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Abstract. Background: The aim of this study was to assess the effects of supplementation with flaxseed on anthropometric measurements, lipid profile, insulin resistance, and inflammatory biomarkers in overweight and obese adults. Methods: Fifty overweight and obese adults with body mass index (BMI) of 30.72 ± 3.31 kg/m2 participated in this study. Participants were randomly assigned to take lifestyle advice or lifestyle advice plus 30 g/day milled flaxseed for 12 weeks. The primary outcome was body weight; secondary outcomes included other anthropometric parameters, lipid profile and inflammatory biomarkers. Results: At the end of the study, the following significant mean differences were seen in flaxseed and control groups, respectively: weight [−9.36 vs. −3.09 kg; P 2; P Conclusion: These results suggest that flaxseed supplementation in addition to lifestyle modification is significantly superior to lifestyle modification alone for weight loss. More studies with different dosages of flaxseed are needed to find the optimal dosage. This trial was registered at clinicaltrials.gov as NCT02410668.

Background: Abdominal obesity is associated with increased risk of myocardial infarction and death events. Thus, obtaining data on the status of abdominal obesity is important in risk factor assessment and prevention of non-communicable diseases. This study aimed to evaluate the validity of using pictograms to classify abdominal obesity indices (waist circumference [WC], waist-hip ratio [WHR], and waist-height ratio [WHtR]) into normal and at-risk categories and determine the effects of demographic characteristics on this validity. Methods: This cross-sectional study used data from Pars Cohort Study (PCS). Participants chose the most similar pictogram scores to their body size at 15, 30 years, and current age. Optimal normal/at-risk cut-off values for pictograms were calculated using sensitivity/specificity plots. Receiver operating characteristic curves were used to evaluate the validity of pictograms. Validity measures were analyzed across different subgroups of demographic characteristics. Results: A total of 9263 participants (46% males) were included in the study. The estimated area under the curves were 84% for WC, 77% for WHR, and 89% for WHtR in males, and 84% for WC, 73% for WHR, and 90% for WHtR in females. Optimal pictogram cutoffs to classify central obesity for WC, WHR, and WHtR were 4, 4, and 5 in males and 4, 4, and 6 in females, respectively. The majority of demographic characteristics were not associated with the validity of pictograms. Conclusion: Using pictograms to determine normal and at-risk categories of abdominal obesity indices is valid among adult population with a wide range of demographic characteristics. However, the results need to be interpreted with caution in those with a positive history of weight fluctuation.

Tooth loss and periodontal disease have been associated with several cancers, and poor oral health may be an important risk factor for upper gastrointestinal (UGI, i.e., esophageal and gastric) cancers. We assessed the relationship between oral health and UGI cancers using a large prospective study of over 50,000 adults living in Golestan Province, Iran, a high-incidence area for these cancers. Hazard ratios (HRs) and 95% confidence intervals (CI) were estimated for the association between three different measures of oral health [frequency of tooth brushing; number of missing teeth; and the sum of decayed, missing, and filled teeth (DMFT)] and UGI cancers. During a median follow-up duration of 13 years, there were 794 incident UGI cancers (396 esophageal and 398 gastric cancers). Daily tooth brushing was associated with a decreased risk of developing both esophageal (HR = 0.670; 95% CI: 0.486–0.924) and gastric (HR = 0.741; 95% CI: 0.544–1.01) cancers (combined UGI cancer HR = 0.697; 95% CI: 0.558–0.871) compared with never brushing. Tooth loss in excess of the loess smoothed, age- and sex-specific median number of teeth lost was significantly associated with esophageal (HR = 1.64; 95% CI: 1.08–2.47) and gastric cancers (HR = 1.58; 95% CI: 1.05–2.38). There were some adverse associations between DMFT and UGI cancers but most were not statistically significant. These results suggest increased risk of developing UGI cancers among individuals with poor oral health, and those who do not perform regular oral hygiene.Prevention Relevance:Poor oral health is associated with the risk of upper gastrointestinal cancers, and oral hygiene practices may help prevent these cancers.

Association of different combinations of four antibodies (CagA, VacA, NapA, and GroEL) with gastric adenocarcinoma and its subtypes.

The reported associations with gastric adenocarcinoma and seropositivity to different Helicobacter pylori antigens using multiplex serology have not been consistent across studies. We aimed to investigate the association between 15 different multiplex serology antigens and the risk of gastric cardia (GCA) and gastric noncardia (GNCA) adenocarcinomas in northeastern Iran, a population with high rates of gastric adenocarcinoma. We included 272 cases of gastric adenocarcinoma (142 GCA, 103 GNCA, and 27 unspecified) and 524 controls who were individually matched to cases for age, sex, and place of residence in a population-based case–control study. Seropositivity to H. pylori was assessed using both multiplex serology and H. pylori IgG ELISA. Ninety-five percent of controls were seropositive to H. pylori. Of the 15 antibodies in the multiplex assay, 11 showed no significant association with gastric adenocarcinomas. CagA and VacA were associated with a significantly increased risk of all gastric adenocarcinoma and GNCA in multivariate models. Surprisingly, GroEL and NapA were significantly associated with a reduced risk of these tumors. Only CagA antigen was associated with significantly elevated risk of GCA. We found no associations between H. pylori seropositivity overall either by whole-cell ELISA test or multiplex serology, likely due to the high prevalence of seropositivity. Individual antigen testing showed that CagA positivity was associated with increased risk of both noncardia and cardia adenocarcinoma, which is similar to some other Asian populations, whereas two antigens were associated with lower risk of gastric cancer. This latter result was unexpected and should be retested in other populations. Cancer Res; 75(22); 4876–83. ©2015 AACR.

