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Background: Future trends in disease burden and drivers of health are of great interest to policy makers and the public at large. This information can be used for policy and long-term health investment, planning, and prioritisation. We have expanded and improved upon previous forecasts produced as part of the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) and provide a reference forecast (the most likely future), and alternative scenarios assessing disease burden trajectories if selected sets of risk factors were eliminated from current levels by 2050., Methods: Using forecasts of major drivers of health such as the Socio-demographic Index (SDI; a composite measure of lag-distributed income per capita, mean years of education, and total fertility under 25 years of age) and the full set of risk factor exposures captured by GBD, we provide cause-specific forecasts of mortality, years of life lost (YLLs), years lived with disability (YLDs), and disability-adjusted life-years (DALYs) by age and sex from 2022 to 2050 for 204 countries and territories, 21 GBD regions, seven super-regions, and the world. All analyses were done at the cause-specific level so that only risk factors deemed causal by the GBD comparative risk assessment influenced future trajectories of mortality for each disease. Cause-specific mortality was modelled using mixed-effects models with SDI and time as the main covariates, and the combined impact of causal risk factors as an offset in the model. At the all-cause mortality level, we captured unexplained variation by modelling residuals with an autoregressive integrated moving average model with drift attenuation. These all-cause forecasts constrained the cause-specific forecasts at successively deeper levels of the GBD cause hierarchy using cascading mortality models, thus ensuring a robust estimate of cause-specific mortality. For non-fatal measures (eg, low back pain), incidence and prevalence were forecasted from mixed-effects models with SDI as the main covariate, and YLDs were computed from the resulting prevalence forecasts and average disability weights from GBD. Alternative future scenarios were constructed by replacing appropriate reference trajectories for risk factors with hypothetical trajectories of gradual elimination of risk factor exposure from current levels to 2050. The scenarios were constructed from various sets of risk factors: environmental risks (Safer Environment scenario), risks associated with communicable, maternal, neonatal, and nutritional diseases (CMNNs; Improved Childhood Nutrition and Vaccination scenario), risks associated with major non-communicable diseases (NCDs; Improved Behavioural and Metabolic Risks scenario), and the combined effects of these three scenarios. Using the Shared Socioeconomic Pathways climate scenarios SSP2-4.5 as reference and SSP1-1.9 as an optimistic alternative in the Safer Environment scenario, we accounted for climate change impact on health by using the most recent Intergovernmental Panel on Climate Change temperature forecasts and published trajectories of ambient air pollution for the same two scenarios. Life expectancy and healthy life expectancy were computed using standard methods. The forecasting framework includes computing the age-sex-specific future population for each location and separately for each scenario. 95% uncertainty intervals (UIs) for each individual future estimate were derived from the 2·5th and 97·5th percentiles of distributions generated from propagating 500 draws through the multistage computational pipeline., Findings: In the reference scenario forecast, global and super-regional life expectancy increased from 2022 to 2050, but improvement was at a slower pace than in the three decades preceding the COVID-19 pandemic (beginning in 2020). Gains in future life expectancy were forecasted to be greatest in super-regions with comparatively low life expectancies (such as sub-Saharan Africa) compared with super-regions with higher life expectancies (such as the high-income super-region), leading to a trend towards convergence in life expectancy across locations between now and 2050. At the super-region level, forecasted healthy life expectancy patterns were similar to those of life expectancies. Forecasts for the reference scenario found that health will improve in the coming decades, with all-cause age-standardised DALY rates decreasing in every GBD super-region. The total DALY burden measured in counts, however, will increase in every super-region, largely a function of population ageing and growth. We also forecasted that both DALY counts and age-standardised DALY rates will continue to shift from CMNNs to NCDs, with the most pronounced shifts occurring in sub-Saharan Africa (60·1% [95% UI 56·8-63·1] of DALYs were from CMNNs in 2022 compared with 35·8% [31·0-45·0] in 2050) and south Asia (31·7% [29·2-34·1] to 15·5% [13·7-17·5]). This shift is reflected in the leading global causes of DALYs, with the top four causes in 2050 being ischaemic heart disease, stroke, diabetes, and chronic obstructive pulmonary disease, compared with 2022, with ischaemic heart disease, neonatal disorders, stroke, and lower respiratory infections at the top. The global proportion of DALYs due to YLDs likewise increased from 33·8% (27·4-40·3) to 41·1% (33·9-48·1) from 2022 to 2050, demonstrating an important shift in overall disease burden towards morbidity and away from premature death. The largest shift of this kind was forecasted for sub-Saharan Africa, from 20·1% (15·6-25·3) of DALYs due to YLDs in 2022 to 35·6% (26·5-43·0) in 2050. In the assessment of alternative future scenarios, the combined effects of the scenarios (Safer Environment, Improved Childhood Nutrition and Vaccination, and Improved Behavioural and Metabolic Risks scenarios) demonstrated an important decrease in the global burden of DALYs in 2050 of 15·4% (13·5-17·5) compared with the reference scenario, with decreases across super-regions ranging from 10·4% (9·7-11·3) in the high-income super-region to 23·9% (20·7-27·3) in north Africa and the Middle East. The Safer Environment scenario had its largest decrease in sub-Saharan Africa (5·2% [3·5-6·8]), the Improved Behavioural and Metabolic Risks scenario in north Africa and the Middle East (23·2% [20·2-26·5]), and the Improved Nutrition and Vaccination scenario in sub-Saharan Africa (2·0% [-0·6 to 3·6])., Interpretation: Globally, life expectancy and age-standardised disease burden were forecasted to improve between 2022 and 2050, with the majority of the burden continuing to shift from CMNNs to NCDs. That said, continued progress on reducing the CMNN disease burden will be dependent on maintaining investment in and policy emphasis on CMNN disease prevention and treatment. Mostly due to growth and ageing of populations, the number of deaths and DALYs due to all causes combined will generally increase. By constructing alternative future scenarios wherein certain risk exposures are eliminated by 2050, we have shown that opportunities exist to substantially improve health outcomes in the future through concerted efforts to prevent exposure to well established risk factors and to expand access to key health interventions., Funding: Bill & Melinda Gates Foundation., (Copyright © 2024 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.)

Background: Detailed, comprehensive, and timely reporting on population health by underlying causes of disability and premature death is crucial to understanding and responding to complex patterns of disease and injury burden over time and across age groups, sexes, and locations. The availability of disease burden estimates can promote evidence-based interventions that enable public health researchers, policy makers, and other professionals to implement strategies that can mitigate diseases. It can also facilitate more rigorous monitoring of progress towards national and international health targets, such as the Sustainable Development Goals. For three decades, the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) has filled that need. A global network of collaborators contributed to the production of GBD 2021 by providing, reviewing, and analysing all available data. GBD estimates are updated routinely with additional data and refined analytical methods. GBD 2021 presents, for the first time, estimates of health loss due to the COVID-19 pandemic., Methods: The GBD 2021 disease and injury burden analysis estimated years lived with disability (YLDs), years of life lost (YLLs), disability-adjusted life-years (DALYs), and healthy life expectancy (HALE) for 371 diseases and injuries using 100 983 data sources. Data were extracted from vital registration systems, verbal autopsies, censuses, household surveys, disease-specific registries, health service contact data, and other sources. YLDs were calculated by multiplying cause-age-sex-location-year-specific prevalence of sequelae by their respective disability weights, for each disease and injury. YLLs were calculated by multiplying cause-age-sex-location-year-specific deaths by the standard life expectancy at the age that death occurred. DALYs were calculated by summing YLDs and YLLs. HALE estimates were produced using YLDs per capita and age-specific mortality rates by location, age, sex, year, and cause. 95% uncertainty intervals (UIs) were generated for all final estimates as the 2·5th and 97·5th percentiles values of 500 draws. Uncertainty was propagated at each step of the estimation process. Counts and age-standardised rates were calculated globally, for seven super-regions, 21 regions, 204 countries and territories (including 21 countries with subnational locations), and 811 subnational locations, from 1990 to 2021. Here we report data for 2010 to 2021 to highlight trends in disease burden over the past decade and through the first 2 years of the COVID-19 pandemic., Findings: Global DALYs increased from 2·63 billion (95% UI 2·44-2·85) in 2010 to 2·88 billion (2·64-3·15) in 2021 for all causes combined. Much of this increase in the number of DALYs was due to population growth and ageing, as indicated by a decrease in global age-standardised all-cause DALY rates of 14·2% (95% UI 10·7-17·3) between 2010 and 2019. Notably, however, this decrease in rates reversed during the first 2 years of the COVID-19 pandemic, with increases in global age-standardised all-cause DALY rates since 2019 of 4·1% (1·8-6·3) in 2020 and 7·2% (4·7-10·0) in 2021. In 2021, COVID-19 was the leading cause of DALYs globally (212·0 million [198·0-234·5] DALYs), followed by ischaemic heart disease (188·3 million [176·7-198·3]), neonatal disorders (186·3 million [162·3-214·9]), and stroke (160·4 million [148·0-171·7]). However, notable health gains were seen among other leading communicable, maternal, neonatal, and nutritional (CMNN) diseases. Globally between 2010 and 2021, the age-standardised DALY rates for HIV/AIDS decreased by 47·8% (43·3-51·7) and for diarrhoeal diseases decreased by 47·0% (39·9-52·9). Non-communicable diseases contributed 1·73 billion (95% UI 1·54-1·94) DALYs in 2021, with a decrease in age-standardised DALY rates since 2010 of 6·4% (95% UI 3·5-9·5). Between 2010 and 2021, among the 25 leading Level 3 causes, age-standardised DALY rates increased most substantially for anxiety disorders (16·7% [14·0-19·8]), depressive disorders (16·4% [11·9-21·3]), and diabetes (14·0% [10·0-17·4]). Age-standardised DALY rates due to injuries decreased globally by 24·0% (20·7-27·2) between 2010 and 2021, although improvements were not uniform across locations, ages, and sexes. Globally, HALE at birth improved slightly, from 61·3 years (58·6-63·6) in 2010 to 62·2 years (59·4-64·7) in 2021. However, despite this overall increase, HALE decreased by 2·2% (1·6-2·9) between 2019 and 2021., Interpretation: Putting the COVID-19 pandemic in the context of a mutually exclusive and collectively exhaustive list of causes of health loss is crucial to understanding its impact and ensuring that health funding and policy address needs at both local and global levels through cost-effective and evidence-based interventions. A global epidemiological transition remains underway. Our findings suggest that prioritising non-communicable disease prevention and treatment policies, as well as strengthening health systems, continues to be crucially important. The progress on reducing the burden of CMNN diseases must not stall; although global trends are improving, the burden of CMNN diseases remains unacceptably high. Evidence-based interventions will help save the lives of young children and mothers and improve the overall health and economic conditions of societies across the world. Governments and multilateral organisations should prioritise pandemic preparedness planning alongside efforts to reduce the burden of diseases and injuries that will strain resources in the coming decades., Funding: Bill & Melinda Gates Foundation., Competing Interests: Declaration of interests S Afzal reports support for the present manuscript from King Edward Medical University including study material, research articles, valid data sources and authentic real time information for this manuscript; payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from King Edward Medical University and collaborative partners including University of Johns Hopkins, University of California, University of Massachusetts, KEMCAANA, KEMCA-UK Scientific Conferences and Webinars; support for attending meetings and/or travel from King Edward Medical University to attend meetings; participation on a Data Safety Monitoring Board or Advisory Board with National Bioethics Committee Pakistan, King Edward Medical University Ethical Review Board, as well as Ethical Review Board Fatima Jinnah Medical University and Sir Ganga Ram Hospital; leadership or fiduciary roles in board, society, committee or advocacy groups, paid or unpaid with Pakistan Association of Medical Editors, Fellow of Faculty of Public Health Royal Colleges UK (FFPH), and Society of Prevention, Advocacy And Research, King Edward Medical University (SPARK); and other support as Dean of Public Health and Preventive Medicine at King Edward Medical University, as the Chief Editor Annals of King Edward Medical University, as the Director of Quality Enhancement Cell King Edward Medical University, as an international-level Fellow of Faculty of Public Health UK, as an Advisory Board Member and Chair Scientific Session KEMCA-UK, as a Chairperson of KEMCAANA (the International Scientific Conference), as a national-level member on the Research and Publications Higher Education Commission (HEC Pakistan), as a member of the Research and Journals Committee (Pakistan) the Medical and Dental Council (Pakistan), the National Bioethics Committee (Pakistan), the Corona Experts Advisory Group (Punjab), the Chair of the Dengue Experts Advisory Group, and a member of the Punjab Residency Program Research Committee; all outside the submitted work. R Ancuceanu reports consulting fees from AbbVie; payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from AbbVie, Sandoz, and B. Braun; all outside the submitted work. D B Anderson reports leadership or fiduciary roles in