PMID- 37393092 OWN - NLM STAT- MEDLINE DCOM- 20230703 LR - 20240410 IS - 2468-2667 (Electronic) VI - 8 IP - 7 DP - 2023 Jul TI - Effect on life expectancy of temporal sequence in a multimorbidity cluster of psychosis, diabetes, and congestive heart failure among 1.7 million individuals in Wales with 20-year follow-up: a retrospective cohort study using linked data. PG - e535-e545 LID - S2468-2667(23)00098-1 [pii] LID - 10.1016/S2468-2667(23)00098-1 [doi] AB - BACKGROUND: To inform targeted public health strategies, it is crucial to understand how coexisting diseases develop over time and their associated impacts on patient outcomes and health-care resources. This study aimed to examine how psychosis, diabetes, and congestive heart failure, in a cluster of physical-mental health multimorbidity, develop and coexist over time, and to assess the associated effects of different temporal sequences of these diseases on life expectancy in Wales. METHODS: In this retrospective cohort study, we used population-scale, individual-level, anonymised, linked, demographic, administrative, and electronic health record data from the Wales Multimorbidity e-Cohort. We included data on all individuals aged 25 years and older who were living in Wales on Jan 1, 2000 (the start of follow-up), with follow-up continuing until Dec 31, 2019, first break in Welsh residency, or death. Multistate models were applied to these data to model trajectories of disease in multimorbidity and their associated effect on all-cause mortality, accounting for competing risks. Life expectancy was calculated as the restricted mean survival time (bound by the maximum follow-up of 20 years) for each of the transitions from the health states to death. Cox regression models were used to estimate baseline hazards for transitions between health states, adjusted for sex, age, and area-level deprivation (Welsh Index of Multiple Deprivation [WIMD] quintile). FINDINGS: Our analyses included data for 1 675 585 individuals (811 393 [48.4%] men and 864 192 [51.6%] women) with a median age of 51.0 years (IQR 37.0-65.0) at cohort entry. The order of disease acquisition in cases of multimorbidity had an important and complex association with patient life expectancy. Individuals who developed diabetes, psychosis, and congestive heart failure, in that order (DPC), had reduced life expectancy compared with people who developed the same three conditions in a different order: for a 50-year-old man in the third quintile of the WIMD (on which we based our main analyses to allow comparability), DPC was associated with a loss in life expectancy of 13.23 years (SD 0.80) compared with the general otherwise healthy or otherwise diseased population. Congestive heart failure as a single condition was associated with mean a loss in life expectancy of 12.38 years (0.00), and with a loss of 12.95 years (0.06) when preceded by psychosis and 13.45 years (0.13) when followed by psychosis. Findings were robust in people of older ages, more deprived populations, and women, except that the trajectory of psychosis, congestive heart failure, and diabetes was associated with higher mortality in women than men. Within 5 years of an initial diagnosis of diabetes, the risk of developing psychosis or congestive heart failure, or both, was increased. INTERPRETATION: The order in which individuals develop psychosis, diabetes, and congestive heart failure as combinations of conditions can substantially affect life expectancy. Multistate models offer a flexible framework to assess temporal sequences of diseases and allow identification of periods of increased risk of developing subsequent conditions and death. FUNDING: Health Data Research UK. CI - Copyright (c) 2023 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved. FAU - Owen, Rhiannon K AU - Owen RK AD - Population Data Science, Health Data Research, Swansea University Medical School, Faculty of Medicine, Health and Life Science, Swansea University, Swansea, UK. Electronic address: r.k.owen@swansea.ac.uk. FAU - Lyons, Jane AU - Lyons J AD - Population Data Science, Health Data Research, Swansea University Medical School, Faculty of Medicine, Health and Life Science, Swansea University, Swansea, UK. FAU - Akbari, Ashley AU - Akbari A AD - Population Data Science, Health Data Research, Swansea University Medical School, Faculty of Medicine, Health and Life Science, Swansea University, Swansea, UK. FAU - Guthrie, Bruce AU - Guthrie B AD - Advanced Care Research Centre, Usher Institute, University of Edinburgh, Edinburgh, UK. FAU - Agrawal, Utkarsh AU - Agrawal U AD - Nuffield Department of Primary Care Health Sciences, University of Oxford, Oxford, UK. FAU - Alexander, Daniel C AU - Alexander DC AD - Centre for Medical Image Computing, Department of Computer Science, Faculty of Engineering Sciences, University College London, London, UK. FAU - Azcoaga-Lorenzo, Amaya AU - Azcoaga-Lorenzo A AD - School of Medicine, University of St Andrews, St Andrews, UK; Hospital Rey Juan Carlos, Instituto de Investigacion Sanitaria Fundacion Jimenez Diaz, Madrid, Spain. FAU - Brookes, Anthony J AU - Brookes AJ AD - Department of Genetics, University of Leicester, Leicester, UK. FAU - Denaxas, Spiros AU - Denaxas S AD - Institute of Health Informatics, University College London, London, UK. FAU - Dezateux, Carol AU - Dezateux C AD - Clinical Effectiveness Group, Wolfson Institute of Population Health, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, UK. FAU - Fagbamigbe, Adeniyi Francis AU - Fagbamigbe AF AD - School of Medicine, University of St Andrews, St Andrews, UK. FAU - Harper, Gill AU - Harper G AD - Clinical Effectiveness Group, Wolfson Institute of Population Health, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, UK. FAU - Kirk, Paul D W AU - Kirk PDW AD - MRC Biostatistics Unit, University of Cambridge, Cambridge, UK; Cambridge Institute of Therapeutic Immunology and Infectious Disease, University of Cambridge, Cambridge, UK. FAU - Ozyigit, Eda Bilici AU - Ozyigit EB AD - Centre for Medical Image Computing, Department of Computer Science, Faculty of Engineering Sciences, University College London, London, UK. FAU - Richardson, Sylvia AU - Richardson S AD - MRC Biostatistics Unit, University of Cambridge, Cambridge, UK. FAU - Staniszewska, Sophie AU - Staniszewska S AD - Division of Health Sciences, Warwick Medical School, University of Warwick, Coventry, UK. FAU - McCowan, Colin AU - McCowan C AD - School of Medicine, University of St Andrews, St Andrews, UK. FAU - Lyons, Ronan A AU - Lyons RA AD - Population Data Science, Health Data Research, Swansea University Medical School, Faculty of Medicine, Health and Life Science, Swansea University, Swansea, UK. FAU - Abrams, Keith R AU - Abrams KR AD - Department of Statistics, University of Warwick, Coventry, UK; Centre for Health Economics, University of York, York, UK. LA - eng GR - MR/V028367/1/MRC_/Medical Research Council/United Kingdom GR - MC_PC_20059/MRC_/Medical Research Council/United Kingdom GR - MC_PC_20051/MRC_/Medical Research Council/United Kingdom GR - MR/S027750/1/MRC_/Medical Research Council/United Kingdom GR - MC_UU_00002/13/MRC_/Medical Research Council/United Kingdom GR - MC_PC_20030/MRC_/Medical Research Council/United Kingdom PT - Case Reports PT - Journal Article PL - England TA - Lancet Public Health JT - The Lancet. Public health JID - 101699003 SB - IM MH - Male MH - Humans MH - Female MH - Adult MH - Middle Aged MH - Aged MH - Semantic Web MH - Multimorbidity MH - Retrospective Studies MH - Wales/epidemiology MH - *Diabetes Mellitus/epidemiology MH - *Heart Failure/epidemiology MH - *Psychotic Disorders/epidemiology MH - Life Expectancy COIS- Declaration of interests RKO is a member of the National Institute for Health and Care Excellence (NICE) Technology Appraisal Committee, member of the NICE Decision Support Unit, and associate member of the NICE Technical Support Unit; has served as a paid consultant to the pharmaceutical industry, providing unrelated methodological advice; and reports teaching fees from the Association of British Pharmaceutical Industry (ABPI) and the University of Bristol. KRA is a member of the NICE Diagnostics Advisory Committee and the NICE Decision and Technical Support Units; is a National Institute for Health Research (NIHR) Senior Investigator Emeritus (NF-SI-0512-10159); has served as a paid consultant, providing unrelated methodological and strategic advice, to the pharmaceutical and life sciences industry generally, as well as to the Department of Health and Social Care and NICE; has received unrelated research funding from ABPI, European Federation of Pharmaceutical Industries & Associations, Pfizer, Sanofi, and Swiss Precision Diagnostics; has received course fees from ABPI; and is a Partner and Director of Visible Analytics Limited, a health technology assessment consultancy company. All other authors declare no competing interests. EDAT- 2023/07/02 01:10 MHDA- 2023/07/03 06:41 CRDT- 2023/07/01 20:56 PHST- 2022/08/25 00:00 [received] PHST- 2023/04/28 00:00 [revised] PHST- 2023/05/02 00:00 [accepted] PHST- 2023/07/03 06:41 [medline] PHST- 2023/07/02 01:10 [pubmed] PHST- 2023/07/01 20:56 [entrez] AID - S2468-2667(23)00098-1 [pii] AID - 10.1016/S2468-2667(23)00098-1 [doi] PST - ppublish SO - Lancet Public Health. 2023 Jul;8(7):e535-e545. doi: 10.1016/S2468-2667(23)00098-1.