The association between anthropometric indices and ischemic heart disease: a large-scale cross-sectional study on the Iranian population.

This study aimed to evaluate the superiority of anthropometric indices compared to others for predicting ischemic heart disease (IHD) or cardiometabolic risk factors. This study was a cross-sectional analysis of the Pars Cohort Study data. In total, 9229 Valashahr inhabitants aged 40-75 were included in the analysis. The area under the receiver operating characteristic curve (AUC) analyses was used to compare the predictive accuracy of four anthropometric measures, including body mass index, waist to height ratio (WHtR), waist to hip ratio (WHR), and waist circumference (WC). IHD prevalence was 10.4% in our sample. The prevalence of diabetes mellitus (DM), hypertension, dyslipidemia, and metabolic syndrome was 12.7%, 29.2%, 58.4%, and 22.3%, respectively. All anthropometric indices had poor to good accuracy in predicting IHD risk factors, with AUCs ranging between 0.580 and 0.818. WHR was the most accurate measure for predicting IHD in both genders. All indexes had a better accuracy for predicting DM, dyslipidemia, and metabolic syndrome (MetS) in males than in females. To conclude, anthropometric measures, especially WC and WHtR, are recommended for predicting metabolic syndrome in primary prevention settings. These simple indices could help physicians find those who need further evaluation for MetS.

Volatile organic compounds and mortality from ischemic heart disease: A case-cohort study.

Background: Volatile organic compounds (VOCs) are major components of air pollution and tobacco smoke, two known risk factors for cardiovascular diseases. VOCs are ubiquitous in the environment and originate from a wide range of sources, including the burning of biomass, fossil fuels, and consumer products. Direct evidence for associations between specific VOCs and ischemic heart disease (IHD) mortality in the general population is scarce. Methods: In a case-cohort study (stratified by age groups, sex, residence, and tobacco smoking), nested within the population-based Golestan cohort study (n = 50,045, 40-75 years, 58% women, enrollment: 2004-2008) in northeastern Iran, we measured urinary concentrations of 20 smoking-related VOC biomarkers using ultra high-performance liquid chromatography coupled with electrospray ionization tandem mass spectrometry. We calculated hazard ratio (HR) and 95% confidence interval (CI) for their associations with IHD mortality during follow-up to 2018, using Cox regression models adjusted for age, ethnicity, education, marital status, body mass index, physical activity, wealth, and urinary cotinine. Results: There were 575 non-cases from random subcohort and 601 participants who died from IHD, mean (standard deviation) age, 58.2 (9.3) years, with a median of 8.4 years follow-up. Significant associations [3rd vs. 1st tertile, HR (95% CI), P for trend] were observed between biomarkers of acrylamide [1.68(1.05,2.69), 0.025], acrylonitrile [2.06(1.14,3.72), 0.058], acrolein [1.98(1.30,3.01), 0.003 and 2.44(1.43,4.18), 0.002], styrene/ethylbenzene [1.83(1.19,2.84), 0.007 and 1.44(1.01,2.07), 0.046], dimethylformamide/methylisocyanate [2.15(1.33,3.50), 0.001], and 1,3butadiene [2.35(1.52,3.63),<0.001] and IHD mortality. These associations were independent of tobacco smoking, and they were only present in the non-smoking subgroup. Conclusion: Our findings provide direct evidence for associations between exposure to several VOCs with widespread household and commercial use and IHD mortality many years after these exposures. These results highlight the importance of VOC exposure in the general population as a risk factor for cardiovascular diseases and underline the importance of bio-monitoring non-tobacco VOC exposure.

Polypharmacy and medication usage patterns in hypertensive patients: Findings from the Pars Cohort Study.

