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1. Statin Use and Incidence of Parkinson's Disease in Women from the French <scp>E3N</scp> Cohort Study

Author

Thi Thu Ha Nguyen, Agnès Fournier, Émeline Courtois, Fanny Artaud, Sylvie Escolano, Pascale Tubert‐Bitter, Marie‐Christine Boutron‐Ruault, Isabelle Degaey, Emmanuel Roze, Marianne Canonico, Ismaïl Ahmed, Anne C.M. Thiébaut, Alexis Elbaz, HAL UVSQ, Équipe, APPEL À PROJETS GÉNÉRIQUE 2018 - Facteurs de risque de la Maladie de Parkinson chez les femmes de la cohorte E3N - - PARKIN-WOMEN2018 - ANR-18-CE36-0006 - AAPG2018 - VALID, 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, Sorbonne Université (SU), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Institut du Cerveau = Paris Brain Institute (ICM), 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], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), T.T.H.N. was supported by post‐doctoral grants from the Michael J Fox foundation and the France Parkinson association. E.C. was supported by post‐doctoral grants from the Michael J Fox foundation. F.A. reports no disclosures. S.E. reports no disclosures. P.T.‐B. reports no disclosures. M.‐C.B.‐R. received speaker fees in 2020 from MAYOLI‐SPINDLER and GILEAD outside the field of the present paper. I.D. reports no disclosures. E.R. received honorarium for speech from Orkyn Aguettant, Elivie and for participating in an advisory board from Allergan and has received research support from Merz‐Pharma, Orkyn, Aguettant, Elivie, Ipsen, Allergan, Everpharma, Fondation Desmarest, AMADYS, ADCY5.org , ANR, Societé Française de Médecine Esthétique, and Dystonia Medical Research Foundation. M.C. has obtained research grant from French National Research Agency (ANR). I.A. reports no disclosures. A.C.M.T. reports no disclosures. A.E. has obtained research grants from Plan Ecophyto (French ministry of agriculture) and France Parkinson., T.T.H.N. was supported by postdoctoral grants from The Michael J. Fox Foundation and the France Parkinson Association. E.C. was supported by postdoctoral grants from The Michael J. Fox foundation. F.A., S.E., P.T.‐B., I.A., and A.C.M.T. report no disclosures. M.‐C.B.‐R. received speaker fees in 2020 from Mayoli‐Spindler and Gilead outside the field of the present article. I.D. reports no disclosures. E.R. received honorarium for speeches from Orkyn Aguettant and Elivie and for participating in an advisory board from Allergan and has received research support from Merz‐Pharma, Orkyn, Aguettant, Elivie, Ipsen, Allergan, Everpharma, Fondation Desmarest, AMADYS, ADCY5.org , French National Research Agency (ANR), Societé Française de Médecine Esthétique, and the Dystonia Medical Research Foundation. M.C. obtained a research grant from the ANR. A.E. has obtained research grants from Plan Ecophyto (French Ministry of Agriculture) and France Parkinson Association. The work reported in this article was performed during A.F.'s term as a visiting scientist at the International Agency for Research on Cancer. The authors declare no other relationships or activities that could appear to have influenced the submitted work. Relevant conflicts of interest/financial disclosures, This work was realized with data of the E3N cohort (INSERM) and supported by the Mutuelle Générale de l'Education Nationale (MGEN), Gustave Roussy Institute, and French League against Cancer for the constitution and maintenance of the cohort. This work has benefited from State aid managed by the National Research Agency (ANR) under the program 'Investment in the future' bearing the reference ANR‐10‐COHO‐0006 and under the program 'Young researcher' bearing the reference ANR‐18‐CE36‐0006‐01, as well as a subsidy from the Ministry of Higher Education, Research and Innovation for public service charges bearing the reference N°2102918823, 2103236497, and 2103586016, and from IRESP (Institut de Recherche En Santé Publique). The authors acknowledge all women enrolled in the E3N cohort for their continued participation. They are also grateful to all members of the E3N study group., This project was funded by the Michael J. Fox Foundation for Parkinson's Research and the France Parkinson Association. Funding agencies., and ANR-18-CE36-0006,PARKIN-WOMEN,Facteurs de risque de la Maladie de Parkinson chez les femmes de la cohorte E3N(2018)

Subjects
[SDV] Life Sciences [q-bio], pharmacoepidemiology, cohort studies, drug repurposing, Neurology, Parkinson's disease, [SDV]Life Sciences [q-bio], Neurology (clinical), statins
Abstract

International audience; Background: Statins represent candidates for drug repurposing in Parkinson's disease (PD). Few studies examined the role of reverse causation, statin subgroups, and dose–response relations based on time-varying exposures. Objectives: We examined whether statin use is associated with PD incidence while attempting to overcome the limitations described previously, especially reverse causation. Method: We used data from the E3N cohort study of French women (follow-up, 2004–2018). Incident PD was ascertained using multiple sources and validated by experts. New statin users were identified through linked drug claims. We set up a nested case-control study to describe trajectories of statin prescriptions and medical consultations before diagnosis. We used time-varying multivariable Cox proportional hazards regression models to examine the statins–PD association. Exposure indexes included ever use, cumulative duration/dose, and mean daily dose and were lagged by 5 years to address reverse causation. Results: The case-control study (693 cases, 13,784 controls) showed differences in case-control trajectories, with changes in the 5 years before diagnosis in cases. Of 73,925 women (aged 54–79 years), 524 developed PD and 11,552 started using statins in lagged analyses. Ever use of any statin was not associated with PD (hazard ratio [HR] = 0.87, 95% confidence interval [CI] = 0.67–1.11). Alternatively, ever use of lipophilic statins was significantly associated with lower PD incidence (HR = 0.70, 95% CI = 0.51–0.98), with a dose–response relation for the mean daily dose (P-linear trend = 0.02). There was no association for hydrophilic statins. Conclusion: Use of lipophilic statins at least 5 years earlier was associated with reduced PD incidence in women, with a dose–response relation for the mean daily dose. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society

