Search

Severe eosinophilic asthma (SEA) is associated with multiple exacerbations. Fractional exhaled nitric oxide (FeNO), a biomarker of airway T2 inflammation, is known to be correlated with the risk of exacerbations. While the use of FeNO is well established to predict the therapeutic response to dupilumab (anti-IL-4/IL-13), it remains uncertain for biologics targeting the IL-5 pathway.We conducted an observational, retrospective, monocentric analysis of adults with SEA who started mepolizumab (anti-IL-5) or benralizumab (anti-IL-5R) between January 1, 2016 and December 31, 2020.Data were collected for 109 patients. All participants reported uncontrolled asthma with a median of 3 annual exacerbations and a medianIn this real-world cohort, adults with SEA who had a baseline FeNO ≥50 ppb experienced a greater decrease in exacerbations after 12 months of anti-IL-5 or IL-5R biologics than those with a FeNO50 ppb.

Asthma is a chronic airway condition defined by hyperresponsiveness, bronchial remodeling and chronic inflammation. A significant proportion of severe asthmatic patients remain uncontrolled despite recent therapeutic breakthroughs (biotherapies). Better understanding of the signaling pathways involved in the pathophysiological mechanisms underlying severe asthma could successfully address this unmet need. Rac GTPase acts as a molecular switch and has already been convincingly associated with airway hyperresponsiveness and bronchial remodeling in asthma. Having been elucidated by acquired knowledge regarding other pathologies. Its role in the inflammation mechanisms characterizing asthma is currently under specific evaluation.

International audience; Asthma is often associated with a Th2-type immune response with well-known cellular and molecular actors such as eosinophils, Th2 lymphocytes and associated cytokines such as interleukin-5 or IL-4. Nevertheless, some of the asthmatic patients show clinical manifestations and characteristics that do not correspond to the current pattern of the pathophysiology of asthma. Thus, recently new cellular and molecular actors in the development of asthma have been demonstrated in animal models and in humans. Among these are components of the innate immune system such as type 2 innate lymphoid cells or adaptive immune system such as Th9 lymphocytes. At the cellular level, the role of small G proteins in asthma is also highlighted as well as the role of major cytokines like IL-17 or those derived from the epithelium. A better knowledge of the physiopathology of asthma and the taking into account of these new actors allows the identification of new therapeutic targets for different endotypes of patients.

Resume Objectif Elaborer des recommandations de pratiques cliniques des methodes de contraception naturelle et des methodes barrieres feminines et masculines. Materiels et methodes Une revue systematique de la litterature en langue francaise et anglaise, concernant la place, la securite et l’efficacite des methodes de contraception naturelle et des methodes barrieres, a ete realisee sur PubMed, Cochrane Library et sur les recommandations des societes savantes internationales ainsi que celles de l’Organisation mondiale de la sante (OMS) et des mises a jour du Center for Disease Control and Prevention (CDC). Resultats Les contraceptions naturelles comprennent les methodes basees sur la determination de la periode fertile, la methode de l’allaitement maternel et de l’amenorrhee (MAMA) et le retrait. Leur prevalence reste faible (4,6 % d’utilisatrices) et stable depuis plusieurs annees. L’identification des periodes fertiles se fait soit sur la constatation de symptomes glaire cervicale (Billings), methode des deux jours, temperature, methode symptothermique)) soit en calculant sur le calendrier les jours fertiles (Ogino-Knaus, Standard Day Method®). Le taux de grossesse au bout d’un an est de 0,4 a 5 % en pratique correcte et reguliere mais 8 % en pratique courante. L’abstinence sexuelle (absence de penetration vaginale) en augmente l’efficacite et l’utilisation d’une methode barriere, qui peut-etre incorrectement utilisee, la diminue. Il manque de donnees sur la fiabilite et l’efficacite des moniteurs et kits de detection du pic de LH largement commercialises sur internet. La methode de l’allaitement maternel et de l’amenorrhee (MAMA) est tres efficace (98 %) quand les trois criteres suivants sont respectes : etre dans les 6 premiers mois qui suivent la naissance, etre en amenorrhee et faire un allaitement complet (jour/nuit) ou quasi complet et exclusif. La methode du retrait est peu efficace et contraignante. Preservatif masculin et feminin, diaphragme, cape cervical et spermicides sont des methodes barrieres physiques ou chimiques qui empechent les spermatozoides de monter dans la filiere genitale et empecher ainsi la fecondation. Les preservatifs masculin et feminin offrent une double protection, prevention de la grossesse non prevue mais aussi de la majorite des IST et du VIH. Ils sont efficaces a condition de respecter des regles rigoureuses d’utilisation pour la mise en place. Le preservatif masculin est le moyen le plus utilise par les 15–19 ans (45,6 %) parfois en association avec la pilule (dans 16,0 % des cas). La proportion de femmes y ayant recours decline au fil de l’âge. Le taux de grossesse observe avec ces methodes est compris entre 5 et 26 % en utilisation correcte et reguliere et entre 20 et 32 % en utilisation courante, au cours de la premiere annee d’utilisation. Diaphragme et cape doivent etre utilises en association avec des spermicides. Les spermicides seuls ont une faible efficacite. Conclusion Les methodes naturelles et les methodes barrieres sont beaucoup moins efficaces et plus contraignantes en pratique courante que les methodes medicalisees. Elles peuvent trouver leur place a certaines periodes de la vie de la femme ou du couple qui considerent alors comme possible ou acceptable la survenue d’une grossesse non prevue qui sera poursuivie ou pas. Les femmes/couples devront etre informes du mode d’emploi de ces methodes, des inconvenients et des risques d’echec en pratique courante ainsi qu’un rappel de la possibilite des contraceptions d’urgence (hormonal ou par DIU) apres un rapport non protege.

