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1. Gonadotropin administration to mimic mini-puberty in hypogonadotropic males: pump or injections?

Author

Tristan Avril, Quentin Hennocq, Anne-Sophie Lambert, Juliane Leger, Dominique Simon, Laetitia Martinerie, and Claire Bouvattier

Subjects
recombinant gonadotropins, mini-puberty, boys, hypogonadotropic hypogonadism, pump, injections, Diseases of the endocrine glands. Clinical endocrinology, RC648-665
Abstract

Objective: Newborns with congenital hypogonadotropic hypogonadism (CHH) have an impaired postnatal activation of the gonadotropic axis. Substitutive therapy with recombinant gonadotropins can be proposed to mimic physiological male mini-puberty during the first months of life. The aim of this study was to co mpare the clinical and biological efficacy of two treatment modalities of gonadotropins administration during mini-puberty in CHH neonates. Design: Multicenter retrospective analytical epidemiological study comparing two treatments, pump vs injection, between 2004 and 2019. Methods: Clinical (penile size, testis size, testicular descent) and biological parameters (serum concentrations of testosterone, anti-Müllerian hormone (AMH) and Inhibin B) were compared between the two groups by multivariate analyses. Results: Thirty-five patients were included. A significantly higher incre ase in penile length and testosterone level was observed in the injection group compared to the pump group (+0.16 ± 0.02 mm vs +0.10 ± 0.02 mm per day, P = 0.002; and +0.04 ± 0.007 ng/mL vs +0.01 ± 0.008 ng/mL per day, P = 0.001). In both groups, significant increases in penile length and width, testosterone, AMH, and Inhibin B levels were observed, as well as improved testicular descent (odds ratio of not being in a scrotal position at the end of treatment = 0.97 (0.96; 0.99)). Conclusions: Early postnatal administration of recombinant gonadotropins in CHH boys is effective in stimulating penile growth, Sertoli cell proliferati on, and testicular descent, with both treatment modalities.

Published
2023
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2. Glucocorticoid induced adrenal insufficiency in children: Morning cortisol values to avoid LDSST

Author

Margaux Laulhé, Cécile Dumaine, Didier Chevenne, Fallou Leye, Albert Faye, Blandine Dozières, Marion Strullu, Jérome Viala, Julien Hogan, Véronique Houdouin, Juliane Léger, Dominique Simon, Jean-Claude Carel, Caroline Storey, Sophie Guilmin-Crépon, and Laetitia Martinerie

Subjects
adrenal insufficency, low dose short synacthen test, glucocorticoid withdrawal, cortisol, pediatric, Pediatrics, RJ1-570
Abstract

ObjectivesGlucocorticoid-induced adrenal insufficiency (GI-AI) is a common side effect of glucocorticoid therapy. However, its diagnosis currently relies on the realization of a Low Dose Short Synacthen Test (LD-SST) that requires an outpatient hospital and several blood samples. Our goal was to evaluate whether morning cortisol values could predict the response to LD-SST, in children, to avoid useless dynamic tests and facilitate diagnosis of glucocorticoid induced adrenal insufficiency.Study DesignWe recorded data of 91 pediatric patients who underwent a LD-SST in our center between 2016 and 2020 in a retrospective observational study. We selected LD-SST realized following administration of supra-physiologic doses of glucocorticoids during more than 3 weeks and performed at least four weeks after treatment was stopped. Adrenal deficiency was defined as a plasma cortisol concentration inferior to 500 nmol/l at LD-SST.ResultsGlucocorticoid-induced adrenal insufficiency was diagnosed in 60% of our cohort. Morning cortisol values were predictive of the response to the LD-SST (AUC ROC 0.78). A plasma cortisol concentration of less than 144 nmol/l predicted glucocorticoid induced adrenal insufficiency with a specificity of 94% and a value over 317 nmol/l predicted recovery of the HPA axis with a sensitivity of 95%. We did not find any other predictive factor for glucocorticoid-induced adrenal insufficiency.ConclusionsMorning cortisol values can safely assess recovery of the HPA axis in children treated chronically with glucocorticoids. Using these thresholds, more than 50% of LD-SST could be avoided in children.

Published
2022
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3. Innate Immune Basis for Rift Valley Fever Susceptibility in Mouse Models

Author

Rashida Lathan, Dominique Simon-Chazottes, Grégory Jouvion, Ophélie Godon, Marie Malissen, Marie Flamand, Pierre Bruhns, and Jean-Jacques Panthier

Subjects
Medicine, Science
Abstract

Abstract Rift Valley fever virus (RVFV) leads to varied clinical manifestations in animals and in humans that range from moderate fever to fatal illness, suggesting that host immune responses are important determinants of the disease severity. We investigated the immune basis for the extreme susceptibility of MBT/Pas mice that die with mild to acute hepatitis by day 3 post-infection compared to more resistant BALB/cByJ mice that survive up to a week longer. Lower levels of neutrophils observed in the bone marrow and blood of infected MBT/Pas mice are unlikely to be causative of increased RVFV susceptibility as constitutive neutropenia in specific mutant mice did not change survival outcome. However, whereas MBT/Pas mice mounted an earlier inflammatory response accompanied by higher amounts of interferon (IFN)-α in the serum compared to BALB/cByJ mice, they failed to prevent high viral antigen load. Several immunological alterations were uncovered in infected MBT/Pas mice compared to BALB/cByJ mice, including low levels of leukocytes that expressed type I IFN receptor subunit 1 (IFNAR1) in the blood, spleen and liver, delayed leukocyte activation and decreased percentage of IFN-γ-producing leukocytes in the blood. These observations are consistent with the complex mode of inheritance of RVFV susceptibility in genetic studies.

Published
2017
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4. Growth and Adult Height in Patients with Crohn's Disease Treated with Anti-Tumor Necrosis Factor α Antibodies.

Author

Sarah Bamberger, Christine Martinez Vinson, Damir Mohamed, Jérôme Viala, Jean-Claude Carel, Jean-Pierre Hugot, and Dominique Simon

Subjects
Medicine, Science
Abstract

Inflammation contributes to growth failure associated with inflammatory bowel diseases. Anti-TNFα therapy induces sustained remission and short-term improvements in height velocity and/or height standard deviation score (H-SDS) patients with Crohn's disease. The purpose of this study was to evaluate growth and adult height in patients with Crohn's disease taking maintenance infliximab or adalimumab therapy.This university-hospital based retrospective study included 61 patients, with a median follow-up of 2.6 years (2.0; 3.3). 38 patients (62%) reached their adult height. H-SDS was collected at diagnosis and together with disease activity markers (Harvey-Bradshaw Index, albumin, and C-reactive protein) at treatment initiation (baseline), and follow-up completion. Wilcoxon's signed-rank test was chosen for comparisons. Median H-SDS decreased from diagnosis to baseline (-0.08 [-0.73; +0.77] to -0.94 [-1.44; +0.11], p

Published
2016
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5. I-SceI-mediated double-strand break does not increase the frequency of homologous recombination at the Dct locus in mouse embryonic stem cells.

Author

Myriam Fenina, Dominique Simon-Chazottes, Sandrine Vandormael-Pournin, Jihane Soueid, Francina Langa, Michel Cohen-Tannoudji, Bruno A Bernard, and Jean-Jacques Panthier

Subjects
Medicine, Science
Abstract

Targeted induction of double-strand breaks (DSBs) at natural endogenous loci was shown to increase the rate of gene replacement by homologous recombination in mouse embryonic stem cells. The gene encoding dopachrome tautomerase (Dct) is specifically expressed in melanocytes and their precursors. To construct a genetic tool allowing the replacement of Dct gene by any gene of interest, we generated an embryonic stem cell line carrying the recognition site for the yeast I-SceI meganuclease embedded in the Dct genomic segment. The embryonic stem cell line was electroporated with an I-SceI expression plasmid, and a template for the DSB-repair process that carried sequence homologies to the Dct target. The I-SceI meganuclease was indeed able to introduce a DSB at the Dct locus in live embryonic stem cells. However, the level of gene targeting was not improved by the DSB induction, indicating a limited capacity of I-SceI to mediate homologous recombination at the Dct locus. These data suggest that homologous recombination by meganuclease-induced DSB may be locus dependent in mammalian cells.

Published
2012
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8. Hommage à Anne Fagot-Campagna

Author

Beverley Balkau, Bruno Detournay, Eveline Eschwège, Sandrine Fosse-Edorh, Dominique Simon, and Alain Weill

Subjects
Nutrition and Dietetics, Endocrinology, Diabetes and Metabolism, Internal Medicine, Cardiology and Cardiovascular Medicine
Published
2022

9. Marine Science Communication in Europe: A Way Forward

Author

Jan Seys, Lucy Cox, Ezgi Şahin Yücel, Daria Ezgeta-Balić, Marco Faimali, Francesca Garaventa, M. Carmen García-Martínez, Claudia Gili, Kathrin Kopke, Francesca Petrera, Dominique Simon, Andreas Villwock, Tymon Zielinski, Kelle Moreau, and Angel Muñiz Piniella

Subjects
ComputingMethodologies_SIMULATIONANDMODELING, marine science communication, ocean literacy, ComputerApplications_COMPUTERSINOTHERSYSTEMS, GeneralLiterature_MISCELLANEOUS, ComputingMethodologies_COMPUTERGRAPHICS
Abstract

Marine Science Communication (MSC) aims to increase understanding and to raise awareness of Ocean science. It also increases curiosity about scientific discoveries and issues related to our Ocean. MSC is a tool to improve understanding of the importance of Ocean science, to help create awareness and inspire responsible behaviour at all levels of society, and to advocate for policy that is committed to a sustainable Ocean and planet. The purpose of this Future Science Brief is to shed light on the state of the art, the impact, the visibility and the future of MSC actions in Europe. This document aims to highlight MSC as a critical field of activity, and to share recommendations for its future development. It also examines lessons learnt during the process of MSC, considers the role of different stakeholders in this process, and highlights the challenges and opportunities that arise when communicating about Ocean science. Finally, it delivers specific recommendations on how to recognize, support and improve MSC in Europe. The main target audience are professional communicators within Ocean/marine research institutions, Ocean conservation organizations, or scientists who communicate their own research. This document is also aimed at marine scientific organization managers, research funders, European and national policy-makers and NGOs, who support a healthy Ocean, the local economy, food provision, tourism, etc. Over the coming decade, MSC will become critical to achieve a more Ocean literate and sustainable society. To strengthen the capacity of MSC in Europe, we make the following recommendations: 1. Marine Science Communication should not hide facts, but should avoid only presenting the ‘negative bias’ in Ocean news. It should also show the opportunities, and when possible, the positive side of a story. 2. Marine science institutions and funders should change their culture in order to stimulate science communication and to acknowledge and value science communication. 3. Marine science communicators should look for connections with science communicators outwith marine science, and with communicators in non-scientific domains (e.g. marketing). Communication experts should increase interaction with all stakeholders (scientists, citizens, media, aquaria & science centres, students, policy-makers, industry, educators) in the MSC process. 4. A marine science communication platform or database should be developed by the communication community to share expertise and resources, especially to help those with reduced resources. 5. Additional funding and human resources are needed to cope with future MSC needs. The European Marine Board Communications Panel recommends that marine science institutions should dedicate at least 10% of their staff time to MSC. This can include both staff dedicated to MSC and/or time spent on MSC by scientists and other staff. 6. Marine science communicators should make better use of new technologies and approaches to reach the wider public in order to enhance successful traditional methods (story-telling, hands-on activities, arts, visuals, etc.), ‘to make the invisible visible’, to stimulate curiosity and hunger for knowledge, and to actively connect with a wider audience. 7. There is a clear need for professional communication and outreach training programs, workshops and events (e.g. the CommOCEAN conferences), both for marine scientists and for other MSC stakeholders. It is recommended that a structural means for supporting the continuation of these conferences is sought, possibly in partnership with the European Commission. 8. Marine science communicators should communicate as much as possible under the umbrella of the Ocean Decade and of the EU Mission: Restore our Ocean and waters by 2030, both unique opportunities to enhance MSC. An evaluation by the conveners of these efforts should be made in order to learn from the experience and to be prepared to underpin similar future actions. 9. A general communication baseline for marine science should be established by the communication community, which emphasizes the ‘Why’ of Ocean science and MSC. This should be based on the rationale shaping the international Ocean Literacy movement

Published
2022
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10. Prevalence and course of thyroid dysfunction in neonates at high risk of Graves’ disease or with non-autoimmune hyperthyroidism

Author

Amélie Poidvin, Dominique Simon, Didier Chevenne, Caroline Storey, Juliane Léger, Nicolas de Roux, Cécile Dumaine, Jean-Claude Carel, Laetitia Martinerie, Hassina Benlarbi, and Jonathan Rosenblatt

Subjects
Male, endocrine system, medicine.medical_specialty, Pediatrics, endocrine system diseases, Endocrinology, Diabetes and Metabolism, Graves' disease, 030209 endocrinology & metabolism, Trab, Context (language use), Disease, Thyroid Function Tests, Hyperthyroidism, Thyroid function tests, Infant, Newborn, Diseases, Cohort Studies, 03 medical and health sciences, Neonatal Screening, 0302 clinical medicine, Endocrinology, Pregnancy, Risk Factors, Internal medicine, Prevalence, medicine, Central hypothyroidism, Humans, Genetic Predisposition to Disease, medicine.diagnostic_test, business.industry, Infant, Newborn, Infant, General Medicine, Prognosis, medicine.disease, Thyroid Diseases, Graves Disease, Pregnancy Complications, 030220 oncology & carcinogenesis, Disease Progression, Female, Maternal Inheritance, Thyroid function, business, hormones, hormone substitutes, and hormone antagonists
Abstract

Objective Neonatal hyperthyroidism may be caused by a permanent non-autoimmune genetic disorder or, more frequently, by maternally transmitted high serum TRAb levels. Variable thyroid dysfunction may be observed in this second context. We aimed to evaluate the prevalence of neonatal non-autoimmune hyperthyroidism and of the different types of thyroid function in neonates with a high risk of hyperthyroidism due to maternal Graves’ disease (GD). Design and methods This observational cohort study included all neonates identified in the database of a single academic pediatric care center, over a period of 13 years, as having non-autoimmune hyperthyroidism or an autoimmune disorder with high TRAb levels (above 6 IU/L) transmitted by their mothers. Patients were classified as having neonatal hyperthyroidism, hypothyroidism, or euthyroidism with a permanent or transient disorder. Results Two of the 34 consecutive neonates selected (6%) had permanent non-autoimmune hyperthyroidism due to germline (n = 1) or somatic (n = 1) mutations of the TSH receptor gene. The patients with high serum TRAb levels at birth had transient hyperthyroidism (n = 23), hypothyroidism (primary n = 2, central n = 3) or persistent euthyroidism (n = 4). Conclusion These original findings highlight the need for careful and appropriate monitoring of thyroid function in the long term, not only for the rare patients with non-autoimmune neonatal hyperthyroidism, but also for repeat monitoring during the first month of life in neonates with maternally transmitted high TRAb levels, to ensure the early identification of thyrotoxicosis in more than two thirds of cases and to detect primary or central hypothyroidism, thereby potentially decreasing associated morbidity.

Published
2021

11. Prevalence and clinical characteristics of isolated forms of central precocious puberty: a cohort study at a single academic center

Author

Dominique Simon, Emmanuel Ecosse, Caroline Storey, Laetitia Martinerie, Nicolas de Roux, Jean-Claude Carel, Carole Harbulot, Soucounda Lessim, and Juliane Léger

Subjects
Male, Pediatrics, medicine.medical_specialty, Referral, Endocrinology, Diabetes and Metabolism, Birth weight, Central precocious puberty, Puberty, Precocious, 030209 endocrinology & metabolism, Cohort Studies, 03 medical and health sciences, 0302 clinical medicine, Endocrinology, Internal medicine, Prevalence, Birth Weight, Humans, Medicine, Family, Child, Medical History Taking, business.industry, Infant, Newborn, General Medicine, Prognosis, Penetrance, Pathophysiology, Pedigree, Phenotype, 030220 oncology & carcinogenesis, Etiology, Female, Observational study, business, Hypothalamic Diseases, Cohort study
Abstract

Objective Isolated central precocious puberty (CPP) includes sporadic, familial and adoption-related forms, and the characterization of its etiology is challenging. This study investigated the prevalence and clinical characteristics of isolated CPP. Design and methods This observational cohort study included all patients (n = 395) with CPP included in the database of a single academic pediatric care center over a period of 11.5 years. Results In total, 332 of the 395 patients (84%) had isolated forms of CPP; the proportion of male patients was lower in this group than for non-isolated CPP (4 vs 33%, P < 0.0001). These patients had sporadic (n = 228, 68.5%), familial (n = 82, 25%) or adoption-related (n = 22, 6.5%) forms. Clinical characteristics at diagnosis were similar between groups, but girls with sporadic CPP were older at referral than those with familial or adoption-related CPP (P < 0.02), and birth weight SDS was lower in adopted patients than in those from the sporadic and familial groups (P < 0.01). In the 72 families containing patients with familial forms, both recessive and dominant transmissions were observed between first-degree relatives. Potential maternal or paternal transmission was identified in two-thirds of the studied families, in similar proportions. An autosomal dominant mode of transmission with low penetrance was suggested by the high proportion of affected parents (33 of the 72 families, 46%). Clinical presentation was similar whatever the mode of inheritance. Conclusion These findings highlight the need for careful monitoring of the various forms of CPP. Future studies should explore pathophysiological mechanisms, particularly for familial forms.

Published
2021

12. Expanding DSD Phenotypes Associated with Variants in the DEAH-Box RNA Helicase DHX37

Author

Anu Bashamboo, Mehdi Totonchi, Masomeh Askari, Dominique Simon, Joelle Bignon-Topalovic, Daisylyn Senna Tan, Raja Brauner, Dalila Satta, Noureddine Abadi, Yasmina Benelmadani, Inas Mazen, Djalila Rezgoune, Karima Sifi, Asmahane Ladjouze, Mehrshad Seresht-Ahmadi, Mandana Rastari, Juliane Léger, Ralf Jauch, Housna Zidoune, Ken McElreavey, Laetitia Martinerie, Asma Boukri, Génétique du Développement humain - Human developmental genetics, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Université frères Mentouri Constantine I (UMC), Université Salah Boubnider Constantine 3, Centre de Référence des Maladies Endocriniennes Rares de la Croissance [APHP Robert Debré], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Robert Debré-Université Paris Cité (UPCité), The Chinese University of Hong Kong [Hong Kong], Academic Center for Education, Culture and Research (ACECR), Centre Hospitalier Universitaire de Bab-el-Oued, Centre Hospitalier Universitaire de Bab-el-Oued, Alger, Algérie., CHU Ibn Badis Constantine [Algérie], National Research Center [Caire, Egypte], Fondation Ophtalmologique Adolphe de Rothschild [Paris], Université Paris Descartes - Paris 5 (UPD5), ANR-17-CE14-0038,MGonDev,Etude des mécanismes du développement des gonades chez l'homme(2017), ANR-19-CE14-0012,RNA-SEX,Fonction de l'ARN hélicase dans la détermination du sexe chez les vertébrés et les troubles du développement du sexe chez l'homme (DSD)(2019), and ANR-19-CE14-0022,SexDiff,Régulation de la détermination du sexe et de la différenciation ovarienne : implications dans les troubles du développement sexuel(2019)

Subjects
Male, DHX37, Disorders of sexual development, endocrine system, Embryology, Ribosomopathy, [SDV]Life Sciences [q-bio], Endocrinology, Diabetes and Metabolism, Genetic disease, XY DSD, Gonadal dysgenesis, Biology, Gonadal Dysgenesis, XY gonadal dysgenesis, Ambiguous genitalia, Testis, Testicular regression syndrome, medicine, Humans, Missense mutation, Gonadal Dysgenesis, 46,XY, Genetics, Sex determination/differentiation, medicine.disease, RNA Helicase A, Phenotype, Testicular Regression, RNA Helicases, Developmental Biology, Congenital disorder
Abstract

Missense variants in the RNA-helicase DHX37 are associated with either 46,XY gonadal dysgenesis or 46,XY testicular regression syndrome (TRS). DHX37 is required for ribosome biogenesis, and this subgroup of XY DSD is a new human ribosomopathy. In a cohort of 140 individuals with 46,XY DSD, we identified 7 children with either 46,XY complete gonadal dysgenesis or 46,XY TRS carrying rare or novel DHX37 variants. A novel p.R390H variant within the RecA1 domain was identified in a girl with complete gonadal dysgenesis. A paternally inherited p.R487H variant, previously associated with a recessive congenital developmental syndrome, was carried by a boy with a syndromic form of 46,XY DSD. His phenotype may be explained in part by a novel homozygous loss-of-function variant in the NGLY1 gene, which causes a congenital disorder of deglycosylation. Remarkably, a homozygous p.T477H variant was identified in a boy with TRS. His fertile father had unilateral testicular regression with typical male genital development. This expands the DSD phenotypes associated with DHX37. Structural analysis of all variants predicted deleterious effects on helicase function. Similar to all other known ribosomopathies, the mechanism of pathogenesis is unknown.