Polypharmacy, defined here as the concomitant use of five or more medications, is a significant health issue, particularly affecting individuals with chronic diseases like hypertension (HTN). To compare individuals with and without HTN in term of polypharmacy, and to investigate correlates of polypharmacy and medication use patterns in individuals with HTN in southwest Iran. This cross-sectional study used the baseline data of 9270 participants of the Pars Cohort Study (PCS) with a mean age of 52.6 ± 9.7 years. Poisson multivariable modeling was applied to identify correlates of polypharmacy, and Lexicomp® was used to assess drug-drug interactions. Anatomical Therapeutic Chemical classification was used to describe the pattern of medication use. The prevalence of polypharmacy in individuals without hypertension was 4.7 % (4.2%-5.2 %) vs. 23.7 % (22.1%-25.3 %) in individuals with hypertension (P < 0.001). Individuals with hypertension from middle-high socioeconomic status (SES) had a 1.51-fold higher prevalence of polypharmacy than vs. low SES. Those with more than three comorbidities had a 5.18 times higher prevalence of polypharmacy than those with isolated hypertension. Calcium channel blockers were the most common antihypertensives (20.9 %). In terms of drug-drug interactions, type C interactions were most prevalent among participants with hypertension and polypharmacy (76.0 %). Our findings imply a fairly high prevalence of polypharmacy and drug-drug interactions among individuals with hypertension; to tackle this issue, we recommend a national pharmacovigilance system, training programs for primary care physicians, public education and awareness campaigns, drug-checking campaigns, targeted screenings to alter modifiable risk factors, and the use of safe combination pills.

Meat consumption and incident type 2 diabetes: an individual-participant federated meta-analysis of 1·97 million adults with 100 000 incident cases from 31 cohorts in 20 countries.

BACKGROUND: Meat consumption could increase the risk of type 2 diabetes. However, evidence is largely based on studies of European and North American populations, with heterogeneous analysis strategies and a greater focus on red meat than on poultry. We aimed to investigate the associations of unprocessed red meat, processed meat, and poultry consumption with type 2 diabetes using data from worldwide cohorts and harmonised analytical approaches. METHODS: This individual-participant federated meta-analysis involved data from 31 cohorts participating in the InterConnect project. Cohorts were from the region of the Americas (n=12) and the Eastern Mediterranean (n=2), European (n=9), South-East Asia (n=1), and Western Pacific (n=7) regions. Access to individual-participant data was provided by each cohort; participants were eligible for inclusion if they were aged 18 years or older and had available data on dietary consumption and incident type 2 diabetes and were excluded if they had a diagnosis of any type of diabetes at baseline or missing data. Cohort-specific hazard ratios (HRs) and 95% CIs were estimated for each meat type, adjusted for potential confounders (including BMI), and pooled using a random-effects meta-analysis, with meta-regression to investigate potential sources of heterogeneity. FINDINGS: Among 1 966 444 adults eligible for participation, 107 271 incident cases of type 2 diabetes were identified during a median follow-up of 10 (IQR 7-15) years. Median meat consumption across cohorts was 0-110 g/day for unprocessed red meat, 0-49 g/day for processed meat, and 0-72 g/day for poultry. Greater consumption of each of the three types of meat was associated with increased incidence of type 2 diabetes, with HRs of 1·10 (95% CI 1·06-1·15) per 100 g/day of unprocessed red meat (I2=61%), 1·15 (1·11-1·20) per 50 g/day of processed meat (I2=59%), and 1·08 (1·02-1·14) per 100 g/day of poultry (I2=68%). Positive associations between meat consumption and type 2 diabetes were observed in North America and in the European and Western Pacific regions; the CIs were wide in other regions. We found no evidence that the heterogeneity was explained by age, sex, or BMI. The findings for poultry consumption were weaker under alternative modelling assumptions. Replacing processed meat with unprocessed red meat or poultry was associated with a lower incidence of type 2 diabetes. INTERPRETATION: The consumption of meat, particularly processed meat and unprocessed red meat, is a risk factor for developing type 2 diabetes across populations. These findings highlight the importance of reducing meat consumption for public health and should inform dietary guidelines. FUNDING: The EU, the Medical Research Council, and the National Institute of Health Research Cambridge Biomedical Research Centre.

Body Mass Index and Risk of Colorectal Cancer Incidence and Mortality in Asia.

