Molecular Characterization of Antimicrobial Resistance and Virulence Genotyping among Helicobacter pylori-Positive Dyspeptic Patients in North Iran.

BACKGROUND: Iran has a relatively high prevalence of H. pylori, which correlates with high-risk areas for gastric cancer worldwide. METHODS: Our study aimed to investigate the underlying genetic mechanisms associated with resistance to metronidazole (frxA, rdxA), clarithromycin (23S rRNA), tetracycline (16S rRNA), and fluoroquinolone (gyrA) in H. pylori-positive dyspeptic patients using PCR and sequencing. We further examined the potential correlation between resistance profiles and various virulence genotypes. RESULTS: The rates of genetic mutations associated with resistance to metronidazole, fluoroquinolone, clarithromycin, and tetracycline were found to be 68%, 32.1%, 28.4%, and 11.1%, respectively. Well-documented multiple antibiotic resistance mutations were detected, such as rdxA and frxA (with missense and frameshift alterations), gyrA (Asp91, Asn87), 23S rRNA (A2142G, A2143G), and 16S rRNA (triple-base-pair substitutions AGA926-928→TTC). The cagA+ and vacA s1/m1 types were the predominant genotypes in our study. With the exception of metronidazole and tetracycline, no significant correlation was observed between the cagA+ and cagL+ genotypes and resistance-associated mutations. CONCLUSION: The prevalence of antibiotic resistance-associated mutations in H. pylori was remarkably high in this region, particularly to metronidazole, ciprofloxacin, and clarithromycin. By conducting a simultaneous screening of virulence and resistance genotypes, clinicians can make informed decisions regarding the appropriate therapeutic regimen to prevent the escalation of antibiotic resistance against H. pylori infection in this specific geographical location.

Cost effectiveness analysis of a fixed dose combination pill for primary prevention of cardiovascular disease from an individual participant data meta-analysis.

Background: Cardiovascular disease (CVD) continues to impart a large burden on the global population, especially in lower income countries where affordability limits the use of cardiovascular medicines. A fixed dose combination strategy of at least 2 blood pressure lowering medications and a statin with aspirin in a single pill has been shown to reduce the risk of incident CVD by 38% in primary prevention in a recent meta-analysis. We report the in-trial (median follow-up: 5 years) cost-effectiveness of a fixed dose combination (FDC) pill in different income groups based on data from that meta-analysis. Methods: Countries were categorized using World Bank economic groups: Lower Middle Income Countries (LMIC), Upper Middle Income Countries (UMIC) and High Income Countries (HIC). Country specific costs were obtained for hospitalized events, procedures, and non-study medications (2020 USD). FDC price was based on the cheapest equivalent substitute (CES) for each component. Findings: For the CES-FDC pill versus control the difference in cost was $346 (95% CI: $294-$398) per participant in Lower Middle Income Countries, $838 (95% CI: $781-$895) in Upper Middle Income Countries and $42 (95% CI: -$155 to $239) (cost-neutral) in High Income Countries. During the study period the CES-FDC pill was associated with incremental gain in quality-adjusted life years of 0.06 (95% CI: 0.04-0.08) resulting in an incremental cost-effectiveness ratio (ICER) of $5767 (95% CI: 5735-$5799), $13,937 (95% CI: $13,893-$14,041) and $700 (95% CI: $662-$738) respectively. In subgroups analyses, the highest 10 years CVD risk subgroup had ICERs of $2033, $7322 and -$6000/QALY. Interpretation: A FDC pill produced at CES costs is cost-neutral in HIC. Governments of LMI and UMI countries should assess these results based on the ICER threshold accepted in their own country and own specific health care priorities but should consider prioritizing this strategy for patients with high 10 years CVD risk as a first step. Funding: Population Health Research Institute.

Population attributable fractions of cancer mortality related to indoor air pollution, animal contact, and water source as environmental risk factors: Findings from the Golestan Cohort Study.