Published
2023

2. Sex Differences in Outcomes of Tetralogy of Fallot Patients With Implantable Cardioverter-Defibrillators

Author

Victor Waldmann, Abdeslam Bouzeman, Guillaume Duthoit, Linda Koutbi, Francis Bessière, Fabien Labombarda, Christelle Marquié, Jean-Baptiste Gourraud, Pierre Mondoly, Jean Marc Sellal, Pierre Bordachar, Alexis Hermida, Alain Al Arnaout, Frédéric Anselme, Caroline Audinet, Yvette Bernard, Serge Boveda, Sok Sithikun Bun, Morgane Chassignolle, Gaël Clerici, Antoine Da Costa, Maxime de Guillebon, Pascal Defaye, Nathalie Elbaz, Romain Eschalier, Rodrigue Garcia, Charles Guenancia, Benoit Guy-Moyat, Franck Halimi, Didier Irles, Laurence Iserin, François Jourda, Magalie Ladouceur, Philippe Lagrange, Mikael Laredo, Jacques Mansourati, Grégoire Massoulié, Amel Mathiron, Philippe Maury, Anne Messali, Kumar Narayanan, Cédric Nguyen, Sandro Ninni, Marie-Cécile Perier, Bertrand Pierre, Penelope Pujadas, Frédéric Sacher, Pascal Sagnol, Ardalan Sharifzadehgan, Camille Walton, Pierre Winum, Cyril Zakine, Laurent Fauchier, Raphaël Martins, Jean-Luc Pasquié, Jean-Benoit Thambo, Xavier Jouven, Nicolas Combes, Eloi Marijon, Chrystelle Akret, Jean-Paul Albenque, Vincent Algalarrondo, Christine Alonso, Denis Amet, Frédéric Ansselme, Anouk Asselin, Nicolas Badenco, Hugues Bader, Marc Badoz, Pierre Baudinaud, Nathalie Behar, Mouna Ben Kilani, Géraldine Bertaux, Cathy Bertrand, Francis Bessiere, Hughes Blangy, Damien Bonnet, Pierre Bordchar, Paul Bru, Adrien Carabelli, Christèle Cardin, Bruno Cauchemez, Tej Chalbia, Laure Champ-Rigot, Thomas Chastre, Philippe Chevallier, Nicolas Clementy, Stéphane Combes, Christian De Chillou, Maxime De Guillebon, Bruno Degand, Jean-Claude Deharo, Nicolas Derval, Sylvie Di Filippo, Guillaume Domain, Antoine Dompnier, Arnaud Dulac, Alexandre Duparc, D Cécile Duplantier, Rim El Bouazzaoui, Bogdan Enache, Fabrice Extramiana, Pierre Fiorello, Pierre Frey, Luc Freysz, Vincent Galand, Estelle Gandjbakhch, Kevin Gardey, Olivier Geoffroy, Bénédicte Godin, Samuel Goussot, Caroline Grimard, Jean-Baptiste Guichard, Michel Haissaguerre, David Hamon, Sébastien Hascoet, Karim Hasni, Jean-Sylvain Hermida, Françoise Hidden-Lucet, Mélèze Hocini, Jérome Hourdain, Peggy Jacon, Gaël Jauvert, Frédéric Jean, Nicolas Johnson, Pierre Khattar, Ziad Khoueiry, Rita Koutbi, Guillaume Laborie, Gabriel Lactu, Pierre-Marc Lallemand, Gabriel Laurent, Thomas Lavergne, Arnaud Lazarus, Laurianne Le Gloan, Christophe Leclercq, Antoine Leenhardt, Nicolas Lellouche, Christophe Loose, Philippe Mabo, Alice Maltret, Franck Mandel, Christelle Marquie, Carole Maupain, Antoine Milhelm, Paul Milliez, Adrian Mirolo, Ghassan Moubarak, Stéphane Mourot, Jacky Ollitrault, Pierre Ollitrault, Akli Otmani, Jean-Luc Pasquie, Dominique Pavin, Séverinne Philibert, Damien Poindron, Charlotte Potelle, Vincent Probst, Paul Puie, Anne Rollin, Cécile Romeyer-Bouchard, Nicolas Sadoul, Audrey Sagnard, Arnaud Savoure, Didier Scarlatti, Fabien Squara, Nikita Tanese, Jean Benoit Thambo, Olivier Thomas, Emie Varlet, Sandrine Venier, Quentin Voglimacci Stephanopoli, Xavier Waintraub, Françoise Wiart, Alexandre Zhao, Amir Zouaghi, Paris-Centre de Recherche Cardiovasculaire (PARCC (UMR_S 970/ U970)), 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)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), CHU Pontchaillou [Rennes], Laboratoire Traitement du Signal et de l'Image (LTSI), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM), 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), Clinique Pasteur, Clinique Pasteur [Toulouse], and This work was supported by the French Institute of Health and Medical Research, Fédération Française de Cardiologie, and Société Française de Cardiologie. The authors have reported that they have no relationships relevant to the contents of this paper to disclose.

Subjects
Male, Adult, Heart Defects, Congenital, Sex Characteristics, sudden death, Middle Aged, congenital heart disease, Defibrillators, Implantable, Cohort Studies, implantable cardioverter-defibrillator, Death, Sudden, Cardiac, Tetralogy of Fallot, sex, Humans, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Female, women, ventricular arrhythmia
Abstract

International audience; Background: Women with congenital heart disease at high risk for sudden cardiac death have been poorly studied thus far.Objectives: The aim of this study was to assess sex-related differences in patients with tetralogy of Fallot (TOF) and implantable cardioverter-defibrillators (ICDs).Methods: Data were analyzed from the DAI-T4F (French National Registry of Patients With Tetralogy of Fallot and Implantable Cardioverter Defibrillator) cohort study, which has prospectively enrolled all patients with TOF with ICDs in France since 2010. Clinical events were centrally adjudicated by a blinded committee.Results: A total of 165 patients (mean age 42.2 ± 13.3 years) were enrolled from 40 centers, including 49 women (29.7%). Among the 9,692 patients with TOF recorded in the national database, the proportion of women with ICDs was estimated to be 1.1% (95% CI: 0.8%-1.5%) vs 2.2% (95% CI: 1.8%-2.6%) in men (P < 0.001). The clinical profiles of patients at implantation, including the number of risk factors for ventricular arrhythmias, were similar between women and men. During a median follow-up period of 6.8 years (IQR: 2.5-11.4 years), 78 patients (47.3%) received at least 1 appropriate ICD therapy, without significant difference in annual incidences between women (12.1%) and men (9.9%) (HR: 1.22; 95% CI: 0.76-1.97; P = 0.40). The risk for overall ICD-related complications was similar in women and men (HR: 1.33; 95% CI: 0.81-2.19; P = 0.30), with 24 women (49.0%) experiencing at least 1 complication.Conclusions: Our findings suggest that women with TOF at high risk for sudden cardiac death have similar benefit/risk balance from ICD therapy compared with men. Whether ICD therapy is equally offered to at-risk women vs men warrants further evaluation in TOF as well as in other congenital heart disease populations. (French National Registry of Patients With Tetralogy of Fallot and Implantable Cardioverter Defibrillator [DAI-T4F]; NCT03837574)