Importance: The global burden of obesity is increasing, as are colorectal cancer (CRC) incidence and mortality. Objectives: To assess the association between body mass index (BMI) and risks of incident CRC and CRC-related death in the Asian population. Design, Setting, and Participants: This cohort study includes data pooled from 17 prospective cohort studies included in The Asia Cohort Consortium. Cohort enrollment was conducted from January 1, 1984, to December 31, 2002. Median follow-up time was 15.2 years (IQR, 12.1-19.2 years). Data were analyzed from January 15, 2023, through January 15, 2024. Exposure: Body mass index, calculated as weight in kilograms divided by height in meters squared. Main Outcomes and Measures: The primary outcomes were CRC incidence and CRC-related mortality. The risk of events is reported as adjusted hazard ratios (AHRs) and 95% CIs for incident CRC and death from CRC using the Cox proportional hazards regression model. Results: To assess the risk of incident CRC, 619 981 participants (mean [SD] age, 53.8 [10.1] years; 52.0% female; 11 900 diagnosed incident CRC cases) were included in the study, and to assess CRC-related mortality, 650 195 participants (mean [SD] age, 53.5 [10.2] years; 51.9% female; 4550 identified CRC deaths) were included in the study. A positive association between BMI and risk of CRC was observed among participants with a BMI greater than 25.0 to 27.5 (AHR, 1.09 [95% CI, 1.03-1.16]), greater than 27.5 to 30.0 (AHR, 1.19 [95% CI, 1.11-1.29]), and greater than 30.0 (AHR, 1.32 [95% CI, 1.19-1.46]) compared with those with a BMI greater than 23.0 to 25.0 (P < .001 for trend), and BMI was associated with a greater increase in risk for colon cancer than for rectal cancer. A similar association between BMI and CRC-related death risk was observed among participants with a BMI greater than 27.5 (BMI >27.5-30.0: AHR, 1.18 [95% CI, 1.04-1.34]; BMI >30.0: AHR, 1.38 [95% CI, 1.18-1.62]; P < .001 for trend) and was present among men with a BMI greater than 30.0 (AHR, 1.87 [95% CI, 1.49-2.34]; P < .001 for trend) but not among women (P = .15 for trend) (P = .02 for heterogeneity). Conclusions and Relevance: In this cohort study that included a pooled analysis of 17 cohort studies comprising participants across Asia, a positive association between BMI and CRC incidence and related mortality was found. The risk was greater among men and participants with colon cancer. These findings may have implications to better understand the burden of obesity on CRC incidence and related deaths in the Asian population.

One-carbon metabolism biomarkers and upper gastrointestinal cancer in the Golestan Cohort Study.

Incidence of esophageal and gastric cancer has been linked to low B-vitamin status. We conducted matched nested case-control studies of incident esophageal squamous cell carcinoma (ESCC; 340 case-control pairs) and gastric cancer (GC; 352 case-control pairs) within the Golestan Cohort Study. The primary exposure was plasma biomarkers: riboflavin and flavin mononucleotide (FMN) (vitamin B2), pyridoxal phosphate (PLP) (B6), cobalamin (B12), para-aminobenzoylglutamate (pABG) (folate), and total homocysteine (tHcy); and indicators for deficiency: 3-hydroxykyurenine-ratio (HK-r for vitamin B6) and methylmalonic acid (MMA for B12). We estimated odds ratios (ORs) and 95% confidence intervals (CIs) using conditional logistic regression adjusting for matching factors and potential confounders. High proportions of participants had low B-vitamin and high tHcy levels. None of the measured vitamin B levels was associated with the risk of ESCC and GC, but elevated level of MMA was marginally associated with ESCC (OR = 1.42, 95% CI = 0.99-2.04) and associated with GC (OR = 1.53, 95% CI = 1.05-2.22). Risk of GC was higher for the highest versus lowest quartile of HK-r (OR = 1.95, 95%CI = 1.19-3.21) and for elevated versus non-elevated HK-r level (OR = 1.59, 95% CI = 1.13-2.25). Risk of ESCC (OR = 2.81, 95% CI = 1.54-5.13) and gastric cancer (OR = 2.09, 95%CI = 1.17-3.73) was higher for the highest versus lowest quartile of tHcy. In conclusion, insufficient vitamin B12 was associated with higher risk of ESCC and GC, and insufficient vitamin B6 status was associated with higher risk of GC in this population with prevalent low plasma B-vitamin status. Higher level of tHcy, a global indicator of OCM function, was associated with higher risk of ESCC and GC.

Prevalence and Characteristics of Metabolic Dysfunction-Associated Fatty Liver Disease among an Iranian Adult Population with Ethnic and Genetic Diversity: Results of the PolyIran-Liver Study.