Red meat and processed meat are associated with some gastrointestinal cancers. Our study aims to investigate the association of different meat types with esophageal and gastric cancer (EC, GC) in a high-risk population. The Golestan Cohort Study (GCS) is a population-based cohort of 50 045 individuals aged 40 to 75 from northeast Iran. Detailed data on different exposures were collected using validated questionnaires. We considered quintiles of meat consumption, using grams and density (g/1000 kcal/day). We calculated intake of red, processed, organ and white meat, as well as total red meat, including the first three. We used proportional hazards regression models to estimate hazard ratios (HRs) and corresponding 95% confidence intervals (CIs) for the association between meat types and cancer. During 12 years of follow-up, out of 49 585 participants (57.4% women), 369 developed EC (48.2% women) and 368 developed GC (27.5% women), including 309 esophageal squamous cell, 20 esophageal adenocarcinomas, 216 cardia and 95 non-cardia GC. No association was found for EC except for red meat among females (HR for one quintile increase 1.13, 95% CI = 1.00-1.27). The risk of GC increased for intake of total red meat (HR 1.08, 95% CI = 1.00-1.17) and red meat separately (HR 1.09, 95% CI = 1.00-1.18). The HR for red meat and non-cardia GC was 1.23 (95% CI = 1.02-1.48). No associations were observed for other types of meat. In conclusion, in this high-risk population red meat intake is associated with GC, but not EC, suggesting a substantial role of this modifiable factor in determining the burden of GC.

BACKGROUND: Immunosuppressive agents used in the treatment of inflammatory bowel diseases (IBDs) could potentially increase the risk of coronavirus disease 2019 (COVID-19). We aimed to compare COVID-19 frequency in patients with IBD with their households and identify the related risk factors. METHODS: Firstly, a multi-centered, observational study on 2110 patients with IBD and 2110 age-matched household members was conducted to compare COVID-19 frequency. Secondly, the data of patients with IBD and COVID-19 who had called the COVID-19 hotline were added. Multivariable logistic regression was used to evaluate the effect of age, type and severity of IBD, the number of comorbidities, and medications on the frequency of COVID-19 among the patients with IBD. RESULTS: The prevalence of COVID-19 in patients with IBD and household groups was similar (34 [1.61%] versus 35 [1.65%]; P = 0.995). The prevalence of COVID-19 increased from 2.1% to 7.1% in those with three or more comorbidities (P = 0.015) and it was significantly higher in those with severe IBD (P = 0.026). The multivariable analysis only showed a significant association with anti-TNF monotherapy (OR: 2.5, CI: 0.97-6.71, P = 0.05), and other medications were not associated with COVID-19. CONCLUSION: The prevalence of COVID-19 in patients with IBD was similar to the household members. Only patients with IBD receiving anti-TNF monotherapy had a higher risk of COVID-19 susceptibility. This finding could be attributed to the higher exposure to the virus during administration in health care facilities.

BackgroundCohort studies play essential roles in assessing causality, appropriate interventions. The study, Post-crash Prospective Epidemiological Research Studies in IrAN Traffic Safety and Health Cohort, aims to investigate the common health consequences of road traffic injuries (RTIs) postcrash through multiple follow-ups.MethodsThis protocol study was designed to analyse human, vehicle and environmental factors as exposures relating to postcrash outcomes (injury, disability, death, property damage, quality of life, etc). Population sources include registered injured people and followed up healthy people in precrash cohort experienced RTIs. It includes four first-year follow-ups, 1 month (phone-based), 3 months (in-person, video/phone call), 6 and 12 months (phone-based) after crash. Then, 24-month and 36-month follow-ups will be conducted triennially. Various questionnaires such as Post-traumatic Stress Disorder Questionnaire, Patient Health Questionnaire, WHO Disability Assessment Schedules, Cost-related Information, etc are completed. Counselling with a psychiatrist and a medical visit by a practitioner are provided accompanied by extra tools (simulator-based driving assessment, and psychophysiological tests). Through preliminary recruitment plan, 5807, 2905, 2247 and 1051 subjects have been enrolled, respectively at the baseline, first, second and third follow-ups by now. At baseline, cars and motorcycles accounted for over 30% and 25% of RTIs. At first follow-up, 27% of participants were pedestrians engaged mostly in car crashes. Around a fourth of injuries were single injuries. Car occupants were injured in 40% of collisions.DiscussionThe study provides an opportunity to investigate physical-psychosocial outcomes of RTIs, predictors and patterns at follow-up phases postinjury through longitudinal assessments, to provide advocates for evidence-based safety national policy-making.

Aims Individuals with non-alcoholic steatohepatitis or elevated liver enzymes have increased cardiovascular mortality but are often excluded from prevention trials. We investigated the effectiveness of fixed-dose combination therapy for the prevention of major cardiovascular events (MCVE) among individuals with and without presumed non-alcoholic steatohepatitis (pNASH). Methods and results Two thousand four hundred participants over 50 were randomized into the intervention and control groups. Consent was obtained post-randomization. Consenting participants in the intervention group were given a pill containing aspirin, atorvastatin, hydrochlorothiazide, and valsartan (polypill). Participants were followed for 5 years. Presumed non-alcoholic steatohepatitis was diagnosed by ultrasonography and elevated liver enzymes. The primary outcome was MCVE. ClinicalTrials.gov: NCT01245608. Among the originally randomized population, 138 of 1249 in the intervention group (11.0%) and 137 of 1017 controls (13.5%) had MCVE during the 5-year follow-up [unadjusted risk ratio (RR) 0.83, 95% confidence interval (CI) 0.66–1.03]. Of the 1508 participants who consented to additional measurements and treatment, 63 of 787 (8.0%) intervention group participants and 86 of 721 (11.9%) controls had MCVE (adjusted RR 0.61, 95% CI 0.44–0.83). Although the adjusted relative risk of MCVE in participants with pNASH (0.35, 95% CI 0.17–0.74) was under half that for participants without pNASH (0.73, 95% CI 0.49–1.00), the difference did not reach statistical significance. There was no change in liver enzymes in participants taking polypill but among those with pNASH, there was a significant decrease after 60 months of follow-up (intragroup −12.0 IU/L, 95% CI −14.2 to −9.6). Conclusion Among patients consenting to receive fixed-dose combination therapy, polypill is safe and effective for the prevention of MCVE, even among participants with fatty liver and increased liver enzymes.