board, society, committee or advocacy groups, paid or unpaid with PM&R journal as Senior Editor, which includes an annual stipend, outside the submitted work. P Atorkey reports infrastructure support for the present manuscript from the Australian College of Applied Professions, Discipline of Psychological Sciences, Sydney, Australia and the School of Medicine and Public Health, The University of Newcastle, Australia. J L Baker reports grants paid to their institution from Novo Nordisk Foundation, World Cancer Research Fund, Independent Research Council Denmark, and EU Horizon; consulting fees from Novo Nordisk Denmark A/S; unpaid leadership or fiduciary role in other board, society, committee or advocacy group with European Association for the Study of Obesity; all outside the submitted work. S Barteit reports research grants from the Carl-Zeiss Foundation and the German Research Foundation (DFG); stock or stock options from CHEERS company, a for-profit company focusing on climate change and health evaluation and response systems; all outside the submitted work. M L Bell reports grants or contracts paid to their institution from US Environmental Protection Agency (EPA), US National Institutes of Health (NIH), High Tide Foundation, Health Effects Institute, Yale Women Faculty Forum, Environmental Defense Fund, Wellcome Trust Foundation, Yale Climate Change and Health Center, Robert Wood Johnson Foundation, and Hutchinson Postdoctoral Fellowship; consulting fees from Clinique and SciQuest; payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Colorado School of Public Health, Duke University, University of Texas, Data4Justice, Korea University, Organization of Teratology Information Specialists, University of Pennsylvania, and Boston University for speaking events, IOP Publishing for editorial duties, NIH, Health Canada, PAC-10, UK Research and Innovation, and AXA Research Fund Fellowship for grant review, Korea University for adjunct teaching/research, Harvard University and University of Montana for external advisory committee membership; support for travel from Colorado School of Public Health, University of Texas, Duke University, Boston University, University of Pennsylvania, Harvard University, American Journal of Public Health, and Columbia University; paid leadership or fiduciary roles in board, society, committee or advocacy groups, with US EPA Clean Air Scientific Advisory Committee (CASAC), and unpaid roles with Johns Hopkins EHE Advisory Board, Harvard external advisory committee for training grant, WHO Global Air Pollution and Health Technical Advisory Group, National Academies Panels and Committees; all outside the submitted work. P J G Bettencourt reports patents planned, issued or pending WO2020229805A1, BR112021022592A2, EP3965809A1, OA1202100511, US2023173050A1, EP4265271A2 and EP4275700A2; other interests as project reviewer at Botnar Foundation; all outside the submitted work. S Bhaskar reports grants or contracts from a Grant-in-Aid for Scientific Research (KAKENHI) from Japan Society for the Promotion of Science (JSPS), Japanese Ministry of Education, Culture, Sports, Science and Technology (MEXT) and a Japan Society for the Promotion of Science (JSPS) International Fellowship from JSPS and the Australian Academy of Science; leadership or fiduciary roles in board, society, committee or advocacy groups, paid or unpaid, with Rotary District 9675 as District Chair, Diversity, Equity & Inclusion, with Global Health & Migration Hub Community, Global Health Hub Germany, Berlin, Germany as Chair and Manager, with PLoS One, BMC Neurology, Frontiers in Neurology, Frontiers in Stroke, Frontiers in Public Health, and BMC Medical Research Methodology as Editorial Board Member, and with College of Reviewers, Canadian Institutes of Health Research (CIHR), and Government of Canada as Member; all outside the submitted work. B Bikbov reports grants or contracts from European Commission and University of Rome; support for attending meetings and/or travel from European Renal Association via reimbursement of hotel stay for congress lecturers; leadership or fiduciary role in other board, society, committee or advocacy group, unpaid, with Advocacy Group, International Society of Nephrology and Western Europe Regional Board, International Society of Nephrology; other non-financial support from Scientific-Tools.Org for a public health consultancy; all outside the submitted work. M Carvalho reports other support from The Laboratório Associado para a Química Verde (LAQV/REQUIMTE), University of Porto, Porto, Portugal, and Foundation for Science and Technology (FCT) and the Portuguese Ministry of Science, Technology, and Higher Education (MCTES) under the scope of the project UIDP/50006/2020 (DOI 10.54499/UIDP/50006/2020), outside the submitted work. A L Catapano reports grants or contracts from Amryt Pharma, Menarini, and Ultragenyx; payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Amarin, Amgen, Amryt Pharma, AstraZeneca, Daiichi Sankyo, Esperion, Ionis Pharmaceutical, Medscaper, Menarini, Merck, Novartis, Novo Nordisk, Peervoice, Pfizer, Recordati, Regeneron, Sandoz, Sanofi, The Corpus, Ultragenyx, and Viatris; all outside the submitted work. A Caye reports consulting fees from Knight Therapeutics outside the submitted work. J Conde reports grants or contracts from European Research Council Starting Grant (ERC-StG-2019-848325. Funding 1.5M€); patents planned, issued, or pending from Universidade Nova de Lisboa for Surfactant-Based Hydrogel, Methods and Uses Thereof; all outside the submitted work. S Das reports unpaid leadership or fiduciary roles in board, society, committee, or advocacy groups with Association for Diagnostics & Laboratory Medicine (ADLM) India Section as Program Chair, Clinical & Laboratory Standards Institute (CLSI) nominating committee as a member, Women in Global Health India as a member; all outside the submitted work. L Degenhardt reports untied educational grants to examine new opioid medications in Australia from Indivior and Seqirus, outside the submitted work. A K Demetriades reports leadership or fiduciary roles in board, society, committee or advocacy groups, paid or unpaid, with AO Knowledge Forum Degen as Steering Committee Member, Global Neuro Foundation as Board Member, and European Association of Neurosurgical Societies (EANS) as Board Member/Officer; all outside the submitted work. A Faro reports support for the present manuscript from the National Council for Scientific and Technological Development, CNPq, Brazil. D Flood reports grants or contracts from the National Heart, Lung, and Blood Institute (NHLBI; award number K23HL161271), the University of Michigan Claude D Pepper Older Americans Independence Center (award number 5P30AG024824), and the University of Michigan Caswell Diabetes Institute Clinical Translational Research Scholars Program; consulting fees paid to their institution serving as a diabetes consultant for WHO; unpaid leadership or fiduciary roles in board, society, committee, or advocacy groups with Maya Health Alliance, a non-governmental health organisation in Guatemala, as Staff Physician to carry out diabetes advocacy and solicit funding for clinical diabetes programs; all outside the submitted work. L M Force reports support for the present manuscript from the Bill & Melinda Gates foundation; grants or contracts from Conquer Cancer Foundation, St Jude Children's Research Hospital, St Baldrick's Foundation, and NIH Loan Repayment Program, outside the submitted work; unpaid leadership or fiduciary roles in board, society, committee or advocacy groups with The Lancet Oncology International Advisory Board, outside the submitted work. M Foschi reports consulting fees from Roche and Novartis; payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from Roche, Novartis, Sanofi, Merck, Biogen, and Bristol Myers Squibb for speaking at sponsored congresses; support for attending meetings and/or travel from Roche, Novartis, Sanofi, Merck, Biogen, and Bristol Myers Squibb; unpaid leadership or fiduciary roles in board, society, committee or advocacy groups with MSBase scientific leadership group; all outside the submitted work. R C Franklin reports grants or contracts from Heatwaves in Queensland – Queensland Government, Mobile Plant Safety – Agrifutures, Arc Flash – Human Factors – Queensland Government; support for attending meetings and/or travel from Australasian College of Tropical Medicine (ACTM) – Tropical Medicine and Travel Medicine Conference 2022, 2023, and International Society of Travel Medicine (ISTM) – Travel Medicine Conference, Basel 2023; leadership or fiduciary roles in board, society, committee or advocacy groups, paid or unpaid, with Kidsafe as President/Director, Farmsafe as Director, Auschem as Director, PHAA Injury Prevention SIG Convenor, ISASH Governance Committee, and ACTM as Vice President; all outside the submitted work. A Guha reports grants or contracts from the American Heart Association and the US Department of Defense; consulting fees from Pfizer, Novartis, and Myovant; leadership or fiduciary roles in board, society, committee or advocacy groups, paid or unpaid, with ZERO Prostate Cancer – health equity task force and Doctorpedia as a founding medical partner; all outside the submitted work. A Hassan reports consulting fees from Novartis, Sanofi Genzyme, Biologix, Merck, Hikma Pharma, Janssen, Inspire Pharma, Future Pharma, and Elixir Pharma; payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from Novartis, Allergan, Merck, Biologix, Janssen, Roche, Sanofi Genzyme, Bayer, Hikma Pharma, Al Andalus, Chemipharm, Lundbeck, Inspire Pharma, Future Pharma and Habib Scientific Office, and Everpharma; support for attending meetings and/or travel from Novartis, Allergan, Merck, Biologix, Roche, Sanofi Genzyme, Bayer, Hikma Pharma, Chemipharm, and Al Andalus and Clavita Pharm; all outside the submitted work. I M Ilic reports support for the present manuscript from Ministry of Science, Technological Development and Innovation of the Republic of Serbia (project no. 175042, 2011-2023). M D Ilic reports support for the present manuscript from Ministry of Science, Technological Development and Innovation of the Republic of Serbia (project no. 451-03-47/2023-01/200111). S M S Islam reports support for the present manuscript from an Investigator Grant from the National Health and Medical Research Council (NHMRC; Australia) and a Vanguard Grant from the Heart Foundation. N E Ismail reports leadership or fiduciary role in other board, society, committee, or advocacy group, paid or unpaid, with The Bursar (Council Member), Malaysia, and the Academy of Pharmacy, Malaysia, outside the submitted work. T Joo reports support for the present manuscript from National Research, Development, and Innovation Office in Hungary (RRF-2.3.1-21-2022-00006), Data-Driven Health Division of National Laboratory for Health Security. J J Jozwiak reports payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from Novartis, Adamed, and Amgen, outside the submitted work. N Kawakami reports grants or contracts from Junpukai Foundation and Department of Digital Mental Health is an endowment department, supported with an unrestricted grant from 15 enterprises (https://dmh.m.u-tokyo.ac.jp/c); consulting fees from Riken Institute, JAXA, Sekisui Chemicals, and SB@WORK; leadership or fiduciary role in other board, society, committee, or advocacy group, paid or unpaid, with Japan Society for Occupational Health; all outside the submitted work. J H Kempen reports grants or contracts from Sight for Souls and Mass Eye and Ear Global Surgery Program; leadership or fiduciary role in other board, society, committee, or advocacy group, paid or unpaid, with the Sight for Souls board (US 501(c)(3)); stock or stock options in Betaliq and Tarsier; all outside the submitted work. K Krishan reports non-financial support from the UGC Centre of Advanced Study, CAS II, awarded to the Department of Anthropology, Panjab University, Chandigarh, India, outside the submitted work. B Lacey reports support for the present manuscript from UK Biobank, funded largely by the UK Medical Research Council and Wellcome. B Langguth reports support for the present manuscript from the EU paid to their institution; grants or contracts paid to their institution from German Research Foundation, German Bundesministerium für Bildung und Forschung, EU, Bavarian-Czech University Association, and Bavarian State; consulting fees from Schwabe, Neuromod, Sea Pharma, and Rovi; payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from Schwabe and Neuromod; payment for expert testimony from Bavarian State; leadership or fiduciary role in other board, society, committee, or advocacy group, unpaid, with Tinnitus Research Initiative and the German Society for Brain Stimulation in Psychiatry; stock or stock options in Sea Pharma; receipt of equipment, materials, drugs, medical writing, gifts or other services from Neurocare and Daymed; all outside the submitted work. M Lee reports support for the present manuscript from the Ministry of Education of the Republic of Korea and the National Research Foundation of Korea (NRF-2023S1A3A2A05095298) and Bio-convergence Technology Education Program through the Korea Institute for Advancement Technology (KIAT) funded by the Ministry of Trade, Industry and Energy (No. P0017805). M-C Li reports grants or contracts form The National Science and Technology Council in Taiwan (NSTC 112-2410-H-003-031); leadership or fiduciary role in other board, society, committee, or advocacy group, paid or unpaid, with the Journal of the American Heart Association as Technical Editor; all outside the submitted work. P W Mahasha reports support for attending meetings and/or travel South African Medical Research Council, Department of Nuclear Medicine, School of Medicine, University of Pretoria, and Discipline of Traditional Medicine, School of Nursing and Public Health, University of KwaZulu Natal; participation on a Data Safety Monitoring Board or Advisory Board with the Journal Current Research in Public Health (CRPH) as Editorial Board Member, the journal of Frontiers in Reproductive Health section HIV and STIs as Associate Editorial Board Member, and the journal BMC Public Health as Editorial Board Member; leadership or fiduciary role in other board, society, committee or advocacy group, unpaid, as member of the Federation of Infectious Diseases Societies of Southern Africa (FIDSSA; November 2021–ongoing), Member of the International Society for Infectious Diseases (ISID; November, 2021–ongoing), Member of the COVID-19 Clinical Research Coalition (August, 2021–ongoing), Member of the Global Burden of Disease Collaborator Network (February, 2019–ongoing), Fellow Member of the Scholars Academic and Scientific Society (SAS Society; FSASS; August 2021–ongoing), Member of the South African Council for Natural Scientific Professions (SACNASP; 2018–ongoing), Member of the African Organisation for Standardisation (ARSO), ARSO TC 82 dealing with African Traditional Medicine standards (2023–ongoing, Member of the South African Bureau of Standards (SABS)'s National Committee dealing with African Traditional Medicine standards (2024–ongoing), Member of