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1. Psychiatric and physical outcomes of long-term use of lithium in older adults with bipolar disorder and major depressive disorder: A cross-sectional multicenter study

Author

Elise Morlet, Jean-François Costemale-Lacoste, Emmanuel Poulet, Kibby McMahon, Nicolas Hoertel, Frédéric Limosin, J Adès, C Alezrah, I Amado, G Amar, O Andréi, D Arbault, G Archambault, G Aurifeuille, S Barrière, C Béra-Potelle, Y Blumenstock, H Bardou, M Bareil-Guérin, P Barrau, C Barrouillet, E Baup, N Bazin, B Beaufils, J Ben Ayed, M Benoit, K Benyacoub, T Bichet, F Blanadet, O Blanc, J Blanc-Comiti, D Boussiron, AM Bouysse, A Brochard, O Brochart, B Bucheron, M Cabot, V Camus, JM Chabannes, V Charlot, T Charpeaud, C Clad-Mor, C Combes, M Comisu, B Cordier, F Costi, JP Courcelles, M Creixell, H Cuche, C Cuervo-Lombard, A Dammak, D Da Rin, JB Denis, H Denizot, A Deperthuis, E Diers, S Dirami, D Donneau, P Dreano, C Dubertret, E Duprat, D Duthoit, C Fernandez, P Fonfrede, N Freitas, P Gasnier, J Gauillard, F Getten, F Gierski, F Godart, R Gourevitch, A Grassin Delyle, J Gremion, H Gres, V Griner, C Guerin-Langlois, C Guggiari, O Guillin, H Hadaoui, E Haffen, C Hanon, S Haouzir, C Hazif-Thomas, A Heron, B Hubsch, I Jalenques, D Januel, A Kaladjian, JF Karnycheff, O Kebir, MO Krebs, C Lajugie, M Leboyer, P Legrand, M Lejoyeux, V Lemaire, E Leroy, D Levy-Chavagnat, A Leydier, C Liling, PM Llorca, P Loeffel, P Louville, S Lucas Navarro, N Mages, M Mahi, O Maillet, A Manetti, C Martelli, P Martin, M Masson, I Maurs-Ferrer, J Mauvieux, S Mazmanian, E Mechin, L Mekaoui, M Meniai, A Metton, A Mihoubi, M Miron, G Mora, V Niro Adès, P Nubukpo, C Omnes, S Papin, P Paris, C Passerieux, J Pellerin, J Perlbarg, S Perron, A Petit, F Petitjean, C Portefaix, D Pringuey, A Radtchenko, H Rahiou, D Raucher-Chéné, A Rauzy, L Reinheimer, M Renard, M René, CE Rengade, P Reynaud, D Robin, C Rodrigues, A Rollet, F Rondepierre, B Rousselot, S Rubingher, G Saba, JP Salvarelli, JC Samuelian, C Scemama-Ammar, F Schurhoff, JP Schuster, D Sechter, B Segalas, T Seguret, AS Seigneurie, A Semmak, F Slama, S Taisne, M Taleb, JL Terra, D Thefenne, E Tran, R Tourtauchaux, MN Vacheron, P Vandel, V Vanhoucke, E Venet, H Verdoux, A Viala, G Vidon, M Vitre, JL Vurpas, C Wagermez, M Walter, L Yon, X. Zendjidjian, Service de psychiatrie [Le Kremlin-Bicêtre], Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Bicêtre, Centre Hospitalier le Vinatier [Bron], Institut de psychiatrie et neurosciences (U894 / UMS 1266), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), PELLENC S.A., Franche-Comté Électronique Mécanique, Thermique et Optique - Sciences et Technologies (UMR 6174) (FEMTO-ST), Université de Technologie de Belfort-Montbeliard (UTBM)-Ecole Nationale Supérieure de Mécanique et des Microtechniques (ENSMM)-Centre National de la Recherche Scientifique (CNRS)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Laboratoire d'Informatique Fondamentale de Lille (LIFL), Université de Lille, Sciences et Technologies-Institut National de Recherche en Informatique et en Automatique (Inria)-Université de Lille, Sciences Humaines et Sociales-Centre National de la Recherche Scientifique (CNRS), Génomique et Médecine Personnalisée du Cancer et des Maladies Neuropsychiatriques (GPMCND), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), French Society for Biological Psychiatry and Neuropsychopharmacology, Partenaires INRAE, Centre interuniversitaire de recherche et d'ingenierie des matériaux (CIRIMAT), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT), Département d'Astrophysique (ex SAP) (DAP), Institut de Recherches sur les lois Fondamentales de l'Univers (IRFU), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay, Università degli studi di Genova = University of Genoa (UniGe), Fondation FondaMental [Créteil], Fédération Française de Triathlon (FFTRI), Institut de génétique humaine (IGH), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Commissariat à l'énergie atomique et aux énergies alternatives - Laboratoire d'Electronique et de Technologie de l'Information (CEA-LETI), Direction de Recherche Technologique (CEA) (DRT (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Cognition, Santé, Société (C2S), Université de Reims Champagne-Ardenne (URCA)-SFR CAP Santé (Champagne-Ardenne Picardie Santé), Université de Reims Champagne-Ardenne (URCA)-Université de Reims Champagne-Ardenne (URCA)-Maison des Sciences Humaines de Champagne-Ardenne (MSH-URCA), Université de Reims Champagne-Ardenne (URCA), Laboratoire de Neurosciences Intégratives et Cliniques - UFC (UR 481) (NEURO), Université de Franche-Comté (UFC), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service hospitalo-universitaire, centre hospitalier du Rouvray, 4, rue Paul-Eluard, 76300 Sotteville-lès-Rouen, France., CHRU Brest - Psychiatrie Adulte (CHU - Brest- Psychiatrie), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Centre de Physique Théorique [Palaiseau] (CPHT), École polytechnique (X)-Centre National de la Recherche Scientifique (CNRS), Centres d'addictologies - Région Centre, CHU Clermont-Ferrand, Unité de recherche clinique 93G03, établissement public de santé de Ville Evrard, 93330 Neuilly-sur-Marne, France., Laboratoire de Physique des Lasers (LPL), Université Paris 13 (UP13)-Centre National de la Recherche Scientifique (CNRS), Université Montpellier 1 (UM1), CEA-Direction des Energies (ex-Direction de l'Energie Nucléaire) (CEA-DES (ex-DEN)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Neuro-Psycho Pharmacologie des Systèmes Dopimanégiques sous-corticaux (NPsy-Sydo), CHU Clermont-Ferrand-Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), Sonatrach Exploration, Monash University [Clayton], Centre de Recherche en Sciences et Technologies de l'Information et de la Communication - EA 3804 (CRESTIC), Clinique de Psychiatrie et de Psychologie Médicale, Hôpital Pasteur, Nice, France, Centre Hospitalier Universitaire de Nice (CHU Nice), Department of Engineering Cybernetics [Trondheim] (ITK NTNU), Norwegian University of Science and Technology [Trondheim] (NTNU), Norwegian University of Science and Technology (NTNU)-Norwegian University of Science and Technology (NTNU), Jeune Equipe Hémopathogènes Vectorisés, VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS), Silicon-on-Insulator Technologies (SOITEC), Parc Technologique des Fontaines, Recherches en Psychopathologie, nouveaux symptômes et lien social (EA 4050), Université de Poitiers-Université de Brest (UBO)-Université Catholique de l'Ouest (UCO)-Université de Rennes 2 (UR2), Agriculture et forêt méditerranéenne (UR AFAX), Centre national du machinisme agricole, du génie rural, des eaux et forêts (CEMAGREF), Kantar – Health Division, Institut National de Recherche en Génie Rural Eaux et Forêts (INRGREF), Ecole Nationale du Génie Rural, des Eaux et des Forêts (ENGREF)-Institution de la Recherche et de l'Enseignement Supérieur Agricoles [Tunis] (IRESA), Département de psychiatrie [CHRU de Besançon], Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Institut de biologie et chimie des protéines [Lyon] (IBCP), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Pôle Universitaire de Psychiatrie Adulte, Différenciation et communication neuronale et neuroendocrine (DC2N), Centre de Psychiatrie et Neurosciences (U894), Université de Technologie de Belfort-Montbeliard (UTBM)-Ecole Nationale Supérieure de Mécanique et des Microtechniques (ENSMM)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie du CNRS (INC), Dipartimento di Scienze della Terra, Universita degli studi di Genova, Université de Reims Champagne-Ardenne (URCA)-Université de Picardie Jules Verne (UPJV)-Université de Reims Champagne-Ardenne (URCA)-Université de Picardie Jules Verne (UPJV)-Maison des Sciences Humaines de Champagne-Ardenne (MSH-URCA), Laboratoire de Neurosciences Intégratives et Cliniques - UFC (EA 481) (NEURO), Centre National de la Recherche Scientifique (CNRS)-École polytechnique (X), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Ecole Nationale Supérieure de Mécanique et des Microtechniques (ENSMM)-Centre National de la Recherche Scientifique (CNRS)-Université de Technologie de Belfort-Montbeliard (UTBM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), and Université Fédérale Toulouse Midi-Pyrénées