BACKGROUND: Environmental risk factors are significant contributors to cancer mortality, which are neglected. PURPOSE: This study aimed to estimate the population attributable fraction of cancer mortality due to the environmental risk factors. METHODS: Golestan cohort study is a population-base cohort on 50045 participants between 40-75 with about 18 years of follow up. We detected 2,196 cancer mortality and applied a multiple Cox model to compute the hazard ratio of environmental risk factor on all cancer and cancer-specific mortality. The population attributable fraction was calculated, accordingly. RESULTS: Biomass fuels for cooking, as an indoor air pollution, increased the risk of colorectal, esophageal, gastric cancer, and all-cancer mortality by 84%, 66%, 37%, and 17% respectively. Using gas for cooking, particularly in rural areas, could save 6% [Population Attributable Fraction: 6.36(95%CI: 1.82, 10.70)] of esophageal cancer, 3% [Population Attributable Fraction: 3.43 (0, 7.33)] of gastric cancer, and 6% [Population Attributable Fraction: 6.25 (1.76, 13.63)] of colorectal cancer mortality. Using a healthy tap water source could save 5% [Population Attributable Fraction:5.50(0, 10.93)] of esophageal cancer mortality, particularly in rural areas. There was no significant association between indoor air pollution for heating purposes and animal contact with cancer mortality. CONCLUSION: Considering the results of this study, eliminating solid fuel for most daily usage, among the population with specific cancer types, is required to successfully reduce cancer related mortality. Adopting appropriate strategies and interventions by policymakers such as educating the population, allocating resources for improving the healthy environment of the community, and cancer screening policies among susceptible populations could reduce cancer related mortalities.

Incidence Rates and Time Trends of Skin Cancer in Golestan Province, Northeastern Iran, 2005-2018.

BACKGROUND: Given the significant occurrence of skin cancer in the Middle East and the existing research gap concerning its incidence and trends, this research aimed to study the epidemiology and trend changes of skin cancer in the Golestan province, Northeastern Iran. METHODS: The Golestan Population-based Cancer Registry's (GPCR's) data bank was utilized to gather information on confirmed skin cancer cases in the province during 2005-2018. We used Poisson regression analysis for comparing incidence rates between groups. P values less than 0.05 were considered statistically significant. RESULTS: Of 1690 patients (mean age: 62.05±15.83 years), most were male (60.1%) and resided in urban areas (61.5%). The age-standardized rate (ASR) of non-melanoma and melanoma skin cancer was 8.49 and 0.56 per 100000 persons-year, respectively. A notably higher ASR for non-melanoma skin cancer (NMSC) was observed in men (ASR: 10.60; 95% CI: 9.91-11.29) (P<0.01) and urban residents (ASR: 10.19; 95% CI: 9.52-10.82) (P<0.01). There was no significant difference in the ASR of melanoma skin cancer based on gender (P=0.24) and place of residence (P=0.48). The incidence trend of melanoma (estimated annual percent change [EAPC]: -3.28; 95% CI: -18.54 to 14.83) and NMSC (EAPC: 0.39; 95% CI: -3.99 to 4.97) did not differ significantly. CONCLUSION: During the 14-year study period, the ASR of both types of skin cancer exhibited a consistent pattern, except for NMSC, which showed higher rates among men and urban residents. This should be taken into consideration when formulating preventive and control strategies in the study area.

Incidence and risk factors of pancreatic cancer during 15 years follow-up in the Golestan Cohort Study in Iran.

BACKGROUND: Cancer is one of the main causes of death in the worldwide. Pancreatic Cancer (PC) is prevalent in developed and increasing in developing countries. PC is important because of its low survival rate, high fatality, and increasing incidence. Therefore, identifying risk factors to prevent its development is necessary. This study aimed to determine incidence of PC and its risk factors in the Golestan Cohort Study (GCS) in Iran. METHOD: This study is a prospective population-based cohort study in the frame of GCS with 15 years of follow-up for PC. GCS was launched in the Golestan province of Iran with 50045 participants who were 40 to 75 years old. variables included: age, gender, education status, smoking, alcohol consumption, opium usage, type of blood group, dyslipidemia, body mass index (BMI), waist circumference (WC), family history (FH) of PC, ethnicity, and history of diabetes mellitus (DM). RESULT: Among 50045 participants of GCS during 15 years of follow up, 100 people were diagnosed PC. PC incidence was 0.2%. Age-standardized incidence rate (ASR) of PC in the study population was 11.12 per 100,000 person-years. People with age ≥60 years were 46, in 50-59 years old group were 36, and 18 of them were <50 years (p<0.001). The smoking rate in PC group was 27% (p<0.01). Univariate model of cox regression analysis showed age 50-59, ≥60 years compared to <50 years [HR:3.006, 95%CI (1.707-5.294), p<0.001], [HR: 6.727, 95% CI (3.899-11.608), p<0.001], male gender [HR:1.541, 95%CI (1.041-2.281), p = 0.031], opium use [HR:1.436, 95% CI (0.887-2.324), p = 0.141], and smoking [HR:1.884, 95%CI (1.211-2.929), p = 0.005] were predictors for PC. In the multivariate model after adjusting, age 50-59 [HR:2.99, 95% CI (1.698-5.265), p<0.001], and ≥60 years [HR: 6.564, 95% CI (3.797-11.346), p<0.001] was the only predictor for PC. CONCLUSION: This study revealed an incidence of PC 0.2% in GCS in Iran. Main risk factor for PC was older age.