the Global Forum for Research Ethics and Integrity (GFREI; 2023–ongoing); all outside the submitted work. M A Mahmoud reports grants or contracts from Deputyship for Research & Innovation, Ministry of Education in Saudi Arabia for research through project number 445-5-762 outside the submitted work. L G Mantovani reports support for the present manuscript from the Italian Ministry of Health. H R Marateb reports grants or contracts outside the submitted work from The Beatriu de Pinós post-doctoral programme from the Office of the Secretary of Universities and Research from the Ministry of Business and Knowledge of the Government of Catalonia (programme: 2020 BP 00261) received through their institution, Universitat Politècnica de Catalunya · Barcelona Tech – UPC. A-F A Mentis reports grants or contract funding from 'MilkSafe: A novel pipeline to enrich formula milk using omics technologies', a research co-financed by the European Regional Development Fund of the EU and Greek national funds through the Operational Program Competitiveness, Entrepreneurship and Innovation, under the call RESEARCH - CREATE - INNOVATE (project code: T2EDK-02222), as well as from ELIDEK (Hellenic Foundation for Research and Innovation, MIMS-860; both outside of the present manuscript); payment for expert testimony from serving as external peer-reviewer for FONDAZIONE CARIPLO, ITALY; participation in a Data Safety Monitoring or Advisory Board as Editorial Board Member for “Systematic Reviews”, for Annals of Epidemiology, and as Associate Editor for Translational Psychiatry; stock or stock options from a family winery; and other financial interests as the current scientific officer for BGI Group; outside the submitted work. S A Meo reports support for the present manuscript from Research Supporting Project, King Saud University, Riyadh, Saudi Arabia (RSP-2024 R47). P B Mitchell reports payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from Janssen (Australia); participation on a Data Safety Monitoring Board or Advisory Board with Janssen (Australia); all outside the submitted work. L Monasta reports support from the present manuscript from the Italian Ministry of Health (Ricerca Corrente 34/2017), payments made to the Institute for Maternal and Child Health IRCCS Burlo Garofolo. R S Moreira reports grants or contracts from the National Council for Scientific and Technological Development (CNPq) Research Productivity Scholarship (registration number 316607/2021-5), outside the submitted work. J F Mosser reports support for the present manuscripts from the Bill & Melinda Gates Foundation via grant funding; grants or contracts outside the submitted work from Gavi; support for attending meetings or travel from the Bill & Melinda Gates Foundation, outside the submitted work. S Muthu reports support for attending meetings or travel from AO Spine KF Degen LV Award 2024 (travel grants to attend GSC 2024); leadership or fiduciary roles in board, society, committee, or advocacy groups, paid or unpaid, with AOSpine KF Degen as Associate Member, SICOT Grants Committee as a member; ICRS Next Gen Committee as a member; all outside the submitted work. S Nomura reports grant support for the present manuscript from Ministry of Education, Culture, Sports, Science and Technology of Japan (21H03203) and Precursory Research for Embryonic Science and Technology from the Japan Science and Technology Agency (JPMJPR22R8). B Norrving reports participation on a Data Safety Monitoring Board with Simbec Orion in HOVID trial, outside the submitted work. A P Okekunle reports support for the present manuscript from the National Research Foundation of Korea funded by the Ministry of Science and ICT (2020H1D3A1A04081265); support for attending meetings and/or travel from National Research Foundation of Korea funded by the Ministry of Science and ICT (2020H1D3A1A04081265), outside the submitted work. S Onie reports support for attending meetings and/or travel from Black Dog Institute for travel to the International Association for Suicide Prevention World Congress, Piran, 2023; leadership or fiduciary roles in board, society, committee, or advocacy groups, paid or unpaid, with International Association for Suicide Prevention as Elected National Representative for Indonesia and Indonesian Association for Suicide Prevention as Founding President; all outside the submitted work. A Ortiz reports grants or contracts from Sanofi, Institution: IIS-FJD; consultancy or speaker fees or travel support from Advicciene, Astellas, AstraZeneca, Amicus, Amgen, Boehringer Ingelheim, Fresenius Medical Care, GSK, Bayer, Sanofi-Genzyme, Menarini, Mundipharma, Kyowa Kirin, Lilly, Alexion, Freeline, Idorsia, Chiesi, Otsuka, Novo Nordisk, Sysmex, and Vifor Fresenius Medical Care Renal Pharma and is Director of the Catedra Mundipharma-UAM of diabetic kidney disease and the Catedra Astrazeneca-UAM of chronic kidney disease and electrolytes; leadership or fiduciary roles in board, society, committee, or advocacy groups, paid or unpaid, with European Renal Association; stock or stock options in Telara Farma; all outside the submitted work. C Palladino reports grants or contracts from FCT – Fundação para a Ciência e a Tecnologia, I.P. (national funding), under a contract-programme as defined by DL No. 57/2016 and Law No. 57/2017 (DL57/2016/CP1376/CT0004). DOI 10.54499/DL57/2016/CP1376/CT0004 (https://doi.org/10.54499/DL57/2016/CP1376/CT0004), outside the submitted work. R Passera reports participation on a Data Safety Monitoring Board or Advisory Board, unpaid, as senior biostatistician member of the Data Safety Monitoring Board for the no-profit clinical trial “Consolidation with ADCT-402 (loncastuximab tesirine) after immunochemotherapy: a phase II study in BTKi-treated/ineligible Relapse/Refractory Mantle Cell Lymphoma (MCL) patients” - sponsor FIL, Fondazione Italiana Linfomi, Alessandria-I; leadership or fiduciary roles in board, society, committee, or advocacy groups, unpaid, as Member of the Statistical Committee of the EBMT, the European Society for Bone and Marrow Transplantation, Paris-F; all outside the submitted work. A E Peden reports support for the present manuscript from the Australian National Health and Medical Research Council (grant number: APP2009306). V C F Pepito reports grants or contracts from Sanofi Consumer Healthcare and the International Initiative for Impact Evaluation; outside the submitted work. M Pigeolet reports a grant from The Belgian Kids' Fund for Pediatric Research, outside the submitted work. A Rane reports stock or stock options in Agios as an employee. L F Reyes reports grants or contracts from MSD, Pfizer, and GSK; consulting fees from GSK and MSD; payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from GSK, Pfizer, and MSD; support for attending meetings and/or travel from GSK and Pfizer; all outside the submitted work. L Ronfani reports support for the present manuscript from the Italian Ministry of Health (Ricerca Corrente 34/2017), payments made to the Institute for Maternal and Child Health IRCCS Burlo Garofolo. S Sacco reports grants or contracts from Novartis and Uriach; consulting fees from Novartis, Allergan-Abbvie, Teva, Lilly, Lundbeck, Pfizer, Novo Nordisk, Abbott, and AstraZeneca; payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Novartis, Allergan-AbbVie, Teva, Lilly, Lundbeck, Pfizer, Novo Nordisk, Abbott, and AstraZeneca; support for attending meetings and/or travel from Lilly, Novartis, Teva, and Lundbeck; leadership or fiduciary role in other board, society, committee, or advocacy group, paid or unpaid, with the European Stroke Organisation as President-elect and the European Headache Federation as Second Vice-President; receipt of equipment, materials, drugs, medical writing, gifts or other services from Allergan-AbbVie and Novo Nordisk; all outside the submitted work. P S Sachdev reports grants or contracts from National Health and Medical Research Council of Australia and the NIH; Payment or honoraria for lectures from Alkem Labs for the Frontiers of Psychiatry June 2023 Seminar, Mumbai, India; Participation on a Data Safety Monitoring Board or Advisory Board with Biogen Australia and Roche Australia; leadership or fiduciary role in other board, society, committee or advocacy group, unpaid, with the VASCOG Society and the World Psychiatric Association; all outside the submitted work. Y L Samodra reports grants or contracts from Taipei Medical University; leadership or fiduciary role in other board, society, committee, or advocacy group, paid or unpaid, with the Benang Merah Research Center; all outside the submitted work. J Sanabria reports support for attending meetings and/or travel from the Department of Surgery, Marshall University School of Medicine (MUSOM); three patents pending; participation in quality assessment and assurance for surgeries of the Department of Surgery MUSOM; leadership or fiduciary role in other board, society, committee or advocacy group, paid or unpaid with SSAT, ASTS, AHPBA, IHPBA, and AASLD; all outside the submitted work. N Scarmeas reports grants or contracts with Novo Nordisk as the Local Principal Investigator of recruiting site for multinational, multicentre industry sponsored phase 3 treatment trial for Alzheimer's disease with funding paid to the institution; Participation on a Data Safety Monitoring Board or Advisory Board with Albert Einstein College of Medicine (NIH-funded study) as the Chair of Data Safety Monitoring Board; all outside the submitted work. B M Schaarschmidt reports research grants from Else Kröner-Fresenius Foundatuin, DFG, and PharmaCept; payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from AstraZeneca; support for attending meetings and/or travel from Bayer AG; all outside the submitted work. S Setoguchi reports grants or contracts paid to their institution from NIH, Cystic Fibrosis Foundation, Pfizer Inc, Daiichi Sankyo, and Bristol Myers Squibb; consulting fees from Pfizer Japan, Merck Inc, Bristol Myers Squibb, and Regeneron for providing scientific advise on study design and analytic approaches for validation studies, post-market safety studies and pre-market studies for medications and medical conditions; all outside the submitted work. A Sharifan reports leadership or fiduciary role in other board, society, committee or advocacy group, unpaid with Cochrane as a steering member of the Cochrane Early Career Professionals Network; and receipt of 30 days of complimentary access to ScienceDirect, Scopus, Reaxys, and Geofacets after reviewing manuscripts for two journals published by Elsevier; outside the submitted work. S Sharma reports support for the present manuscript from the John J Bonica Postdoctoral Fellowship from the International Association for the Study of Pain (IASP; 2021-2023); payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events and a travel grant for delivering a talk on “Technologies for pain education in developing countries” conducted by the Pain Education SIG of the IASP at the World Pain Congress in Toronto (2022); outside the submitted work. V Sharma reports other financial or non-financial support from DFSS (MHA)'s research project (DFSS28(1)2019/EMR/6) at Institute of Forensic Science & Criminology, Panjab University, Chandigarh, India, outside the submitted work. V Shivarov reports one patent and one utility model with the Bulgarian Patent Office; stock or stock options from ICONplc (RSUs); and other financial interests from an ICONplc salary; all outside the submitted work. S Shrestha reports other financial interests from the Graduate Research Merit Scholarship from the School of Pharmacy at Monash University Malaysia, outside the submitted work. J P Silva reports support for the present manuscript from the Portuguese Foundation for Science and Technology through payment of their salary (contract with reference 2021.01789.CEECIND/CP1662/CT0014). C R Simpson reports grants or contracts from MBIE (New Zealand), HRC (New Zealand), Ministry of Health (New Zealand), Medical Research Council (UK), and Chief Scientist Office (UK); leadership or fiduciary role in other board, society, committee, or advocacy group, paid or unpaid with the New Zealand Government Data Ethics Advisory Group as the Chair; outside the submitted work. J A Singh reports consulting fees from AstraZeneca, Crealta/Horizon, Medisys, Fidia, PK Med, Two labs Inc, Adept Field Solutions, Clinical Care options, Clearview healthcare partners, Putnam associates, Focus forward, Navigant consulting, Spherix, MedIQ, Jupiter Life Science, UBM LLC, Trio Health, Medscape, WebMD, and Practice Point communications; and the NIH and the American College of Rheumatology; payment for lectures, presentations, speakers bureaus, manuscript writing, or educational events as a member of the speaker's bureau of Simply Speaking; support for attending meetings and/or travel as a past steering committee member of OMERACT; participation on a Data Safety Monitoring Board or Advisory Board with the US Food and Drug Administration Arthritis Advisory Committee; leadership or fiduciary role in other board, society, committees or advocacy group, paid or unpaid, as a past steering committee member of the OMERACT, an international organisation that develops measures for clinical trials and receives arm's length funding from 12 pharmaceutical companies, Co-Chair of the Veterans Affairs Rheumatology Field Advisory Committee, and editor and Director of the UAB Cochrane Musculoskeletal Group Satellite Center on Network Meta-analysis; stock or stock options in Atai life sciences, Kintara therapeutics, Intelligent Biosolutions, Acumen pharmaceutical, TPT Global Tech, Vaxart pharmaceuticals, Atyu biopharma, Adaptimmune Therapeutics, GeoVax Labs, Pieris Pharmaceuticals, Enzolytics Inc, Seres Therapeutics, Tonix Pharmaceuticals Holding Corp, and Charlotte's Web Holdings Inc, and previously owned stock options in Amarin, Viking, and Moderna pharmaceuticals; outside the submitted work. S T Skou reports grants or contracts from European Research Council paid to their university from the EU's Horizon 2020 research innovation program (grant agreement No 801790), EU's Horizon 2020 research innovation program paid to their hospital (grant agreement No 945377), and Region Zealand paid to their hospital; royalties or licenses from Munksgaard for book chapters and TrustMe-Ed for online lectures; payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from Nestlé Health Science for a presentation at a webinar on osteoarthritis; participation on a Data Safety Monitoring Board or Advisory Board, paid or unpaid, with UK-based National Institute for Health and Care Research (NIHR)-funded trial PERFORM: Personalised Exercise-Rehabilitation FOR people with Multiple long-term conditions (multimorbidity, NIHR 202020); other support as co-founder of GLA:D, a not-for profit initiative hosted at University of Southern Denmark; all outside the submitted work. D J Stein reports consulting fees from Discovery Vitality, Johnson & Johnson, Kanna, L'Oreal, Lundbeck, Orion, Sanofi, Servier, Takeda, and Vistagen, outside the submitted work. A P Stoian reports consulting fees paid to their institution from AstraZeneca, Boehringer Ingelheim, Eli Lilly, Novo