Subjects
Male, Aging, medicine.medical_specialty, Bipolar Disorder, Lithium (medication), Population, [SHS.PSY]Humanities and Social Sciences/Psychology, Comorbidity, [SHS]Humanities and Social Sciences, law.invention, Benzodiazepines, Depressive Disorder, Treatment-Resistant, 03 medical and health sciences, 0302 clinical medicine, Randomized controlled trial, law, medicine, Humans, Bipolar disorder, education, Psychiatry, ComputingMilieux_MISCELLANEOUS, Aged, Depressive Disorder, Major, education.field_of_study, Depression, business.industry, Middle Aged, medicine.disease, Antidepressive Agents, 3. Good health, 030227 psychiatry, Hospitalization, Psychiatry and Mental health, Clinical Psychology, Cross-Sectional Studies, Mood disorders, Tolerability, Schizophrenia, Lithium Compounds, Major depressive disorder, Female, business, 030217 neurology & neurosurgery, Antipsychotic Agents, medicine.drug
Abstract

Although lithium is widely used in current practice to treat bipolar disorder (BD) and treatment-resistant major depressive disorder (MDD) among older adults, little is known about its efficacy and tolerability in this population, which is generally excluded from randomized clinical trials. The objective of this study was to evaluate the efficacy and tolerability of long-term use of lithium among older adults with BD and MDD.Data from the Cohort of individuals with Schizophrenia and mood disorders Aged 55 years or more (CSA) were used. Two groups of patients with BD and MDD were compared: those who were currently receiving lithium versus those who were not. The effects of lithium on psychiatric (i.e., depressive symptoms severity, perceived clinical severity, rates of psychiatric admissions in the past-year), geriatric (overall and cognitive functioning) and physical outcomes (i.e., rates of non-psychiatric medical comorbidities and general hospital admissions in the past-year) were evaluated. All analyses were adjusted for age, sex, duration of disorder, diagnosis, smoking status, alcohol use, and use of antipsychotics, antiepileptics or antidepressants.Among the 281 older participants with BD or MDD, 15.7% were taking lithium for a mean duration of 12.5(SD = 11.6) years. Lithium use was associated with lower intensity of depressive symptoms, reduced perceived clinical global severity and lower benzodiazepine use (all p 0.05), without being linked to greater rates of medical comorbidities, except for hypothyroidism.Data were cross-sectional and data on lifetime history of psychotropic medications was not assessed.Our results suggest that long-term lithium use may be efficient and relatively well-tolerated in older adults with BD or treatment-resistant MDD.

Published
2019

2. A study of the real-world effectiveness of group psychoeducation for bipolar disorders: Is change in illness perception a key mediator of benefit?

Author

Noémie Drancourt, Frank Bellivier, Barbara Cochet, Mohamed Lajnef, Jan Scott, Sophie Lauer, C. Boudebesse, Chantal Henry, Damien Fouques, Bruno Etain, L. Yon, Marion Leboyer, I. Dusser, Jean-Romain Richard, Variabilité de réponse aux Psychotropes (VariaPsy - U1144), Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Fondation FondaMental [Créteil], Hôpitaux Universitaire Saint-Louis, Lariboisière, Fernand-Widal, Université Paris Diderot, Sorbonne Paris Cité, Paris, France, Université Paris Diderot - Paris 7 (UPD7), Newcastle University [Newcastle], Pôle de Psychiatrie [Hôpital Henri Mondor], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital H. Mondor - A. Chenevier, Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Clinique, Psychanalyse, Développement (CliPsyD), Université Paris Nanterre (UPN), HAL Nanterre, Administrateur, Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Descartes - Paris 5 (UPD5), Hôpital Saint-Louis, Université Paris Diderot - Paris 7 (UPD7)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-IFR10, Biomécanique cellulaire et respiratoire (BCR), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Centre National de la Recherche Scientifique (CNRS), Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), and Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)

Subjects
Adult, Male, Mandatory treatment, medicine.medical_specialty, Bipolar Disorder, medicine.medical_treatment, [SDV.NEU.PC] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Psychology and behavior, [SHS.PSY]Humanities and Social Sciences/Psychology, Medication adherence, Effectiveness, Clinical state, Sample attrition, Medication Adherence, [SHS.PSY] Humanities and Social Sciences/Psychology, Illness perceptions, 03 medical and health sciences, 0302 clinical medicine, Patient Education as Topic, Recurrence, Secondary Prevention, Bipolar disorders, Illness perception, Psychoeducation, medicine, Humans, Functioning, 030212 general & internal medicine, Psychiatry, Mediators, Social functioning, Cognitive Behavioral Therapy, [SDV.NEU.PC]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Psychology and behavior, Middle Aged, 030227 psychiatry, 3. Good health, Psychiatry and Mental health, Clinical Psychology, Treatment Outcome, [SCCO.PSYC] Cognitive science/Psychology, [SCCO.PSYC]Cognitive science/Psychology, Patient Compliance, Female, Observational study, [No keyword], sense organs, Psychology, Clinical psychology
Abstract

International audience; BACKGROUND: Findings from efficacy trials of group psychoeducation (PE) for bipolar disorders (BD) led to its inclusion in evidence-based guidelines as a first-line mandatory treatment. However, pragmatic trials and observational studies are needed to determine its real-world effectiveness, impact on outcomes deemed important to patients and to clarify potential mediators of any benefits. METHODS: Individuals with BD were offered the opportunity to participate in 20h of PE and asked to complete pre- and post-intervention ratings of symptoms, knowledge about BD, medication adherence, and illness perception. A priori, two key patient outcomes were identified (social functioning and self-esteem); sample attrition due to dropout or relapse was recorded. RESULTS: Of 156 individuals who completed the pre-PE assessments, 103 completed the program and post-PE assessments. Only 4 of 53 dropouts were associated with BD relapse. Post-intervention, the PE completers demonstrated a statistically significant improvement in social functioning (p = 0.003, Effect Size (ES) = 0.26) and a trend towards improved self-esteem (ES = 0.14). Whilst there were significant changes in medication adherence (p = 0.002, ES = 0.28), knowledge of BD (p < 0.001, ES = 1.20), and illness perception (p < 0.001, ES = -0.37), mediational analysis demonstrated that only change in illness perception was associated to change in functioning (p=0.03) with no contribution from changes in knowledge of BD or medication adherence. CONCLUSIONS: In real-world settings, over 60% individuals completed 10-session course of PE. After controlling for demography and baseline clinical state, change in illness perception, rather than change in knowledge or medication adherence, emerged as a potential mediator of some benefits of PE.

Published
2018

3. Effects of depression and cognitive impairment on quality of life in older adults with schizophrenia spectrum disorder: Results from a multicenter study