The contribution of metabolic risk factors to cardiovascular mortality in Golestan cohort study: Population attributable fraction estimation.

Background: Cardiovascular diseases (CVDs) are the leading causes of global mortality and disability. Several studies demonstrated that metabolic risk factors increase cardiovascular mortality. The aim of this study is to examine CVDs deaths and population attributable fractions (PAFs) of their metabolic risk factors in Iran. Methods: This is a study on 8621 participants aged 45-75 years and older, recruited in the repeated measurement phase of the Golestan cohort study (GCS) in northeast of Iran. The Cox proportional hazards model was used to determine the adjusted hazard ratios (HRs). PAFs were calculated to enumerate CVDs mortality avoidable in the population if metabolic risk factors were eliminated. Results: The mortality of CVDs was attributable to metabolic factors, including high waist circumference (PAF, 28 %, [95 % CI: 16%-38 %]), high fasting blood sugar (FBS) (20 %, [15%-24 %]), overweight and obesity (19 %, [8%-28 %]), high blood pressure (16 %, [11%-21 %]), high low-density lipoprotein cholesterol (LDL-C) (8 %, [1%-15 %]), and high triglyceride (TG) (7 %, [3%-11 %]). Collectively, these metabolic risk factors accounted for 50 % of CVDs deaths. Females (67 %, [50%-78 %]) had a higher joint PAF of metabolic risk factors compared to males (43 %, [27%-55 %]). Conclusions: The pattern of CVDs mortality attributable to metabolic risk factors in this study is not the same as similar studies in other parts of the world and previous studies in Iran. It is imperative that CVDs risk factors be specifically evaluated and addressed in various populations due to variety in geographical and temporal patterns in contribution of metabolic risk factors to CVD mortality.

Colorectal Cancer: Epidemiology, Risk Factors, and Prevention.

Colorectal cancer (CRC) is the third most common cancer and the second most common cause of cancer mortality worldwide. There are disparities in the epidemiology of CRC across different populations, most probably due to differences in exposure to lifestyle and environmental factors related to CRC. Prevention is the most effective method for controlling CRC. Primary prevention includes determining and avoiding modifiable risk factors (e.g., alcohol consumption, smoking, and dietary factors) as well as increasing protective factors (e.g., physical activity, aspirin). Further studies, especially randomized, controlled trials, are needed to clarify the association between CRC incidence and exposure to different risk factors or protective factors. Detection and removal of precancerous colorectal lesions is also an effective strategy for controlling CRC. Multiple factors, both at the individual and community levels (e.g., patient preferences, availability of screening modalities, costs, benefits, and adverse events), should be taken into account in designing and implementing CRC screening programs. Health policymakers should consider the best decision in identifying the starting age and selection of the most effective screening strategies for the target population. This review aims to present updated evidence on the epidemiology, risk factors, and prevention of CRC.

Colorectal Cancer Incidence in Iran Based on Sex, Age, and Geographical Regions: A Study of 2014-2017 and Projected Rates to 2025.

