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OBJECTIVES: To identify the genetic determinants of fracture risk and assess the role of 15 clinical risk factors on osteoporotic fracture risk. DESIGN: Meta-analysis of genome wide association studies (GWAS) and a two-sample mendelian randomisation approach. SETTING: 25 cohorts from Europe, United States, east Asia, and Australia with genome wide genotyping and fracture data. PARTICIPANTS: A discovery set of 37\u2009857 fracture cases and 227\u2009116 controls; with replication in up to 147\u2009200 fracture cases and 150\u2009085 controls. Fracture cases were defined as individuals (>18 years old) who had fractures at any skeletal site confirmed by medical, radiological, or questionnaire reports. Instrumental variable analyses were performed to estimate effects of 15 selected clinical risk factors for fracture in a two-sample mendelian randomisation framework, using the largest previously published GWAS meta-analysis of each risk factor. RESULTS: Of 15 fracture associated loci identified, all were also associated with bone mineral density and mapped to genes clustering in pathways known to be critical to bone biology (eg, SOST, WNT16, and ESR1) or novel pathways (FAM210A, GRB10, and ETS2). Mendelian randomisation analyses showed a clear effect of bone mineral density on fracture risk. One standard deviation decrease in genetically determined bone mineral density of the femoral neck was associated with a 55% increase in fracture risk (odds ratio 1.55 (95% confidence interval 1.48 to 1.63; P=1.5\u00d710-68). Hand grip strength was inversely associated with fracture risk, but this result was not significant after multiple testing correction. The remaining clinical risk factors (including vitamin D levels) showed no evidence for an effect on fracture. CONCLUSIONS: This large scale GWAS meta-analysis for fracture identified 15 genetic determinants of fracture, all of which also influenced bone mineral density. Among the clinical risk factors for fracture assessed, only bone mineral density showed a major causal effect on fracture. Genetic predisposition to lower levels of vitamin D and estimated calcium intake from dairy sources were not associated with fracture risk.
\n \n\n \n \nBACKGROUND: Public Health England advises 400 IU/day vitamin D supplementation for children over 1\u2009year. Commercially available children's multivitamin and vitamin D supplements were surveyed to determine the vitamin D content. METHODS: Multivitamins and vitamin D supplements marketed at children <12 years and sold by nine UK supermarkets and health supplement retailers were surveyed. Vitamin D content was determined from manufacturer's websites and product packaging. RESULTS: 67 multivitamins were surveyed, containing 0-800 IU/day vitamin D. Only 25%-36%, depending on the child's age, provided \u2265400\u2009IU/day vitamin D. Supplements containing only vitamin D or labelled as for 'healthy bones' typically had higher vitamin D content (57%-67% contained \u2265400\u2009IU/day). CONCLUSIONS: Few multivitamin products supply the recommended 400 IU/day vitamin D. Clinicians need to be aware of this when recommending vitamin D supplementation and advise parents/carers to choose a product that contains \u2265400\u2009IU/day vitamin D.
\n \n\n \n \nOBJECTIVE: Statins have several pleiotropic effects, but the literature regarding the possible relationship between statins use and outcomes in knee osteoarthritis (OA) is limited. We investigated whether statins use is associated with lower risk of radiographic (ROA), radiographic symptomatic knee OA (SxOA) and pain in North American people. METHODS: A total of 4,448 community-dwelling adults from the Osteoarthritis Initiative were followed-up for 4 years. Statins use (including the time from baseline and the type) was defined through self-report information and confirmed by a trained interviewer. Knee OA outcomes included incident (1) ROA, (2) SxOA, as the new onset of a combination of a painful knee and ROA, (3) knee pain worsening, i.e. a Western Ontario and McMaster Universities Osteoarthritis Index difference between baseline and each annual exam \u226514%. RESULTS: At baseline, 1,127 participants (=25.3%) used statins. Based on a multivariable Poisson regression analysis with robust variance estimators, any statins use was not associated with lower risk of pain worsening (relative risk, RR=0.97; 95%CI, confidence intervals: 0.93-1.02), incident ROA or SxOA. However, statins use > 5 years (RR=0.91; 95%CI: 0.83-0.997) and atorvastatin use (RR=0.95; 95%CI: 0.91-0.996) were associated with a reduced risk of developing pain, whilst rosuvastatin to a higher risk (RR=1.18; 95%CI: 1.12-1.24). The adjustment for the propensity score confirmed these findings. CONCLUSION: The effect of statins use on knee OA outcomes remains unclear, although in our study those using statins for over five years and those using atorvastatin reported a significant lower risk of developing knee pain. This article is protected by copyright. All rights reserved.