Author

A. Brochard, F. Slama, B. Beaufils, O. Guillin, P. Reynaud, M Masson, E. Duprat, M. Miron, Christine Passerieux, A. Rollet, Isabelle Amado, R. Tourtauchaux, H. Hadaoui, A. Leydier, Vincent Camus, Pierre Lavaud, C.E. Rengade, V. Vanhoucke, Nicolas Hoertel, S. Lucas Navarro, Thomas Charpeaud, C. Rodrigues, L. Yon, J. Adès, E. Venet, M.N. Vacheron, V. Griner, Ghassen Saba, T. Bichet, M. Bareil-Guérin, F. Limosin, C. Hanon, Olivier Blanc, H. Gres, L. Mekaoui, J. Mauvieux, Emmanuel Haffen, A. Radtchenko, Frédéric Limosin, D. Arbault, C. Fernandez, B. Rousselot, I. Maurs-Ferrer, A. Mihoubi, A. Heron, E. Tran, R. Gourevitch, O. Maillet, P. Legrand, S. Rubingher, J. Gremion, Xavier Zendjidjian, F. Getten, A.S. Seigneurie, P. Fonfrede, C. Clad-Mor, N. Freitas, A.M. Bouysse, Dominique Januel, Marion Leboyer, P. Vandel, L. Reinheimer, F. Petitjean, A. Rauzy, V. Niro Adès, V. Lemaire, Fabien Gierski, D. Levy-Chavagnat, C. Guggiari, J.F. Karnycheff, M. Cabot, C. Omnes, M. Mahi, A. Grassin Delyle, Hélène Verdoux, D. Robin, Cédric Lemogne, E. Diers, P. Gasnier, J.L. Vurpas, D. Da Rin, Christine Cuervo-Lombard, F. Blanadet, C. Hazif-Thomas, D. Duthoit, Céline Béra-Potelle, J.M. Chabannes, B. Segalas, Hugo Peyre, Hélène Denizot, J.B. Denis, A. Viala, Didier Boussiron, A. Semmak, P. Martin, C. Lajugie, Sarah Barrière, G. Mora, C. Barrouillet, M. Meniai, Michel Walter, J. Ben Ayed, J.P. Salvarelli, K. Benyacoub, T. Seguret, D. Thefenne, M. Benoit, Isabelle Jalenques, B. Bucheron, S. Papin, B. Cordier, D. Pringuey, E. Baup, M. Renard, A. Deperthuis, S. Haouzir, Pierre-Michel Llorca, Y. Blumenstock, A. Dammak, Bérengère Hübsch, D. Donneau, D. Sechter, E. Mechin, Jean-Pierre Schuster, Yvonne Blumenstock, N. Mages, J.C. Samuelian, J.L. Terra, Carlos Blanco, C. Wagermez, H. Bardou, Christophe Guerin-Langlois, A. Petit, A. Kaladjian, J. Gauillard, M. Taleb, M. Creixell, C. Scemama-Ammar, P. Nubukpo, S. Mazmanian, M. Lejoyeux, J. Perlbarg, F. Schürhoff, O. Kebir, G. Amar, O. Brochart, Christophe Portefaix, Christine-Vanessa Cuervo-Lombard, F. Costi, Rachel Pascal de Raykeer, H. Rahiou, C. Alezrah, J.P. Courcelles, N. Bazin, Delphine Raucher-Chéné, J. Pellerin, H. Cuche, V. Charlot, P. Paris, E. Leroy, M. Comisu, M. René, C. Martelli, Arthur Kaladjian, G. Vidon, C. Combes, O. Andréi, A. Manetti, A. Metton, J. Blanc-Comiti, Caroline Dubertret, S. Taisne, S. Perron, M.O. Krebs, M. Vitre, G. Archambault, P. Barrau, S. Dirami, F. Rondepierre, F. Godart, P. Dreano, N. Hoertel, G. Aurifeuille, P. Loeffel, P. Louville, C. Liling, Université Paris Descartes - Paris 5 (UPD5), Centre d’Etudes et de Recherches en Psychopathologie et Psychologie de la Santé (CERPPS), Université Toulouse - Jean Jaurès (UT2J), Maladies neurodéveloppementales et neurovasculaires (NeuroDiderot (UMR_S_1141 / U1141)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), Interactions cellulaires et moléculaires (ICM), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Centre National de la Recherche Scientifique (CNRS), Service psychiatrique de l'enfant et de l'adolescent [CHU Hôpital Robert Debré], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Robert Debré, Institut de psychiatrie et neurosciences (U894 / UMS 1266), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), PELLENC S.A., Franche-Comté Électronique Mécanique, Thermique et Optique - Sciences et Technologies (UMR 6174) (FEMTO-ST), Université de Technologie de Belfort-Montbeliard (UTBM)-Ecole Nationale Supérieure de Mécanique et des Microtechniques (ENSMM)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Centre National de la Recherche Scientifique (CNRS), Laboratoire d'Informatique Fondamentale de Lille (LIFL), Université de Lille, Sciences et Technologies-Institut National de Recherche en Informatique et en Automatique (Inria)-Université de Lille, Sciences Humaines et Sociales-Centre National de la Recherche Scientifique (CNRS), Génomique et Médecine Personnalisée du Cancer et des Maladies Neuropsychiatriques (GPMCND), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), French Society for Biological Psychiatry and Neuropsychopharmacology, Partenaires INRAE, Centre interuniversitaire de recherche et d'ingenierie des matériaux (CIRIMAT), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées, Département d'Astrophysique (ex SAP) (DAP), Institut de Recherches sur les lois Fondamentales de l'Univers (IRFU), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay, Dipartimento di Scienze della Terra, Universita degli studi di Genova, Unité de recherche Biométrie (UB), Institut National de la Recherche Agronomique (INRA), Fondation FondaMental [Créteil], Fédération Française de Triathlon (FFTRI), Institut de génétique humaine (IGH), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Commissariat à l'énergie atomique et aux énergies alternatives - Laboratoire d'Electronique et de Technologie de l'Information (CEA-LETI), Direction de Recherche Technologique (CEA) (DRT (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Cognition, Santé, Société (C2S), Université de Reims Champagne-Ardenne (URCA)-SFR CAP Santé (Champagne-Ardenne Picardie Santé), Université de Reims Champagne-Ardenne (URCA)-Université de Picardie Jules Verne (UPJV)-Université de Reims Champagne-Ardenne (URCA)-Université de Picardie Jules Verne (UPJV)-Maison des Sciences Humaines de Champagne-Ardenne (MSH-URCA), Université de Reims Champagne-Ardenne (URCA), Laboratoire de Neurosciences Intégratives et Cliniques - UFC (EA 481) (NEURO), Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service hospitalo-universitaire, centre hospitalier du Rouvray, 4, rue Paul-Eluard, 76300 Sotteville-lès-Rouen, France., CHRU Brest - Psychiatrie Adulte (CHU - Brest- Psychiatrie), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Centre de Physique Théorique [Palaiseau] (CPHT), École polytechnique (X)-Centre National de la Recherche Scientifique (CNRS), Centres d'addictologies - Région Centre, CHU Clermont-Ferrand, Unité de recherche clinique 93G03, établissement public de santé de Ville Evrard, 93330 Neuilly-sur-Marne, France., Service de Psychiatrie pour Adultes [CHU Reims], Centre Hospitalier Universitaire de Reims (CHU Reims), Université Montpellier 1 (UM1), CEA-Direction des Energies (ex-Direction de l'Energie Nucléaire) (CEA-DES (ex-DEN)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Neuro-Psycho Pharmacologie des Systèmes Dopimanégiques sous-corticaux (NPsy-Sydo), Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-CHU Clermont-Ferrand, Sonatrach Exploration, Monash University [Clayton], Centre de Recherche en Sciences et Technologies de l'Information et de la Communication - EA 3804 (CRESTIC), Clinique de Psychiatrie et de Psychologie Médicale, Hôpital Pasteur, Nice, France, Centre Hospitalier Universitaire de Nice (CHU Nice), Department of Engineering Cybernetics [Trondheim] (ITK NTNU), Norwegian University of Science and Technology [Trondheim] (NTNU), Norwegian University of Science and Technology (NTNU)-Norwegian University of Science and Technology (NTNU), Jeune Equipe Hémopathogènes Vectorisés, VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS), Silicon-on-Insulator Technologies (SOITEC), Parc Technologique des Fontaines, Recherches en Psychopathologie, nouveaux symptômes et lien social (EA 4050), Université de Poitiers-Université de Brest (UBO)-Université Catholique de l'Ouest (UCO)-Université de Rennes 2 (UR2), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES), Agriculture et forêt méditerranéenne (UR AFAX), Centre national du machinisme agricole, du génie rural, des eaux et forêts (CEMAGREF), Kantar – Health Division, Institut National de Recherche en Génie Rural Eaux et Forêts (INRGREF), Ecole Nationale du Génie Rural, des Eaux et des Forêts (ENGREF)-Institution de la Recherche et de l'Enseignement Supérieur Agricoles [Tunis] (IRESA), Département de psychiatrie [CHU de Besançon], Centre Hospitalier Régional Universitaire [Besançon] (CHRU Besançon), Institut de biologie et chimie des protéines [Lyon] (IBCP), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Pôle Universitaire de Psychiatrie Adulte, Différenciation et communication neuronale et neuroendocrine (DC2N), and PHRC 2008-N11-01, Ministère des Affaires Sociales et de la Santé