Published
2022

3. Statin Use and Skin Cancer Risk: A Prospective Cohort Study

Author

Trude Eid Robsahm, Agnès Fournier, Yahya Mahamat-Saleh, Reza Ghiasvand, Marina Kvaskoff, Manon Cairat, Marie-Christine Boutron-Ruault, Iris Cervenka, Marie Al Rahmoun, Gianluca Severi, 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, Oslo University Hospital [Oslo], Cancer Registry of Norway, International Agency for Cancer Research (IACR), Università degli Studi di Firenze = University of Florence (UniFI), 2102 918823, NCT03285230, Centre International de Recherche sur le Cancer, CIRC, Agence Nationale de la Recherche, ANR: ANR-10-COHO-0006, Institut National de la Santé et de la Recherche Médicale, Inserm, Institut National Du Cancer, INCa: INCa_13539, Institut Gustave-Roussy, Mutuelle Générale de l'Education Nationale, MGEN, We are grateful to the study participants for their continued participation and to practitioners for providing pathology reports. We also thank all members of the E3N study group, particularly Rafika Cha?t, Ghizlane Bajawi-Esselma, Amandine Gelot, Marie Fangon, Pascale Gerbouin-R?rolle, Sabine Moreira-Faria, Nad?ge Senina, Sofiane Harizi, Lyan Hoang, Anita Kowal, and Camille Laplanche for their technical assistance. The E3N cohort from the French National Institute of Health and Medical Research (Inserm) was supported by the Mutuelle G?n?rale de l'Education Nationale, the Gustave Roussy Institute, and the French League against Cancer. E3N-E4N is also supported by the French National Research Agency under the Investment for the Future Program (ANR-10-COHO-0006) and by the French Ministry of Higher Education, Research and Innovation (subsidy for public service charges #2102 918823). MAR, YMS, and IC were supported by research scholarships from the French National Cancer Institute (MAR: INCa_13539), the Paris Ile-de-France region, and the French Ministry of Research, respectively. This study is listed at ClinicalTrials.gov as NCT03285230. The work reported in this paper was performed during Agn?s Fournier's term as a Visiting Scientist at the International Agency for Research on Cancer. Conceptualization: MK, AF, Data Curation: MAR, AF, Formal Analysis: MAR, Funding Acquisition: MAR, MK, AF, Investigation: MAR, MK, AF, Methodology: MK, AF, Project Administration: MK, AF, Resources: GS, MCBR, MK, AF, Software: MAR, AF, Supervision: MK, AF, Visualization: MAR, Validation: MK, AF, Writing - Original Draft Preparation: MAR, RG, TER, MK, AF, Writing - Review and Editing: MAR, RG, MC, YMS, IC, GS, MCBR, TER, MK, AF, Funding sources had no role in study design, collection, analysis, and interpretation of data, writing of the report, and the decision to submit the article for publication., ANR-10-COHO-0006,E4N,Etude Epidémiologique des Enfants de femmes de l'Education Nationale(2010), HAL UVSQ, Équipe, and Cohortes - Etude Epidémiologique des Enfants de femmes de l'Education Nationale - - E4N2010 - ANR-10-COHO-0006 - COHO - VALID

Subjects
Male, medicine.medical_specialty, Skin Neoplasms, [SDV]Life Sciences [q-bio], [SDV.CAN]Life Sciences [q-bio]/Cancer, Dermatology, Biochemistry, Cohort Studies, [SDV.CAN] Life Sciences [q-bio]/Cancer, Risk Factors, Internal medicine, Epidemiology, medicine, Humans, Basal cell carcinoma, Prospective Studies, Prospective cohort study, Melanoma, Molecular Biology, Proportional Hazards Models, Aged, 80 and over, business.industry, Hazard ratio, Cell Biology, [SDV.MHEP.DERM] Life Sciences [q-bio]/Human health and pathology/Dermatology, medicine.disease, Confidence interval, [SDV] Life Sciences [q-bio], Defined daily dose, Carcinoma, Basal Cell, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, [SDV.SP.PHARMA] Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, Carcinoma, Squamous Cell, [SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, Female, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Skin cancer, business, Body mass index, [SDV.MHEP.DERM]Life Sciences [q-bio]/Human health and pathology/Dermatology
Abstract

International audience; Epidemiological studies on statin use in relation to skin cancer risk are scarce and yielded conflicting results. We explored this association in Etude Epidémiologique auprès de femmes de l'Education Nationale, a prospective cohort of French women born in 1925–1950. Health and lifestyle data were self-reported biennially and matched with drug reimbursement data, allowing the identification of participants’ statin use since 2004. Multivariable cause-specific hazards regression models adjusted for skin cancer risk factors estimated hazard ratios with 95% confidence intervals. Over 2004–2014, 455 cutaneous melanoma, 1,741 basal cell carcinoma, and 268 squamous cell carcinoma cases were ascertained among 62,473 women. Compared with never use, there were no associations between ever use of statins and melanoma (hazard ratio = 1.16, 95% confidence interval = 0.94–1.44) or squamous cell carcinoma (hazard ratio = 0.89, 95% confidence interval = 0.66–1.19) risks and a decrease in basal cell carcinoma risk with ever use of statins (hazard ratio = 0.89, 95% confidence interval = 0.79–0.996). We found no trend of increasing or decreasing risks with dose, duration of use, time since first use, or age at first use and no statistically significant effect modification by pigmentary traits or residential UVR exposure. Because of the limited number of studies evaluating the associations between the use of statins and the risks of melanoma, basal cell carcinoma, and squamous cell carcinoma, these findings would deserve further investigation in other settings.

Published
2022

4. Use of nonsteroidal anti-inflammatory drugs and breast cancer risk in a prospective cohort of postmenopausal women

Author

Agnès Fournier, Marc J. Gunter, Gianluca Severi, Manon Cairat, Laure Dossus, Marie Al Rahmoun, Nutrition and Metabolism Section, International Agency for Research on Cancer, Lyon, France, International Agency for Cancer Research (IACR), 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), Institut Gustave Roussy (IGR), Università degli Studi di Firenze = University of Florence [Firenze] (UNIFI), Ligue Contre le Cancer Mutuelle Générale de l'Education Nationale, MGEN Institut Gustave-Roussy Institut National de la Santé et de la Recherche Médicale, Inserm, Ligue Contre le Cancer (support for the E3N cohort and PhD fellowship to Manon Cairat). Acknowledgements Disclaimer, and The research was carried out using data from the Inserm (French National Institutes for Health and Medical Research) E3N cohort, which was established and maintained with the support of the Mutuelle Générale de l’Education Nationale (MGEN), Gustave Roussy, and the French League against Cancer (LNCC). We are grateful to the study participants for their continued participation and to medical practitioners for providing pathology reports. We also thank all members of the E3N-EPIC study group, in particular Rafika Chaït, Ghizlane Esselma, Marie Fangon, Pascale Gerbouin-Rérolle, Lyan Hoang, Roselyn Gomes and the data management team, and Amandine Gelot for data management and/or technical assistance. The work reported in this paper was performed during Agnès Fournier’s term as a Visiting Scientist at the International Agency for Research on Cancer.