Published
2021

13. Impact of diabetes on COVID-19 prognosis beyond comorbidity burden: the CORONADO initiative

Author

Bertrand, Cariou, Matthieu, Wargny, Anne-Sophie, Boureau, Sarra, Smati, Blandine, Tramunt, Rachel, Desailloud, Maylis, Lebeault, Coralie, Amadou, Deborah, Ancelle, Beverley, Balkau, Lyse, Bordier, Sophie, Borot, Muriel, Bourgeon, Olivier, Bourron, Emmanuel, Cosson, Martin, Eisinger, Céline, Gonfroy-Leymarie, Jean-Baptiste, Julla, Lucien, Marchand, Laurent, Meyer, Dominique, Seret-Bégué, Dominique, Simon, Ariane, Sultan, Charles, Thivolet, Anne, Vambergue, Camille, Vatier, Patrice, Winiszewski, Pierre-Jean, Saulnier, Bernard, Bauduceau, Pierre, Gourdy, Samy, Hadjadj, Centre hospitalier universitaire de Nantes (CHU Nantes), unité de recherche de l'institut du thorax UMR1087 UMR6291 (ITX), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Nantes Université - UFR de Médecine et des Techniques Médicales (Nantes Univ - UFR MEDECINE), Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ), Centre d’Investigation Clinique de Nantes (CIC Nantes), Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre hospitalier universitaire de Nantes (CHU Nantes), Service de Santé publique - Clinique des données [CHU Nantes] (Pôle Hospitalo-Universitaire 11), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Institut des Maladies Métaboliques et Casdiovasculaires (UPS/Inserm U1297 - I2MC), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Amiens-Picardie, Périnatalité et Risques Toxiques - UMR INERIS_I 1 (PERITOX), Institut National de l'Environnement Industriel et des Risques (INERIS)-Université de Picardie Jules Verne (UPJV)-CHU Amiens-Picardie, Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), Centre Hospitalier Sud Francilien, Université Paris-Saclay, CH Le Havre, Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Hôpital d'Instruction des Armées Begin, Service de Santé des Armées, Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), AP-HP - Hôpital Antoine Béclère [Clamart], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)), École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPCité), Institut de Cardiométabolisme et Nutrition = Institute of Cardiometabolism and Nutrition [CHU Pitié Salpêtrière] (IHU ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Hôpital Avicenne [AP-HP], Centre de Recherche en Nutrition Humaine d'Ile-de-France (CRNH-IDF), Institut de Veille Sanitaire (INVS)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Institut National Agronomique Paris-Grignon (INA P-G)-CETAF-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Sorbonne Paris Nord, Centre Intégré Nord Francilien de l'Obésité (CINFO), Unité de Recherche en Epidémiologie Nutritionnelle (UREN), Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Sorbonne Paris Nord, Hôpital de la Conception [CHU - APHM] (LA CONCEPTION), Centre recherche en CardioVasculaire et Nutrition = Center for CardioVascular and Nutrition research (C2VN), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Centre Hospitalier René Dubos [Pontoise], Hôpital Lariboisière-Fernand-Widal [APHP], Centre hospitalier Saint Joseph - Saint Luc [Lyon], Les Hôpitaux Universitaires de Strasbourg (HUS), Centre Hospitalier de Gonesse, Physiologie & médecine expérimentale du Cœur et des Muscles [U 1046] (PhyMedExp), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Hospices Civils de Lyon (HCL), Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Société Francophone du Diabète, Partenaires INRAE, CHU Lille, CHU Saint-Antoine [AP-HP], Centre de Recherche Saint-Antoine (CRSA), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Hôpital Nord Franche-Comté [Hôpital de Trévenans] (HNFC), CIC - Poitiers, Université de Poitiers-Centre hospitalier universitaire de Poitiers (CHU Poitiers)-Direction Générale de l'Organisation des Soins (DGOS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre hospitalier universitaire de Poitiers (CHU Poitiers), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), École pratique des hautes études (EPHE), Centre National de Référence des Pathologies Rares de l'Insulino-Sécrétion et de l'Insulino-Sensibilité [CHu Saint-Antoine] (PRISIS), and MORNET, Dominique

Subjects
Male, SARS-CoV-2, Endocrinology, Diabetes and Metabolism, [SDV]Life Sciences [q-bio], Diabetes, Charlson index, COVID-19, Comorbidity, Prognosis, [SDV] Life Sciences [q-bio], Death, Cohort Studies, Internal Medicine, Diabetes Mellitus, Humans, Female, Invasive mechanical ventilation
Abstract

International audience; Aims/hypothesis: Diabetes has been recognised as a pejorative prognostic factor in coronavirus disease 2019 (COVID-19). Since diabetes is typically a disease of advanced age, it remains unclear whether diabetes remains a COVID-19 risk factor beyond advanced age and associated comorbidities. We designed a cohort study that considered age and comorbidities to address this question.Methods: The Coronavirus SARS-CoV-2 and Diabetes Outcomes (CORONADO) initiative is a French, multicentric, cohort study of individuals with (exposed) and without diabetes (non-exposed) admitted to hospital with COVID-19, with a 1:1 matching on sex, age (±5 years), centre and admission date (10 March 2020 to 10 April 2020). Comorbidity burden was assessed by calculating the updated Charlson comorbidity index (uCCi). A predefined composite primary endpoint combining death and/or invasive mechanical ventilation (IMV), as well as these two components separately, was assessed within 7 and 28 days following hospital admission. We performed multivariable analyses to compare clinical outcomes between patients with and without diabetes.Results: A total of 2210 pairs of participants (diabetes/no-diabetes) were matched on age (mean±SD 69.4±13.2/69.5±13.2 years) and sex (36.3% women). The uCCi was higher in individuals with diabetes. In unadjusted analysis, the primary composite endpoint occurred more frequently in the diabetes group by day 7 (29.0% vs 21.6% in the no-diabetes group; HR 1.43 [95% CI 1.19, 1.72], p

Published
2021

15. SRY ‐negative 46,XX testicular/ovotesticular DSD: Long‐term outcomes and early blockade of gonadotropic axis

Author

Cécile Brachet, Michel Peuchmaur, Juliane Léger, Capucine Hyon, Jean-Claude Carel, Claire Bouvattier, Alaa El Ghoneimi, Matthieu Peycelon, Dominique Simon, Ken McElreavey, Jérôme Bouligand, Jean-Pierre Siffroi, Dinane Samara-Boustani, Annabel Paye-Jaouen, Laurence Dumeige, Sophie Lambert, Laetitia Martinerie, Elodie Fiot, Centre de Référence des Maladies Endocriniennes Rares de la Croissance [APHP Robert Debré], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Robert Debré-Université Paris Cité (UPCité), Clinique CHC MontLégia [Liège, Belgium], Hôpital Universitaire des Enfants Reine Fabiola [Bruxelles, Belgique] (HUDERF), Service d'endocrinologie, gynécologie et diabétologie pédiatriques [CHU Necker], CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Maladies génétiques d'expression pédiatrique [CHU Trousseau] (Inserm U933), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), UF de Génétique moléculaire [CHU Trousseau], CHU Trousseau [APHP], Signalisation Hormonale, Physiopathologie Endocrinienne et Métabolique, Université Paris-Sud - Paris 11 (UP11)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), Service de Pathologie [Hôpital Robert Debré - APHP], Sorbonne Paris Cité-Hôpital Robert Debré-Université Paris Diderot - Paris 7 (UPD7), Service de Génétique Moléculaire Pharmacogénétique et Hormonologie [CHU Bicêtre], AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), UF de Génétique chromosomique [CHU Trousseau], Institut Pasteur [Paris] (IP), GHU AP-HP Centre Université de Paris, Service d'endocrinologie pédiatrique [CHU Bicêtre], Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Couvet, Sandrine, Maladies génétiques d'expression pédiatrique (U933), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Génétique du Développement humain - Human developmental genetics, and Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)

Subjects
Male, medicine.medical_specialty, Endocrinology, Diabetes and Metabolism, media_common.quotation_subject, [SDV]Life Sciences [q-bio], Population, 030209 endocrinology & metabolism, Ovary, [SDV.GEN.GH] Life Sciences [q-bio]/Genetics/Human genetics, Y chromosome, 03 medical and health sciences, 0302 clinical medicine, Endocrinology, Internal medicine, Testis, medicine, Humans, Girl, education, testicular DSD, media_common, Retrospective Studies, Gynecology, Pregnancy, education.field_of_study, minipuberty, business.industry, Virilization, XX-SRY-negative DSD, Infant, Newborn, medicine.disease, Blockade, Ovotesticular Disorders of Sex Development, [SDV] Life Sciences [q-bio], GnRH analog, Testis determining factor, medicine.anatomical_structure, [SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics, 030220 oncology & carcinogenesis, Female, ovotesticular DSD, medicine.symptom, business
Abstract

International audience; Objective: SRY-negative 46,XX testicular and ovotesticular disorders/differences of sex development (T/OTDSD) represent a very rare and unique DSD condition where testicular tissue develops in the absence of a Y chromosome. To date, very few studies have described the phenotype, clinical and surgical management and long-term outcomes of these patients. Particularly, early blockade of the gonadotropic axis in patients raised in the female gender to minimize postnatal androgenization has never been reported.Design: Retrospective description of sixteen 46,XX T/OTDSD patients.Results: Sixteen 46,XX SRY-negative T/OTDSD were included. Most (12/16) were diagnosed in the neonatal period. Sex of rearing was male for six patients and female for ten, while the clinical presentation varied, with an external masculinization score from 1 to 10. Five patients raised as girl were successfully treated with GnRH analog to avoid virilization during minipuberty. Ovotestes/testes were found bilaterally for 54% of the patients and unilaterally for the others (with a contralateral ovary). Gonadal surgery preserved appropriate tissue in the majority of cases. Spontaneous puberty occurred in two girls and one boy, while two boys required hormonal induction of puberty. One of the girls conceived spontaneously and had an uneventful pregnancy. DNA analyses (SNP-array, next-generation sequencing and whole-exome sequencing) were performed. A heterozygous frameshit mutation in the NR2F2 gene was identified in one patient.Conclusions: This study presents a population of patients with 46,XX SRY-negative T/OTDSD. Early blockade of gonadotropic axis appears efficient to reduce and avoid further androgenization in patients raised as girls.

Published
2021

16. The NSs protein encoded by the virulent strain of Rift Valley fever virus targets the expression of Abl2 and the actin cytoskeleton of the host affecting cell mobility, cell shape and cell-cell adhesion

Author

Jean-Jacques Panthier, Magali Boissière, Dominique Simon, Marie Flamand, Mattea Romani, Sylvie Soues, Zeyni Mansuroglu, Florence Niedergang, Vasco Marcato, Carole Tamietti, Eliette Bonnefoy, Aline Bamia, Guanfang Tian, Niedergang, Florence, BLANC - Identification de voies cellulaires et de gènes clés pour la pathogénicité et la résistance au virus de la fièvre de la Vallée du Rift - - GenRift2011 - ANR-11-BSV3-0007 - BLANC - VALID, Centre interdisciplinaire chimie biologie-Paris (CICB-Paris FR3567), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Virologie Structurale - Structural Virology, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Institut Cochin (IC UM3 (UMR 8104 / U1016)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Génétique fonctionnelle de la Souris, Agence Nationale de la Recherche (ANR) provided funding to Eliette Bonnefoy, Marie Flamand, and Jean-Jacques Panthier under grant number ANR-11-BSV3-007. The DIM-Malinf project from Région Ile-de-France provided funding to Vasco Marcato., ANR-11-BSV3-0007,GenRift,Identification de voies cellulaires et de gènes clés pour la pathogénicité et la résistance au virus de la fièvre de la Vallée du Rift(2011), Université Paris Descartes - Paris 5 (UPD5)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC), Centre National de la Recherche Scientifique (CNRS)-Institut Pasteur [Paris], and Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP)

Subjects
actin cytoskeleton, innate antiviral response, Rift Valley Fever, Virulence Factors, Immunology, Virulence, Viral Nonstructural Proteins, Biology, Virus Replication, Microbiology, Arbovirus, Cell Line, Adherens junction, Mice, 03 medical and health sciences, Cell Movement, Virology, Cell Adhesion, medicine, Animals, Cell adhesion, Cell Shape, Pathogen, 030304 developmental biology, [SDV.MP.VIR] Life Sciences [q-bio]/Microbiology and Parasitology/Virology, 0303 health sciences, Abl2, 030302 biochemistry & molecular biology, Protein-Tyrosine Kinases, medicine.disease, Actin cytoskeleton, Rift Valley fever virus, Immunity, Innate, Virus-Cell Interactions, 3. Good health, Viral replication, Insect Science, Host-Pathogen Interactions, Mutation, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Ectopic expression
Abstract

International audience; Rift Valley fever virus (RVFV) is a highly pathogenic zoonotic arbovirus endemic in many African countries and the Arabian Peninsula. Animal infections cause high rates of mortality and abortion among sheep, goats, and cattle. In humans, an estimated 1 to 2% of RVFV infections result in severe disease (encephalitis, hepatitis, or retinitis) with a high rate of lethality when associated with hemorrhagic fever. The RVFV NSs protein, which is the main virulence factor, counteracts the host innate antiviral response to favor viral replication and spread. However, the mechanisms underlying RVFV-induced cytopathic effects and the role of NSs in these alterations remain for the most part unknown. In this work, we have analyzed the effects of NSs expression on the actin cytoskeleton while conducting infections with the NSs-expressing virulent (ZH548) and attenuated (MP12) strains of RVFV and the non-NSs-expressing avirulent (ZH548ΔNSs) strain, as well as after the ectopic expression of NSs. In macrophages, fibroblasts, and hepatocytes, NSs expression prevented the upregulation of Abl2 (a major regulator of the actin cytoskeleton) expression otherwise induced by avirulent infections and identified here as part of the antiviral response. The presence of NSs was also linked to an increased mobility of ZH548-infected cells compared to ZH548ΔNSs-infected fibroblasts and to strong changes in cell morphology in nonmigrating hepatocytes, with reduction of lamellipodia, cell spreading, and dissolution of adherens junctions reminiscent of the ZH548-induced cytopathic effects observed in vivo. Finally, we show evidence of the presence of NSs within long actin-rich structures associated with NSs dissemination from NSs-expressing toward non-NSs-expressing cells.IMPORTANCE: Rift Valley fever virus (RVFV) is a dangerous human and animal pathogen that was ranked by the World Health Organization in 2018 as among the eight pathogens of most concern for being likely to cause wide epidemics in the near future and for which there are no, or insufficient, countermeasures. The focus of this work is to address the question of the mechanisms underlying RVFV-induced cytopathic effects that participate in RVFV pathogenicity. We demonstrate here that RVFV targets cell adhesion and the actin cytoskeleton at the transcriptional and cellular level, affecting cell mobility and inducing cell shape collapse, along with distortion of cell-cell adhesion. All these effects may participate in RVFV-induced pathogenicity, facilitate virulent RVFV dissemination, and thus constitute interesting potential targets for future development of antiviral therapeutic strategies that, in the case of RVFV, as with several other emerging arboviruses, are presently lacking.

Published
2020

17. Early Determinants of Thyroid Function Outcomes in Children with Congenital Hypothyroidism and a Normally Located Thyroid Gland: A Regional Cohort Study

Author

Carole Saba, Jean-Claude Carel, Damir Mohamed, Dominique Simon, D. Zenaty, Jeremie Haignere, Caroline Storey, Sophie Guilmin-Crepon, Sophie Dos Santos, Juliane Léger, Laetitia Martinerie, and Anne Paulsen

Subjects
Male, Pediatrics, medicine.medical_specialty, endocrine system diseases, Endocrinology, Diabetes and Metabolism, Thyroid Gland, 030209 endocrinology & metabolism, Thyroid Function Tests, Thyroid function tests, Cohort Studies, 03 medical and health sciences, Transient hypothyroidism, Neonatal Screening, 0302 clinical medicine, Endocrinology, 030225 pediatrics, Congenital Hypothyroidism, Prevalence, Humans, Medicine, medicine.diagnostic_test, business.industry, Incidence (epidemiology), Thyroid, Infant, Newborn, Prognosis, medicine.disease, Infant newborn, Congenital hypothyroidism, medicine.anatomical_structure, Child, Preschool, Female, Thyroid function, business, Cohort study
Abstract

An increase in the incidence of congenital hypothyroidism (CH) with a normally located gland has been reported worldwide. Affected individuals display transient or permanent CH during follow-up in childhood. This study aimed to determine the prevalence of transient CH and to investigate the possibility of distinguishing between transient and permanent CH in early infancy.This observational cohort study included all patients identified by systematic neonatal screening for CH in the northern Parisian region between 2002 and 2012 and treated for CH with a normally sited gland. A standardized data collection form was completed prospectively at diagnosis. Patients were classified during follow-up as having transient or permanent CH.Of the 92 patients initially treated for CH with a normally located gland during the neonatal period, 49 (54%) had a transient form of CH after the cessation of levothyroxine (LT4) treatment at 1.5 (0.6-3.2) years of age. Multivariate analysis revealed that transient CH was associated with a lower likelihood of having a first-degree family history of CH (p = 0.03) and a lower LT4 dose at six months of age (p = 0.03) than permanent CH. Sex, ethnicity, neonatal problems (e.g., prematurity, being small for gestational age, and/or neonatal distress), iodine status, coexisting malformations, initial CH severity, and thyroid morphology at diagnosis had no effect. Receiver operating characteristics curve analysis showed that a cutoff of 3.2 μg/kg/day for LT4 dose requirement at six months of age had a sensitivity of 71% and a specificity of 79% for predicting transient CH, with values below this threshold considered predictive of transient CH.In patients with CH and a normally located gland, these findings highlight the need to evaluate LT4 dose requirements early, at six months of age, particularly in patients with no family history of CH, for early identification of the approximately 50% of patients for whom treatment should be stopped.

