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1. Identifying how GPs spend their time and the obstacles they face: a mixed-methods study

Author

Janet Willars, Mary Dixon-Woods, Guillaume Lamé, Lucy Hocking, Alexandros Georgiadis, Jordan M Moxey, Sarah Ball, Brandi Leach, Sonja Marjanovic, Carol Sinnott, Department of Public Health and Primary Care [Cambridge, UK] (Institute of Public Health), University of Cambridge [UK] (CAM), RAND Europe [Cambridge], Laboratoire Génie Industriel (LGI), CentraleSupélec-Université Paris-Saclay, Department of Health Sciences [Leicester], University of Leicester, Sinnott, Carol [0000-0002-8620-7461], Moxey, Jordan M [0000-0003-0165-7963], Marjanovic, Sonja [0000-0002-6956-2007], Leach, Brandi [0000-0003-3262-1541], Hocking, Lucy [0000-0002-8319-962X], Ball, Sarah [0000-0001-7300-7463], Georgiadis, Alexandros [0000-0001-7300-7463], Lamé, Guillaume [0000-0001-9514-1890], Willars, Janet [0000-0002-7886-3223], Dixon-Woods, Mary [0000-0002-5915-0041], and Apollo - University of Cambridge Repository

Subjects
mixed methods, Attitude of Health Personnel, Qualitative property, Primary care, Task completion, ethnography, Patient care, operational failures, 03 medical and health sciences, 0302 clinical medicine, General Practitioners, Medicine, Humans, Operations management, 030212 general & internal medicine, Anthropology, Cultural, Qualitative Research, general practice, business.industry, 030503 health policy & services, time and motion studies, 3. Good health, Identification (information), Work (electrical), England, Global Positioning System, [SHS.GESTION]Humanities and Social Sciences/Business administration, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, 0305 other medical science, Family Practice, business, Work systems, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, operations research
Abstract

BackgroundAlthough problems that impair task completion — known as operational failures — are an important focus of concern in primary care, they have remained little studied.AimTo quantify the time GPs spend on different activities during clinical sessions; to identify the number of operational failures they encounter; and to characterise the nature of operational failures and their impact for GPs.Design and settingMixed-method triangulation study with 61 GPs in 28 NHS general practices in England from December 2018 to December 2019.MethodTime–motion methods, ethnographic observations, and interviews were used.ResultsTime–motion data on 7679 GP tasks during 238 hours of practice in 61 clinical sessions suggested that operational failures were responsible for around 5.0% (95% confidence interval [CI] = 4.5% to 5.4%) of all tasks undertaken by GPs and accounted for 3.9% (95% CI = 3.2% to 4.5%) of clinical time. However, qualitative data showed that time–motion methods, which depend on pre-programmed categories, substantially underestimated operational failures. Qualitative data also enabled further characterisation of operational failures, extending beyond those measured directly in the time–motion data (for example, interruptions, deficits in equipment/supplies, and technology) to include problems linked to GPs’ coordination role and weaknesses in work systems and processes. The impacts of operational failures were highly consequential for GPs’ experiences of work.ConclusionGPs experience frequent operational failures, disrupting patient care, impairing experiences of work, and imposing burden in an already pressurised system. This better understanding of the nature and impact of operational failures allows for identification of targets for improvement and indicates the need for coordinated action to support GPs.

Published
2022
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2. Estimating prevalence of subjective cognitive decline in and across international cohort studies of aging: a COSMIC study

Author

Annalisa Davin, Carol Brayne, Xin Yi Gwee, Sanmei Chen, Nicolas Cherbuin, Pierre-Marie Preux, Tze Pin Ng, Richard B. Lipton, Yuda Turana, Ji Won Han, Frank Jessen, Martin P.J. van Boxtel, Normah Che Din, Roberta Vaccaro, Mindy J. Katz, Perminder S. Sachdev, Suzana Shahar, Julian N. Trollor, Fiona E. Matthews, Qi Gao, Javier Santabárbara, Mary Ganguli, Antonio Lobo, Henry Brodaty, Alexander Pabst, Susanne Röhr, Shuzo Kumagai, Marie-Laure Ancelin, Kaarin J. Anstey, Maëlenn Guerchet, Seung Wan Suh, Erin Jacobsen, Darren M. Lipnicki, Cuiling Wang, Antonio Guaita, Sebastian Köhler, Ki Woong Kim, Karen Ritchie, Yvonne Suzy Handajani, Beth E. Snitz, Divya Vanoh, Pascal M'Belesso, Isabelle Carrière, Kenji Narazaki, Blossom C. M. Stephan, Steffi G. Riedel-Heller, Raúl López-Antón, Nicole A. Kochan, John D. Crawford, Psychiatrie & Neuropsychologie, Section Neuropsychology, RS: FPN NPPP I, RS: MHeNs - R1 - Cognitive Neuropsychiatry and Clinical Neuroscience, Occupational Health and Public Health (ISAP), Universität Leipzig [Leipzig]-Occupational Health and Public Health (ISAP)-Institute of Social Medicine, Trinity College Dublin, Faculty of Medicine [Cologne], University Hospital of Cologne [Cologne]-University of Cologne, DZNE, Bonn, Germany, Faculty of Medicine [Jakarta, Indonesia], Universitas Indonesia [Jakarta, Indonesia], Department of Public Health and Primary Care [Cambridge, UK] (Institute of Public Health), University of Cambridge [UK] (CAM), MRC Biostatistics Unit [Cambridge, UK], Institute of Health & Society [Newcastle upon Tyne, UK], Newcastle University [Newcastle], Institute of Health & Society, Saul B. Korey Department of Neurology, Yeshiva University- Albert Einstein College of Medicine [New York], Neuroépidémiologie Tropicale (NET), CHU Limoges-Institut d'Epidémiologie Neurologique et de Neurologie Tropicale-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST), Université de Limoges (UNILIM)-Université de Limoges (UNILIM), Service de l'Information Médicale et de l'Évaluation [CHU Limoges] (SIME), CHU Limoges, Laboratoire de Biostatistique et d'Informatique Médicale, Université de Limoges (UNILIM), University of Edinburgh, Seoul National University [Seoul] (SNU), Seoul National University Hospital, University Kebangsaan Malaysia, University Sains Malaysia, Partenaires INRAE, Maastricht University Medical Centre (MUMC), Maastricht University [Maastricht], University of Pittsburgh School of Medicine, Pennsylvania Commonwealth System of Higher Education (PCSHE), University of Fukuoka, Röhr, Susanne [0000-0001-9385-0669], and Apollo - University of Cambridge Repository