Subjects
Male, Quality of life, Schizoaffective disorder, [SDV]Life Sciences [q-bio], [SHS.PSY]Humanities and Social Sciences/Psychology, Structural equation modeling, [SHS]Humanities and Social Sciences, Cohort Studies, 03 medical and health sciences, 0302 clinical medicine, Cognition, Elderly, medicine, Humans, Cognitive Dysfunction, Depression (differential diagnoses), ComputingMilieux_MISCELLANEOUS, Aged, Aged, 80 and over, Psychiatric Status Rating Scales, business.industry, Depression, Middle Aged, medicine.disease, 3. Good health, 030227 psychiatry, Psychiatry and Mental health, Clinical Psychology, Cross-Sectional Studies, Schizophrenia, Older adults, Cohort, Female, Schizophrenic Psychology, business, 030217 neurology & neurosurgery, Clinical psychology, Schizophrenia spectrum
Abstract

Little is known about the respective effects of depression and cognitive impairment on quality of life among older adults with schizophrenia spectrum disorder.We used data from the Cohort of individuals with Schizophrenia Aged 55-years or more (CSA) study, a large multicenter sample of older adults with schizophrenia or schizoaffective disorder (N = 353). Quality of life (QoL), depression and cognitive impairment were assessed using the Quality of Life Scale (QLS), the Center of Epidemiologic Studies Depression scale and the Mini-Mental State Examination, respectively. We used structural equation modeling to examine the shared and specific effects of depression and cognitive impairment on QoL, while adjusting for sociodemographic characteristics, general medical conditions, psychotropic medications and the duration of the disorder.Depression and cognitive impairment were positively associated (r = 0.24, p 0.01) and both independently and negatively impacted on QoL (standardized β = -0.41 and β = -0.32, both p 0.01) and on each QLS quality-of-life domains, except for depression on instrumental role and cognitive impairment on interpersonal relations in the sensitivity analyses excluding respondents with any missing data. Effects of depression and cognitive impairment on QoL were not due to specific depressive symptoms or specific cognitive domains, but rather mediated through two broad dimensions representing the shared effects across all depressive symptoms and all cognitive deficits, respectively.Because of the cross-sectional design of this study, measures of association do not imply causal associations.Mechanisms underlying these two broad dimensions should be considered as important potential targets to improve quality of life of this vulnerable population.

Published
2019

4. Exploring venlafaxine pharmacokinetic variability with a phenotyping approach, a multicentric french-swiss study (MARVEL study)

Author

Philippe Le Corvoisier, Jules Alexandre Desmeules, Célia Lloret-Linares, Jean-Luc Cracowski, Wissam El-Hage, L. Yon, Kyle Heron, Frank Bellivier, Frédéric Haesebaert, Siamak Davani, Damien Montange, Thomas Desmidt, Olivier Doumy, Antoine Yrondi, Fanny Moliere, Raphaëlle-Marie Richieri, Philippe Vignaud, Sophie Morange, Marie Besson, Sylvie Chevret, Isabelle Nieto, Marion Leboyer, Jérôme Holtzmann, F. Galtier, Fabienne Calvas, Julien Déglon, Pierre-Michel Llorca, Emmanuel Haffen, Philippe Courtet, Youssef Daali, Biostatistique et épidemiologie clinique, Université Paris Diderot - Paris 7 ( UPD7 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Pathologies du système nerveux : recherche épidémiologique et clinique, Université Montpellier 1 ( UM1 ) -IFR76-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Centre de pharmacologie et innovation dans le diabète ( CPID ), Université Montpellier 1 ( UM1 ) -Centre Hospitalier Régional Universitaire [Montpellier] ( CHRU Montpellier ) -Centre National de la Recherche Scientifique ( CNRS ), Centre d'Investigation Clinique ( CIC ), Hospices Civils de Lyon ( HCL ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -CHU de Lyon, Neuro-Psycho Pharmacologie des Systèmes Dopimanégiques sous-corticaux - Clermont Auvergne ( NPsy-Sydo ), CHU Clermont-Ferrand-Université Clermont Auvergne ( UCA ), Clinique Psychiatrique Universitaire [Tours], CHRU Tours, Imagerie et cerveau, Université de Tours-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Hypoxie : Physiopathologie Respiratoire et Cardiovasculaire ( HP2 ), Université Joseph Fourier - Grenoble 1 ( UJF ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Service de psychiatrie, Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Henri Mondor-Hôpital Albert Chenevier, Institut Mondor de Recherche Biomédicale ( IMRB ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 ( UPEC UP12 ), CIC - CHU Henri Mondor, Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université Paris-Est Créteil Val-de-Marne - Paris 12 ( UPEC UP12 ), Centre Hospitalier Régional Universitaire [Besançon] ( CHRU Besançon ), UR 1341 Alimentation et adaptations digestives, nerveuses et comportementales, Institut National de la Recherche Agronomique ( INRA ) -Alimentation Humaine ( ALIM.H ) -Alimentation et adaptations digestives, nerveuses et comportementales ( ADNC ), Cognition, Action, et Plasticité Sensorimotrice [Dijon - U1093] ( CAPS ), Université de Bourgogne ( UB ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Optimisation thérapeutique en Neuropsychopharmacologie (OPTeN (UMR_S_1144 / U1144)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), Hôpital Lariboisière-Fernand-Widal [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Geneva University Hospital (HUG), Service de biostatistique et information médicale de l’hôpital Saint Louis (Equipe ECSTRA) (SBIM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut national du cancer [Boulogne] (INCA)-Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université de Paris (UP), Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], CHU Montpellier, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Assistance Publique - Hôpitaux de Marseille (APHM), CHU Clermont-Ferrand, Neuro-Psycho Pharmacologie des Systèmes Dopimanégiques sous-corticaux (NPsy-Sydo), CHU Clermont-Ferrand-Université Clermont Auvergne (UCA), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Centre d’Investigation Clinique [Tours] CIC 1415 (CIC ), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau-Université de Tours-Institut National de la Santé et de la Recherche Médicale (INSERM), Imagerie et cerveau (iBrain - Inserm U1253 - UNIV Tours ), Université de Tours-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de recherche en neurosciences de Lyon (CRNL), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université Laval [Québec] (ULaval), Centre Hospitalier Universitaire [Grenoble] (CHU), Centre d'Investigation Clinique [Grenoble] (CIC Grenoble ), CHU Grenoble-Hôpital Michallon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Hôpital Albert Chenevier, Fondation FondaMental [Créteil], CHU Toulouse [Toulouse], Toulouse Neuro Imaging Center (ToNIC), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse]-CHU Toulouse [Toulouse], Centre d'investigation clinique de Toulouse (CIC 1436), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre d'Investigation Clinique Henri Mondor (CIC Henri Mondor), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), CHU Bordeaux [Bordeaux], University of Bristol [Bristol], Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Lausanne University Hospital, Cognition, Action, et Plasticité Sensorimotrice [Dijon - U1093] (CAPS), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Cité (UPCité), CHU Clermont-Ferrand-Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau-Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de recherche en neurosciences de Lyon - Lyon Neuroscience Research Center (CRNL), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Toulouse Mind & Brain Institut (TMBI), Université Toulouse - Jean Jaurès (UT2J), Université de Toulouse (UT)-Université de Toulouse (UT)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université Toulouse - Jean Jaurès (UT2J), Université de Toulouse (UT)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Pôle Santé publique et médecine publique [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Toulouse Mind & Brain Institut (TMBI), Université Toulouse - Jean Jaurès (UT2J)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Université Toulouse - Jean Jaurès (UT2J)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées, Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Pôle Santé publique et médecine publique [CHU Toulouse], Douhairie, Marie-Laurence, and Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-IFR10

