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Background The health consequences of the use of Swedish snus, including its relationship with mortality, have not been fully established. We investigated the relationship between snus use and all-cause and cause-specific mortality (death due to cardiovascular diseases, cancer diseases and all other reasons, respectively) in a nationwide collaborative pooling project. Methods We followed 169 103 never-smoking men from eight Swedish cohort studies, recruited in 1978–2010. Shared frailty models with random effects at the study level were used in order to estimate adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs) of mortality associated with snus use. Results Exclusive current snus users had an increased risk of all-cause mortality (aHR 1.28, 95% CI 1.20–1.35), cardiovascular mortality (aHR 1.27, 95% CI 1.15–1.41) and other cause mortality (aHR 1.37, 95% CI 1.24–1.52) compared with never-users of tobacco. The risk of cancer mortality was also increased (aHR 1.12, 95% CI 1.00–1.26). These mortality risks increased with duration of snus use, but not with weekly amount. Conclusions Snus use among men is associated with increased all-cause mortality, cardiovascular mortality, with death from other causes and possibly with increased cancer mortality.

ObjectivesAs part of the International Cancer Benchmarking Partnership (ICBP) SURVMARK-2 project, we provide the most recent estimates of colon and rectal cancer survival in seven high-income countries by age and stage at diagnosis.MethodsData from 386 870 patients diagnosed during 2010–2014 from 19 cancer registries in seven countries (Australia, Canada, Denmark, Ireland, New Zealand, Norway and the UK) were analysed. 1-year and 5-year net survival from colon and rectal cancer were estimated by stage at diagnosis, age and country,Results(One1-year) and 5-year net survival varied between (77.1% and 87.5%) 59.1% and 70.9% and (84.8% and 90.0%) 61.6% and 70.9% for colon and rectal cancer, respectively. Survival was consistently higher in Australia, Canada and Norway, with smaller proportions of patients with metastatic disease in Canada and Australia. International differences in (1-year) and 5-year survival were most pronounced for regional and distant colon cancer ranging between (86.0% and 94.1%) 62.5% and 77.5% and (40.7% and 56.4%) 8.0% and 17.3%, respectively. Similar patterns were observed for rectal cancer. Stage distribution of colon and rectal cancers by age varied across countries with marked survival differences for patients with metastatic disease and diagnosed at older ages (irrespective of stage).ConclusionsSurvival disparities for colon and rectal cancer across high-income countries are likely explained by earlier diagnosis in some countries and differences in treatment for regional and distant disease, as well as older age at diagnosis. Differences in cancer registration practice and different staging systems across countries may have impacted the comparisons.

IntroductionLung cancer has a poor prognosis that varies internationally when assessed by the two major histological subgroups (non-small cell (NSCLC) and small cell (SCLC)).Method236 114 NSCLC and 43 167 SCLC cases diagnosed during 2010–2014 in Australia, Canada, Denmark, Ireland, New Zealand, Norway and the UK were included in the analyses. One-year and 3-year age-standardised net survival (NS) was estimated by sex, histological type, stage and country.ResultsOne-year and 3-year NS was consistently higher for Canada and Norway, and lower for the UK, New Zealand and Ireland, irrespective of stage at diagnosis. Three-year NS for NSCLC ranged from 19.7% for the UK to 27.1% for Canada for men and was consistently higher for women (25.3% in the UK; 35.0% in Canada) partly because men were diagnosed at more advanced stages. International differences in survival for NSCLC were largest for regional stage and smallest at the advanced stage. For SCLC, 3-year NS also showed a clear female advantage with the highest being for Canada (13.8% for women; 9.1% for men) and Norway (12.8% for women; 9.7% for men).ConclusionDistribution of stage at diagnosis among lung cancer cases differed by sex, histological subtype and country, which may partly explain observed survival differences. Yet, survival differences were also observed within stages, suggesting that quality of treatment, healthcare system factors and prevalence of comorbid conditions may also influence survival. Other possible explanations include differences in data collection practice, as well as differences in histological verification, staging and coding across jurisdictions.

