Cardiovascular mortality in a Western Asian country: results from the Iran Cohort Consortium.

OBJECTIVES: Cardiovascular mortality in Western Asia is high and still rising. However, most data documented on risk prediction has been derived from Western countries and few population-based cohort studies have been conducted in this region. The current study aimed to present the process of pooling data and cardiovascular disease (CVD) mortality incidences for four Iranian cohorts. METHODS: From the Iran Cohort Consortium, the Golestan Cohort Study (GCS), Tehran Lipid and Glucose Study, Isfahan Cohort Study (ICS) and the Shahroud Eye Cohort Study (ShECS) were eligible for the current study since they had appropriate data and follow-up visits. Age-standardised CVD mortality rates were estimated for ages 40-80 and 40-65 years. Cox regression was used to compare mortalities among cohorts. Adjusted marginal rates were calculated using Poisson regression. RESULTS: Overall, 61 291 participants (34 880 women) aged 40-80 years, free of CVD at baseline, were included. During 504 606 person-years of follow-up, 1981 CVD deaths (885 women) occurred. Age-standardised/sex-standardised premature CVD mortality rates were estimated from 133 per 100 000 person-years (95% CI 81 to 184) in ShECS to 366 (95% CI 342 to 389) in the GCS. Compared with urban women, rural women had higher CVD mortality in the GCS but not in the ICS. The GCS population had a higher risk of CVD mortality, compared with the others, adjusted for conventional CVD risk factors. CONCLUSIONS: The incidence of CVD mortality is high with some differences between urban and rural cohorts in Iran as a Western Asian country. Pooling data facilitates the opportunity to globally evaluate risk prediction models.

Pars cohort study of non-communicable diseases in Iran: protocol and preliminary results.

OBJECTIVES: The pars cohort study (PCS) is a 10-year cohort study aiming to investigate the burden and the major risk factors of non-communicable diseases, and to establish a setting to launch interventions for prevention of these diseases and controlling their risk factors. METHODS: All inhabitants of Valashahr district in South of Iran, aged 40-75 years, were invited to undergo interviews and physical examination, and to provide biological samples. A total of 9264 invitees accepted to participate in the study (95 % participation rate) and were recruited from 2012 to 2014. Active follow-up was also carried out after 12 months. RESULTS: About 46 % of participants were male and 54 % were female. About 14.0 % of the participants were current smokers and 8.4 % were ever opium users. The prevalence of overweight and obesity were 37.3 and 18.2 %, respectively. The prevalence of hypertension was 26.9 %. A total of 49 participants died during a median follow-up of one year. CONCLUSIONS: PCS with its large scale and wealth of socio-economic and medical data can be a unique platform for studying the etiology of non-communicable diseases and effective interventions in Iran.

Reliability Analysis of a Newly Developed Questionnaire for Quality Control of Follow-up Visits in PolyIran Study.

BACKGROUND: The PolyIran study is a large-scale pragmatic cluster randomized controlled trial of fixed-dose combination therapy (Polypill) for prevention of cardiovascular diseases (CVD) in Iran. The PolyIran Quality Control Program (PIQCP) including a new questionnaire was developed to assess the quality of data collection during follow-up visits. The aim of this study was to assess the inter-rater reliability of PIQCP questionnaire. METHODS: The study was conducted in 26 (11%) randomly selected clusters (from a total of 236 PolyIran clusters). All participants within these 26 clusters were enrolled. The quality scores were measured according to the PIQCP guidelines by two independent raters. The intraclass correlation coefficients (ICC) were measured. In addition, the quality scores were categorized into good (70%) and poor (<70%). The kappa coefficient was used to assess inter-rater agreement for this categorical quality scores. RESULTS: A total number of 945 PolyIran participants were enrolled of which, 501 (53%) were from intervention arm. In 934 participants (98.8%), the quality score could be successfully identified by both raters. The ICC (95%CI) of the overall quality scores was 0.985 (0.983-0.987). It was 0.976 (0.972-0.980) and 0.988 (0.986-0.990) in intervention and control arms, respectively. We found excellent agreement between the two raters in identifying participants with good and poor quality scores (kappa = 0.988, P < 0.001). The kappa values were 0.972 (P < 0.001) and 1.000 (P < 0.001) in intervention and control arms, respectively. DISCUSSION: Our results suggested that the PIQCP questionnaire is a reliable tool for assessing quality of data collection in PolyIran follow-up visits. Using this measure will help us in efficient monitoring of the PolyIran follow-ups and may ensure high quality data.

