Intervention targets for reducing mortality between mid-adolescence and mid-adulthood: a protocol for a machine-learning facilitated systematic umbrella review
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Abstract
Introduction
A rise in premature mortality—defined here as death during the most productive years
of life, between adolescence and middle adulthood (15–60 years)—is contributing to
stalling life expectancy in high-income countries. Causes of mortality vary, but often
include substance misuse, suicide, unintentional injury and non-communicable disease.
The development of evidence-informed policy frameworks to guide new approaches to
prevention require knowledge of early targets for intervention, and interactions between
higher level drivers. Here, we aim to: (1) identify systematic reviews with or without
meta-analyses focused on intervention targets for premature mortality (in which intervention
targets are causes of mortality that can, at least hypothetically, be modified to
reduce risk); (2) evaluate the review quality and risk of bias; (3) compare and evaluate
each review’s, and their relevant primary studies, findings to identify existing evidence
gaps.
Methods and analysis
In May 2023, we searched electronic databases (MEDLINE, PubMed, Embase, Cochrane Library)
for peer-reviewed papers published in the English language in the 12 years from 2012
to 2023 that examined intervention targets for mortality. Screening will narrow these
papers to focus on systematic reviews with or without meta-analyses, and their primary
papers. Our outcome is death between ages 15 and 60 years; with potential intervention
targets measured prior to death. A MeaSurement Tool to Assess systematic Reviews (AMSTAR
2) will be used to assess quality and risk of bias within included systematic reviews.
Results will be synthesised narratively due to anticipated heterogeneity between reviews
and between primary studies contained within included reviews.
Ethics and dissemination
This review will synthesise findings from published systematic reviews and meta-analyses,
and their primary reviewed studies, meaning ethics committee approval is not required.
Our findings will inform cross-cohort consortium development, be published in a peer-reviewed
journal, and be presented at national and international conferences.
Systematic reviews should build on a protocol that describes the rationale, hypothesis, and planned methods of the review; few reviews report whether a protocol exists. Detailed, well-described protocols can facilitate the understanding and appraisal of the review methods, as well as the detection of modifications to methods and selective reporting in completed reviews. We describe the development of a reporting guideline, the Preferred Reporting Items for Systematic reviews and Meta-Analyses for Protocols 2015 (PRISMA-P 2015). PRISMA-P consists of a 17-item checklist intended to facilitate the preparation and reporting of a robust protocol for the systematic review. Funders and those commissioning reviews might consider mandating the use of the checklist to facilitate the submission of relevant protocol information in funding applications. Similarly, peer reviewers and editors can use the guidance to gauge the completeness and transparency of a systematic review protocol submitted for publication in a journal or other medium.
The number of published systematic reviews of studies of healthcare interventions has increased rapidly and these are used extensively for clinical and policy decisions. Systematic reviews are subject to a range of biases and increasingly include non-randomised studies of interventions. It is important that users can distinguish high quality reviews. Many instruments have been designed to evaluate different aspects of reviews, but there are few comprehensive critical appraisal instruments. AMSTAR was developed to evaluate systematic reviews of randomised trials. In this paper, we report on the updating of AMSTAR and its adaptation to enable more detailed assessment of systematic reviews that include randomised or non-randomised studies of healthcare interventions, or both. With moves to base more decisions on real world observational evidence we believe that AMSTAR 2 will assist decision makers in the identification of high quality systematic reviews, including those based on non-randomised studies of healthcare interventions.
Summary Background Global development goals increasingly rely on country-specific estimates for benchmarking a nation's progress. To meet this need, the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2016 estimated global, regional, national, and, for selected locations, subnational cause-specific mortality beginning in the year 1980. Here we report an update to that study, making use of newly available data and improved methods. GBD 2017 provides a comprehensive assessment of cause-specific mortality for 282 causes in 195 countries and territories from 1980 to 2017. Methods The causes of death database is composed of vital registration (VR), verbal autopsy (VA), registry, survey, police, and surveillance data. GBD 2017 added ten VA studies, 127 country-years of VR data, 502 cancer-registry country-years, and an additional surveillance country-year. Expansions of the GBD cause of death hierarchy resulted in 18 additional causes estimated for GBD 2017. Newly available data led to subnational estimates for five additional countries—Ethiopia, Iran, New Zealand, Norway, and Russia. Deaths assigned International Classification of Diseases (ICD) codes for non-specific, implausible, or intermediate causes of death were reassigned to underlying causes by redistribution algorithms that were incorporated into uncertainty estimation. We used statistical modelling tools developed for GBD, including the Cause of Death Ensemble model (CODEm), to generate cause fractions and cause-specific death rates for each location, year, age, and sex. Instead of using UN estimates as in previous versions, GBD 2017 independently estimated population size and fertility rate for all locations. Years of life lost (YLLs) were then