\n \n\n \n \nBACKGROUND: We consider the relationships between a clinical and radiological diagnosis of knee or hip OA and activities of daily-living (ADL) in older adults. METHODS: Data were available for 222 men and 221 women from the Hertfordshire Cohort Study (HCS) who also participated in the UK component of the European Project on Osteoarthritis (EPOSA). Participants completed the EuroQoL survey where they reported if they had difficulties with mobility, self-care, usual activities and movement around their house. Hip and knee radiographs were graded for overall Kellgren and Lawrence score (positive definition defined as a 2 or above). Clinical OA was defined using American College of Rheumatology criteria. RESULTS: In men, a clinical diagnosis of hip or knee OA were both associated with reported difficulties in mobility, ability to self-care and performing usual-activities (hip OA: OR 17.6, 95% CI 2.07, 149, p\u2009=\u20090.009; OR 12.5, 95% CI 2.51, 62.3, p\u2009=\u20090.002; OR 4.92, 95% CI 1.06, 22.8, p\u2009=\u20090.042 respectively. Knee OA: OR 8.18, 95% CI 3.32, 20.2, p\u2009<\u20090.001; OR 4.29, 95% CI 1.34, 13.7, p\u2009=\u20090.014; OR 5.32, 95% CI 2.26, 12.5, p\u2009<\u20090.001 respectively). Similar relationships were seen in women, where in addition, a radiological diagnosis of knee OA was associated with difficulties performing usual activities (OR 3.25, 95% CI 1.61, 6.54, p\u2009=\u20090.001). In general, men with OA reported stronger associations between moving around the house, specifically around the kitchen (clinical hip OA: OR 13.7, 95% CI 2.20, 85.6, p\u2009=\u20090.005; clinical knee OA OR 8.45, 95% CI 1.97, 36.2, p\u2009=\u20090.004) than women. DISCUSSION AND CONCLUSION: Clinical OA is strongly related to the ability to undertake ADL in older adults and should be considered in clinic consultations when seeing patients with OA.
\n \n\n \n \nOsteoporosis is a major health issue. By 2050, a greater than 2-fold increase in patients number with hip fractures will occur in Asia representing 50% of all hip fractures worldwide. For the Asia-Pacific (AP) region, more efforts on controlling osteoporosis and the subsequent fractures are crucial. Bone mineral density (BMD) by dual energy X-ray absorptiometry (DXA) is commonly used to diagnose osteoporosis and monitor osteoporosis treatment. However, the inconvenience, cost, limited availability of DXA and the delay in detection of BMD changes after treatment initiation support an important role for bone turnover markers (BTMs), as short-term tools to monitor therapy. With regards to low adherence rates of medical treatment of osteoporosis, the experts reached consensus on the use of BTMs for both raising awareness and short-term monitoring of osteoporosis treatment in the AP region. The experts endorse the use of BTMs, especially serum C-terminal telopeptide of type 1 collagen (CTX) and serum procollagen type 1 N propeptide (P1NP), as short-term monitoring tools to help clinicians assess the responses to osteoporosis therapies and appropriately adjust treatment regimens earlier than BMD. Either the absolute values or the degree of change from baseline in BTMs can be used to monitor the potential efficacy of osteoporosis therapies. The use of BTMs can be incorporated in osteoporosis care programs, such as fracture liaison service (FLS), to improve patient adherence and treatment outcomes. Encouraging sufficient reimbursement from health care systems may facilitate widespread use of BTMs in clinical practice in the AP region.
