Occupational exposures and risk of kidney and renal pelvis cancer in the Nordic countries

Munuaisen ja munuaisaltaan kasvaimet ovat merkittävä osa kaikista syövistä. Sekä urologisen onkologian että epidemiologian tieteenaloilla kiinnostaa tietämys munuaissyövän ja munuaisaltaan syövän syistä. Vaikka aihetta on jo tutkittu laajasti, mikään aiemmista tutkimuksista ei ole kattanut kokonaisia väestöjä. Aihepiirin tutkimukset ovat pääasiassa tehty suppeissa tutkimusväestöissä, joten tulosten yleistettävyys on usein ongelmallista. Tämän väitöskirjan tavoitteena oli tunnistaa yhteyksiä työperäisten altisteiden ja munuaissyövän ja munuaisaltaan syövän riskin välillä. Tutkimuksen yksityiskohtaisiin tavoitteisiin vastaamiseksi tehtiin yhteensä viisi tutkimusta (Osatyöt I-V). Ensin tehtiin kohorttitutkimukset, joissa kuvailtiin munuaissyövän (Osatyö I) ja munaisaltaan syövän (Osatyö II) ilmaantuvuuden vaihtelua eri ammattiryhmien välillä Pohjoismaiden väestöissä. Seuraavaksi tulokset vakioitiin tupakointia arvioivalla muuttujalla ja siten tutkittiin muiden tekijöiden kuin tupakan itsenäistä yhteyttä munuaissyövän (Osatyö III) ja munuaisaltaan syövän (Osatyö IV) riskiin. Osatyössä V asetelmana oli upotettu tapaus-verrokki -tutkimus ja siinä arvoitiin ensisijaisesti työperäisen raskasmetalleille (kromi (VI), rauta, nikkeli ja lyijy), hitsauskaasuille altistumisen ja toissijaisesti muiden työperäisten altisteiden mahdollista yhteyttä munuaisen ja munuaisaltaan syöpien riskiin. Tässä tutkimuksessa käytettiin Nordic Occupational Cancer Study (NOCCA) - aineistoa kaikista viidestä Pohjoismaasta. Tutkimusväestöön kuului 14,9 miljoonaa henkilöä (7,4 miljoonaa miestä ja 7,5 miljoonaa naista). Ammattia koskevat tiedot saatiin kansallisista, vuosina 1960-1990 tehdyistä väestölaskennoista. Osatöissä I-IV altistemuuttujana oli ammattinimike. Osatyössä V altistumista arvioitiin tarkemmin NOCCA työaltistusmatriisin avulla. Syövän ilmaantumista tutkimusväestössä seurattiin maastamuuttoon, kuolemaan tai seuraavien vuosien joulukuun 31. päivään saakka: Tanskassa 2003, Islannissa 2004 ja Suomessa ja Ruotsissa 2005. Tiedot kuolemista ja maasta muutosta saatiin kunkin maan väestörekisteristä ja tiedot syöpätapauksista kunkin maan syöpärekisteristä. Mistään näistä maista ei ollut saatavilla yksilötason tietoa tupakointitottumuksista, mutta osatöitä III ja IV varten arvioitiin lineaarisella regressiomallilla tupakoinnin yleisyyttä kussakin ammattiryhmässä NOCCA-aineiston keuhkosyövän vakioidun ilmaantuvuussuhteen (standardized incidence ratio, SIR) perusteella. Osatyössä I oli mukana 85 940 munuaissyöpätapausta. Osatyössä II oli mukana 11 237 munaisaltaan syövän tapausta. Osatöissä III ja IV analyyseihin otettiin mukaan vain miehet. Naisia ei otettu mukaan, koska tupakointitottumukset muuttuivat eri ammattiryhmissä niin epäsäännöllisellä tavalla, että oli vaikeaa arvioida tupakointitapojen kokonaisvaikutusta tietyssä väestössä. Osatyön III aineistossa löydettiin 50 330 munuaissyöpätapausta. Osatyön IV aineistossa löydettiin 6732 munaisaltaan syövän tapausta. Osatyössä V oli mukana 59 778 munaissyövän ja munuaisaltaan syövän tapausta ja 298 890 heille valittua sukupuolen, iän ja maan mukaan kaltaistettua verrokkia. Osatyö V perustui kolmen maan – Islannin, Suomen ja Ruotsin – aineistoon. Norjaa ja Tanskaa ei otettu mukaan, koska yksilötason tietoja ei ollut saatavilla. Osatyössä III havaittiin korkeimmat tupakointivakioidut munuaissyövän ilmaantuvuussuhteet (SIRvak) hammaslääkäreillä (SIRvak 1.32, 95 %:n luottamusväli [conjidence interval, 95%CIJ 1.06-1.62), toimittajilla (SIRvak 1.20, 95%CI 1.00-1.42) ja lääkäreillä (SIRvak 1.19, 95%CI 1.03-1.36). Matalin SIRvak havaittiin metsureilla (SIRvak 0.82, 95%CI 0.76-0.88). Osatyössä IV havaittiin korkeimmat SIRvak -luvut lääkäreillä (SIRvak 1.63, 95%CI 1.16-2.23), taitelijoilla (SIRvak 1.43, 95%CI 1.03-1.94) ja turvallisuusalan työntekijöillä (SIRvak 1.38, 95%CI 1.14-1.65). Matalimmat SIRvak luvut havaittiin metsureilla (SIRvak 0.51, 95%CI 0.38-0.66), maanviljelijöillä (SIRvak 0.76, 95%CI 0.69-0.83) ja kouluttamattomilla rakennusalan työntekijöillä (SIRvak 0.78, 95%CI 0.68-0.90). Osatyössä V millään tutkituista tekijöistä (raskasmetallit ja hitsauskaasut) ei ollut tilastollisesti merkitsevää annos-vastesuhdetta, kun analysoitiin molemmat sukupuolet ja kaikki ikäryhmät yhdessä. Kun analyysi ositettiin diagnoosi-iällä, alle 59-vuotiaiden ryhmässä havaittiin tilastollisesti merkitsevä riski (odds ratio, OR) suurelle nikkelialtistukselle (OR 1.49, 95%CI 1.03-2.17). Lisäksi 59-74-vuotiaiden ryhmässä havaittiin tilastollisesti merkitsevä OR suurelle altistukselle raudalle (OR 1.41, 95%CI 1.07-1.85), kohtalaiselle altistukselle hitsauskaasuille (OR 1.27, 95%CI 1.02-1.56) ja suurelle altistukselle hitsauskaasuille (OR 1.43, 95%CI 1.09-1.89). Yhteenvetona voidaan todeta, että tämän tutkimuksen tulosten mukaan ammatti on yhteydessä munuaissyövän ja munuaisaltaan syövän riskiin. Tupakoimisen yleisyys vaihtelee suuresti ammattiryhmien välillä, mikä selittää paljon ammattiryhmittäistä vaihtelua sekä munuaissyövän että munuaisen altaan syövän ilmaantuvuudessa. Tupakoinnilla vakioitu munuaissyövän ja munuaisen syövän ilmaantuvuus on merkittävästi suurentunut monissa korkean koulutuksen vaativissa ammateissa ja turvallisuusalan työntekijöillä, joiden yhteinen piirre on työn alhainen fyysinen rasittavuus. Raskasmetalleille ja hitsauskaasuille altistumisen ja munaissyövän tai munuaisaltaan syövän välillä ei havaittu mainittavaa yhteyttä. Tämä väitöskirja on toistaiseksi eniten syöpätapauksia sisältävä tutkimusprojekti ammatin yhteydestä munuaissyövän ja munuaisenaltaan syövän ilmaantuvuuteen. Lisäksi se on ensimmäinen projekti, joka hyödyntää kokonaisia väestöjä kattavaa aineistoa, joten tulokset edustavat koko väestöä ja ovat yleistettäviä.Tumors of kidney and renal pelvis are an important component of the overall cancer burden. Knowledge of causes of kidney and renal pelvis cancer is an area of interest both within the field of urological