Lead poisoning among asymptomatic individuals with a long-term history of opiate use in Golestan Cohort Study.

BACKGROUND: Recent reports of lead poisoning suggest that people who use opium may be exposed to high amounts of lead. Here, we investigate the association between opium use and blood lead levels (BLL) in a population-based cohort study. METHODS: In 2017, we studied a random sample of 410 people who currently (both within the past year and the past month) used opium and 104 who did not from participants of the Golestan Cohort Study in northeast Iran. Participants were stratified by sex and tobacco use history, completed a comprehensive opiate and tobacco use questionnaire and provided blood. BLL was measured by Lead Care® II Blood Lead Test Kit, validated by inductively coupled plasma triple quadrupole mass spectrometry. BLL was categorized as "<5 µg/dL", "elevated" (5-10 µg/dL), "high" (10-50 µg/dL), and "very high" (above 50 µg/dL). To assess the association between BLL categories and opiate use, route of consumption and weekly use, we used ordered logistic regression models, and report OR (odds ratio) and 95% CI (confidence interval) adjusted for age, sex, place of residence, education, occupation, household fuel type, and tobacco use. RESULTS: In the cohort, participants used only raw (teriak) or refined (shireh) opium, which were smoked (45%, n = 184), taken orally (46%, n = 189), or both (9%, n = 37), for a mean duration of 24.2 (standard deviation: 11.6) years. The median BLL was significantly higher in people who currently used opium (11.4 µg/dL; IQR: 5.2-23.4) compared with those who did not (2.3 µg/dL; IQR: 2.3-4.2), and the highest median BLL was seen in oral use (21.7 µg/dL; IQR: 12.1-34.1). The BLL was <5 µg/dL among 79.8% of people with no opiate use, compared with only 22.7% in those using opium. BLL was elevated in 21.7%, high in 50.5% and very high in 5.1% of people using opium. About 95% of those with oral (180/189) or dual use (35/37) and 55% (102/184) of those who smoked opium had levels of blood lead above 5 µg/dL. The OR for the association between any opium use and each unit of increase in BLL category was 10.5 (95%CI: 5.8-19.1), and oral use of opium was a very strong predictor of increasing BLL category (OR=74.1; 95%CI: 35.1-156.3). This odds ratio was 38.8 (95%CI: 15.9-95.1) for dual use and 4.9 (95%CI: 2.6-9.1) for opium smoking. There was an independent dose-response association between average weekly dose and BLL among people using opium, overall and when stratified by route of use. CONCLUSION: Our results indicate that regular use of lead-adulterated opium can expose individuals to high levels of lead, which may contribute to mortality and cancer risks associated with long-term opium use.

All-Cause and Cause-Specific Mortality in Middle-Aged Individuals with Positive HBsAg: Findings from a Prospective Cohort Study.

BACKGROUND: While hepatitis B virus (HBV) is the most prevalent cause of adult liver transplants in Iran, the mortality rates and leading causes of death in HBV patients are not well-understood. This study aimed to investigate all-cause and cause-specific mortality among HBsAg positive individuals in a large Iranian cohort. METHODS: The Golestan Cohort Study includes 50045 individuals aged 40-75 residing in Iran's Golestan province, enrolled during 2004-2008. HBsAg test was performed at baseline. For the present study, individuals with hepatitis C coinfection were excluded. All-cause mortality was considered as the primary outcome. The association between HBsAg and different mortality causes was evaluated using Cox proportional hazard models. P value<0.05 was considered significant. RESULTS: The current study included 49667 participants. After 11.33 (median) follow-up years, there were 7,686 total deaths, with 635 deaths in the HBsAg positive group. In the multivariate Cox proportional hazard model, HBsAg positive individuals had higher all-cause (adjusted hazard ratio [aHR]=1.15, 95% CI: 1.06-1.24) and liver-related mortality risk (aHR=7.13; 5.19-9.79). Mortality from colorectal and pancreatic cancers was higher among male HBsAg positive participants (aHRs=2.41 and 2.22, respectively). Nevertheless, cardiovascular diseases (CVDs) and extrahepatic malignancies were the leading causes of death among both HBsAg positive and negative individuals, and liver-related deaths contributed to an overall 10% of deaths in HBsAg positive patients. CONCLUSION: HBV is associated with significant mortality risk from different causes in Iranian adults. However, solely focusing on liver outcomes in Iranian HBV patients might result in overlooking non-liver events, especially CVD and extrahepatic cancers.

