HLA–B27 heavy chains distinguished by a micropolymorphism exhibit differential flexibility

Objective: Although the products of the HLA subtypes B*2705 and B*2709 differ only in residue 116 (Asp versus His) within their peptide-binding grooves, they are differentially associated with inflammatory rheumatic diseases such as ankylosing spondylitis (AS): B*2705 occurs in AS patients, whereas B*2709 is only rarely encountered. The reasons for this distinct association are still unclear but could include subtypespecific conformational and dynamic properties of these antigens. The present study was undertaken to investigate structural and dynamic differences between B*2705 and B*2709 and their possible relationship to subtypespecific disease association. Methods: The membrane-distal segments of the B*2705 and B*2709 heavy chains were expressed in vitro and reconstituted together with ß2-microglobulin and a peptide. HLA–B27 complexes loaded with 2 self peptides (TIS [RRLPIFSRL] and pVIPR [RRKWRRWHL]) and a sequence-related viral peptide (pLMP2 [RRRWRRLTV]) were studied by isotope-edited infrared spectroscopy to detect differences in their structure and flexibility at physiologic temperature. Results: Our analyses revealed the existence of subtype-specific conformational differences between the 2 HLA–B27 heavy chains at physiologic temperature, which are undetectable using x-ray crystallography. Irrespective of the bound peptide, the heavy chain of the B*2705 complex exhibited higher conformational flexibility than the B*2709 heavy chain. Conclusion: The present study demonstrates the existence of previously undetected systematic conformational and dynamic differences between the heavy chains of the 2 HLA–B27 subtypes. Since effector cell recognition of cells expressing HLA antigens is dependent on the dynamic properties of the interacting cell surface molecules, this HLA–B27 subtype–specific heavy chain flexibility could have a role in the distinct association of HLA–B27 subtypes with spondylarthritides

Feasibility of Conducting a Trial Assessing Benefits and Risks of Planned Caesarean Section Versus Planned Vaginal Birth: A Cross-Sectional Study

Introduction: Though interest is growing for trials comparing planned delivery mode (vaginal delivery [VD]; cesarean section [CS]) in low-risk nulliparous women, appropriate study design is unclear. Our objective was to assess feasibility of three designs (preference trial [PCT], randomized controlled trial [RCT], partially randomized patient preference trial [PRPPT]) for a trial comparing planned delivery mode in low-risk women. Methods: A cross-sectional survey of low-risk, nulliparous pregnant women (N = 416) and healthcare providers (N = 168) providing prenatal care and/or labor/delivery services was conducted in Argentina (2 public, 2 private hospitals). Proportion of pregnant women and providers willing to participate in each design and reasons for not participating were determined. Results: Few women ( 85%). Believing randomization unacceptable (RCT, PRPPT) and desiring choice of delivery mode (RCT) were women’s reasons for not participating. For providers, commonly cited reasons for not participating included unacceptability of performing CS without medical indication, difficulty obtaining informed consent, discomfort enrolling patients (all designs), and violating women’s right to choose (RCT). Conclusions for Practice: Important limitations were found for each trial design evaluated. The necessity of stronger evidence regarding delivery mode in low-risk women suggests consideration of additional designs, such as a rigorously designed cohort study or an RCT within an obstetric population with equivocal CS indications.Fil: Amyx, Melissa Michele. Instituto de Efectividad Clínica y Sanitaria; Argentina. University of Tulane; Estados UnidosFil: Althabe, Fernando. University of Tulane; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones en Epidemiología y Salud Pública. Instituto de Efectividad Clínica y Sanitaria. Centro de Investigaciones en Epidemiología y Salud Pública; ArgentinaFil: Rivo, Julie. Instituto de Efectividad Clínica y Sanitaria; ArgentinaFil: Pingray, María Verónica. University of Duke; Estados UnidosFil: Minckas, Nicole. Instituto de Efectividad Clínica y Sanitaria; ArgentinaFil: Belizán, María. Instituto de Efectividad Clínica y Sanitaria; ArgentinaFil: Gibbons, Luz. Instituto de Efectividad Clínica y Sanitaria; ArgentinaFil: Murga, Gerardo T.. Instituto de Maternidad Y Ginecología Nuestra Señora de Las Mercedes; ArgentinaFil: Fiorillo, Angel Eduardo. Centro de Educación Médica e Investigaciones Clínicas "Norberto Quirno"; ArgentinaFil: Malamud, Julio D.. Centro de Educación Medica E Invest.clinicas; ArgentinaFil: Casale, Roberto A.. Sanatorio de la Mujer.; ArgentinaFil: Cormick, Gabriela. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones en Epidemiología y Salud Pública. Instituto de Efectividad Clínica y Sanitaria. Centro de Investigaciones en Epidemiología y Salud Pública; Argentina. Hospital Nacional Profesor Alejandro Posadas; ArgentinaFil: Belizan, Jose. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones en Epidemiología y Salud Pública. Instituto de Efectividad Clínica y Sanitaria. Centro de Investigaciones en Epidemiología y Salud Pública; Argentin