Esophageal squamous cell carcinoma (ESCC) shows remarkable variation in incidence that is not fully explained by known lifestyle and environmental risk factors. It has been speculated that an unknown exogenous exposure(s) could be responsible. Here we combine the fields of mutational signature analysis with cancer epidemiology to study 552 ESCC genomes from eight countries with varying incidence rates. Mutational profiles were similar across all countries studied. Associations between specific mutational signatures and ESCC risk factors were identified for tobacco, alcohol, opium and germline variants, with modest impacts on mutation burden. We find no evidence of a mutational signature indicative of an exogenous exposure capable of explaining differences in ESCC incidence. Apolipoprotein B mRNA-editing enzyme, catalytic polypeptide-like (APOBEC)-associated mutational signatures single-base substitution (SBS)2 and SBS13 were present in 88% and 91% of cases, respectively, and accounted for 25% of the mutation burden on average, indicating that APOBEC activation is a crucial step in ESCC tumor development.

Background: Polypharmacy can negatively affect the life of type 2 diabetes (T2DM) patients. There is little evidence on the associated factors of, and patterns of polypharmacy among T2DM patients in developing regions. The aim of this study is to determine the population-based prevalence of polypharmacy, its associated factors, and pattern in southern Iran. Methods: We used baseline data from the Pars Cohort Study (PCS). Age-standardized prevalence of polypharmacy and its 95% confidence interval (CI) were estimated. Association of polypharmacy with demographic and socio-economic factors, anthropometric measures, serum biomarkers, physical activity, cigarette and tobacco smoking, and multimorbidity was assessed by applying multivariable Poisson modeling. Prevalence ratio (PR) and its CI were estimated. The Anatomical Therapeutic Chemical (ATC) classification system was used for drug classification. Results: Totally, 874 previously diagnosed T2DM patients with a mean age of 56.3±9.2 participated in the study. The estimated age-standardized prevalence for men and women was 17.2% (CI: 12.0–22.0) and 34.1% (CI: 33.2–39.4), respectively. The prevalence of hypertension, hyperlipidemia and cardiovascular disorders among the study population was 39%, 58% and 20%, respectively. Having more than four comorbidities (PR, 3.90; CI, 2.39–6.34), central obesity (PR, 2.66; CI, 1.03–6.84), and female gender (PR, 1.49; CI, 1.14–1.97) were associated with polypharmacy. Also, 56.0% of patients and 23.0% of elder patients (>59 years old) reported using anti-diabetic agents. Conclusion: Polypharmacy was low among T2DM patients. More than 75% of the elder population were not on anti-diabetic medications. Polypharmacy was higher among patients with multiple comorbidities, central obesity, lower physical activity, lower socio-economic status, younger age at diagnosis, and longer duration of T2DM.

Purpose: To report the study protocol, methodology and latest enrollment data of a large epidemiological multi-central eye cohort named PERSIAN Eye Cohort Study (PECS) originated from the ongoing PERSIAN Cohort Study, to investigate the distribution of ophthalmic disorders in different regions and ethnicities of Iran, and determine their associations with various exposures of ophthalmic and non-ophthalmic nature. Methods: A central committee designed the study and equipped 6 chosen centers (Khameneh, Some’e Sara, Hoveizeh, Yazd, Rafsanjan and Zahedan), a focal point in each center supervised and managed conduction of the study and the data gathering under close supervision of the central committee. Results: This ongoing study launched in 2015. Out of 65,580 eligible participants of 6 centers of the PERSIAN Cohort, 48,618 individuals aged 35-70 have been enrolled in the PECS (response rate: 74.13%) until September 2021. Slit lamp and fundus photography were performed for 28,702 (59.03%) and 27,437 (56.43%) individuals, respectively. The number of participants who were referred for ophthalmology visit was 12,884, of whom, 6,885 completed the ophthalmology visit (response rate: 53.44%). Conclusion: This large epidemiological multi-central eye cohort can improve our epidemiological knowledge of prevalent ophthalmic disorders in different regions and ethnicities of Iran, and determine their associations with various exposures of ophthalmic and non-ophthalmic nature. This will be very useful for future planned nationwide and global interventions.