Burden of Gastrointestinal and Liver Diseases in Middle East and North Africa: Results of Global Burden of Diseases Study from 1990 to 2010.

BACKGROUND Gastrointestinal and liver diseases (GILDs) are major causes of death and disability in Middle East and North Africa (MENA). However, they have different patterns in countries with various geographical, cultural, and socio-economic status. We aimed to compare the burden of GILDs in Iran with its neighboring countries using the results of the Global Burden of Disease (GBD) Study in 2010. METHODS Classic metrics of GBD have been used including: age-standardized rates (ASRs) of death, years of life lost due to premature death (YLL), years of life lost due to disability (YLD), and disability adjusted life years (DALY). All countries neighboring Iran have been selected. In addition, all other countries classified in the MENA region were included. Five major groups of gastrointestinal and hepatic diseases were studied including: infections of gastrointestinal tract, gastrointestinal and pancreatobilliary cancers, acute hepatitis, cirrhosis, and other digestive diseases. RESULTS The overall burden of GILDs is highest in Afghanistan, Pakistan, and Egypt. Diarrheal diseases have been replaced by gastrointestinal cancers and cirrhosis in most countries in the region. However, in a number of countries including Afghanistan, Pakistan, Turkmenistan, Egypt, and Yemen, communicable GILDs are still among top causes of mortality and morbidity in addition to non-communicable GILDs and cancers. These countries are experiencing the double burden. In Iran, burden caused by cancers of stomach and esophagus are considerably higher than other countries. Diseases that are mainly diagnosed in outpatient settings have not been captured by GBD. CONCLUSION Improving the infrastructure of health care system including cancer registries and electronic recording of outpatient care is a necessity for better surveillance of GILDs in MENA. In contrast to expensive treatment, prevention of most GILDs is feasible and inexpensive. The health care systems in the region can be strengthened for prevention and control.

Trend of Gastrointestinal and Liver Diseases in Iran: Results of the Global Burden of Disease Study, 2010.

BACKGROUND The general pattern of epidemiologic transition from communicable to noncommunicable diseases is also observed for gastrointestinal and liver diseases (GILD), which constitute a heterogeneous array of causes of death and disability. We aimed to describe the trend of GILD in Iran based on the global burden of disease (GBD2010) study from 1990 to 2010. METHODS The trend of number of deaths, disability, adjusted life years (DALYs) and their age-standardized rates caused by 5 major GILD have been reported. The change in the rankings of major causes of death and DALY has been described as well. RESULTS The age standardized rates of death and DALYs in both sexes have decreased from 1990 to 2010 for most GILD. The most prominent decreases in death rates are observed for diarrheal diseases, gastritis and duodenitis, and peptic ulcer disease. Positive trends are observed for liver cancer, pancreatic cancer, and gall bladder cancer. Diarrheal diseases have retained their 1st rank among children under 5. Among adults, decreased ranks are observed for diarrheal diseases, appendicitis, gastritis and duodenitis, gall bladder diseases, pancreatitis, and all types of cirrhosis. The trends in age standardized rates of DALYs, deaths, and YLLs are negative for almost all GILD, and especially for diarrheal diseases. However, there is no upward or downward trend in rates of years lost due to disability (YLDs) for most diseases. Total numbers of DALYs and deaths due to acute hepatitis C, stomach cancer, and liver cancers are rising. The total DALYs due to overall digestive diseases except cirrhosis and DALYs due to cirrhosis are both somehow stable. No data has been reported for GILD that are mainly diagnosed in outpatient settings, including gastroesophageal reflux disease, irritable bowel syndrome, and non-alcoholic fatty liver disease. CONCLUSION The results of GBD 2010 demonstrate that the rates of most GILD are decreasing in Iran but total DALYs are somehow stable. However, as diseases detected in outpatient settings have not been captured, the burden of GILD seems to be underestimated. Population-based studies at national level are required for accurate reports.

