Health and Medical Research, Institut National de la Santé Et de la Évaluer les données de la Rémunération sur Objectifs de Santé Publique (ROSP) concernant le
	Recherche Médicale traitement par benzodiazépines hors délai chez les médecins généralistes (MG) formés en
	hypnothérapie.
	représentait 52000 patients.
	38,3% des prescriptions d'hypnotiques et 14,8% des prescriptions d'anxiolytiques étaient prolongées
	hors délai pour des taux nationaux respectivement de 42.8% et 14,8%, sans différence statistiquement
	significative.
	Article: 2613 words, 13820 characters.

IUD : Inter-University Diploma, Diplôme Inter-Universitaire LAPCOS : Laboratoire d'Anthropologie et de Psychologie Cliniques, cOgnitives et Sociales ROSP : Compensation on Public Health Objectives, Rémunération sur Objectifs de Santé Publique UD: University Diploma, Diplôme Universitaire Training 1 Abstract: 273 words, 1563 characters.

RESUMÉ Introduction : En France, les benzodiazépines sont largement prescrites et 15% de leurs instaurations sont prolongées hors des délais. La Haute Autorité de Santé (HAS, French National Authority for Health) recommande de privilégier des alternatives non médicamenteuses. L'hypnose pourrait être une de ces alternatives.

Méthodes :

Une étude descriptive de cohorte a été menée de juin à décembre 2019. Les données de la ROSP des prescriptions en 2019 de médecins généralistes formés à l'hypnose, ont été recueillies. Les deux critères de jugement principaux étaient le taux de prescriptions hors délai par rapport au nombre total de prescriptions de benzodiazépines hypnotiques et anxiolytiques (critères ROSP).

Résultats :

189 médecins ont été contactés soit 30 % de la population nationale des médecins généralistes formés à l'hypnose. Parmi les 189 médecins, seuls 81 exerçaient en libéral avec une convention. 24 n'ont pas pu être contacté et cinq ont refusé de répondre. Au total, 52 MG libéraux français sur un échantillon de 81 (64%) ont été interrogés par téléphone ou courriel. La somme des patientèles étudiées

Table 1 -

 1 Population characteristics. *ROSP : Rémunération sur Objectifs de Santé Publique, Public Health Objective Remuneration.

						Patient > 80
		Age (years-old)	Seniority (years)	Duration of consultation (min)	Patients (n)	years of age
						(nb)
	N	52	52	52	52	52
	Missing	0	0	0	0	0
	Mean	51.3	18.4	18.8	1030	63.6
	Median	53.0	20.0	15.0	1000	50.5
	Standard deviation	9.67	9.87	6.01	535	54.2
	Minimum	29	2.00	10	5	0
	Maximum	71	35.0	45	2686	288

màj27/09/19

Funding:

This research received no specific grant from any funding agency in the public, commercial or not-forprofit sectors.

ABSTRACT:

Background:

In France, benzodiazepines are widely prescribed and 15% of their introduction will be extended beyond the time limit. The HAS (French National Authority for Health, Haute Autorité de Santé) recommends the use of non-medicinal alternatives. Hypnosis could be one of these alternatives.

Objective:

To evaluate the data of the Compensation on Public Health Objectives (ROSP in French) concerning prescriptions of benzodiazepines past the statutory deadline by the general practitioners (GP) trained in hypnotherapy.

Methods:

A cohort descriptive study was conducted from June to December 2019. The ROSP data for the prescriptions in 2019 of GP trained in hypnotherapy were collected. The two primary outcome measures were the rate of out of time limit prescriptions relative to the total number of hypnotic and anxiolytic benzodiazepines prescriptions (ROSP data).

Results:

189 GPs were contacted, representing 30% of the national population of GPs trained in hypnosis.

Among the 189 GPs, only 81 were practicing in private practice with a convention. 24 could not be contacted and five refused to answer.

A total of 52 French private GP out of a sample of 81 (64%) were interviewed by phone or email. The total number of patients surveyed was 52,000.

38.3% of hypnotic prescriptions and 14,8% of anxiolytic prescriptions were extended out of time limit for a national rate of respectively 42.8% and 14.8%, with statistically no significant difference.

Conclusions:

The high participation rate and the sample size suggest that these results are representative. Training in hypnosis is not significantly correlated with better prescriptions of hypnotics or anxiolytics. A qualitative study is underway to better understand these results.