BACKGROUND: While there has been extensive research on colorectal cancer (CRC) incidence and its associated factors in Iran, a significant gap exists in studies predicting its future trends. Our study aimed to thoroughly report CRC incidence across Iran from 2014 to 2017, by sex, age, and geographical regions, and provide a projection for 2025. METHODS: This retrospective study utilized data from the Iranian National Population-based Cancer Registry (INPCR). Patients with the International Classification of Diseases for Oncology, 3rd Edition (ICD-O-3) codes C18 to C21 were included. The age-standardized incidence rate (ASR), was calculated per 100000 individuals annually, and crude incidence rates were retrieved for various demographic groups and years. RESULTS: Between 2014 and 2017, a total of 43580 new CRC cases (55.96% males) were registered. Men exhibited an ASR of 134.45, while women's ASR was 94.85. The highest ASRs were observed in Tehran, Qom, and Ilam (18.99, 18.26, and 18.06, respectively). Incidence rates surpassed 20 after age 50 for both genders, reaching their peak within the 80-84 age group. Adenocarcinoma was the most frequent histological type of CRC in nearly all provinces. Case numbers and ASRs are projected to continuously rise until 2025, with a predominance of male cases. CONCLUSION: The anticipated increase in CRC incidence in Iran emphasizes the need for additional studies to better identify risk factors. Furthermore, implementing screening programs is recommended for individuals at a higher risk of CRC, including men, the elderly population, and those residing in regions with a notable prevalence of CRC.

Burden of upper gastrointestinal cancers in the east of Golestan province (Golestan cohort study).

BACKGROUND: Cancers, especially Upper Gastrointestinal Cancers (UGCs), pose a substantial burden on society, particularly in developing nations. Golestan province, Iran, is known for its high UGC rates globally. AIMS: This study delves into the disease burden of UGCs in the eastern part of Golestan province. METHODS AND RESULTS: This study was conducted using the results of the Golestan cohort study. 2711 patients participating in this cohort, who visited Atrak Clinic during 2001-2020, participated in this study. After excluding patients with incomplete records, 2481 patients were included in the study. To compute the metrics of years of life lost (YLL), years of life lived with disability (YLD), and disability-adjusted life years (DALY), we utilized the World Health Organization's standard life table, stratified by age and gender. The majority of UGC patients in our study were married (81.8%), had limited formal education (82.6%), and were predominantly male (61.1%). A substantial proportion resided in suburban areas (85.8%), and over half of the patients (52%) reported a history of drug addiction. The mean age at diagnosis for men was 65.76 years with a standard deviation of 11.34, while for women, it was 64.38 years with a standard deviation of 11.66. Regarding disease impact, YLL, YLD, and DALY for men were 21 240, 1956, and 23 196 (307.8 per 100 000), respectively. For women, these figures were 15 609 for YLL, 1367 for YLD, and 16 976 (223.1 per 100 000) for DALY. CONCLUSION: After the increasing trend of the burden of UGCs in Golestan province in the early years of the study, this rate has been decreasing in recent years. Effective strategies necessitate collaborative efforts across various sectors to alleviate this burden, focusing on preventive measures, timely diagnosis, and well-coordinated therapeutic interventions.

Effectiveness of polypill for primary and secondary prevention of cardiovascular disease: a pragmatic cluster-randomised controlled trial (PolyPars).

BACKGROUND: We aimed to investigate the effectiveness of fixed-dose combination therapy (polypill) for primary and secondary prevention of major cardiovascular diseases in a typical rural setting. METHODS: The PolyPars Study is a two-arm pragmatic cluster-randomised trial nested within the PARS cohort study, including all residents aged over 50 years in the entire district in southern Iran. The 91 villages underwent random allocation into two arms: the control arm, encompassing 45 clusters, was subjected to non-pharmacological intervention (educational training on healthy lifestyle), whereas the intervention arm, comprising 46 clusters, received the non-pharmacological interventions in conjunction with a once-daily polypill tablet. This tablet comprised two antihypertensive agents, a statin and aspirin. The primary outcome was the first occurrence of major cardiovascular events defined as a composite of hospitalisation for acute coronary syndrome (non-fatal myocardial infarction and unstable angina), fatal myocardial infarction, non-fatal and fatal stroke, sudden death and heart failure. The Cox regression model, with shared frailty, was used to account for clustering effect. RESULTS: During December 2015-December 2016, a total of 4415 participants aged 50-75 years were recruited (2200 participants in the intervention arm and 2215 participants in the control arm). The overall median of follow-up duration was 4.6 years (interquartile interval 4.4-4.9). The achieved adherence rate to polypill in intervention arm was 86%. In the control group, 176 (8.0%) of 2215 participants developed primary outcome, compared with 88 (4.0%) of 2200 participants in the polypill group. We found substantial reduction in risk of primary outcome both in relative and absolute scales (HR 0.50, 95% CI 0.38 to 0.65; absolute risk reduction 4.0%, 95% CI 2.5% to 5.3%). No difference in serious adverse events was observed between the two groups. CONCLUSIONS: The fixed-dose combination therapy using polypill can safely halve the risk of major cardiovascular diseases at the population level. TRIAL REGISTRATION NUMBER: NCT03459560.