La anticoncepcion vaginal se basa en la creacion de una barrera fisica o quimica para impedir la progresion de los espermatozoides por las vias genitales y, en consecuencia, la fecundacion. Las barreras vaginales fisicas son los preservativos femeninos, los diafragmas y los capuchones cervicales. Las barreras quimicas son los espermicidas en forma de ovulos, cremas o esponjas. El preservativo femenino es el unico metodo que es al mismo tiempo un metodo de anticoncepcion y de prevencion de las infecciones de transmision sexual (ITS) y del virus de la inmunodeficiencia humana (VIH). La prevalencia mundial de los metodos vaginales es del 0,2%. En Europa, estos metodos son usados por el 1,4% de las mujeres, pero solo el 0,3% corresponde a Europa occidental. La tasa de embarazos es del 5-26% si se usan de forma correcta y con regularidad, y del 20-32% en uso corriente durante el primer ano. La ventaja de estos metodos es su total inocuidad, pero en condiciones de uso corriente son mucho menos eficaces que el dispositivo intrauterino (DIU) y los metodos hormonales, y requieren una fuerte implicacion de ambos miembros de la pareja. Como anticoncepcion regular en cada relacion sexual o como metodo de respaldo asociado a metodos naturales durante los periodos identificados como de riesgo, la anticoncepcion vaginal puede tener su lugar en algunos periodos de la vida de la mujer o de la pareja, si consideran posible o aceptable un embarazo imprevisto.

Introduction Severe asthma is a chronic lung disease characterized by inflammation, airway hyperresponsiveness (AHR) and airway remodelling with hyperplasia of airway smooth muscle cells (aSMC). Small G proteins of the Rho family (RhoA, Rac1 and Cdc42) are key regulators of smooth muscle functions and we recently demonstrated that Rac1 controls bronchoconstriction. The objective of this study was to assess the role of Rac1 in severe asthma associated airway remodelling. Methods We have studied the level of Rac1 activation by immunofluorescence in bronchial biopsies from severe asthmatic patients and control patients. In order to identify the role of Rac1 in aSMC remodelling, mice with specific deletion of Rac1 in SMC were sensitized to house dust mite to mimic the characteristics of severe allergic asthma in humans. Results Immunofluorescence analysis in human bronchial biopsies revealed an increased Rac1 activity in aSMC from severe asthmatic patients compared to control subjects. The basal proliferation rate of aSMC from severe asthmatics subjects is increased compared to control subjects. We have also observed that bFGF and PDGF-BB, growth factors described to be implicated in airway remodelling, stimulate the proliferation of aSMC from severe asthmatic subjects by 33% and 37% respectively. Moreover, the inhibition of Rac1 by EHT1864 decreased this proliferation by more than 50%. By a biochemical approach we have demonstrated that Rac1 signalling controlled human aSMC proliferation induced by mitogenic stimuli through the STAT3 signalling pathway. In vivo, we have demonstrated that specific deletion of Rac1 in SMC prevents aSMC hyperplasia and hypertrophy. Conclusion This study demonstrates that Rac1 is overactive in the airways of patients with severe asthma and is essential for aSMC proliferation and airway remodelling. Inhibition of Rac1 dependant signalling pathway may represent an interesting target for the treatment of severe asthma.

Asthma is an inflammatory airway disease which presentation is highly heterogeneous. Last two decades provided new clinical and basic data concerning asthma physiopathology that make global understanding much complex. Phenotypes based on clinical settings and paraclinical investigations from large cohorts confirm old paradigm (eosinophilic vs. non-eosinophilic asthma) but also introduce new concepts (obesity-related asthma, late onset asthma, etc.). Conversely, improvement of big data analytics allows to initiate new cohorts aiming at better understanding the pathophysiology underlying those phenotypes and unraveling new ones. However, clinical and therapeutic impacts of those big data need to be further detailed. In parallel, biotherapies and innovative techniques as bronchial thermoplasty become available for severe asthmatic patients who did not respond to specific treatment in the past. Development of a personalized medicine in severe asthma becomes an important challenge for tomorrow. This review will focus on new pathophysiological concepts arisen from large cohorts and new therapeutic strategies available and in progress for severe asthma., L’asthme est une pathologie inflammatoire chronique touchant les voies aériennes, hétérogène tant dans sa présentation que dans sa physiopathologie. Les données fondamentales et cliniques sur la compréhension de l’asthme se sont considérablement complexifiées au cours des dernières décennies. Dépassant l’archétype de l’asthme allergique de l’adulte jeune, de nouveaux paradigmes sont apparus. Des phénotypes d’asthme déterminés à partir de données cliniques et paracliniques simples ont permis la caractérisation de formes inflammatoires diverses (éosinophiliques et non éosinophiliques) ainsi que de nouveaux phénotypes jusqu’alors peu explorés (obésité, âge avancé, etc.). L’avènement des techniques d’analyses de données à haut débit a rendu possible le développement de nouvelles cohortes de patients visant à préciser les multiples mécanismes physiopathologiques sous-tendant ces nouveaux phénotypes. De nouvelles données apparaissent régulièrement, mais leurs impacts cliniques et thérapeutiques restent à déterminer. Parallèlement, des biothérapies et des techniques innovantes telles que la thermoplastie bronchique se sont développées afin d’améliorer la prise en charge des patients asthmatiques sévères pour lesquels il n’existait jusqu’alors que le recours à une corticothérapie systémique au long cours, non dénuée d’effets indésirables. Le développement de la médecine personnalisée du patient asthmatique sévère est désormais devenu une priorité. L’objectif de cette revue est de tracer un tour d’horizon des nouveaux concepts physiopathologiques et de présenter les nouvelles stratégies thérapeutiques dans l’asthme sévère.