oncology and epidemiology. Although extensive research has been carried out on the topic, no single study exists which deploys whole national populations. Research on the subject has been mostly restricted to limited study populations, and its generalizability is in many cases problematic. The aim of this thesis was to identify associations between occupational exposures and risk of kidney and renal pelvis cancer. To accomplish the specific objectives of the thesis, in total, five studies were conducted (Studies I-V). First, cohort study design was applied to describe the occupational variation in the incidence of kidney cancer (Study I) and renal pelvis cancer (Study II) in the population of the Nordic countries. Next, the independent role of factors other than smoking was estimated, by adjusting with proxy of smoking, for kidney cancer (Study III) and renal pelvis cancer (Study IV). In Study V, nested case-control study design was adopted, to assess associations between occupational exposure to heavy metals (chromium (VI), iron, nickel, lead) and welding fumes, and the risk of kidney and renal pelvis cancer, and to describe other occupational exposures possibly associated with the risk of kidney cancer. This research was conducted based on the data of the Nordic Occupational Cancer Study (NOCCA) encompassing five Nordic countries, namely, Denmark, Iceland, Finland, Norway, and Sweden. Its population included 14.9 million individuals (7.4 million males, and 7.5 million females). Data on occupation (exposure) were leveraged from national population censuses handled in 1960-1990. In Studies I-IV, occupational categories were considered as exposures. In Study V, for the purpose of the detailed exposure estimation, NOCCA Job-Exposure Matrix was used. Cancer incidence in the study population was followed-up until emigration, death, or December 31st of the following year: 2003 in Denmark and Norway, 2004 in Iceland, 2005 in Finland and Sweden. Data on mortality and emigration were retrieved from the Central Population Registries in each country. Data on cancer cases were obtained from the Nordic cancer registries. For none of the countries, information about smoking habits on an individual level was provided. Therefore, in Studies I, II and V, no stratification regarding smoking was applied. However, to examine smoking-adjusted occupational variation in the incidence of kidney cancer, smoking prevalence by occupation was approximated using a model derived with linear regression from the standardized incidence ratio (SIR) of lung cancer, and used in adjustment for smoking (Studies III and IV). In Study I, 85,940 cases of kidney cancer were identified. In Study II, 11,237 cases of the renal pelvis cancers were included. In Studies III and IV, analyses were conducted for males only. Females were not included since in different occupational categories smoking patterns were changing in such an irregular manner that it is hard to estimate the sum effect of the smoking habits in a given population. In Study III, 50,330 cases of kidney cancer were identified. In Study IV, 6,732 cases of renal pelvis cancer were identified. In Study V, there were 59,778 kidney and renal pelvis cancer cases for which 298,890 sex-, age-, and country-matched controls were identified. Study V was based on data from three countries, namely, Iceland, Finland, and Sweden. Norway and Denmark were excluded because of lack of access to the individual level records. In Study III, the highest smoking-adjusted standardized incidence ratios (SIRadj) of kidney cancer were observed among dentists (SIRadj 1.32, 95% confidence interval (CI) 1.06-1.62), journalists (SIRadj 1.20, 95%CI 1.00-1.42), and physicians (SIRadj 1.19, 95%CI 1.03-1.36). The lowest SIRadj was observed among forestry workers (SIRadj 0.82, 95%CI 0.76-0.88). In Study IV, the highest SIRadj were observed among physicians (SIRadj 1.63, 95%CI 1.16-2.23), artistic workers (SIRadj 1.43, 95%CI 1.03-1.94), and public safety workers (SIRadj 1.38, 95%CI 1.14-1.65). The lowest SIRadj were observed among forestry workers (SIRadj 0.51, 95%CI 0.38-0.66), farmers (SIRadj 0.76, 95%CI 0.69- 0.83), and unskilled construction workers (SIRadj 0.78, 95%CI 0.68-0.90). In Study V, in the analysis of odds ratio (OR)for both sexes and all age groups combined, for none of the studied agents (heavy metals and welding fumes), the dose-response trend was statistically significant. In the analysis with stratification by age at the index date (date of diagnosis of the case), in the group of <59 years, OR for the high exposure to nickel was significant (OR 1.49, 95%CI 1.03-2.17). In the group of 59-74 years ORs for the following were statistically significant: high exposure to iron (OR 1.41, 95%CI 1.07-1.85), moderate exposure to welding fumes (OR 1.27, 95%CI 1.02-1.56), and high exposure to welding fumes (OR 1.43, 95%CI 1.09-1.89). In conclusion, the results of this investigation show that there is an association between occupation and the risk of cancers of kidney and renal pelvis. Diverse prevalence of smoking among different occupational categories plays an important role in occupational variation in the incidence of both kidney cancer and renal pelvis cancer. The studies identified that the smoking-adjusted incidence of kidney and renal pelvis cancers is considerably increased among occupations with higher education and in public safety workers. One of the characteristics in many of these occupations is low physical workload. In the nested case-control study, there was no association between exposure to chromium (VI) or lead and the risk of kidney or renal pelvis cancer. This thesis is so far the most comprehensive research project in terms of a number of observed cancer cases dealing with the association between the occupation and incidence of kidney and renal pelvis cancer. Moreover, it is the first project that benefits from data covering the entire national populations, making the presented results population-representative and generalizable