\n \n\n \n \nBACKGROUND: Improved maternal nutrition and glycaemic control before and during pregnancy are thought to benefit the health of the mother, with consequent benefits for infant body composition and later obesity risk. Maternal insulin resistance and glycaemia around conception and in early pregnancy may be key determinants of maternal physiology and placental function, affecting fetal nutrient supply and maternal-feto-placental communications throughout gestation, with implications for later postnatal health. METHODS/DESIGN: This double-blind randomised controlled trial will recruit up to 1800 women, aged 18-38 years, who are planning a pregnancy in the United Kingdom (UK), Singapore and New Zealand, with a view to studying 600 pregnancies. The primary outcome is maternal glucose tolerance at 28\u00a0weeks' gestation following an oral glucose tolerance test. Secondary outcomes include metabolic, molecular and health-related outcomes in the mother and offspring, notably infant body composition. Participants will be randomly allocated to receive a twice-daily control nutritional drink, enriched with standard micronutrients, or a twice-daily intervention nutritional drink enriched with additional micronutrients, myo-inositol and probiotics, both demonstrated previously to assist in maintaining healthy glucose metabolism during pregnancy. Myo-inositol is a nutrient that enhances cellular glucose uptake. The additional micronutrients seek to address deficiencies of some B-group vitamins and vitamin D that are both common during pregnancy and that have been associated with maternal dysglycaemia, epigenetic changes and greater offspring adiposity. Women who conceive within a year of starting the nutritional drinks will be followed through pregnancy and studied with their infants at six time points during the first year of life. Blood, urine/stool, hair and cheek swabs will be collected from the mothers for genetic, epigenetic, hormone, nutrient and metabolite measurements, and assessments of the mother's body composition, anthropometry, health, diet and lifestyle will be made. Infants will also undergo hair, cheek swab, urine and stool sampling for similar biological measurements; infant body composition will be assessed and feeding recorded. DISCUSSION: There is an increasing focus on the need to optimise maternal nutrition starting prior to conception. This trial will provide evidence on the potential for nutritional interventions beginning prior to conception to promote healthy maternal and offspring outcomes. TRIAL REGISTRATION: ClinicalTrials.gov, identifier: NCT02509988 , Universal Trial Number U1111-1171-8056. Registered on 16 July 2015. This is an academic-led study by the EpiGen Global Research Consortium.
\n \n\n \n \nBACKGROUND: Physical activity decreases through childhood, adolescence and into adulthood: parents of young children are particularly inactive, potentially negatively impacting their children's activity levels. This study aimed to determine the association between objectively measured maternal and 6-year-old children's physical activity; explore how this association differed by demographic and temporal factors; and identify change during the transition to school (from age 4-6). METHODS: Data were from the UK Southampton Women's Survey. Physical activity of 530 6-year-olds and their mothers was measured concurrently using accelerometry for \u22647\u2009days. Cross-sectionally, two-level mixed-effects linear regression was used to model the association between maternal-child daily activity behaviour at age 6 [minutes sedentary (SED); in moderate-to-vigorous physical activity (MVPA)]. Interactions with demographic factors and time of the week were tested; how the association differed across the day was also explored. Change in the association between maternal-child physical activity (from age 4-6) was assessed in a subset (n\u2009=\u2009170) [outcomes: SED, MVPA and light physical activity (LPA)]. RESULTS: Mother-child daily activity levels were positively associated (SED: \u03b2\u2009=\u20090.23 [0.20, 0.26] minutes/day; MVPA: 0.53 [0.43, 0.64] minutes/day). The association was stronger at weekends (vs. weekdays) (interaction term: SED: \u03b2i\u2009=\u20090.07 [0.02, 0.12]; MVPA: 0.44 [0.24, 0.64]). For SED, the association was stronger for those children with older siblings (vs. none); for MVPA, a stronger association was observed for those who had both younger and older siblings (vs. none) and a weaker relationship existed in spring compared to winter. Longitudinally, the association between mother-child activity levels did not change for SED and LPA. At age 6 (vs. age 4) the association between mother-child MVPA was weaker across the whole day (\u03b2i: -\u20090.16 [-\u20090.31, -\u20090.01]), but remained similar at both ages between 3 and 11\u2009pm. CONCLUSIONS: More active mothers have more active 6-year-olds; this association was similar for boys and girls but differed by time of week, season and by age of siblings at home. Longitudinally, the association weakened for MVPA between 4 and 6\u2009years, likely reflecting the differing activities children engage in during school hours and increased independence. Family-based physical activity remains an important element of children's activity behaviour regardless of age. This could be exploited in interventions to increase physical activity within families.