Background In this study, we assessed the risk of cardiovascular diseases (CVDs) and all-cause mortality in subjects having an only physical activity or a healthy diet or both compared to those having none of these healthy behaviors in the Golestan Cohort Study (GCS). Methods A total of 50,045 participants aged ≥ 40 years were recruited from Golestan Province, Iran, from 2004 to 2008 and followed for a median of 13.9 years. Four lifestyles were compared: healthy diet and active (HDA), healthy diet but inactive (HDI), unhealthy diet but active (UDA), and unhealthy diet and inactive (UDI), with UDI being considered as the reference group. Diet quality was assessed by the Dietary Approaches to Stop Hypertension diet score, which was calculated based on a validated food frequency questionnaire. The primary outcomes were death from any cause and CVDs. Adjusted Cox models were used to estimate the hazards ratio (HR) and 95% confidence intervals (CI) for overall and CVDs mortality. Results During 467,401 person-years of follow-up, 6,256 overall deaths and 2,043 confirmed CVDs deaths were reported. After adjustment for potential confounders, there was a significant lower risk for all-cause mortality in participants with both healthy behaviors (HR = 0.79, 95% CI = 0.73 to 0.86) or only one healthy behavior [HDI: HR = 0.84, 95% CI = 0.78 to 0.90)] and [UDI: HR = 0.91, 95% CI = 0.85 to 0.97] compared to those with both unhealthy behaviors. For CVDs mortality, the HDA lifestyle (HR = 0.74, 95%CI = 0.65 to 0.86), as well as the UDA lifestyle (HR = 0.83, 95%CI = 0.74 to 0.94) indicated a significant lower risk compared to the UDI lifestyle. The HDI lifestyle was not more effective than UDI. Conclusion The greatest reduction in all-cause and CVDs mortality was related to the HDA. For all-cause mortality, both HDI and UDA lifestyles were associated with a decreased risk in comparison to UDI, but for CVDs mortality, only UDA but not HDI decreased the risk.

Background: We aim to present the development and the initial results of the Golestan Cancer Biobank (GoCB), in a low resource setting in northern Iran. Methods: The GoCB protocol and its standard operation procedures (SOP) were developed according to internationally accepted standards and protocols with some modifications considering the limited resources in our setting. The main biological samples collected by the GoCB include blood sample, urine sample, fresh endoscopy tissue sample, fresh surgical tissue sample and formalin fixed paraffin embedded (FFPE) tissue sample. The GoCB collects patients' demographic data, tumor characteristics as well as data on risk factors. We developed a specific GoCB software for management of patient data and biological sample information. The GoCB dataset is annually linked with the Golestan cancer registry dataset to add complementary data (e.g., survival data). Results: The GoCB started collection of data and biological samples in December 2016. By November 2020, a total number of 1217 cancer patients participated in the GoCB. The majority of the GoCB participants (n = 942, 77) were those with gastrointestinal and breast cancers. Data on risk factors were successfully collected in 684 (56.2) of the participants. Overall, 3563 samples were collected from the GoCB participants and 730 samples were used in 7 national and international research projects. Conclusion: We considered specific strategies to overcome major limitations, especially budget shortage, in the development and maintenance of a cancer-specific biological repositories in our setting. The GoCB may be considered as a model for the development of biobank in low- and middle-income countries (LMICs). © 2021 Academy of Medical Sciences of I.R. Iran. All rights reserved.

BACKGROUND In December 2019, COVID-19 emerged from China and spread to become a pandemic, killing over 1,350,000 up to November 18, 2020. Some patients with COVID-19 have abnormal liver function tests. We aimed to determine the clinical significance of liver chemistries in patients with COVID-19. METHODS We performed a cross-sectional study of 1044 consecutive patients with confirmed COVID-19 in two referral hospitals in Tehran, Iran, from February to April 2020. All cases were diagnosed by clinical criteria and confirmed by characteristic changes in the spiral chest computed tomography (CT) and nucleic acid testing of the nasopharyngeal samples. We evaluated the association between abnormal liver enzymes or function tests and survival, intensive care unit (ICU) admission and fatty liver changes in CT scans. RESULTS The mean age was 61.01 ± 16.77 years, and 57.68% were male. Of 495 patients with elevated alanine transaminase (ALT) levels, 194 had chest CT scans, in which fatty liver disease was seen in 38.1%. 41 patients (21.13%) had moderate to severe, and 33 (17.01%) had borderline fatty liver disease. Bilirubin, albumin, and partial thromboplastin time (PTT), along with other markers such as HCO3 , C-reactive protein (CRP), triglyceride, and length of admission, were significantly associated with ICU admission and mortality. Prothrombin time (PT), platelet count, and low-density lipoprotein (LDL) levels were also correlated with mortality. Fasting blood sugar (FBS) and pH were important indices in ICU admitted patients. CONCLUSION Liver function tests accurately predict a worse prognosis in patients with COVID-19. However, liver enzymes were only slightly increased in those who died or needed ICU admission and were not related to the fatty liver changes.

Prior studies have conflicting findings regarding the association between gastroesophageal reflux disease (GERD) and esophageal squamous cell carcinoma (ESCC). We examined this relationship in a prospective cohort in a region of high ESCC incidence. Baseline exposure data were collected from 50 045 individuals using in-person interviews at the time of cohort entry. Participants were followed until they developed cancer, died, or were lost to follow up. Participants with GERD symptoms were categorized into any GERD (heartburn or regurgitation), mixed symptoms, or heartburn alone. Multivariable Cox regression was used to assess the relationship between GERD symptom group and histologically confirmed ESCC. The model was adjusted for known risk factors for GERD and ESCC. 49 559 individuals were included in this study, of which 9005 had GERD symptoms. Over 13.0 years of median follow up, 290 individuals were diagnosed with ESCC. We found no association between any GERD and risk of ESCC (aHR 0.90, 95% CI: 0.66-1.24, P = .54). Similar findings were observed for the GERD symptom subtypes. Significant interactions between any GERD and sex (P = .013) as well as tobacco smoking (P = .028) were observed. In post-hoc analyses, GERD was associated with a decreased risk of ESCC in men (aHR 0.51, 95% CI: 0.27-0.98 P = .04) and in smokers (aHR 0.26, 95% CI: 0.08-0.83 P = .02). While there was little evidence for an overall association between GERD symptoms and ESCC risk, significant interactions with sex and smoking were observed. Men and smokers with GERD symptoms had a lower risk of ESCC development.