Heavy metals, welding fumes, and other occupational exposures, and the risk of kidney cancer : A population-based nested case-control study in three Nordic countries

Objectives: To determine whether occupational exposure to heavy metals (chromium (VI), iron, nickel, lead) and welding fumes is associated with the risk of kidney cancer and to describe whether other occupational exposures included in the Job Exposure Matrix of the Nordic Occupational Cancer (NOCCA) study are associated with the risk. Materials and methods: Nested case-control study among individuals registered in population censuses in Finland, Iceland, and Sweden in 1960-1990. A total of 59,778 kidney cancer cases, and 298,890 controls matched on sex, age, and country. Cumulative occupational exposures to metals (chromium (VI), iron, nickel, lead), welding fumes, and 24 other occupational exposure covariates, lagged 0, 10, and 20 years. Results: Overall, there was no or very little association between kidney cancer and exposures studied. The risk was elevated in individuals with high exposure to asbestos (OR 1.19, 95%CI 1.08-1.31). The risk was significantly decreased for individuals characterized with high perceived physical workload (OR 0.86, 95%CI 0.82-0.91), high exposure to ultraviolet radiation (OR 0.85, 95%CI 0.79-0.92), and high exposure to wood dust (OR 0.82, 95%CI 0.71-0.94). The risk of kidney cancer under the age of 59 was elevated in individuals with high exposure to nickel (OR 1.49, 95%CI 1.03-2.17). The risk of kidney cancer in age 59-74 years was elevated for individuals with high exposure to iron (OR 1.41, 95%CI 1.07-1.85), and high exposure to welding fumes (OR 1.43, 95%CI 1.09-1.89). Conclusions: The only markedly elevated risks of kidney cancer were seen for the highest exposures of nickel and iron/welding fumes in specific age strata.Peer reviewe