Asthma is an inflammatory airway disease which presentation is highly heterogeneous. Last two decades provided new clinical and basic data concerning asthma physiopathology that make global understanding much complex. Phenotypes based on clinical settings and paraclinical investigations from large cohorts confirm old paradigm (eosinophilic vs. non-eosinophilic asthma) but also introduce new concepts (obesity-related asthma, late onset asthma, etc.). Conversely, improvement of big data analytics allows to initiate new cohorts aiming at better understanding the pathophysiology underlying those phenotypes and unraveling new ones. However, clinical and therapeutic impacts of those big data need to be further detailed. In parallel, biotherapies and innovative techniques as bronchial thermoplasty become available for severe asthmatic patients who did not respond to specific treatment in the past. Development of a personalized medicine in severe asthma becomes an important challenge for tomorrow. This review will focus on new pathophysiological concepts arisen from large cohorts and new therapeutic strategies available and in progress for severe asthma.

To develop clinical practice recommendations for the use of natural contraception and female and male barrier methods.A systematic review of English and French literatures related to the safety and effectiveness of natural contraceptive methods based on PubMed, Cochrane Library, practice recommendations issued by international scientific societies and guidelines provided by the World Health Organization (WHO) as well as updates from the Center for Disease Control and Prevention (CDC).Natural contraceptives methods include fertility awareness-based methods, lactational amenorrhea method (LAM) and withdrawal method. The prevalence is low (4.6% of users) and remains stable over the years. Identification of the fertile period can be symptom-based cervical mucus (Billings), two-day method, basal body temperature, symptom-thermal method or based on calendar calculation (Ogino-Knauss, standard day method). Pregnancy rate after one-year utilization varies from 0.4% to 5% in perfect use but 8% in common practice. Effectiveness increases with absence of vaginal sex and decreases when combined to barriers method inadequately implemented. Data is scarce on reliability and effectiveness of ovulation predictor kits readily available on internet. Lactational amenorrhea method (LAM) can be very effective (98%) provided three conditions are fulfilled: within 6 months after birth, amenorrhea is effective, and breastfeeding is exclusive or quasi exclusive (day/night). Withdrawal method is constraining and of limited effectiveness. Male and female condom, diaphragm, cervical cap and spermicides are mechanical and chemical barrier methods, preventing spermatozoids from passing through the cervix into the uterus and therefore preventing fecundation. Female and male condoms offer a double protection to avoid pregnancy and prevent STD's. They are effective provided strict conditions of use are fulfilled. Male condom is favored by teenagers (45.6% among 15 to 19 years old), sometimes in combination with contraceptive pill (16% of cases). Women on the pill decreases according to their age. Pregnancy rates within the first year of consistent and correct use of these methods vary between 5 to 26% and reach 20 to 32% in practical use. Diaphragm and cervical cap need to be used in combination with spermicides. Spermicides have limited effectiveness when used alone.In common practice, natural and barrier contraceptive methods are more constraining and less effective than modern contraceptive method. They can be an alternative at given time and/or in situations where the women or the couple accept the possibility of an unexpected pregnancy which might be terminated or not. Women/couples need to be properly informed on how to use such methods, on their disadvantages and possible failures in common practice. Reminders are to be given on emergency contraceptive methods (IUD, hormonal) after unprotected sex.

The French College of Obstetrics and Gynecology (CNGOF) releases its first global recommendations for clinical practice in contraception, to provide physicians with an updated synthesis of available data as a basis for their practice. The French Health Authority (HAS) methodology was used. Twelve practical issues were selected by the organizing committee and the task force members. The available literature was screened until December 2017, and allowed the release of evidence-based, graded recommendations. This synthesis is issued from 12 developed texts, previously reviewed by experts and physicians from public and private practices, with an experience in the contraceptive field. Male and female sterilization, as well as the use of hormonal treatments without contraceptive label were excluded from the field of this analysis. Specific practical recommendations on the management of contraception prescription, patient information including efficacy, risks, and benefits of the different contraception methods, follow up, intrauterine contraception, emergency contraception, local and natural methods, contraception in teenagers and after 40, contraception in vascular high-risk situations, and in case of cancer risk are provided. The short/mid-term future of contraception mostly relies on improving the use of currently available methods. This includes reinforced information for users and increased access to contraception for women, whatever the social and clinical context. That is the goal of these recommendations.