Background Elevated blood pressure is associated with cardiovascular disease, stroke and chronic kidney disease. In this study, we examined the socioeconomic inequality and its related factors in prevalence, Awareness, Treatment and Control (ATC) of hypertension (HTN) in Iran. Method The study used data from the recruitment phase of The Prospective Epidemiological Research Studies in IrAN (PERSIAN). A sample of 162,842 adults aged > = 35 years was analyzed. HTN was defined according to the Joint National Committee)JNC-7(. socioeconomic inequality was measured using concentration index (Cn) and curve. Results The mean age of participants was 49.38(SD = ± 9.14) years and 44.74% of the them were men. The prevalence of HTN in the total population was 22.3%(95% CI: 20.6%; 24.1%), and 18.8%(95% CI: 16.8%; 20.9%) and 25.2%(95% CI: 24.2%; 27.7%) in men and women, respectively. The percentage of awareness treatment and control among individuals with HTN were 77.5%(95% CI: 73.3%; 81.8%), 82.2%(95% CI: 70.2%; 81.6%) and 75.9%(95% CI: 70.2%; 81.6%), respectively. The Cn for prevalence of HTN was -0.084. Two factors, age (58.46%) and wealth (32.40%), contributed most to the socioeconomic inequality in the prevalence of HTN. Conclusion The prevalence of HTN was higher among low-SES individuals, who also showed higher levels of awareness. However, treatment and control of HTN were more concentrated among those who had higher levels of SES, indicating that people at a higher risk of adverse event related to HTN (the low SES individuals) are not benefiting from the advantage of treatment and control of HTN. Such a gap between diagnosis (prevalence) and control (treatment and control) of HTN needs to be addressed by public health policymakers.

Background & Aims High mortality rate of pancreatic cancer (PC) as one of the most common cancers worldwide made it a center of attention for recent researches on its pathology, etiology, screening and early diagnosis. In previous researches, association of dietary intake and plasma levels of fatty acids with risk of pancreatic cancer was investigated. In this study we aimed to evaluate the correlation between dietary and plasma fatty acids in case and control groups. Methods From 50,045 adults between 40–75 years old participated in Golestan cohort study, fifty incident cases of PC were diagnosed and 150 controls matched by age, sex and residence place were randomly selected. Dietary intakes and plasma levels of fatty acids was evaluated by validated food-frequency questionnaire (FFQ) and Gas Chromatography – Flame Ionization Detector (GC-FID), respectively. Then, Spearman's correlation was used to measure the correlation between dietary and plasma levels of fatty acids in case and control groups. Results Among all the fatty acids, there was a significant association between plasma and dietary intake of a few fatty acids including trans fatty acids (TFA), polyunsaturated fatty acids (PUFA), 22:6n-3 and 14:0 only in control group. Only total PUFA intake modified plasma level of some fatty acids in case group. There was no difference between association of desaturase enzymes and fatty acids in case and controls. Conclusions Since, plasma levels of fatty acids might be influenced by recent diet, we did not find any specific differences between the associations of plasma levels of fatty acids with dietary intake of fats in case and control groups.

Background Polypharmacy in patients with cardiovascular diseases (CVDs) has been linked to several adverse outcomes. This study aimed to investigate the pattern of medication use and prevalence of polypharmacy among CVDs patients in Iran. Method We used the baseline data of the Pars cohort study (PCS). The participants were asked to bring their medication bags; then, the medications were classified using the Anatomical Therapeutic Chemical classification. Polypharmacy was defined as using five or more medications concurrently. Poisson regression modeling was applied. The adjusted prevalence ratios (PR) and its 95% confidence interval (CI) were estimated. Results Totally, 9262 participants were enrolled in the PCS, of whom 961 had CVDs. The prevalence of polypharmacy in participants with and without CVDs was 38.9% and 7.1%, respectively. The highest prevalence of polypharmacy (51.5%) was among obese patients. Abnormal waist-hip ratio (PR: 2.79; 95% CI 1.57–4.94), high socioeconomic status (PR: 1.65; 95% CI 1.07–2.54), tobacco-smoking (PR: 1.35; 95% CI 1.00–1.81), patients with more than three co-morbidities (PR: 1.41; 95% CI 1.30–1.53), high physical activity (PR: 0.66; 95% CI 0.45–0.95), use of opiate ever (PR: 0.46; 95% CI 0.26–0.82), and healthy overweight subjects (PR: 0.22; 95% CI 0.12–0.39) were associated with polypharmacy. Cardiovascular drugs (76.1%), drugs acting on blood and blood-forming organs (50.4%), and alimentary tract and metabolism drugs (33.9%) were the most frequently used drugs. Agents acting on the renin-angiotensin system were the mostly used cardiovascular system drugs among men and those above 60 years old, while beta-blocking agents were mostly prevalent among cardiovascular system drugs in women with CVDs. Conclusion Given the high prevalence of polypharmacy among CVDs patients, and subsequent complications, programs to educate both physicians and patients to prevent this issue is crucial.