Global, regional and national burden of bladder cancer and its attributable risk factors in 204 countries and territories, 1990–2019: a systematic analysis for the Global Burden of Disease study 2019

Introduction The current study determined the level and trends associated with the incidence, death and disability rates for bladder cancer and its attributable risk factors in 204 countries and territories, from 1990 to 2019, by age, sex and sociodemographic index (SDI; a composite measure of sociodemographic factors). Methods Various data sources from different countries, including vital registration and cancer registries were used to generate estimates. Mortality data and incidence data transformed to mortality estimates using the mortality to incidence ratio (MIR) were used in a cause of death ensemble model to estimate mortality. Mortality estimates were divided by the MIR to produce incidence estimates. Prevalence was calculated using incidence and MIR-based survival estimates. Age-specific mortality and standardised life expectancy were used to estimate years of life lost (YLLs). Prevalence was multiplied by disability weights to estimate years lived with disability (YLDs), while disability-adjusted life years (DALYs) are the sum of the YLLs and YLDs. All estimates were presented as counts and age-standardised rates per 100 000 population. Results Globally, there were 524 000 bladder cancer incident cases (95% uncertainty interval 476 000 to 569 000) and 229 000 bladder cancer deaths (211 000 to 243 000) in 2019. Age-standardised death rate decreased by 15.7% (8.6 to 21.0), during the period 1990–2019. Bladder cancer accounted for 4.39 million (4.09 to 4.70) DALYs in 2019, and the age-standardised DALY rate decreased significantly by 18.6% (11.2 to 24.3) during the period 1990–2019. In 2019, Monaco had the highest age-standardised incidence rate (31.9 cases (23.3 to 56.9) per 100 000), while Lebanon had the highest age-standardised death rate (10.4 (8.1 to 13.7)). Cabo Verde had the highest increase in age-standardised incidence (284.2% (214.1 to 362.8)) and death rates (190.3% (139.3 to 251.1)) between 1990 and 2019. In 2019, the global age-standardised incidence and death rates were higher among males than females, across all age groups and peaked in the 95+ age group. Globally, 36.8% (28.5 to 44.0) of bladder cancer DALYs were attributable to smoking, more so in males than females (43.7% (34.0 to 51.8) vs 15.2% (10.9 to 19.4)). In addition, 9.1% (1.9 to 19.6) of the DALYs were attributable to elevated fasting plasma glucose (FPG) (males 9.3% (1.6 to 20.9); females 8.4% (1.6 to 19.1)). Conclusions There was considerable variation in the burden of bladder cancer between countries during the period 1990–2019. Although there was a clear global decrease in the age-standardised death, and DALY rates, some countries experienced an increase in these rates. National policy makers should learn from these differences, and allocate resources for preventative measures, based on their country-specific estimates. In addition, smoking and elevated FPG play an important role in the burden of bladder cancer and need to be addressed with prevention programmes.publishedVersio

Diabetes mortality and trends before 25 years of age : an analysis of the Global Burden of Disease Study 2019

Background: Diabetes, particularly type 1 diabetes, at younger ages can be a largely preventable cause of death with the correct health care and services. We aimed to evaluate diabetes mortality and trends at ages younger than 25 years globally using data from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019. Methods: We used estimates of GBD 2019 to calculate international diabetes mortality at ages younger than 25 years in 1990 and 2019. Data sources for causes of death were obtained from vital registration systems, verbal autopsies, and other surveillance systems for 1990–2019. We estimated death rates for each location using the GBD Cause of Death Ensemble model. We analysed the association of age-standardised death rates per 100 000 population with the Socio-demographic Index (SDI) and a measure of universal health coverage (UHC) and described the variability within SDI quintiles. We present estimates with their 95% uncertainty intervals. Findings: In 2019, 16 300 (95% uncertainty interval 14 200 to 18 900) global deaths due to diabetes (type 1 and 2 combined) occurred in people younger than 25 years and 73·7% (68·3 to 77·4) were classified as due to type 1 diabetes. The age-standardised death rate was 0·50 (0·44 to 0·58) per 100 000 population, and 15 900 (97·5%) of these deaths occurred in low to high-middle SDI countries. The rate was 0·13 (0·12 to 0·14) per 100 000 population in the high SDI quintile, 0·60 (0·51 to 0·70) per 100 000 population in the low-middle SDI quintile, and 0·71 (0·60 to 0·86) per 100 000 population in the low SDI quintile. Within SDI quintiles, we observed large variability in rates across countries, in part explained by the extent of UHC (r2=0·62). From 1990 to 2019, age-standardised death rates decreased globally by 17·0% (−28·4 to −2·9) for all diabetes, and by 21·0% (–33·0 to −5·9) when considering only type 1 diabetes. However, the low SDI quintile had the lowest decline for both all diabetes (−13·6% [–28·4 to 3·4]) and for type 1 diabetes (−13·6% [–29·3 to 8·9]). Interpretation: Decreasing diabetes mortality at ages younger than 25 years remains an important challenge, especially in low and low-middle SDI countries. Inadequate diagnosis and treatment of diabetes is likely to be major contributor to these early deaths, highlighting the urgent need to provide better access to insulin and basic diabetes education and care. This mortality metric, derived from readily available and frequently updated GBD data, can help to monitor preventable diabetes-related deaths over time globally, aligned with the UN's Sustainable Development Targets, and serve as an indicator of the adequacy of basic diabetes care for type 1 and type 2 diabetes across nations. Funding: Bill & Melinda Gates Foundation.publishedVersionPeer reviewe