Burden of Gastrointestinal and Liver Diseases in Iran: Estimates Based on the Global Burden of Disease, Injuries, and Risk Factors Study, 2010.

BACKGROUND Gastrointestinal and liver diseases (GILD) constitute a noteworthy portion of causes of death and disability in Iran. However, data on their prevalence and burden is sparse in Iran. The Global Burden of Disease (GBD) study in 2010 has provided invaluable comprehensive data on the burden of GILD in Iran. METHODS Estimations of death, years of life lost due to premature death (YLL), years of life lost due to disability (YLD), disability-adjusted life years (DALY), life expectancy, and healthy life expectancy have been reported for 291 diseases, 67 risk factors, 1160 sequelae, for both sexes and 19 age groups, form 1990 to 2010 for 187 countries. In the current paper, 5 major categories of gastrointestinal (GI) and liver diseases have been investigated as follows: GI infectious diseases, GI and liver cancers, liver infections, chronic end stage liver disease, and other digestive diseases. RESULTS Among women, 7.6% of all deaths and 3.9% of all DALYs were due to digestive and liver diseases in 2010. The respective figures in men were 7.8% of deaths and 4.6% of DALYs. The most important cause of death among children under 5 is diarrhea. Among adults between 15 to 49 years old, the main causes of death are GI and liver cancers and cirrhosis, while diarrhea still remains a major cause of DALY. Among adults 50 years and above, GI and liver cancers and cirrhosis are the main causes of both deaths and DALYs. Gastritis and duodenitis, diarrheal diseases, gall bladder and bile duct diseases, acute hepatitis A, peptic ulcer disease, appendicitis, and acute hepatitis A mainly cause disability rather than death. CONCLUSION GBD study provides invaluable source of data on burden of GILD in Iran. However, there exist limitations, namely overestimation of burden of liver cancer and underestimation of the burden of GI diseases that are usually diagnosed in outpatient settings. The collaboration of scientists across the world and specifically those from developing countries is necessary for improving the accuracy of future updates of GBD in these countries.

National and sub-national prevalence, trend, and burden of asthma in Iran from 1990 to 2013; the study protocol.

BACKGROUND: Asthma is a chronic inflammatory airway disease caused or worsened by environmental factors in genetically vulnerable people. The study of national and sub-national burden of asthma aims to provide a quantitative method and valid estimates for the prevalence, incidence, and economic burden of asthma disease in Iran from 1990 to 2013 and this papers explains measures, data sources, methods, and challenges that we will use in the study. METHODS: In order to conduct this study, we will use all available unpublished data sources, including claim databases and data collected by the food and drug organization (FDO). Moreover, we will devise and run a systematic review of all studies and literature published about asthma epidemiology in Iran, which includes all cross-sectional, cohort and case-control studies with asthma epidemiology focus that are population based. In this study, we will use two statistical models, including spatio-temporal and multilevel autoregressive models to estimate mean and uncertainty intervals for the parameters under study by gender, age, year, and province. All programs will be written in R statistical packages (version 3.0.1). CONCLUSION: This study helps to obtain information concerning the variation among regions and provinces, and in general among sub-national divisions. Our study can be contribute to better allocation of resources, since it helps policymakers to recognize inequalities between regions and provinces and consequently help them to allocate resources more efficiently.

National and sub-national trend and burden of injuries in Iran, 1990 - 2013: a study protocol.