Published
2018

18. SMS-based intervention in type 2 diabetes: clinical trial in Senegal

Author

Beverley Balkau, Dominique Simon, Line Kleinebreil, Matthieu Wargny, Saïd Norou Diop, Mady Ba, and Maimouna Ndour-Mbaye

Subjects
Complete data, medicine.medical_specialty, Short Message Service, business.industry, Psychological intervention, 030209 endocrinology & metabolism, General Medicine, Type 2 diabetes, medicine.disease, Clinical trial, 03 medical and health sciences, 0302 clinical medicine, Quartile, Family medicine, Intervention (counseling), Clinical endpoint, medicine, 030212 general & internal medicine, business
Abstract

ObjectiveSince 2014 Senegal has benefited from regular awareness-raising Short Message Service (SMS) campaigns (Be He@lthy, Be Mobile initiative) directed at people who have signed up, for free, to the ‘mDiabète’ programme. We report on an evaluation of its impact on diabetes control.DesignThe clinical trial was designed to send daily SMS during 3 months to people with type 2 diabetes. Due to centre randomisation, SMS were sent from inclusion (M0) to month 3 (M3) to people in centre S and from M3 to month 6 (M6) to people in centre P.SettingMedical centre S in the northwestern suburbs of Dakar; centre P in Popenguine, 70 km south of Dakar.ParticipantsIn February 2017, people with type 2 diabetes were consecutively recruited in the two centres. Complete data were available from 186 of these people.Main outcome measuresHbA1c was measured in the two centres with the same assay throughout the study. The primary end point was the difference between centres for the change in HbA1c from M0 to M3. Secondary end points were the evolution of HbA1c in centres S and P between M3 and M6.ResultsThe HbA1c change from M0 to M3 in centre S was better than in centre P, with a median difference of −0.4%, quartiles (−1.0; 0.3) versus 0.2% (-0.5; 0.8), respectively (p=0.0038). HbA1c decreased over the 3 months after having stopped SMS in centre S and was confirmed in centre P. The campaign cost was €2.5 (US$3.1) per person.ConclusionsIn Senegal, SMS sending was associated with an improved glycaemic control in people with type 2 diabetes. As SMS has a high penetration in low-income, middle-income countries where medical resources are scarce, health interventions using mobile telephones should be developed to facilitate exchanges between people with diabetes and medical teams; this may reduce diabetes-related complications.

Published
2018

20. Association of fasting serum insulin and cancer mortality in a healthy population – 28-year follow-up of the French TELECOM Study

Author

Matthieu Wargny, Philippe Giral, Beverley Balkau, Dominique Simon, Céline Lange, Marie-Aline Charles, unité de recherche de l'institut du thorax UMR1087 UMR6291 (ITX), Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Institute of cardiometabolism and nutrition (ICAN), Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Épidémiologie et recherches translationnelles sur les maladies rénales et cardiovasculaires (EPREC) (U1018 (Équipe 5)), Centre de recherche en épidémiologie et santé des populations (CESP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris-Sud - Paris 11 (UP11)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris-Sud - Paris 11 (UP11)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité (CRESS (U1153 / UMR_A_1125 / UMR_S_1153)), Université Paris Diderot - Paris 7 (UPD7)-Université Sorbonne Paris Cité (USPC)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Recherche Agronomique (INRA), none, Unité de recherche de l'institut du thorax (ITX-lab), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National de la Recherche Agronomique (INRA)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [APHP], Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM), unité de recherche de l'institut du thorax UMR1087 UMR6291 ( ITX ), Université de Nantes ( UN ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Institute of cardiometabolism and nutrition ( ICAN ), Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Assistance publique - Hôpitaux de Paris (AP-HP)-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -CHU Pitié-Salpêtrière [APHP], Epidémiologie rénale et cardiovasculaire ( Equipe 5 : EpReC ), Centre de recherche en épidémiologie et santé des populations ( CESP ), Université de Versailles Saint-Quentin-en-Yvelines ( UVSQ ) -Université Paris-Sud - Paris 11 ( UP11 ) -Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université de Versailles Saint-Quentin-en-Yvelines ( UVSQ ) -Université Paris-Sud - Paris 11 ( UP11 ) -Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité ( CRESS (U1153 / UMR_A 1125) ), Institut National de la Recherche Agronomique ( INRA ) -Université Sorbonne Paris Cité ( USPC ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Balkau, Beverley, and Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Recherche Agronomique (INRA)-Université Paris Descartes - Paris 5 (UPD5)-Université Sorbonne Paris Cité (USPC)

Subjects
Adult, Male, medicine.medical_specialty, Fasting serum insulin, Epidemiology, Endocrinology, Diabetes and Metabolism, Population, 030209 endocrinology & metabolism, Cancer mortality, Type 2 diabetes, Ethnic origin, 03 medical and health sciences, 0302 clinical medicine, Endocrinology, Insulin resistance, Neoplasms, Internal medicine, Diabetes mellitus, Internal Medicine, medicine, Humans, Insulin, education, 2. Zero hunger, education.field_of_study, Proportional hazards model, business.industry, MESH : Cancer mortality, Fasting serum insulin, Diabetes, Cohort study, Epidemiology, Fractional polynomial, Diabetes, [ SDV.SPEE ] Life Sciences [q-bio]/Santé publique et épidémiologie, Fasting, General Medicine, Middle Aged, medicine.disease, 3. Good health, Diabetes Mellitus, Type 2, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, 030220 oncology & carcinogenesis, MESH: Cancer mortality, Fasting serum insulin, Diabetes, Cohort study, Epidemiology, Fractional polynomial, Fractio, Female, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, France, Cohort study, business, Body mass index
Abstract

some of the above not known at this stage; International audience; Aims—Epidemiologic, pharmacoepidemiologic and pathophysiologic evidence points consistently to an association between type 2 diabetes and cancer. This asso-ciation could be explained by hyperinsulinemia induced by insulin resistance. We studied the association between fasting serum insulin (FSI) and cancer mortality in a population of non-diabetic individuals.Methods—We followed 3117 healthy workers (50.2% women), included in the TEL-ECOM cohort study, between 1985 and 1987; their median age was 38 years (Q1-Q3 = 30-50). Baseline FSI was measured by radioimmunoassay, the INSI-PR meth-od. People with diabetes or cancer at baseline were excluded. Vital status and caus-es of death were available until December 2013. The association between FSI and cancer deaths was analyzed by sex, using a Cox proportional hazards model with age as the time scale, adjusting for body mass index, smoking habits, alcohol con-sumption, occupational category and ethnic origin.Results—After 28 years follow-up, 330 (10.6%) deaths were reported, among which, 150 were cancer-related (80 men, 70 women). In men, the association between FSI and death by cancer was J-shaped: compared to the average FSI of 7.1 mU/l, men with 5 mU/l and 12.9 mU/l had respectively adjusted Hazard-Ratios (HR) of 1.88 (95% Confidence Interval, 1.00-3.56) and 2.30 (95% CI, 1.34-3.94). Among women, no significant association was found (adjusted HR, 1.03; 95% CI, 0.96-1.11) for an increase of 1 mU/l in FSI. Conclusion—These results strengthen the hypothesis of an independent risk of cancer death associated with extreme values of FSI, mainly the highest, among men, but not among women.

Published
2018

21. Predictors of Quality of Life and Other Patient-Reported Outcomes in the PANORAMA Multinational Study of People With Type 2 Diabetes

Author

Eveline Eschwège, Dominique Simon, H. Vandenberghe, Linda Gonder-Frederick, Clare Bradley, Klaus G. Parhofer, and Pedro de Pablos-Velasco

Subjects
Adult, Blood Glucose, Male, Research design, Pediatrics, medicine.medical_specialty, Internationality, Visual analogue scale, Cross-sectional study, Endocrinology, Diabetes and Metabolism, media_common.quotation_subject, 030209 endocrinology & metabolism, Prom, Type 2 diabetes, Anxiety, 03 medical and health sciences, 0302 clinical medicine, Quality of life, Internal Medicine, medicine, Humans, Patient Reported Outcome Measures, 030212 general & internal medicine, Aged, Glycemic, media_common, Glycated Hemoglobin, Advanced and Specialized Nursing, business.industry, Middle Aged, medicine.disease, Hypoglycemia, Cross-Sectional Studies, Treatment Outcome, Editorial, Diabetes Mellitus, Type 2, Quality of Life, Physical therapy, Female, Self Report, Worry, business
Abstract

OBJECTIVE PANORAMA, a nine-country cross-sectional type 2 diabetes study, investigated factors associated with quality of life (QoL), health status, and other patient-reported outcome measures (PROMs). RESEARCH DESIGN AND METHODS Patients were randomly or consecutively selected from primary/secondary care. PROMs included the Audit of Diabetes-Dependent Quality of Life (ADDQoL) (generic QoL item and average weighted impact [AWI] scores), Diabetes Treatment Satisfaction Questionnaire (DTSQ) (patient- and physician-completed), Hypoglycemia Fear Survey-II worry subscale, and the EuroQoL–5 Dimension visual analog scale (EQ-VAS) measuring patient-reported health. Multivariable linear regression analyses determined predictors of each PROM including patient characteristics, physician-reported adherence, complications, and glycosylated hemoglobin. RESULTS In 5,813 patients, mean PROM scores indicated that generic QoL approximated “good” (0.93); perceived impact of diabetes on QoL was negative (AWI –1.69). Treatment satisfaction exceeded physicians’ estimates (patient-reported: 29.76; physician-estimated: 27.75), but so did patients’ perceived frequency of hypo-/hyperglycemia. Worry about hypoglycemia (13.27) was apparent. Intensifying treatments to three oral agents or insulin regimens predicted worse QoL (AWI P < 0.01). Insulin alone use predicted worse QoL (generic P < 0.02; AWI P < 0.001) and hypoglycemia worry (P < 0.007). No treatment had significant associations with EQ-VAS health status. CONCLUSIONS Predictors for different PROMs differed markedly and provided insights for understanding and improving these important outcomes. Intensive treatment regimens had significant negative associations with all PROMs, except the EQ-VAS health status measure. The findings demonstrate the importance of measuring QoL alongside health status and other patient-reported outcomes when evaluating diabetes treatments with a view to protecting QoL and facilitating adherence and long-term glycemic control.

Published
2017

22. Direct Medical Costs of Type 2 Diabetes in France: An Insurance Claims Database Analysis

Author

Julie Gourmelen, Isabelle Bureau, Dominique Simon, Sylvie Dejager, Jean Dallongeville, Laurie Levy-Bachelot, B. Charbonnel, and B. Detournay

Subjects
Pharmacology, education.field_of_study, Actuarial science, business.industry, Health Policy, Population, Type 2 Diabetes Mellitus, 030209 endocrinology & metabolism, Type 2 diabetes, medicine.disease, 03 medical and health sciences, Nursing care, Indirect costs, 0302 clinical medicine, Diabetes mellitus, Health care, medicine, Per capita, Pharmacology (medical), Original Research Article, 030212 general & internal medicine, education, business, health care economics and organizations, Demography
Abstract

Objectives Our objects was to estimate the direct healthcare costs of type 2 diabetes mellitus (T2DM) in France in 2013. Methods Data were drawn from a random sample of ≈600,000 patients registered in the French national health insurances database, which covers 90% of the French population. An algorithm was used to select patients with T2DM. Direct healthcare costs from a collective perspective were derived from the database and compared with those from a control group to estimate the cost of diabetes and related comorbidities. Overall direct costs were also compared according to the diabetes therapies used throughout the year 2013. Results Cost analysis was available for a sample of 25,987 patients with T2DM (mean age 67.5 ± standard deviation 12.5; 53.9% male) matched with a control group of 76,406 individuals without diabetes. Overall per patient per year medical expenditures were €6506 ± 10,106 in the T2DM group as compared with €3668 ± 6954 in the control group. The cost difference between the two groups was €2838 per patient per year, mainly due to hospitalizations, medication and nursing care costs. Total per capita annual costs were lowest for patients receiving metformin monotherapy (€4153 ± 6170) and highest for those receiving insulin (€12,890). However, apart from patients receiving insulin, costs did not differ markedly across the different oral treatment patterns. Conclusion Extrapolating these results to the whole T2DM population in France, total direct costs of diagnosed T2DM in 2013 was estimated at over €8.5 billion. This estimate highlights the substantial economic burden of this condition on society. Electronic supplementary material The online version of this article (doi:10.1007/s41669-017-0050-3) contains supplementary material, which is available to authorized users.

Published
2017

23. Puberty During Sickle Cell Anemia In Cameroonian Children: A Case Control Study

Author

Ritha Mbono Betoko, Suzanne Sap Ngo Um, Anastasie Yanda Alima, David Chelo, Jocelyn Tony Nengom, Dominique Simon, Didier Chevenne, and Paul Koki Ndombo

Abstract

Background Puberty is reported to be impaired in children with Sickle Cell Anemia (SCA). We therefore, aimed to explore clinical and hormonal features of puberty in Cameroonian children with emphasis on the factors associated with delayed puberty during SCA.Methods During a case-control study, we included 64 children aged 8 to 18 years with SCA matched to healthy controls. We assessed height, weight, body mass index, body composition and Tanner stages. Hormonal measurements included Follicle Stimulating Hormone, Luteinizing Hormone and sex steroids (estrogens/ testosterone) with radio-immunologic assays. We used a non-parametric test (Mann U Whitney Wilcoxon) to compare the median values ​​between cases and controls. We looked into associations between severity criteria of SCA and delayed puberty through multivariate analysis.Results Delayed puberty was reported in 27.3% of girls and 10% of boys with SCA. Median age of menarche was delayed by 2 years compared to controls. SCA patients had low free fat mass compared to controls (p = 0.03). Abnormal levels of Antimullerian hormone were reported in cases. History of severe infection, acute chest syndrome as well as low hemoglobin level were associated with delayed sexual maturation in children with SCA.Conclusion Our study reveals delayed puberty in children with SCA. Moreover, puberty is affected by severity of the disease. This highlights importance of regular monitoring of puberty during follow-up of these children.

Published
2019

24. Factors Affecting Loss to Follow-Up in Children and Adolescents with Chronic Endocrine Conditions

Author

Sophie Guilmin-Crepon, Delphine Zenaty, Dominique Simon, Laetitia Martinerie, Jean-Claude Carel, Anne Paulsen, Priscilla Boizeau, Juliane Léger, Laura Atger-Lallier, and Caroline Storey

Subjects
Male, Pediatrics, medicine.medical_specialty, Multivariate analysis, Adolescent, Endocrinology, Diabetes and Metabolism, Psychological intervention, 030209 endocrinology & metabolism, Endocrine System Diseases, 03 medical and health sciences, 0302 clinical medicine, Endocrinology, Hypogonadotropic hypogonadism, Risk Factors, Turner syndrome, Health care, Epidemiology, Medicine, Endocrine system, Humans, Child, 030219 obstetrics & reproductive medicine, business.industry, Infant, Patient Acceptance of Health Care, medicine.disease, Child, Preschool, Pediatrics, Perinatology and Child Health, Chronic Disease, Female, Lost to Follow-Up, business, Cohort study
Abstract

Objective: Most children with endocrine diseases require long-term continuity of care. We investigated the prevalence of loss to follow-up (LTFU) in pediatric patients with chronic endocrine diseases and the risk factors associated with LTFU. Methods: This observational cohort study included all children with chronic endocrine diseases included in the database of a single academic pediatric care center over a period of 8 years. LTFU was defined as a lack of attendance at clinical visits for over 2 years, for unknown reasons. Results: LTFU was recorded for 154 of the 1,067 patients included (14%). Median age at diagnosis was 5.8 (0.3–11.8) vs. 1.2 (0.0–6.9) years, and age at last visit was 14.1 (9.7–16.1) vs. 11.7 (6.1–15.8) years, for the LTFU and no-LTFU groups, respectively. In multivariate analysis, the risk of LTFU increased with age at diagnosis (OR 1.18; 95% CI 1.12–1.24) and was higher for patients diagnosed before 2006 (vs. after 2006; OR 4.80; 95% CI 3.00–7.66), with fewer visits in the last 3 years (OR 0.72; 95% CI 0.65–0.80; p < 0.0001) and a lower health insurance classification (OR 1.79; 95% CI 1.10–2.89; p = 0.02). The risk of LTFU was higher for patients with isolated growth hormone deficiency than for those with other endocrine conditions, such as multiple pituitary deficiencies, hypogonadotropic hypogonadism, Turner syndrome, or thyroid, adrenal, or gonadal disorders (OR 5.24; 95% CI 1.13–24.37; p = 0.03). Conclusion: This study provides the first epidemiological data for LTFU in children and adolescents with chronic endocrine diseases. It should facilitate the targeting of interventions to improve adherence to medical care and healthcare organization during the pediatric period.

Published
2019

25. Genetic dissection of Rift Valley fever pathogenesis: Rfvs2 on mouse chromosome 11 enables survival to acute-onset hepatitis

Author

Jean-Jacques Panthier, Tania Zaverucha do Valle, Marie Flamand, Odile Burlen-Defranoux, Ana Cumano, Xavier Montagutelli, Leandro Batista, Magali Boissière, Grégory Jouvion, Denis Houzelstein, Dominique Simon-Chazottes, and Satoko Tokuda

Subjects
Pathogenesis, Hepatitis, Liver disease, medicine.anatomical_structure, medicine, Bone marrow, Viral disease, Rift Valley fever, Biology, medicine.disease, Virology, Encephalitis, Virus
Abstract

The systemic inoculation of mice with Rift Valley fever virus (RVFV) reproduces major pathological features of severe human disease, notably the acute-onset hepatitis and delayed-onset encephalitis. We previously reported that a genomic interval(Rvfs2)derived from the susceptible MBT/Pas strain is associated with reduced survival time after RVFV infection. In this study, we investigated the pathophysiological mechanisms by whichRvfs2confers increased susceptibility to BALB/c mice that are congenic forRvfs2(C.MBT-Rvfs2) after infection with virulent RVFV. Clinical traits, biochemical parameters, and histopathological features indicated similar liver damage in BALB/c and C.MBT-Rvfs2mice between the third and fifth days after infection. However, C.MBT-Rvfs2mice died at that point from acute liver injury while most BALB/c mice recovered from this condition but eventually died of encephalitis. We observed that hepatocytes proliferated actively within the infected liver of BALB/c mice on the sixth day after infection, promoting organ regeneration on the eighth day after infection and recovery from liver damage. We found that the production of infectious virions was up to 100-fold lower in the peripheral blood and liver of BALB/c compared to C.MBT-Rvfs2mice. Likewise, RVFV protein amounts were much lower in BALB/c liver compared to C.MBT-Rvfs2liver. Primary cultured hepatocytes showed higher viral replication rate in C.MBT-Rvfs2which could contribute to the susceptibility conferred byRvfs2. Using bone marrow chimera experiments, we uncovered that both hematopoietic and non-hematopoietic cells are required for the BALB/c allele ofRvfs2to exert its protective effects against the RVFV-induced acute liver disease. Taken together, we have established thatRvfs2acts as an important RVFV restriction factor by limiting virus multiplication in mice.Author SummaryRift Valley fever (RVF) is a mosquito-borne viral disease with potential to generate a public health emergency. The wide variation in RVF symptoms and severity observed within patient population suggests that natural host genetic determinants, among other factors, can influence the disease outcome. Infection of mice mimics several features of the pathology in humans, including acute-onset hepatitis and delayed-onset encephalitis. BALB/c inbred mice bearing the BALB/c haplotype at theRvfs2locus survive longer than those bearing the MBT haplotype. In this study, we investigated clinical traits, biochemical parameters, virological evidence, and histological features to characterize the pathogenesis of RVF in early and late susceptible mice. We show that animals of both groups develop acute liver disease shortly after infection. We demonstrate that, by comparison with early susceptible mice, BALB/c mice exhibit significantly reduced replication of RVF virusin vivoin the blood and liver andin vitroin primary cultured hepatocytes, and eventually self-recover from the liver damages. We use reciprocal transplantations of bone marrow cells between early and late susceptible mice to show that survival to severe liver disease requires both hematopoietic and non-hematopoietic cells. Taken together, we establishRvfs2as a single locus that enables mice to survive RVF virus-induced liver disease.