Mapping development and health effects of cooking with solid fuels in low-income and middle-income countries, 2000-18 : a geospatial modelling study

Background More than 3 billion people do not have access to clean energy and primarily use solid fuels to cook. Use of solid fuels generates household air pollution, which was associated with more than 2 million deaths in 2019. Although local patterns in cooking vary systematically, subnational trends in use of solid fuels have yet to be comprehensively analysed. We estimated the prevalence of solid-fuel use with high spatial resolution to explore subnational inequalities, assess local progress, and assess the effects on health in low-income and middle-income countries (LMICs) without universal access to clean fuels.Methods We did a geospatial modelling study to map the prevalence of solid-fuel use for cooking at a 5 km x 5 km resolution in 98 LMICs based on 2.1 million household observations of the primary cooking fuel used from 663 population-based household surveys over the years 2000 to 2018. We use observed temporal patterns to forecast household air pollution in 2030 and to assess the probability of attaining the Sustainable Development Goal (SDG) target indicator for clean cooking. We aligned our estimates of household air pollution to geospatial estimates of ambient air pollution to establish the risk transition occurring in LMICs. Finally, we quantified the effect of residual primary solid-fuel use for cooking on child health by doing a counterfactual risk assessment to estimate the proportion of deaths from lower respiratory tract infections in children younger than 5 years that could be associated with household air pollution.Findings Although primary reliance on solid-fuel use for cooking has declined globally, it remains widespread. 593 million people live in districts where the prevalence of solid-fuel use for cooking exceeds 95%. 66% of people in LMICs live in districts that are not on track to meet the SDG target for universal access to clean energy by 2030. Household air pollution continues to be a major contributor to particulate exposure in LMICs, and rising ambient air pollution is undermining potential gains from reductions in the prevalence of solid-fuel use for cooking in many countries. We estimated that, in 2018, 205000 (95% uncertainty interval 147000-257000) children younger than 5 years died from lower respiratory tract infections that could be attributed to household air pollution.Interpretation Efforts to accelerate the adoption of clean cooking fuels need to be substantially increased and recalibrated to account for subnational inequalities, because there are substantial opportunities to improve air quality and avert child mortality associated with household air pollution. Copyright (C) 2022 The Author(s). Published by Elsevier Ltd.Peer reviewe

Spatial, temporal, and demographic patterns in prevalence of smoking tobacco use and attributable disease burden in 204 countries and territories, 1990-2019 : a systematic analysis from the Global Burden of Disease Study 2019

Background Ending the global tobacco epidemic is a defining challenge in global health. Timely and comprehensive estimates of the prevalence of smoking tobacco use and attributable disease burden are needed to guide tobacco control efforts nationally and globally. Methods We estimated the prevalence of smoking tobacco use and attributable disease burden for 204 countries and territories, by age and sex, from 1990 to 2019 as part of the Global Burden of Diseases, Injuries, and Risk Factors Study. We modelled multiple smoking-related indicators from 3625 nationally representative surveys. We completed systematic reviews and did Bayesian meta-regressions for 36 causally linked health outcomes to estimate non-linear dose-response risk curves for current and former smokers. We used a direct estimation approach to estimate attributable burden, providing more comprehensive estimates of the health effects of smoking than previously available. Findings Globally in 2019, 1.14 billion (95% uncertainty interval 1.13-1.16) individuals were current smokers, who consumed 7.41 trillion (7.11-7.74) cigarette-equivalents of tobacco in 2019. Although prevalence of smoking had decreased significantly since 1990 among both males (27.5% [26. 5-28.5] reduction) and females (37.7% [35.4-39.9] reduction) aged 15 years and older, population growth has led to a significant increase in the total number of smokers from 0.99 billion (0.98-1.00) in 1990. Globally in 2019, smoking tobacco use accounted for 7.69 million (7.16-8.20) deaths and 200 million (185-214) disability-adjusted life-years, and was the leading risk factor for death among males (20.2% [19.3-21.1] of male deaths). 6.68 million [86.9%] of 7.69 million deaths attributable to smoking tobacco use were among current smokers. Interpretation In the absence of intervention, the annual toll of 7.69 million deaths and 200 million disability-adjusted life-years attributable to smoking will increase over the coming decades. Substantial progress in reducing the prevalence of smoking tobacco use has been observed in countries from all regions and at all stages of development, but a large implementation gap remains for tobacco control. Countries have a dear and urgent opportunity to pass strong, evidence-based policies to accelerate reductions in the prevalence of smoking and reap massive health benefits for their citizens. Copyright (C) 2021 The Author(s). Published by Elsevier Ltd.Peer reviewe