Opium use was recently classified as a human carcinogen for lung cancer by the International Agency for Research on Cancer. We conducted a large, multicenter case-control study evaluating the association between opium use and the risk of lung cancer. We recruited 627 cases and 3477 controls from May 2017 to July 2020. We used unconditional logistic regression analyses to estimate the odds ratios (OR) and 95% confidence intervals (CI) and measured the association between opium use and the risk of lung cancer. The ORs were adjusted for the residential place, age, gender, socioeconomic status, cigarettes, and water pipe smoking. We found a 3.6-fold risk of lung cancer for regular opium users compared to never users (95% CI: 2.9, 4.6). There was a strong dose-response association between a cumulative count of opium use and lung cancer risk. The OR for regular opium use was higher for small cell carcinoma than in other histology (8.3, 95% CI: 4.8, 14.4). The OR of developing lung cancer among opium users was higher in females (7.4, 95% CI: 3.8, 14.5) than in males (3.3, 95% CI: 2.6, 4.2). The OR for users of both opium and tobacco was 13.4 (95% CI: 10.2, 17.7) compared to nonusers of anything. The risk of developing lung cancer is higher in regular opium users, and these results strengthen the conclusions on the carcinogenicity of opium. The association is stronger for small cell carcinoma cases than in other histology.

Background: Evidence on seroconversion profile of the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infected patients is limited. We mainly aimed to evaluate seroconversion and persistence of virus-specific antibodies in patients infected by coronavirus disease 2019 (COVID-19). Methods: This prospective study was conducted on 118 patients with COVID-19 presentations admitted to three hospitals in Iran and recovered from the disease, during April and May 2020. Presence of COVID-19 was confirmed by Polymerase Chain Reaction (PCR) testing on nasopharyngeal swabs. Serum samples were collected at different time points, including 0-5, 6-15, 16-25, 26-35, and 36-95 days of clinical symptom onset. For measurement of SARS-CoV-2-specific IgG and IgM antibody titers, Iran's Food and Drug Administration-approved SARS-CoV-2 ELISA kits were used. Results: Serologic assay revealed that 37.3% of patients (n=44) were positive for IgM at 0-5 days interval after clinical symptom onset. This rate was 60.2% (n=71) for IgG. There were increasing IgM and IgG seroconversion rates during first 25 days of clinical symptom onset, but seropositivity started to decrease thereafter, which was more evident for IgM (17.9%) than IgG (58.9%) at the 36-95 days post symptoms appearance. In other words, it was found that 83.6% of IgM-positive and 32.9% of IgG-positive patients in the first month of clinical symptom onset became seronegative in the third month of clinical symptom onset. Conclusion: The findings demonstrated that antibody responses to SARS-CoV-2 infection were developed in recovered COVID-19 patients; however, some of them were seronegative three months after onset of relevant symptoms. Furthermore, the stability of anti-SARS-CoV-2 antibodies could also correct our expectations from COVID-19 vaccination responses.

The prevalence of smoking in developing countries is known as a significant public health problem, and it is correlated with different demographic and socio-economic factors. This study aimed to determine the environmental and economical related factors of smoking among Iranian adults aged 35 to 70 years. The study sample consisted of 20,152 of Ardabil population aged 35-70 years which was enrolled in the PERSIAN cohort study. Smoking status during the last year was defined as dependent variable and demographic and socio-economic factors considered as independent variables. To identify the main socio-economic factors affecting the smoking prevalence in Ardabil, multivariable logistic regression was used. The prevalence of smoking was 16.1 (95%, CI 15.5-16.4) in this study, where the prevalence of smoking was for men and women 33.4% and 1.4%, respectively. The prevalence of smoking had significant association with old age (2.05, 95% CI, 1.66 to 2.53), male gender (45.15, 95% CI, 37.14 to 54.89), being married (2.60, 95% CI, 1.51 to 4.46), having cardiovascular disease (1.54, 95% CI, 1.32 to 1.79), and negative association with illiteracy (0.50, 95% CI, 0.40 to 0.64), being obese (0.83, 95% CI, 0.73 to 0.94), and lower socio-economic status (0.74, 95% CI, 0.64 to 0.84). The study showed that the prevalence of smoking in Ardabil is higher than many other countries, and different factors, especially socio-economic status, have an association with the prevalence. There are deep needs to policies and regulations such as increasing the taxation on a cigarette to reduce the negative effect of smoking in Iran.

Background: Poor oral health is common in the world, especially in low-income and developing countries. We evaluated oral health status and its association with sociodemographic and economic variables in one of the largest cohort studies in Iran. Methods: This cross-sectional study was conducted using data from the Pars Cohort Study which is conducted in a rural area in southern Iran. A total of 9264 individuals were enrolled in the initial registry. Data on sociodemographic and clinical characteristics were collected. Oral assessment was completed by trained physicians. Generalized negative binomial regression modeling was applied. Results: Overall, data from 9264 participants entered the final analysis. The participants’ mean age was 52.6 ± 9.7 years. In total, 8975 participants (96.8%) had at least one tooth loss and 1790 participants (19.3%) were edentulous. Female gender (incidence rate ratio [IRR]: 1.05, 95% CI: 1.02, 1.08) (IRR: 1.12, 95% CI: 1.07, 1.16), opium consumption (IRR: 1.17, 95% CI: 1.12, 1.22) (IRR: 1.23, 95% CI: 1.16 1.30), lower socioeconomic status (SES) (IRR: 1.07, 95% CI: 1.03, 1.10) (IRR: 1.10, 95% CI: 1.06, 1.15) and being illiterate (IRR: 1.23, 95% CI: 1.20, 1.26) (IRR: 1.36, 95% CI: 1.32, 1.41) were associated with higher decayed, missing and filled teeth (DMFT) and more tooth loss. Conclusion: Oral health was poor in our study sample, especially among older individuals, people with lower SES, illiterate participants, smokers and opiate consumers, which shows the need for improvement in oral health care.