Background: Metabolic dysfunction-associated fatty liver disease (MAFLD) is a rising global public health concern. It has been demonstrated that its prevalence and characteristics vary by region and racial/ethnicity. We aimed to investigate the prevalence of MAFLD and its characteristics among Turkmen and non-Turkmen ethnic groups in a multiethnic population region of Iran. Methods: In this cross-sectional study, we analyzed baseline data for 1614 participants, aged above 50 years, from the PolyIran-Liver trial who were randomly selected from Gonabad city and determined the prevalence of MAFLD and its demographic and metabolic disorders for both the Turkmen and non-Turkmen ethnic groups. Multivariate binary logistic regressions were applied to identify MAFLD-associated factors for men and women separately for the Turkmen and non-Turkmen populations. Results: The mean (SD) age of the participants was 59.1(6.7) years. Of the participants, 51.5% (n=831) were men, and 52.9% (n=854) were Turkmen. The prevalence of MAFLD among the overall study population was 39.8% (n=614). It was more common among women (45.8% vs. 34.1% in men, P<0.001), non-Turkmens (43.9% vs. 36.1% in Turkmens, P<0.001), and at age 50-64 (41.5% vs.36.1% in age≥65 P=0.004). The fully adjusted multivariate analysis in sex strata exhibited an independent negative association between Turkmen ethnicity only among men but not among women. The increased waist circumference (WC) was the most common metabolic disorder, observed in more than 95.5% of patients with MAFLD (P<0.001). Multivariate analysis in sex/ethnic strata with adjustment for potential confounders revealed an independent association of MAFLD with increased WC, insulin resistance, impaired fasting glucose/diabetes type 2, and high alanine aminotransferase (ALT) among women in both ethnic groups while with elevated triglyceride (TG) only among Turkmen and high body mass index (BMI) only among non-Turkmen women. Increased WC had the strongest independent association with MAFLD among women and the highest odds ratio (OR) with MAFLD in Turkmen women (OR: 6.10; 95% CI 1.56-23.86 vs. 4.80 in non-Turkmen women). Among men, MAFLD was independently associated with insulin resistance, high BMI, and high ALT in both ethnic groups and elevated TG only in non-Turkmen men (all P<0.001). Insulin resistance had the strongest independent OR with MAFLD among men with similar size in both ethnic groups (4.68 [95% CI 2.56-8.55]) in non-Turkmen men and 4.37 (95% CI 2.27-8.42 in Turkmen men). Conclusion: This study revealed the high prevalence of MAFLD with a sex and ethnic disparity in the middle-aged population of Gonabad city. Further research is needed to understand the factors contributing to the higher prevalence of MAFLD in this region, particularly in women. Furthermore, considering the diverse ethnic population of Iran, it is suggested that future investigations on the sex and ethnic aspects of MAFLD in the Iranian population be conducted to provide targeted prevention strategies better suited for the Iranian population.

Descriptive Epidemiology of Early-Onset Gastrointestinal Cancers in Iran, 2014-2018.

Background: We aim to present incidence rates and geographical distribution of most common early-onset gastrointestinal cancers (EOGICs), including early-onset esophageal cancer (EOEC), gastric cancer (EOGC) and colorectal cancer (EOCRC) in Iran, 2014-2018. Methods: Data on new cases of EOEC, EOGC and EOCRC were obtained from publicly available annual reports of the Iranian National Population-based Cancer Registry (INPCR). Incidence rates were calculated using the population data available from the Statistical center of Iran. We considered the World standard population for calculation of age-standardized incidence rates (ASR). We also calculated 95% confidence intervals (CIs) for ASR. All rates are presented per 100000 person-years. Results: Overall, 19,679 new cases of EOGIC were registered by the INPCR between 2014 and 2018. The ASRs (95% CI) of EOEC, EOGC and EOCRC were 0.49 (95% CI: 0.47-0.51), 1.67 (1.63-1.71), and 3.07 (3.01-3.13) per 100,000 person-years, respectively. Our findings indicate decreasing and constant trends in the ASR of EOEC and EOGC during the study period, 2014-2018. There was an increasing trend in the ASR of EOCRC. We also found geographical disparities in the incidence rates of EOGICs across provinces of Iran, suggesting the highest ASRs of EOEC in Golestan (1.3), EOGC in Ilam (2.99) and EOCRC in Ilam (4.49). Conclusion: Our findings suggested that the incidence rate of EOCRC is consistently increasing. We also found variations in the incidence of EOGICs among different provinces. Further investigations are recommended to clarify the time trends and risk factors of EOGICs in Iran.

Causes of Colectomy in Patients with Ulcerative Colitis: Findings from an Iranian National Registry.

