The global, regional, and national burden of colorectal cancer and its attributable risk factors in 195 countries and territories, 1990–2017: a systematic analysis for the Global Burden of Disease Study 2017

Background Data about the global, regional, and country-specific variations in the levels and trends of colorectal cancer are required to understand the impact of this disease and the trends in its burden to help policy makers allocate resources. Here we provide a status report on the incidence, mortality, and disability caused by colorectal cancer in 195 countries and territories between 1990 and 2017. Methods Vital registration, sample vital registration, verbal autopsy, and cancer registry data were used to generate incidence, death, and disability-adjusted life-year (DALY) estimates of colorectal cancer at the global, regional, and national levels. We also determined the association between development levels and colorectal cancer age-standardised DALY rates, and calculated DALYs attributable to risk factors that had evidence of causation with colorectal cancer. All of the estimates are reported as counts and age-standardised rates per 100 000 person-years, with some estimates also presented by sex and 5-year age groups. Findings In 2017, there were 1·8 million (95% UI 1·8–1·9) incident cases of colorectal cancer globally, with an agestandardised incidence rate of 23·2 (22·7–23·7) per 100 000 person-years that increased by 9·5% (4·5–13·5) between 1990 and 2017. Globally, colorectal cancer accounted for 896 000 (876 300–915 700) deaths in 2017, with an agestandardised death rate of 11·5 (11·3–11·8) per 100 000 person-years, which decreased between 1990 and 2017 (–13·5% [–18·4 to –10·0]). Colorectal cancer was also responsible for 19·0 million (18·5–19·5) DALYs globally in 2017, with an age-standardised rate of 235·7 (229·7–242·0) DALYs per 100 000 person-years, which decreased between 1990 and 2017 (–14·5% [–20·4 to –10·3]). Slovakia, the Netherlands, and New Zealand had the highest age-standardised incidence rates in 2017. Greenland, Hungary, and Slovakia had the highest age-standardised death rates in 2017. Numbers of incident cases and deaths were higher among males than females up to the ages of 80–84 years, with the highest rates observed in the oldest age group (≥95 years) for both sexes in 2017. There was a non-linear association between the Socio-demographic Index and the Healthcare Access and Quality Index and age-standardised DALY rates. In 2017, the three largest contributors to DALYs at the global level, for both sexes, were diet low in calcium (20·5% [12·9–28·9]), alcohol use (15·2% [12·1–18·3]), and diet low in milk (14·3% [5·1–24·8]). Interpretation There is substantial global variation in the burden of colorectal cancer. Although the overall colorectal cancer age-standardised death rate has been decreasing at the global level, the increasing age-standardised incidence rate in most countries poses a major public health challenge across the world. The results of this study could be useful for policy makers to carry out cost-effective interventions and to reduce exposure to modifiable risk factors, particularly in countries with high incidence or increasing burde

Marked increase in breast cancer incidence in young women : A 10-year study from Northern Iran, 2004-2013

Introduction: Breast cancer is the most frequent cancer among women worldwide. Breast cancer incidence in young women is a health issue of concern, especially in middle-income countries such as Iran. The aim of this study is to report the breast cancer incidence variations in Golestan province, Iran, over a 10-year period (2004-2013). Methods: We analyzed data from the Golestan Population-based Cancer Registry (GPCR), which is a high-quality cancer registry collecting data on primary cancers based on standard protocols throughout the Golestan province. Age-standardized incidence rates (ASRs) and age-specific incidence rates per 100,000 person-years were calculated. Time trends in ASRs and age-specific rates were evaluated using Joinpoint regressions. The average annual percentage change (AAPC) with correspondence 95% confidence intervals (95%CIs) were calculated. Results: A total of 2106 new breast cancer cases were diagnosed during the study period. Most cases occurred in women living in urban areas: 1449 cases (68%) versus 657 cases (31%) in rural areas. Statistically significant increasing trends were observed over the 10-year study period amongst women of all ages (AAPC = 4.4; 95%CI: 1.2-7.8) as well as amongst women in the age groups 20-29 years (AAPC = 10.0; 95%CI: 1.7-19.0) and 30-39 years (AAPC = 5.1; 95%CI: 1.4-9.0). Conclusion: The incidence of breast cancer increased between 2004 and 2013 in Golestan province amongst all age groups, and in particular amongst women aged 20-39 years. Breast cancer should be considered a high priority for health policy making in our community.Peer reviewe

Ethical issues in cluster randomized trials conducted in low- and middle-income countries: an analysis of two case studies.