Subjects
medicine.medical_specialty, Proton pump inhibitors, Breast Neoplasms, [SDV.CAN]Life Sciences [q-bio]/Cancer, Comorbidity, Lower risk, lcsh:RC254-282, Cohort Studies, 03 medical and health sciences, 0302 clinical medicine, Breast cancer, Risk Factors, Surveys and Questionnaires, Internal medicine, medicine, Humans, Medical history, Prospective Studies, Prospective cohort study, Aged, Proportional Hazards Models, 030304 developmental biology, 0303 health sciences, Aspirin, business.industry, Proportional hazards model, Incidence, Incidence (epidemiology), Anti-Inflammatory Agents, Non-Steroidal, Hazard ratio, Nonsteroidal anti-inflammatory drugs, Middle Aged, medicine.disease, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, Postmenopausal women, 3. Good health, Postmenopause, 030220 oncology & carcinogenesis, Female, France, business, Research Article, Cohort study
Abstract

BackgroundAlthough anti-inflammatory agents could theoretically have anticancer properties, results from cohort studies on nonsteroidal anti-inflammatory drugs (NSAIDs) and breast cancer (BC) risk are inconsistent.MethodsWe investigated the association between NSAID use and BC incidence in the French E3N prospective cohort, which includes 98,995 women born between 1925 and 1950 and insured by a health insurance plan that covers mostly teachers. Self-reported information on lifestyle and medical history has been collected biennially by questionnaires and matched with data from a drug reimbursement database covering the period 2004–2014. Women who self-reported current NSAID use in the 2000 or 2002 questionnaires or with at least two reimbursements in any previous 3-month period were defined as exposed to NSAIDs. Multivariable Cox regression models were used to estimate hazard ratios (HRs) for the association of NSAID use with BC risk.ResultsIn the current analysis, 62,512 postmenopausal women were followed between 2004 and 2014 (9 years on average, starting at a mean age of 63 years; 2864 incident BC). In multivariable models, there was no statistically significant association between NSAID use and BC risk [HR = 1.00 (0.92–1.08), compared with non-exposed women]. The NSAID-BC associations did not differ by NSAID types, BC subtypes, risk factors, and comorbidities, nor by duration and dose of use. However, a statistically significant interaction was observed by proton pump inhibitor (PPI) drug use (Pinteraction = 0.01) whereby a decreased risk of BC with NSAID use was only observed among women who also used PPI before.ConclusionOnly women who used NSAIDs after having used PPI had a lower risk of BC. This result is novel and requires replication in other studies.

Published
2020

5. Long-term risk of stroke and its predictors in transient ischaemic attack patients in Germany

Author

Karel Kostev, Louis Jacob, Christian Tanislav, Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), and The authors have received no financial support for the research, authorship and/or publication of this paper.

Subjects
Male, associated predictors, Cohort Studies, 0302 clinical medicine, general practices, Germany, Atrial Fibrillation, 030212 general & internal medicine, Stroke, Aged, 80 and over, Incidence, Hazard ratio, Age Factors, Atrial fibrillation, Middle Aged, stroke, 3. Good health, Neurology, Ischemic Attack, Transient, Hypertension, Cohort, Platelet aggregation inhibitor, Female, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Risk, medicine.medical_specialty, transient ischaemic attack, 03 medical and health sciences, Sex Factors, Diabetes mellitus, Internal medicine, parasitic diseases, medicine, Humans, long-term risk, In patient, cardiovascular diseases, Aged, Ischemic Stroke, business.industry, Anticoagulants, Protective Factors, medicine.disease, nervous system diseases, Long term risk, Neurology (clinical), business, Platelet Aggregation Inhibitors, 030217 neurology & neurosurgery
Abstract

International audience; Background and purpose: Little is known about the long-term association between transient ischaemic attack (TIA) and stroke. Therefore, the goal of this study was to analyze the long-term risk of stroke and associated predictors in a large cohort of TIA patients followed in general practices in Germany. Methods: This study included patients with an initial TIA diagnosis and subsequently followed up in one of 1262 general practices in Germany between January 2007 and December 2016 (N = 19 824 patients). The primary outcome of the study was the risk of ischaemic stroke within 10 years of the initial diagnosis of TIA. The secondary outcome was the identification of demographic, clinical and pharmaceutical variables significantly associated with stroke in TIA patients. Results: Within 10 years of the initial TIA diagnosis, 18.3% of individuals were diagnosed with stroke. Age was positively associated with stroke, with hazard ratios ranging from 1.88 in patients aged 51–60 years to 4.00 in those aged >80 years (reference group: patients aged ≤50 years). Furthermore, male sex, hypertension, diabetes mellitus, atrial fibrillation and ischaemic heart diseases had an additional impact on the risk of stroke. Finally, new oral anticoagulants, heparins, diuretics, angiotensin II receptor blockers and platelet aggregation inhibitors were identified as protective factors. Conclusions: In a cohort of almost 20 000 TIA patients, 18.3% were diagnosed with stroke within 10 years after the TIA index event. Several demographic, clinical and pharmaceutical variables significantly predicted the long-term risk of stroke in TIA patients.

Published
2020

6. Consumption of Fish and ω-3 Fatty Acids and Cancer Risk: An Umbrella Review of Meta-Analyses of Observational Studies

Author

Hans Oh, Mingyang Song, Jae Il Shin, Ai Koyanagi, Louis Jacob, Andreas Kronbichler, Gaeun Kim, Michael Eisenhut, Eun Kyoung Choi, Sun Jae Jung, Lin Yang, Marco Solmi, Gwang Hun Jeong, Eunyoung Jung, Brendon Stubbs, Keum Hwa Lee, Eunyoung Cho, Joaquim Radua, Edward Giovannucci, NaNa Keum, Hyo Jin Seong, Nicola Veronese, Hyunbong Park, Lee Smith, Gabriele Gamerith, Giuseppe Grosso, Trevor Thompson, Elena Dragioti, Sarah E Jackson, Leandro Fórnias Machado de Rezende, Shuji Ogino, Jong Yeob Kim, Hans van Vliet, Sung Hwi Hong, Université de Versailles Saint-Quentin-en-Yvelines - UFR Sciences de la santé Simone Veil (UVSQ Santé), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), South London and Maudsley NHS Foundation Trust National Institute for Health Research, NIHR NIHR Collaboration for Leadership in Applied Health Research and Care South London National Institutes of Health, NIH: R35 CA197735 Maudsley Charity King’s College London National Institutes of Health, NIH: R35 CA197735, KHL, HJS, GK, GHJ, and JYK contributed equally to this work. The authors report no funding received for this study. Author Disclosures: The authors report no conflicts of interest. BS is supported by a Clinical Lectureship (ICA-CL-2017-03-001) jointly funded by Health Education England (HEE) and the National Institute for Health Research (NIHR), is in part funded by the NIHR Biomedical Research Centre at South London and Maudsley NHS Foundation Trust, and is also supported by the Maudsley Charity, King’s College London, and the NIHR South London Collaboration for Leadership in Applied Health Research and Care (CLAHRC) funding. The time effort of SO was in part supported by US National Institutes of Health grant R35 CA197735. This paper presents independent research. The views expressed in this publication are those of the authors and not necessarily those of the acknowledged institutions. Address correspondence to JIS (e-mail: shinji@yuhs.ac) or EKC (e-mail: ekchoi@yuhs.ac). Supplemental Table 1 is available from the 'Supplementary data'link in the online posting of the article and from the same link in the online table of contents at https://academic.oup.com/advances. Abbreviation used: ALA, α-linolenic acid, AMSTAR2, A Measurement Tool to Assess Systematic Reviews 2, CUP, Continuous Update Project, DPA, docosapentaenoic acid, GRADE, Grading of Recommendations Assessment, Development and Evaluation, HCC, hepatocellular carcinoma, NA, not assessable, PI, prediction interval, PRISMA, Preferred Reporting Items for Systematic Reviews and Meta-Analyses, WCRF/AICR, Word Cancer Research Fund/American Institute for Cancer Research., The time effort of SO was in part supported by US National Institutes of Health grant R35 CA197735., Lee, K.H., Seong, H.J., Kim, G., Jeong, G.H., Kim, J.Y., Park, H., Jung, E., Kronbichler, A., Eisenhut, M., Stubbs, B., Solmi, M., Koyanagi, A., Hong, S.H., Dragioti, E., De Rezende, L.F.M., Jacob, L., Keum, N., Van Der Vliet, H.J., Cho, E., Veronese, N., Grosso, G., Ogino, S., Song, M., Radua, J., Jung, S.J., Thompson, T., Jackson, S.E., Smith, L., Yang, L., Oh, H., Choi, E.K., Shin, J.I., Giovannucci, E.L., and Gamerith, G.