calculated as the sum of each death multiplied by the standard life expectancy at each age. All rates reported here are age-standardised. Findings At the broadest grouping of causes of death (Level 1), non-communicable diseases (NCDs) comprised the greatest fraction of deaths, contributing to 73·4% (95% uncertainty interval [UI] 72·5–74·1) of total deaths in 2017, while communicable, maternal, neonatal, and nutritional (CMNN) causes accounted for 18·6% (17·9–19·6), and injuries 8·0% (7·7–8·2). Total numbers of deaths from NCD causes increased from 2007 to 2017 by 22·7% (21·5–23·9), representing an additional 7·61 million (7·20–8·01) deaths estimated in 2017 versus 2007. The death rate from NCDs decreased globally by 7·9% (7·0–8·8). The number of deaths for CMNN causes decreased by 22·2% (20·0–24·0) and the death rate by 31·8% (30·1–33·3). Total deaths from injuries increased by 2·3% (0·5–4·0) between 2007 and 2017, and the death rate from injuries decreased by 13·7% (12·2–15·1) to 57·9 deaths (55·9–59·2) per 100 000 in 2017. Deaths from substance use disorders also increased, rising from 284 000 deaths (268 000–289 000) globally in 2007 to 352 000 (334 000–363 000) in 2017. Between 2007 and 2017, total deaths from conflict and terrorism increased by 118·0% (88·8–148·6). A greater reduction in total deaths and death rates was observed for some CMNN causes among children younger than 5 years than for older adults, such as a 36·4% (32·2–40·6) reduction in deaths from lower respiratory infections for children younger than 5 years compared with a 33·6% (31·2–36·1) increase in adults older than 70 years. Globally, the number of deaths was greater for men than for women at most ages in 2017, except at ages older than 85 years. Trends in global YLLs reflect an epidemiological transition, with decreases in total YLLs from enteric infections, respiratory infections and tuberculosis, and maternal and neonatal disorders between 1990 and 2017; these were generally greater in magnitude at the lowest levels of the Socio-demographic Index (SDI). At the same time, there were large increases in YLLs from neoplasms and cardiovascular diseases. YLL rates decreased across the five leading Level 2 causes in all SDI quintiles. The leading causes of YLLs in 1990—neonatal disorders, lower respiratory infections, and diarrhoeal diseases—were ranked second, fourth, and fifth, in 2017. Meanwhile, estimated YLLs increased for ischaemic heart disease (ranked first in 2017) and stroke (ranked third), even though YLL rates decreased. Population growth contributed to increased total deaths across the 20 leading Level 2 causes of mortality between 2007 and 2017. Decreases in the cause-specific mortality rate reduced the effect of population growth for all but three causes: substance use disorders, neurological disorders, and skin and subcutaneous diseases. Interpretation Improvements in global health have been unevenly distributed among populations. Deaths due to injuries, substance use disorders, armed conflict and terrorism, neoplasms, and cardiovascular disease are expanding threats to global health. For causes of death such as lower respiratory and enteric infections, more rapid progress occurred for children than for the oldest adults, and there is continuing disparity in mortality rates by sex across age groups. Reductions in the death rate of some common diseases are themselves slowing or have ceased, primarily for NCDs, and the death rate for selected causes has increased in the past decade. Funding Bill & Melinda Gates Foundation.
[1
]departmentDepartment of Psychological Medicine , University of Otago , Christchurch, New Zealand
[2
]departmentCentre for Adolescent Health , Murdoch Children’s Research Institute , Parkville, Victoria, Australia
[3
]departmentDepartment of Paediatrics , The University of Melbourne , Parkville, Victoria, Australia
[4
]departmentCentre for Community Child Health , Murdoch Children’s Research Institute , Parkville, Victoria, Australia
[5
]departmentMelbourne Graduate School of Education , The University of Melbourne , Parkville, Victoria, Australia
[6
]departmentCentre for Social and Early Emotional Development, School of Psychology, Faculty of
Health , Ringgold_2104Deakin University , Burwood, Victoria, Australia
[7
]departmentCentre for Health Equity, Justice Health Unit, Melbourne School of Population and
Global Health , Ringgold_2281The University of Melbourne , Melbourne, Victoria, Australia
[8
]departmentDepartment of Psychiatry, Warneford Hospital , University of Oxford , Oxford, UK
[9
]departmentMelbourne School of Psychological Sciences , The University of Melbourne , Parkville, Victoria, Australia
[10
]departmentClinical Epidemiology and Biostatistics Unit , Ringgold_34361Murdoch Children’s Research Institute , Parkville, Victoria, Australia
[11
]departmentDepartment of Social Work , The University of Melbourne , Parkville, Victoria, Australia
[12
]departmentSchool of Population Health , Ringgold_7800University of New South Wales , Sydney, New South Wales, Australia
[13
]departmentChild Health Research Centre , The University of Queensland , South Brisbane, Queensland, Australia
[14
]departmentChild and Youth Mental Health Service , Children’s Health Queensland , South Brisbane, Queensland, Australia
[15
]departmentSchool of Psychological Science , Ringgold_2720The University of Western Australia , Perth, Western Australia, Australia
[16
]departmentThe Raine Study, School of Population and Global Health , Ringgold_2720The University of Western Australia , Perth, Western Australia, Australia
[17
]departmentSchool of Population Health , Ringgold_1649Curtin University , Perth, Western Australia, Australia
[18
]departmentGriffith Criminology Institute , Griffith University , Brisbane, Queensland, Australia
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History
Date
received
: 28
September
2022
Date
accepted
: 28
September
2023
Funding
Funded by:
Victorian Government, Australia;
Award ID: N/A
Funded by:
FundRef http://dx.doi.org/10.13039/501100001505, Health Research Council of New Zealand;
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