Subjects
Male, Aging, epidemiology [Cognitive Dysfunction], Black african, Epidemiology, Disease, Neuropsychological Tests, MINI-MENTAL-STATE, lcsh:RC346-429, lcsh:RC321-571, Cohort Studies, Medical advice, PEOPLE, Prevalence, Medicine, Humans, CRITERIA, Cognitive Dysfunction, ddc:610, Cognitive decline, lcsh:Neurosciences. Biological psychiatry. Neuropsychiatry, lcsh:Neurology. Diseases of the nervous system, business.industry, Research, Data harmonization, Individual participant data, DEMENTIA, subjective cognitive decline, prevalence, epidemiology, individual participant data, data harmonization, cohort study, Middle Aged, PERFORMANCE, FRAMEWORK, COMMUNITY, Subjective cognitive decline, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Female, DETERIORATION, HEALTH, business, Cohort study, MEMORY COMPLAINTS, Demography
Abstract

International audience; Background: Subjective cognitive decline (SCD) is recognized as a risk stage for Alzheimer's disease (AD) and other dementias, but its prevalence is not well known. We aimed to use uniform criteria to better estimate SCD prevalence across international cohorts. Methods: We combined individual participant data for 16 cohorts from 15 countries (members of the COSMIC consortium) and used qualitative and quantitative (Item Response Theory/IRT) harmonization techniques to estimate SCD prevalence. Results: The sample comprised 39,387 cognitively unimpaired individuals above age 60. The prevalence of SCD across studies was around one quarter with both qualitative harmonization/QH (23.8%, 95%CI = 23.3-24.4%) and IRT (25.6%, 95%CI = 25.1-26.1%); however, prevalence estimates varied largely between studies (QH 6.1%, 95%CI = 5.1-7.0%, to 52.7%, 95%CI = 47.4-58.0%; IRT: 7.8%, 95%CI = 6.8-8.9%, to 52.7%, 95%CI = 47.4-58.0%). Across studies, SCD prevalence was higher in men than women, in lower levels of education, in Asian and Black African people compared to White people, in lower- and middle-income countries compared to high-income countries, and in studies conducted in later decades. Conclusions: SCD is frequent in old age. Having a quarter of older individuals with SCD warrants further investigation of its significance, as a risk stage for AD and other dementias, and of ways to help individuals with SCD who seek medical advice. Moreover, a standardized instrument to measure SCD is needed to overcome the measurement variability currently dominant in the field.

Published
2020
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3. Estimating prevalence of subjective cognitive decline acrossinternational cohort studies of ageing: a cosmic study

Author

Roehr, Susanne, pabst, Alexander, Riedel-Heller, Steffi G., Ancelin, Marie-Laure, Anstey, Kaarin J., Brayne, Carol, Brodaty, Henry, Ganguli, Mary, Guerchet, Maëlenn, Katz, Mindy, Kim, Ki Woong, Koehler, Sebastian, Kumagai, Shuzo, Lipton, Richard, Lobo, Antonio, Ng, Tze Pin, Guaita, Antonio, Preux, Pierre-Marie, Ritchie, Karen, Shahar, Suzana, Turana, Yuda, van Boxtel, Martin, Lipnicki, Darren, Sachdev, Perminder, Institute of Social Medicine, Occupational Health and Public Health, Universität Leipzig [Leipzig], Neuropsychiatrie : recherche épidémiologique et clinique (PSNREC), Université Montpellier 1 (UM1)-Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM), UNSW Faculty of Medicine [Sydney], University of New South Wales [Sydney] (UNSW), Department of Public Health and Primary Care [Cambridge, UK] (Institute of Public Health), University of Cambridge [UK] (CAM), Centre for Healthy Brain Ageing [Sydney], The University of Sydney, University of Pittsburgh School of Medicine, Pennsylvania Commonwealth System of Higher Education (PCSHE), Neuroépidémiologie Tropicale (NET), Institut Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST), Université de Limoges (UNILIM)-Université de Limoges (UNILIM)-CHU Limoges-Institut d'Epidémiologie Neurologique et de Neurologie Tropicale-Institut National de la Santé et de la Recherche Médicale (INSERM), Albert Einstein College of Medicine [New York], Seoul National University Bundang Hospital, Department of Psychiatry and Neuropsychology [Maastricht], Maastricht University [Maastricht], Kyushu University [Fukuoka], Department of Medicine [Zaragoza, Spain], University of Zaragoza - Universidad de Zaragoza [Zaragoza], Centro de Investigación Biomédica en Red Salud Mental [Madrid] (CIBER-SAM), Yong Loo Lin School of Medicine, National University of Singapore, Seoul National University [Seoul] (SNU), Laboratoire de Biostatistique et d'Informatique Médicale, Université de Limoges (UNILIM), Service de l'Information Médicale et de l'Évaluation [CHU Limoges] (SIME), CHU Limoges, University Malaysia, Atma Jaya Yogyakarta University, Dementia Collaborative Research Centre, and Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)

Subjects
hemic and lymphatic diseases, preclinical Alzheimer's disease, harmonization, COSMIC, prevalence, item response theory, epidemiology, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, individual participant data, subjective cognitive decline, cross-cohort analysis
Abstract