Serum transthyretin (TTR) may be an early biomarker for Alzheimer's disease and related disorders (ADRD). We investigated associations of TTR measured at baseline with cognitive decline and incident ADRD and whether TTR trajectories differ between ADRD cases and non-cases, over 22 years before diagnosis. A total of 6024 adults aged 45-69 in 1997-1999 were followed up until 2019. TTR was assessed three times, and 297 cases of dementia were recorded. Higher TTR was associated with higher cognitive function at baseline; however, TTR was unrelated to subsequent change in cognitive function. TTR at baseline did not predict ADRD risk (hazard ratio per SD TTR (4.8 mg/dL) = 0.97; 95% confidence interval: 0.94-1.00). Among those later diagnosed with ADRD, there was a marginally steeper downward TTR trajectory than those free of ADRD over follow-up (P=0.050). Our findings suggest TTR is not neuroprotective. The relative decline in TTR level in the preclinical stage of ADRD is likely to be a consequence of disease processes.

Background Cancer-related causes of death (cancer CoD) are the main etiologies of death in cancer patients. Recent increase in survival rates of cancer patients resulted in higher risk of dying from causes other than cancer, called competing causes of death (competing CoD). We aim to characterize competing CoD among cancer patients in Golestan province, Northern Iran. Methods Data on cancer incidence was obtained from the Golestan population-based cancer registry (GPCR) dataset. Data on causes of death was obtained from the Golestan death registry (GDR) dataset. Using a linkage method between the GPCR and GDR dataset, we prepared the study dataset including data on vital status and causes of death in our cancer patients. The proportions of cancer CoD and competing CoD were calculated. Multivariate logistic regression analysis was considered to assess the relationship between competing CoD and other variables. Results Overall, 4,184 cancer patients died in the study population, including 2,488 men (59.9%). Cause of death in 3,455 cases was cancer and 729 cases (17.4%) died due to competing CoD. Ischemic heart disease (40.7%) was the most common competing CoD in our population. Higher survival rate was the strongest variable related to the competing CoD (adjusted OR=1.91; 95%CI: 1.61-2.26). Residence area, age group and year of death were other indicators of competing CoD in our population. Conclusion Our results suggest high rates of competing CoD in our cancer patients. Competing CoD should be mentioned in cancer control planning both in clinical practice as well as in public health policy making. .

We sought to understand the role of stage at diagnosis in observed age disparities in colon cancer survival among people aged 50 to 99 years using population-based cancer registry data from seven high-income countries: Australia, Canada, Denmark, Ireland, New Zealand, Norway and the United Kingdom. We used colon cancer incidence data for the period 2010 to 2014. We estimated the 3-year net survival, as well as the 3-year net survival conditional on surviving at least 6 months and 1 year after diagnosis, by country and stage at diagnosis (categorised as localised, regional or distant) using flexible parametric excess hazard regression models. In all countries, increasing age was associated with lower net survival. For example, 3-year net survival (95% confidence interval) was 81% (80-82) for 50 to 64 year olds and 58% (56-60) for 85 to 99 year olds in Australia, and 74% (73-74) and 39% (39-40) in the United Kingdom, respectively. Those with distant stage colon cancer had the largest difference in colon cancer survival between the youngest and the oldest patients. Excess mortality for the oldest patients with localised or regional cancers was observed during the first 6 months after diagnosis. Older patients diagnosed with localised (and in some countries regional) stage colon cancer who survived 6 months after diagnosis experienced the same survival as their younger counterparts. Further studies examining other prognostic clinical factors such as comorbidities and treatment, and socioeconomic factors are warranted to gain further understanding of the age disparities in colon cancer survival.