Background Pleuroparenchymal fibroelastosis (PPFE) is a very rare interstitial lung disease (ILD) characterized by progressive fibrotic lesions of the visceral pleura and the sub-pleural parenchyma, affecting predominantly the upper lobes. PPFE may occur in different contextes like bone marrow or lung transplantations, but also in the context of telomeropathy with mutations of telomerase reverse transcriptase (TERT), telomerase RNA component (TERC) or regulator of telomere elongation helicase 1 (RTEL1) genes. PPFE-like lesions have recently been described in patients with connective tissue disease (CTD)-related ILD. We report here the first detailed case of PPFE associated to systemic sclerosis (SSc) in a woman free of telomeropathy mutations. Case presentation A caucasian 46 year old woman was followed for SSc in a limited form with anti-centromere Ab since 1998, and seen in 2008 for a routine visit. Her SSc was stable, and she had no respiratory signs. Pulmonary function tests showed an isolated decreased cTLCO at 55.9% (of predicted value). Cardiac ultrasonography was normal. Thoracic CT-scan showed upper lobes predominant mild and focal pleural and subpleural thickenings, suggestive of PPFE, with a slight worsening at 8 years of follow-up. She remained clinically stable. Biology only found a moderate and stable peripheral thrombocytopenia, and sequencing analysis did not find any mutations in TERT and TERC genes. Conclusions ILD is frequent in SSc but isolated PPFE has never been described so far. In our case, PPFE is not related to telomeropathy, has indolent outcome and seems to have good prognosis. PPFE might be an extremely rare form of SSc-related ILD, although a fortuitous association remains possible.

Introduction L’asthme est une pathologie inflammatoire chronique touchant les voies aeriennes, heterogene tant dans sa presentation que dans sa physiopathologie. Les donnees fondamentales et cliniques acquises sur les trente dernieres annees ont considerablement etoffe la conceptualisation de la maladie asthmatique notamment severe (phenotypes et endotypes). Parallelement a ces progres, des biotherapies et des techniques innovantes telles que la thermoplastie bronchique sont apparues ameliorant l’arsenal therapeutique disponible. L’ensemble de ces elements a considerablement modifie la population d’asthmatiques severes. L’objectif principal de cette etude est de decrire les principales caracteristiques demographiques, cliniques, fonctionnelles respiratoires et therapeutiques d’une population d’asthmatiques severes telle que suivie en 2018. Methodes Tous les patients asthmatiques severes (criteres de l’American Thoracic Society) s’etant presentes a la consultation specialisee d’asthme severe du CHU de Nantes en novembre 2018 ont ete evalues pour inclusion. Afin de pouvoir s’appuyer sur le theoreme central limite et ainsi estimer des intervalles de confiance selon la loi normale, un effectif cible de 30 patients a ete retenu. Les donnees ont ete recueillies a partir des dossiers medicaux. Resultats Trente patients asthmatiques severes ont ete recrutes sur le mois de novembre 2018. Les patients presentent un âge moyen de 57 ans avec un sexe ratio equilibre. L’atopie concerne une proportion importante des patients (56,67 %) ainsi que la polypose nasosinusienne (40 %). La fonction respiratoire est globalement conservee (VEMS a 81,7 % de la valeur theorique) mais un nombre restreint de patients conservent une reversibilite significative sous beta-2 mimetiques (25 %). La frequence des exacerbations est relativement elevee (2,48 par an). On note un recours frequent aux corticoides oraux continus (40 %) bien que les biotherapies (53,3 %) prennent une place desormais significative. Bien que des phenotypes se dessinent, aucune difference significative en terme clinique et paraclinique n’a ete mise en evidence. Conclusion Malgre un effectif reduit, les principales caracteristiques demographiques, cliniques et paracliniques decrites dans les cohortes de grande envergure sont retrouvees. L’arrivee des nouvelles biotherapies a nettement modifie les modalites de prise en charge therapeutique des patients asthmatiques severes. Le suivi des modifications induites par ces nouveaux traitements sera certainement important afin de s’adapter aux patients dans un objectif de medecine personnalisee.