BACKGROUND: Cluster randomized trials are common in health research in low- and middle-income countries raising issues that challenge interpretation of standard ethical guidelines. While the Ottawa Statement on the ethical design and conduct of cluster randomized trials provides guidance for researchers and research ethics committees, it does not explicitly focus on low- and middle-income settings. MAIN BODY: In this paper, we use the lens of the Ottawa Statement to analyze two cluster randomized trials conducted in low- and middle-income settings in order to identify gaps or ethical issues requiring further analysis and guidance. The PolyIran trial was a parallel-arm, cluster trial examining the effectiveness of a polypill for prevention of cardiovascular disease in Golestan province, Iran. The PASTAL trial was an adaptive, multistage, parallel-arm, cluster trial evaluating the effect of incentives for human immunodeficiency virus self-testing and follow-up on male partners of pregnant women in Malawi. Through an in-depth case analysis of these two studies we highlight several issues in need of further exploration. First, standards for verbal consent and waivers of consent require methods for operationalization if they are to be employed consistently. Second, the appropriate choice of a control arm remains contentious. Particularly in the case of implementation interventions, locally available care is required as the comparator to address questions of comparative effectiveness. However, locally available care might be lower than standards set out in national guidelines. Third, while the need for access to effective interventions post-trial is widely recognized, it is often not possible to guarantee this upfront. Clarity on what is required of researchers and sponsors is needed. Fourth, there is a pressing need for ethics education and capacity building regarding cluster randomized trials in these settings. CONCLUSION: We identify four issues in cluster randomized trials conducted in low- and middle-income countries for which further ethical analysis and guidance is required

Association between heavy metals and colon cancer: an ecological study based on geographical information systems in North-Eastern Iran

Background: Colorectal cancer has increased in Middle Eastern countries and exposure to environmental pollutants such as heavy metals has been implicated. However, data linking them to this disease are generally lacking. This study aimed to explore the spatial pattern of age-standardized incidence rate (ASR) of colon cancer and its potential association with the exposure level of the amount of heavy metals existing in rice produced in north-eastern Iran. Methods: Cancer data were drawn from the Iranian population-based cancer registry of Golestan Province, northeastern Iran. Samples of 69 rice milling factories were analysed for the concentration levels of cadmium, nickel, cobalt, copper, selenium, lead and zinc. The inverse distance weighting (IDW) algorithm was used to interpolate the concentration of this kind of heavy metals on the surface of the study area. Exploratory regression analysis was conducted to build ordinary least squares (OLS) models including every possible combination of the candidate explanatory variables and chose the most useful ones to show the association between heavy metals and the ASR of colon cancer. Results: The highest concentrations of heavy metals were found in the central part of the province and particularly counties with higher amount of cobalt were shown to be associated with higher ASR of men with colon cancer. In contrast, selenium concentrations were higher in areas with lower ASR of colon cancer in men. A significant regression equation for men with colon cancer was found (F(4,137) = 38.304, P < .000) with an adjusted R2 of 0.77. The predicted ASR of men colon cancer was − 58.36 with the coefficients for cobalt = 120.33; cadmium = 80.60; selenium = − 6.07; nickel = − 3.09; and zinc = − 0.41. The association of copper and lead with colon cancer in men was not significant. We did not find a significant outcome for colon cancer in women. Conclusion: Increased amounts of heavy metals in consumed rice may impact colon cancer incidence, both positively and negatively. While there were indications of an association between high cobalt concentrations and an increased risk for colon cancer, we found that high selenium concentrations might instead decrease the risk. Further investigations are needed to clarify if there are ecological or other reasons for these discrepancies. Regular monitoring of the amount of heavy metals in consumed rice is recommended.This study was supported by Golestan University of Medical Sciences (grant number of 90–10–1-30209)

The global, regional, and national burden of oesophageal cancer and its attributable risk factors in 195 countries and territories, 1990–2017: a systematic analysis for the Global Burden of Disease Study 2017