Published
2019
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26. Variable expressivity of HJV related hemochromatosis: 'Juvenile' hemochromatosis?

Author

Houda Hamdi-Rozé, Martine Ropert, Gilles Pelletier, Véronique David, Samira Aggoune, Yves Deugnier, Dominique Simon, Zeineb Ben Ali, Edouard Bardou-Jacquet, Lénaïck Détivaud, CHU Pontchaillou [Rennes], Institut de Génétique et Développement de Rennes (IGDR), Université de Rennes (UR)-Centre National de la Recherche Scientifique (CNRS)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Centre de référence des surcharges en fer rares d'origine génétique, Nutrition, Métabolismes et Cancer (NuMeCan), Institut National de la Recherche Agronomique (INRA)-Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Robert Debré, AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), HHR, ZBA, LD and EBJ gathered and analyzed the data and wrote the manuscript. HHR and VD performed the genetic testing. MR performed the biochemical testing. SA, DS, GP and YD included the patient and gathered the data. All authors critically reviewed the manuscript., Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )-Centre National de la Recherche Scientifique (CNRS)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES), Université de Rennes 1 (UR1), and Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)

Subjects
Adult, Male, medicine.medical_specialty, Iron Overload, GPI-Linked Proteins, Gastroenterology, 03 medical and health sciences, Young Adult, 0302 clinical medicine, Hepcidins, Hepcidin, Internal medicine, medicine, Humans, Age of Onset, Child, Hemochromatosis Protein, Molecular Biology, Hemochromatosis, 030304 developmental biology, Genetic testing, Hemojuvelin, 0303 health sciences, biology, medicine.diagnostic_test, Transferrin saturation, business.industry, Transferrin, Genetic Variation, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, Cell Biology, Hematology, medicine.disease, Juvenile hemochromatosis, 3. Good health, 030220 oncology & carcinogenesis, biology.protein, Molecular Medicine, Female, HAMP, Age of onset, business
Abstract

International audience; Juvenile hemochromatosis is a rare autosomal recessive disease due to variants in the Hemojuvelin (HJV) gene. Although biological features mimic HFE hemochromatosis, clinical presentation is worst with massive iron overload diagnosed during childhood.Our study describes clinical features and results of genetic testing for a group of patients initially referred for a hepcidino-deficiency syndrome and for whom HJV hemochromatosis was finally diagnosed. 662 patients with iron overload and high serum transferrin saturation were tested, and five genes (HFE, HJV, HAMP, TFR2, SLC40A1) were sequenced.Among our cohort, ten unrelated patients were diagnosed with HJV hemochromatosis. Genetic testing revealed five previously published and five undescribed variants: p.Arg41Pro, p.His180Arg, p.Lys299Glu, p.Cys361Arg and p.Ala384Val.Surprisingly, this study revealed a late age of onset in some patients, contrasting with the commonly accepted definition of “juvenile” hemochromatosis. Five of our patients were 30 years old or older, including two very late discoveries. Biological features and severity of iron overload were similar in younger and older patients.Our study brings new insight on HJV hemochromatosis showing that mild phenotype and late onset are possible. Genetic testing for HJV variants should thus be performed for all patients displaying a non-p.Cys282Tyr homozygous HFE hemochromatosis with hepcidin deficiency phenotype.

Published
2019

27. Garçonnes : Recueil d'illustrations

Author

Dominique Simon and Dominique Simon

Abstract

Ce qui vous est proposé ici c'est d'entrer, par privilège, dans le monde de ces aventureuses, déterminées dans leurs aspirations au charnel, celui de celles qui tentent par leur comportement d'incarner la réalité sensuelle de la Psychée qui n'a que faire des entraves sociétales et respectent les lois véritables du simplement désir… Celui de ces aventureuses qui trouvent en elles la force qu'il faut pour trancher d'un coup le nœud gordien des conventions sociales.À PROPOS DE L'AUTEURDominique Simon : Né en 1969, et ayant embrassé une carrière diplomatique internationale j'ai mené de front aussi celle d'écrivain. Porté par le succès de mes premiers titres publiés chez des « majors » de l'édition parisienne traduit dans le monde entier, aussi scénariste et metteur en scène, j'ai contribué à porter aux yeux du public nombre de projets. Souvent d'ailleurs sous des hétéronymes puisque j'écris aussi pour les enfants. Abordant tous les genres ou thèmes j'ai aussi une passion pour le dessin donc fondamentalement éclectique de toutes les façons…

Published
2020

28. Golgotha : Roman

Author

Stéphanie Perreault, Dominique Simon, Stéphanie Perreault, and Dominique Simon

Abstract

Qui n'a jamais entendu parler du fameux soldat romain devenu préfet en Judée, Ponce Pilate? Ses mémoires, prises en note par son scribe, n'ont a priori rien d'extraordinaire, et pourtant...À l'an 26 de notre ère, Ponce Pilate, un soldat romain rude de la classe équestre, est nommé préfet de la province romaine de Judée alors que la Palestine est la scène de soulèvements populaires.Ses mémoires, prises en note par son scribe sous sa dictée, relatent ici des faits qui, au quotidien, n'avaient rien d'extraordinaire. Or, il s'avère qu'ils ont constitué ceux qui ont précédé le plus grand événement que notre Histoire ait connu et dans lequel Pilate a joué un rôle central, nous laissant les citations connues «Ecce homo» et «Je m'en lave les mains» : l'exécution de Jésus de Nazareth.Découvrez un roman historique minutieux autour de l'un des plus grands événements de notre Histoire, la mise à mort de Jésus, rapporté du point de vue du scribe de Ponce Pilate, Eusébius.EXTRAITIl paraissait très mal en point, mais connaissant la cause de son malaise, je me gardai bien de sourire et, me composant un visage de circonstance, m'efforçai de le rassurer.- Mais non! Maître! Mais non! Tu ne vas pas mourir. Personne n'est jamais mort d'avoir un peu abusé de bon vin! C'est là tout ton mal! Hier soir, tu as bu comme un Ilote… Ce matin, tu es malade… De quoi te plains-tu? Je te l'ai déjà dit et redit, Maître, tu bois souvent trop…- Eusébius… Oh ma tête! Je n'ai que faire de tes critiques. Je veux que tu me soignes, c'est tout! Ton breuvage magique. Vite! Tu sais, ce que tu me fais boire dans ces cas-là… Vas-tu le préparer oui ou non?- Tu veux dire un rince cochon, Maître?- Donne-lui le nom que tu voudras, mais fais vite! Si tu attends encore, je sens que je vais mourir!- J'en étais sûr! Ce vin de Grec ne te vaut rien. Il est bien trop fort.- Mais tais-toi donc! Le son de ta voix me martyrise. Prépare cette potion!- Et que crois-tu donc? Il faut le temps pour faire les choses. Je ne perds pas le mien, mais ce remède doit se boire le plus chaud possible. Laisse agir le feu… Voilà! Nous y sommes! Je te préviens! J'ai forcé la dose, ce sera mauvais! Très mauvais…- Donne! Ha! C'est horrible! Assez!CE QU'EN PENSE LA CRITIQUEMais ce livre est-il réellement un fiction? Cela pourrait très bien être le reflet de la vie d'autrefois, à l'époque où les gens vivaient effectivement de cette manière, où les pauvres devaient être au service des plus riches afin de pouvoir survivre un minimum. Poignant par moment, troublant par d'autres, ou encore touchant. Un roman à lire sans hésiter. - Brigitte Alouqua, GoodreadsÀ PROPOS DE L'AUTEURStéphanie Perreault a toujours été passionnée par l'écriture et l'histoire. Ses romans impliquent toujours des recherches approfondies et celui-ci ne fait pas exception à la règle. Demeurant à Gatineau, au Quebec, elle a d'abord œuvré dans les hautes sphères gouvernementales et politiques canadiennes avant de se dédier entièrement à l'écriture.

Published
2019

29. Amours immoraux : Nouvelles érotiques

Author

Dominique Simon and Dominique Simon

Abstract

Découvrez cinq cas de perversions sexuelles extraordinaires et curieuses, basées sur les notes d'un psychanaliste. « Un livre obscène, c'est tout simplement un livre mal écrit. Le talent n'est jamais obscène. Ni à plus forte raison immoral. »Raymond Poincaré (Procès de La Chanson des Gueux, de Jean Richepin – Raymond Poincaré« Il n'existe pas de livre moral ou immoral. Les livres sont bien ou mal écrits. C'est tout. »Le portrait de Dorian Gray – Oscar WildeCe livre aurait pu s'intituler « brèves de psy » ou encore « Troubles de jouissances ». Mais comment ne pas nommer simplement ce qui est? De certains diront qu'il est question d'amours, d'autres de soumissions, ou de perversités…Quelle importance? Ce sont des faits, ces réalités que l'on ignorent ou que l'on tait. Alors, cette lecture ne peut pas nuire, pas plus qu'un roman à l'eau de rose. Toutes ces petites histoires ont été vécues, puis relatées. Certes à ne pas mettre entre toutes les mains, le plaisir sera partagé.Ces cinq nouvelles, basées sur des faits authentiques et véritables, nous font voyager dans la psyché humaine et découvrir les fantasmes et les désirs secrets. EXTRAITLa patronne la détaillait en affichant un sourire sucré.C'était une femme de très grande taille, géante même, et qui eut pu facilement travailler dans un cirque qui aurait présenté des étrangetés de la nature ; bien en chair, fessue et avantageusement michée. Voulant faire sa discrète, elle les observait du coin de l'œil avec le peu de discrétion dont elle était capable.Iris dès qu'elle l'eut envisagée Iris pensa :Nom de dieux quelle belle bête! Et sûrement très productive... Chose qu'elle appréciait particulièrement, car elle adorait ce genre d'inondation. Focalisée par l'exceptionnelle anatomie de la propriétaire, la fascinée n'avait d'attention que pour elle.David qui sans doute s'était aperçu qu'Iris ne l'écoutait plus que d'une oreille, plus intéressée par la mastodonte que par les quelques badineries ou souvenirs qu'il évoquait, continuait pourtant d'essayer de se montrer charmeur. Puis cancanier comme il l'avait toujours été en vînt à lui raconter une drôle d'histoire sur la patronne qui, dès son entrée, lui avait adressé une œillade appuyée.L'air de dire...A PROPOS DE L'AUTEUR Dominique Simon, c'est plus de trente-quatre publications à ce jour sous nom ou sous des pseudonymes…Et traduit dans le monde entier…

Published
2019

30. Central Diabetes Insipidus in Infancy With or Without Hypothalamic Adipsic Hypernatremia Syndrome: Early Identification and Outcome

Author

Dominique Simon, Adel Djermane, Monique Elmaleh, Juliane Léger, Jean-Claude Carel, and Amélie Poidvin

Subjects
Male, medicine.medical_specialty, Adolescent, Endocrinology, Diabetes and Metabolism, Pituitary Function Tests, Clinical Biochemistry, Drinking, 030209 endocrinology & metabolism, Context (language use), Biochemistry, Adipsia, Cohort Studies, 03 medical and health sciences, 0302 clinical medicine, Endocrinology, 030225 pediatrics, Internal medicine, Humans, Hypoglycemic Agents, Medicine, Deamino Arginine Vasopressin, Age of Onset, Child, Retrospective Studies, Optic nerve hypoplasia, Hypernatremia, business.industry, Sodium, Biochemistry (medical), Infant, Newborn, Infant, Septo-optic dysplasia, Retrospective cohort study, medicine.disease, Diabetes Insipidus, Neurogenic, Treatment Outcome, Child, Preschool, Diabetes insipidus, Female, business, Hyponatremia, Hypothalamic Diseases
Abstract

Context: Neonatal central diabetes insipidus (CDI) with or without adipsia is a very rare complication of various complex hypothalamic disorders. It is associated with greater morbidity and a high risk of developing both hypernatremia and hyponatremia, due to the condition itself or secondary to treatment with vasopressin analogs or fluid administration. Its outcomes have yet to be evaluated. Objective: To investigate the clinical outcomes of patients with neonatal-onset CDI or adipsic CDI with hypernatremia. Design, Setting, and Participants: All patients diagnosed with neonatal CDI in a university hospital-based observational study and followed between 2005 and 2015 were included and analyzed retrospectively. Main Outcome Measures: The various causes of CDI were grouped. Clinical outcome and comorbidities were analyzed. Results: Ten of the 12 patients had an underlying condition with brain malformations: optic nerve hypoplasia (n = 3), septo-optic dysplasia (n = 2), semilobar holoprosencephaly (n = 1), ectopic neurohypophysis (n = 3), and unilateral absence of the internal carotid artery (n = 1). The other two were idiopathic cases. During the median follow-up period of 7.8 (4.9–16.8) years, all but one patient displayed anterior pituitary deficiency. Transient CDI was found in three (25%) patients for whom a posterior pituitary hyperintense signal was observed with (n = 2) and without (n = 1) structural hypothalamic pituitary abnormalities, and with no other underlying cerebral malformations. Patients with permanent CDI with persistent adipsia (n = 4) and without adipsia (n = 5) required adequate fluid intake and various doses of desamino-D-arginine-8-vasopressin. Those with adipsia were more likely to develop hypernatremia (45 vs 33%), hyponatremia (16 vs 4%) (P < .0001), and severe neurodevelopmental delay (P < .05) than those without adipsia. Comorbidities were common. The underlying cause remains unknown at the age of 23 years for one patient with CDI and normal thirst. Conclusion: Neonatal CDI may be transient or permanent. These vulnerable patients have high rates of comorbidity and require careful monitoring.

Published
2016

31. Mutations in the maternally imprinted gene MKRN3 are common in familial central precocious puberty

Author

Mariacarolina Salerno, Nancy Mekhail, Monique Jesuran Perelroizen, Rachel Reynaud, Nicolas de Roux, Jean-Claude Carel, Delphine Zenaty, Ibrahima Ba, Juliane Léger, Muriel Houang, Gilbert Simonin, Gianpaolo De Filippo, Dominique Simon, Emmanuel Ecosse, Anne Paulsen, Simon, Dominique, Ba, Ibrahima, Mekhail, Nancy, Ecosse, Emmanuel, Paulsen, Anne, Zenaty, Delphine, Houang, Muriel, Jesuran Perelroizen, Monique, de Filippo, Gian Paolo, Salerno, Mariacarolina, Simonin, Gilbert, Reynaud, Rachel, Carel, Jean Claude, Léger, Juliane, and de Roux, Nicolas

Subjects
Male, 0301 basic medicine, Heterozygote, medicine.medical_specialty, Ubiquitin-Protein Ligases, Endocrinology, Diabetes and Metabolism, Mutation, Missense, Mothers, Puberty, Precocious, 030209 endocrinology & metabolism, Context (language use), Biology, medicine.disease_cause, Precocious puberty, MKRN3 mutations, Pituitary-gonadal-axis, Frameshift mutation, Fathers, 03 medical and health sciences, 0302 clinical medicine, Endocrinology, Internal medicine, medicine, Humans, Missense mutation, Child, Frameshift Mutation, Gene, Genetics, Mutation, Puberty, Heterozygote advantage, General Medicine, Phenotype, Pedigree, 030104 developmental biology, Italy, Ribonucleoproteins, Child, Preschool, Female, France, Genomic imprinting
Abstract

Context and objectiveIdiopathic central precocious puberty (iCPP) is defined as early activation of the hypothalamic–pituitary–gonadal axis in the absence of identifiable central lesions. Mutations of the makorin RING finger 3 (MKRN3) gene are associated with iCPP. We aimed to assess the frequency of MKRN3 mutations in iCPP and to compare the phenotypes of patients with and without MKRN3 mutations.DesignAn observational study was carried out on patients recruited at pediatric hospitals in France and Italy. Forty-six index CPP cases were screened for mutations in the MKRN3 coding sequence: 28 index cases of familial cases and 18 cases did not report any familial history of CPP. The endocrine phenotype was compared between MKRN3 mutated and non-mutated patients.ResultsMKRN3 mutations were identified in one sporadic and 13 familial cases. We identified five new heterozygous missense mutations predicted to be deleterious for protein function and two frameshift mutations, one new and the other recurrent, predicted to result in truncated proteins. Age at puberty onset varied very little among patients with MKRN3 mutations and puberty occurred earlier in these patients than in those without MKRN3 mutations (6.0 years (5.4–6.0) vs 7.0 years (6.0–7.0), P=0.01).ConclusionsMKRN3 mutations are common in familial iCPP. MKRN3 is one of the gatekeepers of the postnatal activation of the gonadotropic axis.

Published
2016

32. Growth outcomes after GH therapy of patients given long-term corticosteroids for Juvenile Idiopathic Arthritis

Author

Baptiste Louveau, Camille Aupiais, Jean-Claude Carel, Dominique Simon, Pierre Quartier, Hélène David, and Evelyne Jacqz-Aigrain

Subjects
Male, Parents, medicine.medical_specialty, Adolescent, Endocrinology, Diabetes and Metabolism, Clinical Biochemistry, Arthritis, 030209 endocrinology & metabolism, Context (language use), Growth, Logistic regression, Biochemistry, 03 medical and health sciences, 0302 clinical medicine, Endocrinology, Adrenal Cortex Hormones, Interquartile range, Internal medicine, Humans, Medicine, Juvenile, Prospective Studies, Sexual Maturation, Prospective cohort study, Child, 030203 arthritis & rheumatology, Inflammation, Human Growth Hormone, business.industry, Biochemistry (medical), Odds ratio, medicine.disease, Arthritis, Juvenile, Body Height, Confidence interval, Clinical trial, Treatment Outcome, Female, business, Follow-Up Studies
Abstract

Context Growth hormone (GH) therapy may improve statural growth outcomes in patients with severe juvenile idiopathic arthritis (JIA). Objectives To evaluate the effect of GH treatment on adult height and to identify determinants of growth outcomes in JIA. Design and Patients Data from 58 patients with JIA, including 53 receiving GH, enrolled in three prospective clinical trials between 1997 and 2002 were analyzed. Intervention GH (0.056 mg/kg/d [interquartile range (IQR), 0.050 to 0.062]) for a median duration of 6.5 years (IQR, 4.7 to 7.9 years). Main Outcome Measures Factors associated with a favorable growth outcome (adult height - target height ≤ -1.5 standard deviations) were identified by multivariate logistic regression. Results Adult height was available for 48 patients 8.6 years after GH initiation (IQR, 6.0 to 10.2 years). Height standard deviation score (SDS) increased from -2.9 (IQR, -4.4 to -1.6) at baseline to -1.7 (IQR, -3.9 to -0.1) in adulthood (P < 0.001). Median adult height was below target height [SDS, -0.2 (IQR, -1.4 to 0.4); P < 0.001]. Corrected adult height SDS was -1.3 (IQR, -3.0 to -0.2). Growth outcome was favorable in 24 (52.2%) patients. Significant independent determinants of growth outcome were age at GH initiation [adjusted odds ratio (aOR), 0.68 per additional year; 95% confidence interval (CI), 0.47 to 0.99], height at GH initiation (aOR, 2.6 per additional SDS; 95% CI, 1.15 to 5.9), and mean C-reactive protein levels during follow up (aOR, 0.51 per additional 10 mg/L; 95% CI, 0.28 to 0.92). Conclusion Long-term GH treatment significantly increased growth in patients with JIA but did not fully restore the genetic growth potential. The response showed marked interindividual variability and was weaker in patients with severe inflammation.