Introduction Les atteintes pulmonaires polykystiques peuvent etre d’etiologies diverses notamment infectieuse ou neoplasique. Nous rapportons ici le cas d’un diagnostic d’expression pulmonaire d’une maladie de Sezary diagnostiquee au decours d’une pneumocystose. Description Un homme de 73 ans rapporte l’apparition subaigue et l’aggravation progressive d’une dyspnee d’effort associee a une toux seche dans un contexte d’alteration de l’etat general. Il presente comme principal antecedent un syndrome de Sezary (lymphome cutane T epidermotrope) stabilise sous bexarotene et dermocorticoides. Les explorations initiales concluent a une pneumocystose devant la symptomatologie, l’atteinte radiologique compatible (verre depoli diffus et kystes pulmonaires a la tomodensitometrie thoracique) et la positivite de la PCR pneumocystis dans le lavage bronchoalveolaire (LBA). Malgre un traitement de 3 semaines par cotrimoxazole, les symptomes generaux et respiratoires persistent 3 mois plus tard. La maladie de Sezary est alors jugee comme toujours stable sur le plan cutane et biologique. Le controle tomodensitometrique retrouve une extension du verre depoli (aspect patchy), des condensations peri-bronchovasculaires migratrices et une augmentation du nombre de kystes pulmonaires. Le bilan biologique retrouve une lymphopenie profonde a 0.65 G/L et une hypereosinophilie a 0,52 G/L. Il n’y a pas de documentation microbiologique sur les prelevements endoscopiques (PCR pneumocystis negative). Le LBA retrouve une formule lymphocytaire (65 %) avec elements atypiques d’aspect sezariforme et eosinophilique (26 %) evoquant une localisation pulmonaire du syndrome de Sezary. Les biopsies transbronchiques confirment ce diagnostic par l’identification d’un infiltrat lymphoide perivasculaire de phenotype sezariforme. Une chimiotherapie par doxorubicine est initiee. A 3 mois de l’instauration de la chimiotherapie, une amelioration de l’etat general ainsi que de la dyspnee est observee. La tomodensitometrie thoracique retrouve quant a elle une nette diminution des lesions en verre depoli et une persistance de plusieurs lesions kystiques bilaterales. Conclusion Les localisations pulmonaires des lymphomes cutanes T epidermotropes sont peu decrites dans la litterature [1] . L’analyse precise du LBA peut suffire a elle seule a poser le diagnostic. L’aggravation de lesions kystiques pulmonaires en contexte de lymphome connu doit amener a eliminer une pathologie infectieuse. En l’absence d’amelioration malgre une therapeutique adaptee, une localisation pulmonaire de la pathologie lymphoproliferative doit etre recherchee.

Introduction La recherche exhaustive des expositions notamment professionnelles est determinante dans la prise en charge des pneumopathies d’hypersensibilites. Nous rapportons le cas d’une bronchiolite severe initialement suspectee comme infectieuse s’averant etre secondaire a une intoxication au dioxyde d’azote (« maladie des ensileurs »). Resultats Un patient non fumeur âge de 62 ans consulte aux urgences pour une hemoptysie de moyenne abondance associee a l’apparition progressive d’une dyspnee d’effort. Il n’a pas d’antecedent et ne recoit aucun traitement. Il est eleveur de bovins et rapporte dans les semaines precedentes le deces brutal de plusieurs animaux par asphyxie. La radiographie thoracique retrouve une atteinte micronodulaire diffuse bilaterale sans autre anomalie. Une antibiotherapie probabiliste est mise en place (amoxicilline-acide clavulanique, 7 jours). Le controle tomodensitometrique thoracique au decours retrouve une atteinte micronodulaire bronchiolaire diffuse bilaterale sans autre anomalie interstitielle. Les epreuves fonctionnelles respiratoires retrouvent un trouble ventilatoire obstructif isole avec rapport de Tiffeneau a 0,66 et VEMS a 3,16L (102 % de la normale). Le lavage bronchoalveolaire retrouve une lymphocytose (44 % avec rares formes plasmocytoides) associee a de minimes modifications macrophagiques (transformation epithelioide). Les biopsies transbronchiques objectivent des lesions alveolaires avec amas cohesifs lymphocytaires et macrophagiques, sans organisation conjonctive, evocatrices d’un mecanisme d’hypersensibilite. Tous les prelevements microbiologiques sont negatifs. L’expertise veterinaire au decours precise que les echantillons de gaz preleves dans l’etable contenaient de forte teneur en dioxyde d’azote. Le diagnostic porte est celui d’une bronchiolite avec hypersensibilite dans le cadre d’une maladie des ensileurs. L’arret de l’exposition et une corticotherapie systemique ont permis une amelioration clinique, fonctionnelle respiratoire et radiologique en plusieurs semaines. Conclusion La maladie des ensileurs est une pathologie bien connue des veterinaires, mais peu decrite en medecine humaine. Elle peut se presenter sous la forme d’une bronchiolite mais aussi d’un œdeme lesionnel [1] parfois letal, necessitant une reconnaissance rapide de l’exposition et sa correction.