Spatial, temporal, and demographic patterns in prevalence of chewing tobacco use in 204 countries and territories, 1990-2019 : a systematic analysis from the Global Burden of Disease Study 2019

Interpretation Chewing tobacco remains a substantial public health problem in several regions of the world, and predominantly in south Asia. We found little change in the prevalence of chewing tobacco use between 1990 and 2019, and that control efforts have had much larger effects on the prevalence of smoking tobacco use than on chewing tobacco use in some countries. Mitigating the health effects of chewing tobacco requires stronger regulations and policies that specifically target use of chewing tobacco, especially in countries with high prevalence. Findings In 2019, 273 center dot 9 million (95% uncertainty interval 258 center dot 5 to 290 center dot 9) people aged 15 years and older used chewing tobacco, and the global age-standardised prevalence of chewing tobacco use was 4 center dot 72% (4 center dot 46 to 5 center dot 01). 228 center dot 2 million (213 center dot 6 to 244 center dot 7; 83 center dot 29% [82 center dot 15 to 84 center dot 42]) chewing tobacco users lived in the south Asia region. Prevalence among young people aged 15-19 years was over 10% in seven locations in 2019. Although global agestandardised prevalence of smoking tobacco use decreased significantly between 1990 and 2019 (annualised rate of change: -1 center dot 21% [-1 center dot 26 to -1 center dot 16]), similar progress was not observed for chewing tobacco (0 center dot 46% [0 center dot 13 to 0 center dot 79]). Among the 12 highest prevalence countries (Bangladesh, Bhutan, Cambodia, India, Madagascar, Marshall Islands, Myanmar, Nepal, Pakistan, Palau, Sri Lanka, and Yemen), only Yemen had a significant decrease in the prevalence of chewing tobacco use, which was among males between 1990 and 2019 (-0 center dot 94% [-1 center dot 72 to -0 center dot 14]), compared with nine of 12 countries that had significant decreases in the prevalence of smoking tobacco. Among females, none of these 12 countries had significant decreases in prevalence of chewing tobacco use, whereas seven of 12 countries had a significant decrease in the prevalence of tobacco smoking use for the period. Summary Background Chewing tobacco and other types of smokeless tobacco use have had less attention from the global health community than smoked tobacco use. However, the practice is popular in many parts of the world and has been linked to several adverse health outcomes. Understanding trends in prevalence with age, over time, and by location and sex is important for policy setting and in relation to monitoring and assessing commitment to the WHO Framework Convention on Tobacco Control. Methods We estimated prevalence of chewing tobacco use as part of the Global Burden of Diseases, Injuries, and Risk Factors Study 2019 using a modelling strategy that used information on multiple types of smokeless tobacco products. We generated a time series of prevalence of chewing tobacco use among individuals aged 15 years and older from 1990 to 2019 in 204 countries and territories, including age-sex specific estimates. We also compared these trends to those of smoked tobacco over the same time period. Findings In 2019, 273 & middot;9 million (95% uncertainty interval 258 & middot;5 to 290 & middot;9) people aged 15 years and older used chewing tobacco, and the global age-standardised prevalence of chewing tobacco use was 4 & middot;72% (4 & middot;46 to 5 & middot;01). 228 & middot;2 million (213 & middot;6 to 244 & middot;7; 83 & middot;29% [82 & middot;15 to 84 & middot;42]) chewing tobacco users lived in the south Asia region. Prevalence among young people aged 15-19 years was over 10% in seven locations in 2019. Although global age standardised prevalence of smoking tobacco use decreased significantly between 1990 and 2019 (annualised rate of change: -1 & middot;21% [-1 & middot;26 to -1 & middot;16]), similar progress was not observed for chewing tobacco (0 & middot;46% [0 & middot;13 to 0 & middot;79]). Among the 12 highest prevalence countries (Bangladesh, Bhutan, Cambodia, India, Madagascar, Marshall Islands, Myanmar, Nepal, Pakistan, Palau, Sri Lanka, and Yemen), only Yemen had a significant decrease in the prevalence of chewing tobacco use, which was among males between 1990 and 2019 (-0 & middot;94% [-1 & middot;72 to -0 & middot;14]), compared with nine of 12 countries that had significant decreases in the prevalence of smoking tobacco. Among females, none of these 12 countries had significant decreases in prevalence of chewing tobacco use, whereas seven of 12 countries had a significant decrease in the prevalence of tobacco smoking use for the period. Interpretation Chewing tobacco remains a substantial public health problem in several regions of the world, and predominantly in south Asia. We found little change in the prevalence of chewing tobacco use between 1990 and 2019, and that control efforts have had much larger effects on the prevalence of smoking tobacco use than on chewing tobacco use in some countries. Mitigating the health effects of chewing tobacco requires stronger regulations and policies that specifically target use of chewing tobacco, especially in countries with high prevalence. Copyright (c) 2021 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license.Peer reviewe