Universite Nice

Sophia Antipolis

Faculte De Medecine

M Baqué Patrick

Mme Askenazy-Gittard

Florence Pédopsychiatrie

) M Barranger

Emmanuel Gynécologie

) M Bérard

Étienne Pédiatrie

) M Bongain

André Gynécologie-Obstétrique

Mme Breuil

Véronique Rhumatologie

) M Castillo

) M Chevallier

Patrick Radiologie

M Ferrero

Thierry Piche

Gastro

Dominique Hématologie

) M Rosenthal Éric

Mme Alunni

Véronique Médecine Légale

M Bahadoran

Philippe Cytologie

Stéphanie Ophtalmologie

Sylvie Génétique

M Favre

Guillaume Néphrologie

) M Fournier

Jean-Paul Thérapeutique

M Ambrosetti

Damien Cytologie

Mme Bernard-Pomier

Ghislaine Immunologie

M Fosse

Thierry Bactériologie

M Garraffo

Rodolphe Pharmacologie Fondamentale

Humbert Olivier Biophysique

Mme Lamy

Brigitte Bactérilogie

Mme Long-Mira

Elodie Cytologie

Marie -Noëlle

Mme Seitz-Polski

Barbara Immunologie

M Squara

Fabien Cardiologie

) M Testa

Jean Épidémiologie

M Amiel

Jean M Gastaud

Pierre M Albertini

Marc M Gérard

Jean-Pierre M Balas

Daniel M Gillet

Jean-Yves M Batt

Michel M Grellier

Patrick M Blaive

Bruno M Grimaud

Dominique M Boquet

Patrice M Hofliger

Philippe M Bourgeon

André M Jourdan

Jacques M Boutté

Patrick M Lambert

Jean-Claude M Bruneton

Jean-Noël M Lazdunski

Michel Mme

Bussiere Françoise

M Lefebvre

Jean-Claude M Camous

Jean-Pierre M Le Fichoux

Yves M Canivet

Bertrand Mme Lebreton

Elisabeth M Cassuto

Jill-Patrice M Mariani

Roger M Chatel

Marcel M Masseyeff

René M Coussement

Alain M Mattei Mathieu

Mme Crenesse

Dominique M Mouiel

Jean M Darcourt

MYQUEL Guy Mme

Martine M Dellamonica

Pierre M Ortonne

Jean-Paul M Delmont

Jean M Pringuey

Dominique M Demard

François M Santini

Joseph M Desnuelle

Claude M Sautron

Jean Baptiste

M Dolisi

Claude M Schneider

Maurice Mme

Euller-Ziegler Liana

M Toubol

Jacques M Fenichel

Patrick M Tran

Dinh Khiem

M Franco

Alain M Van Obberghen

Emmanuel M Freychet

Pierre M Ziegler

Gérard M C U Honoraires

M Arnold

Jacques M Giudicelli

Jean M Basteris

Bernard M Magné

Jacques M Benoliel

José Mme Memran

Nadine Mlle Chichmanian

Rose-Marie M Mengual

Raymond Mme Donzeau

Michèle M Philip

Patrick M Emiliozzi

Roméo M Poirée

Jean-Claude M Franken

Philippe Mme

Roure Marie-Claire

M Gastaud

de Nice PROFESSEURS PREMIERE CLASSE

A mon Directeur de Thèse, Monsieur le Docteur Arnaud MARTEL

Tu as accepté de m'accompagner tout au long de ce travail. Merci pour ton soutien, pour tes encouragements. J'ai beaucoup appris à tes côtés. Je te remercie pour ta patience et tes conseils.

Cela a été́ un plaisir de travailler avec toi.

A Monsieur le Professeur Jacques LEVRAUT

Je vous prie de recevoir mes sincères remerciements pour avoir accepter de juger mon travail.

Veuillez croire en l'expression de ma respectueuse considération.

A Monsieur de Professeur Associé Gilles GARDON

Merci pour le temps que vous passez au service des étudiants, pour nous apporter une formation de qualité, et transmettre combien la médecine générale est une discipline noble et passionnante.

Je vous témoigne ma profonde et respectueuse reconnaissance.

A Monsieur le Docteur Andreas KAUERT

Vous me faites l'honneur d'apporter votre expérience à la critique de ce travail en siégeant dans mon jury de thèse. La médecine hyperbare est une spécialité qui mérite d'être connue et reconnue. Je vous prie de bien vouloir accepter ma respectueuse considération.

A Thomas,

Pour toutes ces années où tu m'as soutenue, sans faille. Pour ton amour, ta présence, ton écoute et bien sûr ta patience ! Tu es l'épaule sur laquelle je m'appuie, tu m'es si précieux... Et pour ne rien gâcher, tu es un papa formidable. Merci pour tout, je t'aime.

A Olivia,

Mon bébé, tu n'as qu'un an mais je suis déjà tellement fière d'être ta maman.

Peut être qu'un jour tu seras intéressée par la lecture de ce travail… Mais en attendant, découvre le monde avec ton regard et ton émerveillement de petite fille. Je t'aime plus que tout.

A mes parents,

Pour votre soutien inconditionnel tout au long du chemin parcouru, pour être toujours là dans les moments qui comptent pour moi, les meilleurs comme les moins bons. C'est grâce à vous si j'en suis là aujourd'hui. Merci pour tout. Je vous aime.

A mon frère et ma soeur,

Même si nous sommes parfois éloignés, je sais que l'on pense les uns aux autres, et que les liens qui nous unissent sont forts. Merci pour votre soutien tout au long de ces années. Je vous aime.

A mes beaux-parents,

Vous m'avez accueillie, soutenue et choyée comme votre fille. Je vous en remercie. J'ai trouvé en vous des deuxièmes parents. Vous avez une grande place dans mon coeur.

Merci tout particulier à toi Laurence, qui sera probablement la dernière personne à lire ce manuscrit avant qu'il ne parte à l'impression, histoire de vérifier la mise en page pour la 100 BRAO is characterized by a sudden visual field defect sometimes associated with a decreased BCVA depending on the location of the occlusion (6). To date, no standard treatment for CRAO has been clearly defined. Several treatments have been used such as pentoxyphylline, carbogen inhalation, sublingual isosorbide dinitrate, ocular massage with a three-mirror contact lens, acetazolamide, mannitol, methylprednisolone, tissue plasminogen activator or Neodymium:yttrium-aluminium-garnet (Nd:YAG) laser (7)(8) as well as surgical modalities such as anterior chamber decompression, pars plana vitrectomy with removal of the embolus [START_REF] Agarwal | Endovascular Management of Central Retinal Arterial Occlusion[END_REF][START_REF] Hwang | Hyperbaric Oxygen Therapy to Avoid Blindness From Filler Injection[END_REF][START_REF] Duker | Recovery following acute obstruction of the retinal and choroidal circulations. A case history[END_REF][START_REF] Stone | Visual recovery after central retinal artery occlusion: two cases[END_REF].

The Undersea and Hyperbaric Medical Society (UHMS) and the European Committee for Hyperbaric Medicine recommend the use of Hyperbaric Oxygen Therapy (HBOT) for the treatment of CRAO. It consists in delivering a high oxygen pressure through the respiratory tract. HBOT allows increasing both the hydrostatic pressure and the inhaled partial oxygen pressure [START_REF] Fosen | Hyperbaric oxygen, vasculogenic stem cells, and wound healing[END_REF], as well as enhancing red blood cell deformability. HBOT is assumed to act by increasing oxygen supply to hypoxic tissues through the choroidal circulation, thereby preserving the ischemic tissue affected by the occluded retinal artery (2)(14) [START_REF] Yu | Retinal degeneration and local oxygen metabolism[END_REF]. However, these actions are effective when a high increase in blood oxygen pressure is achieved [START_REF] Chen | Intra-Arterial Thrombolytic Therapy Is Not a Therapeutic Option for Filler-Related Central Retinal Artery Occlusion[END_REF].