BACKGROUND: Ulcerative colitis (UC) is a form of inflammatory bowel disease (IBD) marked by rectal and colon inflammation, leading to relapsing symptoms. Its prevalence is increasing, particularly in developed nations, impacting patients' health. While its exact cause remains unclear, genetic and environmental factors are implicated, elevating the risk of colorectal cancer (CRC). Colectomy, though declining, is still performed in select UC cases, necessitating further study. METHODS: We analyzed data from the Iranian Registry of Crohn's and Colitis (IRCC) to examine UC patients undergoing colectomy. We collected demographic and clinical data from 91 patients, focusing on dysplasia. Statistical analyses assessed dysplasia risk factors. RESULTS: Patients with dysplasia were older at diagnosis and surgery compared to those without dysplasia. Age emerged as a significant risk factor for dysplasia in UC patients undergoing colectomy. No significant associations were found between dysplasia and other factors. CONCLUSION: Age plays a crucial role in dysplasia risk among UC patients undergoing colectomy. Older age at diagnosis and surgery may indicate a higher risk of dysplasia and CRC. Clinicians should consider age when managing UC patients and implementing screening protocols. Further research with larger samples is needed to confirm these findings.

How Similar Are Drug Data and Disease Self-report? Estimating the Prevalence of Chronic Diseases in Less Developed Settings.

BACKGROUND: Drug data has been used to estimate the prevalence of chronic diseases. Disease registries and annual surveys are lacking, especially in less-developed regions. At the same time, insurance drug data and self-reports of medications are easily accessible and inexpensive. We aim to investigate the similarity of prevalence estimation between self-report data of some chronic diseases and drug data in a less developed setting in southwestern Iran. METHODS: Baseline data from the Pars Cohort Study (PCS) was re-analyzed. The use of disease-related drugs were compared against self-report of each disease (hypertension [HTN], diabetes mellitus [DM], heart disease, stroke, chronic obstructive pulmonary disease [COPD], sleep disorder, anxiety, depression, gastroesophageal reflux disease [GERD], irritable bowel syndrome [IBS], and functional constipation [FC]). We used sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and the Jaccard similarity index. RESULTS: The top five similarities were observed in DM (54%), HTN (53%), heart disease (32%), COPD (30%), and GERD (15%). The similarity between drug use and self-report was found to be low in IBS (2%), stroke (5%), depression (9%), sleep disorders (10%), and anxiety disorders (11%). CONCLUSION: Self-reports of diseases and the drug data show a different picture of most diseases' prevalence in our setting. It seems that drug data alone cannot estimate the prevalence of diseases in settings similar to ours. We recommend using drug data in combination with self-report data for epidemiological investigation in the less-developed setting.

Sex and age differences in inflammatory bowel disease patients; a nationwide study based on Iranian Registry of Crohn's and Colitis (IRCC).

BACKGROUND: Despite the rising prevalence of Inflammatory Bowel Disease (IBD), age and sex differences in its outcomes remain understudied. We investigated age and sex differences in IBD patients using a nationwide study in Iran, the Iranian Registry of Crohn's and Colitis (IRCC). METHODS: The IRCC is a national registry that gathered information on adult IBD patients since 2017. The collected data included demographic information, medication history, disease activity, comorbidities, diagnosis age, prognosis, the extent of ulcerative colitis (UC), Crohn's disease (CD) location, and extraintestinal manifestations. The statistical methods included the independent Student's t-test, Chi-square test, and binary logistic regression, using R version 4.2.2. RESULTS: Among the 9,392 IBD patients, 7,496 (3,600 females) and 1,896 (808 females) had UC and CD, respectively. Sex difference showed higher odds of active disease in the past six months in male CD patients (OR 1.24 [95%CI 1.03, 1.49]) vs. females, but in male UC patients, the OR was 0.85 [0.78, 0.93]. Severe disease was less likely in CD patients aged 19-59 and >60 vs. <18. Similarly, UC patients <18 had lower odds of severe disease vs. those aged 19-59 and >60. CONCLUSIONS: This study emphasizes the importance of understanding age and sex differences in IBD outcomes. These findings contribute to the ongoing global discussion on IBD management and facilitate the development of targeted interventions and personalized care.

Prevalence and risk factors of gastroesophageal reflux disease in Iran: A cross-sectional analysis from the PERSIAN cohort.