Obstetrical providers’ preferred mode of delivery and attitude towards non-medically indicated caesarean sections: a cross-sectional study

Objective: To describe obstetrical providers’ delivery preferences and attitudes towards caesarean section without medical indication, including on maternal request, and to examine the association between provider characteristics and preferences/attitudes. Design: Cross-sectional study. Setting: Two public and two private hospitals in Argentina. Population: Obstetrician-gynaecologists and midwives who provide prenatal care and/or labour/delivery services. Methods: Providers in hospitals with at least 1000 births per year completed a self-administered, anonymous survey. Main outcome measures: Provider delivery preference for low-risk women, perception of women's preferred delivery method, support for a woman's right to choose her delivery method and willingness to perform caesarean section on maternal request. Results: 168 providers participated (89.8% coverage rate). Providers (93.2%) preferred a vaginal delivery for their patients in the absence of a medical indication for caesarean section. Whereas 74.4% of providers supported their patient's right to choose a delivery method in the absence of a medical indication for caesarean section and 66.7% would perform a caesarean section upon maternal request, only 30.4% would consider a non-medically indicated caesarean section for their own personal delivery or that of their partner. In multivariate adjusted analysis, providers in the private sector [odds ratio (OR) 4.70, 95% CI 1.19–18.62] and obstetrician-gynaecologists (OR 4.37, 95% CI 1.58–12.09) were more willing than either providers working in the public/both settings or midwives to perform a caesarean section on maternal request. Conclusions: Despite the ethical debate surrounding non-medically indicated caesarean sections, we observe very high levels of support, especially by providers in the private sector and obstetrician-gynaecologists, as aligned with the high caesarean section rates in Argentina. Tweetable abstract: Non-medically indicated c-section? 74% of sampled Argentine OB providers support women's right to choose.Fil: Rivo, J. C.. Duke University Medical Center; Estados UnidosFil: Amyx, Melissa Michele. University of Tulane; Estados Unidos. Instituto de Efectividad Clínica y Sanitaria; ArgentinaFil: Pingray, María Verónica. Instituto de Efectividad Clínica y Sanitaria; ArgentinaFil: Casale, R. A.. Hospital Nacional Profesor Dr. Alejandro Posadas; ArgentinaFil: Fiorillo, Angel Eduardo. Centro de Educación Médica e Investigaciones Clínicas “Norberto Quirno”; ArgentinaFil: Krupitzki, Hugo Bernardo. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. CEMIC-CONICET. Centro de Educaciones Médicas e Investigaciones Clínicas "Norberto Quirno". CEMIC-CONICET; ArgentinaFil: Malamud, J. D.. Sanatorio de la Mujer; ArgentinaFil: Mendilaharzu, M.. Instituto de Maternidad y Ginecología Nuestra Señora de Las Mercedes; ArgentinaFil: Medina, M. L.. Instituto de Maternidad y Ginecología Nuestra Señora de Las Mercedes; ArgentinaFil: del Pino, A. B.. Sanatorio de la Mujer; ArgentinaFil: Ribola, L.. Hospital Nacional Professor Dr. Alejandro Posadas; ArgentinaFil: Schvartzman, Javier Alfonso. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. CEMIC-CONICET. Centro de Educaciones Médicas e Investigaciones Clínicas "Norberto Quirno". CEMIC-CONICET; ArgentinaFil: Tartalo, G. M.. Instituto de Maternidad y Ginecología Nuestra Señora de Las Mercedes; ArgentinaFil: Trasmonte, Monica. Hospital Nacional Profesor Dr. Alejandro Posadas; ArgentinaFil: Varela, S.. Hospital Nacional Profesor Dr. Alejandro Posadas; ArgentinaFil: Althabe, Fernando. Instituto de Efectividad Clínica y Sanitaria; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Belizán, J. M.. Instituto de Efectividad Clínica y Sanitaria; Argentin

Odon device for instrumental vaginal deliveries: results of a medical device pilot clinical study