Aortic stiffness is associated with an increased risk of cardio- and cerebrovascular disease and mortality and may increase risk of dementia. The aim of the present study is to examine the association between arterial stiffness and cognitive decline in a large prospective cohort study with three repeated cognitive assessment over 7 years of follow-up. Aortic pulse wave velocity (PWV) was measured among 4300 participants (mean ± standard deviation age 65.1 ± 5.2 years) in 2007–2009 and categorized based on the tertiles: (lowest third: 8.91 m/s). A global cognitive score was calculated in 2007–2009, 2012–2013, and 2015–2016 based on responses to memory, reasoning and fluency tests. Standardized global cognitive score (mean = 0, SD = 1) in highest third versus lowest third of PWV category was lower at baseline (− 0.12, 95% CI − 0.18, − 0.06). Accelerated 7-year cognitive decline was observed among individuals with the highest PWV [difference in 7-year cognitive change for highest third versus lowest third PWV: − 0.06, 95% CI − 0.11, − 0.01, P

Aims: Worldwide, smokeless-tobacco use is a major risk factor for oral cancer. Evidence regarding the particular association between Swedish snus use and oral cancer is, however, less clear. We used pooled individual data from the Swedish Collaboration on Health Effects of Snus Use to assess the association between snus use and oral cancer. Methods: A total of 418,369 male participants from nine cohort studies were followed up for oral cancer incidence through linkage to health registers. We used shared frailty models with random effects at the study level, to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) adjusted for confounding factors. Results: During 9,201,647 person-years of observation, 628 men developed oral cancer. Compared to never-snus use, ever-snus use was not associated with oral cancer (adjusted HR 0.90, 95% CI: 0.74, 1.09). There were no clear trends in risk with duration or intensity of snus use, although lower intensity use (⩽ 4 cans/week) was associated with a reduced risk (HR 0.65, 95% CI: 0.45, 0.94). Snus use was not associated with oral cancer among never smokers (HR 0.87, 95% CI: 0.57, 1.32). Conclusions: Swedish snus use does not appear to be implicated in the development of oral cancer in men.

Background There is uncertainty around the health impact and economic costs of the recent slowing of the historical decline in cardiovascular disease (CVD) incidence and the future impact on dementia and disability. Methods Previously validated IMPACT Better Ageing Markov model for England and Wales, integrating English Longitudinal Study of Ageing (ELSA) data for 17,906 ELSA participants followed from 1998 to 2012, linked to NHS Hospital Episode Statistics. Counterfactual design comparing two scenarios: Scenario 1. CVD Plateau—age-specific CVD incidence remains at 2011 levels, thus continuing recent trends. Scenario 2. CVD Fall—age-specific CVD incidence goes on declining, following longer-term trends. The main outcome measures were age-related healthcare costs, social care costs, opportunity costs of informal care, and quality adjusted life years (valued at £60,000 per QALY). Findings The total 10 year cumulative incremental net monetary cost associated with a persistent plateauing of CVD would be approximately £54 billion (95% uncertainty interval £14.3-£96.2 billion), made up of some £13 billion (£8.8-£16.7 billion) healthcare costs, £1.5 billion (-£0.9-£4.0 billion) social care costs, £8 billion (£3.4-£12.8 billion) informal care and £32 billion (£0.3-£67.6 billion) value of lost QALYs. Interpretation After previous, dramatic falls, CVD incidence has recently plateaued. That slowdown could substantially increase health and social care costs over the next ten years. Healthcare costs are likely to increase more than social care costs in absolute terms, but social care costs will increase more in relative terms. Given the links between COVID-19 and cardiovascular health, effective cardiovascular prevention policies need to be revitalised urgently.