Subjects
Male, Oncology, [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, [SDV.NEU.PC] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Psychology and behavior, Venlafaxine, Pharmacology, 030226 pharmacology & pharmacy, ATP-Binding Cassette, Sub-Family B, Member 1/metabolism, Adolescent, Adult, Aged, Aged, 80 and over, Antidepressive Agents, Second-Generation/blood, Antidepressive Agents, Second-Generation/pharmacokinetics, Antidepressive Agents, Second-Generation/therapeutic use, Cytochrome P-450 CYP2C19/metabolism, Cytochrome P-450 CYP2D6/metabolism, Cytochrome P-450 CYP3A/metabolism, Depressive Disorder, Major/drug therapy, Depressive Disorder, Major/metabolism, Female, France, Genotype, Humans, Middle Aged, Phenotype, Switzerland, Treatment Outcome, Venlafaxine Hydrochloride/blood, Venlafaxine Hydrochloride/pharmacokinetics, Venlafaxine Hydrochloride/therapeutic use, Young Adult, Study Protocol, [ SDV.NEU.SC ] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Cognitive Sciences, 0302 clinical medicine, 80 and over, Cytochrome P-450 CYP3A, Medicine, Pharmacology (medical), Major depressive episode, ComputingMilieux_MISCELLANEOUS, ddc:615, ddc:617, [SDV.NEU.PC]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Psychology and behavior, Venlafaxine Hydrochloride, Area under the curve, [SDV.NEU.SC]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Cognitive Sciences, Antidepressive Agents, 3. Good health, Cytochrome P-450 CYP2D6, [ SDV.NEU.NB ] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, [ SCCO.NEUR ] Cognitive science/Neuroscience, Antidepressive Agents, Second-Generation, medicine.symptom, medicine.drug, CYP2D6, medicine.medical_specialty, Major/drug therapy/metabolism, CYP2C19, [ SDV.NEU.PC ] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Psychology and behavior, 03 medical and health sciences, Pharmacokinetics, lcsh:RA1190-1270, Internal medicine, Member 1/metabolism, ATP Binding Cassette Transporter, Subfamily B, Member 1, Dosing, lcsh:Toxicology. Poisons, Second-Generation/blood/pharmacokinetics/therapeutic use, Depressive Disorder, Depressive Disorder, Major, Sub-Family B, business.industry, [SCCO.NEUR]Cognitive science/Neuroscience, lcsh:RM1-950, [SCCO.NEUR] Cognitive science/Neuroscience, [SDV.NEU.NB] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, Cytochrome P-450 CYP2C19, lcsh:Therapeutics. Pharmacology, Venlafaxine Hydrochloride/blood/pharmacokinetics/therapeutic use, ATP-Binding Cassette, Personalized medicine, business, [SDV.NEU.SC] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Cognitive Sciences, 030217 neurology & neurosurgery
Abstract

It is well known that the standard doses of a given drug may not have equivalent effects in all patients. To date, the management of depression remains mainly empirical and often poorly evaluated. The development of a personalized medicine in psychiatry may reduce treatment failure, intolerance or resistance, and hence the burden and costs of mood depressive disorders. The Geneva Cocktail Phenotypic approach presents several advantages including the “in vivo” measure of different cytochromes and transporter P-gp activities, their simultaneous determination in a single test, avoiding the influence of variability over time on phenotyping results, the administration of low dose substrates, a limited sampling strategy with an analytical method developed on DBS analysis. The goal of this project is to explore the relationship between the activity of drug-metabolizing enzymes (DME), assessed by a phenotypic approach, and the concentrations of Venlafaxine (VLX) + O-demethyl-venlafaxine (ODV), the efficacy and tolerance of VLX. This study is a multicentre prospective non-randomized open trial. Eligible patients present a major depressive episode, MADRS over or equal to 20, treatment with VLX regardless of the dose during at least 4 weeks. The Phenotype Visit includes VLX and ODV concentration measurement. Following the oral absorption of low doses of omeprazole, midazolam, dextromethorphan, and fexofenadine, drug metabolizing enzymes activity is assessed by specific metabolite/probe concentration ratios from a sample taken 2 h after cocktail administration for CYP2C19, CYP3A4, CYP2D6; and by the determination of the limited area under the curve from the capillary blood samples taken 2–3 and 6 h after cocktail administration for CYP2C19 and P-gp. Two follow-up visits will take place between 25 and 40 days and 50–70 days after inclusion. They include assessment of efficacy, tolerance and observance. Eleven french centres are involved in recruitment, expected to be completed within approximately 2 years with 205 patients. Metabolic ratios are determined in Geneva, Switzerland. By showing an association between drug metabolism and VLX concentrations, efficacy and tolerance, there is a hope that testing drug metabolism pathways with a phenotypical approach would help physicians in selecting and dosing antidepressants. The MARVEL study will provide an important contribution to increasing the knowledge of VLX variability and in optimizing the use of methods of personalized therapy in psychiatric settings. ClinicalTrials.gov NCT02590185 (10/27/2015). This study is currently recruiting participants.

Published
2017

5. Adenocarcinoma of the uterine cervix metastatic to lymph nodes

Author

Howard G. Muntz, Benjamin E. Greer, Rae Wu, Hisham K. Tamimi, Michael R. Smith, Rodney A. Schmidt, David E. Cohn, William A. Peters, Barbara A. Goff, Joseph L. Yon, and Charles W. Drescher

Subjects
Adult, Oncology, medicine.medical_specialty, Adenosquamous carcinoma, Uterine Cervical Neoplasms, Adenocarcinoma, Hysterectomy, Metastasis, Carcinoma, Adenosquamous, Internal medicine, medicine, Adjuvant therapy, Humans, Radical Hysterectomy, Cervix, Lymph node, Aged, Neoplasm Staging, Retrospective Studies, business.industry, Obstetrics and Gynecology, Combination chemotherapy, Middle Aged, Prognosis, medicine.disease, Combined Modality Therapy, Survival Analysis, Surgery, medicine.anatomical_structure, Lymphatic Metastasis, Female, business
Abstract

OBJECTIVE: We set out to evaluate the prognostic factors in cervical adenocarcinoma metastatic to lymph nodes. STUDY DESIGN: We performed a retrospective review of 40 patients with cervical adenocarcinoma and lymph node metastasis from 1976 to 1996. RESULTS: Thirty-four patients had adenocarcinoma, and six had adenosquamous carcinoma. Median survival was 50 months. The median survival for patients with stage I disease was 69 months. Stage at diagnosis, treatment with radical hysterectomy, and receiving adjuvant therapy were associated with prolonged survival. A trend toward improved survival was noted with the use of concurrent radiation and chemotherapy as an adjuvant therapy. CONCLUSIONS: Adenocarcinoma metastatic to the lymph nodes does not have a uniformly poor prognosis, especially with early-stage disease. Improved survival was observed with the use of adjuvant therapy, specifically the use of combined chemotherapy and radiation after radical hysterectomy. The optimal therapy in this setting is yet to be determined. (Am J Obstet Gynecol 1998;178:1131-7.)

Published
1998

6. Clinical and dimensional characteristics of euthymic bipolar patients with or without suicidal behavior

Author

Frank Bellivier, Mohamed Lajnef, Bruno Etain, C. Parmentier, Renaud Cohen, Jean-Pierre Kahn, Flavie Mathieu, C. Henry, Aurélie Raust, Barbara Cochet, Hélène Misson, O. Wajsbrot-Elgrabli, L. Yon, Marion Leboyer, Pôle de Psychiatrie [Hôpital Henri Mondor], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital H. Mondor - A. Chenevier, Fondation FondaMental [Créteil], Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Psychiatrie et Psychologie Clinique de Liaison [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Université Paris-Est Créteil Val-de-Marne - Faculté de médecine (UPEC Médecine), and Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)

Subjects
Adult, Male, medicine.medical_specialty, Poison control, Suicide, Attempted, Hostility, Irritability, Impulsivity, 03 medical and health sciences, Sex Factors, 0302 clinical medicine, Severity of illness, mental disorders, medicine, Humans, Bipolar disorder, Psychiatry, [SHS.STAT]Humanities and Social Sciences/Methods and statistics, Suicide attempt, [SCCO.NEUR]Cognitive science/Neuroscience, Middle Aged, medicine.disease, Cyclothymic Disorder, 030227 psychiatry, Psychiatry and Mental health, [SCCO.PSYC]Cognitive science/Psychology, Anxiety, Female, medicine.symptom, Psychology, [STAT.ME]Statistics [stat]/Methodology [stat.ME], 030217 neurology & neurosurgery, Clinical psychology
Abstract

BackgroundThe clinical and dimensional features associated with suicidal behaviour in bipolar patients during euthymic states are not well characterised.MethodsIn a sample of 652 euthymic bipolar patients, we assessed clinical features with the Diagnostic Interview for Genetics Studies (DIGS) and dimensional characteristics with questionnaires measuring impulsivity/hostility and affective lability/intensity. Bipolar patients with and without suicidal behaviour were compared for these clinical and dimensional variables.ResultsOf the 652 subjects, 42.9% had experienced at least one suicide attempt. Lifetime history of suicidal behaviour was associated with being a woman, a history of head injury, tobacco misuse and indicators of severity of bipolar disorder including early age at onset, high number of depressive episodes, positive history of rapid cycling, alcohol misuse and social phobia. Indirect hostility and irritability were dimensional characteristics associated with suicidal behaviour in bipolar patients, whereas impulsivity and affective lability/intensity were not associated with suicidal behaviour.LimitationsThis study had a retrospective design with no replication sample.ConclusionsBipolar patients with earlier onset, mood instability (large number of depressive episodes, rapid cycling) and/or particular addictive and anxiety comorbid disorders might be at high risk of suicidal behaviour. In addition, hostility dimensions (indirect hostility and irritability), may be trait components associated with suicidal behaviour in euthymic bipolar patients.