Background Oesophageal cancer is a common and often fatal cancer that has two main histological subtypes: oesophageal squamous cell carcinoma and oesophageal adenocarcinoma. Updated statistics on the incidence and mortality of oesophageal cancer, and on the disability-adjusted life-years (DALYs) caused by the disease, can assist policy makers in allocating resources for prevention, treatment, and care of oesophageal cancer. We report the latest estimates of these statistics for 195 countries and territories between 1990 and 2017, by age, sex, and Socio-demographic Index (SDI), using data from the Global Burden of Diseases, Injuries, and Risk Factors Study 2017 (GBD). Methods We used data from vital registration systems, vital registration-samples, verbal autopsy records, and cancer registries, combined with relevant modelling, to estimate the mortality, incidence, and burden of oesophageal cancer from 1990 to 2017. Mortality-to-incidence ratios (MIRs) were estimated and fed into a Cause of Death Ensemble model (CODEm) including risk factors. MIRs were used for mortality and non-fatal modelling. Estimates of DALYs attributable to the main risk factors of oesophageal cancer available in GBD were also calculated. The proportion of oesophageal squamous cell carcinoma to all oesophageal cancers was extracted by use of publicly available data, and its variation was examined against SDI, the Healthcare Access and Quality (HAQ) Index, and available risk factors in GBD that are specific for oesophageal squamous cell carcinoma (eg, unimproved water source and indoor air pollution) and for oesophageal adenocarcinoma (gastro-oesophageal reflux disease). Findings There were 473 000 (95% uncertainty interval [95% UI] 459 000–485 000) new cases of oesophageal cancer and 436 000 (425 000–448 000) deaths due to oesophageal cancer in 2017. Age-standardised incidence was 5·9 (5·7–6·1) per 100 000 population and age-standardised mortality was 5·5 (5·3–5·6) per 100 000. Oesophageal cancer caused 9·78 million (9·53–10·03) DALYs, with an age-standardised rate of 120 (117–123) per 100 000 population. Between 1990 and 2017, age-standardised incidence decreased by 22·0% (18·6–25·2), mortality decreased by 29·0% (25·8–32·0), and DALYs decreased by 33·4% (30·4–36·1) globally. However, as a result of population growth and ageing, the total number of new cases increased by 52·3% (45·9–58·9), from 310 000 (300 000–322 000) to 473 000 (459 000–485 000); the number of deaths increased by 40·0% (34·1–46·3), from 311 000 (301 000–323 000) to 436 000 (425 000–448 000); and total DALYs increased by 27·4% (22·1–33·1), from 7·68 million (7·42–7·97) to 9·78 million (9·53–10·03). At the national level, China had the highest number of incident cases (235 000 [223 000–246 000]), deaths (213 000 [203 000–223 000]), and DALYs (4·46 million [4·25–4·69]) in 2017. The highest national-level age-standardised incidence rates in 2017 were observed in Malawi (23·0 [19·4–26·5] per 100 000 population) and Mongolia (18·5 [16·4–20·8] per 100 000). In 2017, age-standardised incidence was 2·7 times higher, mortality 2·9 times higher, and DALYs 3·0 times higher in males than in females. In 2017, a substantial proportion of oesophageal cancer DALYs were attributable to known risk factors: tobacco smoking (39·0% [35·5–42·2]), alcohol consumption (33·8% [27·3–39·9]), high BMI (19·5% [6·3–36·0]), a diet low in fruits (19·1% [4·2–34·6]), and use of chewing tobacco (7·5% [5·2–9·6]). Countries with a low SDI and HAQ Index and high levels of indoor air pollution had a higher proportion of oesophageal squamous cell carcinoma to all oesophageal cancer cases than did countries with a high SDI and HAQ Index and with low levels of indoor air pollution. Interpretation Despite reductions in age-standardised incidence and mortality rates, oesophageal cancer remains a major cause of cancer mortality and burden across the world. Oesophageal cancer is a highly fatal disease, requiring increased primary prevention efforts and, possibly, screening in some high-risk areas. Substantial variation exists in age-standardised incidence rates across regions and countries, for reasons that are unclear.publishedVersio

Effectiveness of polypill for primary and secondary prevention of cardiovascular diseases (PolyIran):a pragmatic, cluster-randomised trial