Background: Thyroid cancer is the most common type of endocrine cancer. We aimed to determine the incidence rates of thyroid cancer across a 10-year period (2004-2013) in Golestan, Iran. Methods: We obtained the thyroid cancer data from Golestan Population-Based Cancer Registry (GPCR). Age-standardized incidence rates (ASR) were calculated and reported per 100000 person-years. The Joinpoint software was used to assess time trends, and average annual percent changes (AAPCs) and their corresponding 95% confidence intervals (CIs) were reported. Results: Of 326 registered patients, 83 (25.5%) were men and 243 (74.5%) were women. The mean age was 51.3 and 42.6 years for males and females, respectively. Overall, the ASR of thyroid cancer was 2.2 per 100000 person-year (AAPC = 2.76; 95% CI: -3.68 to 9.64). The test of co-incidence showed a statistically significant difference in the incidence of thyroid cancer between men (1.3) and women (3.2) (P < 0.001). According to our results, the ASR of thyroid cancer in western parts of Golestan is higher, including Gorgan and Aliabad cities. Conclusion: Increasing trends in incidence rates of thyroid cancer were found in the Golestan province during the study period, especially in women. We found significantly higher rates of thyroid cancer in women. Geographical diversities were seen in incidence rates of thyroid cancer in the Golestan province. Our results may be helpful for designing further researches to investigate the epidemiological aspects of thyroid cancer in the Golestan province.

Brain and other central nervous system (CNS) tumors represent almost 3% of all new cancer cases worldwide and comprise a heterogeneous group of tumors with varying epidemiologic and clinical characteristics. The aim of this study is to present the distribution and trends in brain and other CNS cancer incidence in Golestan, Iran during a 10-year period.Data on primary brain and other CNS cancers diagnosed between 2004 and 2013 were obtained from the Golestan population-based cancer registry (GPCR) dataset. We computed age-standardized incidence rates (ASRs) per 100000 personyears. In order to assess changes in incidence over time, we calculated the estimated annual percentage change (EAPC) and corresponding 95% confidence intervals (CIs) to detect significant trends.Over the 10-year period (2004-2013), the incidence of brain and other CNS cancer was observed to increase for all ages (EAPC: 1.13, 95% CI: -6.06, 8.87). After 2008, the trends appear to have stabilized. Incidence rates were higher in males than females (ratio: 1.2) and glioblastoma was the most common tumor subtype (15.1% of all malignant tumors).Trends and patterns in the burden of brain and other CNS cancer require careful monitoring alongside future research to increase our understanding of potential risk factors.

Colorectal cancer (CRC) is the third most common cancer worldwide and the fourth most common cause of cancer death. Predictions of the future burden of the disease inform health planners and raise awareness of the need for cancer control action. Data from the World Health Organization (WHO) mortality database for 1989-2016 were used to project colon and rectal cancer mortality rates and number of deaths in 42 countries up to the year 2035, using age-period-cohort (APC) modelling. Mortality rates for colon cancer are predicted to continue decreasing in the majority of included countries from Asia, Europe, North America and Oceania, except Latin America and Caribbean countries. Mortality rates from rectal cancer in general followed those of colon cancer, however rates are predicted to increase substantially in Costa Rica (+73.6%), Australia (+59.2%), United States (+27.8%), Ireland (+24.2%) and Canada (+24.1%). Despite heterogeneous trends in rates, the number of deaths is expected to rise in all countries for both colon and rectal cancer by 60.0% and 71.5% until 2035, respectively, due to population growth and ageing. Reductions in colon and rectal cancer mortality rates are probably due to better accessibility to early detection services and improved specialized care. The expected increase in rectal cancer mortality rates in some countries is worrisome and warrants further investigations.