HBOT includes the inhalation of 100% oxygen at pressures greater than 1 ATA, thus increasing by 20 to 30 the amount of oxygen dissolved in the plasma [START_REF] Cope | Retinal artery occlusion: visual outcome after treatment with hyperbaric oxygen[END_REF]. Under normal physiological conditions, about 60% of the oxygen consumed by the retina is supplied by the choroidal circulation, whereas, under hyperoxic conditions, the choroid can supply 100% of the oxygen required by the retina [START_REF] Li | Reversal of Visual Loss with Hyperbaric Oxygen Treatment in a Patient with Susac Syndrome[END_REF]. It has been suggested that raised oxygen pressures may lead to retinal artery vasoconstriction (18) [START_REF] Haddad | Effect of hyperbaric oxygenation on microcirculation: use in therapy of retinal vascular disorders[END_REF]. Interestingly, the choroidal blood flow does not seem to be affected by raised oxygen pressures so that the use of HBOT can significantly increase retinal oxygen supply (15) [START_REF] Li | Reversal of Visual Loss with Hyperbaric Oxygen Treatment in a Patient with Susac Syndrome[END_REF].

HBOT has been previously studied with favorable outcomes when used within 8-24 hours after the occurrence of CRAO [START_REF] Weiss | Hyperbaric oxygen treatment of nonacute central retinal artery occlusion[END_REF][START_REF] Weinberger | Treatment of Acute Central Retinal Artery Occlusion (CRAO) by Hyperbaric Oxygenation Therapy (HBO)--Pilot study with 21 patients[END_REF][START_REF] Beiran | Hyperbaric oxygenation combined with nifedipine treatment for recent-onset retinal artery occlusion[END_REF][START_REF] Aisenbrey | Hyperbaric oxygen therapy in retinal artery occlusion[END_REF][START_REF] Menzel-Severing | Early Hyperbaric Oxygen Treatment for Nonarteritic Central Retinal Artery Obstruction[END_REF][START_REF] Anderson | THE EFFECTS OF HYPERBARIC OXYGENATION ON RETINAL ARTERIAL OCCLUSION[END_REF][START_REF] Beiran | Early Hyperbaric Oxygen Therapy for Retinal Artery Occlusion[END_REF]. However, these studies have some limitations, including a small sample size, a lack of ophthalmological examination including fluorescein angiography (FA), a lack of consensus on the HBOT protocol to be used or the main outcome measure.

In addition, a large study has assessed the natural evolution of CRAO without any treatment and has only shown a slight BCVA improvement (3). This finding reinforces the relevance of using HBOT in patients with CRAO.

The aim of our study was to assess the efficacy and safety of a standardized HBOT protocol based on FA in patients experiencing RAO (i.e. CRAO or BRAO).

MATERIAL AND METHODS

Study design and protocol

A retrospective study was conducted in our French tertiary care center (University Hospital of were referred to the emergency department and were then excluded from the protocol.

Inclusion and exclusion criteria

All patients diagnosed with CRAO or BRAO that occurred less than seven days before referral were included. Patients presenting a cilioretinal artery, a concomitant venous occlusion seen on retinal FA, who had received an ophthalmological treatment before referral (anterior chamber puncture, acetazolamide, laser or surgical treatment), who experienced concomitant heart or cerebral stroke, without ophthalmological follow-up or with a HBOT contraindication (sinus and ear disorders, pulmonary emphysema, recent pneumothorax, unbalanced epileptic disease, behavioral disorder, hemodynamic instability) were excluded.

Data recorded

Data recorded included: age, sex, type of retinal occlusion (CRAO or BRAO), complete ophthalmological examination findings (BCVA, slit-lamp examination, fundus, OCT and FA), medical history (diabetes status, arterial high blood pressure [HBP], dyslipidemia), medications (antiplatelet or anticoagulant therapy), etiology of CRAO (carotid stenosis or dissection, embolic cardiopathy, other), associated cerebral stroke assessed on the cervical and cerebral CT-scan with contrast injection, occurrence of a hypertensive episode during the HBOT session, time between the occurrence of ocular symptoms and HBOT initiation, number of HBOT sessions and adverse events.

Arterial HBP was defined as a systolic blood pressure ≥140 mmHg and/or a diastolic blood pressure ≥90 mmHg, confirmed on two separate measurements or by the intake of antihypertensive medications. Dyslipidemia was defined according to the French Health Authority as a LDL cholesterol level ≥130 mg/dL (3.37 mmol/L) or a HDL cholesterol level <40 mg/dL (1.04 mmol/L) or the use of a lipid-lowering treatment. The diagnosis of embolic heart disease was defined according to the French Society of Cardiology as the presence of atrial fibrillation, atrial flutter, mitral valve disease, patent oval foramen, myocardial infarction, left ventricular aneurysm, bacterial or marastic endocarditis, and myxoma. Carotid stenosis was considered significant when it was symptomatic and greater than 50% or when it was greater than 70% in the absence of symptoms.

Outcome measures

The main outcome measure was a BCVA improvement defined as a decrease by 0.3 logMAR measured between the referral and Day 30 post-HBOT according to Hadanny et al. [START_REF] Hadanny | Reversibility of retinal ischemia due to central retinal artery occlusion by hyperbaric oxygen[END_REF]. The numeric logMAR values for profound low vision categories (counting fingers, hand motion, light perception, and no light perception) were used as proposed by Lange et al. [START_REF] Lange | Resolving the clinical acuity categories "hand motion" and "counting fingers" using the Freiburg Visual Acuity Test (FrACT)[END_REF].

The secondary outcome measure was a BCVA improvement defined as a decrease by 0.1 logMAR. HBOT side effects were also recorded.

Ethics

This study was conducted in accordance with the principles outlined in the declaration of Helsinki. Because of the retrospective design of the study, no institutional approval was required. All patients gave their informed consent to participate in the study. Data were anonymized and the study was approved by the French Commission Nationale Informatique et Liberté (CNIL number: 2216502).

Statistical analyzes

Descriptive statistics are presented as numbers and percentages for categorial variables and means ± standard deviations (SD) for continuous variables. Analyzes were performed using a Fisher exact test and Student t-tests to compare qualitative and quantitative data, respectively.