Nordisk, Novartis, Sandoz, Sanofi, and Servier; payment or honoraria paid to their institution for lectures, presentations, speakers bureaus, manuscript writing, or educational events from AstraZeneca, Boehringer Ingelheim, Eli Lilly, Novo Nordisk, Novartis, Medochemie, Sandoz, Sanofi, and Servier; support for attending meetings and/or travel, paid to their institution, from Novo Nordisk, Medochemie, and Sanofi; participation on a Data Safety Monitoring Board or Advisory Board, paid to their institution, with AstraZeneca, Eli Lilly, Novo Nordisk, and Sanofi; leadership or fiduciary roles in board, society, committee or advocacy groups, unpaid, with Central European Diabetes Association (CEDA) and Association for Renal-Metabolic & Nutritional Studies (ASRMN); receipt of medical writing (unpaid) from Novo Nordisk and Sanofi; all outside the submitted work. C K Suemoto reports grants or contracts Alzheimer's Association and São Paulo Research Foundation (FAPESP), paid to their institution, and CNPq, paid to them; support for attending meetings and/or travel from Alzheimer's Association; leadership or fiduciary roles in other board, society, committee, or advocacy group, unpaid, with Brazilian Society of Geriatrics and Gerontology; all outside the submitted work. J H V Ticoalu reports a leadership or fiduciary role in other board, society, committee or advocacy group with Benang Merah Research Center as Co-founder, outside the submitted work. S J Tromans reports grants or contracts from the 2023 Adult Psychiatric Morbidity Survey team, collecting epidemiological data on community-based adults living in England. This is a contracted study from NHS Digital, via the Department of Health and Social Care; outside the submitted work. P Willeit reports consulting fees from Novartis; outside the submitted work. A Wimo reports grants or contracts from VINNOVA program: PREDEM, EU-project JPND: ADDITION, EU-project JPND: EURO-FINGER, EU-project IHI: PROMINENT, EU-project JPND: PMI-AD, and EU-project H2020: PRODEMOS; royalties or licenses as license holder of RUD-instrument (part); leadership or fiduciary roles in other board, society, committee, or advocacy group, unpaid, with ADI: MSAP; all outside the submitted work. M Zielińska reports other financial interest as an AstraZeneca employee, outside the submitted work. A Zumla reports grants or contracts from The Pan-African Network on Emerging and Re-Emerging Infections (PANDORA-ID-NET, CANTAM-3, and EACCR-3) funded by the European and Developing Countries Clinical Trials Partnership, the EU Horizon 2020 Framework Programme, UK NIHR Senior Investigator, and Mahathir Science Award and EU-EDCTP Pascoal Mocumbi Prize Laureate; participation on a Data Safety Monitoring Board or Advisory Board member of the WHO Mass Gatherings Expert Group and WHO Health Emergencies Programme in Geneva, a member of the EU-EDCTP3-Global Health (Brussells) Scientific Committee; all outside the submitted work., (Copyright © 2024 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.)

Background: Regular, detailed reporting on population health by underlying cause of death is fundamental for public health decision making. Cause-specific estimates of mortality and the subsequent effects on life expectancy worldwide are valuable metrics to gauge progress in reducing mortality rates. These estimates are particularly important following large-scale mortality spikes, such as the COVID-19 pandemic. When systematically analysed, mortality rates and life expectancy allow comparisons of the consequences of causes of death globally and over time, providing a nuanced understanding of the effect of these causes on global populations., Methods: The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021 cause-of-death analysis estimated mortality and years of life lost (YLLs) from 288 causes of death by age-sex-location-year in 204 countries and territories and 811 subnational locations for each year from 1990 until 2021. The analysis used 56 604 data sources, including data from vital registration and verbal autopsy as well as surveys, censuses, surveillance systems, and cancer registries, among others. As with previous GBD rounds, cause-specific death rates for most causes were estimated using the Cause of Death Ensemble model-a modelling tool developed for GBD to assess the out-of-sample predictive validity of different statistical models and covariate permutations and combine those results to produce cause-specific mortality estimates-with alternative strategies adapted to model causes with insufficient data, substantial changes in reporting over the study period, or unusual epidemiology. YLLs were computed as the product of the number of deaths for each cause-age-sex-location-year and the standard life expectancy at each age. As part of the modelling process, uncertainty intervals (UIs) were generated using the 2·5th and 97·5th percentiles from a 1000-draw distribution for each metric. We decomposed life expectancy by cause of death, location, and year to show cause-specific effects on life expectancy from 1990 to 2021. We also used the coefficient of variation and the fraction of population affected by 90% of deaths to highlight concentrations of mortality. Findings are reported in counts and age-standardised rates. Methodological improvements for cause-of-death estimates in GBD 2021 include the expansion of under-5-years age group to include four new age groups, enhanced methods to account for stochastic variation of sparse data, and the inclusion of COVID-19 and other pandemic-related mortality-which includes excess mortality associated with the pandemic, excluding COVID-19, lower respiratory infections, measles, malaria, and pertussis. For this analysis, 199 new country-years of vital registration cause-of-death data, 5 country-years of surveillance data, 21 country-years of verbal autopsy data, and 94 country-years of other data types were added to those used in previous GBD rounds., Findings: The leading causes of age-standardised deaths globally were the same in 2019 as they were in 1990; in descending order, these were, ischaemic heart disease, stroke, chronic obstructive pulmonary disease, and lower respiratory infections. In 2021, however, COVID-19 replaced stroke as the second-leading age-standardised cause of death, with 94·0 deaths (95% UI 89·2-100·0) per 100 000 population. The COVID-19 pandemic shifted the rankings of the leading five causes, lowering stroke to the third-leading and chronic obstructive pulmonary disease to the fourth-leading position. In 2021, the highest age-standardised death rates from COVID-19 occurred in sub-Saharan Africa (271·0 deaths [250·1-290·7] per 100 000 population) and Latin America and the Caribbean (195·4 deaths [182·1-211·4] per 100 000 population). The lowest age-standardised death rates from COVID-19 were in the high-income super-region (48·1 deaths [47·4-48·8] per 100 000 population) and southeast Asia, east Asia, and Oceania (23·2 deaths [16·3-37·2] per 100 000 population). Globally, life expectancy steadily improved between 1990 and 2019 for 18 of the 22 investigated causes. Decomposition of global and regional life expectancy showed the positive effect that reductions in deaths from enteric infections, lower respiratory infections, stroke, and neonatal deaths, among others have contributed to improved survival over the study period. However, a net reduction of 1·6 years occurred in global life expectancy between 2019 and 2021, primarily due to increased death rates from COVID-19 and other pandemic-related mortality. Life expectancy was highly variable between super-regions over the study period, with southeast Asia, east Asia, and Oceania gaining 8·3 years (6·7-9·9) overall, while having the smallest reduction in life expectancy due to COVID-19 (0·4 years). The largest reduction in life expectancy due to COVID-19 occurred in Latin America and the Caribbean (3·6 years). Additionally, 53 of the 288 causes of death were highly concentrated in locations with less than 50% of the global population as of 2021, and these causes of death became progressively more concentrated since 1990, when only 44 causes showed this pattern. The concentration phenomenon is discussed heuristically with respect to enteric and lower respiratory infections, malaria, HIV/AIDS, neonatal disorders, tuberculosis, and measles., Interpretation: Long-standing gains in life expectancy and reductions in many of the leading causes of death have been disrupted by the COVID-19 pandemic, the adverse effects of which were spread unevenly among populations. Despite the pandemic, there has been continued progress in combatting several notable causes of death, leading to improved global life expectancy over the study period. Each of the seven GBD super-regions showed an overall improvement from 1990 and 2021, obscuring the negative effect in the years of the pandemic. Additionally, our findings regarding regional variation in causes of death driving increases in life expectancy hold clear policy utility. Analyses of shifting mortality trends reveal that several causes, once widespread globally, are now increasingly concentrated geographically. These changes in mortality concentration, alongside further investigation of changing risks, interventions, and relevant policy, present an important opportunity to deepen our understanding of mortality-reduction strategies. Examining patterns in mortality concentration might reveal areas where successful public health interventions have been implemented. Translating these successes to locations where certain causes of death remain entrenched can inform policies that work to improve life expectancy for people everywhere., Funding: Bill & Melinda Gates Foundation., Competing Interests: Declaration of interests S Afzal reports support for the present manuscript from King Edward Medical University including study material, research articles, valid data sources and authentic real time information for this manuscript; payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from King Edward Medical University and collaborative partners including University of Johns Hopkins, University of California, University of Massachusetts, KEMCAANA, KEMCA-UK Scientific Conferences and Webinars; support for attending meetings and/or travel from King Edward Medical University to attend meetings; participation on a Data Safety Monitoring Board or Advisory Board with National Bioethics Committee Pakistan, King Edward Medical University Ethical Review Board, as well as Ethical Review Board Fatima Jinnah Medical University and Sir Ganga Ram Hospital; leadership or fiduciary roles in board, society, committee or advocacy groups, paid or unpaid with Pakistan Association of Medical Editors, Fellow of Faculty of Public Health Royal Colleges UK (FFPH), and Society of Prevention, Advocacy And Research, King Edward Medical University (SPARK); and other support as Dean of Public Health and Preventive Medicine at King Edward Medical University, as the Chief Editor Annals of King Edward Medical University, as the Director of Quality Enhancement Cell King Edward Medical University, as an international-level Fellow of Faculty of Public Health United Kingdom, as an Advisory Board Member and Chair Scientific Session KEMCA-UK, as a Chairperson of KEMCAANA (the International Scientific Conference), as a national-level member on the Research and Publications Higher Education Commission (HEC Pakistan), as a member of the Research and Journals Committee (Pakistan) the Medical and Dental Council (Pakistan), the National Bioethics Committee (Pakistan), the Corona Experts Advisory Group (Punjab), the Chair of the Dengue Experts Advisory Group, and a member of the Punjab Residency Program Research Committee; all outside the submitted work. R Ancuceanu reports consulting fees from Abbvie; payment or honoraria for lectures, presentations, speakers' bureaus, manuscript writing or educational events from Abbvie, Sandoz, B. Braun, Laropharm, and MagnaPharm; all outside the submitted work. J Ärnlöv reports payment or honoraria for lectures, presentations, speakers' bureaus, manuscript writing or educational events from AstraZeneca and Novartis for lecture fees; participation on a Data Safety Monitoring Board or Advisory Board with AstraZeneca, Astella, Boehringer Ingelheim; all outside the submitted work. O C Baltatu reports support for the present manuscript from National Council for Scientific and Technological Development (CNPq, 304224/2022-7) and Anima Institute (AI research professor fellowship); Leadership or fiduciary role in other board, society, committee or advocacy group, paid or unpaid, as Founding Member of the Health and Biotechnology Advisory Board at Technology Park São José dos Campos–Center for Innovation in Health Technologies (CITS), outside the submitted work. T W Bärnighausen reports grants or contracts from National Institutes of Health, Alexander von Humboldt Foundation, German National Research Foundation (DFG), European Union, German Ministry of Education and Research, German Ministry of the Environment, Wellcome, and KfW, all as payments to their institution; participation on a Data Safety Monitoring Board or Advisory Board on two Scientific Advisory Boards for NIH-funded research projects in Africa on Climate Change and Health; stock or stock options in CHEERS, an SME focusing on approaches to measure climate change and health-related variables in population cohorts; all outside the submitted work. S Barteit reports grants from Carl-Zeiss Foundation and the German research foundation (DFG); stock or stock options in CHEERS, a for-profit company focusing on climate change and health evaluation and response systems; all outside the submitted work. M Beghi reports consulting fees from Lundbeck and Angelini, all outside the submitted work. Y Bejot reports consulting fees from Medtronic and Novartis; payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from BMS, Pfizer, Medtronic, Amgen, NovoNordisk, and Servier; support for attending meetings and/or travel from Medtronic; leadership or fiduciary role in other board, society, committee or advocacy group, unpaid, with the French Neurovascular Society; all outside the submitted work. M Bell reports grants or contracts from US EPA, NIH, High Tide Foundation, Health Effects Institute, Yale Women Faculty Forum, Environmental Defense Fund, Yale Climate Change and Health Center, Wellcome Trust Foundation, Robert Wood Johnson Foundation, and the Hutchinson Postdoctoral Fellowship (all paid to their institution); Consulting fees from Clinique; Payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or education events from Colorado School of Public Health, Duke University, University of Texas, Data4Justice, Korea University, Organization of Teratology Information Specialists, University of Pennsylvania, Boston University, IOP Publishing, NIH, Health Canada, PAC-10, UKRI, AXA Research Fund Fellowship, Harvard University and the University of Montana; Support for attending meeting and/or travel from Colorado School of Public Health, University of Texas, Duke University, Boston University, University of Pennsylvania, Harvard University, American Journal of Public Health, Columbia University and Harvard