Abstract Background A prolonged and complicated second stage of labour is associated with serious perinatal complications. The Odon device is an innovation intended to perform instrumental vaginal delivery presently under development. We present an evaluation of the feasibility and safety of delivery with early prototypes of this device from an early terminated clinical study. Methods Hospital-based, multi-phased, open-label, pilot clinical study with no control group in tertiary hospitals in Argentina and South Africa. Multiparous and nulliparous women, with uncomplicated singleton pregnancies, were enrolled during the third trimester of pregnancy. Delivery with Odon device was attempted under non-emergency conditions during the second stage of labour. The feasibility outcome was delivery with the Odon device defined as successful expulsion of the fetal head after one-time application of the device. Results Of the 49 women enrolled, the Odon device was inserted successfully in 46 (93%), and successful Odon device delivery as defined above was achieved in 35 (71%) women. Vaginal, first and second degree perineal tears occurred in 29 (59%) women. Four women had cervical tears. No third or fourth degree perineal tears were observed. All neonates were born alive and vigorous. No adverse maternal or infant outcomes were observed at 6-weeks follow-up for all dyads, and at 1 year for the first 30 dyads. Conclusions Delivery using the Odon device is feasible. Observed genital tears could be due to the device or the process of delivery and assessment bias. Evaluating the effectiveness and safety of the further developed prototype of the BD Odon Device™ will require a randomized-controlled trial. Trial registration ANZCTR ACTRN12613000141741 Registered 06 February 2013. Retrospectively registered

Feasibility and safety study of a new device (Odón device) for assisted vaginal deliveries: study protocol

Background Intrapartum complications are responsible for approximately half of all maternal deaths, and two million stillbirth and neonatal deaths per year. Prolonged second stage of labour is associated with potentially fatal maternal complications such as haemorrhage and infection and it is a major cause of stillbirth and newborn morbidity and mortality. Currently, the three main options for managing prolonged second stage of labour are forceps, vacuum extractor and caesarean section. All three clinical practices require relatively expensive equipment (e.g., a surgical theatre for caesarean section) and/or highly trained staff which are often not available in low resource settings. The specific aim of the proposed study is to test the safety and feasibility of a new device (Odón device) to effectively deliver the fetus during prolonged second stage of labour. The Odón device is a low-cost technological innovation to facilitate operative vaginal delivery and designed to minimize trauma to the mother and baby. These features combined make it a potentially revolutionary development in obstetrics, particularly for improving intrapartum care and reducing maternal and perinatal morbidity and mortality in low resource settings. Methods/design This will be a hospital-based, multicenter prospective phase 1 cohort study with no control group. Delivery with the Odón device will be attempted under normal labour and non-emergency conditions on all the women enrolled in the study. One-hundred and thirty pregnant women will be recruited in tertiary care facilities in Argentina. Safety will be assessed by examining maternal and infant outcomes until discharge. Feasibility will be evaluated by observing successful expulsion of the fetal head after one-time application of the device under standardized conditions (full cervical dilation, anterior presentation, +2 station, normal fetal heart rate).Fil: Schvartzman, Javier A.. Centro de Educaciones Médicas e Investigación Clínica "Norberto Quirno"; ArgentinaFil: Krupitzki, Hugo Bernardo. Centro de Educación Médica e Investigaciones Clínicas “Norberto Quirno”; ArgentinaFil: Betran, Ana Pilar. Department of Reproductive Health and Research. Ginebra; SuizaFil: Requejo, Jennifer. Department of Reproductive Health and Research. Ginebra; SuizaFil: Bergel, Eduardo. Instituto de Efectividad Clínica y Sanitaria; ArgentinaFil: Fiorillo, Angel Eduardo. Centro de Educación Médica e Investigaciones Clínicas “Norberto Quirno”; ArgentinaFil: Gadow, Enrique Curt. Centro de Educación Médica e Investigaciones Clínicas “Norberto Quirno”; ArgentinaFil: Vizcaino, Francisco M.. Centro de Educación Médica e Investigaciones Clínicas “Norberto Quirno”; ArgentinaFil: Von Petery, Felicitas. Centro de Educación Médica e Investigaciones Clínicas “Norberto Quirno”; ArgentinaFil: Althabe, Fernando. Instituto de Efectividad Clínica y Sanitaria; ArgentinaFil: Belizan, Jose. Instituto de Efectividad Clínica y Sanitaria; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Borruto, Franco. Centre Hospitalier Princesse Grace; MónacoFil: Boulvain, Michel. Hopitaux Universitaires de Ginebra. Ginebra; SuizaFil: Di Renzo, Gian Carlo. Santa Maria Della Misericordia University Hospital; ItaliaFil: Gülmezoglu , Metin. World Health Organization. Ginebra; SuizaFil: Hofmeyr, Justus. University of the Witwatersrand; SudáfricaFil: Judge, Kevin. Becton Dr. Franklin Lakes. New York; Estados UnidosFil: Leung, Tak Yeung. The Chinese University of Hong Kong; Hong KongFil: Nguyen, My Huong. Department of Reproductive Health and Research. Ginebra; SuizaFil: Saugstad, Ola Didrik. University of Oslo; NoruegaFil: Temmerman, Marleen. Department of Reproductive Health and Research. Ginebra; SuizaFil: Treisser, Alain. Centre Hospitalier Princesse Grace; MónacoFil: Vayena, Effy. Universitat Zurich; SuizaFil: Merialdi, Mario. Department of Reproductive Health and Research. Ginebra; Suiz