\n \n\n \n \nBACKGROUND: The Australian/Canadian hand Osteoarthritis Index (AUSCAN) and the Western Ontario and McMaster Universities knee and hip Osteoarthritis Index (WOMAC) are the most commonly used clinical tools to manage and monitor osteoarthritis (OA). Few studies have as yet reported longitudinal changes in the AUSCAN index regarding the hand. While there are published data regarding WOMAC assessments of the hip and the knee, the two sites have always evaluated separately. The current study therefore sought to determine the minimal clinically important difference (MCID) in decline in the AUSCAN hand and WOMAC hip/knee physical function scores over 1 year using anchor-based and distribution-based methods. METHODS: The study analysed data collected by the European Project on Osteoarthritis, a prospective observational study investigating six adult cohorts with and without OA by evaluating changes in the AUSCAN and WOMAC physical function scores at baseline and 12-18\u2009months later. Pain and stiffness scores, the performance-based grip strength and walking speed and health-related quality of life measures were used as the study's anchors. Receiver operating characteristic curves and distribution-based methods were used to estimate the MCID in the AUSCAN and WOMAC physical function scores; only the data of those participants who possessed paired (baseline and follow up-measures) AUSCAN and WOMAC scores were included in the analysis. RESULTS: Out of the 1866 participants who were evaluated, 1842 had paired AUSCAN scores and 1845 had paired WOMAC scores. The changes in the AUSCAN physical function score correlated significantly with those in the AUSCAN pain score (r\u00a0=\u20090.31). Anchor- and distribution-based approaches converged identifying 4 as the MCID for decline in the AUSCAN hand physical function. Changes in the WOMAC hip/knee physical function score were significantly correlated with changes in both the WOMAC pain score (r\u00a0=\u20090.47) and the WOMAC stiffness score (r\u00a0=\u20090.35). The different approaches converged identifying two as the MCID for decline in the WOMAC hip/knee physical function. CONCLUSIONS: The most reliable MCID estimates of decline over 1 year in the AUSCAN hand and WOMAC hip/knee physical function scores were 4 and 2 points, respectively.
\n \n\n \n \nBACKGROUND: Underweight, overweight, and obesity in childhood and adolescence are associated with adverse health consequences throughout the life-course. Our aim was to estimate worldwide trends in mean body-mass index (BMI) and a comprehensive set of BMI categories that cover underweight to obesity in children and adolescents, and to compare trends with those of adults. METHODS: We pooled 2416 population-based studies with measurements of height and weight on 128\u00b79 million participants aged 5 years and older, including 31\u00b75 million aged 5-19 years. We used a Bayesian hierarchical model to estimate trends from 1975 to 2016 in 200 countries for mean BMI and for prevalence of BMI in the following categories for children and adolescents aged 5-19 years: more than 2 SD below the median of the WHO growth reference for children and adolescents (referred to as moderate and severe underweight hereafter), 2 SD to more than 1 SD below the median (mild underweight), 1 SD below the median to 1 SD above the median (healthy weight), more than 1 SD to 2 SD above the median (overweight but not obese), and more than 2 SD above the median (obesity). FINDINGS: Regional change in age-standardised mean BMI in girls from 1975 to 2016 ranged from virtually no change (-0\u00b701 kg/m2 per decade; 95% credible interval -0\u00b742 to 0\u00b739, posterior probability [PP] of the observed decrease being a true decrease=0\u00b75098) in eastern Europe to an increase of 1\u00b700 kg/m2 per decade (0\u00b769-1\u00b735, PP>0\u00b79999) in central Latin America and an increase of 0\u00b795 kg/m2 per decade (0\u00b764-1\u00b725, PP>0\u00b79999) in Polynesia and Micronesia. The range for boys was from a non-significant increase of 0\u00b709 kg/m2 per decade (-0\u00b733 to 0\u00b749, PP=0\u00b76926) in eastern Europe to an increase of 0\u00b777 kg/m2 per decade (0\u00b750-1\u00b706, PP>0\u00b79999) in Polynesia and Micronesia. Trends in mean BMI have recently flattened in northwestern Europe and the high-income English-speaking and Asia-Pacific regions for both sexes, southwestern Europe for boys, and central and Andean Latin America for girls. By contrast, the rise in BMI has accelerated in east and south Asia for both sexes, and southeast Asia for boys. Global age-standardised prevalence of obesity increased from 0\u00b77% (0\u00b74-1\u00b72) in 1975 to 5\u00b76% (4\u00b78-6\u00b75) in 2016 in girls, and from 0\u00b79% (0\u00b75-1\u00b73) in 1975 to 7\u00b78% (6\u00b77-9\u00b71) in 2016 in boys; the prevalence of moderate and severe underweight decreased from 9\u00b72% (6\u00b70-12\u00b79) in 1975 to 8\u00b74% (6\u00b78-10\u00b71) in 2016 in girls and from 14\u00b78% (10\u00b74-19\u00b75) in 1975 to 12\u00b74% (10\u00b73-14\u00b75) in 2016 in boys. Prevalence of moderate and severe underweight was highest in India, at 22\u00b77% (16\u00b77-29\u00b76) among girls and 30\u00b77% (23\u00b75-38\u00b70) among boys. Prevalence of obesity was more than 30% in girls in Nauru, the Cook Islands, and Palau; and boys in the Cook Islands, Nauru, Palau, Niue, and American Samoa in 2016. Prevalence of obesity was about 20% or more in several countries in Polynesia and Micronesia, the Middle East and north Africa, the Caribbean, and the USA. In 2016, 75 (44-117) million girls and 117 (70-178) million boys worldwide were moderately or severely underweight. In the same year, 50 (24-89) million girls and 74 (39-125) million boys worldwide were obese. INTERPRETATION: The rising trends in children's and adolescents' BMI have plateaued in many high-income countries, albeit at high levels, but have accelerated in parts of Asia, with trends no longer correlated with those of adults. FUNDING: Wellcome Trust, AstraZeneca Young Health Programme.