BACKGROUND: Worldwide, injuries are a major public health concern and make a considerable contribution to the disease burden. The present study is a component of the National and Subnational Burden of Diseases, Injuries, and Risk Factors from 1990 to 2013 (NASBOD) study in Iran, which was designed to investigate the burden of most important injuries (road traffic injuries, falls, burns, poisonings and drownings) at the national and sub-national levels in Iran. In this paper we explain definitions, organization, injuries selection process, data sources, data gathering methods, and data analyses of the national and sub-national burden of injuries study in Iran. METHODS: The burden of most important injuries in current metric of DALYs at the national and sub-national levels in Iran over 1990-2013 will be estimated through comprehensive reviews of either published or national data sources. Statistical modeling will be used to impute the missing data on the burden of selected important injuries for each district-year. CONCLUSION: The results of present study can help health policy makers to plan more comprehensive and cost-effective strategies at national and sub-national level for prevention and control of burden caused by injuries.

Inpatient data, inevitable need for policy making at national and sub-national levels: a lesson learned from NASBOD.

BACKGROUND: Estimating burden of disease, injuries and risk factors is crucial for health policy decision making. The Burden of Diseases (BoD) studies provide data about the magnitude and distribution of health problems among the population at national and sub-national levels. The BoD studies are designed to use secondary data for estimating prevalence and incidence of diseases, injuries and risk factors. However, due to the scarcity of data sometimes it becomes unavoidable to collect data from medical records. Among all needed source of data, including surveys, registries, censuses, inpatient and outpatient data, hospital data are an essential source for BoD studies. Hospital Data Survey (HDS) aims to estimate the prevalence and incidence of diseases and injuries that led to admission to hospitals. This paper aims to describe the required steps for data gathering, sampling, analytical methods, and other needed procedures for HDS. STUDY DESIGN: The designed questionnaire includes demographic data, current health status, diseases, injuries and co-morbidities with their ICD10 codes, curative procedures, and treatment. A pilot study was conducted on 302 medical records from 6 hospitals to evaluate the validity and reliability of the questionnaire. Sampling frame was designed and probability proportional was used after being tested in the pilot study. In the next step, we will collect 367500 medical files from 863 hospitals (0.5% of all inpatient records in hospitals from1996 - 2013). The HDS is the first national study in Iran that is gathering data through an online-offline web-based system based on electronic version of the questionnaire which makes the process of data cleaning and analyses more comfortable.

The trend of national and sub-national burden of gastrointestinal and liver diseases in Iran 1990 to 2013; study protocol.

BACKGROUND: It is expected that gastrointestinal (GI) and liver diseases inflict considerable burden on health systems in Iran; therefore, highlighting the significance of GI disorders across the other most burdensome diseases requires comprehensive assessment and regular updates of the statistics of such diseases in Iran. OBJECTIVE: To assess in-depth sub-national estimates and trends for the incidence and prevalence of selected GI and liver diseases by age, gender and province over the period 1990 - 2013 in Iran. METHODS: This is a national and sub-national burden of disease study on 21 GI diseases using all available data sources, including cancer registry, death registration system data, hospital data, and all available published data. Analyses will be performed separately by gender, age groups, year, and province. We will conduct 21 separated systematic reviews of the literature for 21 diseases categories through searching online international electronic databases (i.e. the Medline database of the National Library of Medicine, Web of Science, and Scopus), Iranian search engines (i.e., IranMedex, Scientific Information Database (SID), and IRANDOC), and gray literature. We will search the medical literature published between January 1985 and December 2013. We generated two models, Spatio-temporal and Multilevel Autoregressive models, to estimate mean and uncertainty interval for the parameters of interest by gender, age, year, and province. The models will be informed by data of gender, age, year, and province. Markov Chain Monte Carlo (MCMC) methods will be used to perform Bayesian inference in both modeling framework. All programs will be written in R statistical packages (version 3.0.1). RESULTS: We will calculate and present 1990 to 2013 trends in terms of prevalence, years of life lost due to premature mortality (YLLs), years lived with disability (YLDs), and disability-adjusted life years DALYs for the 21 selected GI diseases by gender, and province. We will also quantify the uncertainty interval for the estimates of interest. CONCLUSION: Results of the present study will have implications for policy making; as they allow for understanding geographic distributions of the selected GI diseases, and identifying health disparities across provinces.