University; Leadership or fiduciary role in other board, society, committee or advocacy group, unpaid with Fifth National Climate Assessment and Lancet Countdown, Johns Hopkins Advisory Board, Harvard external advisory committee for training grant, WHO Global Air Pollution and Health Technical Advisory group and the National Academies Panels and Committee; and paid with the US EPA Clean Air Scientific Advisory Committee (CASAC); outside the submitted work. L Belo reports other financial or non-financial interests with UCIBIO – FFUP through support from FCT in the scope of the project UIDP/04378/2020 and UIDB/04378/2020 of UCIBIO and the project LA/P/0140/2020 of i4HB, all outside the submitted work. R S Bernstein reports other financial or non-financial support as a full-time Medical Consultant employee of the California Department of Public Health in the Center for Heal Care Quality; outside the submitted work. P J G Bettencourt reports patents planned, issued, or pending (WO2020229805A1, BR112021022592A2, EP3965809A1, OA1202100511, US2023173050A1, EP4265271A2, and EP4275700A2); other financial or non-financial interests with the Botnar Foundation as project reviewer, outside the submitted work. S Bhaskar reports grants or contracts from the Japan Society for the Promotion of Science (JSPS), Japanese Ministry of Education, Culture, Sports, Science and Technology (MEXT) and JSPS and the Australian Academy of Science; Leadership or fiduciary role in other board, society, committee or advocacy group, paid or unpaid with Rotary District 9675 as the district chair, Global Health & Migration Hub Community as Chair and Manager (Berlin, Germany), PLOS One, BMC Neurology, Frontiers in Neurology, Frontiers in Stroke, Frontiers in Public Health and the BMC Medical Research Methodology as an Editorial Board Member, and as a Member of the College of Reviewers (Canadian Institutes of Health Research, Canada); outside the submitted work. B Bikbov reports grants or contracts from the European Commission and The University of Rome; Support for attending meetings/travel from the European Renal Association; Leadership or fiduciary role in other board, society, committee or advocacy group, unpaid in an advocacy group with the International Society of Nephrology and unpaid on the Western Europe Regional Board of the International Society of Nephrology; Other financial or non-financial support from Scientific-Tools.org; outside the submitted work. A Biswas reports consulting fees from INTAS Pharmaceuticals Ltd, India, Lupin Pharmaceuticals, Ltd, India, and Alkem Laboratories, India as personal payments; payment or honoraria for lectures, presentations, speakers' bureaus, manuscript writing or educational events from Roche Diagnostics, India, as personal payments; all outside the submitted work. E J Boyko reports payment or Honoria for lectures, presentations, speakers bureaus, manuscript writing or education events from the Korean Diabetes Association, Diabetes Association of the R.O.C (Taiwan), the American Diabetes Association, and the International Society for the Diabetic Foot; Support for attending meetings and/or travel from the Korean Diabetes Association; Diabetes Association of the R.O.C (Taiwan), International Society for the Diabetic Foot; outside the submitted work. M Carvalho reports other financial or non-financial interests from LAQV/REQUIMTE, University of Porto (Porto, Portugal) and acknowledges the support from FCT under the scope of the project UIDP/50006/2020; outside the submitted work. E Chung reports support for the present manuscript from the National Institute of Health NICHD T32HD007233. J Conde reports grants or contracts form the European Research Council Starting Grant ERC-StG-2019-848325 (funding 1.5M Euro), outside the submitted work. S Cortese reports grants or contracts from National Institute for Health and Care Research (NIHR)and the European Research Executive Agency; payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from the Association of Child and Adolescent Mental Health, British Association of Psychopharmacology, Medice, and Canadian ADHD Resource Alliance; support for attending meetings and/or travel the Association of Child and Adolescent Mental Health, British Association of Psychopharmacology, Medice, and Canadian ADHD Resource Alliance; leadership or fiduciary role in other board, society, committee or advocacy group, unpaid, with the European ADHD Guidelines Group and the European Network for Hyperkinetic Disorders; all outside the submitted work. Sa Das reports leadership or fiduciary role in other board, society, committee or advocacy group, unpaid, with the Association for Diagnostics and Laboratory Medicine as program chair, and the Women in Global Health India Chapter, outside the submitted work. A Dastiridou reports support for attending meetings and/or travel from THEA and ABBVIE, outside the submitted work. L Degenhardt reports untied educational grants from Indivior and Seqirus to examine new opioid medications in Australia, outside the submitted work. A K Demetriades reports leadership or fiduciary role in other board, society, committee or advocacy group, unpaid, with the AO Knowledge Forum Degenerative Steering Committee, Global Neuro Foundation Board, and the European Association of Neurological Societies Board of Officers, all outside the submitted work. A Faro reports support for the present manuscript from National Council for Scientific and Technological Development, CNPq, Brazil as CNPq Researcher (scholarship). I Filip reports support for the present manuscript from Avicenna Medical and Clinical Research Institute. D Flood reports grants or contracts from NHLBI (award number K23HL161271), the University of Michigan Claude D. Pepper Older Americans Independence Center (award number 5P30AG024824), and the University of Michigan Caswell Diabetes Institute Clinical Translational Research Scholars Program; consulting fees from the World Health Organization as payments to their institution; leadership or fiduciary role in other board, society, committee or advocacy group, unpaid, as Staff Physician for Maya Health Alliance, a non-governmental health organization in Guatemala; all outside the submitted work. A A Fomenkov reports support for the present manuscript from Development of effective biotechnologies based on cell cultures, tissues and organs of higher plants, microalgae and cyanobacteria. The research carried out within the state assignment of Ministry of Science and Higher Education of the Russian Federation (theme No. 122042600086-7). M Foschi reports consulting fees from Roche and Novartis; support for attending meetings and/or travel from Biogen, Roche, Novartis, Sanofi, Bristol, and Merck; leadership or fiduciary role in other board, society, committee or advocacy group, unpaid, with MBase Foundation; all outside the submitted work. R Franklin reports grants or contracts from Heatwaves (Queensland Government, Queensland, Australia) and Arc Flash (Human Factors, Queensland Government, Queensland, Australia), and Mobile Plant Safety (Agrifutures); Support for attending meetings and/or travel from ACTM Tropical Medicine and Travel Medicine Conference 2022 and 2023, and ISTM Travel Medicine Conference in Basel 2023; leadership or fiduciary role in other board, society, committee or advocacy group, paid or unpaid as the president/director of Kidsafe, the director of Auschem, a member of the governance committee of ISASH, the director of Farmsafe, the Vice President of ACTM, and as a PHAA Injury Prevention SIG Convenor; outside the submitted work. P S Gill reports support for the present manuscript from the National Institute for Health and Care Research (NIHR) as Senior Investigator with payments to their institution; the views expressed in this publication are those of the author(s) and not necessarily those of the NIHR or the UK Department of Health and Social Care. A Guha reports grants or contracts from the American Heart Association and Department of Defense; consulting fees from Pfizer, Novartis, and Myovant; leadership or fiduciary role in other board, society, committee or advocacy group, paid or unpaid, with ZERO Prostate Cancer Health Equity Task Force and Doctopedia as a founding medical partner; all outside the submitted work. C Herteliu reports grants or contracts from the Romanian Ministry of Research Innovation and Digitalization, MCID, project number ID-585-CTR-42-PFE-2021; grant of the European Commission Horizon 4P-CAN (Personalised Cancer Primary Prevention Research through Citizen Participation and Digitally Enabled Social Innovation); Project “Societal and Economic Resilience within multi-hazards environment in Romania” funded by European Union – NextgenerationEU and Romanian Government, under National Recovery and Resilience Plan for Romania, contract no.760050/ 23.05.2023, cod PNRR-C9-I8-CF 267/ 29.11.2022, through the Romanian Ministry of Research, Innovation and Digitalization, within Component 9, Investment I8; Project “A better understanding of socio-economic systems using quantitative methods from Physics” funded by European Union–NextgenerationEU and Romanian Government, under National Recovery and Resilience Plan for Romania, contract number 760034/ 23.05.2023, cod PNRR-C9-I8-CF 255/ 29.11.2022, through the Romanian Ministry of Research, Innovation and Digitalization, within Component 9, Investment I8; outside the submitted work. M Hultström reports support for the present manuscript from Knut och Alice Wallenberg Foundation and the Swedish Heart-Lung Foundation, all as payments to their institution; Support for attending meetings and/or travel from the American Physiological Society and the Swedish Society for Anaesthesiology and Intensive Care; leadership or fiduciary role in other board, society, committee or advocacy group, paid or unpaid, with the American Physiological Society, Water and Electrolyte Section; all outside the submitted work. I Ilic and M Ilic report support for the present manuscript from Ministry of Science, Technological Development and Innovation of the Republic of Serbia. S M Islam reports support for the present manuscript from NHMRC and Heart Foundation, N E Ismail reports leadership or fiduciary role in other board, society, committee or advocacy group, unpaid, as Bursar (Council Member) of the Malaysian Academy of Pharmacy, outside the submitted work. T Joo reports support for the present manuscript from National Research, Development, and Innovation Office in Hungary (RRF-2.3.1-21-2022-00006), Data-Driven Health Division of National Laboratory for Health Security. G Joshy reports grants or contracts from the Department of Health and Aged Care 2023 (Understanding the fatal burden of COVID-19 in residential aged care facilities); support for attending meetings and/or travel from the Statistical Society of Australia Grant 2023 supporting conference registration; participation on a Data Safety Monitoring Board with the Australian Mathematical Sciences Institute (AMSI) and the Statistical Society of Australia (SSA) for the project Community-led nutrition and Lifestyle program for weight loss and metabolic Health: a randomised Controlled trial (ELCHO), 2022; all outside the submitted work. J Jozwiak reports payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Novartis, Adamed, and Amgen; outside the submitted work. N Kawakami reports grants or contracts from the Junpukai Foundation and the Department of Digital Mental Health is an endowment department, supported with an unrestricted grant from 15 enterprises (https://dmh.m.u-tokyo.ac.jp/c); consulting fees from Riken Institute, JAXA, Sekisui Chemicals, and SB@WORK; leadership or fiduciary role in other board, society, committee or advocacy group, paid or unpaid, with the Japan Society for Occupational Health; all outside the submitted work. J H Kempen reports grants or contracts from the Massachusetts Eye and Ear Surgery Program and Sight for Souls through payments to their institution; leadership or fiduciary role in other board, society, committee or advocacy group, paid or unpaid, as President of Sight for Souls; stock or stock options with Betaliq and Tarsier; all outside the submitted work. T Kocsis reports grants or contracts from Novartis Magyarország Ltd through payment for market access activities, outside the submitted work. K Krishan reports other non-financial interests from the UGC Centre of Advanced Study, CAS II, awarded to the Department of Anthropology, Panjab University (Chandigarh, India); outside the submitted work. B Lacey reports support for the present manuscript from the UK Biobank, funded largely by the UK Medical Research Council and Wellcome, through their employment at the University of Oxford. M Lee reports support for the present manuscript from the Ministry of Education of the Republic of Korea and the National Research Foundation of Korea (NRF-2021R1I1A4A01057428) and Bio-convergence Technology Education Program through the Korea Institute for Advancement Technology (KIAT) funded by the Ministry of Trade, Industry and Energy (No. P0017805). M-C Li reports grants or contracts from The National Science and Technology Council in Taiwan (NSTC 112-2410-H-003-031; leadership or fiduciary role in other board, society, committee or advocacy group, paid or unpaid, as the technical editor of the Journal of the American Heart Association; outside the submitted work. J Liu reports support for the present manuscript from the National Natural Science Foundation of China (grant number: 72122001; 72211540398). S Lorkowski reports grants or contracts from Akcea Therapeutics Germany through payments to their institution; consulting fees from Danone, Novartis Pharma, Swedish Orphan Biovitrum (SOBI), and Upfield; payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Akcea Therapeutics Germany, AMARIN Germany, Amedes Holding, AMGEN, Berlin-Chemie, Boehringer Ingelheim Pharma, Daiichi Sankyo Deutschland, Danone, Hubert Burda Media Holding, Janssen-Cilag, Lilly Deutschland, Novartis Pharma, Novo Nordisk Pharma, Roche Pharma, Sanofi-Aventis, and SYNLAB Holding Deutschland & SYNLAB Akademie; support for attending meetings and/or travel from AMGEN; participation on a Data Safety Monitoring Board or Advisory Board with Akcea Therapeutics Germany, AMGEN, Daiichi Sankyo Deutschland, Novartis Pharma, and Sanofi-Aventis; all outside the submitted work. M A Mahmoud reports grant or contract funding from the Deputyship for Research and Innovation, Ministry of Education in Saudi Arabia (project number 445-5-748). L G Mantovani reports support for the present manuscript from the Italian Ministry of Health. H R Marateb reports support for the present manuscript from The Beatriu de Pinós post-doctoral programme from the Office of the Secretary of Universities and Research from the Ministry of Business and Knowledge of the Government of Catalonia programme: 2020 BP 00261. R Matzopoulos reports consulting fees from New York University and DG Murray Trust; Support for attending meetings/travel paid by SA MRC and University of Cape Town; leadership or fiduciary role in other board, society, committee or advocacy group, unpaid, as a Board member of Gun Free South Africa; Stock or Stock options with