Published
2012

7. [Treatment initiation in psychotic and manic episodes: French attitudes collected by Focus Group]

Author

M, Benoit, F, Bellivier, P-M, Llorca, B, Millet, M, Passamar, R, Schwan, L, Marty, L, Cailhol, B, Giordana, F, Naudet, L, Samalin, M, Tadri, L, Yon, E, Hacques, and V, Moreau-Mallet

Subjects
Adult, Male, Bipolar Disorder, Evidence-Based Medicine, Focus Groups, Middle Aged, Drug Administration Schedule, Medication Adherence, Psychotic Disorders, Antimanic Agents, Practice Guidelines as Topic, Schizophrenia, Adverse Drug Reaction Reporting Systems, Humans, Drug Interactions, Drug Therapy, Combination, Female, Schizophrenic Psychology, Aged, Antipsychotic Agents
Abstract

An accurate treatment of first episodes in schizophrenia and bipolar disorders has a significant impact on compliance and prognosis. However, existing therapeutic guidelines may be poorly respected and may concern only typical clinical situations. Medical attitudes in clinical practice have been collected and structured on the basis of small interactive meetings (Focus Group [FG]), and a synthesis of practical attitudes has been compared with updated guidelines. The FG method applied to treatment initiation in schizophrenia and bipolar disorder is seen as complementary to evidence-based guidelines. It reveals that, in a reflexive manner, clinical attitudes are often more diverse and frequently consider first treatments after global evaluation, taking more into account external factors such as clinicians' experience, patient's history and willingness, clinical setting, and environment. A symptomatic approach is sometimes preferred, and a better alliance is always considered as a main objective. The FG method could be a supplementary support to continuous medical education.

Published
2012

8. The Antiestrogen Tamoxifen in the Treatment of Recurrent Benign Cystic Mesothelioma

Author

Joseph L. Yon and Gerard S. Letterie

Subjects
Adult, Oncology, medicine.medical_specialty, Antineoplastic Agents, Hormonal, Bone density, Multicystic Mesothelioma, Asymptomatic, Internal medicine, medicine, Humans, Radical surgery, skin and connective tissue diseases, Peritoneal Neoplasms, business.industry, Obstetrics and Gynecology, Mesothelioma, Cystic, medicine.disease, Antiestrogen, Surgery, Menopause, Tamoxifen, Female, Liver function, Neoplasm Recurrence, Local, medicine.symptom, business, medicine.drug
Abstract

Benign cystic mesothelioma is a tumor characteristically found in women during the reproductive years. These tumors are infrequently found after castration or menopause, suggesting some degree of hormonal sensitivity. Such aspects of the tumor suggest a potential role for antiestrogens as medical management and an alternative to radical surgery. We treated a 19-year-old woman with a symptomatic pelvic mass secondary to a recurrent benign cystic mesothelioma 2 years after radical surgery with the antiestrogen tamoxifen. An initial reduction in volume and arrest of growth was followed by stabilization in size and disappearance of symptoms. Therapy was continued for 18 months with no change in the volume of the cystic structure. The patient continued to be asymptomatic. Periodic surveillance with quantitative digital radiography for bone density showed no change in bone mineral density. Serum testing for liver function studies was normal throughout treatment. This case suggests that antiestrogens may have a role in the medical management of these rare estrogen-dependent neoplasms. The initial reduction in size and arrest in growth further suggest extreme sensitivity of this tumor to manipulation of the hormonal milieu. Therapy with the antiestrogen tamoxifen in this setting may provide an option for long-term medical management in cases of symptomatic recurrent cystic mesotheliomas.

Published
1998

9. Biochemical characterisation and immunohistochemical localisation of the secretogranin II-derived peptide EM66 in the hypothalamus of the jerboa (Jaculus orientalis): modulation by food deprivation

Author

M, Boutahricht, J, Guillemot, M, Montero-Hadjadje, S, Bellafqih, S, El Ouezzani, A, Alaoui, L, Yon, H, Vaudry, Y, Anouar, and R, Magoul

Subjects
Male, Molecular Sequence Data, Arcuate Nucleus of Hypothalamus, Rodentia, Feeding Behavior, Immunohistochemistry, Peptide Fragments, Secretogranin II, Chromogranins, Animals, Female, Amino Acid Sequence, Food Deprivation, Paraventricular Hypothalamic Nucleus
Abstract

The neuroendocrine protein secretogranin II is the precursor of several neuropeptides, including secretoneurin and a novel 66-amino acid peptide, EM66, the sequence of which has been highly conserved across the vertebrae phylum. The presence of EM66 has been detected in the adult and fetal human adrenal gland, as well as the rat pituitary and adrenal glands. The present study aimed to explore a possible neuroendocrine role of EM66 by analysing its occurrence and distribution within the jerboa hypothalamus, and its potential implication in the control of feeding behaviour. High-performance liquid chromatography analysis of jerboa hypothalamic extracts combined with a radioimmunoassay of EM66 revealed a single peak of immunoreactive material exhibiting the same retention time as recombinant EM66. Immunocytochemical labelling showed that EM66-producing neurones are widely distributed in several hypothalamic regions, including the preoptic area, the suprachiasmatic, supraoptic, parvocellular paraventricular and arcuate nuclei, and the lateral hypothalamus. Food deprivation for 5 days induced a significant increase in the number of EM66-containing neurones within the arcuate nucleus (105% increase) and the parvocellular aspect of the paraventricular nucleus (115% increase), suggesting that EM66 could be involved in the control of feeding behaviour and/or the response to stress associated with fasting. Altogether, these data reveal the physiological plasticity of the EM66 system in the hypothalamus and implicate this novel peptide in the regulation of neuroendocrine functions.

Published
2005

10. Use of a long-acting GnRH agonist for benign cystic mesothelioma

Author

Gerard S. Letterie and Joseph L. Yon

Subjects
Agonist, medicine.medical_specialty, Adolescent, medicine.drug_class, Multicystic Mesothelioma, Urology, Gonadotropin-Releasing Hormone, Internal medicine, medicine, Humans, Cyst, Peritoneal Neoplasms, Pelvic Neoplasms, business.industry, Estrogen Replacement Therapy, Obstetrics and Gynecology, Mesothelioma, Cystic, medicine.disease, Discontinuation, Menopause, Endocrinology, Estrogen, Delayed-Action Preparations, Concomitant, Female, Progestins, business, Progestin
Abstract

Background: Benign cystic mesothelioma, a tumor characteristically found in women during the reproductive years, is rare after bilateral oophorectomy or menopause, suggesting hormonal sensitivity. Case: We treated a 17-year-old woman with a rapidly increasing and symptomatic benign cystic mesothelioma with a long-acting GnRH agonist. A rapid and continued reduction in volume corresponded to the induction and maintenance of a hypoestrogenic state over a 6-month period. However, the subsequent addition of a combination of estrogen and progestin (known as add-back therapy) resulted in a gradual increase in cyst volume, which progressed after discontinuation of all therapy. Resumption of GnRH-analog therapy alone reduced cyst volume again, and the patient underwent surgical removal. Conclusion: Long-acting GnRH agonists may have a role in the conservative management of these rare neoplasms. The reduction in volume concomitant with a hypoestrogenic state and regrowth with addition of add-back therapy further suggest extreme sensitivity of this tumor to one or both hormones.

Published
1995

11. Localization, Characterization, and Second Messenger Coupling of Pituitary Adenylate Cyclase-Activating Polypeptide Receptors in the Fetal Human Adrenal Gland during the Second Trimester of Gestation*

Author

L, Yon, L, Breault, V, Contesse, G, Bellancourt, C, Delarue, A, Fournier, J G, Lehoux, H, Vaudry, N, Gallo-Payet, Neuroendocrinologie cellulaire et moléculaire, Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Fédératif de Recherches Multidisciplinaires sur les Peptides (IFRMP 23), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre de Lutte Contre le Cancer Henri Becquerel Normandie Rouen (CLCC Henri Becquerel)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Université Le Havre Normandie (ULH), Normandie Université (NU)-CHU Rouen, Normandie Université (NU)-Centre National de la Recherche Scientifique (CNRS), Faculté de médecine et des sciences de la santé [Sherbrooke] (UdeS), Université de Sherbrooke (UdeS), Université du Québec à Montréal = University of Québec in Montréal (UQAM), Institut Armand Frappier (INRS-IAF), Institut National de la Recherche Scientifique [Québec] (INRS)-Réseau International des Instituts Pasteur (RIIP), This work was supported by the Medical Research Council of Canada (MRC MT13679, to N.G.-P. and J.-G.L.), the Institut National de la Santé et de la Recherche Médicale (INSERM U413), a France-Québec exchange programme (Coopération Scientifique et Technologique Franco-Québécoise (PVP-73–9, to N.G.-P. and H.V.), and the Conseil Régional de Haute-Normandie., and The authors would like to thank Ms. Huguette Lemonnier (INSERM U413) and Lucie Chouinard (Service of Endocrinology, Sherbrooke) for skillful technical assistance. We appreciate the advice from Drs. Magali Basille and Bruno Gonzalez (INSERM U413) for autoradiography.