International audience; Abstract:INTRODUCTION Subjective cognitive decline (SCD), i.e. a self-experienced decline in cognitive ability in the absence of objective cognitive impairment, is recognized as the first notable cognitive syndrome in the preclinical stage of Alzheimer’s disease (AD) and other dementias. However, estimates on the prevalence of SCD are scarce. Therefore, we aimed to estimate SCD prevalence based on consensus research criteria for SCD across international cohort studies of ageing.METHODS Analyses were based on the combined baseline data for 16 international cohort studies from 15 countries. All studies were members of COSMIC (Cohort Studies of Memory in an International Consortium). Qualitative/semantic and quantitative (Item Response Theory/IRT) approaches were used to a) harmonize SCD items across studies and b) derive SCD prevalence estimates, applying a uniform operationalization algorithm based on current SCD research criteria and implementation guidelines.RESULTS Analyses included data from 39,387 cognitively unimpaired individuals at least 60 years of age (mean age: M = 73.1 years; SD = 7.1 years); 57.7% were women. Variety of SCD items was high between studies; however, qualitative harmonization (QH) and IRT both robustly suggested a total SCD prevalence of around one quarter (QH: 23.8%, 95%CI = 23.3%-24.4%; IRT: 25.6%, 95%CI = 25.1%-26.1%) across uniform criteria. SCD prevalence was lower in a) women compared to men, b) individuals with educational levels above primary, c) high-income countries compared to countries with lower income levels, and d) in White people compared to Asian people.DISCUSSION SCD occurs relatively frequently in ageing populations around the globe, as estimated across 16 international cohorts. However, SCD measurement techniques vary in the absence of standardized instruments, and therefore, our prevalence estimates may be associated with someinaccuracy. Nevertheless, with almost a quarter of all elderly reporting SCD, further investigation of its significance as the first cognitive syndrome in preclinical AD and other dementia is needed. This may lead to improved strategies for early identification and prevention of dementia.