Background: A fixed-dose combination therapy (polypill strategy) has been proposed as an approach to reduce the burden of cardiovascular disease, especially in low-income and middle-income countries (LMICs). The PolyIran study aimed to assess the effectiveness and safety of a four-component polypill including aspirin, atorvastatin, hydrochlorothiazide, and either enalapril or valsartan for primary and secondary prevention of cardiovascular disease. Methods: The PolyIran study was a two-group, pragmatic, cluster-randomised trial nested within the Golestan Cohort Study (GCS), a cohort study with 50 045 participants aged 40�75 years from the Golestan province in Iran. Clusters (villages) were randomly allocated (1:1) to either a package of non-pharmacological preventive interventions alone (minimal care group) or together with a once-daily polypill tablet (polypill group). Randomisation was stratified by three districts (Gonbad, Aq-Qala, and Kalaleh), with the village as the unit of randomisation. We used a balanced randomisation algorithm, considering block sizes of 20 and balancing for cluster size or natural log of the cluster size (depending on the skewness within strata). Randomisation was done at a fixed point in time (Jan 18, 2011) by statisticians at the University of Birmingham (Birmingham, UK), independent of the local study team. The non-pharmacological preventive interventions (including educational training about healthy lifestyle�eg, healthy diet with low salt, sugar, and fat content, exercise, weight control, and abstinence from smoking and opium) were delivered by the PolyIran field visit team at months 3 and 6, and then every 6 months thereafter. Two formulations of polypill tablet were used in this study. Participants were first prescribed polypill one (hydrochlorothiazide 12·5 mg, aspirin 81 mg, atorvastatin 20 mg, and enalapril 5 mg). Participants who developed cough during follow-up were switched by a trained study physician to polypill two, which included valsartan 40 mg instead of enalapril 5 mg. Participants were followed up for 60 months. The primary outcome�occurrence of major cardiovascular events (including hospitalisation for acute coronary syndrome, fatal myocardial infarction, sudden death, heart failure, coronary artery revascularisation procedures, and non-fatal and fatal stroke)�was centrally assessed by the GCS follow-up team, who were masked to allocation status. We did intention-to-treat analyses by including all participants who met eligibility criteria in the two study groups. The trial was registered with ClinicalTrials.gov, number NCT01271985. Findings: Between Feb 22, 2011, and April 15, 2013, we enrolled 6838 individuals into the study�3417 (in 116 clusters) in the minimal care group and 3421 (in 120 clusters) in the polypill group. 1761 (51·5) of 3421 participants in the polypill group were women, as were 1679 (49·1) of 3417 participants in the minimal care group. Median adherence to polypill tablets was 80·5 (IQR 48·5�92·2). During follow-up, 301 (8·8) of 3417 participants in the minimal care group had major cardiovascular events compared with 202 (5·9) of 3421 participants in the polypill group (adjusted hazard ratio HR 0·66, 95% CI 0·55�0·80). We found no statistically significant interaction with the presence (HR 0·61, 95% CI 0·49�0·75) or absence of pre-existing cardiovascular disease (0·80; 0·51�1·12; pinteraction=0·19). When restricted to participants in the polypill group with high adherence, the reduction in the risk of major cardiovascular events was even greater compared with the minimal care group (adjusted HR 0·43, 95% CI 0·33�0·55). The frequency of adverse events was similar between the two study groups. 21 intracranial haemorrhages were reported during the 5 years of follow-up�ten participants in the polypill group and 11 participants in the minimal care group. There were 13 physician-confirmed diagnoses of upper gastrointestinal bleeding in the polypill group and nine in the minimal care group. Interpretation: Use of polypill was effective in preventing major cardiovascular events. Medication adherence was high and adverse event numbers were low. The polypill strategy could be considered as an additional effective component in controlling cardiovascular diseases, especially in LMICs. Funding: Tehran University of Medical Sciences, Barakat Foundation, and Alborz Darou. © 2019 World Health Organization. Published by Elsevier Ltd/Inc/BV. All rights reserved

Global Burden of Multiple Myeloma ASystematic Analysis for the Global Burden of Disease Study 2016