A multivariate analysis was performed using a multiple logistic regression. SPSS software v.25 (IBM, Chicago, Illinois) was used and a p-value <0.05 was considered statistically significant. patients. Seven (25%) patients experienced a hypertensive episode during the HBOT session, and 6 (21.4%) experienced a barotrauma for which no HBOT discontinuation was required.

RESULTS

Twenty

In the univariate analysis, arterial HBP (p= 0.008), dyslipidemia (p=0.038), the use of antiplatelets (p=0.033) and a low baseline BCVA (p=0.001) were identified as poor prognostic factors for BCVA improvement. Experiencing a barotrauma during a HBOT session was associated with a better prognosis (p=0.036). In the multivariate analysis, only arterial HBP (p=0.039) and a low baseline BCVA (p=0.005) were associated with a poor prognosis (Table 4).

In the subgroup of CRAO patients (n=15), diabetes (p=0.042) and an embolic heart disease (p=0.049) were associated with a poor prognosis in the univariate analysis (Table 5) whereas benefiting from a rapid initial management (p=0.042) and receiving HBOT sessions twice daily (p=0.032) were considered as favorable prognostic factors. The multivariate analysis failed to identify any prognostic factor.

DISCUSSION

In this retrospective study, we focused on the improvement in BCVA in patients with CRAO and BRAO treated with HBOT in our tertiary care center. In our study, 14 (50%) patients achieved a BCVA improvement ≥0.3 logMAR. No major side effects were reported during the HBOT sessions.

As shown in Table 6, comparing our results with the current literature appears challenging because of a lack of consensus regarding the main outcome measures, the recommended HBOT protocol (number of sessions, pressure applied) and the ancillary procedures performed (ocular massage, acetazolamide, anterior chamber paracentesis…) [START_REF] Wu | Oxygen therapy in patients with retinal artery occlusion: A meta-analysis[END_REF].

In addition, the ophthalmological examination is often limited to BCVA measurement and fundus examination [START_REF] Menzel-Severing | Early Hyperbaric Oxygen Treatment for Nonarteritic Central Retinal Artery Obstruction[END_REF].

Our results are in accordance with most of the previous studies that have reported a BCVA improvement following HBOT in RAO patients ( 14)(21)(26)(27)(30) (Table 6). In their study, Beiran et al. have observed a BCVA improvement in 82.9% of patients, a value that is higher than our results [START_REF] Beiran | Early Hyperbaric Oxygen Therapy for Retinal Artery Occlusion[END_REF]. This could be explained by a better baseline BCVA in their study (1 logMAR) compared to our patients (1.5 logMAR) [START_REF] Beiran | Early Hyperbaric Oxygen Therapy for Retinal Artery Occlusion[END_REF]. This could also be explained by the fact that their main outcome measure was a BCVA improvement ≥3 lines in the Snellen chart whereas we used the logMAR visual scale in our study. In addition, they have only included patients whose symptoms appeared less than eight hours before referral.

Weinberger et al. have found a BCVA improvement in 90.5% of their patients [START_REF] Weinberger | Treatment of Acute Central Retinal Artery Occlusion (CRAO) by Hyperbaric Oxygenation Therapy (HBO)--Pilot study with 21 patients[END_REF]. However, these results should be interpreted with caution because the BCVA was not evaluated by an ophthalmologist but by the patients themselves (subjective evaluation).

CRAO etiologies have been investigated in previous studies. In our study, we identified an embolic heart disease and significant carotid stenosis in Our study is the first to investigate the rate of cerebral stroke in patients treated with HBOT for RAO. We identified 10.7% of patients experiencing cerebral stroke. Hadanny et al.

have only recorded a past medical history of cerebral stroke in their patients [START_REF] Hadanny | Reversibility of retinal ischemia due to central retinal artery occlusion by hyperbaric oxygen[END_REF]. Some studies have shown that RAO was associated with increased rates of cerebral stroke and mortality within five years of the vascular event [START_REF] Chang | Retinal Artery Occlusion and the 3-Year Risk of Stroke in Taiwan: A Nationwide Population-Based Study[END_REF][START_REF] Tyler Hyungtaek | Retinal Artery Occlusion and the Risk of Stroke Development[END_REF][START_REF] Ueda | Retinal Vascular Obstruction and Asymptomatic Cerebral Infarction[END_REF]. In addition, it should be noted that the beneficial effects of HBOT on stroke have been suggested in several experimental studies [START_REF] Hadanny | Hyperbaric oxygen therapy improves neurocognitive functions of post-stroke patientsa retrospective analysis[END_REF]. However, the efficacy of HBOT in patients experiencing cerebral stroke is not well established due to the lack of randomized clinical trials [START_REF] Zhai | Hyperbaric oxygen therapy in experimental and clinical stroke[END_REF].

In our study, a prompt management with HBOT was identified as a favorable prognostic factor in the univariate analysis (p=0.042). This finding is consistent with the study by Elder et al. [START_REF] Elder | Hyperbaric oxygen in the treatment of acute retinal artery occlusion[END_REF]. We performed two daily HBOT sessions as many other authors [START_REF] Elder | Hyperbaric oxygen in the treatment of acute retinal artery occlusion[END_REF]. This could be explained by the fact that we performed two daily sessions until revascularization of the retinal artery assessed on FA (on day 15 or day 21). To date, no clear international consensus on HBOT for the treatment of RAO has been proposed.

(
We identified HBP (p=0.008), dyslipidemia (p=0.038), diabetes mellitus (p=0.042), embolic heart disease (p=0.049) and the use of antiplatelets (p=0.033) as poor prognostic factor in RAO. This could be explained by the fact that hypertensive and diabetic patients have a weaker arterio-venous network, partially sclerosed or overloaded with atheroma [START_REF] Petrie | Diabetes, Hypertension, and Cardiovascular Disease: Clinical Insights and Vascular Mechanisms[END_REF].

The role of antiplatelets is debated. In our study, being treated with acetyl salicylic acid was associated with a poorer prognosis whereas in the study conducted by Menzel et al., it has been identified as a good prognostic factor [START_REF] Menzel-Severing | Early Hyperbaric Oxygen Treatment for Nonarteritic Central Retinal Artery Obstruction[END_REF]. It could be assumed that antiplatelets could reduce the size of the embolus by reducing platelet aggregation. On the other hand, patients treated with antiplatelets are at higher vascular risk with an impaired vascular network.