Published
2018

33. High prevalence of syndromic disorders in patients with non-isolated central precocious puberty

Author

Jean Claude Carel, Anne Paulsen, Laetitia Martinerie, Dominique Simon, Nicolas de Roux, Emmanuel Ecosse, D. Zenaty, Georges Gelwane, Caroline Storey, Selmen Wannes, Monique Elmaleh-Bergès, and Juliane Léger

Subjects
Male, medicine.medical_specialty, Pathology, Endocrinology, Diabetes and Metabolism, Encephalopathy, Hypothalamus, Puberty, Precocious, 030209 endocrinology & metabolism, Cohort Studies, 03 medical and health sciences, 0302 clinical medicine, Endocrinology, Internal medicine, medicine, Prevalence, Humans, Testosterone, Neurofibromatosis, Child, Optic nerve hypoplasia, Estradiol, business.industry, General Medicine, medicine.disease, Pathophysiology, Ectopic Posterior Pituitary, Child, Preschool, Autism, Female, business, Sentinel Surveillance, 030217 neurology & neurosurgery, Narcolepsy, Cohort study
Abstract

Objective Non-idiopathic CPP is caused by acquired or congenital hypothalamic lesions visible on MRI or is associated with various complex genetic and/or syndromic disorders. This study investigated the different types and prevalence of non-isolated CPP phenotypes. Design and Methods This observational cohort study included all patients identified as having non-idiopathic CPP in the database of a single academic pediatric care center over a period of 11.5 years. Patients were classified on the basis of MRI findings for the CNS as having either hypothalamic lesions or complex syndromic phenotypes without structural lesions of the hypothalamus. Results In total, 63 consecutive children (42 girls and 21 boys) with non-isolated CPP were identified. Diverse diseases were detected, and the hypothalamic lesions visible on MRI (n = 28, 45% of cases) included hamartomas (n = 17; either isolated or with an associated syndromic phenotype), optic gliomas (n = 8; with or without neurofibromatosis type 1), malformations (n = 3) with interhypothalamic adhesions (n = 2; isolated or associated with syndromic CNS midline abnormalities, such as optic nerve hypoplasia, ectopic posterior pituitary) or arachnoid cysts (n = 1). The patients with non-structural hypothalamic lesions (n = 35, 55% of cases) had narcolepsy (n = 9), RASopathies (n = 4), encephalopathy or autism spectrum disorders with or without chromosomal abnormalities (n = 15) and other complex syndromic disorders (n = 7). Conclusion Our findings suggest that a large proportion (55%) of patients with non-isolated probable non-idiopathic CPP may have complex disorders without structural hypothalamic lesions on MRI. Future studies should explore the pathophysiological relevance of the mechanisms underlying CPP in these disorders.

Published
2018

34. SFE/SFEDP adrenal insufficiency French consensus: Introduction and handbook

Author

Dinane Samara Boustani, Olivier Chabre, Bernard Goichot, Claire Bouvattier, Emmanuelle Proust-Lemoine, Frederic Castinetti, Damien Gruson, Delphine Zenaty, Laurence Guignat, Antoine Tabarin, Marie-Laure Raffin Sanson, C. Cortet, Yves Reznik, Brigitte Delemer, Pascal Barat, Rachel Reynaud, Jérôme Bertherat, Philippe Chanson, Dominique Simon, Service Endocrinologie - Diabétologie [CHU Caen], Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN), Service d’endocrinologie et diabétologie pédiatriques [CHU de Bordeaux], CHU Bordeaux [Bordeaux]-hôpital des Enfants [CHU Bordeaux], Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service d'endocrinologie pédiatrique [CHU Bicêtre], Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre de recherche en neurobiologie - neurophysiologie de Marseille (CRN2M), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service d'endocrinologie-diabétologie-nutrition [CHU Grenoble-Alpes], Centre Hospitalier Universitaire Grenoble Alpes (CHU Grenoble Alpes), Signalisation Hormonale, Physiopathologie Endocrinienne et Métabolique, AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Sud - Paris 11 (UP11), Service d'Endocrinologie et des Maladies de la Reproduction [AP-HP Hôpital de Bicêtre], AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), Service d’endocrinologie, diabétologie et maladies métaboliques [CHRU LIlle], Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Service d'Endocrinologie - Diabète - Nutrition [Reims], Université de Reims Champagne-Ardenne (URCA)-Hôpital Robert Debré-Centre Hospitalier Universitaire de Reims (CHU Reims), Service de Médecine Interne, Endocrinologie et Nutrition [CHU Strasbourg], Les Hôpitaux Universitaires de Strasbourg (HUS)-CHU Strasbourg, Département d'Endocrinologie et Nutrition [Brussels, Belgium] (LOUVAIN - Endocrino), Université Catholique de Louvain = Catholic University of Louvain (UCL), Polyclinique d’Aguilera [Biarritz], Infection et inflammation (2I), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service d’endocrinologie et nutrition [AP-HP Ambroise-Paré], Hôpital Ambroise Paré [AP-HP], Service de pédiatrie multidisciplinaire [Hôpital de la Timone Enfants - APHM], Hôpital de la Timone [CHU - APHM] (TIMONE), Service d'endocrinologie, gynécologie et diabétologie pédiatriques [CHU Necker], CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service d'Endocrinologie et Diabétologie Pédiatriques [AP-HP Hôpital Robert-Debré], Hôpital Robert Debré-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service d'Endocrinologie (BORDEAUX - Endocrino), CHU Bordeaux [Bordeaux], UCL - SSS/IREC/EDIN - Pôle d'endocrinologie, diabète et nutrition, UCL - (SLuc) Service de biochimie médicale, Centre Hospitalier Universitaire [Grenoble] (CHU), Université Paris-Sud - Paris 11 (UP11)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), CHU Strasbourg-Les Hôpitaux Universitaires de Strasbourg (HUS), and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Robert Debré

Subjects
Adult, Pediatrics, medicine.medical_specialty, Primary and secondary, Consensus, Adolescent, Pediatric endocrinology, medicine.drug_class, Endocrinology, Diabetes and Metabolism, [SDV]Life Sciences [q-bio], Primaire et secondaire, 030209 endocrinology & metabolism, Primary Adrenal Insufficiency, Adults and children, Young Adult, 03 medical and health sciences, 0302 clinical medicine, Endocrinology, Adrenocorticotropic Hormone, Adrenal insufficiency, Humans, Medicine, Congenital adrenal hyperplasia, Insuffisance surrénale, Child, Societies, Medical, Hydrocortisone, Adultes et enfants, business.industry, Adrenal crisis, General Medicine, [SDV.MHEP.EM]Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, medicine.disease, 3. Good health, Mineralocorticoid, 030220 oncology & carcinogenesis, Practice Guidelines as Topic, France, Pituitary-Adrenal Function Tests, medicine.symptom, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Blood sampling, medicine.drug
Abstract

International audience; The French endocrinology society (SFE) and the French pediatric endocrinology society (DFSDP) have drawn up recommendations for the management of primary and secondary adrenal insufficiency in the adult and child, based on an analysis of the literature by 19 experts in 6 work-groups. A diagnosis of adrenal insufficiency should be suspected in the presence of a number of non-specific symptoms except hyperpigmentation which is observed in primary adrenal insufficiency. Diagnosis rely on plasma cortisol and ACTH measurement at 8am and/or the cortisol increase after synacthen administration. When there is a persistant doubt of secondary adrenal insufficiency, insulin hypoglycemia test should be carried out in adults, adolescents and children older than 2 years. For determining the cause of primary adrenal insufficiency, measurement of anti-21-hydroxylase antibodies is the initial testing. An adrenal CT scan should be performed if auto-antibody tests are negative, then assay for very long (Y. Reznik). chain fatty acids is recommended in young males. In children, a genetic anomaly is generally found, most often congenital adrenal hyperplasia. In the case of isolated corticotropin (ACTH) insufficiency, it is recommended to first eliminate corticosteroid-induced adrenal insufficiency, then perform an hypothalamic-pituitary MRI. Acute adrenal insufficiency is a serious condition, a gastrointestinal infection being the most frequently reported initiating factor. After blood sampling for cortisol and ACTH assay, treatment should be commenced by parenteral hydrocortisone hemisuccinate together with the correction of hypoglycemia and hypovolemia. Prevention of acute adrenal crisis requires an education of the patient and/or parent in the case of pediatric patients and the development of educational programs. Treatment of adrenal insufficiency is based on the use of hydrocortisone given at the lowest possible dose, administered several times per day. Mineralocorticoid replacement is often necessary for primary adrenal insufficiency but not for corticotroph deficiency. Androgen replacement by DHEA may be offered in certain conditions. Monitoring is based on the detection of signs of under-and over-dosage and on the diagnosis of associated auto-immune disorders.; La Société française d'endocrinologie (SFE) et la Société française d'endocrinologie pédiatrique (SFEDP) ont élaboré des recommandations sur la prise en charge de l'insuffisance surrénale primaire et secondaire de l'adulte et de l'enfant, à partir d'une analyse de la littérature réalisée par 19 experts répartis en 6 groupes de travail. Le diagnostic d'insuffisance surrénale doit être évoqué devant l'association de signes cliniques et biologiques non spé-cifiques, en dehors de la mélanodermie observée dans l'insuffisance surrénale primaire. Le diagnostic repose sur les dosages du cortisol et de l'ACTH le matin et/ou le dosage du cortisol après stimulation par l'ACTH synthétique (synacthène). En cas de doute, le test d'hypoglycémie insulinique est le test de référence chez l'adulte l'adolescent et l'enfant de plus de 2 ans. La recherche étiologique est basée sur le dosage en 1 re intention des anticorps anti 21-hydroxylase. En cas de négativité, un scanner surrénalien sera réalisé, puis le dosage des acides gras à chaînes longues sera effectué chez le garçon. Chez l'enfant, une cause génétique sera recherchée, principalement l'hyperplasie congénitale des surrénales. Devant un déficit corticotrope, après la recherche d'une prise prolongée de glucocorticoïdes sera effectuée une imagerie hypothalamo-hypophysaire. L'insuffisance surrénale aiguë est une complication grave souvent déclenchée par une infection gastro-intestinale. Elle nécessite après prélèvement pour dosage du cortisol et ACTH l'administration parentérale d'hémisuccinate d'hydrocortisone et la correction de l'hypovolémie et/ou de l'hypoglycémie. Sa prévention repose sur l'éducation thérapeutique du patient pour laquelle des programmes seront développés. Le traitement de l'insuffisance surrénale s'appuie sur la prise pluriquotidienne d'hydrocortisone à la dose la plus faible possible. La substitution minéralocorticoïde est réalisée en cas d'insuffisance surrénale primaire mais n'est pas nécessaire en cas d'insuffisance surrénale secondaire. La substitution androgénique par la DHEA peut être proposée dans cer-taines indications précises. La monitoring comportera la recherche de signes cliniques et biologiques de sous/surdosage et de maladies auto-immunes associées.

Published
2018

35. Group 2: Adrenal insufficiency: screening methods and confirmation of diagnosis

Author

Antoine Tabarin, Rachel Reynaud, Laurence Guignat, Olivier Chabre, Dinane Samara Boustani, Bernard Goichot, Damien Gruson, Marie-Laure Raffin Sanson, Philippe Chanson, Yves Reznik, and Dominique Simon

Subjects
Adult, Pediatrics, medicine.medical_specialty, Consensus, Hydrocortisone, Endocrinology, Diabetes and Metabolism, 030209 endocrinology & metabolism, 030204 cardiovascular system & hematology, Primary Adrenal Insufficiency, 03 medical and health sciences, 0302 clinical medicine, Endocrinology, Adrenocorticotropic Hormone, Adrenal Cortex Hormones, Adrenal insufficiency, Medicine, Humans, Mass Screening, Congenital adrenal hyperplasia, Child, Metyrapone, business.industry, Virilization, General Medicine, medicine.disease, Surgery, Addison's disease, medicine.symptom, business, Hyponatremia, medicine.drug, Adrenal Insufficiency
Abstract

A diagnosis of adrenal insufficiency should be suspected in the presence of a number of non-specific symptoms (fatigue, anorexia, weight loss, hypotension, hyponatremia and hyperkalemia amongst adrenal causes of insufficiency). The diagnosis should be considered in case of pituitary disease or a state of shock. Treatment should be commenced immediately without waiting for confirmation from biochemical tests, which rely on cortisol level at 8am (expected to be low) and on ACTH level (expected to be high in the case of primary adrenal insufficiency). If these tests are inconclusive, a Synacthen test should be carried out. The threshold limits are provided as a guide. Low plasma cortisol and normal to low plasma ACTH indicates a pituitary origin for the deficiency. In this situation, the Synacthen test can give a false normal result, and if this adrenal insufficiency is strongly suspected, an insulin hypoglycemia test or metyrapone (Metopirone®) test should be carried out. In children younger than 2yr, hypoglycemia, dehydration and convulsions are frequently observed and in young girls, virilization is suspect of congenital adrenal hyperplasia . The circadian rhythm of cortisol is not present until after 4months of age and the Synacthen test is the only one that is feasible. In children older than 2yrs, the signs and diagnostic methods are the same as in the adult. Cessation of corticosteroid treatment is a frequent circumstance however there is little published data and no evidence for definitive guidelines. After ceasing a short period of corticosteroid treatment, patient education is all that is required. After longer treatment, consensus leaves the choice up to the physician, between educating the patient and prescribing hydrocortisone in case of stress, or prescribing low daily dose hydrocortisone and evaluating the ACTH axis over time until normal function is recovered.

Published
2017

36. Glycated heamoglobin A1c as a tool for epidemiological studies to assess diabetes prevalence: How has it been used since its official recommendation for diabetes diagnosis?

Author

Dominique Simon

Subjects
Blood Glucose, Glycated Hemoglobin, Pathology, medicine.medical_specialty, Pediatrics, Diabetes diagnosis, business.industry, Endocrinology, Diabetes and Metabolism, Diabetes prevalence, 030209 endocrinology & metabolism, General Medicine, medicine.disease, 03 medical and health sciences, Epidemiologic Studies, 0302 clinical medicine, Endocrinology, Diabetes mellitus, Epidemiology, Internal Medicine, medicine, Diabetes Mellitus, Prevalence, Humans, 030212 general & internal medicine, business
Abstract

Diabetes & Metabolism - In Press.Proof corrected by the author Available online since mardi 14 novembre 2017

Published
2017

37. Impact of the underlying etiology of growth hormone deficiency on serum IGF-I SDS levels during GH treatment in children

Author

Dominique Simon, Jean-Claude Carel, Myriam Ben Azoun, Corinne Alberti, Sophie Guilmin-Crepon, Anne Paulsen, Laetitia Martinerie, Damir Mohamed, Sophie Dos Santos, Didier Chevenne, Juliane Léger, and Delphine Zenaty

Subjects
Male, medicine.medical_specialty, Endocrinology, Diabetes and Metabolism, Injections, Subcutaneous, 030209 endocrinology & metabolism, Context (language use), Growth hormone deficiency, Cohort Studies, 03 medical and health sciences, Pubertal stage, 0302 clinical medicine, Endocrinology, Internal medicine, medicine, Humans, Insulin-Like Growth Factor I, Child, Dwarfism, Pituitary, Immunoradiometric assay, business.industry, Human Growth Hormone, Infant, General Medicine, medicine.disease, Treatment Outcome, 030220 oncology & carcinogenesis, Child, Preschool, Etiology, IGHD, Female, business, Biomarkers, Cohort study, Hormone
Abstract

ContextRegular monitoring of serum IGF-I levels during growth hormone (GH) therapy has been recommended, for assessing treatment compliance and safety.ObjectiveTo investigate serum IGF-I SDS levels during GH treatment in children with GH deficiency, and to identify potential determinants of these levels.Design, patients and methodsThis observational cohort study included all patients (n = 308) with childhood-onset non-acquired or acquired GH deficiency (GHD) included in the database of a single academic pediatric care center over a period of 10 years for whom at least one serum IGF-I SDS determination during GH treatment was available. These determinations had to have been carried out centrally, with the same immunoradiometric assay. Serum IGF-I SDS levels were determined as a function of sex, age and pubertal stage, according to our published normative data.ResultsOver a median of 4.0 (2–5.8) years of GH treatment per patient, 995 serum IGF-I SDS determinations were recorded. In addition to BMI SDS, height SDS and GH dose (P P ConclusionsThese original findings have important clinical implications for long-term management and highlight the need for careful and appropriate monitoring of serum IGF-I SDS and GH dose, particularly in patients with acquired GHD, to prevent the unnecessary impact of potential comorbid conditions.