Summary Background The overall incidence of colorectal cancer is decreasing in many high-income countries, yet analyses in the USA and other high-income countries such as Australia, Canada, and Norway have suggested increasing incidences among adults younger than 50 years. We aimed to examine longitudinal and generational changes in the incidence of colon and rectal cancer in seven high-income countries. Methods We obtained data for the incidence of colon and rectal cancer from 20 population-based cancer registries in Australia, Canada, Denmark, Norway, New Zealand, Ireland, and the UK for the earliest available year until 2014. We used age–period–cohort modelling to assess trends in incidence by age group, period, and birth cohort. We stratified cases by tumour subsite according to the 10th edition of the International Classification of Diseases. Age-standardised incidences were calculated on the basis of the world standard population. Findings An overall decline or stabilisation in the incidence of colon and rectal cancer was noted in all studied countries. In the most recent 10-year period for which data were available, however, significant increases were noted in the incidence of colon cancer in people younger than 50 years in Denmark (by 3·1%; per year), New Zealand (2·9% per year), Australia (2·9% per year), and the UK (1·8% per year). Significant increases in the average annual percentage change in the incidence of rectal cancer were also noted in this age group in Canada (by 3·4% per year), Australia (2·6% per year), and the UK (1·4% per year). Contemporaneously, in people aged 50–74 years, the average annual percentage change in the incidence of colon cancer decreased significantly in Australia (by 1·6% per year), Canada (1·9% per year), and New Zealand (3·4% per year) and of rectal cancer in Australia (2·4% per year), Canada (1·2% per year), and the UK (1·2% per year). Increases in the incidence of colorectal cancer in people younger than 50 years were mainly driven by increases in distal (left) tumours of the colon. In all countries, we noted non-linear cohort effects, which were more pronounced for rectal than for colon cancer. Interpretation We noted a substantial increase in the incidence of colorectal cancer in people younger than 50 years in some of the countries in this study. Future studies are needed to establish the root causes of this rising incidence to enable the development of potential preventive and early-detection strategies. Funding Canadian Partnership Against Cancer, Cancer Council Victoria, Cancer Institute New South Wales, Cancer Research UK, Danish Cancer Society, National Cancer Registry Ireland, the Cancer Society of New Zealand, NHS England, Norwegian Cancer Society, Public Health Agency Northern Ireland, Scottish Government, Western Australia Department of Health, and Wales Cancer Network.

Aims: Although smoking is considered to be an established risk factor for colorectal cancer, the current evidence on the association between smokeless tobacco and colorectal cancer is scant and inconclusive. We used pooled individual data from the Swedish Collaboration on Health Effects of Snus Use to assess this association. Methods: A total of 417,872 male participants from nine cohort studies across Sweden were followed up for incidence of colorectal cancer and death. Outcomes were ascertained through linkage to health registers. We used shared frailty models with random effects at the study level to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). Results: During 7,135,504 person-years of observation, 4170 men developed colorectal cancer. There was no clear association between snus use and colorectal cancer overall. Exclusive current snus users, however, had an increased risk of rectal cancer (HR 1.40: 95% CI 1.09, 1.79). There were no statistically significant associations between snus use and either all-cause or colorectal cancer-specific mortality after colorectal cancer diagnosis. Conclusions: Our findings, from a large sample, do not support any strong relationships between snus use and colorectal cancer risk and survival among men. However, the observed increased risk of rectal cancer is noteworthy, and in merit of further attention.

Although overall colorectal cancer (CRC) incidence rates in the United States are declining, rates among younger persons (age < 55 years) are increasing, particularly among US whites. We assessed how these trends will impact the future burden (up to 2040) of CRC among US blacks and whites using an age-period-cohort model. Over the last four decades (1973 to 2014), CRC incidence rates for all ages (both sexes) have dropped by 6.6% and 33.9% in US blacks and whites, respectively. Yet we predict an upward turn in CRC cancer incidence rates over the next quarter century, particularly among US whites. The age-standardized rates of CRC were 55.4 and 43.2 per 100 000 among US blacks and whites in 2014, respectively, and are projected to be 49.5 and 43.1 in 2040, respectively. Future interventions are needed to reduce the striking differences in CRC incidence between blacks and whites.