To explore the association of visceral adipose tissue (VAT) area and non-alcoholic fatty liver disease (NAFLD) in patients with type 2 diabetes mellitus (T2DM). This was a cross-sectional study comprising 100 patients with T2DM and 100 non-T2DM individuals, matched for age, sex, and body mass index (BMI). Transient elastography was used to assess hepatic steatosis and liver stiffness measurements (LSM). Controlled attenuation parameter (CAP) was used to quantify hepatic steatosis. To distinguish grades of hepatic steatosis, cutoff values were as follows: S1 ≥ 302, S2 ≥ 331, and S3 ≥ 337 dB/m. Moreover, VAT area was measured by dual-energy X-ray absorptiometry in accordance with validated protocols. CAP score was significantly higher in participants with T2DM (294.61 ± 3.82 vs. 269.86 ± 3.86 dB/ m; P S1: 302 dB/m), while this figure was 26% in non-T2DM group (P

INTRODUCTION: Nonalcoholic fatty liver disease (NAFLD), as the most common liver disease in the world, can range from simple steatosis to steatohepatitis. We evaluated the association between meat consumption and risk of NAFLD in the Golestan Cohort Study (GCS).METHODS: The GCS enrolled 50,045 participants, aged 40-75 years in Iran. Dietary information was collected using a 116-item semiquantitative food frequency questionnaire at baseline (2004-2008). A random sample of 1,612 cohort members participated in a liver-focused study in 2011. NAFLD was ascertained through ultrasound. Total red meat consumption and total white meat consumption were categorized into quartiles based on the GCS population, with the first quartile as the referent group. Multivariable logistic regression models were used to estimate odds ratios (ORs) and 95% confidence intervals (CIs).RESULTS: The median intake of total red meat was 17 and total white meat was 53 g/d. During follow-up, 505 individuals (37.7%) were diagnosed with NAFLD, and 124 of them (9.2%) had elevated alanine transaminase. High total red meat consumption (ORQ4 vs Q1 = 1.59, 95% CI = 1.06-2.38, P trend = 0.03) and organ meat consumption (ORQ4 vs Q1 = 1.70, 95% CI = 1.19-2.44, P trend = 0.003) were associated with NAFLD. Total white meat, chicken, or fish consumption did not show significant associations with NAFLD.[GRAPHICS].DISCUSSION: In this population with low consumption of red meat, individuals in the highest group of red meat intake were at increased odds of NAFLD. Furthermore, this is the first study to show an association between organ meat consumption and NAFLD (see Visual Abstract, http://links.lww.com/AJG/B944).

Background: The International Agency for Research on Cancer (IARC) recently classified opium use as a Group 1 carcinogen. However, much remains to be studied on the relation between opium and cancer. We designed the Iranian Opium and Cancer (IROPICAN) study to further investigate the association of opium use and cancers of the head and neck, bladder, lung, and colon and rectum. In this paper, we describe the rationale, design, and some initial results of the IROPICAN Study. Methods: The IROPICAN is a multi-center case-control study conducted in 10 provinces of Iran. The cases were all histologically confirmed and the controls were selected from hospital visitors who were free of cancer, were not family members or friends of the cancer patients, and were visiting the hospital for reasons other than their own ailment. The questionnaires included detailed questions on opium use (including age at initiation, duration, frequency, typical amount, and route), and potential confounders, such as tobacco use (e.g., cigarettes, nass and water-pipe), and dietary factors. Biological samples, including blood and saliva, were also collected. Results: The validation and pilot phases showed reasonably good validity, with sensitivities of 70% and 69% for the cases and controls, respectively, in reporting opium use. The results also showed excellent reliability, with intra-class correlation coefficients of 0.96 for ever opium use and 0.88 (95% CI: 0.80, 0.92) for regular opium use. In the main phase, we recruited 3299 cancer cases (99% response rate) and 3477 hospital visitor controls (89% response rate). The proportion of ever-use of opium was 40% among cases and 18% among controls. Conclusion: The IROPICAN study will serve as a major resource in studies addressing the effect of opium on risk of cancers of the head and neck, bladder, lung, and colon and rectum. publishedVersion

Aims Cardiovascular diseases (CVDs) are the leading cause of death in the world. Many modifiable risk factors have been reported to synergistically act in the development of CVDs. We aimed to compare the predictive power of anthropometric indices, as well as to provide the best cut-off point for these indicators in a large population of Iranian people for the prediction of CVDs and CVD risk factors. Methods and results All the data used in the present study were obtained from Khuzestan comprehensive health study (KCHS). Anthropometric indices, including BMI (body mass index), WC (waist circumference), HC (hip circumference), WHR (waist-to-hip ratio), WHtR (waist-to-height ratio), ABSI (a body shape index), as well as CVD risk factors [dyslipidaemia, abnormal blood pressure (BP), and hyperglycaemia] were recorded among 30 429 participants. WHtR had the highest adjusted odds ratios amongst anthropometric indices for all the risk factors and CVDs. WC had the highest predictive power for dyslipidaemia and hyperglycaemia [area under the curve (AUC) = 0.622, 0.563; specificity 61%, 59%; sensitivity 69%, 60%; cut-off point 87.95, 92.95 cm, respectively], while WHtR had the highest discriminatory power for abnormal BP (AUC = 0.585; specificity 60%; sensitivity 65%; cut-off point 0.575) and WHR tended to be the best predictor of CVDs (AUC = 0.527; specificity 58%; sensitivity 64%; cut-off point 0.915). Conclusion In this study, we depicted a picture of the Iranian population in terms of anthropometric measurement and its association with CVD risk factors and CVDs. Different anthropometric indices showed different predictive power for CVD risk factors in the Iranian population.