Efficacy of a self-monitoring traffic light diary on outcomes of patients with heart failure: A randomized controlled trial.

BACKGROUND AND OBJECTIVE: Patients with heart failure experience high hospitalization. However, patients cannot recognize symptoms according to current approaches, which needs to be improved by new self-monitoring instruments and strategies. Thus, we aimed to assess a self-monitoring traffic light diary on outcomes of patients with heart failure. METHODS: This was a single-blind, two-arm parallel group randomized controlled trial at the heart failure clinic of Tehran Heart Center (Tehran, Iran). Adult patients with a definitive diagnosis of heart failure with reduced ejection fraction (i.e., ejection fraction of less than 40 %), and New York Heart Association functional classes II-IV were included. A block-balanced randomization method was used to assign eligible subjects to the intervention or control group. Baseline data were collected before random allocation. Participants in the intervention group received a comprehensive intervention consisting of (1) self-care education by an Australian Heart Foundation booklet on heart failure, (2) regular self-monitoring of weight and shortness of breath at home, and (3) scheduled call follow-ups for three months. Patients in the control group received usual care. The primary outcome was heart failure self-care; the secondary outcomes were heart failure quality of life, knowledge, and all-cause hospitalization. RESULTS: From June to August 2017, 68 patients were included in the study. The overall age of participants was 55 (13.6) years old, and 71 % of patients were male. A significant association between the intervention and self-care maintenance (ß 5.1; 95 % CI 2.50 to 7.70, P < 0.001), self-care management (ß 10.6; 95 % CI 6.50 to 14.8, P < 0.001), self-care confidence (ß 8.0; 95 % CI 5.0 to 11.0, P < 0.001) and heart failure knowledge (ß 1.7; 95 % CI 1.30, 2.04; P < 0.001) was found. However, there was no association between the intervention and quality of life (ß 2.5; 95 % CI -0.79, 5.88, P 0.135) and hospitalization-free survival of the two groups (Log-Rank P 0.540). CONCLUSION: A self-monitoring traffic light diary can improve self-care behaviors and heart failure knowledge in patients with heart failure with reduced ejection fraction. RCT APPROVAL ID: Iranian Registry of Clinical Trials IRCT2017021032476N1. STUDY PROTOCOL: PMCID: PMC6262204.

Epidemiology of cervical cancer in Iran in 2016: A nationwide study of incidence and regional variation.

BACKGROUND: Cervical cancer is a common, and fatal cancer in women worldwide. This cancer is the fourth most common cancer in women after breast, colorectal, and lung cancer. AIMS: This study aims to investigate the age-standardized incidence rate (ASR) and the geographical distribution of Cervical Cancer in Iran. METHODS: This study was designed as a descriptive cross-sectional investigation. The study sample comprised all individuals registered as cervical cancer patients in the National Cancer Registry system in 2016. The crude rate and ASR for each province were computed independently. Furthermore, we employed ArcMap10.5 software and geographic information system to conduct an analysis of the gathered data. In order to ascertain the spatial distribution and clustering of cervical cancer incidence, we utilized Moran's I, which measures spatial autocorrelation. RESULTS: We studied a total of 808 cases of cervical cancer with a median age to be 52.19 years (IQR≈1.35). Among these cases, 685 (84.7%) were diagnosed based on the pathological reports with morphological verification, while 81 patients (10.1%) were clinically identified, and 42 cases (5.2%) were diagnosed using the death certificate-only method. Squamous cell carcinoma accounted for 61% of all cases (n = 497). The ASR of cervical cancer in Iran was 1.90 per 100 000 populations. The provincial ASR ranged from 0.29 to 5.03 per 100 000, with the highest rates observed in Golestan (5.03), East Azerbaijan (4.07), and Ilam (3.72). We found no clustering patterns in the distribution of provincial crude, age-specific, and age-standardized incidence rates (p > .05). CONCLUSION: The incidence of cervical cancer in Iran was lower than the global average, and we did not identify any significant disparities in the incidence rates among the provinces. Although there were differences in incidence rates among the areas, these were not clustered. It is crucial to remember that cervical cancer is still a major public health issue in Iran, and in order to lessen the disease's burden, national initiatives to enhance screening, early identification, and access to efficient treatment should continue to be top priorities.