We found that a low baseline BCVA was associated with a poorer visual prognosis. This is in line with Hadanny et al. who have found that the presence of a cherry red spot in the fundus upon presentation was a poor factor for referral [START_REF] Hadanny | Reversibility of retinal ischemia due to central retinal artery occlusion by hyperbaric oxygen[END_REF]. A cherry red spot usually appears a few hours after the occurrence of RAO and leads to a late referral.

In [START_REF] Hadanny | Reversibility of retinal ischemia due to central retinal artery occlusion by hyperbaric oxygen[END_REF]. The relationship between the occurrence of a barotrauma and a better visual recovery could not be clearly explained. An early management and receiving two daily sessions were also associated with a favorable prognosis. Seven (25%) patients experienced a hypertensive episode during the HBOT session. Apart from the reported cases of barotrauma, 5 patients in

Hadanny's study have experienced HBOT-related adverse events: two (1.5%) patients had otalgia without barotrauma signs and one of them (0.7%) underwent myringotomy in order to continue the HBOT sessions; one (0.7%) patient experienced mild epistaxis unrelated to the barotrauma that resolved spontaneously; one (0.7%) patient experienced dyspnea during one of the sessions and recovered a few minutes after the session [START_REF] Hadanny | Reversibility of retinal ischemia due to central retinal artery occlusion by hyperbaric oxygen[END_REF] .

In our study, the protocol was terminated early in 5 patients (three with recent stroke and two claustrophobic patients). These patients received 3, 5, 14, 16, and 21 HBOT sessions, respectively. These early discontinuations could have biased our results even if it could be assumed that this potential bias would rather be in disfavor of the efficacy of HBOT.

Regarding the events leading to early treatment discontinuation, Elder et al. have reported respiratory infection and an episode of claustrophobia [START_REF] Elder | Hyperbaric oxygen in the treatment of acute retinal artery occlusion[END_REF].

Our study has some limitations. First, it is a retrospective study with a small sample size. However, CRAO and BRAO are rare disorders and this could explain the small number of patients included. Due to its retrospective design, some examinations such as FA could sometimes not be performed. Second, our study was not comparative. However, no standard of care for treating CRAO has been proposed in the literature (3). The strength of this study is the cooperation between the ophthalmological and hyperbaric departments. All patients underwent a complete ophthalmological examination before referral to the HBOT department. The protocol also included the monitoring of cardiovascular disorders as well as a close multidisciplinary follow-up when possible. HBOT discontinuation was based on retinal FA performed by the ophthalmology department and allowed a better monitoring of the retinal revascularization. In case of arterial reperfusion on Day 14, HBOT discontinuation was decided. This HBOT protocol was more in line with the pathophysiology of RAO and we recommend the use of our protocol in such cases. Finally, our primary outcome measure was based on a previous robust study [START_REF] Hadanny | Reversibility of retinal ischemia due to central retinal artery occlusion by hyperbaric oxygen[END_REF] and was assessed by an ophthalmologist and not subjectively by the patients themselves (3) [START_REF] Weinberger | Treatment of Acute Central Retinal Artery Occlusion (CRAO) by Hyperbaric Oxygenation Therapy (HBO)--Pilot study with 21 patients[END_REF].

CONCLUSION

HBOT, administered twice a day at a pressure of 2.5 ATA and monitored by FA, appears to be an effective and safe treatment for RAO (CRAO and BRAO). Half of our patients achieved a BCVA improvement (≥0.3 logMAR) at one month. Implementing an international standardized HBOT protocol is needed for conducting further prospective, comparative studies. HBOT duration should be based on FA monitoring.

ACKNOWLEGEMENTS

To all the secretaries of the Hyperbaric Oxygen department and Ophthalmology department for their help to organize all the appointments.

FUNDINGS

None.

From: 1 )

 1 séances bi quotidiennes d'OHB, à une pression de 2.5 ATA, dont la durée totale du traitement est déterminée par l'angiographie à la fluorescéine, semble être un traitement efficace et sûr pour la prise en charge des OACR. La moitié de nos patients a connu une amélioration de l'AV (diminution ≥ 0.3 logMAR) à un mois. La mise en place d'un protocole international et standardisé d'OHB semble justifiée pour réaliser des études prospectives et comparatives plus poussées. Deuxième partie : Thèse au format article EFFICACY AND SAFETY OF A STANDARDIZED HYPERBARIC OXYGEN THERAPY PROTOCOL FOR RETINAL ARTERY OCCLUSION Helene Di Vincenzo (1), Andreas Kauert (1), David Martiano (2), Jeremy Chiabo (2), Dominique Di Vincenzo (1), Igor Sozonoff (1), Stéphanie Baillif (2), Arnaud Martel (2) Hyperbaric Oxygen Therapy department, Pasteur University Hospital, Cote d'Azur University, France. 2) Ophthalmology department, Pasteur University Hospital, Cote d'Azur University, France. Word count: 3256 1 figure (colored) and 6 tables. This work received no grants, no financial support. No financial or proprietary interests to disclose. Conflict of interest: none. Corresponding author: Dr MARTEL Arnaud, MD Pasteur 2 Hospital, Department of Ophthalmology 30, avenue de la voie Romaine, 06000 Nice, France Phone: +33 492038025 Mail: martel.a@chu-nice.fr Article submitted for publication in the medical journal RETINA, the journal of retinal and vitreous diseases, on June 14, 2020.INTRODUCTIONCentral retinal artery occlusion (CRAO) is a serious and rare vascular disorder involving the retina. The incidence of CRAO is estimated to be approximately 8.5 per 100.000 inhabitants[START_REF] Rumelt | Aggressive systematic treatment for central retinal artery occlusion[END_REF]. Retinal vascularization relies on the central retinal artery for its inner part whereas the external part relies on the choroidal vessels[START_REF] Butler | Hyperbaric oxygen therapy and the eye[END_REF]. The occlusion may involve the central retinal artery (CRAO) or one of its branches (Branch Retinal Artery Occlusion: BRAO) (3). The retinal vasculature is terminal without anastomoses between the retinal and choroidal vessels, except when a cilioretinal artery is present as reported in about 25% of patients (4). When CRAO occurs, retinal cells can survive for a few hours due to the oxygen present within the vitreous cavity and the increased anaerobic glycolysis in the visual cells[START_REF] Hayreh | Central retinal artery occlusion. Retinal survival time[END_REF]. Clinically, CRAO is characterized by a sudden painless loss of vision with a Best-