Sanlam; outside the submitted work. R J Maude reports support for the present manuscript from Wellcome Trust [Grant number 220211] as it provides core funding for Mahidol Oxford Tropical Medicine Research and contributes to his salary. A-F A Mentis reports grants or contract funding from ‘MilkSafe: A novel pipeline to enrich formula milk using omics technologies’, a research co financed by the European Regional Development Fund of the European Union and Greek national funds through the Operational Program Competitiveness, Entrepreneurship and Innovation, under the call RESEARCH - CREATE - INNOVATE (project code: T2EDK-02222), as well as from ELIDEK (Hellenic Foundation for Research and Innovation, MIMS-860) (both outside of the present manuscript); payment for expert testimony from serving as external peer-reviewer for FONDAZIONE CARIPLO, ITALY; participation in a Data Safety Monitoring or Advisory Board as Editorial Board Member for “Systematic Reviews”, for “Annals of Epidemiology”, and as Associate Editor for “Translational Psychiatry”; stock or stock options from a family winery; and other financial interests as the current scientific officer for BGI Group; outside the submitted work. S A Meo reports support from King Saud University, Riyadh, Saudi Arabia (RSP-2024 R47). T R Miller reports grants or contracts from AB InBev Foundation, National Institute for Mental Health (Santa Clara County, CA), and Everytown for Gun Safety; payment for expert testimony in the states of Michigan, Nevada & New Mexico Mobile County Board of Health; outside the submitted work. P B Mitchell reports payment or honoraria for lectures, presentations, speakers' bureaus, manuscript writing or educational events, from Janssen (Australia), outside the submitted work. L Monasta reports support for the present manuscript from the Ministry of Health (Ricerca Corrente 34/2017) through payments made to the Institute for Maternal and Child Health IRCCS Burlo Garofolo. R S Moreira reports grants or contracts from CNPq Research Productivity Scholarship (National Council for Scientific and Technological Development) scholarship registration number 316607/2021-5; outside the submitted work. J Mosser reports support for the present manuscript from the Bill and Melinda Gates Foundation; grants or contractions from Gavi; Support for attending meetings and/or travel from the Bill and Melinda Gates Foundation; outside the submitted work. S Nomura reports support for the present manuscript from Ministry of Education, Culture, Sports, Science and Technology of Japan (21H03203) and Precursory Research for Embryonic Science and Technology from the Japan Science and Technology Agency (JPMJPR22R8). B Norrving reports participation on a Data Safety Monitoring Board or Advisory Board with Simbec Orion, outside the submitted work. A P Okekunle reports support for the present manuscript from the National Research Foundation of Korea funded by the Ministry of Science and ICT (2020H1D3A1A04081265). A Ortiz reports grants or contracts from Sanofi as payments to their institution; consulting fees, speaker fees or support for travel from, Advicciene, Astellas, Astrazeneca, Amicus, Amgen, Boehringer Ingelheim, Fresenius Medical, Care, GSK, Bayer, Sanofi-Genzyme, Menarini, Mundipharma, Kyowa Kirin, Lilly, Alexion, Freeline, Idorsia, Chiesi, Otsuka, Novo-Nordisk, Sysmex and Vifor Fresenius Medical Care Renal, Pharma and is Director of the Catedra, Mundipharma-UAM of diabetic kidney disease, and the Catedra Astrazeneca-UAM of chronic, kidney disease and electrolytes; Leadership or fiduciary role in other board, society, committee or advocacy group, paid or unpaid, with the European Renal Association; stock or stock options with Telara Farma; all outside the submitted work. P K Pal reports grants or contracts paid to their institution from the Indian Council of Medical Research (ICMR), the Department of Science & Technology (DST)-Science and Engineering Research Board, the Department of Biotechnology (DBT), DST-Cognitive Science Research Initiative, Wellcome Trust UK-India Alliance DBT, PACE scheme of BIRAC, Michael J. Fox Foundation, and SKAN (Scientific Knowledge for Ageing and Neurological ailments)-Research Trust; Payment and honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events as Faculty/Speaker/Author from the International Parkinson and Movement Disorder Society, and Movement Disorder Societies of Korea, Taiwan and Bangladesh; support for attending meetings and/or travel from the National Institute of Mental Health and Neurosciences (NIMHANS), International Parkinson and Movement Disorder Society, and Movement Disorder Societies of Korea, Taiwan and Bangladesh; Leadership or fiduciary role in other board, society, committee or advocacy group, unpaid, as the Past President of Indian Academy of Neurology, Past Secretary of Asian and Oceanian subsection of International Parkinson and Movement Disorder Society (MDS-AOS), Editor-in-Chief of Annals of Movement Disorders, Chair of the Education Committee of International Parkinson and Movement Disorder Society (IPMDS), President of the Parkinson Society of Karnataka, Chair of Infection Related Movement Disorders Study Group of MDS, Member of Rare Movement Disorders Study Group of International Parkinson and Movement Disorder Society (IPMDS), Member of Education Committee of IAPRD, Member of Rating Scales Education and Training Program Committee of IPMDS, Member of Neurophysiology Task Force of IPMDS, Member of Movement Disorders in Asia Study Group, Member of Post-Stroke Movement Disorders, Member of Ataxia Study Group of IPMDS, and as a Member of Ataxia Global Initiative; all outside the submitted work. C Palladino reports grants or contracts from FCT – Fundação para a Ciência e a Tecnologia, I.P. (national funding), under a contract-programme as defined by DL No. 57/2016 and Law No. 57/2017 (DL57/2016/CP1376/CT0004). DOI 10.54499/DL57/2016/CP1376/CT0004 (https://doi.org/10.54499/DL57/2016/CP1376/CT0004). R F Palma-Alvarez reports payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Angelini, Lundbeck, Casen Recordati and Takeda; support for attending meetings and/or travel from Janssen and Lundbeck; all outside the submitted work. A M Pantea Stoian reports consulting fees from AstraZeneca, Boehringer Ingelheim, Eli Lilly, Novo Nordisk, Novartis, Sandoz, and Sanofi; payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Astra Zeneca, Boehringer Ingelheim, Eli Lilly, Novo Nordisk, Novartis, Sandoz, Medochemie, Servier, and Sanofi; support for attending meetings and/or travel from Sanofi, Novo Nordisk, and Medochemie; Participation on a Data Safety Monitoring Board or Advisory Board with Astra Zeneca, Eli Lilly, Novo Nordisk, and Sanofi; Leadership or fiduciary role in other board, society, committee or advocacy group, unpaid, with the Central European Diabetes Association and the Association for Renal-Metabolic & Nutritional Studies(ASRMN); outside the submitted work. R Passera reports Participation on a Data Safety Monitoring Board or Advisory Board with the non-profit clinical trial “Consolidation with ADCT-402 (loncastuximab tesirine) after immunochemotherapy: a phase II study in BTKi-treated/ineligible Relapse/Refractory Mantle Cell Lymphoma (MCL) patients” - sponsor FIL, Fondazione Italiana Linfomi, Alessandria-I (unpaid role); leadership or fiduciary role in other board, society, committee or advocacy group, paid or unpaid, Member of the Statistical Committee of the EBMT – European Society for Bone and Marrow Transplantation, Paris-F (unpaid role); outside the submitted work. A E Peden reports support for the present manuscript from the [Australian] National Health and Medical Research Council (Grant Number: APP2009306). V C F Pepito reports grants or contracts from Sanofi Consumer Healthcare and the International Initiative for Impact Evaluation; outside the submitted work. M Pigeolet reports a grant from the Belgian Kids' Fund for Pediatric Research, outside the submitted work. T Pilgrim reports grants paid to the institution without personal remuneration from Biotronik, Edwards Lifesciences, and ATSens; Payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Biotronik, Boston Scientific, Edwards Lifesciences, Abbott, Medtronic, Biosensors, and Highlife; Participation on a Data Safety Monitoring Board or Advisory Board for EMPIRE study sponsored by Biosensors; and receipt of equipment (AT-Patches) from ATSens; outside the submitted work. D Prieto-Alhambra reports support for the present manuscript from European Medicines Agency and Innovative Medicines Initiative, through their institution; grants or contracts from Amgen, Chiesi-Taylor, Lilly, Janssen, Novartis, and UCB Biopharma through their institution; consulting fees from Astra Zeneca and UCB Biopharma; other financial or non-financial interest in Amgen, Astellas, Janssen, Synapse Management Partners and UCB Biopharma for supported training programmes; outside the submitted work. A Radfar reports support for the present manuscript from Avicenna Medical and Clinical Research Institute. A Rane reports stock or stock options as a full-time employee at Agios Pharmaceuticals; outside the submitted work. L F Reyes reports grants or contracts form MSD and Pfizer; consulting fees from GSK, MSD, and Pfizer; Payment or honoraria for lectures, presentations, speakers' bureaus, manuscript writing or educational events from GSK and Pfizer; payment for expert testimony from GSK and MSD; support for attending meetings and/or travel from GSK; outside the submitted work. T G Rhee reports grants or contracts from the NIH (R21AG070666; R21DA057540; R21AG078972; R01MH131528; R01AG080647); outside the submitted work. S Sacco reports grants or contracts from Novartis and Uriach; consulting fees from Novartis, Allergan-Abbvie, Teva, Lilly, Lundbeck, Pfizer, Novo Nordisk, Abbott, AstraZeneca; Payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Novartis, Allergan-Abbvie, Teva, Lilly, Lundbeck, Pfizer, Novo Nordisk, Abbott, AstraZeneca; support for attending meetings and/or travel from Lilly, Novartis, Teva, Lundbeck; leadership or fiduciary role in other board, society, committee or advocacy group, paid or unpaid, as the President elect of the European Stroke Organization, and the Second vice-president of the European Headache Federation; receipt of equipment, materials, drugs, medical writing, gifts or other services from Allergan-Abbvie, Novo Nordisk; all outside the submitted work. P Sachdev reports grants or contracts from national Health and Medical Research Council of Australia and the US National Institutes of Health; Payment or honoraria for lectures from Alkem Labs for the Frontiers of Psychiatry June 2023 Seminar, Mumbai, India; Participation on a Data Safety Monitoring Board or Advisory Board with Biogen Australia and Roche Australia; leadership or fiduciary role in other board, society, committee or advocacy group, unpaid, with the VASCOG Society and the World Psychiatric Association; all outside the submitted work. Y L Samodra reports grants or contracts from Taipei Medical University; leadership or fiduciary role in other board, society, committee or advocacy group, paid or unpaid, with the Benang Merah Research Center; all outside the submitted work. J Sanabria reports support for attending meetings and/or travel from the Department of Surgery, Marshall University School of Medicine; three patents pending; participation in quality assessment and assurance for surgeries of the Department of Surgery; leadership or fiduciary role in other board, society, committee or advocacy group, paid or unpaid with SSAT, ASTS, AHPBA, IHPBA, and AASLD; all outside the submitted work. N Scarmeas reports grants or contracts with Novo Nordisk as the Local PI of recruiting site for multinational, multicenter industry sponsored phase III treatment trial for Alzheimer's disease with funding paid to the institution; Participation on a Data Safety Monitoring Board or Advisory Board with Albert Einstein College of Medicine (NIH funded study) as the Chair of Data Safety Monitoring Board; all outside the submitted work. A E Schutte reports Speaker Honoraria from Servier, Novartis, Sanofi, Medtronic, Abbott, Omron, Aktiia; Support for attending meetings and/or travel from Servier, Medtronic, and Abbott; Participation on a Data Safety Monitoring Board or Advisory Board with Abbott Pharmaceuticals Advisory Board, Skylabs devices Advisory Board; Leadership or fiduciary role in other board, society, committee or advocacy group, paid or unpaid, with Co-Chair: National Hypertension Taskforce of Australia, Board Member: Hypertension Australia, Company Secretary: Australian Cardiovascular Alliance; all outside the submitted work. B M Schaarschmidt reports research grants from Else Kröner-Fresenius Foundatuin, DFG, and PharmaCept; Payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from AstraZeneca; support for attending meetings and/or travel from Bayer AG; all outside the submitted work. M Šekerija reports consulting fees from Roche; Payment or Honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Johnson and Johnson, and Astellas; outside the submitted work. A Sharifan reports leadership or fiduciary role in other board, society, committee or advocacy group, unpaid with Cochrane as a steering member of the Cochrane Early Career Professionals Network; and receipt of thirty days of complimentary access to ScienceDirect, Scopus, Reaxys, and Geofacets after reviewing manuscripts for two journals published by Elsevier; outside the submitted work. S Sharma reports support for the present manuscript from the John J. Bonica Postdoctoral Fellowship from the International Association for the Study of Pain (IASP; 2021-2023); Payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events and a travel grant for delivering a talk on “Technologies for pain education in developing countries” conducted by the Pain Education SIG of the IASP at the World Pain Congress in Toronto (2022); outside the submitted work. V Sharma reports other financial or non-financial support from DFSS (MHA)'s research project (DFSS28(1)2019/EMR/6) at Institute of Forensic Science & Criminology, Panjab University, Chandigarh, India, outside the submitted work. K Shibuya reports support for the present manuscript from Tokyo Foundation for Policy Research. V Shivarov reports one patent and one utility model with the Bulgarian Patent Office; stock or stock options from ICONplc (RSUs); and other financial interests from an ICONplc salary; all outside the submitted work. S Shrestha reports other financial interests from the Graduate Research Merit Scholarship from the School of Pharmacy at Monash University Malaysia, outside the submitted work. J P Silva reports support for the present manuscript from the Portuguese Foundation for Science and Technology through payment of their salary (contract with reference 2021.01789.CEECIND/CP1662/CT0014). L M L R Silva reports grants or contracts from CENTRO-04-3559-FSE-000162, Fundo Social Europeu (FSE), outside the submitted work. C R Simpson reports grants or contracts from MBIE (NZ), HRC (NZ), Ministry of Health (NZ), MRC (UK), and CSO (UK); Leadership or fiduciary role in other board, society, committee or advocacy group, paid