Subjects
Male, Risk, Oncology, medicine.medical_specialty, [SDV]Life Sciences [q-bio], BF, Medicine (miscellaneous), Review, Cohort Studies, 03 medical and health sciences, Prostate cancer, 0302 clinical medicine, Breast cancer, ω-3 fatty acid, Meta-Analysis as Topic, Neoplasms, Internal medicine, Fatty Acids, Omega-3, medicine, Animals, Humans, cancer, 030212 general & internal medicine, ω-3 fatty acid, fish, cancer, umbrella review, meta-analysis, chemistry.chemical_classification, fish, Nutrition and Dietetics, umbrella review, business.industry, Endometrial cancer, Fishes, Fatty acid, Cancer, medicine.disease, R1, 3. Good health, meta-analysis, Observational Studies as Topic, chemistry, Case-Control Studies, 030220 oncology & carcinogenesis, Meta-analysis, Female, Skin cancer, business, Liver cancer, Food Science
Abstract

Multiple studies have suggested that ω-3 fatty acid intake may have a protective effect on cancer risk; however, its true association with cancer risk remains controversial. We performed an umbrella review of meta-analyses to summarize and evaluate the evidence for the association between ω-3 fatty acid intake and cancer outcomes. We searched PubMed, Embase, and the Cochrane Database of Systematic Reviews from inception to December 1, 2018. We included meta-analyses of observational studies that examined associations between intake of fish or ω-3 fatty acid and cancer risk (gastrointestinal, liver, breast, gynecologic, prostate, brain, lung, and skin) and determined the level of evidence of associations. In addition, we appraised the quality of the evidence of significant meta-analyses by using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system. We initially screened 598 articles, and 15 articles, including 57 meta-analyses, were eligible. Among 57 meta-analyses, 15 reported statistically significant results. We found that 12 meta-analyses showed weak evidence of an association between ω-3 fatty acid intake and risk of the following types of cancer: liver cancer (n = 4 of 6), breast cancer (n = 3 of 14), prostate cancer (n = 3 of 11), and brain tumor (n = 2 of 2). In the other 3 meta-analyses, studies of endometrial cancer and skin cancer, there were no assessable data for determining the evidence levels. No meta-analysis showed convincing, highly suggestive, or suggestive evidence of an association. In the sensitivity analysis of meta-analyses by study design, we found weak associations between ω-3 fatty acid intake and breast cancer risk in cohort studies, but no statistically significant association in case-control studies. However, the opposite results were found in case of brain tumor risk. Although ω-3 fatty acids have been studied in several meta-analyses with regard to a wide range of cancer outcomes, only weak associations were identified in some cancer types, with several limitations. Considering the nonsignificant or weak evidence level, clinicians and researchers should cautiously interpret reported associations between ω-3 fatty acid consumption and cancer risks. Copyright © 2020 The Author(s) on behalf of the American Society for Nutrition.

Published
2020

7. Cluster Analysis of Physical Activity Patterns, and Relationship with Sedentary Behavior and Healthy Lifestyles in Prepubertal Children: Genobox Cohort

Author

Gloria Bueno, Francisco Jesus Llorente-Cantarero, Concepción M. Aguilera, Juan Jose Bedoya-Carpente, Augusto Anguita-Ruiz, Mercedes Gil-Campos, Jose Manuel Jurado-Castro, Rosaura Leis, Azahara Iris-Rupérez, Rocío Vázquez-Cobela, Universidade de Santiago de Compostela. Departamento de Ciencias Forenses, Anatomía Patolóxica, Xinecoloxía e Obstetricia, e Pediatría, [Leis,R, Bedoya-Carpente,JJ, Vázquez-Cobela,R] Unidad de Investigación en Nutrición, Crecimiento y Desarrollo Humano de Galicia, Departamento de Pediatría, Hospital Clínico Universitario de Santiago, Universidad de Santiago de Compostela, IDIS, Santiago de Compostela, Spain. [Leis,R, Llorente-Cantarero,FJ, Anguita-Ruiz,A, Vázquez-Cobela,R, Aguilera,CM, Bueno,G, Gil-Campos,M] CIBEROBN, (Physiopathology of Obesity and Nutrition) Institute of Health Carlos III (ISCIII), Madrid, Spain. [Jurado-Castro,JM, Gil-Campos,M] Metabolism and Investigation Unit, Reina Sofia University Hospital, Maimónides Institute of Biomedicine Research of Córdoba (IMIBIC), University of Córdoba, Córdoba, Spain. [Llorente-Cantarero,FJ] Department of Artistic and Corporal Education, Faculty of Education, University of Córdoba, Córdoba, Spain. [Anguita-Ruiz,A, Aguilera,CM] Department of Biochemistry and Molecular Biology II, Institute of Nutrition and Food Technology 'José Mataix', Center of Biomedical Research, University of Granada, Armilla, Granada, Spain. [Anguita-Ruiz,A, Aguilera,CM] Instituto de Investigación Biosanitaria ibs, Granada, Spain. [Iris-Rupérez,A] GENUD Research Group, University of Zaragoza, Instituto Agroalimentario de Aragón (IA2), Instituto de Investigación Sanitaria (IIS) Aragón, Zaragoza, Spain. [Bueno,G] Unidad de Endocrinología Pediátrica, Hospital Clínico Lozano Blesa, Facultad de Medicina, Universidad de Zaragoza, Zaragoza, Spain., and This work was supported bythe Plan Nacional de Investigación Científica, Desarrollo e InnovaciónTecnológica (I + D + I), Instituto de Salud Carlos III-Health Research Funding (FONDOS FEDER) (PI051968, PI1102042 and PI1600871) and Redes temáticas de investigación cooperativa RETIC (Red SAMID RD12/0026/0015). The authors also acknowledge Instituto de Salud Carlos III for personal funding of A.A.-R: Contratos i-PFIS: doctorados IIS empresa en ciencias y tecnologías de la salud de la convocatoria 2017 de la Acción Estratégica en Salud 2013–2016 (IFI17/00048).This paper will be included in J.M.J.-C. doctorate, under the 'Social and Legal Sciences Program' at theUniversity of Córdoba, Spain.