Subjects
MESH: Receptors, Pituitary Hormone/metabolism, [SDV]Life Sciences [q-bio], Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide, MESH: Logistic Models, Second Messenger Systems, Embryonic and Fetal Development, MESH: Autoradiography, MESH: Pregnancy, Pregnancy, MESH: Analysis of Variance, Adrenal Glands, Humans, Receptors, Pituitary Hormone, Cells, Cultured, MESH: Embryonic and Fetal Development/physiology, Analysis of Variance, MESH: Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide, MESH: Second Messenger Systems/physiology, MESH: Humans, MESH: Adrenal Glands/metabolism, MESH: Adrenal Glands/embryology, Logistic Models, Pregnancy Trimester, Second, MESH: Pregnancy Trimester, Second, MESH: Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide, Type I, Autoradiography, Female, MESH: Female, Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide, Type I, MESH: Cells, Cultured
Abstract

International audience; The distribution and pharmacological properties of pituitary ad-enylate cyclase-activating polypeptide (PACAP) receptors were studied in the fetal human adrenal gland during the second trimester of gestation. Autoradiographic studies, using [ 125 I]PACAP27 as a ra-dioligand, revealed that PACAP-binding sites are exclusively located on chromaffin cells of adrenals from fetuses 14 –20 weeks old. Biochemical characterization of binding revealed the occurrence of a single class of PACAP-binding sites with a dissociation constant value of 0.32– 0.74 nmol/L and a binding capacity of 0.30 – 0.81 pmol/mg wet tissue. PACAP27 and PACAP38 were equipotent in competing for [ 125 I]PACAP27 binding (IC 50 0.28 – 0.64 nmol/L and 0.15– 0.81 nmol/L, respectively), and the Hill coefficients were close to 1. In contrast, vasoactive intestinal polypeptide was much less efficient in displacing the tracer (IC 50 4 –362 nmol/L), and the Hill coefficients were less than 0.6. PACAP38 induced a dose-dependent increase in cAMP production in fetal human adrenal cell suspension (ED 50 0.07 0.02 nmol/L), as well as in cells maintained in culture for 5 days (5.4 1.8 nmol/L). In constrast, PACAP38 induced a modest increase in inositol phosphate formation. These data indicate that type I PACAP receptors are present in the early stages of the human me-dulla organization during the process of migration of chromaffin cells from the periphery to the central part of the gland. The present results suggest that PACAP could be involved in the regulation of the human adrenochromaffin cells during ontogenesis. (J Clin Endocrinol Metab 83: 1299 –1305, 1998)

Published
1997

13. Carcinomatous meningitis complicating cervical cancer: a clinicopathologic study and literature review

Author

Lynne P. Taylor, R. H. Rudolph, David M. Aboulafia, Robert Crane, and Joseph L. Yon

Subjects
Adult, medicine.medical_specialty, Systemic disease, Pathology, Carcinosis, Uterine Cervical Neoplasms, Adenocarcinoma, Metastasis, Fatal Outcome, medicine, Meningeal Neoplasms, Humans, Meningitis, Cervical cancer, business.industry, Cranial Nerves, Obstetrics and Gynecology, medicine.disease, Oncology, Female, Radiology, Complication, business, Tomography, X-Ray Computed, Medical literature
Abstract

Patients with gynecologic malignancies may develop metastases throughout the neuraxis. Cervix-related carcinomatous meningitis is a distinctly unusual clinical event with only two previous cases reported in the English medical literature. We review clinical, radiographic, and pathologic findings of a woman with advanced adenocarcinoma of the uterine cervix, whose course was complicated by leptomeningeal metastases. Carcinomatous meningitis occurs in the setting of rapidly advancing systemic disease and represents a terminal complication of cervical cancer.

Published
1996

14. Intraperitoneal P-32 is not an effective consolidation therapy after a negative second-look laparotomy for epithelial carcinoma of the ovary

Author

William A. Peters, Joseph L. Yon, Joanna M. Cain, Michael R. Smith, and Roger B. Lee

Subjects
Adult, Chromium, Reoperation, medicine.medical_specialty, medicine.medical_treatment, Brachytherapy, Phosphates, chemistry.chemical_compound, Laparotomy, Chromium Compounds, medicine, Carcinoma, Humans, Life Tables, Stage (cooking), Radiation Injuries, Peritoneal Cavity, Aged, Neoplasm Staging, Ovarian Neoplasms, Chemotherapy, Epithelioma, business.industry, Obstetrics and Gynecology, Induction chemotherapy, Combination chemotherapy, Dose-Response Relationship, Radiation, Middle Aged, medicine.disease, Combined Modality Therapy, Survival Analysis, Carboplatin, Surgery, Intestines, Oncology, chemistry, Female, business, Phosphorus Radioisotopes
Abstract

Thirty-four patients with epithelial carcinoma of the ovary were entered into a trial of adjuvant intraperitoneal P-32 following induction chemotherapy and a negative second-look laparotomy. The breakdown by initial Stage was Stage IC, 5; Stage II, 3; Stage III optimal, 22; and Stage III suboptimal, 4. Previous treatment consisted of 4-12 cycles (median 6) of cisplatin or carboplatin-based combination chemotherapy. Fifteen millicuries of P-32 were instilled via a Tenckhoff catheter placed at the time of second-look laparotomy. Because of a 22% incidence of bowel injury in the first 23 patients, the P-32 dose was reduced to 12 mCi in the last 11 patients. To date, there have been no bowel injuries at the lower dose. Eighteen of the 34 (53%) patients have relapsed with a median time to relapse of 20 months and a median follow-up for all patients of 31 months. There has been no difference in the relapse rate between a dose of 12 and 15 mCi. Intraperitoneal P-32 does not appear to reduce the relapse rate following a negative second-look laparotomy. The incidence of bowel injury is dose dependent and is higher than that seen in patients treated as an adjuvant following initial surgery without subsequent chemotherapy or second-look laparotomy.

Published
1992

15. Alternating combination chemotherapy for stages III and IV ovarian carcinoma

Author

J Kroener, Sidney L. Saltzstein, J A Koziol, J A Young, T N Campbell, A Johnson, J L Yon, William E. Lucas, and Mark R. Green

Subjects
Adult, Oncology, Cancer Research, medicine.medical_specialty, Cyclophosphamide, medicine.medical_treatment, Adenocarcinoma, Gastroenterology, Internal medicine, Ovarian carcinoma, Antineoplastic Combined Chemotherapy Protocols, medicine, Humans, Aged, Ovarian Neoplasms, Cisplatin, Chemotherapy, business.industry, Combination chemotherapy, Middle Aged, Debulking, medicine.disease, Combined Modality Therapy, Female, Methotrexate, business, medicine.drug
Abstract

Thirty-nine previously untreated patients with stages III and IV ovarian carcinoma were treated with debulking surgery, followed by alternating combination chemotherapy with cisplatin, Adriamycin (Adria Laboratories, Columbus, Ohio), and cyclophosphamide (PAC); and hexamethylmelamine, cyclophosphamide, methotrexate, and 5-fluorouracil (HexaCAF). Of 19 patients with measureable disease at the onset of therapy, ten (53%) had at least a partial response to chemotherapy. Seven (18% of total) patients were found to be pathologically free of disease at secondlook surgery, but four patients relapsed 19 to 31 months after initiating therapy. The median progression-free survival period of all 39 patients entered into the study is 12 months, and the median crude survival is 21 months. The PAC/HexaCAF alternating combination chemotherapy regimen may be administered with moderate toxicity, but the treatment results are not superior to those reported for PAC or HexaCAF alone in advanced ovarian carcinoma.