Published
2020

4. Serum magnesium and calcium levels in relation to ischemic stroke Mendelian randomization study

Author

Susanna C. Larsson, Matthew Traylor, Stephen Burgess, Giorgio B. Boncoraglio, Christina Jern, Karl Michaëlsson, Hugh S. Markus, Rainer Malik, Ganesh Chauhan, Muralidharan Sargurupremraj, Yukinori Okada, Aniket Mishra, Loes Rutten-Jacobs, Anne-Katrin Giese, Sander W van der Laan, Solveig Gretarsdottir, Christopher D Anderson, Michael Chong, Hieab HH Adams, Tetsuro Ago, Peter Almgren, Philippe Amouyel, Hakan Ay, raci M Bartz, Oscar R Benavente, Steve Bevan, Giorgio B Boncoraglio, Robert D Brown, Adam S Butterworth, Caty Carrera, Cara L Carty, Daniel I Chasman, Wei-Min Chen, John W Cole, Adolfo Correa, Ioana Cotlarciuc, Carlos Cruchaga, John Danesh, Paul IW de Bakker, Anita L DeStefano, Marcel den Hoed, Qing Duan, Stefan T Engelter, Guido J Falcone, Rebecca F Gottesman, Raji P Grewal, Vilmundur Gudnason, Stefan Gustafsson, Jeffrey Haessler, Tamara B Harris, Ahamad Hassan, Aki S Havulinna, Susan R Heckbert, Elizabeth G Holliday, George Howard, Fang-Chi Hsu, Hyacinth I Hyacinth, M Arfan Ikram, Erik Ingelsson, Marguerite R Irvin, Xueqiu Jian, Jordi Jiménez-Conde, Julie A Johnson, J Wouter Jukema, Masahiro Kanai, Keith L Keene, Brett M Kissela, Dawn O Kleindorfer, Charles Kooperberg, Michiaki Kubo, Leslie A Lange, Carl D Langefeld, Claudia Langenberg, Lenore J Launer, Jin-Moo Lee, Robin Lemmens, Didier Leys, Cathryn M Lewis, Wei-Yu Lin, Arne G Lindgren, Erik Lorentzen, Patrik K Magnusson, Jane Maguire, Ani Manichaikul, Patrick F McArdle, James F Meschia, Braxton D Mitchell, Thomas H Mosley, Michael A Nalls, Toshiharu Ninomiya, Martin J O'Donnell, Bruce M Psaty, Sara L Pulit, Kristiina Rannikmäe, Alexander P Reiner, Kathryn M Rexrode, Kenneth Rice, Stephen S Rich, Paul M Ridker, Natalia S Rost, Peter M Rothwell, Jerome I Rotter, Tatjana Rundek, Ralph L Sacco, Saori Sakaue, Michele M Sale, Veikko Salomaa, Bishwa R Sapkota, Reinhold Schmidt, Carsten O Schmidt, Ulf Schminke, Pankaj Sharma, Agnieszka Slowik, Cathie LM Sudlow, Christian Tanislav, Turgut Tatlisumak, Kent D Taylor, Vincent NS Thijs, Gudmar Thorleifsson, Unnur Thorsteinsdottir, Steffen Tiedt, Stella Trompet, Christophe Tzourio, Cornelia M van Duijn, Matthew Walters, Nicholas J Wareham, Sylvia Wassertheil-Smoller, James G Wilson, Kerri L Wiggins, Qiong Yang, Salim Yusuf, Najaf Amin, Hugo S Aparicio, Donna K Arnett, John Attia, Alexa S Beiser, Claudine Berr, Julie E Buring, Mariana Bustamante, Valeria Caso, Yu-Ching Cheng, Seung Hoan Choi, Ayesha Chowhan, Natalia Cullell, Jean-François Dartigues, Hossein Delavaran, Pilar Delgado, Marcus Dörr, Gunnar Engström, Ian Ford, Wander S Gurpreet, Anders Hamsten, Laura Heitsch, Atsushi Hozawa, Laura Ibanez, Andreea Ilinca, Martin Ingelsson, Motoki Iwasaki, Rebecca D Jackson, Katarina Jood, Pekka Jousilahti, Sara Kaffashian, Lalit Kalra, Masahiro Kamouchi, Takanari Kitazono, Olafur Kjartansson, Manja Kloss, Peter J Koudstaal, Jerzy Krupinski, Daniel L Labovitz, Cathy C Laurie, Christopher R Levi, Linxin Li, Lars Lind, Cecilia M Lindgren, Vasileios Lioutas, Yong Mei Liu, Oscar L Lopez, Hirata Makoto, Nicolas Martinez-Majander, Koichi Matsuda, Naoko Minegishi, Joan Montaner, Andrew P Morris, Elena Muiño, Martina Müller-Nurasyid, Bo Norrving, Soichi Ogishima, Eugenio A Parati, Leema Reddy Peddareddygari, Nancy L Pedersen, Joanna Pera, Markus Perola, Alessandro Pezzini, Silvana Pileggi, Raquel Rabionet, Iolanda Riba-Llena, Marta Ribasés, Jose R Romero, Jaume Roquer, Anthony G Rudd, Antti-Pekka Sarin, Ralhan Sarju, Chloe Sarnowski, Makoto Sasaki, Claudia L Satizabal, Mamoru Satoh, Naveed Sattar, Norie Sawada, Gerli Sibolt, Ásgeir Sigurdsson, Albert Smith, Kenji Sobue, Carolina Soriano-Tárraga, Tara Stanne, O Colin Stine, David J Stott, Konstantin Strauch, Takako Takai, Hideo Tanaka, Kozo Tanno, Alexander Teumer, Liisa Tomppo, Nuria P Torres-Aguila, Emmanuel Touze, Shoichiro Tsugane, Andre G Uitterlinden, Einar M Valdimarsson, Sven J van der Lee, Henry Völzke, Kenji Wakai, David Weir, Stephen R Williams, Charles DA Wolfe, Quenna Wong, Huichun Xu, Taiki Yamaji, Dharambir K Sanghera, Olle Melander, Daniel Strbian, Israel Fernandez-Cadenas, W T Longstreth, Arndt Rolfs, Jun Hata, Daniel Woo, Jonathan Rosand, Guillaume Pare, Jemma C Hopewell, Danish Saleheen, Kari Stefansson, Bradford B Worrall, Steven J Kittner, Sudha Seshadri, Myriam Fornage, Hugh S Markus, Joanna MM Howson, Yoichiro Kamatani, Stephanie Debette, Martin Dichgans, Berr, Claudine, Unit of Cardiovascular and Nutritional Epidemiology [Stockholm, Sweden], Karolinska Institutet [Stockholm]-Institute of Environmental Medicine [Stockholm, Sweden], Stroke Research Group [London, UK] (Department of Brain Repair and Rehabilitation), University of London - UCL [London, UK], MRC Biostatistics Unit [Cambridge, UK], University of Cambridge [UK] (CAM), Department of Public Health and Primary Care [Cambridge, UK] (Institute of Public Health), Fondazione IRCCS Istituto Neurologico 'Carlo Besta', Section of Clinical Immunology [Uppsala, Sweden] (Department of Immunology, Genetics and Pathology), Uppsala University, Department of Surgical Sciences [Uppsala, Sweden], This work was supported by the Swedish Research Council for Health, Working Life and Welfare (Forte) and the Swedish Research Council. Hugh Markus is supported by an NIHR Senior Investigator award. His and Matthew Traylor’s work is supported by infrastructural support from the Cambridge University Hospitals Trust NIHR Biomedical Research Centre., MEGASTROKE project of the International Stroke Genetics Consortium : Malik R, Chauhan G, Traylor M, Sargurupremraj M, Okada Y, Mishra A, Rutten-Jacobs L, Giese AK, van der Laan SW, Gretarsdottir S, Anderson CD, Chong M, Adams HH, Ago T, Almgren P, Amouyel P, Ay H, Bartz RM, Benavente OR, Bevan S, Boncoraglio GB, Brown RD Jr, Butterworth AS, Carrera C, Carty CL, Chasman DI, Chen WM, Cole JW, Correa A, Cotlarciuc I, Cruchaga C, Danesh J, de Bakker PI, DeStefano AL, Hoed MD, Duan Q, Engelter ST, Falcone GJ, Gottesman RF, Grewal RP, Gudnason V, Gustafsson S, Haessler J, Harris TB, Hassan A, Havulinna AS, Heckbert SR, Holliday EG, Howard G, Hsu FC, Hyacinth HI, Ikram MA, Ingelsson E, Irvin MR, Jian X, Jiménez-Conde J, Johnson JA, Jukema JW, Kanai M, Keene KL, Kissela BM, Kleindorfer DO, Kooperberg C, Kubo M, Lange LA, Langefeld CD, Langenberg C, Launer LJ, Lee JM, Lemmens R, Leys D, Lewis CM, Lin WY, Lindgren AG, Lorentzen E, Magnusson PK, Maguire J, Manichaikul A, McArdle PF, Meschia JF, Mitchell BD, Mosley TH, Nalls MA, Ninomiya T, O'Donnell MJ, Psaty BM, Pulit SL, Rannikmäe K, Reiner AP, Rexrode KM, Rice K, Rich SS, Ridker PM, Rost NS, Rothwell PM, Rotter JI, Rundek T, Sacco RL, Sakaue S, Sale MM, Salomaa V, Sapkota BR, Schmidt R, Schmidt CO, Schminke U, Sharma P, Slowik A, Sudlow CL, Tanislav C, Tatlisumak T, Taylor KD, Thijs VN, Thorleifsson G, Thorsteinsdottir U, Tiedt S, Trompet S, Tzourio C, van Duijn CM, Walters M, Wareham NJ, Wassertheil-Smoller S, Wilson JG, Wiggins KL, Yang Q, Yusuf S, Amin N, Aparicio HS, Arnett DK, Attia J, Beiser AS, Berr C, Buring JE, Bustamante M, Caso V, Cheng YC, Choi SH, Chowhan A, Cullell N, Dartigues JF, Delavaran H, Delgado P, Dörr M, Engström G, Ford I, Gurpreet WS, Hamsten A, Heitsch L, Hozawa A, Ibanez L, Ilinca A, Ingelsson M, Iwasaki M, Jackson RD, Jood K, Jousilahti P, Kaffashian S, Kalra L, Kamouchi M, Kitazono T, Kjartansson O, Kloss M, Koudstaal PJ, Krupinski J, Labovitz DL, Laurie CC, Levi CR, Li L, Lind L, Lindgren CM, Lioutas V, Liu YM, Lopez OL, Makoto H, Martinez-Majander N, Matsuda K, Minegishi N, Montaner J, Morris AP, Muiño E, Müller-Nurasyid M, Norrving B, Ogishima S, Parati EA, Peddareddygari LR, Pedersen NL, Pera J, Perola M, Pezzini A, Pileggi S, Rabionet R, Riba-Llena I, Ribasés M, Romero JR, Roquer J, Rudd AG, Sarin AP, Sarju R, Sarnowski C, Sasaki M, Satizabal CL, Satoh M, Sattar N, Sawada N, Sibolt G, Sigurdsson Á, Smith A, Sobue K, Soriano-Tárraga C, Stanne T, Stine OC, Stott DJ, Strauch K, Takai T, Tanaka H, Tanno K, Teumer A, Tomppo L, Torres-Aguila NP, Touze E, Tsugane S, Uitterlinden AG, Valdimarsson EM, van der Lee SJ, Völzke H, Wakai K, Weir D, Williams SR, Wolfe CD, Wong Q, Xu H, Yamaji T, Sanghera DK, Melander O, Jern C, Strbian D, Fernandez-Cadenas I, Longstreth WT Jr, Rolfs A, Hata J, Woo D, Rosand J, Pare G, Hopewell JC, Saleheen D, Stefansson K, Worrall BB, Kittner SJ, Seshadri S, Fornage M, Markus HS, Howson JM, Kamatani Y, Debette S, Dichgans M., Larsson, Susanna C [0000-0003-0118-0341], Apollo - University of Cambridge Repository, and Neurology