Subjects
Male, obesity, Mediterranean diet, Health Behavior, Obesidad, Child Behavior, Diet, Mediterranean, Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans [Medical Subject Headings], Cohort Studies, 0302 clinical medicine, Surveys and Questionnaires, Cluster Analysis, Insulin, 030212 general & internal medicine, skin and connective tissue diseases, Child, Chemicals and Drugs::Lipids::Glycerides::Triglycerides [Medical Subject Headings], Nutrition and Dietetics, exercise, Psychiatry and Psychology::Behavior and Behavior Mechanisms::Behavior::Health Behavior [Medical Subject Headings], Analytical, Diagnostic and Therapeutic Techniques and Equipment::Therapeutics::Nutrition Therapy::Diet Therapy::Diet, Mediterranean [Medical Subject Headings], Analytical, Diagnostic and Therapeutic Techniques and Equipment::Equipment and Supplies::Electrical Equipment and Supplies [Medical Subject Headings], Conducta sedentaria, Ejercicio físico, Cardiovascular diseases, Psychiatry and Psychology::Behavior and Behavior Mechanisms::Behavior::Child Behavior [Medical Subject Headings], Cohort, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Data Collection::Health Surveys::Nutrition Surveys::Diet Surveys [Medical Subject Headings], Female, Anthropology, Education, Sociology and Social Phenomena::Human Activities::Leisure Activities::Recreation::Sports [Medical Subject Headings], Club, Enfermedades cardiovasculares, lcsh:Nutrition. Foods and food supply, Sports, musculoskeletal diseases, Electrical Equipment and Supplies, Anatomy::Digestive System::Pancreas::Islets of Langerhans::Insulin-Secreting Cells [Medical Subject Headings], Physical activity, Check Tags::Male [Medical Subject Headings], 030209 endocrinology & metabolism, lcsh:TX341-641, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Statistics as Topic::Cluster Analysis [Medical Subject Headings], Disease cluster, Article, Information Science::Information Science::Data Collection::Questionnaires [Medical Subject Headings], 03 medical and health sciences, Screen time, Environmental health, Anthropology, Education, Sociology and Social Phenomena::Human Activities::Exercise [Medical Subject Headings], medicine, Humans, Persons::Persons::Age Groups::Child [Medical Subject Headings], Healthy Lifestyle, Obesity, Exercise, Triglycerides, business.industry, Psychiatry and Psychology::Behavior and Behavior Mechanisms::Psychology, Social::Life Style [Medical Subject Headings], Anthropometry, medicine.disease, Dieta mediterránea, cardiovascular diseases, stomatognathic diseases, Check Tags::Female [Medical Subject Headings], Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Epidemiologic Study Characteristics as Topic::Epidemiologic Studies::Cohort Studies [Medical Subject Headings], Sedentary Behavior, business, Food Science
Abstract

The authors would like to thank the children and parents who participated in the study and Ana Yara Postigo-Fuentes for the assistance with the English editing., Sedentary habits during childhood are associated with adverse health outcomes. The aim of this work was to cluster lifestyle behaviors and metabolic biomarkers to establish different patterns in children. Their physical and sedentary activities were evaluated by accelerometry, and questionnaires that included lifestyle behaviors, such as adherence to a Mediterranean diet, anthropometry and blood biochemical markers. Cluster analysis was performed to establish different groups based on physical activity levels. A total of 489 children were finally selected. Cluster 1 included children with a mostly sedentary state, whereas Cluster 3 included the most active children and Cluster 2 included children that did not fit into either the sedentary or the highly active groups. In Cluster 3, 56% of children were in a sports club, and a lower percentage used electronic devices in their rooms compared to the other groups. Cluster 1 children exhibited higher insulin, HOMA-IR and triacylglycerides with respect to the other groups. No differences were found regarding adherence to a Mediterranean diet. The choice to practice an extracurricular sport could be an influencing factor to increase exercise and ensure an active lifestyle in children. Reducing or limiting screen time mainly in children’s rooms could contribute to an active lifestyle., Plan Nacional de Investigacion Cientifica, Desarrollo e InnovacionTecnologica (I + D + I), Instituto de Salud Carlos III-Health Research Funding (FONDOS FEDER) PI051968 PI1102042 PI1600871, Redes tematicas de investigacion cooperativa RETIC (Red SAMID) RD12/0026/0015, Instituto de Salud Carlos III IFI17/00048

Published
2020

8. Social and non-social autism symptoms and trait domains are genetically dissociable

Author

Freddy Cliquet, Varun Warrier, Roberto Toro, Hyejung Won, Richard Delorme, Thomas Bourgeron, Anders D. Børglum, Janita Bralten, Claire S. Leblond, Geert Poelmans, Jakob Grove, Ward De Witte, Bhismadev Chakrabarti, David A. Hinds, Simon Baron-Cohen, Toro, Roberto [0000-0002-6671-858X], Cliquet, Freddy [0000-0002-9989-0685], Chakrabarti, Bhismadev [0000-0002-6649-7895], Børglum, Anders D. [0000-0001-8627-7219], Grove, Jakob [0000-0003-2284-5744], Hinds, David A. [0000-0002-4911-803X], Apollo - University of Cambridge Repository, University of Cambridge [UK] (CAM), Génétique humaine et fonctions cognitives - Human Genetics and Cognitive Functions (GHFC (UMR_3571 / U-Pasteur_1)), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), University of North Carolina [Chapel Hill] (UNC), University of North Carolina System (UNC), Child and Adolescent Psychiatry Department [AP- HP Hôpital Robert Debré], AP-HP Hôpital universitaire Robert-Debré [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Radboud University Medical Center [Nijmegen], Radboud University [Nijmegen], University of Reading (UOR), The Lundbeck Foundation Initiative for Integrative Psychiatric Research (iPSYCH), Aarhus University [Aarhus], 23andMe Inc., V.W. was funded by St. John’s College, Cambridge, and the Cambridge Commonwealth Trust. This study was funded by grants to SBC from the Medical Research Council, the Wellcome Trust, the Autism Research Trust, the Templeton World Charity Foundation, and to T.B. from the Institut Pasteur, the CNRS, the INSERM, The Fondamental Foundation, the APHP, the BioPsy Labex and the University Paris Diderot. The research was conducted in association with the National Institute for Health Research (NIHR) Collaboration for Leadership in Applied Health Research and Care East of England at Cambridgeshire and Peterborough NHS Foundation Trust. We also received support from the NIHR Cambridge Biomedical Research Centre. We acknowledge with gratitude the generous support of Drs Dennis and Mireille Gillings in strengthening the collaboration between S.B.-C. and T.B., and between Cambridge University and the Institut Pasteur. The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR or the Department of Health. Data obtained from 23andMe was supported by the National Human Genome Research Institute of the National Institutes of Health (grant number R44HG006981). The UK Medical Research Council and Wellcome (grant ref: 102215/2/13/2) and the University of Bristol provide core support for ALSPAC. GWAS data were generated by Sample Logistics and Genotyping Facilities at Wellcome Sanger Institute and LabCorp (Laboratory Corporation of America) using support from 23andMe. This publication is the work of the authors who will serve as guarantors for the content of this paper. The iPSYCH (The Lundbeck Foundation Initiative for Integrative Psychiatric Research) team acknowledges funding from The Lundbeck Foundation (grant nos. R102-A9118 and R155-2014-1724), the Stanley Medical Research Institute, the European Research Council (project no.: 294838), the Novo Nordisk Foundation for supporting the Danish National Biobank resource, and grants from Aarhus and Copenhagen Universities and University Hospitals, including support to the iSEQ Center, the GenomeDK HPC facility, and the CIRRAU Center. The project leading to this application has received funding from the Innovative Medicines Initiative 2 Joint Undertaking (JU) under grant agreement no. 777394. The JU receives support from the European Union’s Horizon 2020 research and innovation programme and EFPIA and AUTISM SPEAKS, Autistica, SFARI. We thank the iPSCH-Broad Autism Group and the EU-AIMS LEAP group for sharing data. A full list of the authors and affiliations in the iPSYCH-Broad autism group and the EU-AIMS LEAP group is provided in the Supplementary Information., The 23andMe Research Team : Michelle Agee, Babak Alipanahi, Adam Auton, Robert K. Bell, Katarzyna Bryc, Sarah L. Elson, Pierre Fontanillas, Nicholas A. Furlotte, Karen E. Huber, Aaron Kleinman, Nadia K. Litterman, Jennifer C. McCreight, Matthew H. McIntyre, Joanna L. Mountain, Carrie A.M. Northover, Steven J. Pitts, J. Fah Sathirapongsasuti, Olga V. Sazonova, Janie F. Shelton, Suyash Shringarpure, Chao Tian, Joyce Y. Tung, Vladimir Vacic & Catherine H. Wilson, European Project: 294838,EC:FP7:ERC,ERC-2011-ADG_20110310,EIMS(2012), Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), and Radboud university [Nijmegen]