Updated clinical recommendations for medical induced abortion procedure.A systematic review of French and English literature, reviewing the evidence relating to the provision of medical induced abortion was carried out on PubMed, Cochrane Library and international scientific societies recommendations.The effectiveness of medical abortion is higher than 95% when the protocols are adjusted to gestational age (EL1). Misoprostol alone is less effective than a combination of mifepristone and misoprostol (EL1). Gemeprost is less effective than misoprostol (EL2). The dose of 200mg of mifepristone should be preferred to 600mg (NP1, Rank A). Mifepristone can be taken at home (professional agreement). The optimum interval between mifepristone and misoprostol intake should be 24 to 48 hours (EL1, grade A). Before 7 weeks LMP, the dose of 400μg misoprostol should be given orally (EL1, grade A) eventually repeated after 3hours if no bleeding occurs. For optimal effectiveness between 7 and 14 LMP, the interval between mifepristone and misoprostol should not be shortened to less than 8hours (grade 1). An interval of 24 to 48hours will not affect the effectiveness of the method provided misoprostol dosage is 800μg (EL1). Vaginal, sublingual or buccal routes of administration are more effective and better tolerated than the oral route, which should be abandoned (EL1). An amount of 800μg sublingual or buccal misoprostol route has the same effectiveness than the vaginal route but more gastrointestinal side effects (EL1, grade A). Between 7 and 9 LMP, it does not seem necessary to repeat misoprostol dose whereas it should be repeated beyond 9 SA (grade B). Between 9 and 14 LMP, the dose of 400μg misoprostol given either vaginally, buccally or sublingually should be repeated every 3hours if needed (with a maximum of 5 doses) (EL2, grade B). There is no strong evidence supporting routine antibiotic prophylaxis for medical abortion (professional agreement). Rare contraindications should be respected (known hypersensitivity to misoprostol or mifepristone, inherited porphyria, severe anemia, hemorrhagic disorders or current anticoagulation therapy, suspected or confirmed ectopic pregnancy) as well as precautions of use (severe disease or on-going corticosteroid therapy). With no risk factors or symptoms, a pregnancy of unknown location (PUL) at the endovaginal ultrasound associated with a level of hCG usually chosen at less than 1500IU (or 2500IU with an abdominal probe) is not a contraindication of medical abortion as long as the woman is informed of the risk of undiagnosed ectopic pregnancy and knows how and when to seek emergency attention. An earlier than usual follow-up of the decrease of hCG levels is highly recommended. Breastfeeding, obesity, twin pregnancy and scared uterus are not contraindications for first trimester medical abortion. Side effects (gastro intestinal and thermoregulation disorders) during the procedure are generally of low intensity and short duration. A prophylactic treatment for nausea should be proposed (professional agreement). The pain increases with gestational age of the pregnancy (EL1). Ibuprofen is the first choice of painkiller (EL1). Ibuprofen will be systematically proposed or given on demand according to the practice of each facility (professional agreement). After a medical abortion, a follow-up assessment to confirm completion of the abortion is recommended (EL2, grade B). Clinical history combined with ultrasound and/or hCG blood level are both reliable methods and can be left with the choice of each facility (grade B). A fall of more than 80% of the initial blood level of hCG, fifteen days after the procedure is in favor of the success of the method (grade B).Medical abortion is a safe and efficient abortion method up to 14 weeks LMP. To be effective, the drug regimen should be adapted to gestational age. Women should be informed of advantages and disadvantages of the method according to the gestational age and side effects so she can choose the method that fits her best.

Introduction La sclerodermie systemique (ScS) se complique d’une pneumopathie interstitielle le plus souvent limitee aux bases (80 %), et plus rarement diffuse et extensive (15 %), de mauvais pronostic, alterant la qualite et l’esperance de vie. L’atteinte interstitielle pulmonaire de la ScS a le plus souvent un aspect de pneumopathie interstitielle non specifique (75 % des cas), alors qu’une pneumopathie interstitielle commune est notee chez 15 % des patients. Il existe aussi de tres rares cas de syndrome emphyseme-fibrose, de tres mauvais pronostic. Nous rapportons ici une atteinte interstitielle pulmonaire jamais decrite a ce jour au cours de la ScS : la fibroelastose pleuroparenchymateuse (FEPP). Observation Une patiente de 46 ans etait suivie pour une ScS cutanee limitee evoluant depuis 1998 associant un phenomene de Raynaud non complique, une sclerodactylie, des telangiectasies et des anticorps anticentromeres positifs. Elle avait egalement un syndrome de Sjogren secondaire avec atteinte oculaire severe (blepharite telangiectasique, keratite seche). Ses autres antecedents etaient un asthme allergique de l’enfance et une hypothyroidie supplementee. Elle prenait comme seul traitement immunosuppresseur de la ciclosporine topique palpebral. Il n’y avait aucun antecedent familial particulier. Elle ne fumait pas et n’etait pas exposee a d’eventuels toxiques. Son bilan annuel de suivi en 2008 montrait un etat clinique stable sans dyspnee d’effort et sans toux avec une auscultation pulmonaire normale. Les epreuves fonctionnelles respiratoires revelaient une diminution de la diffusion libre du monoxyde de carbone (DLCO) a 55,9 % de la theorique sans trouble ventilatoire restrictif ni obstructif associe. L’echocardiographie transthoracique etait normale. Le scanner thoracique retrouvait des epaississements septaux sous-pleuraux avec des micro-nodules predominants aux apex, compatibles avec une PINS debutante. Elle etait revue en 2016 apres une perte de suivi. Elle n’avait aucun signe fonctionnel respiratoire ni signe d’evolutivite de sa ScS. Son traitement medicamenteux etait inchange. Les tests fonctionnels respiratoires etaient stables : DLCOc = 53 % theorique, capacite vitale maximale a 2,03 L (70 % theorique) et capacite pulmonaire totale a 4,72 L (100 % theorique). Cependant, il est apparu une aggravation des lesions pulmonaires avec des condensations sous-pleurales irregulieres a predominance superieure, associees a une alteration de l’interface pleuropulmonaire, realisant un aspect typique de fibro-elastose pleuroparenchymateuse. Discussion La fibroelastose pleuroparenchymateuse (FEPP) est actuellement classee parmi les pneumopathies interstitielles idiopathiques rares selon le consensus international de 2013 [1] . Elle se caracterise par des lesions fibrotiques et riches en elastine de la plevre viscerale, des regions intra-alveolaires sous-pleurales ainsi que des cloisons inter-alveolaires predominantes aux apex [2] . Sa presentation clinique est peu specifique avec une dyspnee d’effort et une toux chronique. La susceptibilite accrue aux pneumothorax et l’apparition d’un platythorax sont des elements parfois evocateurs. Pathologie rare (environ 150 a 200 cas decrits et rapportes), la FEPP est observee dans des contextes heterogenes : greffe de moelle osseuse, transplantation pulmonaire, exposition a certaines chimiotherapies/radiotherapie. On compte aussi des cas familiaux avec une susceptibilite genetique ou sur des terrains auto-immuns (spondylarthropathies, recto-colite hemorragique) [3] . Les mecanismes physiopathologiques ne sont pas identifies a l’heure actuelle. L’evolution naturelle de la maladie tend vers l’aggravation des lesions fibrotiques puis le developpement d’une insuffisance respiratoire chronique restrictive. Il n’existe pas de traitement recommande a l’exception de la transplantation pulmonaire dans les formes evoluees. A notre connaissance, aucun cas de FEPP n’a ete rapporte dans un contexte de ScS, ou d’une maniere plus generale, dans celui d’une connectivite. Dans le cas present, la FEPP semble peu symptomatique avec une stabilite des epreuves fonctionnelles respiratoires. Il a ete decide d’une simple surveillance. Conclusion La recherche d’autres cas similaires permettrait de determiner si la FEPP est a considerer comme une atteinte specifique de la ScS ou s’il s’agit au contraire d’une association fortuite. Le developpement d’une FEPP au cours de la ScS pose naturellement la question de mecanismes fibrosants eventuellement communs au niveau cutane et pulmonaire.