Global, regional, and national burden of stroke and its risk factors, 1990–2019: a systematic analysis for the Global Burden of Disease Study 2019

Background Regularly updated data on stroke and its pathological types, including data on their incidence, prevalence, mortality, disability, risk factors, and epidemiological trends, are important for evidence-based stroke care planning and resource allocation. The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) aims to provide a standardised and comprehensive measurement of these metrics at global, regional, and national levels. Methods We applied GBD 2019 analytical tools to calculate stroke incidence, prevalence, mortality, disability-adjusted life-years (DALYs), and the population attributable fraction (PAF) of DALYs (with corresponding 95% uncertainty intervals [UIs]) associated with 19 risk factors, for 204 countries and territories from 1990 to 2019. These estimates were provided for ischaemic stroke, intracerebral haemorrhage, subarachnoid haemorrhage, and all strokes combined, and stratified by sex, age group, and World Bank country income level. Findings In 2019, there were 12·2 million (95% UI 11·0–13·6) incident cases of stroke, 101 million (93·2–111) prevalent cases of stroke, 143 million (133–153) DALYs due to stroke, and 6·55 million (6·00–7·02) deaths from stroke. Globally, stroke remained the second-leading cause of death (11·6% [10·8–12·2] of total deaths) and the third-leading cause of death and disability combined (5·7% [5·1–6·2] of total DALYs) in 2019. From 1990 to 2019, the absolute number of incident strokes increased by 70·0% (67·0–73·0), prevalent strokes increased by 85·0% (83·0–88·0), deaths from stroke increased by 43·0% (31·0–55·0), and DALYs due to stroke increased by 32·0% (22·0–42·0). During the same period, age-standardised rates of stroke incidence decreased by 17·0% (15·0–18·0), mortality decreased by 36·0% (31·0–42·0), prevalence decreased by 6·0% (5·0–7·0), and DALYs decreased by 36·0% (31·0–42·0). However, among people younger than 70 years, prevalence rates increased by 22·0% (21·0–24·0) and incidence rates increased by 15·0% (12·0–18·0). In 2019, the age-standardised stroke-related mortality rate was 3·6 (3·5–3·8) times higher in the World Bank low-income group than in the World Bank high-income group, and the age-standardised stroke-related DALY rate was 3·7 (3·5–3·9) times higher in the low-income group than the high-income group. Ischaemic stroke constituted 62·4% of all incident strokes in 2019 (7·63 million [6·57–8·96]), while intracerebral haemorrhage constituted 27·9% (3·41 million [2·97–3·91]) and subarachnoid haemorrhage constituted 9·7% (1·18 million [1·01–1·39]). In 2019, the five leading risk factors for stroke were high systolic blood pressure (contributing to 79·6 million [67·7–90·8] DALYs or 55·5% [48·2–62·0] of total stroke DALYs), high body-mass index (34·9 million [22·3–48·6] DALYs or 24·3% [15·7–33·2]), high fasting plasma glucose (28·9 million [19·8–41·5] DALYs or 20·2% [13·8–29·1]), ambient particulate matter pollution (28·7 million [23·4–33·4] DALYs or 20·1% [16·6–23·0]), and smoking (25·3 million [22·6–28·2] DALYs or 17·6% [16·4–19·0]). Interpretation The annual number of strokes and deaths due to stroke increased substantially from 1990 to 2019, despite substantial reductions in age-standardised rates, particularly among people older than 70 years. The highest age-standardised stroke-related mortality and DALY rates were in the World Bank low-income group. The fastest-growing risk factor for stroke between 1990 and 2019 was high body-mass index. Without urgent implementation of effective primary prevention strategies, the stroke burden will probably continue to grow across the world, particularly in low-income countries.publishedVersio

Adolescent transport and unintentional injuries: a systematic analysis using the Global Burden of Disease Study 2019