Subjects
Male, DIAGNOSTIC OBSERVATION SCHEDULE, LD SCORE REGRESSION, 45/43, Medicine (miscellaneous), Genome-wide association study, Genome-wide association studies, Developmental psychology, FUNCTIONING AUTISM, Cohort Studies, 0302 clinical medicine, Heritability of autism, MESH: Cohort Studies, lcsh:QH301-705.5, GENERAL-POPULATION, 631/208/366/1373, 0303 health sciences, MESH: Genetic Predisposition to Disease, article, Autism spectrum disorders, MESH: Reproducibility of Results, Phenotype, Autistic traits, 631/208/727/2000, Trait, Female, General Agricultural and Biological Sciences, Psychology, MESH: Social Behavior, EMPATHY QUOTIENT, MESH: Autistic Disorder, 631/208/205/2138, Genetic predisposition to disease, MESH: Phenotype, General Biochemistry, Genetics and Molecular Biology, 03 medical and health sciences, PSYCHOMETRIC ANALYSIS, All institutes and research themes of the Radboud University Medical Center, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], mental disorders, medicine, Humans, REPETITIVE BEHAVIOR, Autistic Disorder, GENOME-WIDE ASSOCIATION, Social Behavior, Association (psychology), 030304 developmental biology, SYSTEMATIZING QUOTIENT, Neurodevelopmental disorders Donders Center for Medical Neuroscience [Radboudumc 7], MESH: Humans, Reproducibility of Results, SPECTRUM QUOTIENT AQ, medicine.disease, MESH: Male, [SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics, lcsh:Biology (General), MESH: Genome-Wide Association Study, Autism, [INFO.INFO-BI]Computer Science [cs]/Bioinformatics [q-bio.QM], MESH: Female, 030217 neurology & neurosurgery, Genome-Wide Association Study
Abstract

The core diagnostic criteria for autism comprise two symptom domains – social and communication difficulties, and unusually repetitive and restricted behaviour, interests and activities. There is some evidence to suggest that these two domains are dissociable, though this hypothesis has not yet been tested using molecular genetics. We test this using a genome-wide association study (N = 51,564) of a non-social trait related to autism, systemising, defined as the drive to analyse and build systems. We demonstrate that systemising is heritable and genetically correlated with autism. In contrast, we do not identify significant genetic correlations between social autistic traits and systemising. Supporting this, polygenic scores for systemising are significantly and positively associated with restricted and repetitive behaviour but not with social difficulties in autistic individuals. These findings strongly suggest that the two core domains of autism are genetically dissociable, and point at how to fractionate the genetics of autism., Varun Warrier et al. report a genome-wide association study of systemising, a non-social trait associated with autism. They find 3 loci associated with systemising and show that this trait has no significant genetic correlations to social phenotypic measures, demonstrating that the social and non-social aspects of autism are genetically distinct.

Published
2019
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9. Characterization of antibody response in neuroinvasive infection caused by Toscana virus

Author

Giada Rossini, Rémi N. Charrel, Vittorio Sambri, Silvia Morini, P. Cenni, Caterina Vocale, Nazli Ayhan, M. P. Landini, Anna Pierro, Paolo Gaibani, Stefania Varani, Michele Bartoletti, Antonio Mastroianni, F. Prati, Luigi Raumer, S. Schivazappa, Russell E. Lewis, S. Ficarelli, CRREM Laboratory [Bologna, Italy] (Unit of Microbiology), University hospital - Policlinico S.Orsola-Malpighi [Bologna, Italy], Unit of Microbiology [Pievesestina, Italy] (The Romagna Hub Laboratory), The Romagna Hub Laboratory [Pievesestina, Italy], Emergence des Pathologies Virales (EPV), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)-Institut National de la Santé et de la Recherche Médicale (INSERM), Department of Medical and Surgical Science [Bologna, Italy] (Infectious Disease Unit), University of Bologna/Università di Bologna, Infectious Disease Unit [Forlì, Italy], G.B. Morgagni-Pierantoni Hospital [Forlì, Italy], Infectious Disease Division [Reggio Emilia, Italy], Reggio Emilia Hospital [Italy], Emergency Department [Imola, Italy], Imola Hospital S. Maria della Scaletta [Imola, Italy], Department of Experimental, Diagnostic and Specialty Medicine [Bologna, Italy] (DIMES), Alma Mater Studiorum Università di Bologna [Bologna] (UNIBO), This work was supported by the University of Bologna (RFO2013e2015 to SV, MPL) and by the Emilia-Romagna Region (Lab P3 funds). This work was also supported in part by the European Virus Archive goes Global (EVAg) project that has received funding from the European Union's Horizon 2020 research and innovation programme under grant agreement No 653316 (to RNC), the EDENext FP7- n261504 EU project (to RNC) and this paper is catalogued by the EDENext Steering Committee (http://www.edenext.eu) as EDENext467. The work of RNC was done under the frame of EurNegVec COST Action TD1303., European Project: 653316,H2020,H2020-INFRAIA-2014-2015,EVAg(2015), European Project: 261504,EC:FP7:HEALTH,FP7-HEALTH-2010-single-stage,EDENEXT(2011), University of Bologna, BUISINE, Soline, European Virus Archive goes global - EVAg - - H20202015-04-01 - 2019-03-31 - 653316 - VALID, Biology and control of vector-borne infections in Europe - EDENEXT - - EC:FP7:HEALTH2011-01-01 - 2015-06-30 - 261504 - VALID, Pierro, A., Ficarelli, S., Ayhan, N., Morini, S., Raumer, L., Bartoletti, M., Mastroianni, A., Prati, F., Schivazappa, S., Cenni, P., Vocale, C., Rossini, G., Gaibani, P., Sambri, V., Landini, M.P., Lewis, R.E., Charrel, R.N., and Varani, S.