Resume En France, depuis 2001, l’avortement medicamenteux peut se faire en ville dans le cadre d’un reseau avec l’hopital qui assure la prise en charge des complications et des echecs de la methode. Cette etude rapporte l’experience d’un centre de planification et d’education familiale (CPEF) du Mouvement francais de planning familial (MFPF) en relation avec l’hopital Delafontaine. En 2004, le CPEF a pris en charge 161 avortements medicamenteux en utilisant le protocole de 200 mg (1 comprime) de mifepristone le premier jour, suivi 36 a 48 h plus tard par 400 a 800 ug (2 a 4 comprimes) de misoprostol. La moyenne d’âge des femmes etait de 24 ans avec une proportion de jeunes et de femmes en precarite, voire grande precarite. Le choix etait offert aux femmes de rester a la maison ou en observation a l’hopital pour l’expulsion. Le taux de succes defini par l’absence d’intervention chirurgicale atteint 94,5 % et il y a eu une seule complication grave, une hemorragie 40 jours apres la prise de misoprostol. Soixante-quinze pour cent des femmes ont choisi de rester chez elle pour l’expulsion. L’acceptation de la methode est tres bonne avec un nombre de consultations supplementaires tres faible par rapport aux 3 visites du protocole. La qualite du suivi est bon, avec 82 % de femmes revenant a la visite de controle ; cette observance est sans relation avec l’âge, les antecedents obstetricaux ou le niveau socio-economique. L’avortement medicamenteux peut etre realise en toute securite en ville y compris pour des femmes en precarite. Des centres comme celui du MFPF avec une equipe multidisciplinaire impliquant des conseilleres conjugales et familiales et des medecins peuvent offrir un service de grande qualite aux femmes de la region.

To test the feasibility, safety, and efficacy of home use of two doses of misoprostol for medical abortion (MA) in European settings.One hundred thirty women (100 in Sweden, 30 in France) presenting for first-trimester MA were administered oral mifepristone in the clinic and sent home with two 400 microg doses of misoprostol, along with instructions to take the misoprostol at 24 h intervals. Women were also asked to complete a daily symptom diary. Outcomes of interest included effectiveness, side-effects, and adherence to and acceptability of the home-use regimen.Three women (all in France) were lost to follow-up. Of the remaining 127 women, 124 (98%) had a successful MA. All women adhered successfully to the home-use regimen, and satisfaction with home use was high (98%). Most women experienced noticeable, if transitory, side effects after both the first and second doses of misoprostol (97% and 94%, respectively).Misoprostol may successfully and satisfactorily be used at home as part of a MA regimen in European settings as it has been for years in the US. Further research to determine if two doses of misoprostol are more effective than a single dose would be useful.

In France, since 2001, medical abortion can be performed in ambulatory conditions, provided an agreement is signed with a hospital serving as referral for complications or failures of the method. This study, reports on the experience of a family planning center (NGO MFPF, Mouvement français de planning familial) in partnership with Delafontaine Hospital in Saint-Denis. In 2004, the MFPF has managed 161 cases of ambulatory medical abortion using a protocol of 200mg of mifepristone on day 1 and 400 to 800 microg of misoprostol on day 3, with possibility for the women to stay at home or go to the hospital for the expulsion. The average age of the women was 24 years and the proportion of young and vulnerable women quite high. The rate of success, defined as the absence or surgical intervention, approached 94.5% and only one case of severe complication was reported, massive hemorrhage 40 days after the initial intake of misoprostol. 75% of women chose to stay home. Acceptance of the method was very good with minimal request for more consultations than the three visits proposed in the protocol. The quality of the follow-up was high with 82% of women attending the medical check, with no difference being observed with regard to age, obstetrical history or socio-economic groups. Ambulatory medical abortion was successful and safe even among vulnerable women. NGOs with multidisciplinary staff involving counsellors, nurses and doctors can offer high quality preparation and follow-up.