Breast cancer incidence trends in Golestan, Iran: An age-period-cohort analysis by ethnic region, 2004-2018.

BACKGROUND: We aimed to examine the effects of age, diagnosis year (calendar period) and birth year (cohort) on the incidence trends of breast cancer among Golestan women, Northeast Iran, 2004-2018. METHODS: Incidence data were obtained by residential status (urban/rural) and ethnic region (Turkmens/non-Turkmens). We calculated age-standardized incidence rates (ASRs) per 100,000 person-years. The estimated annual percentage change (EAPC) were calculated, and age-period-cohort (APC) models fitted to assess non-linear effects of period and cohort as incidence rate ratios (IRRs). RESULTS: The total number of female breast cancer cases in Golestan, 2004-2018, were 3853, with an overall ASR of 31.3. We found higher rates in urban population (40.5) and non-Turkmens region (38.5) compared to rural area (20.8) and Turkmens region (20.2), respectively. There were increasing trends in incidence rates overall (EAPC= 4.4; 95%CI: 2.2, 6.7), with greater changes in rural areas (EAPC=5.1), particularly among non-Turkmens (EAPC=5.8). The results of the APC analysis indicate the presence of significant non-linear cohort effects with increasing IRRs across successive birth cohorts (IRR=0.1 and IRR= 2.6 for the oldest and the youngest birth cohorts vs. the reference birth cohort, respectively). CONCLUSION: We found increasing trends in breast cancer incidence among Golestan women over the study period, with disparities in patterns and trends by residence area and ethnic region. The observed cohort effects suggest an increasing prevalence of key risk factors for breast cancer in this Iranian population. Further investigations are warranted to clarify the relationships between determinants such as reproductive factors and ethnicity in the region.

Dental health and lung cancer risk in the Golestan Cohort Study.

BACKGROUND: Poor oral health has been linked to various systemic diseases, including multiple cancer types, but studies of its association with lung cancer have been inconclusive. METHODS: We examined the relationship between dental status and lung cancer incidence and mortality in the Golestan Cohort Study, a large, prospective cohort of 50,045 adults in northeastern Iran. Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for associations between three dental health measures (i.e., number of missing teeth; the sum of decayed, missing, or filled teeth (DMFT); and toothbrushing frequency) and lung cancer incidence or mortality with adjustment for multiple potential confounders, including cigarette smoking and opium use. We created tertiles of the number of lost teeth/DMFT score in excess of the loess adjusted, age- and sex-specific predicted numbers, with subjects with the expected number of lost teeth/DMFT or fewer as the reference group. RESULTS: During a median follow-up of 14 years, there were 119 incident lung cancer cases and 98 lung cancer deaths. Higher DMFT scores were associated with a progressively increased risk of lung cancer (linear trend, p = 0.011). Compared with individuals with the expected DMFT score or less, the HRs were 1.27 (95% CI: 0.73, 2.22), 2.15 (95% CI: 1.34, 3.43), and 1.52 (95% CI: 0.81, 2.84) for the first to the third tertiles of DMFT, respectively. The highest tertile of tooth loss also had an increased risk of lung cancer, with a HR of 1.68 (95% CI: 1.04, 2.70) compared with subjects with the expected number of lost teeth or fewer (linear trend, p = 0.043). The results were similar for lung cancer mortality and did not change substantially when the analysis was restricted to never users of cigarettes or opium. We found no associations between toothbrushing frequency and lung cancer incidence or mortality. CONCLUSION: Poor dental health indicated by tooth loss or DMFT, but not lack of toothbrushing, was associated with increased lung cancer incidence and mortality in this rural Middle Eastern population.