Subjects
Adult, Male, 0301 basic medicine, Microbiology (medical), Patients' follow-up, IgG avidity test, 030231 tropical medicine, 030106 microbiology, Antibodies, Viral, Bunyaviridae Infections, Antibody production, Neutralizing antibodies, Immunoglobulin G, Neutralization, Cohort Studies, 03 medical and health sciences, 0302 clinical medicine, Neutralizing antibodie, medicine, Humans, Avidity, Toscana virus infection, [SDV.MP.VIR] Life Sciences [q-bio]/Microbiology and Parasitology/Virology, biology, Toscana virus, Meningoencephalitis, Sandfly fever Naples virus, General Medicine, Middle Aged, medicine.disease, biology.organism_classification, Antibodies, Neutralizing, Meningitis, Viral, Virology, 3. Good health, Infectious Diseases, Immunoglobulin M, Immunology, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, biology.protein, Female, Antibody, Meningitis
Abstract

Among sandfly-borne pathogens, Toscana virus (TOSV) is a prominent cause of summer meningitis in Mediterranean Europe. Here, we assessed the kinetics of anti-TOSV antibodies over time in 41 patients diagnosed with TOSV-meningitis or meningoencephalitis in North-eastern Italy. Objectives: Among sandfly-borne pathogens, Toscana virus (TOSV) is a prominent cause of summer meningitis in Mediterranean Europe. Here, we assessed the kinetics of anti-TOSV antibodies over time in 41 patients diagnosed with TOSV meningitis or meningoencephalitis in northeastern Italy. Methods: Acute and follow-up serum samples were collected up to 20 months after diagnosis of TOSV infection and tested for the presence of specific antibody using immunoenzymatic and indirect immunofluorescence assays. In addition, maturation of anti-TOSV IgG over time was evaluated as well as production of neutralizing antibodies. Results: Specific IgM and IgG response was present at diagnosis in 100% of patients; TOSV-specific IgM and IgG were detected in patients' sera up to 6 and 20 months after diagnosis, respectively. The avidity index (AI) increased over the first month after infection in 100% of patients and most cases exceeded 60% by Day 30 post infection. The AI subsequently plateaued then declined at 20 months after diagnosis. Finally, neutralization assay to TOSV was performed in 217 sera collected from 41 patients; 69.6% of tested samples resulted in reactive and moderate levels of neutralizing antibodies observed during all phases of infection despite high titres of total anti-TOSV IgG. Conclusions: Specific antibody response develops rapidly and is long-lasting for neuroinvasive TOSV infection. Serodiagnosis of neuroinvasive TOSV requires simultaneous detection of specific IgM and IgG. Moderate levels of neutralizing antibodies were maintained over the study period, while the protective role of antibodies lacking neutralizing activity is unclear and requires further evaluation.

Published
2017

10. Use of explicit ICD9-CM codes to identify adult severe sepsis: impacts on epidemiological estimates

Author

J. M. Amate-Blanco, Teresa López-Cuadrado, Carmen Bouza, Plan Nacional de I+D+i (España), Ministerio de Sanidad Política Social e Igualdad (España), Funding was provided by the Spanish National I + D Programme (grant number STPY 1346/09). The funding body had no further role in study design, data collection, analysis, interpretation, writing of the report or the decision to submit the paper for publication., Ministerio de Economía y Competitividad (España), and Ministerio de Sanidad, Servicios Sociales e Igualdad (España)

Subjects
Male, medicine.medical_specialty, Epidemiology, Administrative data, Critical Care and Intensive Care Medicine, Cohort Studies, 03 medical and health sciences, 0302 clinical medicine, International Classification of Diseases, Sepsis, Internal medicine, Humans, Medicine, Health services research, 030212 general & internal medicine, Severe sepsis, Aged, Outcome, Surveillance, business.industry, Mortality rate, Incidence (epidemiology), Incidence, Organ dysfunction, Hospital discharge database, 030208 emergency & critical care medicine, Middle Aged, Epidemiologic Studies, Editorial, Spain, Relative risk, Cohort, Emergency medicine, Female, medicine.symptom, Trends, business
Abstract

Background: Severe sepsis is a challenge for healthcare systems, and epidemiological studies are essential to assess its burden and trends. However, there is no consensus on which coding strategy should be used to reliably identify severe sepsis. This study assesses the use of explicit codes to define severe sepsis and the impacts of this on the incidence and in-hospital mortality rates. Methods: We examined episodes of severe sepsis in adults aged ≥18 years registered in the 2006–2011 national hospital discharge database, identified in an exclusive manner by two ICD-9-CM coding strategies: (1) those assigned explicit ICD-9-CM codes (995.92, 785.52); and (2) those assigned combined ICD-9-CM infection and organ dysfunction codes according to modified Martin criteria. The coding strategies were compared in terms of the populations they defined and their relative implementation. Trends were assessed using Joinpoint regression models and expressed as annual percentage change (APC). Results: Of 222 846 episodes of severe sepsis identified, 138 517 (62.2 %) were assigned explicit codes and 84 329 (37.8 %) combination codes; incidence rates were 60.6 and 36.9 cases per 100 000 inhabitants, respectively. Despite similar demographic characteristics, cases identified by explicit codes involved fewer comorbidities, fewer registered pathogens, greater extent of organ dysfunction (two or more organs affected in 60 % versus 26 % of cases) and higher in-hospital mortality (54.5 % versus 29 %; risk ratio 1.86, 95 % CI 1.83, 1.88). Between 2006 and 2011, explicit codes were increasingly implemented. Standardised incidence rates in this cohort increased over time with an APC of 12.3 % (95 % CI 4.4, 20.8); in the combination code cohort, rates increased by 3.8 % (95 % CI 1.3, 6.3). A decreasing trend in mortality was observed in both cohorts though the APC was −8.1 % (95 % CI −10.4, −5.7) in the combination code cohort and −3.5 % (95 % CI −3.9, −3.2) in the explicit code cohort. Conclusions: Our findings suggest greater and increasing use of explicit codes for adult severe sepsis in Spain. This trend will have substantial impacts on epidemiological estimates, because these codes capture cases featuring greater organ dysfunction and in-hospital mortality. We especially thank the Subdirección General de Información Sanitaria (Ministry of Health, Social Services and Equality) for providing the data used in this study. Funding was provided by the Spanish National I + D Programme (grant number STPY 1346/09). The funding body had no further role in study design, data collection, analysis, interpretation, writing of the report or the decision to submit the paper for publication. Sí

Published
2016