OBJECTIVE: The aim of this article is to describe conditions of abortions practices in France. MATERIALS AND METHODS: The study was based on the COCON survey. This survey was carried out among a representative sample of 2863 women aged 18 to 44 living in metropolitan France. Women were interviewed by telephone. The analysis was performed among a sub-sample of 320 women who had had an abortion between 1996 and 2000. Results were compared with those of the national notification of induced abortions. RESULTS: Altogether, the way in which abortions were carried out was appropriate, but differences were observed according to the type of hospital: access to care was easier in the private sector; however a pre-abortion interview was less often carried out and a post-abortion interview less often proposed in the private sector. Besides, in both sectors, women were rarely allowed to choose the abortion technique, or the type of anesthesia in the case of a surgical abortion. CONCLUSION: The COCON study is the first population based survey describing the characteristics of care regarding voluntary abortion. It shows the persistence of differences in practices between the public and the private sectors.

A pilot study has been conducted in France to estimate the extent of underreporting of induced abortion and the factors linked to underreporting.A representative random sample of 300 women aged between 18 and 44 years of age who had been pregnant during the previous 2 years and 100 women who had not was selected from the telephone directory. Interviews were conducted by telephone.The annual incidence of induced abortion for the 18-44-year-old age group was 6.9 per 1000 (95% confidence interval 2.2-11.6), while the rate derived from national statistics was 15 per 1000. Five women who reported a therapeutic abortion in their lifetime had confused induced abortion and therapeutic abortion. There was no significant difference in the proportion of women reporting induced abortion in their lifetime between those answering with another adult present and those who were alone when answering (13.1% versus 11.1%, p = 0.8). There was also no significant difference according to the sex of the interviewer (10.0% for men versus 12.2% for women, p = 0.6).The results suggest that the context in which the questions were asked does not affect the validity of the answers and that there is a problem in the comprehension of the terminology used. Extensive rewriting and reformulation of the questions is required to minimize the underreporting of induced abortion.

In France, each woman will have an average of one unintended pregnancy in her life and she'll decide to abort once out of two. 21 years after the vote of the law which authorized the abortion, according to certains conditions, the abortion rate decreases slightly. The socioeconomics characteristics of women requesting an abortion are very similar to those found in 1976. The medical and psychological complications are very low. The law is applied except that some difficulties persist: to recruit professionals becomes more difficult, inadequate solutions of public hospitals, inappropriate and not always comprehensive towards the clients, no possibility to choose the methods. The law is limited for the minors, the foreigners and the pregnancies up to 10 weeks which increases the social inegalities. It is a major public health concern to make abortion as safe as possible because it gives accessibility to choose freely motherhood which is the best way for safe pregnancy, birth and parent and child relationship.

For various reasons, including the population policies of the former Socialist countries, abortion is much more frequent than contraception in Central and Eastern Europe. The contrary occurs in Western countries. In the current context, countries in Central and Eastern Europe should improve abortion services and this should be a priority target in their health policy. The study does not detect a clear-cut advantage as concerns substituting contraception to abortion in these countries in terms for instance of reducing maternal mortality. In fact a health policy favouring contraception instead of abortion is firstly inspired by political or ethical reasons. If implemented in Central and Eastern Europe, it would require several decades to bear evident results.Although most countries of Europe have total fertility rates of under 2, these low rates are achieved in western and northern Europe primarily through widespread contraceptive usage with abortion serving as a backup, while in eastern Europe abortion plays the primary role. In eastern European countries, access to abortion preceded diffusion of modern contraception. When modern contraceptive methods became available in the 1960s, they did not reach the eastern European countries because of the lack of communication between Communist societies and the West. Erroneous ideas about the dangers of modern methods have persisted, while abortion is viewed as an everyday occurrence. Public opinion concerning modern methods is generally unfavorable. The availability of safe legal abortions in western Europe has resulted in a very low rate of abortion mortality, around 0.5 deaths per 100,000 abortions. In eastern Europe, abortion mortality rates range from 1 to 10/100,000 abortions, and infertility resulting from abortion is common. Illegal abortions persist because of poor accessibility of quality services. The psychological cost to couples of disorders resulting from abortion is difficult to evaluate but surely considerable. A comparison of the public health results of improving conditions of abortion in eastern Europe while continuing to limit contraceptive use to the traditional methods, or of providing modern contraception, indicates that there is no decisive advantage in favor of modern contraception. The manpower and thus the financial requirements would be less for the policy of providing safe abortions without modern contraception. The major argument against abortion is ethical, not financial or health related. Hungary and the German Democratic Republic have demonstrated that a change from fertility control through abortion to fertility control through contraception is feasible. Such a change would require a very large investment in services and manpower, and would not be fully achieved for many years.