  Nice) from July 2016 to September 2019. The study protocol is summarized in Figure1.Briefly, the diagnosis was made by an ophthalmologist of the University Hospital of Nice.The following examinations were performed: BCVA measurement, slit-lamp examination, dilated fundus examination with color fundus photography, macular Optical Coherence Tomography b-scan (OCT, Heidelberg, Germany), and FA. Once the diagnosis made, the patients were immediately referred to the HBOT department. A clinical examination, a blood test, including blood formulation and inflammatory parameters (sedimentation rate, c-reactive protein) and an electrocardiogram were performed to rule out any contraindication to HBOT.A venous access was obtained when a hypertensive episode occurred during the session.Then, patients received their first HBOT session of 90 minutes at a pressure of 2.5 ATA using a HAUX Comex hyperbaric chamber. At the end of the session, patients underwent a cervical and cerebral CT-scan with contrast injection to rule out any internal carotid dissection or stenosis and/or associated cerebral stroke. In the absence of any cervical and cerebral abnormalities, patients were discharged and advised to perform a complete cardiovascular examination. Patients received two daily sessions of HBOT (90 min, 2.5 ATA) seven days a week, for at least 15 days. On Day 15, a new ophthalmological examination was performed with BCVA measurement, dilated fundus examination with color fundus photography, and FA. In case of retinal reperfusion, HBOT was discontinued. If no reperfusion was seen, treatment was continued for an additional week with an assessment on Day 21. The maximum treatment duration was 21 days. If retinal occlusion persisted on retinal angiography on Day 21, pan retinal photocoagulation was performed to avoid further ophthalmological complications, including neovascular glaucoma. All patients underwent a final ophthalmological examination at one month for monitoring. In case of significant internal carotid abnormality or associated cerebral stroke diagnosed on the initial CT-scan, patients

  Hayreh et al. have studied the natural evolution of CRAO patients and shown that only a minor visual improvement (1.7 to 1.5 logMar) occurred without any treatment (3). Compared to our study, Hayreh et al. haveshown an improvement in visual acuity in 22% of eyes with non-arteritic CRAO, while the visual acuity improved in 50% of our patients, with a mean regression by 0.6 logMAR at the end of the study (1.5 to 0.9 logMAR).

Figure 1a :Figure 1b :Figure 1c :

 1a1b1c Figure 1a: OCT of a physiological vascularization of the retina Figure 1b: OCT of a central retinal artery occlusion Figure 1c: Effect of HBOT on the vascularization of the central retinal artery

Figure 2 :

 2 Figure 2: Standardized HBOT protocol used in the present study

Liste des enseignants au 1er septembre 2019 à la Faculté de Médecine de Nice MAITRES DE CONFÉRENCES DES UNIVERSITÉS

	M.	DARMON David	Médecine Générale (53.03)
	Mme	GROS Auriane	Orthophonie (69)
	PROFESSEURS AGRÉGÉS
	Mme	LANDI Rebecca	Anglais
	PRATICIENS HOSPITALIERS UNIVERSITAIRES
	M.	DURAND Matthieu	Urologie (52.04)
	M.	SICARD Antoine	Néphrologie (52-03)
	PROFESSEURS ASSOCIÉS
	M.	GARDON Gilles	Médecine Générale (53.03)
	Mme	MONNIER Brigitte	Médecine Générale (53.03)
	MAITRES DE CONFÉRENCES ASSOCIÉS
	Mme	CASTA Céline	Médecine Générale (53.03)
	M.	GASPERINI Fabrice	Médecine Générale (53.03)
	M.	HOGU Nicolas	Médecine Générale (53.03)

9

REMERCIEMENTS

A ma Présidente de Jury, Madame le Professeur Stéphanie BAILLIF Vous me faites l'honneur de présider ce jury et de juger mon travail. Je vous témoigne ma profonde et respectueuse reconnaissance.

TABLE DES

 DES

	MATIERES
	Première partie : Résumé	p.
	EFFICACITE ET PROFIL DE SECURITE D'UN PROTOCOLE STANDARDISE
	D'OXYGENOTHERAPIE HYPERBARE CHEZ LES PATIENTS PRESENTANT UNE
	OCCLUSION ARTERIELLE RÉTINIENNE
	Deuxième partie : Thèse au format article	p.
	EFFICACY AND SAFETY OF A STANDARDIZED HYPERBARIC OXYGEN THERAPY
	PROTOCOL FOR RETINAL ARTERY OCCLUSION
	1) Abstract	p.
	2) Introduction	p.
	3) Material and methods	p.
	a. Study design and protocol	p.
	b. Inclusion and exclusion criteria	p.
	c. Data recorded	p.
	d. Outcome measures	p.
	e. Ethics	p.
	f. Statistical analyzes	p.
	4) Results	p.
	5) Discussion	p.
	6) Conclusion	p.
	7) Acknowlegements	p.
	8) Fundings	p.
	9) References	p.
	10) Figure legends	p.
	11)