Exposure to polycyclic aromatic hydrocarbons, volatile organic compounds, and tobacco-specific nitrosamines and incidence of esophageal cancer.

BACKGROUND: Studying carcinogens in tobacco and nontobacco sources may be key to understanding the pathogenesis and geographic distribution of esophageal cancer. METHODS: The Golestan Cohort Study has been conducted since 2004 in a region with high rates of esophageal squamous cell carcinoma. For this nested study, the cases comprised of all incident cases by January 1, 2018; controls were matched to the case by age, sex, residence, time in cohort, and tobacco use. We measured urinary concentrations of 33 exposure biomarkers of nicotine, polycyclic aromatic hydrocarbons, volatile organic compounds, and tobacco-specific nitrosamines. We used conditional logistic regression to calculate odds ratios (ORs) and 95% confidence intervals for associations between the 90th vs the 10th percentiles of the biomarker concentrations and incident esophageal squamous cell carcinoma. RESULTS: Among individuals who did not currently use tobacco (148 cases and 163 controls), 2 acrolein metabolites, 2 acrylonitrile metabolites, 1 propylene oxide metabolite, and one 1,3-butadiene metabolite were significantly associated with incident esophageal squamous cell carcinoma (adjusted odds ratios between 1.8 and 4.3). Among tobacco users (57 cases and 63 controls), metabolites of 2 other volatile organic compounds (styrene and xylene) were associated with esophageal squamous cell carcinoma (OR = 6.2 and 9.0, respectively). In tobacco users, 2 tobacco-specific nitrosamines (NNN and N'-Nitrosoanatabine) were also associated with esophageal squamous cell carcinoma. Suggestive associations were seen with some polycyclic aromatic hydrocarbons (especially 2-hydroxynaphthalene) in nonusers of tobacco products and other tobacco-specific nitrosamines in tobacco users. CONCLUSION: These novel associations based on individual-level data and samples collected many years before cancer diagnosis, from a population without occupational exposure, have important public health implications.

Prevalence and determinants of opioid use disorder among long-term opiate users in Golestan Cohort Study.

BACKGROUND: Number of opiate users worldwide has doubled over the past decade, but not all of them are diagnosed with opioid use disorder. We aimed to identify the prevalence and risk factors for OUD after ten years of follow-up. METHODS: Among 8,500 chronic opiate users at Golestan Cohort Study baseline (2004-2008), we recalled a random sample of 451 subjects in 2017. We used three questionnaires: a questionnaire about current opiate use including type and route of use, the drug use disorder section of the Composite International Diagnostic Interview lifetime version, and the validated Kessler10 questionnaire. We defined opioid use disorder and its severity based on the DSM-5 criteria and used a cutoff of 12 on Kessler10 questionnaire to define psychological distress. RESULTS: Mean age was 61.2 ± 6.6 years (84.7% males) and 58% were diagnosed with opioid use disorder. Starting opiate use at an early age and living in underprivileged conditions were risk factors of opioid use disorder. Individuals with opioid use disorder were twice likely to have psychological distress (OR = 2.25; 95%CI: 1.44-3.52) than the users without it. In multivariate regression, former and current opiate dose and oral use of opiates were independently associated with opioid use disorder. Each ten gram per week increase in opiate dose during the study period almost tripled the odds of opioid use disorder (OR = 3.18; 95%CI: 1.79-5.63). CONCLUSIONS: Chronic opiate use led to clinical opioid use disorder in more than half of the users, and this disorder was associated with psychological distress, increasing its physical and mental burden in high-risk groups.

Incident cancers attributable to using opium and smoking cigarettes in the Golestan cohort study.