Published
2017

38. Incidence of severe critical events in paediatric anaesthesia (APRICOT): a prospective multicentre observational study in 261 hospitals in Europe

Author

Walid Habre, Nicola Disma, Katalin Virag, Karin Becke, Tom G Hansen, Martin Jöhr, Brigitte Leva, Neil S Morton, Petronella M Vermeulen, Marzena Zielinska, Krisztina Boda, Francis Veyckemans, Walter Klimscha, Regina Konecny, Robert Luntzer, Ulrike Morawk-Wintersperger, Franz Neiger, Lydia Rustemeyer, Christian Breschan, Denise Frey, Manuela Platzer, Reinhard Germann, Joachim Oeding, Birgit Stoegermüller, Bernhard Ziegler, Philipp Brotatsch, Anton Gutmann, Gerlinde Mausser, Brigitte Messerer, Wolfgang Toller, Maria Vittinghoff, Gregor Zangl, Natascha Seidel-Ahyai, Christoph Hochhold, Ruth Kroess, Peter Paal, Steven Cnudde, Patricia Coucke, Birgit Loveniers, John Mitchell, David Kahn, Thierry Pirotte, Caroline Pregardien, Marc Coppens, Stefan De Hert, Björn Heyse, Martine Neckebroek, Aliaksandra Parashchanka, Jurgen Van Limmen, Nancy Van Den Eynde, Caroline Vanpeteghem, Piet Wyffels, Michaël Lalot, Jean-Paul Lechat, France Stevens, Sari Casaer, Françoise De Groote, Françoise De Pooter, Andrée De Villé, Marc Gerin, Natalia Magasich, Cristel Sanchez Torres, Denise Van Deenen, Johan Berghmans, Dirk Himpe, Eva Roofthooft, Ellen Joukes, Carine Smitz, Veronique Van Reeth, Christel Huygens, Julie Lauweryns, Karen De Smet, Nadia Najafi, Jan Poelaert, Anne Van de Velde, Veerle Van Mossevelde, Ivan Bekavac, Diana Butkovic, Dubravka Heli Litvic, Ivana Kerovec Soric, Hrvoje Maretic, Djurdjica Moscatello, Ljiljana Popovic, Slobodan Micici, Ivana Stuck Tus, Lada Kalagac Fabris, Tatjana Simurina, Nina Sulen, Gordana Kesic-Valpotic, Dajana Djapic, Jirí Žurek, Lucie Jureckova, Iveta Mackova, Monika Skacel, Stanislava Weinlichova, Jan Divák, Michal Frelich, René Urbanec, Vera Biskupova, Vladimir Mixa, Jana Pavlickova, Arash Afshari, Morten Bøttger, Marguerite B. Ellekvist, Mathias Johansen, Birgitte Ingeborg Madsen, Jens Christian Nilsson, Birgitte MB Schousboe, Nicola G. Clausen, Tom G. Hansen, Nick Phaff Steen, Mari-Liis Ilmoja, Virge Tonise, Juri Karjagin, Reet Kikas, Mika Isohanni, Anniina Lyly, Annika Takala, Johanna Happo, Kai Kiviluoma, Kati Martikainen, Riku Aantaa, Tuula Manner, Sanna Vilo, Catherine Amory, Hugues Ludot, Patricia Lambotte, René Busche, Olivier Jacqmarcq, Corinne Lejus, Julien Corouge, Christian Erb, Delphine Garrigue, Patricia Gillet, Anne Laffargue, Veronique Lambelin, Hélène Le Freche, Daliana Peresbota, Pierre Richart, Jerome Berton, Catherine Chapotte, Laurent Colbus, Thierry Lehousse, Jean Monrigal, Catherine Baujard, Philippe Roulleau, Giuseppe Staiti, Hélène Batoz, Maryline Bordes, Anne Didier, Yann Hamonic, Sylvaine Lagarde, Karine Nouette-Gaulain, François Semjen, Brigitte Zaghet, Jacky Dekens, Axelle Delcuze, Hervé Dupont, Aurélien Legrand, Celine Raffoflandreur, Noémie Audren, Blandine Camus, Marielle Cartal, Chantal Chazelet, Isabelle Davin, Marion Guillier, Luc Desjeux, Claire Larcher, Elodie Grein, Mickeal Leclercq, Roxana Levitchi, Lilica Rosu, Dominique Simon, Aurélien Zang, Anne Migeon, Anne-Charlotte Gagey, Nathalie Bourdaud, Anne-Charlotte Carre, Frédéric Duflo, Jean-Claude Riche, Philippe Robert, Emilie Druot, Olivier Maupain, Gilles Orliaguet, Lucie Sabau, Hanna Taright, Lynn Uhrig, Juliette Verchere-Montmayeur, Lise Debrabant, Clotaire Pilla, Alexandre Podvin, Benjamin Roth, Souhayl Dahmani, Florence Julien-Marsollier, Nada Sabourdin, Bogdan Alexandri, Gilles Brezac, Francois de la Brière, Catherine Hayem, Elizabeth Lhubat, Jean Paul Mission, Charlotte Rémond, Christophe Dadure, Maud Maniora, Anais Marie, Philippe Pirat, Anne-Charlotte Saour, Chrystelle Sola, Claude Ecoffey, Eric Wodey, Christian Adam, Thomas Standl, Ehrenfried Schindler, Tomohiro Yamamoto, Michael Brackhahn, Christoph Bernhard Eich, Holger Guericke, Petra Kindermann, Michael Laschat, Cornel Schink, Frank Wappler, Claudia Hoehne, Natalia Skordou, Johanna Ulrici, Martin Jetzek-Zader, Peter Kienbaum, Tanja Meyer-Treschan, Olaf Picker, Maximilian S. Schaefer, Golo Mielke, Sabine Baethge, Axel Ramminger, Martin Bauer, Matthias Bollinger, José Hinz, Michael Quintel, Sebastian G. Russo, Michael Bauer, Dfominik Geil, Andreas Kortgen, Niels-Peter Preussler, Ulrich Hofmann, Manfred Raber, Doris Reindl, Karin Oppenrieder, Bettina Schierlinger, Jens Roth, Wolfgang Funk, Thomas Fischer, Christian Gernoth, Christina Wiefelspütz, Hauke Volger, Nicole Zederer, Anja Diers, Matthias Huber, Clemens Schorer, Andreas Weyland, Konrad Schwarzkopf, Catharina Grau, Winfried Roth, Rolf Holy, Thomas Mader, Laura Peter, Hauke Supthut, Thomas Kuehhirt, Alexander Milde, Fritz Fiedler, Carsten Isselhorst, Ulrich Grundmann, Alexander Pattar, Jennifer Reinert, Birgit Ehm, Katrin Fritzsche, Ralf Gaebler, Patrick Meybohm, Maximilian Hein, Ines Guzman, Johanna Jokinen, Peter Kranke, Ulrich Goebel, Sarah Harris, Christoph Eisner, Miriam Ochsenreiter, Michael Schoeler, Elke Thil, Richard Ellerkmann, Andreas Hoeft, Claudia Neumann, Stefan Weber, Julia Keilhauer, Jan Kloessing, Michael Schramm, Uwe Trieschmann, Kristina Knauss, Barbara Sinner, Johannes Steinmann, Herbert Koessler, Evagelia Kalliardou, Anna Malisiova, Adelais Tsiotou, Pelagia Chloropoulou, Mpratzou Chrysi, Despoina Iordanidou, Merkourios Ntavlis, Krisztina B Boda, Christilynn Guerin, Janice Irwin, Claire Magner, Solmaz Nakhjavani, Brendan O'Hare, Deborah Galvin, Yosry Jamil, Carlos Lesmes, Yuri Barak, Haran Fisher, Ludmyla Kachko, Jacob Katz, Dmitry Kirilov, Michael Levinzon, Yair Manevich, Konstantin Nekrasov, Elia Peled, Elena Sanko, Dmitri Schmain, Olga Sheinkin, Eliahu Simhi, Alex Tarabikin, Evelina Trabkin, Irena Yagudaev, Yelena Zeitlin, Igor Zunser, Elisabetta Cerutti, Maria Maddalena Schellino, Silvia Valzan, Rosa Lucia Pinciroli, Luciano Bortone, Giorgia Cerati, Fabiana Salici, Leonardo Bussolin, Giuliana Rizzo, Francesca Rossetti, Laura Marchesini, Simonetta Tesoro, Brita De Lorenzo, Fabio Guarracino, Beate Kuppers, Marinella Astuto, Sofia Pitino, Rita Scalisi, Lucia Scordo, Sandra D'Alessandro, Luigi Dei Giudici, Ivano Farinelli, Giuseppe Lofino, Giuliano Marchetti, Sergio Giuseppe Picardo, Simone Reali, Alessandro Vittori, Francesco Antonio Idone, Maria Sammartino, Fabio Sbaraglia, Cinzia Barbera, Michela Bevilacqua, Valeria Cento, Svetlana Kotzeva, Leila Mameli, Giovanni Montobbio, Leandro Passariello, Cinzia Punzo, Rosanna Sileo, Rosanna Viacava, Claudia Volpe, Clelia Zanaboni, Edoardo Calderini, Daniele Genco, Simona Neri, Davide Ottolina, Anna Camporesi, Francesca Izzo, Ida Salvo, Andrea Wolfler, Andrea Sanna, Angela Sciascia, Paolo Stoia, Annamaria Guddo, Maria Lapi, Giorgio Ivani, Annalisa Longobardo, Valeria Mossetti, Dino Pedrotti, Maurizia Grazzini, Luisa Meneghini, Salvatore Metrangolo, Stefania Michelon, Carmelo Minardi, Costanza Tognon, Nicola Zadra, Ilaria Busi, Magda Khotcholava, Bruno Guido Locatelli, Valter Sonzogni, Giusi Starita, Nicole Almenrader, Caterina Aurilio, Pasquale Sansone, Raffaella Albarello, Paolo Bracci, Mariateresa Cecini, Maria Cristina Mondardini, Lorena Pasini, Milo Vason, Gianluca Zani, Roberto Zoppellari, Laura Pistidda, Andrea Cortegiani, Santi Maurizio Raineri, Antigona Hasani, Medita Hashimi, Agris Ancupans, Arta Barzdina, Zane Straume, Anda Zundane, Mikhail Chlopin, Dalia Gestautaite, Laura Lukosiene, Evelina Paliokaite, Ilona Razlevice, Inesa Armoniene, Aurelija Bernotiene, Vidunas Daugelavicius, Ilona Dockiene, Lina Gaidelyte, Nijole Saviciene, Jolita Krikstaponiene, Dominika Sidlovskaite-Baltake, Vladyslav Stasevski, Agne Vaitoskaite, David Gatt, Stephanie Mifsud, Simone Zammit, Celia Allison, Hamid Aslami, Susanne Eberl, Mireille F M van Stijn, Markus F Stevens, Kees Punt, Rob van Osch, Arthur Bauwman, Harm Scholten, Vesna Svircevic, Veronique Adriaens, Maaike Dirckx, Jaap Dogger, Ilse Dons-Sinke, Andreas Machotta, Xavier Moors, Mandana Rad, Lonneke Staals, Anouk van der Knijff - van Dortmont, Caroline van der Marel, Anne Sieben, Tim van der Zwan, Marianne Veldhuizen, David Alders, Wolfgang Buhre, Nicole Engel, Carine Vossen, Ravin Mahadewsing, Patrick Meijer, Volker Gerling, Roelof van der Schatte Olivier, Thea van Doorn, Kristy Vons Mark Hendriks, Sandra Lako, Gert jan Scheffer, Luc Tielens, Marieke Voet, Anthony Absalom, Margot Bergsma, Vera Spanjer, Rob Spanjersberg, Yvette van de Riet, Martin Volkers, Jurgen C. de Graaff, Geranne A.J. Hopman, Teus H. Kappen, J. Hannie, A.M. Megens, Sandra C. Numan, Anton N.J. Schouten, Nigel M. Turner, Désirée B.M. Van Der Werff, Renee T.M. Wensing, Erik Ephraim, Claire Nolte, Tore Reikvam, Ole Fredrik Lund, Lene Skaaden, Kari Marthe Ballovarre, Wenche Bakken Boerke, Guro Grindheim, Pal H H Lindenskov, Anne Beate Solas, Sjur Sponheim, Kyrre Ullensvang, Oddbjorn Viken, Inger Marie Drage, Kasper Gymoese Berthelsen, Bjørn Anders Kroken, Unni Bergland, Miroslaw Pryzmont, Mariola Talalaj, Malgorzata Wasiluk, Dorota Zalewska, Maria Damps, Jadzia Siemek-Mitela, Pawel Wieczorek, Magdalena Juzwa, Jowita Rosada-Kurasinska, Alicja Bartkowska-Sniatkowska, Maciej Cettler, Renata Kopycinska, Iwona Rudewicz, Jaek Sobczyk, Dariusz Wojciechowski, Artur Baranowski, Ewa Basiewicz, Magdalena Mierzewska-Schmidt, Wlodzimierz Retka, Piotr Sawicki, Magdalena Checinska, Magdalena Zurawska, Teresa Leal, Catia Mascarenhas, António Pedro Pina, Maria Joao Susano, Antonio Moniz, Maria Teresa Rocha, Carolina Calvao Santos, M Domingas Patuleia, Ricardo Pereira, Helena Roxo, Rosa Amaral, Isabel Guedes, Cristina Gomes, Marta Gonçalves, Helena Salgado, 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M., Ephraim, Erik, Nolte, Claire, Reikvam, Tore, Fredrik Lund, Ole, Skaaden, Lene, Marthe Ballovarre, Kari, Bakken Boerke, Wenche, Grindheim, Guro, Lindenskov, Pal H. H, Beate Solas, Anne, Sponheim, Sjur, Ullensvang, Kyrre, Viken, Oddbjorn, Marie Drage, Inger, Gymoese Berthelsen, Kasper, Anders Kroken, Bjørn, Bergland, Unni, Pryzmont, Miroslaw, Talalaj, Mariola, Wasiluk, Malgorzata, Zalewska, Dorota, Damps, Maria, Siemek Mitela, Jadzia, Wieczorek, Pawel, Juzwa, Magdalena, Rosada Kurasinska, Jowita, Bartkowska Sniatkowska, Alicja, Cettler, Maciej, Kopycinska, Renata, Rudewicz, Iwona, Sobczyk, Jaek, Wojciechowski, Dariusz, Baranowski, Artur, Basiewicz, Ewa, Mierzewska Schmidt, Magdalena, Retka, Wlodzimierz, Sawicki, Piotr, Checinska, Magdalena, Zurawska, Magdalena, Leal, Teresa, Mascarenhas, Catia, Pedro Pina, António, Joao Susano, Maria, Moniz, Antonio, Teresa Rocha, Maria, Calvao Santos, Carolina, Domingas Patuleia, M., Pereira, Ricardo, Roxo, Helena, Amaral, Rosa, Guedes, Isabel, Gomes, Cristina, Gonçalves, Marta, Salgado, Helena, Santos, Maria, Rodrigues, Sara, Sa, Angela, Machado, Elvira, Pé d'Arca, Sandra, Seabra, Manuel, Mihaela Gheorghe, Ligia, Ivascu, Constantin, Moraru Draghici, Lucia, Suvejan, Mirela, Babici, Remu, Eniko, Kovac, Hogea, Cristiana, Mihaela, Dubau, Nicoleta, Daraban, Barbunc, Danut, Maria Nistor, Alina, Stefan, Violeta, Catalina Ionescu, Gabriela, Davidescu, Irina, Teodora Nastase, Alina, Dumitru Rusu, Florin, Badarau, Victoria, Cindea, Iulia, Moscaliuc, Melania, Olteanu, Dana, Petrescu, Luxita, Ceuca, Daniela, Galinescu, Irena, Badeti, Rodica, Capusan, Alin, Cucui Cozma, Cosmina, Popescu, Barbura, Cimpeanu, Luminita, Birliba, Mihaela Petronela, Miulescu, Magdalena, Balamat, Stefania, Gurita, Adriana, Ilie, Luminita, Mocioiu, Gabriel, Pick, Darina, Sirghie, Rodica, Tabacaru, Radu, Trante, Irinel, Horhota, Lucian, Bandrabur, Daniela, Ciobanu, Tudor, Cuciuc, Veaceslav, Munteanu, Valentin, Olaru, Valentin, Paiu, Corneliu, Savu, Anca, Trifan, Oana, Elena Malos, Anca, Glazunov, Anton, Ivanov, Alexander, Poduskov, Evgeny, Popov, Alexander, Guskov, Igor, Lugovoy, Alexander, Nechaev, Vladislav, Ovezov, Alexey, Basov, Mikhail, Kochkin, Vladimir, Lazarev, Vladimir, Chizhov, Dmitri, Ostreikov, Ivan, Tolasov, Konstantin, Budic, Ivana, Marjanovic, Vesna, Draskovic, Biljana, Pandurov, Marina, Simin, Jovana, Dolinaj, Vladimir, Janjevic, Dusanka, Mandras, Ana, Mircetic, Maja, Petrovic, Sladjana, Rebac, Vlatka, Slavkovic, Bojana, Stevanovic, Vesna, Velcev, Ana, Knezevic, Mirjana, Milojevic, Irina, Puric, Selena, Simic, Irena, Stevic, Marija, Stranjanac, Vladimir, Simic, Dusica, Cabanova, Barbora, Hanula, Miloslav, Grynyuk, Andry, Berger, Jelena, Cerne, Uro, Nastran, Andraz, Pirc, Dejan, Popic, Rok, Stupnik, Spela, Rubio, Paloma, del Río, Cristina, Benito, Pilar, Pino, Gema, Gutierrez, Ignacio, Gutierrez Valcarcel, Andrea, León Carsi, Irene, Perez Garcia, Anibal, López Galera, Sílvia, Marco Valls, Joan, Ricol Lainez, Laura, Vallejo Tarrat, Andrea, Artes, David, Banus, Ester, Chirichiello, Luca, De Abreu, Leidy, De Josemaria, Belen, Helena Gaitan, M., Garces, Antonio, Lazaro, Juan J, Manen Berga, Ferran, Molies, Dolor, Monclus, Enric, Navaro, Montserrat, Pamies, Carmen, Perelló, Marina, Prat, Mar, Ribo, Laura, Angeles Sanz, M., Serrano, Silvia, Sola Ruiz, Eva, Anuncia Escontrela Rodríguez, Blanca, Maria Gago Martinez, Andrea, Martínez Ruiz, Alberto, De La Cruz Benito, Fausto, Gabilondo Garcia, Gustavo, Martinez Maldonado, Ever, Noriega, Bryant, Oller Duque, Lara, Olmos Mendez, Alberto, Perez Ferrer, Antonio, Reinoso Barbero, Francisco, Acevedo Bambaren, Ismael, Domínguez, Fernando, Franco, Teresa, Jiménez, Anabel, Melero, Alicia, Feliu, Montserrat, García, Irene, Montferrer, Núria, Munar, Francisca, Muro, Cristina, Nuño, Rosario, Perera, Remel, Schmucker, Erika, Börjesson, Glenda, Gillberg, Lar, Castellheim, Albert, Sandström, Kerstin, Bauer, Annette, Roos, Torbjörn, Hedlund, Lar, Boegli, Yann, Dolci, Mirko, Marcucci, Carine, Spahr Schopfer, Isabelle, Pellegrini, Michel, Book, Malte, Errass, Loreen, Riggenbach, Christine, Casutt, Mattia, Hölzle, Martin, Hurni, Thoma, Mauch, Jacqueline, Anselmi, Luciano, Anselmi, Irene, Jacomet, Alfred, Oberhauser, Marku, Wossner, Stephanie, Zettl, Angelika, Erb, Thoma, Mackiewicz, Tomasz, Simitzes, Helena, Ozer, Yetkin, Takil, Arzu, Alanoglu, Zekeriyya, Bermede, Onat, Cakar Turhan, K. Sanem, Alkis, Neslihan, Yildirim Guclu, Cigdem, Ceyda Meco, Basak, Hatipoglu, Zehra, Ozcengiz, Dilek, Begec, Zekine, Ilksen Toprak, Huseyin, Kendigelen, Pinar, Cigdem Tütüncü, Ayse, Karadeniz, Meltem Savran, Seyhan Ozkan, Tulay, Sivrikoz, Nuket, Kemal Arslantas, Mustafa, Hizal, Ayse, Tore Altun, Gülbin, Umuroglu, Tumay, Baris, Sibel, Kazak Bengisun, Zuleyha, Goncharenko, Galyna, Khrapak, Maksym, Klymenko, Tetyana, Pavlenko, Vitaliy, Prysiazhniuk, Dmytro, Rudio, Olga, Varyvoda, Mykhailo, Vodianytskyi, Sergii, Boryshkevych, Ivanna, Kyselova, Iryna, Trikash, Nikolay, Albokrinov, Andrew, Perova Sharonova, Valentina, Sklyar, Vitaliy, Surkov, Deni, Abdelaal, Amr, Barber, Nicola, Checuti, Sarah, Godsiff, Leisha, Johanne, Lynch, Simpson, Joanna, Underhill, Helen, Diwan, Rishi, Kelgeri, Nivedita, Masip, Nuria, Ravi, Radha, Roberts, Steve, Cillis, Annagrazia, Marcus, Ritchie, Merella, Federica, Love, David, Baraggia, Paolo, Bird, Victoria, Hussey, Joseph, Alderson, Peter, Bartholomew, Karen, Moncreiff, Michael, Davidson, Sarah, Hare, Alison, Kotecha, Ami, Lee, Corina, Liyanage, Ganga, Patel, Shivali, Samani, Amee, Abou Samra, Mark, Boyd, Matthew, Hullatt, Laurence, Levy, David, Pauling, Mark, Sharman, Sarah Jane, Smith, Natalie, Rutherford, John, Cavalier, Alison, Locke, Christie, Sage, Frederic, Bapat, Smita, Hammerschlag, Jacinda, Ioannou, Ioanni, King, Stephanie, Pegg, Rachel, Salota, Vishal, Sketcher, Jonathan, Thadsad, Muthu, Zeitlin, Deborah, Jack, Ewan, Lang, Colin, Ahmed, Samira, Ayyash, Reema, Bari, Francoise, Bell, Sarah J, Elizabeth Biercamp, Claire, Briggs, Sandra, Gabriella Elena Clement, Maria, Dalton, Mark, Ali Eissa Eid, Mohamed, Gandhi, Monica, Harmen Herrema, Idse, Khaffaf, Ranj, Jeng Min Law, Savio, Mcclintock, Joanna, Ireland, Nichola, Majid Saleem, Mohammed, Smith, Fiona, Cohen, Marc, Lee, Clover Ann, O'Donahue, Lizanne, Powell, Alex, Rawlinson, Ellen, Snoek, Aarjan, Weiss, Katja, Wellesley, Hugo, Crawford, Michael, Abdel Hafiz, Mostafa, Day, Alexandra, Rajamani, Balaji, Saha, Rita, Wright, Dave, Chee, Lew Chin, Bew, Stephanie, Homer, Rachel, Malarkkan, Nalini, Wolfe Barry, Juliet, Angadi, Pradeep, Cagney, Brid, De Melo, Eric, Dekker, Elsa, Helm, Emma, Jones, Gareth, Peiris, Kawshala, Russell, William, Slater, Patricia, Sodhi, Puja, Browning, Mike, Phillips, Trudie, Van Hecke, Rachel, Muir, Vimty, Singh, Piyush, Soskova, Tereza, Cumming, Craig, Farquharson, Pamela, Pearson, Karen, Shaw, Neil, Whiteside, Jonathan, Whyte, Emma, Byers, Gordon, Davies, Kay, Engelhardt, Thoma, Faliszewski, Isabella, Johnston, Graham, Kaufmann, Nil, Kusnirikova, Zuzana, Wilson, Graham, Carachi, Peter, Makin, Andrew, Foster, Brian, Lipczynski, Dariusz, Mawer, Rebecca, Rutherford, William, Rogerson, David, Rushman, Sarah, Taylor, Christopher, Tomlinson, William, Dix, Philippa, Woodward, Tom, Bell, Graham, Boyle, David, Cloherty, Marianne, Cullen, Julia, Cullen, Pauline, Fairgrieve, Ro, Ghent, Robert, Glasgow, Russell, Gordeeva, Elena, Harden, Alison, Hivey, Sarah, Jerome, Kevin, Mckee, Lesley, Morton, Neil, Pribul, Vicky, Sinclair, John, Steiner, Maria, Steward, Heather, Sweeney, Lorraine, Thomson, Wendy, Whiteside, Jeanette, Dalton, Andrew, Ross, Mark, Smith, Carolyn, Allen, Claire, Anders, Nicola, Barlow, Victoria, Bassett, Mike, Darwin, Leanne, Davison, Rachel, Diacono, Jacque, Hobbs, Amy, Hutchinson, Adel, Lomas, Bernadette, Lonsdale, Hannah, Nasser, Leila, Oshan, Vimmi, Patel, Pradip, Raistrick, Christopher, Scott Warren, Victoria, Talbot, Laura, Wai, Carolynn, Childs, Sophie, Dickinson, Matthew, Bloomfield, Tom, Garrioch, Sweyn, Watson, Karen, Gaynor, Jame, Harrison, Richard, Lee, Juliette, Blythe, Elizabeth, Dorman, Teresa, Eissa, Ayman, Ellwood, Jame, Gooch, Ingrid, Hearn, Robert, Hodgetts, Vanessa, John, Robert, Kirton, Christine, Ladak, Nadia, Morgan, Judith, Plant, Nina, Shepherd, Elizabeth, Short, Judith, Stack, Charle, Steel, Simon, Taylor, Matthew, Thomas, Deborah, Wilson, Catharine, Wilson Smith, Elaine, Bradbury, Carol L., Hussain, Nageena, Mayell, Antonia, Mesbah, Ahmed, Qureshi, Arif, Vaidyanath, Chandra, Geary, Tim, Hawksworth, Chri, Parasuraman, Tamaraichelvi, Perry, Nicole, Banerjee, Indrani, Barr, Katharine, Butler, Patrick, Davies, Jack, Flewin, Lisa, Gande, Richard, Montague, Jame, Plumb, Jame, Pratt, Thoma, Sutherland, Paul, Vail, Hannah, Wilkins, Andrew, Hunter, Catherine, Russell, Susan, Thomas, Alun, Mifsud, Mark, Strachan, Dominic, Plichon, Benoit, Harlet, Pierre, Child and Adolescent Psychiatry / Psychology, Morawk-Wintersperger, Ulrike, Seidel-Ahyai, Natascha, Lechat, Jean-Paul, Kesic-Valpotic, Gordana, Ilmoja, Mari-Lii, Nouette-Gaulain, Karine, Gagey, Anne-Charlotte, Carre, Anne-Charlotte, Riche, Jean-Claude, Verchere-Montmayeur, Juliette, Julien-Marsollier, Florence, Saour, Anne-Charlotte, Jetzek-Zader, Martin, Meyer-Treschan, Tanja, Preussler, Niels-Peter, Sidlovskaite-Baltake, Dominika, van Stijn, Mireille F M, Dons-Sinke, Ilse, van der Knijff - van Dortmont, Anouk, Hopman, Geranne A.J., Megens, A.M., Schouten, Anton N.J., Van Der Werff, Désirée B.M., Wensing, Renee T.M., Lindenskov, Pal H H, Siemek-Mitela, Jadzia, Rosada-Kurasinska, Jowita, Bartkowska-Sniatkowska, Alicja, Mierzewska-Schmidt, Magdalena, Moraru-Draghici, Lucia, Cucui-Cozma, Cosmina, Birliba, Mihaela-Petronela, Perez- Ferrer, Antonio, Spahr-Schopfer, Isabelle, Cakar Turhan, K.Sanem, Perova-Sharonova, Valentina, Abou-Samra, Mark, Sharman, Sarah-Jane, McClintock, Joanna, Lee, Clover-Ann, Abdel-Hafiz, Mostafa, Chee, Lew-Chin, McKee, Lesley, Scott-Warren, Victoria, and Wilson-Smith, Elaine