Subjects
medicine.medical_specialty, Neurology, Heredity, Neurologi, [SDV]Life Sciences [q-bio], chemistry.chemical_element, Calcium, Polymorphism, Single Nucleotide, Gastroenterology, Article, Brain Ischemia, Brain ischemia, 03 medical and health sciences, 0302 clinical medicine, Human genetics, Internal medicine, Mendelian randomization, Medicine, Humans, Magnesium, 030212 general & internal medicine, Stroke, Herència (Biologia), Genètica humana, business.industry, Neurosciences, Mendelian Randomization Analysis, Odds ratio, medicine.disease, Confidence interval, 3. Good health, [SDV] Life Sciences [q-bio], Intracranial Embolism, chemistry, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Neurology (clinical), business, 030217 neurology & neurosurgery, Neurovetenskaper
Abstract

Comment inThe yin and yang of magnesium and calcium: New genetic insights for stroke? [Neurology. 2019]; International audience; Objective To determine whether serum magnesium and calcium concentrations are causally associated with ischemic stroke or any of its subtypes using the mendelian randomization approach. Methods Analyses were conducted using summary statistics data for 13 single-nucleotide polymorphisms robustly associated with serum magnesium (n = 6) or serum calcium (n = 7) concentrations. The corresponding data for ischemic stroke were obtained from the MEGASTROKE consortium (34,217 cases and 404,630 noncases). Results In standard mendelian randomization analysis, the odds ratios for each 0.1 mmol/L (about 1 SD) increase in genetically predicted serum magnesium concentrations were 0.78 (95% confidence interval [CI] 0.69-0.89; p = 1.3 × 10 −4) for all ischemic stroke, 0.63 (95% CI 0.50-0.80; p = 1.6 × 10 −4) for cardioembolic stroke, and 0.60 (95% CI 0.44-0.82; p = 0.001) for large artery stroke; there was no association with small vessel stroke (odds ratio 0.90, 95% CI 0.67-1.20; p = 0.46). Only the association with cardioembolic stroke was robust in sensitivity analyses. There was no association of genetically predicted serum calcium concentrations with all ischemic stroke (per 0.5 mg/dL [about 1 SD] increase in serum calcium: odds ratio 1.03, 95% CI 0.88-1.21) or with any subtype. Conclusions This study found that genetically higher serum magnesium concentrations are associated with a reduced risk of cardioembolic stroke but found no significant association of genetically higher serum calcium concentrations with any ischemic stroke subtype.

Published
2019
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5. Association of longitudinal alcohol consumption trajectories with coronary heart disease: a meta-analysis of six cohort studies using individual participant data