Introduction: Multiple myeloma (MM) is a plasma cell neoplasm with substantial morbidity and mortality. A comprehensive description of the global burden of MM is needed to help direct health policy, resource allocation, research, and patient care.Objective: To describe the burden of MM and the availability of effective therapies for 21 world regions and 195 countries and territories from 1990 to 2016.Design and Setting: We report incidence, mortality, and disability-adjusted life-year (DALY) estimates from the Global Burden of Disease 2016 study. Data sources include vital registration system, cancer registry, drug availability, and survey data for stem cell transplant rates. We analyzed the contribution of aging, population growth, and changes in incidence rates to the overall change in incident cases from 1990 to 2016 globally, by sociodemographic index (SDI) and by region. We collected data on approval of lenalidomide and bortezomib worldwide.Main Outcomes and Measures: Multiple myeloma mortality; incidence; years lived with disabilities; years of life lost; and DALYs by age, sex, country, and year.Results: Worldwide in 2016 there were 138 509 (95% uncertainty interval [UI], 121 000-155 480) incident cases of MM with an age-standardized incidence rate (ASIR) of 2.1 per 100 000 persons (95% UI, 1.8-2.3). Incident cases from 1990 to 2016 increased by 126% globally and by 106% to 192% for all SDI quintiles. The 3 world regions with the highest ASIR of MM were Australasia, North America, and Western Europe. Multiple myeloma caused 2.1 million (95% UI, 1.9-2.3 million) DALYs globally in 2016. Stem cell transplantation is routinely available in higher-income countries but is lacking in sub-Saharan Africa and parts of the Middle East. In 2016, lenalidomide and bortezomib had been approved in 73 and 103 countries, respectively.Conclusions and Relevance: Incidence of MM is highly variable among countries but has increased uniformly since 1990, with the largest increase in middle and low-middle SDI countries. Access to effective care is very limited in many countries of low socioeconomic development, particularly in sub-Saharan Africa. Global health policy priorities for MM are to improve diagnostic and treatment capacity in low and middle income countries and to ensure affordability of effective medications for every patient. Research priorities are to elucidate underlying etiological factors explaining the heterogeneity in myeloma incidence

Disability-adjusted life-years (DALYs) for 315 diseases and injuries and healthy life expectancy (HALE) in Iran and its neighboring countries, 1990–2015

BACKGROUND: Summary measures of health are essential in making estimates of health status that are comparable across time and place. They can be used for assessing the performance of health systems, informing effective policy making, and monitoring the progress of nations toward achievement of sustainable development goals. The Global Burden of Diseases, Injuries, and Risk Factors Study 2015 (GBD 2015) provides disability-adjusted life-years (DALYs) and healthy life expectancy (HALE) as main summary measures of health. We assessed the trends of health status in Iran and 15 neighboring countries using these summary measures. METHODS: We used the results of GBD 2015 to present the levels and trends of DALYs, life expectancy (LE), and HALE in Iran and its 15 neighboring countries from 1990 to 2015. For each country, we assessed the ratio of observed levels of DALYs and HALE to those expected based on socio-demographic index (SDI), an indicator composed of measures of total fertility rate, income per capita, and average years of schooling. RESULTS: All-age numbers of DALYs reached over 19 million years in Iran in 2015. The all-age number of DALYs has remained stable during the past two decades in Iran, despite the decreasing trends in all-age and age-standardized rates. The all-cause DALY rates decreased from 47,200 in 1990 to 28,400 per 100,000 in 2015. The share of non-communicable diseases in DALYs increased in Iran (from 42% to 74%) and all of its neighbors between 1990 and 2015; the pattern of change is similar in almost all 16 countries. The DALY rates for NCDs and injuries in Iran were higher than global rates and the average rate in High Middle SDI countries, while those for communicable, maternal, neonatal, and nutritional disorders were much lower in Iran. Among men, cardiovascular diseases ranked first in all countries of the region except for Bahrain. Among women, they ranked first in 13 countries. Life expectancy and HALE show a consistent increase in all countries. Still, there are dissimilarities indicating a generally low LE and HALE in Afghanistan and Pakistan and high expectancy in Qatar, Kuwait, and Saudi Arabia. Iran ranked 11th in terms of LE at birth and 12th in terms of HALE at birth in 1990 which improved to 9th for both metrics in 2015. Turkey and Iran had the highest increase in LE and HALE from 1990 to 2015 while the lowest increase was observed in Armenia, Pakistan, Kuwait, Kazakhstan, Russia, and Iraq. CONCLUSIONS: The levels and trends in causes of DALYs, life expectancy, and HALE generally show similarities between the 16 countries, although differences exist. The differences observed between countries can be attributed to a myriad of determinants, including social, cultural, ethnic, religious, political, economic, and environmental factors as well as the performance of the health system. Investigating the differences between countries can inform more effective health policy and resource allocation. Concerted efforts at national and regional levels are required to tackle the emerging burden of non-communicable diseases and injuries in Iran and its neighbors