Prevalence and determinants of anemia among Iranian population aged ≥35 years: A PERSIAN cohort-based cross-sectional study.

BACKGROUND: So far, no comprehensive studies have been performed to assess burden and determinants of anemia in Iran. In the present study, we aimed to answer this query using the data obtained from the Prospective Epidemiological Research Studies in IrAN (PERSIAN). METHODS: In this cross-sectional study, we included 161,686 adult participants (aged 35 years and older) from 16 provinces of Iran. Anemia was defined as a hemoglobin concentration of <13 g/dL in males and <12 g/dL in females. To evaluate the association between anemia and different factors, we used the multivariable Poisson regression analysis with robust variance by applying adjusted prevalence ratio (PR) with 95% confidence interval (CI). RESULTS: Of the total number of subjects, 72,387 (44.77%) were male and others were female. Mean age was 49.39±9.15 years old. The overall age- and sex-standardized prevalence of anemia was 8.83% (95% CI: 8.70-8.96%) in the included population. The highest and the lowest age- and sex-standardized prevalence of anemia pertained to Hormozgan (37.41%, 95% CI: 35.97-38.85%) and Kurdistan (4.57%, 95% CI: 3.87-5.27%) provinces, respectively. Being female (PR = 2.97), rural residence (PR = 1.24), being retired (PR = 1.53) and housewife (PR = 1.11), third and fourth wealth status quartiles (PR = 1.09 and PR = 1.11, respectively), being underweight (PR = 1.49), drug user (PR = 1.35), inadequate sleep (PR = 1.16), poor physical activity (PR = 1.15), diabetes (PR = 1.09), renal failure (PR = 2.24), and cancer (PR = 1.35) were associated with increased risk of anemia. On the other hand, illiteracy (PR = 0.79) and abdominal obesity (PR = 0.77) decreased the risk of anemia. CONCLUSIONS: According to the results, a variable prevalence of anemia was observed across the included provinces. We tried to provide an informative report on anemia prevalence for health professionals and authorities to take measures for identification and management of the cases of anemia in high-prevalence areas.

Untargeted Metabolomics: Biochemical Perturbations in Golestan Cohort Study Opium Users Inform Intervention Strategies.

Objective: Over 50 million people worldwide are estimated to use opioids, of which ~30 million use opiates (opium and its derivatives). Use of opiates has been associated with a variety of adverse complications such as neurological and behavioral outcomes, addiction, cancers, diabetes, and cardiovascular disease. While it is well known that opiates exert their neurobiological effects through binding with mu, kappa, and delta receptors to exert analgesic and sedative effects, mechanistic links to other health effects are not well understood. Our study focuses on the identification of biochemical perturbations in Golestan Cohort Study (GCS) opium users. Methods: We used untargeted metabolomics to evaluate the metabolic profiles of 218 opium users and 80 non-users participating in the GCS. Urine samples were obtained from adult (age 40-75) opium users living in the Golestan Province of Iran. Untargeted analysis of urine was conducted using a UPLC-Q-Exactive HFx Mass Spectrometry and a 700 MHz NMR Spectrometry. Results: These GCS opium users had a significantly higher intake of tobacco and alcohol and a significantly decreased BMI compared with non-users. Metabolites derived from opium (codeine, morphine, and related glucuronides), nicotine, and curing or combustion of plant material were increased in opium users compared with non-users. Endogenous compounds which differentiated the opium users and non-users largely included vitamins and co-factors, metabolites involved in neurotransmission, Kreb's cycle, purine metabolism, central carbon metabolism, histone modification, and acetylation. Conclusions: Our study reveals biochemical perturbations in GCS opium users that are important to the development of intervention strategies to mitigate against the development of adverse effects of substance abuse.

Intra-familial Transmission of Chronic Hepatitis B Infection: A Large Population-Based Cohort Study in Northern Iran.