National and sub-national prevalence, trend, and burden of metabolic risk factors (MRFs) in Iran: 1990 - 2013, study protocol.

BACKGROUND: Non-communicable diseases (NCDs) and their risk factors are the major public health problems. There are some documented trend and point estimations of metabolic risk factors for Iranian population but there are little information about their exposure distribution at sub-national level and no information about their trends and their effects on the population health.  METHODS: The present study protocol is aimed to provide the standard structure definitions, organization, data sources, methods of data gathering or generating, and data on trend analysis of the metabolic risk factors in NASBOD study. We will estimate 1990 to 2013 trends of prevalence, years of life lost due to premature mortality (YLLs), and years lived with disability (YLDs) and disability-adjusted life years DALYs for MRFs by gender, age group, and province. We will also quantify the uncertainty interval for the estimates of interest. CONCLUSION: The findings of study could provide practical information regarding metabolic risk factors and their burden for better health policy to reduce the burden of diseases, and to plan cost-effective preventive strategies. The results also could be used for future complementary global, regional, national, and sub national studies.

Metformin in nonalcoholic steatohepatitis: a randomized controlled trial.

BACKGROUNDN onalcoholic steatohepatitis (NASH) is a common liver disease that can progress to cirrhosis or hepatocellular carcinoma. It is estimated that up to 3% of the Iranian population have this condition. Although the pathogenesis of NASH is incompletely understood, there is significant evidence pointing to the importance of insulin resistance. Metformin is an oral hypoglycemic agent known to improve insulin resistance. This study examines the effectiveness of metformin on biochemical and histological improvement among NASH patients in a randomized double-blind controlled trial. METHODS This study enrolled 33 biopsy-proven NASH patients. Other causes of liver disorders were excluded. Subjects were randomized to receive either metformin, 500 mg twice daily, or an identical-looking placebo. Overweight patients were also instructed to lose weight. Treatment continued for 6 months. Patients were regularly visited and liver enzyme levels recorded. Compliance and any adverse drug effects were recorded. RESULTS In the metformin group, the mean aspartate aminotransferase (AST) level dropped from 61.2 IU/L to 32.7 IU/L and the mean alanine aminotransferase (ALT) level dropped from 85.1 IU/L to 50.8 IU/L. The mean AST level in the placebo group dropped from 54.3 IU/L to 37.9 IU/L, whereas the mean ALT level dropped from 111.8 IU/L to 55.4 IU/L in the placebo group. The decrease in liver enzymes was significant in both groups, but the magnitude of decrease was not significantly different. CONCLUSION The improvement observed in liver enzyme levels is totally attributable to weight loss. Metformin had no significant effect on liver enzyme levels.

Epidemiology of peptic ulcer disease: endoscopic results of a systematic investigation in iran.

BACKGROUND Peptic ulcer disease is a multifactorial health problem affecting almost all populations worldwide. Large scale population-based studies are crucial to understanding its scope and specifications in various nations. We aimed to explore environmental risk factors of peptic ulcer disease in the first population based study in Ardabil, Northwest Iran. METHODS This study was a part of a larger survey on upper gastrointestinal tract health conducted in Ardabil and Meshkinshahr with a total catchment area population of 600,000 persons during 2000-01. Using a random sampling proportional to place of residence, 1122 persons aged 40 or elder were selected. 1011 (90.1%) accepted participation and underwent a comprehensive medical examination and a systematic upper gastrointestinal endoscopy. Point prevalence of peptic ulcers was correlated to various life style risk factors. RESULTS Gastric and duodenal ulcers were identified in 33 (3.26%) and 50 (4.94%) participants, making an overall prevalence of 8.20%. Based on multivariable logistic regression analyses, H.pylori infection (OR 3.1, 95% CI: 2.1-4.7), Smoking (OR 1.8, 95% CI: 1.1-6.8), and chronic intake of NSAIDs (OR 2.8, 95% CI: 1.3-4.4) were main risk factors of gastric ulcer. For duodenal ulcer, in addition to H.pylori infection (OR 5.6, 95% CI: 1.9-8.8) and Smoking (OR 2.3, 95% CI: 1.4-6.5), male gender (OR 3.6, 95% CI: 1.2-5.8) and living in an urban area (OR 1.9, 95% CI: 1.1-5.2) were among significant risk factors. CONCLUSION This is the first population-based endoscopic study in North West of Iran reporting accurate point prevalence of peptic ulcer disease. The rate of 3.3% for gastric ulcer and 4.9% for duodenal ulcers are substantially lower than the estimates reported in Asian population-based endoscopic studies but higher than European reports.