Background: Opium consumption has recently been identified as a carcinogen, but the impact of opium use on cancer burden is unknown. We aimed to evaluate the fraction of cancers that could be attributed to opium use alone and in combination with cigarette smoking in a region where opium is widely used. Methods: 50,045 Iranian adults were recruited to this prospective cohort study between 2004 and 2008 and were followed through January 2022. We assessed the association between using opium and/or cigarette smoking and various cancers using proportional hazards regression models. We then calculated population attributable fractions (PAFs) for all cancers and for groups of cancers causally linked to opium and cigarette smoking. Findings: Of the total participants, 8% only used opium, 8.3% only smoked cigarettes, and 9% used both substances. During a median 14 years of follow-up, 2195 individuals were diagnosed with cancer, including 215 opium-related cancers (lung, larynx, and bladder) and 1609 tobacco-related cancers (20 types). Opium use alone was estimated to cause 35% (95% CI: 26%-45%) of opium-related cancers, while smoking cigarettes alone was estimated to cause 9% (6%-12%) of tobacco-related cancers in this population. Using opium and/or cigarettes was estimated to cause 13% (9%-16%) of all cancers, 58% (49%-66%) of opium-related cancers, and 15% (11%-18%) of tobacco-related cancers. Moreover, joint exposure to opium and cigarettes had the greatest impact on cancers of the larynx, pharynx, lung, and bladder, with PAFs ranging from 50% to 77%. Interpretation: Using opium and smoking cigarettes account for a large proportion of cancers in this population. To reduce the cancer burden, prevention policies should aim to decrease the use of both substances through public awareness campaigns and interventional efforts. Funding: The Golestan Cohort Study work was funded by the Tehran University of Medical Sciences, Cancer Research UK, U.S. National Cancer Institute, International Agency for Research on Cancer. The presented analysis was supported by the International HundredK+ Cohorts Consortium (IHCC).

REPCAN: Guideline for REporting Population-based CANcer Registry Data.

Background: The objective of this study was to develop a guideline on how to report result of a population-based cancer registry. Methods: The guideline's development involved a core working committee and a scientific committee comprising experts from diverse domains. The process comprised three steps: 1) a comprehensive review of existing tools and guidelines and the development of the initial draft of the guideline based on a review of literature, 2) refinement items through several rounds of focus group discussion among the core group, and development initial draft, and 3) Evaluation of the initial draft by scientific committee members. Items in the guideline were organized to accommodate reports of population-based cancer registries as a scientific manuscript. Results: The core committee developed 47 items distributed in the major heading of a scientific manuscript presented as a checklist. The evaluation of the scientific committee led to a consensus on the majority of the items included in the checklist. Among 10 committee members, 7 provided unreserved approval, validating each item's necessity, applicability, and comprehensibility in the checklist. Feedback from the remaining 3 members was carefully analyzed and integrated to enhance the guideline's robustness. Incorporating feedback, a first final draft was presented in a meeting of scientific and core working committee members. Collaborative discussion ensured clarity of expression for each items and a final checklist was developed. Conclusion: The guideline abbreviated as REPCAN offers a standardized framework for reporting population-based cancer registry, fostering transparency, comparability, and comprehensive data presentation. The guideline encourages flexibility while promoting comprehensive and robust reporting practices.

Correction: Cost-effectiveness of fixed-dose combination pill (Polypill) in primary and secondary prevention of cardiovascular disease: A systematic literature review.

[This corrects the article DOI: 10.1371/journal.pone.0271908.].

Supportive Care Needs (SCN) of Cancer Patients Referred to the Medical Centers in Iran.

OBJECTIVE: The aim of this study was to evaluate the Supportive Care Needs s of cancer patients in Iran. METHODS: This descriptive-analytical, cross-sectional study was conducted on cancer patients referred to public and private medical centers in Gorgan (Northern Iran) in 2020. Cancer patients refered to private medical ccentes were recruited into the study using the convenience sampling method. The reliable and valid "Supportive Care Needs Survey-Short Form" (SCNS-SF) with 34 items in five domains of need (physical and daily living, psychological, sexuality, patient care and support, health system, and information) was used to collect data. RESULTS: Out of 247 patients, 54.7% were females with a mean age of 46.15± 9.36. The most common site of involvement was breast (25.1%), and the duration of involvement was 7.51±6.79 months. The total mean of SCNs was 68.80±18.5 so that the highest (73.68±15.03) and lowest (60.42±27.19) SCNs were related to physical and daily living as well as sexual domains, respectively. The highest frequency (62.3%) of SCNs was related to "fatigue/lack of energy". CONCLUSION: This study showed that cancer patients experienced many unmet needs in various dimensions. Therefore, it is necessary to address these needs simultaneously treating the disease and developing and implementing a care plan based on patients' priorities.