Subjects
Male, Pediatrics, Health Status, OPERATING-ROOM, Respiratory Tract Diseases, CHILDREN, 0302 clinical medicine, REGIONAL ANESTHESIA, Postoperative Complications, 030202 anesthesiology, CARDIAC-ARREST, Medicine, General anaesthesia, Prospective Studies, Prospective cohort study, Child, Intraoperative Complications, COMPLICATIONS, ddc:617, Incidence (epidemiology), Mortality rate, musculoskeletal, neural, and ocular physiology, Incidence, Age Factors, Hospitals, Europe, Cardiovascular Diseases, Child, Preschool, RESPIRATORY ADVERSE EVENTS, Female, Clinical Competence, Cohort study, Pulmonary and Respiratory Medicine, medicine.medical_specialty, Adolescent, macromolecular substances, Anesthesia, General, Drug Hypersensitivity, 03 medical and health sciences, MORBIDITY, Journal Article, Humans, business.industry, Infant, Newborn, Infant, 030208 emergency & critical care medicine, Perioperative, nervous system, PROSPECTIVE COHORT, Relative risk, RISK-FACTORS, Observational study, Human medicine, Nervous System Diseases, business, SYSTEM
Abstract

Background Little is known about the incidence of severe critical events in children undergoing general anaesthesia in Europe. We aimed to identify the incidence, nature, and outcome of severe critical events in children undergoing anaesthesia, and the associated potential risk factors. Methods The APRICOT study was a prospective observational multicentre cohort study of children from birth to 15 years of age undergoing elective or urgent anaesthesia for diagnostic or surgical procedures. Children were eligible for inclusion during a 2-week period determined prospectively by each centre. There were 261 participating centres across 33 European countries. The primary endpoint was the occurence of perioperative severe critical events requiring immediate intervention. A severe critical event was defined as the occurrence of respiratory, cardiac, allergic, or neurological complications requiring immediate intervention and that led (or could have led) to major disability or death. This study is registered with ClinicalTrials.gov, number NCT01878760. Findings Between April 1, 2014, and Jan 31, 2015, 31 127 anaesthetic procedures in 30 874 children with a mean age of 6·35 years (SD 4·50) were included. The incidence of perioperative severe critical events was 5·2% (95% CI 5·0–5·5) with an incidence of respiratory critical events of 3·1% (2·9–3·3). Cardiovascular instability occurred in 1·9% (1·7–2·1), with an immediate poor outcome in 5·4% (3·7–7·5) of these cases. The all-cause 30-day in-hospital mortality rate was 10 in 10 000. This was independent of type of anaesthesia. Age (relative risk 0·88, 95% CI 0·86–0·90; p

Published
2017

39. Growth abnormalities in children and adolescents with juvenile idiopathic arthritis

Author

Susanne Bechtold and Dominique Simon

Subjects
Pediatrics, medicine.medical_specialty, Adolescent, Immunology, Arthritis, Inflammation, Disease, Short stature, Rheumatology, Risk Factors, Internal medicine, medicine, Humans, Immunology and Allergy, Juvenile, Child, Growth Disorders, Human Growth Hormone, business.industry, Age Factors, medicine.disease, Arthritis, Juvenile, Body Height, Growth hormone treatment, Treatment Outcome, Endocrinology, Antirheumatic Agents, Body Composition, medicine.symptom, business, Glucocorticoid, medicine.drug
Abstract

In patients with juvenile idiopathic arthritis (JIA) growth impairment and variance in body composition are well-known long-term complications. In the active phases of the disease, particular patients with systemic and polyarticular JIA reveal growth impairment. Some experience "catch-up" growth following reduction in disease activity and lower glucocorticoid doses. Although new therapeutic options are available, there are still 10-20 % of patients with severe forms of the disease who show continuous growth disturbance. Only few studies have specifically addressed body composition in JIA. Bone mass deficits in part could be related to the deficits of muscle mass. Study data on growth hormone treatment in short children with JIA are promising in respect of growth development, final height and body composition. The major goal for physicians is optimal disease control while maintaining normal growth and body composition. Early recognition of patients who develop prolonged growth and body composition disturbances is important as these abnormalities contribute to long-term morbidity and need to be addressed both diagnostically and therapeutically.

Published
2014

40. Glycemic Control and All-Cause Mortality Risk in Type 1 Diabetes Patients: The EURODIAB Prospective Complications Study

Author

Sabita S. Soedamah-Muthu, John H. Fuller, Danielle A J M Schoenaker, Nish Chaturvedi, and Dominique Simon

Subjects
Adult, Blood Glucose, Male, vascular complications, medicine.medical_specialty, endocrine system diseases, Nutrition and Disease, Adolescent, Endocrinology, Diabetes and Metabolism, Clinical Biochemistry, cardiovascular-disease, rates, Type 2 diabetes, severe hypoglycemia, Biochemistry, Cohort Studies, Young Adult, chemistry.chemical_compound, Endocrinology, hba(1c), Voeding en Ziekte, Cause of Death, death, Internal medicine, Diabetes mellitus, medicine, Humans, Prospective cohort study, VLAG, Glycemic, Type 1 diabetes, business.industry, Biochemistry (medical), trials, cohort, Middle Aged, medicine.disease, Survival Analysis, a1c, Europe, Diabetes Mellitus, Type 1, chemistry, accord, Cohort, Female, Glycated hemoglobin, business, Cohort study
Abstract

Context: Glycemic targets and the benefit of intensive glucose control are currently under debate because intensive glycemic control has been suggested to have negative effects on mortality risk in type 2 diabetes patients. Objective: We examined the association between glycated hemoglobin (HbA1c) and all-cause mortality in patients with type 1 diabetes mellitus. Design, Setting, and Patients: A clinic-based prospective cohort study was performed in 2764 European patients with type 1 diabetes aged 15–60 years enrolled in the EURODIAB Prospective Complications Study. Outcome Measure: Possible nonlinearity of the association between HbA1c and all-cause mortality was examined using multivariable restricted cubic spline regression using three (at HbA1c 5.6%, 8.1%, and 11.8%) and five knots (additionally at HbA1c 7.1% and 9.5%). Mortality data were collected approximately 7 years after baseline examination. Results: HbA1c was related to all-cause mortality in a nonlinear manner after adjustment for age and sex. All-cause mortality risk was increased at both low (5.6%) and high (11.8%) HbA1c compared with the reference (median HbA1c: 8.1%) following a U-shaped association [P overall effect = .008 and .04, P nonlinearity = .03 and .11 (three and five knots, respectively)]. Conclusions: Results from our study in type 1 diabetes patients suggest that target HbA1c below a certain threshold may not be appropriate in this population. We recognize that these low HbA1c levels may be related to anemia, renal insufficiency, infection, or other factors not available in our database. If our data are confirmed, the potential mechanisms underlying this increased mortality risk among those with low HbA1c will need further study.

Published
2014

41. Évaluation d’un programme d’éducation thérapeutique dans le diabète de type 1 : un même programme peut permettre d’atteindre des objectifs différents grâce à une approche centrée sur le patient

Author

T. Obadia, Agnès Hartemann, Annalisa Grimaldi, C. Sachon, M. Halbron, and Dominique Simon

Subjects
Nutrition and Dietetics, Endocrinology, Diabetes and Metabolism, Internal Medicine, Cardiology and Cardiovascular Medicine
Abstract

Resume Les programmes d’education therapeutique pour les patients diabetiques de type 1 (DT1) sont au centre des preoccupations des diabetologues. Quelle prise en charge, et pour quels resultats ? Tous les patients ne sont pas concernes par les memes difficultes : certains sont en desequilibre glycemique chronique, d’autres, au contraire, ont une bonne HbA 1c mais au prix d’hypoglycemies frequentes et/ou severes, d’autres, enfin, n’ont aucun de ces deux types de problemes, mais aimeraient elargir leur liberte alimentaire et ameliorer leur qualite de vie, sans alterer leur niveau glycemique. Nous avons voulu evaluer s’il etait possible qu’un meme programme d’education therapeutique puisse apporter des solutions a des patients ayant des objectifs et des attentes differents. Nous avons inclus consecutivement tous les patients DT1 participant a un programme d’education therapeutique centre sur l’apprentissage de l’insulinotherapie fonctionnelle. Tous les patients ont assiste au meme programme, mais ont beneficie d’une approche centree sur leurs preoccupations. Nous avons montre qu’il etait possible a des patients ayant pourtant des attentes differentes d’atteindre chacun leur objectif prioritaire, a condition que la prise en charge soit reellement centree sur le patient.

Published
2014

42. HbA(1c), fasting and 2 h plasma glucose in current, ex- and never-smokers: a meta-analysis

Author

Paul Zimmet, Yanghu Dong, Soraya Soulimane, Jaakko Tuomilehto, Dominique Simon, Céline Lange, Dorte Vistisen, Giel Nijpels, Edward J. Boyko, Dirk L. Christensen, Wilfred Y. Fujimoto, Coen D.A. Stehouwer, Viswanathan Mohan, Knut Borch-Johnsen, Marguerite J. McNeely, Lei Zhang, Beverley Balkau, Stephen Colagiuri, Crystal Man Ying Lee, Olivier Lantieri, Lydia Kaduka, Jonathan E. Shaw, William H. Herman, Dianna J. Magliano, Sandra Roberta Gouvea Ferreira, Torben Jørgensen, Donna L. Leonetti, Jacqueline M. Dekker, Epidemiology and Data Science, General practice, EMGO - Lifestyle, overweight and diabetes, Interne Geneeskunde, MUMC+: MA Interne Geneeskunde (3), and RS: CARIM - R3 - Vascular biology

Subjects
Blood Glucose, medicine.medical_specialty, Endocrinology, Diabetes and Metabolism, Blood sugar, Gastroenterology, Article, Insulin resistance, Diabetes mellitus, Internal medicine, Linear regression, Epidemiology, Internal Medicine, medicine, Humans, HbA(1c), Glycated Hemoglobin, business.industry, Smoking, METANÁLISE, Fasting, medicine.disease, FPG, Meta-analysis, Endocrinology, Hemoglobin A, 2H-PG, behavior and behavior mechanisms, Population study, business
Abstract

The relationships between smoking and glycaemic variables have not been well explored. We compared HbA1c, fasting plasma glucose (FPG) and 2 h plasma glucose (2H-PG) in current, ex- and never-smokers. This meta-analysis used individual data from 16,886 men and 18,539 women without known diabetes in 12 DETECT-2 consortium studies and in the French Data from an Epidemiological Study on the Insulin Resistance Syndrome (DESIR) and Telecom studies. Means of three glycaemic variables in current, ex- and never-smokers were modelled by linear regression, with study as a random factor. The I 2 statistic was used to evaluate heterogeneity among studies. HbA1c was 0.10% (95% CI 0.08, 0.12) (1.1 mmol/mol [0.9, 1.3]) higher in current smokers and 0.03% (0.01, 0.05) (0.3 mmol/mol [0.1, 0.5]) higher in ex-smokers, compared with never-smokers. For FPG, there was no significant difference between current and never-smokers (−0.004 mmol/l [−0.03, 0.02]) but FPG was higher in ex-smokers (0.12 mmol/l [0.09, 0.14]). In comparison with never-smokers, 2H-PG was lower (−0.44 mmol/l [−0.52, −0.37]) in current smokers, with no difference for ex-smokers (0.02 mmol/l [−0.06, 0.09]). There was a large and unexplained heterogeneity among studies, with I 2 always above 50%; I 2 was little changed after stratification by sex and adjustment for age and BMI. In this study population, current smokers had a prevalence of diabetes that was 1.30% higher as screened by HbA1c and 0.52% lower as screened by 2H-PG, in comparison with never-smokers. Across this heterogeneous group of studies, current smokers had a higher HbA1c and lower 2H-PG than never-smokers. This will affect the chances of smokers being diagnosed with diabetes.

Published
2014

43. Understanding the Revolving Door: Individual and Structural-Level Predictors of Recidivism Among Individuals with HIV Leaving Jail

Author

Jeannia J. Fu, Maua Herme, Amy L. Althoff, Alexander R. Bazazi, Nickolas Zaller, Jeff Porterfield, Martha Lyman, Jeffrey A. Wickersham, Dominique Simon-Levine, Frederick L. Altice, Alison O. Jordan, Ann Avery, and Alexei Zelenev

Subjects
Adult, Male, medicine.medical_specialty, Social Psychology, Substance-Related Disorders, Psychological intervention, HIV Infections, Vulnerable Populations, Article, Recurrence, Criminal Law, Intervention (counseling), medicine, Humans, Psychiatry, Health Services Needs and Demand, Recidivism, Mental Disorders, Prisoners, Public health, Public Health, Environmental and Occupational Health, Middle Aged, Health psychology, Logistic Models, Infectious Diseases, Socioeconomic Factors, Prisons, Ill-Housed Persons, Multivariate Analysis, Cohort, Criminal law, Female, Psychology, Social Adjustment, Follow-Up Studies, Criminal justice
Abstract

Incarceration, particularly when recurrent, can significantly compromise the health of individuals living with HIV. Despite this, the occurrence of recidivism among individuals with HIV has been little examined, particularly among those leaving jail, who may be at especially high risk for return to the criminal justice system. We evaluated individual- and structural-level predictors of recidivism and time to re-incarceration in a cohort of 798 individuals with HIV leaving jail. Nearly a third of the sample experienced at least one re-incarceration event in the 6 months following jail release. Having ever been diagnosed with a major psychiatric disorder, prior homelessness, having longer lifetime incarceration history, having been charged with a violent offense for the index incarceration and not having health insurance in the 30 days following jail release were predictive of recidivism and associated with shorter time to re-incarceration. Health interventions for individuals with HIV who are involved in the criminal justice system should also target recidivism as a predisposing factor for poor health outcomes. The factors found to be associated with recidivism in this study may be potential targets for intervention and need to be further explored. Reducing criminal justice involvement should be a key component of efforts to promote more sustainable improvements in health and well-being among individuals living with HIV.