BACKGROUND: This study assessed the prevalence of gastroesophageal reflux disease (GERD) in a general adult population in Iran. The association between GERD and various factors was also evaluated. METHODS: We performed a cross-sectional study on 163,018 individuals aged over 35 who were enrolled in the PERSIAN cohort. GERD was defined as the occurrence of heartburn and/or regurgitation symptoms at least several days a month. Survey design analysis for pooled data was performed and multiple regression analysis was conducted to determine the independent risk factors for GERD. RESULTS: The prevalence of GERD in our study was estimated at 21.86% (95% confidence interval:17.4%-36.4%). The mean age of the participants was 49.84 years±9.25 (35-70) and 44.75% of the participants were male. Symptoms of heartburn and regurgitation were reported in 18.65% (n: 29,170) and 6.06% (n: 9,717) of participants, respectively. In the multivariate analysis, several factors were found to be associated with a higher prevalence of GERD: female sex, age >50, current smoking, opium use, weekly consumption of fried foods, frequent consumption of hot tea, less than 6 hours of sleep per night, psychiatric disorders, usage of NSAIDs, and poor oral hygiene, were associated with a higher prevalence of GERD. Conversely, higher education levels and average physical activity were found to be less commonly associated with GERD. CONCLUSION: We found a relatively high prevalence of GERD (21.86%) in this population-based study in Iran. By identifying modifiable risk factors, this research offers opportunities for targeted interventions and lifestyle modifications to reduce the burden of GERD.

Prevalence and Incidence of Metabolic Syndrome and Its Components Among Waterpipe Users.

Objectives: To determine the associations between waterpipe use, duration, and intensity of use with prevalence and incidence of metabolic syndrome and its components (increased waist circumference, triglycerides, fasting glucose, blood pressure and decreased high-density lipoprotein cholesterol). Methods: We conducted cross-sectional and prospective analyses using data from the Pars Cohort Study in southern Iran, encompassing 9,264 participants at the baseline, and 5,002 randomly selected in a repeated follow-up. We used multivariate logistic regression models adjusted for age, sex, education, wealth score, physical activity and cigarette pack-years to report odds ratios (OR) and 95% confidence intervals (CI). Results: Among 9,264 participants, 3,119 (33.7%) had metabolic syndrome, and 3,482 (37.6%) had ever smoked waterpipe, with both more common in women than in men. In adjusted models, former waterpipe use was significantly associated with prevalence (OR = 1.43, 95% CI: 1.23-1.68) and incidence (OR = 1.57, 95% CI: 1.19-2.06) of the metabolic syndrome while current waterpipe use was not. Past use was associated with increased risk in all components of metabolic syndrome; current use was associated with increases in all except high blood glucose and hypertension. Past waterpipe users had higher waterpipe use intensity (before quitting) in comparison with current users (2.3 vs. 2.0 waterpipes per day, p < 0.01) and had started waterpipe smoking at a younger age (27.2 vs. 30.1 years, p < 0.01). Conclusion: Waterpipe use was associated with metabolic syndrome and its components, especially among former users potentially due to higher intensity and earlier initiation of use.

Towards hepatitis C virus elimination in Iran: A blueprint for comprehensive strategies.

The hepatitis C virus (HCV) continues to pose a significant public health challenge in Iran, mirroring a worldwide concern. This situation calls for a cohesive strategy that aligns with the World Health Organization's (WHO) goals for HCV elimination by 2030. Central to this strategy is targeting high-risk groups, notably people who inject drugs and prisoners, with prevention, screening and treatment. The deployment of point-of-care testing and treatments in prisons and harm reduction facilities is vital. The adoption of cost-effective generic direct-acting antivirals represents a major step forward. Furthermore, innovative educational initiatives for healthcare providers and awareness campaigns for the public are critical. Additionally, tackling stigma, ensuring treatment affordability and upholding strict surveillance and data management, coupled with ongoing policy reviews, are vital components. This comprehensive and integrated approach is designed to drive Iran towards eliminating HCV and can serve as a blueprint for other countries with similar challenges.

Potential impact of controlling opium use prevalence on future cancer incidence in Iran.