AIM: The aim of this study was to investigate the intra-familial transmission of chronic hepatitis B (CHB) in Golestan province, that has the highest prevalence of CHB in Iran. METHODS: The Golestan Cohort Study (GCS) is a population-based prospective study of 50045 individuals, 40 years or older, initially set-up to study upper GI cancers in Northern Iran. In 2008, a baseline measurement of hepatitis B surface antigen (HBsAg) on the stored serum of all GCS participants identified 3505 HBsAg+ individuals. In 2011, we assessed HBV serological markers in 2590 initially HBsAg+ individuals and their first-degree relatives including spouses (1454) and children (3934). RESULTS: The median (IQR) age of spouses and children were 52 (12) and 25 (12) years respectively. Out of 5388 family members, 2393 (44.5%) had no HBV markers, indicating susceptibility to infection. Of these, 378 (15.8%) were fully-vaccinated children with no apparent response to primary immunization. HBsAg was positive in 2.2% (n = 33) of spouses and 8.2% (n = 325) of children (overall rate of 6.6%). HBcAb was positive in 761 (52.3%) and 914 (23%) spouses and children, respectively. The rate of spontaneous loss of HBsAg (HBsAg-, HBsAb+ and HbcAb+) was 41.3% and 13.9% in spouses and children, respectively. A higher rate of HBsAg+ children (10.2%) was found in families in which the mother was positive for HBsAg compared with families where the father was positive for HBsAg (6.3%) (P < 0.001). When both parents were positive for HBsAg, the rate of HBsAg positivity was high (23.5%, P < 0.001). Despite high virus exposure rates between spouses (52.6 %), the prevalence of HBsAg positivity among them was very low (2.3 %). CONCLUSION: Sexual and parent-to-child transmission are important routes of CHB spread in this population from northern Iran despite the fact that 24 years have passed since the beginning of hepatitis B vaccination in infants. Low percentage of HBsAg positivity in spouses is related to high HBsAg clearance rate among them.

Epidemiological Profile of Hepatitis B Virus Infection in Iran in the Past 25 years; A Systematic Review and Meta-analysis of General Population Studies.

BACKGROUND Chronic hepatitis B virus (HBV) infection is one of the most important health problems worldwide with a high rate of morbidity and mortality. It is a major risk factor for cirrhosis and liver cancer. Currently, Iran is located in the intermediate HBV zone; however, recent studies have provided some evidence indicating an epidemiological change in the country. The aim of this study was to estimate the prevalence of HBV in Iran. METHODS A systematic review was conducted to evaluate the studies performed in the past 25 years that have reported the prevalence of HBV infection and its associated factors in the Iranian general population (1990-2014). Any study assessing and reporting serum Hbs Ag levels was included in this review. RESULTS After excluding all impertinent studies, 19 eligible studies were included in the analysis. The overall prevalence of HBV was 3% (95% CI 2% to 3%). Its distribution showed that the prevalence of HBV varies in different provinces from 0.87% to 8.86%. The HBV rate was highest in the Golestan (8.86%) and lowest in the Kurdistan (0.87%) provinces. CONCLUSION This study provides some evidence about the prevalence of HBV in Iran. However, the collected data was very heterogenic, even within a single province, which made it hard to estimate a single-point prevalence. High quality studies are needed to find reliable information about HBV prevalence and to decrease the heterogeneity of results in the country.

Chronic hepatitis B infection is not associated with increased risk of vascular mortality while having an association with metabolic syndrome.

This study aimed to assess the association of chronic hepatitis B (CHB) with vascular mortality and metabolic syndrome (MS) using data from a large population-based cohort study in Iran. A total of 12,781 participants (2249 treatment-naïve CHB and 10,532 without CHB) were studied. Logistic regression model was used to assess the association between MS and CHB with adjustment for age, ALT, PLT, alcohol intake, smoking, exercise, and socioeconomic status. MS was defined according to the ATPIII guidelines. Cox proportional hazards model was used to assess the hazard ratios for overall and vascular related mortality. There was a significant association between CHB infection and overall mortality (hazard ratio (95%CI) of 1.44 (1.16-1.79), P < 0.001) after adjusting for other confounders. However, we found no association between CHB infection and mortality from vascular events (hazard ratio (95%CI) of 1.31 (0.93-1.84), P = 0.124) even after subgroup analysis by ALT. Furthermore, increased risk of overall mortality in CHB infected individuals was not related to MS and vice versa (P for interaction = 0.06). We noted a significant direct association between CHB infection and MS in women (OR (95%CI); 1.23 (1.07-1.42), P < 0.004). However, CHB was inversely associated with MS in men (OR (95%CI), 0.85 (0.79-0.99). This gender dependent association was related to high BP levels in women. In this study no association between CHB infection and mortality from vascular events was found. Further longitudinal studies should be done to investigate the exact impact of HBV infection on metabolic parameters and vascular pathology.