or unpaid with the New Zealand Government Data Ethics Advisory Group as the Chair; outside the submitted work. D J Stein reports consulting fees from Discovery Vitality, Johnson & Johnson, Kanna, L'Oreal, Lundbeck, Orion, Sanofi, Servier, Takeda, and Vistagen, outside the submitted work. K Stibrant Sunnerhagen reports Leadership or fiduciary role in other board, society, committee or advocacy group, paid or unpaid as the head of the scientific committee of the Sweidhs Stroke Foundation; outside the submitted work. S Stortecky reports grants or contracts paid to their institution from Edwards Lifesciences, Medtronic, Abbott, and Boston Scientific; consulting fees from Teleflex; Payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Boston Scientific/BTG; outside the submitted work. A G Thrift reports grants or contracts paid to their institution from the National Health & Medical Research Council (Australia) (grant numbers 1171966, 1182071), Heart Foundation (Aus) and the Stroke Foundation (Australia); outside the submitted work. J H V Ticoalu reports Leadership or fiduciary role in other board, society, committee or advocacy group, paid or unpaid, with Benang Merah Research Center as co-founder, outside the submitted work. M V Titova reports support for the present manuscript from the Ministry of Science and Higher Education of the Russian Federation (theme No. 122042600086-7). S J Tromans reports grants or contracts from the 2023 Adult Psychiatric Morbidity Survey team, collecting epidemiological data on community-based adults living in England. This is a contracted study from NHS Digital, via the Department of Health and Social Care; outside the submitted work. P Willeit reports consulting fees from Novartis; outside the submitted work. M Zielińska reports other financial interest as an AstraZeneca employee, outside the submitted work. A Zumla reports grants or contracts from The Pan-African Network on Emerging and Re-Emerging Infections (PANDORA-ID-NET, CANTAM-3, and EACCR-3) funded by the European and Developing Countries Clinical Trials Partnership, the EU Horizon 2020 Framework Programme, UK National Institute for Health and Care Research Senior Investigator, and Mahathir Science Award and EU-EDCTP Pascoal Mocumbi Prize Laureate; Participation on a Data Safety Monitoring Board or Advisory Board member of the WHO Mass Gatherings Expert Group and WHO Health Emergencies Programme in Geneva, a member of the EU-EDCTP3-Global Health (Brussels) Scientific Committee; all outside the submitted work., (Copyright © 2024 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.)

Background: Accurate assessments of current and future fertility-including overall trends and changing population age structures across countries and regions-are essential to help plan for the profound social, economic, environmental, and geopolitical challenges that these changes will bring. Estimates and projections of fertility are necessary to inform policies involving resource and health-care needs, labour supply, education, gender equality, and family planning and support. The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021 produced up-to-date and comprehensive demographic assessments of key fertility indicators at global, regional, and national levels from 1950 to 2021 and forecast fertility metrics to 2100 based on a reference scenario and key policy-dependent alternative scenarios., Methods: To estimate fertility indicators from 1950 to 2021, mixed-effects regression models and spatiotemporal Gaussian process regression were used to synthesise data from 8709 country-years of vital and sample registrations, 1455 surveys and censuses, and 150 other sources, and to generate age-specific fertility rates (ASFRs) for 5-year age groups from age 10 years to 54 years. ASFRs were summed across age groups to produce estimates of total fertility rate (TFR). Livebirths were calculated by multiplying ASFR and age-specific female population, then summing across ages 10-54 years. To forecast future fertility up to 2100, our Institute for Health Metrics and Evaluation (IHME) forecasting model was based on projections of completed cohort fertility at age 50 years (CCF50; the average number of children born over time to females from a specified birth cohort), which yields more stable and accurate measures of fertility than directly modelling TFR. CCF50 was modelled using an ensemble approach in which three sub-models (with two, three, and four covariates variously consisting of female educational attainment, contraceptive met need, population density in habitable areas, and under-5 mortality) were given equal weights, and analyses were conducted utilising the MR-BRT (meta-regression-Bayesian, regularised, trimmed) tool. To capture time-series trends in CCF50 not explained by these covariates, we used a first-order autoregressive model on the residual term. CCF50 as a proportion of each 5-year ASFR was predicted using a linear mixed-effects model with fixed-effects covariates (female educational attainment and contraceptive met need) and random intercepts for geographical regions. Projected TFRs were then computed for each calendar year as the sum of single-year ASFRs across age groups. The reference forecast is our estimate of the most likely fertility future given the model, past fertility, forecasts of covariates, and historical relationships between covariates and fertility. We additionally produced forecasts for multiple alternative scenarios in each location: the UN Sustainable Development Goal (SDG) for education is achieved by 2030; the contraceptive met need SDG is achieved by 2030; pro-natal policies are enacted to create supportive environments for those who give birth; and the previous three scenarios combined. Uncertainty from past data inputs and model estimation was propagated throughout analyses by taking 1000 draws for past and present fertility estimates and 500 draws for future forecasts from the estimated distribution for each metric, with 95% uncertainty intervals (UIs) given as the 2·5 and 97·5 percentiles of the draws. To evaluate the forecasting performance of our model and others, we computed skill values-a metric assessing gain in forecasting accuracy-by comparing predicted versus observed ASFRs from the past 15 years (2007-21). A positive skill metric indicates that the model being evaluated performs better than the baseline model (here, a simplified model holding 2007 values constant in the future), and a negative metric indicates that the evaluated model performs worse than baseline., Findings: During the period from 1950 to 2021, global TFR more than halved, from 4·84 (95% UI 4·63-5·06) to 2·23 (2·09-2·38). Global annual livebirths peaked in 2016 at 142 million (95% UI 137-147), declining to 129 million (121-138) in 2021. Fertility rates declined in all countries and territories since 1950, with TFR remaining above 2·1-canonically considered replacement-level fertility-in 94 (46·1%) countries and territories in 2021. This included 44 of 46 countries in sub-Saharan Africa, which was the super-region with the largest share of livebirths in 2021 (29·2% [28·7-29·6]). 47 countries and territories in which lowest estimated fertility between 1950 and 2021 was below replacement experienced one or more subsequent years with higher fertility; only three of these locations rebounded above replacement levels. Future fertility rates were projected to continue to decline worldwide, reaching a global TFR of 1·83 (1·59-2·08) in 2050 and 1·59 (1·25-1·96) in 2100 under the reference scenario. The number of countries and territories with fertility rates remaining above replacement was forecast to be 49 (24·0%) in 2050 and only six (2·9%) in 2100, with three of these six countries included in the 2021 World Bank-defined low-income group, all located in the GBD super-region of sub-Saharan Africa. The proportion of livebirths occurring in sub-Saharan Africa was forecast to increase to more than half of the world's livebirths in 2100, to 41·3% (39·6-43·1) in 2050 and 54·3% (47·1-59·5) in 2100. The share of livebirths was projected to decline between 2021 and 2100 in most of the six other super-regions-decreasing, for example, in south Asia from 24·8% (23·7-25·8) in 2021 to 16·7% (14·3-19·1) in 2050 and 7·1% (4·4-10·1) in 2100-but was forecast to increase modestly in the north Africa and Middle East and high-income super-regions. Forecast estimates for the alternative combined scenario suggest that meeting SDG targets for education and contraceptive met need, as well as implementing pro-natal policies, would result in global TFRs of 1·65 (1·40-1·92) in 2050 and 1·62 (1·35-1·95) in 2100. The forecasting skill metric values for the IHME model were positive across all age groups, indicating that the model is better than the constant prediction., Interpretation: Fertility is declining globally, with rates in more than half of all countries and territories in 2021 below replacement level. Trends since 2000 show considerable heterogeneity in the steepness of declines, and only a small number of countries experienced even a slight fertility rebound after their lowest observed rate, with none reaching replacement level. Additionally, the distribution of livebirths across the globe is shifting, with a greater proportion occurring in the lowest-income countries. Future fertility rates will continue to decline worldwide and will remain low even under successful implementation of pro-natal policies. These changes will have far-reaching economic and societal consequences due to ageing populations and declining workforces in higher-income countries, combined with an increasing share of livebirths among the already poorest regions of the world., Funding: Bill & Melinda Gates Foundation., Competing Interests: Declaration of interests S Afzal reports payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events and webinars with King Edward Medical University and collaborative partners including University of Johns Hopkins, University of California, and University of Massachusetts; participation on a Data Safety Monitoring Board or Advisory Board with the National Bioethics Committee Pakistan, King Edward Medical University Institutional Ethical Review Board, and the Ethical Review Board Fatima Jinnah Medical University and Sir Ganga Ram Hospital; leadership or fiduciary roles in board, society, committee, or advocacy groups, paid or unpaid, with Pakistan Association of Medical Editors, Fellow of Faculty of Public Health Royal Colleges UK (FFPH), the Society of Prevention, Advocacy and Research of King Edward Medical University (SPARK), and as a Member of the Pakistan Society of Infectious Diseases; and other financial support as Dean of Public Health and Preventive Medicine, King Edward Medical University, as the Chief Editor of Annals of King Edward Medical University since 2014, as the Director of Quality Enhancement Cell, King Edward Medical University, and with the Member Research and Publications Higher Education Commission Pakistan; all outside the submitted work. R Ancuceanu reports consulting fees from AbbVie, Sandoz, B Braun, and Laropharm, all outside the submitted work. J Ärnlöv reports payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from AstraZeneca and Novartis; participation on a Data Safety Monitoring Board or Advisory Board with AstraZeneca, Astella, and Boehringer Ingelheim; all outside the submitted work. M Ausloos reports grants or contracts from the Romanian National Authority for Scientific Research and Innovation, CNDS-UEFISCDI (project number PN-III-P4-ID-PCCF-2016-0084), outside the submitted work. R Bai reports support for the present manuscript from the Social Science Fund of Jiangsu Province (grant number 21GLD008). O C Baltatu reports support for the present manuscript from the National Council for Scientific and Technological Development (CNPq, 304224/2022-7) and from Anima Institute (AI research professor fellowship); leadership or fiduciary roles in board, society, committee, or advocacy groups, paid or unpaid, as a Biotech Board Member at São José dos Campos Technology Park, outside the submitted work. T Bärnighausen reports grants or contracts from the National Institutes of Health (NIH), Alexander von Humboldt Foundation, German National Research Foundation (DFG), EU, German Ministry of Education and Research, German Ministry of the Environment, Wellcome Trust, and KfW; payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from PLOS Medicine as the Editor-in-Chief; participation on a Data Safety Monitoring Board or Advisory Board for NIH-funded research projects in Africa on climate change and health; and stock ownership in CHEERS; outside the submitted work. S Barteit reports support for attending meetings or travel from the Wellcome Trust, and stocks or stock options with Climate Change and Health Evaluation and Response System; all outside the submitted work. M L Bell reports grants or contracts from US EPA, NIH, High Tide Foundation, Health Effects Institute, Yale Women Faculty Forum, the Environmental Defense Fund, Wellcome Trust Foundation, Yale Climate Change and Health Center, Robert Wood Johnson Foundation, and the Hutchinson Postdoctoral Fellowship; consulting fees from Clinique; honoraria for lectures, presentations, or speakers bureaus from Colorado School of Public Health, Duke University, University of Texas, Data4Justice, Korea University, Organization of Teratology Information Specialists, UPenn, and Boston University; honorarium for editorial duties from IOP Publishing; honorarium for grant review from NIH, Health Canada, PAC-10, UK Research and Innovation, and AXA Research Fund Fellowship; honorarium for external advisory committee from Harvard University and the University of Montana; support for attending meetings or travel from Colorado School of Public Health, University of Texas, Duke University, Boston University, UPenn, Harvard University, and the American Journal of Public Health; a leadership or fiduciary role in a board, society, committee, or advocacy group, unpaid, with Fifth National Climate Assessment, the Lancet Countdown, Johns Hopkins EHE Advisory Board, a Harvard external advisory committee for training grants, WHO Global Air Pollution and Health Technical Advisory group, and the National Academies Panels and Committees; leadership or fiduciary role in a board, society, committee, or advocacy group, paid, from the US EPA Clean Air Scientific Advisory Committee (CASAC); all outside the submitted work. P J G Bettencourt reports other financial or non-financial support as a Project Reviewer at Botnar Foundation; outside the submitted work. P V Bhardwaj reports stock or stock options with Doximity, outside the submitted work. S Bhaskar reports grants or contracts from Japan Society for the Promotion of Science (JSPS), Japanese Ministry of Education, Culture, Sports, Science and Technology (MEXT), Grant-in-Aid for Scientific Research (KAKENHI), and JSPS and the Australian Academy of Science (JSPS International Fellowship); leadership or fiduciary roles in board, society, committee, or advocacy groups, paid or unpaid, with Rotary District 9675 as the District Chair, Diversity, Equity, and Inclusion, the Global Health and