Author

O'Neill, Dara, Britton, Annie, Hannah, Mary K., Goldberg, Marcel, Kuh, Diana, Khaw, Kay Tee, Bell, Steven, Department of Social Science [London, UK] (CLOSER), University College of London [London] (UCL)-Institute of Education [London, UK], Department of Epidemiology and Public Health, University College of London [London] (UCL), MRC/CSO Social and Public Health Sciences Unit [Glasgow, UK], University of Glasgow-Institute of Health and Wellbeing [Glasgow, UK], Cohortes épidémiologiques en population (CONSTANCES), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay-Université de Paris (UP), UK MRC Unit for Lifelong Health & Ageing [London, UK], Cambridge Institute of Public Health [Cambridge, UK], University of Cambridge [UK] (CAM), Department of Public Health and Primary Care [Cambridge, UK] (Institute of Public Health), This work has been undertaken as part of the Alcohol Life-course Project (http://www.ucl.ac.uk/alcohol-lifecourse), which is funded by the UK Medical Research Council/Alcohol Research UK (MR/M006638/1) and the European Research Council (ERC-StG-2012-309337_AlcoholLifecourse). EPIC-N is supported by programme grants from the UK Medical Research Council (G0401527 and G1000143) and Cancer Research United Kingdom (C864/A8257) with additional support from the Stroke Association, British Heart Foundation, Research Into Ageing and the Academy of Medical Science. GAZEL was partly supported by Agence Nationale De La Recherche (ANR-08-BLAN-0028-01), Agence Française de Sécurité Sanitaire de l’Environnement et du Travail (AFSSET-EST08–35), Electricité de France-Gaz de France and the TGIR Cohortes Santé 2008 Program. NSHD is supported by the UK Medical Research Council (MR_UC_12019/01). Twenty-07 is funded by the UK Medical Research Council (MC_A540_53462and MC_UU_12017/13). WII is supported by the UK Medical Research Council (MR/K013351/1 and G0902037), the British Heart Foundation (RG/13/2/30098) and the US National Institutes of Health (R01HL36310 and R01AG013196)., Bodescot, Myriam, Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay-Université Paris Cité (UPCité), Apollo - University of Cambridge Repository, and O'Neill, Dara [0000-0002-8830-0264]

Subjects
Adult, Male, Alcohol Drinking, Myocardial Infarction, lcsh:Medicine, Coronary Disease, Cohort Studies, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Risk Factors, Humans, Longitudinal Studies, IPD meta-analysis, Aged, Aged, 80 and over, Incidence, lcsh:R, Middle Aged, Longitudinal design, United Kingdom, [SDV.MHEP.CSC] Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Coronary heart disease, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, Disease Progression, Female, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, France, Alcohol, Research Article
Abstract

Background Studies have shown that alcohol intake trajectories differ in their associations with biomarkers of cardiovascular functioning, but it remains unclear if they also differ in their relationship to actual coronary heart disease (CHD) incidence. Using multiple longitudinal cohort studies, we evaluated the association between long-term alcohol consumption trajectories and CHD. Methods Data were drawn from six cohorts (five British and one French). The combined analytic sample comprised 35,132 individuals (62.1% male; individual cohorts ranging from 869 to 14,247 participants) of whom 4.9% experienced an incident (fatal or non-fatal) CHD event. Alcohol intake across three assessment periods of each cohort was used to determine participants’ intake trajectories over approximately 10 years. Time to onset for (i) incident CHD and (ii) fatal CHD was established using surveys and linked medical record data. A meta-analysis of individual participant data was employed to estimate the intake trajectories' association with CHD onset, adjusting for demographic and clinical characteristics. Results Compared to consistently moderate drinkers (males: 1–168 g ethanol/week; females: 1–112 g ethanol/week), inconsistently moderate drinkers had a significantly greater risk of incident CHD [hazard ratio (HR) = 1.18, 95% confidence interval (CI) = 1.02–1.37]. An elevated risk of incident CHD was also found for former drinkers (HR = 1.31, 95% CI = 1.13–1.52) and consistent non-drinkers (HR = 1.47, 95% CI = 1.21–1.78), although, after sex stratification, the latter effect was only evident for females. When examining fatal CHD outcomes alone, only former drinkers had a significantly elevated risk, though hazard ratios for consistent non-drinkers were near identical. No evidence of elevated CHD risk was found for consistently heavy drinkers, and a weak association with fatal CHD for inconsistently heavy drinkers was attenuated following adjustment for confounding factors. Conclusions Using prospectively recorded alcohol data, this study has shown how instability in drinking behaviours over time is associated with risk of CHD. As well as individuals who abstain from drinking (long term or more recently), those who are inconsistently moderate in their alcohol intake have a higher risk of experiencing CHD. This finding suggests that policies and interventions specifically encouraging consistency in adherence to lower-risk drinking guidelines could have public health benefits in reducing the population burden of CHD. The absence of an effect amongst heavy drinkers should be interpreted with caution given the known wider health risks associated with such intake. Trial registration ClinicalTrials.gov, NCT03133689. Electronic supplementary material The online version of this article (10.1186/s12916-018-1123-6) contains supplementary material, which is available to authorized users.

Published
2018
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6. Use of the BOADICEA Web Application in clinical practice: appraisals by clinicians from various countries

Author

Douglas F. Easton, Peter Devilee, Kerstin Rhiem, Léonore Robieux, Jean-Luc Kop, Alex P Cunningham, S. Dolbeault, Antonis C. Antoniou, Marc Tischkowitz, Dominique Stoppa-Lyonnet, Antoine De Pauw, Anne Brédart, Rita Schmutlzer, Hans Ehrencrona, Institut Curie [Paris], Laboratoire de psychologie de l'interaction et des relations intersubjectives (INTERPSY), Université de Lorraine (UL), Department of Public Health and Primary Care [Cambridge, UK] (Institute of Public Health), University of Cambridge [UK] (CAM), Service d'oncogénétique, Departament of Genetics and Pathology, Uppsala University-Rudbeck Laboratory, Brédart, Anne [0000-0002-7734-0332], and Apollo - University of Cambridge Repository

Subjects
0301 basic medicine, Cancer Research, medicine.medical_specialty, Pathology, Multivariate analysis, Service delivery framework, Cross-sectional study, Breast Neoplasms, [SDV.CAN]Life Sciences [q-bio]/Cancer, Clinical practice, Affect (psychology), Risk Assessment, 03 medical and health sciences, 0302 clinical medicine, Breast cancer, Epidemiology, Genetics, medicine, Humans, Genetic Predisposition to Disease, Genetic Testing, Medical Informatics Applications, Seniority, Survey, Genetics (clinical), Genetic testing, BRCA2 Protein, medicine.diagnostic_test, BRCA1 Protein, business.industry, Correction, 3. Good health, Cross-Sectional Studies, 030104 developmental biology, Oncology, 030220 oncology & carcinogenesis, Family medicine, Multivariate Analysis, Mutation, [SCCO.PSYC]Cognitive science/Psychology, Tool, Female, Risk assessment, business, Appraisal, Risk prediction model
Abstract