Background: Globally, transport and unintentional injuries persist as leading preventable causes of mortality and morbidity for adolescents. We sought to report comprehensive trends in injury-related mortality and morbidity for adolescents aged 10–24 years during the past three decades. Methods: Using the Global Burden of Disease, Injuries, and Risk Factors 2019 Study, we analysed mortality and disability-adjusted life-years (DALYs) attributed to transport and unintentional injuries for adolescents in 204 countries. Burden is reported in absolute numbers and age-standardised rates per 100 000 population by sex, age group (10–14, 15–19, and 20–24 years), and sociodemographic index (SDI) with 95% uncertainty intervals (UIs). We report percentage changes in deaths and DALYs between 1990 and 2019. Findings: In 2019, 369 061 deaths (of which 214 337 [58%] were transport related) and 31·1 million DALYs (of which 16·2 million [52%] were transport related) among adolescents aged 10–24 years were caused by transport and unintentional injuries combined. If compared with other causes, transport and unintentional injuries combined accounted for 25% of deaths and 14% of DALYs in 2019, and showed little improvement from 1990 when such injuries accounted for 26% of adolescent deaths and 17% of adolescent DALYs. Throughout adolescence, transport and unintentional injury fatality rates increased by age group. The unintentional injury burden was higher among males than females for all injury types, except for injuries related to fire, heat, and hot substances, or to adverse effects of medical treatment. From 1990 to 2019, global mortality rates declined by 34·4% (from 17·5 to 11·5 per 100 000) for transport injuries, and by 47·7% (from 15·9 to 8·3 per 100 000) for unintentional injuries. However, in low-SDI nations the absolute number of deaths increased (by 80·5% to 42 774 for transport injuries and by 39·4% to 31 961 for unintentional injuries). In the high-SDI quintile in 2010–19, the rate per 100 000 of transport injury DALYs was reduced by 16·7%, from 838 in 2010 to 699 in 2019. This was a substantially slower pace of reduction compared with the 48·5% reduction between 1990 and 2010, from 1626 per 100 000 in 1990 to 838 per 100 000 in 2010. Between 2010 and 2019, the rate of unintentional injury DALYs per 100 000 also remained largely unchanged in high-SDI countries (555 in 2010 vs 554 in 2019; 0·2% reduction). The number and rate of adolescent deaths and DALYs owing to environmental heat and cold exposure increased for the high-SDI quintile during 2010–19. Interpretation: As other causes of mortality are addressed, inadequate progress in reducing transport and unintentional injury mortality as a proportion of adolescent deaths becomes apparent. The relative shift in the burden of injury from high-SDI countries to low and low–middle-SDI countries necessitates focused action, including global donor, government, and industry investment in injury prevention. The persisting burden of DALYs related to transport and unintentional injuries indicates a need to prioritise innovative measures for the primary prevention of adolescent injury. Funding: Bill &amp; Melinda Gates Foundation

The global burden of adolescent and young adult cancer in 2019 : a systematic analysis for the Global Burden of Disease Study 2019

Background In estimating the global burden of cancer, adolescents and young adults with cancer are often overlooked, despite being a distinct subgroup with unique epidemiology, clinical care needs, and societal impact. Comprehensive estimates of the global cancer burden in adolescents and young adults (aged 15-39 years) are lacking. To address this gap, we analysed results from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019, with a focus on the outcome of disability-adjusted life-years (DALYs), to inform global cancer control measures in adolescents and young adults. Methods Using the GBD 2019 methodology, international mortality data were collected from vital registration systems, verbal autopsies, and population-based cancer registry inputs modelled with mortality-to-incidence ratios (MIRs). Incidence was computed with mortality estimates and corresponding MIRs. Prevalence estimates were calculated using modelled survival and multiplied by disability weights to obtain years lived with disability (YLDs). Years of life lost (YLLs) were calculated as age-specific cancer deaths multiplied by the standard life expectancy at the age of death. The main outcome was DALYs (the sum of YLLs and YLDs). Estimates were presented globally and by Socio-demographic Index (SDI) quintiles (countries ranked and divided into five equal SDI groups), and all estimates were presented with corresponding 95% uncertainty intervals (UIs). For this analysis, we used the age range of 15-39 years to define adolescents and young adults. Findings There were 1.19 million (95% UI 1.11-1.28) incident cancer cases and 396 000 (370 000-425 000) deaths due to cancer among people aged 15-39 years worldwide in 2019. The highest age-standardised incidence rates occurred in high SDI (59.6 [54.5-65.7] per 100 000 person-years) and high-middle SDI countries (53.2 [48.8-57.9] per 100 000 person-years), while the highest age-standardised mortality rates were in low-middle SDI (14.2 [12.9-15.6] per 100 000 person-years) and middle SDI (13.6 [12.6-14.8] per 100 000 person-years) countries. In 2019, adolescent and young adult cancers contributed 23.5 million (21.9-25.2) DALYs to the global burden of disease, of which 2.7% (1.9-3.6) came from YLDs and 97.3% (96.4-98.1) from YLLs. Cancer was the fourth leading cause of death and tenth leading cause of DALYs in adolescents and young adults globally. Interpretation Adolescent and young adult cancers contributed substantially to the overall adolescent and young adult disease burden globally in 2019. These results provide new insights into the distribution and magnitude of the adolescent and young adult cancer burden around the world. With notable differences observed across SDI settings, these estimates can inform global and country-level cancer control efforts. Copyright (C) 2021 The Author(s). Published by Elsevier Ltd.Peer reviewe