Migration Hub Community, Global Health Hub Germany (Berlin, Germany) as the Chair and Manager, PLOS One, BMC Neurology, Frontiers in Neurology, Frontiers in Stroke, Frontiers in Public Health, and BMC Medical Research Methodology as an Editorial Board Member; and the College of Reviewers, Canadian Institutes of Health Research (CIHR), Government of Canada as a Member; outside the submitted work. A Biswas reports consulting fees from Lupin Pharmaceuticals (India), Alkem Laboratories (India), and Intas Pharmaceuticals (India); payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from Roche Diagnostics (India); outside the submitted work. J Conde reports grants or contracts from the European Research Council Starting Grant (ERC-StG-2019-848325), outside the submitted work. S Das reports a leadership or fiduciary role in a board, society, committee, or advocacy group, unpaid, as an executive voluntary member and leadership position in the Association for Diagnostic and Laboratory Medicine and Women in Global Health India Chapter; outside the submitted work. A Dastiridou reports payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from AbbVie and Thea; outside the submitted work. A Faro reports support for the present manuscript from Coordination of Superior Level Staff Improvement (CNPq, Brazil) Productivity in Research Scholarship (PQ Scholarship). A A Fomenkov reports support for the present manuscript from the Ministry of Science and Higher Education of the Russian Federation (theme number 121050500047-5). M Foschi reports consulting fees from Roche, Biogen, Merck, Sanofi, and Novartis; support for attending meetings or travel from Roche, Novartis, Biogen, Sanofi, and Merck; leadership or fiduciary role in a board, society, committee, or advocacy group, paid or unpaid, as a current member of the MSBase collaboration scientific leadership group; outside the submitted work. I Filip reports support for the present manuscript from Avicenna Medical and Clinical Research Institute. I Ilic and M Ilic report support for the present manuscript from the Ministry of Science, Technological Development and Innovation of the Republic of Serbia (grants 451-03-47/2023-01/200111 and 175042, 2011-2023). N E Ismail reports a leadership or fiduciary role in a board, society, committee, or advocacy group, unpaid, with The Bursar as a Council Member of the Malaysian Academy of Pharmacy; outside the submitted work. A Hassan reports consulting fees from Novartis, Sanofi Genzyme, Biologix, Merck, Hikma Pharma, Janssen, Inspire Pharma, Future Pharma, and Elixir Pharma; payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from Novartis, Allergan, Merck, Biologix, Janssen, Roche, Sanofi Genzyme, Bayer, Hikma Pharma, Al Andalus, Chemipharm, Lundbeck, Inspire Pharma, Future Pharma and Habib Scientific Office, and Everpharma; support for attending meetings or travel from Novartis, Allergan, Merck, Biologix, Roche, Sanofi Genzyme, Bayer, Hikma Pharma, Chemipharm, Al Andalus Pharmaceuticals, and Clavita Pharmaceuticals; a leadership or fiduciary role in a board, society, committee, or advocacy group, paid or unpaid, as a member of educational, membership, and regional committees of international headache societies; outside the submitted work. C Herteliu reports grants or contracts from the Romanian Ministry of Research Innovation and Digitalization (MCID, project number ID-585-CTR-42-PFE-2021), a grant of the European Commission Horizon 4P-CAN Personalised Cancer Primary Prevention Research through Citizen Participation and Digitally Enabled Social Innovation Project “Societal and Economic Resilience within multi-hazards environment in Romania” funded by EU—NextgenerationEU and Romanian Government, under National Recovery and Resilience Plan for Romania (contract number 760050/23.05.2023, cod PNRR-C9-I8-CF 267/29.11.2022), through the Romanian Ministry of Research, Innovation and Digitalization, within Component 9, Investment I8, and Project “A better understanding of socio-economic systems using quantitative methods from Physics” funded by EU—NextgenerationEU and Romanian Government, under National Recovery and Resilience Plan for Romania (contract number 760034/23.05.2023, cod PNRR-C9-I8-CF 255/29.11.2022), through the Romanian Ministry of Research, Innovation and Digitalization, within Component 9, Investment I8; outside the submitted work. T Joo reports support for the present manuscript from the National Research, Development and Innovation Office in Hungary (RRF-2.3.1-21-2022-00006), Data-Driven Health Division of National Laboratory for Health Security. J Jozwiak reports payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from Novartis, ADAMed, and Amgen, outside the submitted work. J H Kempen reports support for the present manuscript from Sight for Souls and the Mass Eye and Ear Global Surgery Program; participation on a Data Safety Monitoring Board or Advisory Board with Gilead; leadership or fiduciary role in a board, society, committee, or advocacy group, unpaid, on the board of Sight for Souls; stock or stock options with Betaliq and Tarsier; outside the submitted work. K Krishan reports other non-financial support from the UGC Centre of Advanced Study, CAS II, awarded to the Department of Anthropology, Panjab University (Chandigarh, India); outside the submitted work. B Lacey reports support for the present manuscript from UK Biobank, funded largely by the UK Medical Research Council and Wellcome Trust. J Lam reports support for the present manuscript from the National Research, Development and Innovation Fund (project number TKP2021-NVA-11). H J Larson reports grants or contracts from GSK and Moderna; consulting fees from the Gates Medical Research Institute and Apiject; payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events as a 2022 Merrimon Lecturer (UNC); outside the submitted work. M Lee reports support for the present manuscript from the Ministry of Education of the Republic of Korea and the National Research Foundation of Korea (NRF-2021R1I1A4A01057428) and Bio-convergence Technology Education Program through the Korea Institute for Advancement Technology (KIAT) funded by the Ministry of Trade, Industry and Energy (P0017805). M-C Li reports grant support from the National Science and Technology Council in Taiwan (NSTC 112-2410-H-003-031); leadership or fiduciary role in a board, society, committee or advocacy group, paid or unpaid, as the Technical Editor of the Journal of the American Heart Association. M A Mahmoud reports grants or contracts from Deputyship for Research & Innovation, Ministry of Education in Saudi Arabia for funding this research work through the project number 445-5-762; outside the submitted work. R J Maude reports support for the present manuscript from Wellcome Trust (grant number 220211) because it provides core funding for Mahidol Oxford Tropical Medicine Research. A-F A Mentis reports grants or contracts from MilkSafe: a novel pipeline to enrich formula milk using omics technologies, a research co-financed by the European Regional Development Fund of the EU and Greek national funds through the Operational Program Competitiveness, Entrepreneurship and Innovation, under the call RESEARCH–CREATE–INNOVATE (project code T2EDK-02222), as well as from ELIDEK (Hellenic Foundation for Research and Innovation, MIMS-860), both outside of the present manuscript; payment or expert testimony as a peer reviewer for Fondazione Cariplo, Italy; participation on a Data Safety Monitoring Board or Advisory Board as Editorial Board Member for Systematic Reviews and Annals of Epidemiology, and as Associate Editor for Translational Psychiatry; stock or stock options on a family winery; other financial interests as a scientific officer as part of the BGI Group; outside the submitted work. P B Mentis reports payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from Janssen (Australia) and Sanofi (Hangzhou); participation on a Data Safety Monitoring Board or Advisory Board from Janssen (Australia); outside the submitted work. L Monasta and L Ronfani report support for the present manuscript from the Italian Ministry of Health (Ricerca Corrente 34/2017) via payments made to the Institute for Maternal and Child Health Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Burlo Garofolo. R S Moreira reports grants or contracts from the National Council for Scientific and Technological Development CNPq Research Productivity Scholarship (scholarship registration number 316607/2021-5). J Morze reports grants or contracts from SciLifeLab and Wallenberg Data Driven Life Science Program (KAW 2020.0239); consulting fees from ALAB Laboratoria; outside the submitted work. S Muthu reports leadership or fiduciary role in other board, society, committee, or advocacy group, paid or unpaid, on the NEXTGen Committee (ICRS), Grants Committee (SICOT), and with the Knowledge Forum Degenerative Associate as a member (AO Spine); outside the submitted work. S Nomura reports support for the present manuscript from the Ministry of Education, Culture, Sports, Science and Technology of Japan (21H03203) and Precursory Research for Embryonic Science and Technology from the Japan Science and Technology Agency (JPMJPR22R8). A P Okekunle reports support for the present manuscript from the National Research Foundation of Korea funded by the Ministry of Science and ICT (2020H1D3A1A04081265); support for attending meetings or travel from the National Research Foundation of Korea funded by the Ministry of Science and ICT (2020H1D3A1A04081265), outside the submitted work. A Pantea Stoian reports payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from AstraZeneca, Eli Lilly, Merck, Medtronic, Novo Nordisk, Servier, and Sanofi; support for attending meetings or travel from Sanofi, Novo Nordisk, and Eli Lilly; participation on a Data Safety Monitoring Board or Advisory Board with Eli Lilly, Novo Nordisk, and Sanofi; leadership or fiduciary role in other board, society, committee or advocacy group, paid or unpaid, as the Vice-president of the Central European Diabetes Association and as the President of the Romanian National Diabetes Committee; outside the submitted work. R Passera reports participation on a Data Safety Monitoring Board or Advisory Board as the expert biostatistician member for the clinical trial Consolidation with ADCT-402 (loncastuximab tesirine) after immunochemotherapy: a phase II study in BTKi-treated/ineligible Relapse/Refractory Mantle Cell Lymphoma (MCL) patients, sponsor FIL, Fondazione Italiana Linfomi, Alessandria-I; outside the submitted work. M Pigeolet reports grants or contracts from the Belgian Kids' Fund for Pediatric Research; outside the submitted work. A E Peden reports support for the present manuscript from the Australian National Health and Medical Research Council (grant number APP2009306). V C F Pepito reports grants or contracts from Sanofi Consumer Healthcare and International Initiative for Impact Evaluation; outside the submitted work. A Radfar reports support for the present manuscript from Avicenna Medical and Clinical Research Institute. A Rane reports support for the present manuscript from The Bill & Melinda Gates Foundation; stock or stock options as a full-time employee of Agios Pharmaceuticals; outside the submitted work. J Sanabria reports a pending grant award from the NIH, National Cancer Institute (NCI), and DoD; support for attending meetings or travel from Marshall University Medical School; three patents pending; participation on a Data Safety Monitoring Board or Advisory Board as the Chair of quality assessment and assurance for the Marshall University Department of Surgery; leadership or fiduciary role in other board, society, committee, or advocacy group, paid or unpaid with the American Society of Transplant Surgeons, the American Association for the Study of Liver Diseases, International Hepato-Pancreato Biliary Association, the Americas Hepato-Pancreato-Biliary Association, the Society for Surgery of the Alimentary Tract, and the Society of Surgical Oncology; outside the submitted work. N Scarmeas reports grants or contracts from Novo Nordisk; participation on a Data Safety Monitoring Board or Advisory Board with the NIH; outside the submitted work. A Sharifan reports leadership or fiduciary role in other board, society, committee, or advocacy group, unpaid, with Cochrane as a steering member of the Cochrane Early Career Professionals Network; receipt of equipment, materials, drugs, medical writing, gifts, or other services from Elsevier; outside the submitted work. V Sharma acknowledges support from DFSS (MHA)'s research project (DFSS28[1]2019/EMR/6) at Institute of Forensic Science and Criminology, Panjab University (Chandigarh, India); outside the submitted work. V Shivarov reports one patent and one utility model with the Bulgarian Patent Office; stock or stock options from ICONplc (RSUs); and other financial interests from an ICONplc salary; outside the submitted work. J P Silva reports support for the present manuscript from the Portuguese Foundation for Science and Technology. J A Singh reports consulting fees from AstraZeneca, Crealta/Horizon, Medisys, Fidia, PK Med, Two Labs, Adept Field Solutions, Clinical Care Options, Clearview Healthcare Partners, Putnam Associates, Focus Forward, Navigant Consulting, Spherix, MedIQ, Jupiter Life Science, UBM, Trio Health, Medscape, WebMD, and Practice Point Communications; and the NIH and the American College of Rheumatology; payment for lectures, presentations, speakers bureaus, manuscript writing, or educational events as a member of the speakers bureau Simply Speaking; support for attending meetings or travel as a past steering committee member of OMERACT; participation on a Data Safety Monitoring Board or Advisory Board for the FDA Arthritis Advisory Committee; leadership or fiduciary role in a board, society, committee, or advocacy group, paid or unpaid, as a past steering committee member of the OMERACT, an international organisation that develops measures for clinical trials and receives arm's length funding from 12 pharmaceutical companies, as Co-Chair of the Veterans Affairs Rheumatology Field Advisory Committee, and as Editor and Director of the UAB Cochrane Musculoskeletal Group Satellite Center on Network Meta-analysis; stock or stock options in Atai Life Sciences, Kintara Therapeutics, Intelligent Biosolutions, Acumen Pharmaceutical, TPT Global Tech, Vaxart Pharmaceuticals, Atyu Biopharma, Adaptimmune Therapeutics, GeoVax Labs, Pieris Pharmaceuticals, Enzolytics, Seres Therapeutics, Tonix Pharmaceuticals Holding, and Charlotte's Web Holdings, and previously owned stock options in Amarin, Viking, and Moderna Pharmaceuticals; outside the submitted work. M V Titova reports support for the present manuscript from the state assignment of the Ministry of Science and Higher Education of the Russian Federation (theme number 121050500047-5). H Zhang reports grants or contracts from World Health Organization (WHO) funding; outside the submitted work. M Zielinska reports other financial support as an AstraZeneca employee; outside the submitted work. All other authors declare no competing interests., (Copyright © 2024 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.)