International audience; The ‘BOADICEA’ Web Application (BWA) used to assess breast cancer risk, is currently being further developed, to integrate additional genetic and non-genetic factors. We surveyed clinicians’ perceived acceptability of the existing BWA v3. An online survey was conducted through the BOADICEA website, and the British, Dutch, French and Swedish genetics societies. Cross-sectional data from 443 participants who provided at least 50% responses were analysed. Respondents varied in age and, clinical seniority, but mainly comprised women (77%) and genetics professionals(82%). Some expressed negative opinions about the scientific validity of BOADICEA (9%) and BWA v3 risk presentations(7-9%). Data entry time (62%), clinical utility (22%) and ease of communicating BWA v3 risks (13-17%) received additional negative appraisals. In multivariate analyses, controlling for gender and country, data entry time was perceived as longer by genetic counsellors than clinical geneticists (p < 0.05). Respondents who (1) considered hormonal BC risk factors as more important (p < 0.01), and (2) communicated numerical risk estimates more frequently (p < 0.001), judged BWA v3 of lower clinical utility. Respondents who carried out less frequent clinical activity (p < 0.01) and respondents with '11 to 15 years' seniority (p < 0.01) had less favourable opinions of BWA v3 risk presentations. Seniority of '6 to 10 years' (p < 0.05) and more frequent numerical risk communication (p < 0.05) were associated with higher fear of communicating the BWA v3 risks to patients. The level of genetics training did not affect opinions. Further development of BWA should consider technological, genetics service delivery and training initiatives.

Published
2018
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7. Mediation and modification of genetic susceptibility to obesity by eating behaviors

Author

Ken K. Ong, Véronique Pelloux, Emma A.D. Clifton, Felix R. Day, Marie-Aline Charles, Soren Brage, Blandine de Lauzon-Guillain, Karine Clément, Nicholas J. Wareham, Yves Akoli Koudou, Nita G. Forouhi, Barbara Heude, Simon J. Griffin, Equipe 6 : ORCHAD - Origines précoces de la santé du développement de l'enfant (CRESS - U1153), Université Paris Descartes - Paris 5 (UPD5)-Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité (CRESS (U1153 / UMR_A_1125 / UMR_S_1153)), Institut National de la Recherche Agronomique (INRA)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Recherche Agronomique (INRA)-Université Paris Diderot - Paris 7 (UPD7)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM), MRC Epidemiology Unit [Cambridge, UK] (Wellcome Trust-MRC Institute of Metabolic Science), University of Cambridge [UK] (CAM)-Addenbrooke’s Hospital [Cambridge, UK]-Wellcome Trust-MRC Institute of Metabolic Science (IMS), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Institute of cardiometabolism and nutrition (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Université Pierre et Marie Curie - Paris 6 (UPMC), Department of Public Health and Primary Care [Cambridge, UK] (Institute of Public Health), University of Cambridge [UK] (CAM), de Lauzon-Guillain, Blandine [0000-0001-5887-8842], Clifton, Emma Ad [0000-0002-1649-7248], Day, Felix R [0000-0003-3789-7651], Brage, Soren [0000-0002-1265-7355], Forouhi, Nita G [0000-0002-5041-248X], Griffin, Simon J [0000-0002-2157-4797], Wareham, Nicholas J [0000-0003-1422-2993], Charles, Marie-Aline [0000-0003-4025-4390], Heude, Barbara [0000-0002-1565-1629], Ong, Ken K [0000-0003-4689-7530], Apollo - University of Cambridge Repository, Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut de Cardiométabolisme et Nutrition = Institute of Cardiometabolism and Nutrition [CHU Pitié Salpêtrière] (IHU ICAN), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), and de Lauzon-Guillain, Blandine

Subjects
Gerontology, Male, Emotions, Medicine (miscellaneous), Appetite, Eating, 0302 clinical medicine, Cognition, Risk Factors, Surveys and Questionnaires, 030212 general & internal medicine, Body mass index, media_common, 2. Zero hunger, education.field_of_study, Nutrition and Dietetics, Self-control, Emotional eating, Middle Aged, Genetic risk score, 3. Good health, Female, medicine.symptom, Dieting, Clinical psychology, Adult, Mediation (statistics), media_common.quotation_subject, Population, 030209 endocrinology & metabolism, Hyperphagia, Article, Self-Control, 03 medical and health sciences, BMI, Sex Factors, Genetic predisposition, medicine, Genetics, Humans, Genetic Predisposition to Disease, Eating behavior, Obesity, education, business.industry, Feeding Behavior, medicine.disease, [SDV.AEN] Life Sciences [q-bio]/Food and Nutrition, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, Gene-Environment Interaction, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, business, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition
Abstract