\n \n\n \n \nBACKGROUND: The UN's Sustainable Development Goals (SDGs) are grounded in the global ambition of \"leaving no one behind\". Understanding today's gains and gaps for the health-related SDGs is essential for decision makers as they aim to improve the health of populations. As part of the Global Burden of Diseases, Injuries, and Risk Factors Study 2016 (GBD 2016), we measured 37 of the 50 health-related SDG indicators over the period 1990-2016 for 188 countries, and then on the basis of these past trends, we projected indicators to 2030. METHODS: We used standardised GBD 2016 methods to measure 37 health-related indicators from 1990 to 2016, an increase of four indicators since GBD 2015. We substantially revised the universal health coverage (UHC) measure, which focuses on coverage of essential health services, to also represent personal health-care access and quality for several non-communicable diseases. We transformed each indicator on a scale of 0-100, with 0 as the 2\u00b75th percentile estimated between 1990 and 2030, and 100 as the 97\u00b75th percentile during that time. An index representing all 37 health-related SDG indicators was constructed by taking the geometric mean of scaled indicators by target. On the basis of past trends, we produced projections of indicator values, using a weighted average of the indicator and country-specific annualised rates of change from 1990 to 2016 with weights for each annual rate of change based on out-of-sample validity. 24 of the currently measured health-related SDG indicators have defined SDG targets, against which we assessed attainment. FINDINGS: Globally, the median health-related SDG index was 56\u00b77 (IQR 31\u00b79-66\u00b78) in 2016 and country-level performance markedly varied, with Singapore (86\u00b78, 95% uncertainty interval 84\u00b76-88\u00b79), Iceland (86\u00b70, 84\u00b71-87\u00b76), and Sweden (85\u00b76, 81\u00b78-87\u00b78) having the highest levels in 2016 and Afghanistan (10\u00b79, 9\u00b76-11\u00b79), the Central African Republic (11\u00b70, 8\u00b78-13\u00b78), and Somalia (11\u00b73, 9\u00b75-13\u00b71) recording the lowest. Between 2000 and 2016, notable improvements in the UHC index were achieved by several countries, including Cambodia, Rwanda, Equatorial Guinea, Laos, Turkey, and China; however, a number of countries, such as Lesotho and the Central African Republic, but also high-income countries, such as the USA, showed minimal gains. Based on projections of past trends, the median number of SDG targets attained in 2030 was five (IQR 2-8) of the 24 defined targets currently measured. Globally, projected target attainment considerably varied by SDG indicator, ranging from more than 60% of countries projected to reach targets for under-5 mortality, neonatal mortality, maternal mortality ratio, and malaria, to less than 5% of countries projected to achieve targets linked to 11 indicator targets, including those for childhood overweight, tuberculosis, and road injury mortality. For several of the health-related SDGs, meeting defined targets hinges upon substantially faster progress than what most countries have achieved in the past. INTERPRETATION: GBD 2016 provides an updated and expanded evidence base on where the world currently stands in terms of the health-related SDGs. Our improved measure of UHC offers a basis to monitor the expansion of health services necessary to meet the SDGs. Based on past rates of progress, many places are facing challenges in meeting defined health-related SDG targets, particularly among countries that are the worst off. In view of the early stages of SDG implementation, however, opportunity remains to take actions to accelerate progress, as shown by the catalytic effects of adopting the Millennium Development Goals after 2000. With the SDGs' broader, bolder development agenda, multisectoral commitments and investments are vital to make the health-related SDGs within reach of all populations. FUNDING: Bill & Melinda Gates Foundation.