Gender differences in healthy ranges for serum alanine aminotransferase levels in adolescence.

BACKGROUND & AIMS: There is a worldwide epidemic of obesity among adolescents who subsequently are at increased risk for the development of non alcoholic fatty liver disease (NAFLD). The serum alanine aminotransferase (ALT) is the most frequently used test for screening these individuals, but no age and gender-specific upper limits of normal (ULN) based on healthy population data in children are available. The objective of the present study was to define ULN for ALT in healthy children in order to use this as a tool for case finding. METHODS: A total of 975 school children (aged 7-18 years) were included in the study cohort. Highly significant correlations (all p<0.001) were noted between ALT values and measures of BMI, systolic and diastolic blood pressure, insulin levels, HOMA-IR, total cholesterol and triglyceride concentrations. In order to define the population with no risk factors, we excluded subjects having abnormal values for factors that correlated with ALT. This population comprised 186 boys and 185 girls. RESULTS: In boys, median serum ALT levels were 16 IU/L and 9, 11, 18, and 30 IU/L for the 5th, 25th, 75th, and 95th percentiles. In girls, median serum ALT was 13, and 7, 9, 16, and 21 IU/L for the 5th, 25th, 75th, and 95th percentiles, respectively. The ULNs for ALT were 30 IU/L and 21 IU/L for boys and girls respectively. We found a linear relationship between age and ALT in females (p<0.001) but not in males. By multiple logistic regression, independent predictors of an elevated ALT included the BMI, waist hip ratio and levels of serum total cholesterol. In females, age was an additional inverse predictor. CONCLUSIONS: In children and adolescents, these normal limits for ALT should be applied. Those with persistent elevations should be investigated further.

Effectiveness and feasibility of lifestyle and low-cost pharmacologic interventions in the prevention of chronic diseases: a review.

Chronic diseases are already major causes of morbidity and mortality in Iran, similar to what is seen in other countries. However, there doesn't yet exist a comprehensive plan to cope with the epidemic of chronic diseases in Iran. Several lifestyle and low-cost pharmacological interventions have been proposed to reduce the burden of chronic diseases. Lifestyle interventions require a comprehensive infrastructure that can be quite costly in this country, but several components of extensive lifestyle interventions, including self-help materials and brief advice by health workers, can be integrated into the existing system. Pharmacological interventions may have substantial contribution to the capacity and preparation of Iran's healthcare system to confront the epidemic of chronic diseases. Further research needs to be performed to determine the feasibility and efficacy of each of these methods in order for policy makers to take the appropriate measures on adopting each of these strategies to prevent and control chronic diseases.

Reducing the burden of chronic diseases: a neglected agenda in Iranian health care system, requiring a plan for action.

Chronic non-communicable diseases cause substantial morbidity and mortality in both developed and developing countries. Current studies indicate an increasing burden of chronic diseases in the near future, especially in developing countries. Chronic diseases have received much less attention than infectious diseases in Iran's health care system, which is a major cause for concern. Data on the dimensions of the epidemic and its health impact and financial burden in Iran are not adequate. A comprehensive action plan should start with a comprehensive research plan and should end in a multi-faceted intervention plan, involving the entire health network in Iran. Studies in some developed countries have demonstrated that a comprehensive intervention will lead to a reduction in the burden of chronic diseases in a relatively short time. The effect of such interventions and the methods to implement them should be tested in Iran's health system too.