Table legends

 legends

	Première partie : Résumé caisson hyperbare, durant 90 minutes et à une pression de 2.5 ATA. À la fin de la séance, le Dans le sous-groupe de patients atteints d'OACR (n=15), le diabète (p=0.042) et la cardiopathie
	patient réalisait un scanner cérébral et des troncs supra aortiques afin d'exclure toute dissection ou embolique (p=0.049) ont été associés à un mauvais pronostic dans l'analyse univariée, alors que
	EFFICACITE ET PROFIL DE SECURITE D'UN PROTOCOLE STANDARDISE sténose de la carotide interne et/ou un accident vasculaire cérébral associé. Dès le lendemain, le la prise en charge initiale rapide (p=0.042) et les séances bi quotidiennes d'oxygénothérapie
	était effectué, avec une évaluation de l'acuité visuelle, un fond d'oeil, une tomographie par UNE OCCLUSION ARTERIELLE RÉTINIENNE sept jours sur sept, pendant au moins 15 jours. Au 15 ème jour, un nouvel examen ophtalmologique D'OXYGENOTHERAPIE HYPERBARE CHEZ LES PATIENTS PRESENTANT patient bénéficiait de deux séances quotidiennes d'oxygénothérapie hyperbare (90 min, 2.5 ATA) hyperbare (p=0.032) se sont révélées être des facteurs pronostics favorables.
	cohérence optique (OCT) et une angiographie à la fluorescéine. En cas de reperfusion rétinienne
	constatée par l'angiographie, l'OHB était interrompue. Si aucune perfusion n'était constatée, le
	traitement était poursuivi pendant une semaine supplémentaire avec un contrôle au 21 ème jour. La
	durée maximale du traitement était de 21 jours. Si l'occlusion rétinienne persistait lors de
	l'angiographie rétinienne au jour 21, une photocoagulation pan rétinienne était effectuée pour
	éviter d'autres complications ophtalmologiques, notamment le glaucome néovasculaire.
	Les analyses statistiques ont été réalisées à l'aide du test exact de Fisher et des tests de Mann-
	Whitney pour comparer les données qualitatives et quantitatives respectivement. Le logiciel
	SPSS (IBM, Chicago, Illinois) a été utilisé et une valeur p < 0,05 a été considérée comme
	statistiquement significative.
	Résultats :
	Vingt-huit patients ont été inclus pendant la période d'étude. La moyenne de l'acuité visuelle
	(AV) initiale était de 1.5 logMAR (0-2.3). A l'issue du protocole d'OHB, l'AV moyenne était de
	0.9 logMAR (0-2.3) et était statistiquement améliorée (p=0.001). Dans le sous-groupe de patients
	atteints d'occlusion de l'artère centrale de la rétine (OACR), l'AV moyenne au départ était de 1.9
	logMAR (0.1-2.6). À un mois, elle était de 1.4 logMAR (0-2.3) et était également statistiquement
	améliorée (p=0.013).
	de la branche de l'artère centrale de la rétine (OBACR) depuis moins de sept jours, diagnostiquée L'analyse univariée a identifié l'hypertension artérielle (p=0.008), la dyslipidémie (p=0.038), le
	par le service des urgences ophtalmologiques, ont été inclus pendant la période d'étude. Le critère traitement antiplaquettaire (p=0.033) et une faible AV initiale (p=0.001) comme facteurs
	de jugement principal était l'amélioration de l'acuité visuelle, définie comme une diminution de pronostic péjoratifs. Le fait de subir un barotraumatisme pendant une séance d'oxygénothérapie
	p. hyperbare a été associé à un meilleur pronostic (p=0.036). Dans l'analyse multivariée, seules 0,3 logMAR à un mois.
	12) Supplementary materials Notre protocole d'étude était le suivant : le diagnostic d'OACR ou d'OBACR était établi par un l'hypertension artérielle (p=0.039) et la faible valeur initiale de l'AV (p=0.005) étaient associées à p. ophtalmologue du CHU de Nice. Une fois le diagnostic confirmé, le patient était immédiatement un mauvais pronostic.
	orienté vers le service d'oxygénothérapie hyperbare, où il bénéficiait de sa première séance au
	Troisième partie: Serment d'Hippocrate	p.

Introduction :

L'occlusion de l'artère centrale de la rétine (OACR) est une pathologie vasculaire grave et rare, se traduisant par une perte d'acuité visuelle brutale et indolore. Son incidence est estimée à 8.5 pour 100 000 personnes par an, mais elle peut être plus élevée en raison d'une sous-déclaration. Il n'y a actuellement aucun consensus concernant la prise en charge de l'OACR, et peu de preuves pour soutenir une quelconque modalité de traitement. Malgré une série de cas limitée, l'oxygénothérapie hyperbare (OHB) est recommandée pour traiter l'OACR par la Undersea and Hyperbaric Medical Society (UHMS) et par le Comité européen pour la médecine hyperbare. Notre objectif était d'évaluer l'efficacité, en terme d'acuité visuelle, d'un protocole standardisé de traitement par oxygénothérapie hyperbare (OHB) chez les patients souffrant d'une occlusion de l'artère rétinienne (OAR). Matériel et Méthode : Une étude rétrospective a été menée conjointement dans le service d'Ophtalmologie et dans l'Unité de traitement par Oxygénothérapie hyperbare du Centre Hospitalier Universitaire (CHU) de Nice, de juillet 2016 à septembre 2019. Les patients présentant une OACR ou une occlusion

Table 1 .

 1 -eight patients were included during the study period. Patient's characteristics are presented in Patient mean age was 70.1 years (16-89) and 16 (57.1%) patients were

	males. Thirteen (46.4%) and 7 (25%) patients had a history of arterial HBP and dyslipidemia,
	respectively. Ten (35.7%) patients were treated with antiplatelets. Fifteen (53.6%) and 13
	(46.4%) patients were diagnosed with CRAO and BRAO, respectively. The etiology of retinal
	occlusion was unknown in 19 (67.8%) patients. For the remaining patients, embolic heart
	disease was detected in 4 (14.3%) patients and significant carotid stenosis in 5 (17.9%)
	patients. The CT-scan with contrast injection revealed recent-onset cerebral stroke in 3
	(10.7%) patients.

The outcome measures are presented in Table

2

and Table

3

. The mean overall BCVA significantly improved from 1.5 logMAR (0-2.3) at the time of referral to 0.9 logMAR (0-2.3) at one month (p=0.001). In the CRAO subgroup, the mean BCVA significantly improved from 1.9 logMAR (0.1-2.6) at the time of referral to 1.4 logMAR (0-2.3) at one month (p=0.013). Revascularization assessed on FA occurred in 11 (39.2%) patients (14.2% on Day 14 and another 25% on Day 21). Data were missing for the remaining 17 patients. The time between the occurrence of the first ocular symptoms and HBOT initiation was ≤12 hours in 12 (42.9%) patients. Twenty-three (82.1%) patients underwent their first session within one hour of their arrival in the HBOT department. A mean number of 34.4 HBOT sessions were performed per patient, twice daily in 20 (71.4%) patients, and once daily in 8 (28.6%)

  our study, 6 (21.4%) patients experienced a barotrauma for which no HBOT discontinuation was required. One (3.2%) and 3 (2.3%) patients in the studies conducted by Elder et al. and by Hadanny et al. have respectively experienced a barotrauma[START_REF] Elder | Hyperbaric oxygen in the treatment of acute retinal artery occlusion[END_REF]