\n \n\n \n \nBACKGROUND: The Global Burden of Diseases, Injuries, and Risk Factors Study 2016 (GBD 2016) provides a comprehensive assessment of risk factor exposure and attributable burden of disease. By providing estimates over a long time series, this study can monitor risk exposure trends critical to health surveillance and inform policy debates on the importance of addressing risks in context. METHODS: We used the comparative risk assessment framework developed for previous iterations of GBD to estimate levels and trends in exposure, attributable deaths, and attributable disability-adjusted life-years (DALYs), by age group, sex, year, and location for 84 behavioural, environmental and occupational, and metabolic risks or clusters of risks from 1990 to 2016. This study included 481 risk-outcome pairs that met the GBD study criteria for convincing or probable evidence of causation. We extracted relative risk (RR) and exposure estimates from 22\u2008717 randomised controlled trials, cohorts, pooled cohorts, household surveys, census data, satellite data, and other sources, according to the GBD 2016 source counting methods. Using the counterfactual scenario of theoretical minimum risk exposure level (TMREL), we estimated the portion of deaths and DALYs that could be attributed to a given risk. Finally, we explored four drivers of trends in attributable burden: population growth, population ageing, trends in risk exposure, and all other factors combined. FINDINGS: Since 1990, exposure increased significantly for 30 risks, did not change significantly for four risks, and decreased significantly for 31 risks. Among risks that are leading causes of burden of disease, child growth failure and household air pollution showed the most significant declines, while metabolic risks, such as body-mass index and high fasting plasma glucose, showed significant increases. In 2016, at Level 3 of the hierarchy, the three leading risk factors in terms of attributable DALYs at the global level for men were smoking (124\u00b71 million DALYs [95% UI 111\u00b72 million to 137\u00b70 million]), high systolic blood pressure (122\u00b72 million DALYs [110\u00b73 million to 133\u00b73 million], and low birthweight and short gestation (83\u00b70 million DALYs [78\u00b73 million to 87\u00b77 million]), and for women, were high systolic blood pressure (89\u00b79 million DALYs [80\u00b79 million to 98\u00b72 million]), high body-mass index (64\u00b78 million DALYs [44\u00b74 million to 87\u00b76 million]), and high fasting plasma glucose (63\u00b78 million DALYs [53\u00b72 million to 76\u00b73 million]). In 2016 in 113 countries, the leading risk factor in terms of attributable DALYs was a metabolic risk factor. Smoking remained among the leading five risk factors for DALYs for 109 countries, while low birthweight and short gestation was the leading risk factor for DALYs in 38 countries, particularly in sub-Saharan Africa and South Asia. In terms of important drivers of change in trends of burden attributable to risk factors, between 2006 and 2016 exposure to risks explains an 9\u00b73% (6\u00b79-11\u00b76) decline in deaths and a 10\u00b78% (8\u00b73-13\u00b71) decrease in DALYs at the global level, while population ageing accounts for 14\u00b79% (12\u00b77-17\u00b75) of deaths and 6\u00b72% (3\u00b79-8\u00b77) of DALYs, and population growth for 12\u00b74% (10\u00b71-14\u00b79) of deaths and 12\u00b74% (10\u00b71-14\u00b79) of DALYs. The largest contribution of trends in risk exposure to disease burden is seen between ages 1 year and 4 years, where a decline of 27\u00b73% (24\u00b79-29\u00b77) of the change in DALYs between 2006 and 2016 can be attributed to declines in exposure to risks. INTERPRETATION: Increasingly detailed understanding of the trends in risk exposure and the RRs for each risk-outcome pair provide insights into both the magnitude of health loss attributable to risks and how modification of risk exposure has contributed to health trends. Metabolic risks warrant particular policy attention, due to their large contribution to global disease burden, increasing trends, and variable patterns across countries at the same level of development. GBD 2016 findings show that, while it has huge potential to improve health, risk modification has played a relatively small part in the past decade. FUNDING: The Bill & Melinda Gates Foundation, Bloomberg Philanthropies.
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