INTRODUCTION Sleep duration and quality have been associated with obesity. Sleep disturbance has been reported to be associated with stress and depression among non-obese populations, but these relationships have not been previously examined in the obese population. The objective of the current study was to examine the complex associations among sleep disturbance, quality of life, anxiety, and depression in a patient sample with severe obesity. METHODS Two hundred seventy consecutively recruited patients with a mean body mass index (BMI) of 47.0 kg/m² were studied. The correlation coefficient, multiple linear regressions, and structural equation modeling (SEM) analysis were used to evaluate the association between the Pittsburgh Sleep Quality Index (PSQI), Epworth Sleepiness Scale (ESS), Impact of Weight on Quality of Life-Lite (IWQOL-Lite) and Hospital Anxiety and Depression Scale (HADS). RESULTS The mean (standard deviation; SD) PSQI score was 8.59 (5.11), and mean ESS score was 8.84 (5.79). After controlling for potential confounders, poor sleep quality and excessive daytime sleepiness were found to be significantly associated of all the components of IWQOL-Lite; physical function (β = -0.32, β = -0.27; P < 0.01), self-esteem (β = -0.23, β = -0.30; P < 0.05), sexual-life (β = -0.30, β = -0.35; P < 0.05), public distress (β = -0.39, β = -0.39; P < 0.01), and work (β = -0.26, β = -0.48; P < 0.01). We also found that the PSQI global score had a positive significant association with anxiety (β = 0.29; P = 0.01) and depression (β = 0.31; P = 0.01) components of HADS. CONCLUSION Poor sleep quality was strongly associated with mood disturbance and poor quality of life among extremely obese patients. Future interventions are needed to address sleep disturbance to prevent further development of psychological co-morbidity and potentially worsening of obesity among these individuals.

Smoking and nicotine exposure increase insulin resistance and the risk of type 2 diabetes. Swedish smokeless tobacco (snus) is high in nicotine, and its use is prevalent in Scandinavian countries, but few studies have investigated snus use in relation to diabetes risk.To explore the association between snus use and risk of type 2 diabetes using pooled data from five cohorts.Analyses were based on prospective studies conducted between 1990 and 2013 including 54 531 never-smoking men and 2441 incident cases of type 2 diabetes identified through screening, self-reporting and hospital and prescription registries. Hazard ratios (HRs) and 95% confidence intervals (CIs) were assessed and adjusted for age, body mass index, educational level, alcohol consumption and physical activity.Compared to never users, the HR of type 2 diabetes was 1.15 (95% CI: 1.00-1.32) in current users of snus. In individuals consuming 5-6 boxes per week, the HR was 1.42 (95% CI: 1.07-1.87); in those consuming ≥7 boxes per week, the HR was 1.68 (95% CI: 1.17-2.41). Each additional box of snus consumed per week yielded an HR of 1.08 (95% CI: 1.01-1.16).Our findings indicate that high consumption of snus is a risk factor for type 2 diabetes. The risk was similar to that in smokers, implying that smokers will not reduce their risk of type 2 diabetes by changing to snus use. The results also support the notion that nicotine increases the risk of type 2 diabetes.

Background: Cigarette smoking is associated with a lower risk of Parkinson's disease. It is unclear what constituent of tobacco smoke may lower the risk. Use of Swedish moist smokeless tobacco (snus) can serve as a model to disentangle what constituent of tobacco smoke may lower the risk. The aim of this study was to determine whether snus use was associated with a lower risk of Parkinson's disease. Methods: Individual participant data were collected from seven prospective cohort studies, including 348 601 men. We used survival analysis with multivariable Cox regression to estimate study-specific relative risk of Parkinson's disease due to snus use, and random-effects models to pool estimates in a meta-analysis. The primary analyses were restricted to never-smokers to eliminate the potential confounding effect of tobacco smoking. Results: During a mean follow-up time of 16.1 years, 1199 incident Parkinson's disease cases were identified. Among men who never smoked, ever-snus users had about 60% lower Parkinson's disease risk compared with never-snus users [pooled hazard ratio (HR) 0.41, 95% confidence interval (CI) 0.28-0.61]. The inverse association between snus use and Parkinson's disease risk was more pronounced in current (pooled HR 0.38, 95% CI 0.23-0.63), moderate-heavy amount (pooled HR 0.41, 95% CI 0.19-0.90) and long-term snus users (pooled HR 0.44, 95% CI 0.24-0.83). Conclusions: Non-smoking men who used snus had a substantially lower risk of Parkinson's disease. Results also indicated an inverse dose-response relationship between snus use and Parkinson's disease risk. Our findings suggest that nicotine or other components of tobacco leaves may influence the development of Parkinson's disease.