Background: The International Agency for Research on Cancer (IARC) recently classified opium consumption as carcinogenic to humans. This study aimed to estimate the potential reduction in incident cancers by 2035 in Iran, which accounts for 42% of global opium consumption, through decreasing opium use prevalence. Methods: The population attributable fraction (PAF) of opium-related cancers was projected using national cancer incidence, age- and gender-specific opium use prevalence, relative cancer risks associated with opium use, and annual percentage changes in cancer incidence rates in Iran. Opium-related cancers were defined based on IARC monographs as cancers of lung, larynx, bladder, esophagus, stomach, pancreas, and pharynx. The number of preventable cancer cases under different opium prevalence scenarios was determined by subtracting attributable cases in each year based on current prevalence from those in alternative scenarios. Findings: By 2035, an estimated 3,001,421 new cancer cases are expected in Iran, with 904,013 (30.1%) occurring in opium-related sites. Maintaining the current opium prevalence (5.6%) is projected to cause 111,130 new cancer cases (3.7% of all cancers, 12.3% of opium-related). A 10%, 30%, and 50% reduction in opium prevalence could prevent 9,016, 28,161, and 49,006 total incident cancers by 2035 in Iran, respectively. Reducing opium use prevalence by 10%-50% is projected to have the highest impact on lung cancer (prevention of 2,946-15,831 cases), stomach cancer (prevention of 2,404-12,593 cases), and bladder cancer (prevention of 1,725-9,520 cases). Interpretation: Our results highlight the significant benefits that can be achieved through effective cancer prevention policies targeting opium use in Iran. Neglecting this risk factor is estimated to pose a significant burden on cancer incidence in the next decade in this population. Funding: None.

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.

A systematic review and meta-analysis of extra-intestinal manifestation of inflammatory bowel disease in the Eastern Mediterranean Region (EMRO) countries.

Background: Inflammatory bowel disease which is subgrouped mainly to ulcerative colitis and Crohn's disease is thought to be a multi-organ disease. Most organs can be involved in the disease course in addition to gastrointestinal tract involvement. In this systematic review we aimed to assess the prevalence of these manifestations in Eastern Mediterranean Regional Office (EMRO) countries. Method: The present systematic review and meta-analysis study was performed according to the Preferred Reporting Items for Systematic Review and Meta-analysis (PRISMA) guideline. Joanna Briggs Institute (JBI) Critical Appraisal Checklist was admired for the quality evaluation of the included studies. For determining the heterogeneity, we used Cochran test and I2 statistics. Result: Finally, 12 studies were included in our study. Based on the results of our study the prevalence of arthritis in ulcerative colitis and Crohn's disease patients was 7.1% (95% CI: 2.6-18.2%) and 13.5% (95% CI: 2.6-47.3%), respectively. Prevalence of arthralgia in ulcerative colitis patients was 18.4% (95% CI: 14.3-23.3%). skin involvement prevalence was 9.9% (95% CI 4.7-19.6%) in inflammatory bowel disease (IBD) patients. ocular involvement prevalence was 7.2% (95% CI 17-25.8%) in IBD patients. PSC prevalence in ulcerative colitis and Crohn's disease patients was 3.5% (95% CI: 1.7-7.3%) and 2.7% (95% CI: 1.3-5.5%), respectively. Conclusion: Based on the results of this study arthralgia and arthritis were the most common extra-intestinal manifestation of IBD followed by dermatologic and ocular involvements. This extra-intestinal manifestation can challenge the patients' management and identifying their pattern is important during the disease course.

Chitosan-modified manganese oxide-conjugated methotrexate nanoparticles delivering 5-aminolevulinic acid as a dual-modal T1-T2* MRI contrast agent in U87MG cell detection.

OBJECTIVE: Glioblastoma multiforme is a highly aggressive form of brain cancer, and early diagnosis plays a pivotal role in improving patient survival rates. In this regard, molecular magnetic resonance imaging has emerged as a promising imaging modality due to its exceptional sensitivity to minute tissue changes and the ability to penetrate deep into the brain. This study aimed to assess the efficacy of a novel contrast agent in detecting gliomas during MRI scans. MATERIALS AND METHODS: The contrast agent utilized modified chitosan coating on manganese oxide nanoparticles. The modification included adding methotrexate and 5-aminolevulinic acid (MnO2/CS@5-ALA-MTX) to target cells with overexpressed folate receptors and breaking down excess hydrogen peroxide in tumor tissue, resulting in enhanced signal intensity in T1-weighted MR images but diminished signal intensity in T2*-weighted MR images. RESULTS: The nanosystem was characterized and evaluated in MR imaging, safety, and ability to target cells both in vivo and in vitro. MTX-free nanoparticles (MnO2/CS@5-ALA NPs) had no obvious cytotoxicity on cell lines U87MG and NIH3T3 after 24/48 h at a concentration of up to 160 µgr/mL (cell viability more than 80%). In this system, methotrexate enables tumor targeting and the MnO2/5-ALA improves T1-T2*-weighted MRI. In addition, MRI scans of mice with M109 carcinoma indicated significant tumor uptake and NP capacity to improve the positive contrast effect. CONCLUSION: This developed MnO2/CS@5-ALA-MTX nanoparticle system may exhibit great potential in the accurate diagnosis of folate receptor over-expressing cancers such as glioblastoma.