Published
1984

16. Adenosis and adenocarcinoma of the vagina in young women: A review

Author

Robert E. Girtanner, Joseph L. Yon, Myron H. Lutz, and Hervy E. Averette

Subjects
Adenoma, Adult, medicine.medical_specialty, Vaginal Neoplasms, Adolescent, medicine.medical_treatment, Estrogenic Compounds, Adenocarcinoma, Adenosis, Primary adenocarcinoma, Pregnancy, Humans, Medicine, Child, Diethylstilbestrol, Gynecology, business.industry, Age Factors, Complete remission, Obstetrics and Gynecology, medicine.disease, Radiation therapy, First trimester, medicine.anatomical_structure, Oncology, Carcinoma, Squamous Cell, Vagina, Female, business
Abstract

Prior to 1971, adenosis and primary adenocarcinoma of the vagina were unusual entities. Since then, a marked increase in both processes has occurred, felt to be related to maternal ingestion of Diethylstibestrol (DES) and other estrogenic compounds during the first trimester, with subsequent abnormalities in female off-spring. To date, there are over 170 cases of adenocarcinoma reported, and there may be as many as one million patients with adenosis. Treatment of benign adenosis is somewhat of a controversy but adenocarcinoma is treated with surgery, radiation or a combination thereof, depending upon the specifics of the patients. Four patients are presented, one treated surgically and three with radiotherapy, all with complete remission over one to two years. It behooves all physicians caring for young women to be aware of these disease processes for the maximum therapeutic benefit to be achieved.

Published
1974

17. Preoperative whole pelvic external irradiation in stage I endometrial cancer

Author

N, Ritcher, W E, Lucas, J L, Yon, and F G, Sanford

Subjects
Uterine Neoplasms, Methods, Humans, Female, Castration, Adenocarcinoma, Hysterectomy, Prognosis, Follow-Up Studies
Abstract

Between 1966 and 1978, 201 patients with adenocarcinoma of the endometrium were treated at two hospitals in San Diego. Of these patients, 161 had disease limited to the corpus at the time of diagnosis. The majority of these patients received external whole-pelvic irradiation, followed as soon as possible by simple extrafascial hysterectomy and bilateral salpingo-oophorectomy. When this treatment method was used, actuarial survivals of 95% for Stage I disease were achieved. Also reported is the low incidence of wound complications in the group of patients operated soon after cessation of irradiation. The patients treated in this fashion had good survival rates, little morbidity from the adjunctive irradiation, and fewer wound complications than previously anticipated.

Published
1981

19. High-dose cisplatin therapy for cancer of the ovary: neurotoxicity

Author

Joseph L. Yon, Charles M. Bagley, Robert H. Rudolph, and Saul E. Rivkin

Subjects
Oncology, Cisplatin, Ovarian Neoplasms, medicine.medical_specialty, business.industry, Neurotoxicity, Cancer, Ovary, macromolecular substances, General Medicine, medicine.disease, medicine.anatomical_structure, Internal medicine, Internal Medicine, Medicine, Humans, Female, Nervous System Diseases, business, Locomotion, medicine.drug
Abstract

Excerpt To the editor: We wish to call to your readers' attention an unexpectedly severe and disabling neurotoxicity due to very-high-dose cisplatin therapy for cancer of the ovary. The attainment ...

Published
1985

20. Acute leukemia following chlorambucil therapy of advanced ovarian and fallopian tube carcinoma

Author

Joseph L. Yon and John Morrison

Subjects
Oncology, medicine.medical_specialty, Fallopian tube carcinoma, Advanced carcinoma, Neoplasms, Multiple Primary, hemic and lymphatic diseases, Ovarian carcinoma, Internal medicine, medicine, Fallopian Tube Neoplasms, Humans, Ovarian Neoplasms, Acute leukemia, Leukemia, Chlorambucil, Treatment regimen, business.industry, Carcinoma, Obstetrics and Gynecology, Middle Aged, Acute Disease, Female, business, medicine.drug
Abstract

Acute leukemia developed in two patients, one with advanced ovarian carcinoma and the other with advanced carcinoma of the fallopian tubes. Both patients received chlorambucil as a part of their treatment regimen. The literature is reviewed and updated since the report of Sotrel et al. [Obstet. Gynecol.47, No. 1 (Suppl.), 67s–71s (1976)], and a rationale for the use of high-dose intermittent chlorambucil therapy in the treatment of ovarian carcinoma is presented for consideration.

Published
1978

21. Squamous cell carcinoma of the cervix metastatic to the heart

Author

Nick Ritcher and Joseph L. Yon

Subjects
Adult, Pathology, medicine.medical_specialty, Diagnostic methods, Unusual case, business.industry, Heart Ventricles, Obstetrics and Gynecology, Uterine Cervical Neoplasms, Autopsy, medicine.disease, Heart Neoplasms, medicine.anatomical_structure, Oncology, Carcinoma, Carcinoma, Squamous Cell, Medicine, Humans, Basal cell, Sex organ, Female, Neoplasm Metastasis, business, Cervix
Abstract

An unusual case of squamous cell carcinoma of the cervix in a 33 year old with metastases to the right ventricle is presented. The infrequency of this finding is supported by autopsy data from the literature. The postulated mechanisms of spread, clinical presentations, and diagnostic methods of genital malignancies to the heart are discussed.

Published
1979

22. Cecal volvulus in pregnancy

Author

A T, Pratt, R C, Donaldson, L R, Evertson, and J L, Yon

Subjects
Adult, Pregnancy Complications, Pregnancy, Humans, Female, Cecum, Intestinal Obstruction
Abstract

Cecal volvulus in pregnancy is an uncommon complication. A case is reported of a 28-year-old white female, gravida 2, para 1, who presented at 36 weeks' gestation with flu-like symptoms accompanied by regular uterine contractions every 3 minutes; she underwent repeat cesarean section without incident. The patient did well until the second postoperative day, when she developed obstructive bowel symptoms and underwent emergency laparotomy. Operative findings revealed cecal volvulus with partial malrotation of the small bowel, absence of the ligament of Treitz, agenesis of the left kidney, and a redundant sigmoid colon. Medical and surgical management of this case, as well as a general description of the symptoms of cecal volvulus, is discussed. Early diagnosis and operation are essential to avoid the high morbidity and mortality associated with this disease.

Published
1981

23. Effects of environmental pH, sodium concentration, and temperature on the spontaneous motility of isolated human uterine muscle

Author

Harry S. McGaughey, W.Norman Thornton, Joseph L. Yon, and E.L. Corey

Subjects
Spontaneous motility, medicine.medical_specialty, business.industry, Sodium, Uterus, Temperature, Obstetrics and Gynecology, chemistry.chemical_element, Uterine muscle, Environment, Hydrogen-Ion Concentration, Endocrinology, chemistry, Cell Movement, Internal medicine, medicine, Myometrium, Humans, Female, business
Published
1961

25. Intraperitoneal Cisplatin with Systemic Thiosulfate Protection

Author

Wally E. Wung, Craig L. Pfeifle, Richard A. Olshen, Stephen B. Howell, Mark R. Green, Joseph L. Yon, and William E. Lucas

Subjects
Adult, Male, medicine.medical_treatment, Thiosulfates, Sodium thiosulfate, Pharmacology, Nephrotoxicity, Peritoneal dialysis, chemistry.chemical_compound, Internal Medicine, Humans, Medicine, Mesothelioma, Peritoneal Neoplasms, Aged, Body surface area, Cisplatin, Creatinine, business.industry, Ascites, General Medicine, Middle Aged, medicine.disease, Kinetics, chemistry, Toxicity, Drug Therapy, Combination, Female, business, Peritoneal Dialysis, medicine.drug
Abstract

Seventeen patients with intraperitoneal tumors were treated by 4-hour intraperitoneal dialysis with cisplatin alone, or in combination with an intravenous neutralizing agent, sodium thiosulfate. Cisplatin alone, 90 mg/m2 body surface area intraperitoneally, produced nephrotoxicity. When intraperitoneal cisplatin therapy was combined with intravenous thiosulfate treatment, the dose of cisplatin could be escalated to 270 mg/m2 body surface area without causing an increase in serum creatinine levels or undue myelosuppression. Even at doses up to 270 mg/m2, no local toxicity occurred. The peak peritoneal concentration of free reactive cisplatin averaged 21-fold higher than the plasma level, and the area under the peritoneal cisplatin elimination curve averaged 12-fold more than the area under the plasma curve. Neither of these ratios varied significantly with cisplatin dose. Regression of intraperitoneal tumor masses was observed in patients with far-advanced ovarian carcinoma, mesothelioma, and malignant carcinoid.

Published
1982

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