Published
2013

44. Current level of glycaemic control and its associated factors in patients with type 2 diabetes across Europe: data from the PANORAMA study

Author

Klaus G. Parhofer, Pedro de Pablos-Velasco, Ian C. Wood, Pierre Maheux, Linda Gonder-Frederick, Clare Bradley, Dominique Simon, and Eveline Eschwège

Subjects
Blood Glucose, Male, Pediatrics, medicine.medical_specialty, Multivariate analysis, Endocrinology, Diabetes and Metabolism, MEDLINE, Bivariate analysis, Type 2 diabetes, Endocrinology, Diabetes mellitus, Humans, Medicine, Socioeconomic status, Aged, Glycated Hemoglobin, business.industry, Medical record, Middle Aged, medicine.disease, Europe, Diabetes Mellitus, Type 2, Multivariate Analysis, Female, business, Body mass index
Abstract

Objective To provide an update on glycaemic control in European patients with type 2 diabetes based on data from the nine-country, cross-sectional PANORAMA study (NCT00916513). Design Post-hoc analysis to report the number of patients achieving/not achieving glycaemic goal (HbA1c 1 year prior to study entry, and had an available medical record of >1 year. Measurements All data were collected at a single visit, including HbA1c measurement using a common device (A1CNow®). Bivariate and multivariate analyses were used to investigate factors associated with not reaching glycaemic goal. Results Of 5817 patients enrolled (aged 65·9 ± 10·4 years, 53·7% male), 37·4% had an HbA1c ≥7%; (range 25·9% in The Netherlands to 52·0% in Turkey). In adjusted multivariate analyses, higher individual glycaemic target, younger age, poor physician-reported patient adherence to lifestyle/medication, longer diabetes duration, increasing treatment regimen complexity and physician-reported patient's unwillingness to intensify treatment were associated with not achieving goal. However, bivariate analyses also found gender, socioeconomic factors, body mass index, rate of complications and hypoglycaemia to be associated with not achieving goal. Conclusions In PANORAMA, 37·4% of patients enrolled were not at glycaemic goal. Factors relating to patient characteristics, physician selection of individualized HbA1c target and diabetes itself (longer duration, more complex treatment) were strongly associated with not achieving goal. Further studies are warranted to explore these associations and evaluate strategies for improving glycaemic control.

Published
2013

45. Le diabète de type 2 en France : épidémiologie, évolution de la qualité de la prise en charge, poids social et économique. Entred 2007

Author

P. Lecomte, Alain Weill, Isabelle Bourdel-Marchasson, Anne Fagot-Campagna, Cécile Fournier, Alfred Penfornis, Nathalie Poutignat, Michèle Chantry, Dominique Simon, Mathilde Risse, S. Fosse, C. Druet, Arnaud Gautier, C. Attali, and Eveline Eschwège

Subjects
Pediatrics, medicine.medical_specialty, business.industry, General Medicine, Disease, Type 2 diabetes, medicine.disease, Obesity, Surgery, Blood pressure, Quality of life, Diabetes mellitus, medicine, Albuminuria, medicine.symptom, business, Glycemic
Abstract

Between 2001 and 2007, treatments for type 2 diabetes have increased and therapeutic choices have improved. However glycemic control remains insufficient. Cardiovascular risk control has widely increased. Statins, hypertensive and antithrombotic treatments are more often prescribed. Blood pressure and LDL cholesterol levels have decreased whatever age. However, progress remains possible, especially regarding blood pressure control. Obesity has increased between 2001 and 2007 to reach 41% whereas the frequency of dietetic visits has decreased. Insulin therapy (more than obesity) determines the frequency of dietetic visits: dietetic care happens too late. Important improvements of the quality of follow-up are observed. However, fundus exams and more specifically albuminuria measurement remain insufficiently performed and their progression is too slow, as well as the podiatric examination. Only 10% of people with type 2 diabetes have an endocrinology visit, which has been stable between 2001 and 2007. Information expectations of people with type 2 diabetes are strong, especially for diet. Education demand is lower but more important for people who have already benefited. This improvement of medical care leads to an increase in the cost of reimbursements. The consequences of diabetes, more than the disease itself, alter the quality of life.

Published
2013

46. Gender Differences in Baseline Health, Needs at Release, and Predictors of Care Engagement Among HIV-Positive Clients Leaving Jail

Author

Kevin Moore, Dorothy Murphy-Swallow, Jaimie P. Meyer, Anne C. Spaulding, Chyvette T. Williams, Ann Avery, Lawrence J. Ouellet, Seijeoung Kim, Frederick L. Altice, Dominique Simon, Paul A. Teixeira, and Jeffrey A. Wickersham

Subjects
Adult, Male, Program evaluation, Social Work, medicine.medical_specialty, Social Psychology, Health Status, Human immunodeficiency virus (HIV), HIV Infections, Social Welfare, medicine.disease_cause, Health Services Accessibility, Article, Interviews as Topic, Sex Factors, medicine, Humans, Sex Distribution, Substance Abuse, Intravenous, Baseline (configuration management), Psychiatry, Health Services Needs and Demand, Primary Health Care, Social work, business.industry, Prisoners, Public health, Public Health, Environmental and Occupational Health, Continuity of Patient Care, Middle Aged, Patient Acceptance of Health Care, Patient Discharge, Health psychology, Infectious Diseases, Prisons, Female, business, Follow-Up Studies, Program Evaluation, Criminal justice
Abstract

Women represent a significant and growing segment of jail detainees and persons living with HIV. This paper examines gender differences in health status, care and social service needs, and care engagement among jail releasees with HIV. Data are from 1,270 participants in the HRSA-funded Enhancing Linkages to HIV Primary Care and Social Services multisite demonstration project (EnhanceLink). Compared to men, more women reported homelessness, reduced adherence to prescribed ART, worse health, more severe substance use disorders, and more chronic health conditions. Men and women generally reported different needs post-release. As the number of expressed needs increased, women were more likely to drop out of care. Our findings suggest that effective and gender-specific strategies are required to identify needs, link services between jails and communities, and sustain retention of women with HIV in programs after release from criminal justice settings.

Published
2013

47. NNT mutations: a cause of primary adrenal insufficiency, oxidative stress and extra-adrenal defects

Author

Gilles Blondin, Claudine Heinrichs, Sylvie Nivot, Maryline Ronze, Dominique Simon, Yves Morel, Pierre-François Souchon, Catherine Naud-Saudreau, Asmahane Ladjouze, Dinane Samara-Boustani, Christine Lefevre, Florence Roucher-Boulez, Laetitia Lemarchand, Laure Groisne, Houweyda Jilani, Delphine Mallet-Motak, Bruno Leheup, Xavier Bertagna, CHU Lyon, Université Claude Bernard Lyon 1 (UCBL), Université de Lyon, CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre Hospitalier Universitaire de Bab-el-Oued, Centre Hospitalier Universitaire de Bab-el-Oued, Alger, Algérie., American Memorial Hospital (Reims), Service d'Endocrinologie et Diabétologie Pédiatriques, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Robert Debré, CHU Pontchaillou [Rennes], Hôpital Universitaire des Enfants Reine Fabiola, Université libre de Bruxelles (ULB), Université médicale de Vienne, Autriche, Centre hospitalier Lucien Hussel, Institut Cochin (UMR_S567 / UMR 8104), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service de Génétique Médicale [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Nutrition-Génétique et Exposition aux Risques Environnementaux (NGERE), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), CH de Lorient, Hôpital Jeanne de Flandres, Université de Lille, Droit et Santé-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Service de pédiatrie, Hopital Saint-Louis, La Rochelle, Service de pédiatrie, Hopital Saint-Louis , La Rochelle, Université Claude Bernard Lyon 1 ( UCBL ), Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Robert Debré, Université Libre de Bruxelles [Bruxelles] ( ULB ), Institut Cochin ( UMR_S567 / UMR 8104 ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Centre Hospitalier Régional Universitaire de Nancy ( CHRU Nancy ), Nutrition-Génétique et Exposition aux Risques Environnementaux ( NGERE ), Université de Lorraine ( UL ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Université de Lille, Droit et Santé-Centre Hospitalier Régional Universitaire [Lille] ( CHRU Lille ), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Robert Debré, Université Libre de Bruxelles [Bruxelles] (ULB), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5), Université de Lorraine (UL)-Institut National de la Santé et de la Recherche Médicale (INSERM), and Jonchère, Laurent

Subjects
Adult, Male, 0301 basic medicine, medicine.medical_specialty, Adolescent, Endocrinology, Diabetes and Metabolism, [SDV]Life Sciences [q-bio], Puberty, Precocious, Biology, Compound heterozygosity, Primary Adrenal Insufficiency, Young Adult, 03 medical and health sciences, Endocrinology, Hypothyroidism, nicotinamide nucleotide transhydrogenase, Internal medicine, primary adrenal insufficiency, NADP Transhydrogenases, medicine, Adrenal insufficiency, follow-up, Humans, Precocious puberty, oxidative stress, Child, Azoospermia, [SDV.MHEP.EM] Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, [ SDV ] Life Sciences [q-bio], Homozygote, massive parallel sequencing, General Medicine, Middle Aged, [ SDV.MHEP.EM ] Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, [SDV.MHEP.EM]Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, medicine.disease, 3. Good health, Congenital hypothyroidism, [SDV] Life Sciences [q-bio], 030104 developmental biology, Child, Preschool, Mutation, Etiology, Female, Thyroid function, Glucocorticoid, Adrenal Insufficiency, medicine.drug
Abstract

Objective Nicotinamide nucleotide transhydrogenase (NNT), one of the several genes recently discovered in familial glucocorticoid deficiencies (FGD), is involved in reactive oxygen species detoxification, suggesting that extra-adrenal manifestations may occur, due to the sensitivity to oxidative stress of other organs rich in mitochondria. Here, we sought to identify NNT mutations in a large cohort of patients with primary congenital adrenal insufficiency without molecular etiology and evaluate the degree of adrenal insufficiency and onset of extra-adrenal damages. Methods Sanger or massive parallel sequencing of NNT and patient monitoring. Results Homozygous or compound heterozygous NNT mutations occurred frequently (26%, 13 unrelated families, 18 patients) in our cohort. Seven new mutations were identified: p.Met337Val, p.Ala863Glu, c.3G>A (p.Met1?), p.Arg129*, p.Arg379*, p.Val665Profs*29 and p.Ala704Serfs*19. The most frequent mutation, p.Arg129*, was found recurrently in patients from Algeria. Most patients were diagnosed belatedly (8–18 months) after presenting severe hypoglycemia; others experiencing stress conditions were diagnosed earlier. Five patients also had mineralocorticoid deficiency at onset. One patient had congenital hypothyroidism and two cryptorchidism. In follow-up, we noticed gonadotropic and genitalia impairments (precocious puberty, testicular inclusions, interstitial Leydig cell adenoma, azoospermia), hypothyroidism and hypertrophic cardiomyopathy. Intrafamilial phenotype heterogeneity was also observed. Conclusions NNT should be sequenced, not only in FGD, but also in all primary adrenal insufficiencies for which the most frequent etiologies have been ruled out. As NNT is involved in oxidative stress, careful follow-up is needed to evaluate mineralocorticoid biosynthesis extent, and gonadal, heart and thyroid function.

Published
2016

48. Delay discounting of gains and losses, glycemic control and therapeutic adherence in type 2 diabetes

Author

Mathias Pessiglione, Jean-Jacques Altman, Dominique Simon, Agnès Hartemann, Frédéric Limosin, Cédric Lemogne, Gérard Reach, Gaele Lebeau, Silla M. Consoli, Raphaël Le Bouc, and Agnès Sola-Gazagnes

Subjects
Adult, Blood Glucose, Male, Pediatrics, medicine.medical_specialty, Control (management), 030209 endocrinology & metabolism, Type 2 diabetes, Medication Adherence, 03 medical and health sciences, Behavioral Neuroscience, chemistry.chemical_compound, 0302 clinical medicine, Therapeutic Adherence, medicine, Humans, In patient, 030212 general & internal medicine, Glycemic, Aged, Glycated Hemoglobin, Delay discounting, Confounding, General Medicine, Middle Aged, medicine.disease, chemistry, Delay Discounting, Diabetes Mellitus, Type 2, Animal Science and Zoology, Female, Glycated hemoglobin, Psychology, Social psychology
Abstract

Objective Delay discounting is the tendency to prefer smaller, sooner rewards to larger, later ones. Poor adherence in type 2 diabetes could be partially explained by a discounted value of health, as a function of delay. Delay discounting can be described with a hyperbolic model characterized by a coefficient, k. The higher k, the less future consequences are taken into account when making decisions. This study aimed to determine whether k would be correlated with glycated hemoglobin and adherence in type 2 diabetes. Methods Ninety-three patients were recruited in two diabetology departments. Delay discounting coefficients were measured with a computerized task. HbA1c was recorded and adherence was assessed by questionnaires. Potential socio-demographic and clinical confounding factors were collected. Results There was a positive correlation between delay discounting of gains and HbA1c (r = 0.242, P = 0.023). This association remained significant after adjusting for potential confounding factors (F = 4.807, P = 0.031, η 2 = 0.058). This association was partially mediated by adherence to medication (β = 0.048, 95% CI [0.004–0.131]). Conclusions Glycemic control is associated with delay discounting in patients suffering from type 2 diabetes. Should these findings be replicated with a prospective design, they could lead to new strategies to improve glycemic control among these patients.

Published
2016

49. HbA1c, fasting plasma glucose and the prediction of diabetes: Inter99, AusDiab and D.E.S.I.R

Author

Dominique Simon, Soraya Soulimane, Dorte Vistisen, Daniel R. Witte, Knut Borch-Johnsen, Beverley Balkau, Dianna J. Magliano, Sylviane Vol, Jonathan E. Shaw, and Paul Zimmet

Subjects
Blood Glucose, Male, endocrine system diseases, Denmark, Endocrinology, Diabetes and Metabolism, Cohort Studies, 0302 clinical medicine, Endocrinology, Risk Factors, Epidemiology, Prospective Studies, 030212 general & internal medicine, Plasma glucose, Incidence, Incidence (epidemiology), Fasting, General Medicine, Middle Aged, 3. Good health, Female, France, Adult, medicine.medical_specialty, Diabetes risk, Blood sugar, 030209 endocrinology & metabolism, Risk Assessment, Sensitivity and Specificity, Young Adult, 03 medical and health sciences, Predictive Value of Tests, Internal medicine, Diabetes mellitus, Internal Medicine, medicine, Humans, Aged, Glycated Hemoglobin, business.industry, Australia, nutritional and metabolic diseases, medicine.disease, Impaired fasting glucose, Confidence interval, carbohydrates (lipids), Diabetes Mellitus, Type 2, sense organs, business, Biomarkers
Abstract

Introduction With diabetes defined by HbA1c ≥ 6.5% and/or FPG ≥ 7.0 mmol/l and/or diabetes treatment, we investigated HbA1c and fasting plasma glucose (FPG) thresholds/change-points above which the incidence of diabetes increases. Methods Data are Danish (Inter99), Australian (AusDiab) and French (D.E.S.I.R.), with respectively 4930, 6012 and 3784 non-diabetic participants. Results Diabetes incidences at 5 years for Inter99 and AusDiab and at 6 years for D.E.S.I.R. were 2.3%, 3.1% and 2.4% respectively and incidences increased with baseline HbA1c and FPG. As HbA1c distributions differed between cohorts, HbA1c was standardized on D.E.S.I.R. data. Change-points where diabetes incidence increased were identified for HbA1c (%) after standardization: 5.1 (4.9–5.6) (Inter99), 5.4 (5.1–5.6) (AusDiab), 5.3 (5.1–5.7) (D.E.S.I.R.); for FPG change-points (mmol/l) were 5.1 (…–6.1) (Inter99), 5.5 (5.2–5.8) (AusDiab), no change-point for D.E.S.I.R. Using current diabetes risk criteria HbA1c ≥ 5.7% and/or FPG ≥ 5.6 mmol/l to screen for diabetes provided high sensitivity (over 89%) and positive predictive values: 4.3%, 6.9%, and 5.9% respectively. Conclusions HbA1c and FPG change-points predicting incident diabetes did not always exist, differed across studies, when available were generally lower than current criteria with wide confidence intervals. Using jointly HbA1c ≥ 5.7% and/or FPG ≥ 5.6 mmol/l as a criterion for the risk of incident diabetes is appropriate.

Published
2012

50. Therapeutic inertia in type 2 diabetes: insights from the PANORAMA study in France

Author

Dominique Simon

Subjects
Blood Glucose, Male, medicine.medical_specialty, Pediatrics, Attitude of Health Personnel, Endocrinology, Diabetes and Metabolism, media_common.quotation_subject, MEDLINE, Disease, Drug Administration Schedule, Cohort Studies, Endocrinology, Risk Factors, Surveys and Questionnaires, Health care, Epidemiology, Internal Medicine, medicine, Humans, Hypoglycemic Agents, Quality (business), Intensive care medicine, media_common, Therapeutic inertia, Glycated Hemoglobin, business.industry, General Medicine, Europe, Cross-Sectional Studies, Diabetes Mellitus, Type 2, Cardiovascular Diseases, Cohort, Female, France, Guideline Adherence, business, Diabetic Angiopathies, Cohort study
Abstract

"Therapeutic inertia" is usually defined as the failure to change or uptitrate treatment strategy when a disease is uncontrolled. In patients with type 2 diabetes (T2D) this may occur with antidiabetes treatments and/or treatment for various cardiovascular risk factors. The PANORAMA study (NCT00916513) compared individual HbA(1c) targets and actual HbA(1c) levels in 5817 patients with T2D in nine European countries, and investigated the reasons why therapeutic choices made by physicians sometimes differ from expert guidelines for this disease. Thus it provides an insight into therapeutic inertia, a fashionable paradigm which can be challenged. This article reports data specifically from the French cohort of patients (n=759). We will try to demonstrate that criticising physicians for not strictly applying the expert T2D guidelines would not be beneficial as the clinical background for this apparent therapeutic inertia is complex. It appears that it may be more clinically relevant and useful to understand the reasons why the therapeutic choice made by the physician-patient partnership can sometimes differ from guidelines. This pragmatic approach would not detract from the need to develop and implement expert guidelines as it is essential to have benchmarks to assess temporal trends of quality of healthcare delivered to patients with T2D at the national level. However, these treatment targets must be put into perspective for clinical practice. Following the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial, it appears mandatory to individualize glycaemic targets to enable physicians to identify the most appropriate antidiabetes treatment for each patient.

Published
2012

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