The protective effect of dietary folate intake on gastric cancer is modified by alcohol consumption: A pooled analysis of the StoP Consortium.

Dietary folate intake has been identified as a potentially modifiable factor of gastric cancer (GC) risk, although the evidence is still inconsistent. We evaluate the association between dietary folate intake and the risk of GC as well as the potential modification effect of alcohol consumption. We pooled data for 2829 histologically confirmed GC cases and 8141 controls from 11 case-control studies from the international Stomach Cancer Pooling Consortium. Dietary folate intake was estimated using food frequency questionnaires. We used linear mixed models with random intercepts for each study to calculate adjusted odds ratios (OR) and 95% confidence interval (CI). Higher folate intake was associated with a lower risk of GC, although this association was not observed among participants who consumed >2.0 alcoholic drinks/day. The OR for the highest quartile of folate intake, compared with the lowest quartile, was 0.78 (95% CI, 0.67-0.90, P-trend = 0.0002). The OR per each quartile increment was 0.92 (95% CI, 0.87-0.96) and, per every 100 µg/day of folate intake, was 0.89 (95% CI, 0.84-0.95). There was a significant interaction between folate intake and alcohol consumption (P-interaction = 0.02). The lower risk of GC associated with higher folate intake was not observed in participants who consumed >2.0 drinks per day, ORQ4v Q1 = 1.15 (95% CI, 0.85-1.56), and the OR100 µg/day = 1.02 (95% CI, 0.92-1.15). Our study supports a beneficial effect of folate intake on GC risk, although the consumption of >2.0 alcoholic drinks/day counteracts this beneficial effect.

Characterization of multifunctional ß-cyclodextrin-coated Bi2O3 nanoparticles conjugated with curcumin for CT imaging-guided synergetic chemo-radiotherapy in breast cancer.

Nanotechnology-based diagnostic, and therapeutic approaches revolutionized the field of cancer detection, and treatment, offering tremendous potential for cost-effective interventions in the early stages of disease. This research synthesized bismuth oxide (Bi2O3) nanoparticles (NPs) that were modified with polycyclodextrin (PCD), and functionalized with glucose (Glu) to load curcumin (CUR) for CT imaging and chemo-radiotherapy applications in Breast Cancer. The prepared Bi2O3@PCD-CUR-Glu NPs underwent comprehensive characterization, encompassing various aspects, including cell migration, cytotoxicity, cellular uptake, blood compatibility, reactive oxygen species (ROS) generation ability, real-time PCR analysis, in-vivo safety assessment, in-vivo anti-tumor efficacy, as well as in-vitro CT contrast and X-ray RT enhancement evaluation. CT scan was conducted before and after (1 and 3 h) intravenous injection of Bi2O3@PCD-CUR-Glu NPs. Through the use of coupled plasma optical emission spectrometry (ICP-OES) analysis, the final prepared nanoparticle distribution in the Bab/c mice was assessed. The spherical NPs that were ultimately synthesized and had a diameter of around 80 nm demonstrated exceptional toxicity towards the SKBr-3 breast cancer cell line. The cell viability was at its lowest level after 48 h of exposure to a radiation dose of 2 Gy at a concentration of 100 µg/mL. The combined treatment involving using Bi2O3@PCD-CUR-Glu NPs along with X-ray radiation showed a substantial increase in the generation of ROS, specifically a remarkable 420 % growth. Gene expression analysis indicated that the expression levels of P53, and BAX pro-apoptotic genes were significantly increased. The in-vitro CT imaging analysis conducted unequivocally demonstrated the notable superiority of NPs over Omnipaque in terms of X-ray absorption capacity, a staggering 1.52-fold increase at 80 kVp. The resultsdemonstrated that the targeted Bi2O3@PCD-CUR-Glu NPs could enhance the visibility of a small mice tumor that is detectable by computed tomography and made visible through X-ray attenuation. Results suggested that Bi2O3@PCD-CUR-Glu NPs, integrated with CT imaging and chemo-radiotherapy, have great potential as a versatile theranostic system for clinical application.