TABLE LEGENDS Table 1 :

 LEGENDS1 Patient's characteristics

Table 2 :

 2 Primary outcome result

Table 3 :

 3 Secondary outcome result

Table 4 :

 4 Prognostic factors associated with BCVA improvement (BCVA decrease by 0.3 logMAR) in all patients (CRAO + BRAO)

Table 5 :

 5 Prognostic factors associated with BCVA improvement (BCVA decrease by 0.3 logMAR) in CRAO patients only

Table 6 :

 6 Literature review of HBOT in RAO

	Figure 1a

Table 1 : Patient's characteristics

 1

		Number of	Baseline	BCVA at one	Number of	P value
		patients	BCVA	month	patients (%) with
			(range)	(range)	BCVA
					improvement ≥
					0.3 logMar
	All patients
	(CRAO +	28	1.5 (0-2.3)	0.9 (0-2.3)	14 (50%)	0.001
	BRAO)
	CRAO patients only	15	1.9 (0.1-2.6)	1.4 (0-2.3)	10 (66.7%)	0.013

Table 2 : Main outcome results. Number (%) Secondary outcome measure: BCVA improvement ≥ 0.1 logMAR

 2

	(57.1)

Table 3 : Secondary outcomes results (CRAO + BRAO patients). Visual acuity decrease ≥ 0.3 logMAR

 3

	Univariate	Multivariate
	analysis	analysis
	p value	p value

Table 4 : Prognostic factors associated with the main outcome measurement (BCVA decrease ≥ 0.3 logMAR) for all patients (CRAO + BRAO) Visual acuity decreased of 0.3 logMAR Univariate analysis p value

 4

	Multivariate
	analysis
	p value

Table 5 : Prognostic factors associated with the main outcome measurement (BCVA decrease ≥ 0.3 logMAR) for CRAO patients only.

 5

	Authors, year	Beiran et al, 2001	Weinberger et al, 2002	Cope et al, 2011	Menzel-Severing et al, 2012	Hadanny et al, 2016	Elder et al, 2017	Ilbasmis et al, 2018	Di Vincenzo et al, 2020
	Study design	Retrospective Comparative	Prospective Non comparative	Retrospective Non comparative	Retrospective Non comparative	Retrospective	Retrospective Non comparative	Prospective study	Retrospective Non comparative
					80 (51 HBOT
	No. Of patients	72 (35 HBOT vs 37 no treatment)	21	11	+ hemodilution hemodilution vs 29	128	31	16	28
					only)
	Mean age (years)	69.5 group) (HBOT	NA	61	69 group) (HBOT	66.4	70	49	70.1
	Inclusion criteria	RAO <8h	CRAO <12h	CRAO	RAO <12h VA <20/200	CRAO <20h VA < 0.5 logmar	Non arteritic ARAO	RAO	RAO (CRAO + BRAO) <7 days
									Unknown
	Etiology of CRAO	NA	NA	NA	Cardiovascula r disorder Arteritic CRAO excluded	Unknown (66,4%) Carotid atherosclerosi s (18%) Emboli (11%)	Carotid stenosis (9.7%)	NA	(67.8%) carotid stenosis (17.9%) embolic heart disease
									(14.3%)

Troisième partie : Serment d'Hippocrate

Au moment d'être admise à exercer la médecine, je promets et je jure d'être fidèle aux lois de l'honneur et de la probité.

Mon premier souci sera de rétablir, de préserver ou de promouvoir la santé dans tous ses éléments, physiques et mentaux, individuels et sociaux.

Je respecterai toutes les personnes, leur autonomie et leur volonté, sans aucune discrimination selon leur état ou leurs convictions. J'interviendrai pour les protéger si elles sont affaiblies, vulnérables ou menacées dans leur intégrité ou leur dignité. Même sous la contrainte, je ne ferai pas usage de mes connaissances contre les lois de l'humanité. J'informerai les patients des décisions envisagées, de leurs raisons et de leurs conséquences.

Je ne tromperai jamais leur confiance et n'exploiterai pas le pouvoir hérité des circonstances pour forcer les consciences.

Je donnerai mes soins à l'indigent et à quiconque me les demandera. Je ne me laisserai pas influencer par la soif du gain ou la recherche de la gloire.

Admise dans l'intimité des personnes, je tairai les secrets qui me seront confiés. Reçue à l'intérieur des maisons, je respecterai les secrets des foyers et ma conduite ne servira pas à corrompre les moeurs.

Je ferai tout pour soulager les souffrances. Je ne prolongerai pas abusivement les agonies. Je ne provoquerai jamais la mort délibérément.

Je préserverai l'indépendance nécessaire à l'accomplissement de ma mission. Je n'entreprendrai rien qui dépasse mes compétences. Je les entretiendrai et les perfectionnerai pour assurer au mieux les services qui me seront demandés. J'apporterai mon aide à mes confrères ainsi qu'à leurs familles dans l'adversité.

Que les hommes et mes confrères m'accordent leur estime si je suis fidèle à mes promesses ; que je sois déshonorée et méprisée si j'y manque.

Running head: Hyberbaric oxygen therapy in patients with retinal artery occlusion.

Keywords

Main outcome measures:

A BCVA improvement was defined as a decrease by 0.3 logMAR at one month.

Results: Twenty-eight patients were included during the study period. Fifty-seven percent of patients were treated more than 12 hours after the onset of the first symptoms. The mean BCVA was 1.5 logMAR at the time of referral and improved to 0.9 logMAR after HBOT (p=0.001). A multivariate analysis identified a high blood pressure (p=0.039) and a low initial BCVA (p=0.005) as poor prognostic factors.

Conclusion:

Performing HBOT sessions twice daily at a pressure of 2.5 ATA appears to be an effective and safe treatment for RAO. Half of our patients achieved a BCVA improvement. Implementing an international standardized HBOT protocol is needed for further prospective, comparative studies.

Authors, year

Beiran