Background: Many genetic variants show highly robust associations with body mass index (BMI). However, the mechanisms through which genetic susceptibility to obesity operates are not well understood. Potentially modifiable mechanisms, including eating behaviors, are of particular interest to public health.Objective: Here we explore whether eating behaviors mediate or modify genetic susceptibility to obesity.Design: Genetic risk scores for BMI (BMI-GRSs) were calculated for 3515 and 2154 adults in the Fenland and EDEN (Etude des determinants pre et postnatals de la sante et du developpement de l'enfant) population-based cohort studies, respectively. The eating behaviors-emotional eating, uncontrolled eating, and cognitive restraint-were measured through the use of a validated questionnaire. The mediating effect of each eating behavior on the association between the BMI-GRS and measured BMI was assessed by using the Sobel test. In addition, we tested for interactions between each eating behavior and the BMI-GRS on BMI.Results: The association between the BMI-GRS and BMI was mediated by both emotional eating (EDEN: P-Sobel = 0.01; Fenland: P-Sobel = 0.02) and uncontrolled eating (EDEN: P-Sobel = 0.04; Fenland: P-Sobel = 0.0006) in both sexes combined. Cognitive restraint did not mediate this association (P-Sobel > 0.10), except among EDEN women (P-Sobel = 0.0009). Cognitive restraint modified the relation between the BMI-GRS and BMI among men (EDEN: P-interaction = 0.0001; Fenland: P-interaction = 0.04) and Fenland women (P-interaction = 0.0004). By tertiles of cognitive restraint, the association between the BMI-GRS and BMI was strongest in the lowest tertile of cognitive restraint, and weakest in the highest tertile.Conclusions: Genetic susceptibility to obesity was partially mediated by the "appetitive" eating behavior traits (uncontrolled and emotional eating) and, in 3 of the 4 population groups studied, was modified by cognitive restraint. High levels of cognitive control over eating appear to attenuate the genetic susceptibility to obesity. Future research into interventions designed to support restraint may help to protect genetically susceptible individuals from weight gain.

Published
2017
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8. Use of the BOADICEA breast cancer risk prediction tool in clinical practice: Appraisals across clinicians from various countries

Author

Brédart, Anne, Kop, Jean-Luc, Antoniou, Antonis C, Alex, Cunningham, De Pauw, Antoine, Tischkowitz, Marc, Ehrencrona, Hans, Dolbeault, Sylvie, Léonore, Robieux, Rhiem, Kerstin, Easton, Douglas F, Devilee, Peter, Stoppa-Lyonnet, Dominique, Schmutzler, Rita, Unité de psycho-oncologie, Institut Curie [Paris], Laboratoire lorrain de psychologie et neurosciences de la dynamique des comportements (2LPN), Université de Lorraine (UL), Department of Public Health and Primary Care [Cambridge, UK] (Institute of Public Health), University of Cambridge [UK] (CAM), Service d'oncogénétique, Department of Genetics, Portuguese Oncology Institute, Departament of Genetics and Pathology, Uppsala University-Rudbeck Laboratory, Troubles du comportement alimentaire de l'adolescent (UMR_S 669), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Sud - Paris 11 (UP11), Department of Gynaecology and Obstetrics, University Hospital of Cologne [Cologne]-Centre of Familial Breast and Ovarian Cancer-Centre for Integrated Oncology (CIO), Cancer Research U.K. Genetic Epidemiology Unit, Strangeways Research Laboratory, Department of Human Genetics & Department of Pathology, Leiden University Medical Center (LUMC), Unité de génétique et biologie des cancers (U830), Université Paris Descartes - Paris 5 (UPD5)-Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre for Hereditary Breast and Ovarian Cancer, Department of Obstetrics and Gynaecology-University of Cologne, Institut Curie, and Université Paris Descartes - Paris 5 (UPD5)-Institut Curie-Institut National de la Santé et de la Recherche Médicale (INSERM)

Subjects
[SCCO.PSYC]Cognitive science/Psychology, [SDV.CAN]Life Sciences [q-bio]/Cancer, ComputingMilieux_MISCELLANEOUS
Abstract

International audience

Published
2017

9. Role of measurement uncertainties in observed variability in the spectral backscattering ratio: a case study in mineral-rich coastal waters

Author

Violeta Sanjuan Calzado, David McKee, Alex Cunningham, Malik Chami, Ian Brown, David Doxaran, University of Strathclyde [Glasgow], Laboratoire d'océanographie de Villefranche (LOV), Institut national des sciences de l'Univers (INSU - CNRS)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut de la Mer de Villefranche (IMEV), Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), University of Oxford [Oxford], Department of Public Health and Primary Care [Cambridge, UK] (Institute of Public Health), and University of Cambridge [UK] (CAM)

Subjects
Physics, 010504 meteorology & atmospheric sciences, business.industry, Scattering, Materials Science (miscellaneous), Mie scattering, Magnitude (mathematics), 01 natural sciences, Industrial and Manufacturing Engineering, Light scattering, 010309 optics, Wavelength, Optics, 13. Climate action, Attenuation coefficient, 0103 physical sciences, Radiative transfer, 14. Life underwater, Particle size, Business and International Management, business, Physics::Atmospheric and Oceanic Physics, [SDU.STU.OC]Sciences of the Universe [physics]/Earth Sciences/Oceanography, 0105 earth and related environmental sciences
Abstract

The particulate backscattering ratio (b(bp)/b(p)) is a useful indicator of the angular scattering characteristics of natural waters. Recent studies have shown evidence both for and against significant spectral variability in b(bp)/b(p) in the visible domain, but most show significant variability in its magnitude. We present results from a case study in which both backscattering and scattering coefficients were measured at nine wavelengths in a region of UK coastal waters where optical scattering is strongly influenced by inorganic particles and where a wide range of turbidities is found in a small geographic area. Using a new approach based on regression analysis of in situ signals, it is shown that, for this study site, most of the apparent variability in the magnitude of the backscattering ratio can be attributed to measurement uncertainties. Regression analysis suggests that b(bp)/b(p) is wavelength dependent for these mineral-rich waters. This conclusion can only be avoided by positing the existence of undocumented, systematic, wavelength-dependent errors in backscattering measurements made by two independently calibrated sensors. These results are important for radiative transfer simulations in mineral-dominated waters where the backscattering ratio has often been assumed to be spectrally flat. Furthermore, spectral dependence also has profound implications for our understanding of the relationship between b(bp)/b(p) and particle size distributions in coastal waters since the commonly assumed power-law distribution is associated with a spectrally flat particulate backscattering ratio for nonabsorbing particles. (C) 2009 Optical Society of America

Published
2009
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