Background: Irritable bowel syndrome (IBS) is a functional disease with no exact laboratory or imaging findings. IBS is more common in areas with a history of psychological trauma and war. This study aims to report the prevalence and possible determinants of IBS in southwestern Iran, an area with a notable history of war. Methods: We randomly enrolled 1849 permanent residents in 29 cities aged 20 to 65 years. A validated for Farsi version Rome III criteria and a questionnaire, including demographic data and health history, were administered to each subject. Participants who fulfilled the Rome III criteria were categorized into three groups: Diarrhea dominant (IBS-D), Constipation dominant (IBS-C), and Mixed type (IBS-M). Results: The total prevalence of IBS was 3.2%, with 70% of subjects being of Arab descent (P=0.004). IBS was more common in females, singles, illiterate subjects, and people younger than 30 years; however, none of these differences were statistically significant. People with depression, anxiety, self-report of psychological disorders, and very low socioeconomic status had a significantly higher prevalence of IBS (PConclusion: This study shows a higher prevalence of IBS symptoms in a population-based study in the region compared to counterparts in other regions of Iran. Considering the higher prevalence of self-reported psychological disorders, further studies are recommended to focus on the exact diagnosis of mental disorders and their influence on IBS.

Background The first large serosurvey in Iran found a SARS-CoV-2 antibody seroprevalence of 17.1% among the general population in the first wave of the epidemic by April, 2020. The purpose of the current study was to assess the seroprevalence of COVID-19 infection among Iranian general population after the third wave of the disease. Methods This population-based cross-sectional study was conducted on 7411 individuals aged ≥10 years old in 16 cities across 15 provinces in Iran between January and March, 2021. We randomly sampled individuals registered in the Iranian electronic health record system based on their national identification numbers and invited them by telephone to a healthcare center for data collection. Presence of SARS-CoV-2-specific IgG and IgM antibodies was assessed using the SARS-CoV-2 ELISA kits. The participants were also asked about their recent COVID-19-related symptoms, including cough, fever, chills, sore throat, headache, dyspnea, diarrhea, anosmia, conjunctivitis, weakness, myalgia, arthralgia, altered level of consciousness, and chest pain. The seroprevalence was estimated after adjustment for population weighting and test performance. Results The overall population-weighted seroprevalence adjusted for test performance was 34.2% (95% CI 31.0-37.3), with an estimated 7,667,874 (95% CI 6,950,412-8,362,915) infected individuals from the 16 cities. The seroprevalence varied between the cities, from the highest estimate in Tabriz (39.2% [95% CI 33.0-45.5]) to the lowest estimate in Kerman (16.0% [95% CI 10.7-21.4]). In the 16 cities studied, 50.9% of the seropositive individuals did not report a history of symptoms suggestive of COVID-19, implying an estimation of 3,902,948 (95% CI 3,537,760-4,256,724) asymptomatic infected individuals. Conclusions Nearly one in three individuals were exposed to SARS-CoV-2 in the studied cities by March 2021. The seroprevalence increased about two-fold between April, 2020, and March, 2021.

Background: Hearing loss is the fourth leading cause of disability in the world. The growing trend of this disease has made it a serious public health issue that requires well-designed and coordinated measures at the global, regional, and local levels. The current cohort study aimed to estimate the prevalence and incidence of different types of hearing loss and identify the risk and protective factors in the study population.Methods: Hoveyzeh ear cohort (HEC) is a population-based cohort study that focuses on the audiological profile of 10,009 participants 35-70 years old who will recruit between May 2017 to January 2023. This study is conducted in the enrolment phase consisting of three steps registration, audiological assessments, and follow-up phase. Results: A total of 1845 participants, aged 35-70 years old, that have been registered in the Hoveyzeh Cohort Study (HCS) are included in this pilot study. Our findings revealed that 947 participants (51.3%) had some degree of hearing loss in the pilot study. The prevalence of hearing loss was significantly correlated with demographical and socioeconomic variables including age, sex, educational level, marital status, wealth status, skilled levels, Townsend index, and smoking (p-value

Estimating the prevalence of SARS-CoV-2 antibody seropositivity among health care workers (HCWs) is crucial. In this study, the seroprevalence of anti-SARS-CoV-2 antibodies among HCWs of five hospitals of Tehran, Iran with high COVID-19 patient's referrals from April to June, 2020, was assessed. In this cross-sectional study, HCWs from three public and two private hospitals, selected randomly as a pilot, were included. Participants were asked questions on their demographic characteristics, medical history, hospital role, and usage of personal protective equipment (PPE). Iran FDA-approved SARS-CoV-2 ELISA kits were used to detect IgG and IgM antibodies in blood samples. The seroprevalence was estimated on the basis of ELISA test results and adjusted for test performance. Among the 2,065 participants, 1,825 (88.4%) and 240 (11.6%) HCWs were recruited from public and private hospitals, respectively. A total of 340 HCWs were tested positive for SARS-CoV-2-specific IgG or IgM antibodies, and 17.9% of seropositive individuals were asymptomatic. The overall test performance-adjusted seroprevalence estimate among HCWs was 22.6 (95% CI: 20.2–25.1), and PPE usage was significantly higher among HCWs of public vs. private hospitals (66.5 vs. 20.0%). This study found that seroprevalence of SARS-CoV-2 among HCWs was higher in private hospitals (37.0%; 95% CI: 28.6–46.2) than public hospitals (20.7%; 95% CI: 18.2–23.3), and also highest among assistant nurses and nurses, and lowest among janitor or superintendent categories. The PPE usage was especially suboptimal among HCWs in private hospitals. Continued effort in access to adequate PPE and regular screening of hospital staff for detecting asymptomatic personnel, especially during the upcoming wave of infection, are warranted.

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) potentially renders thalassemia patients disease-free with presumably cessation of associated complications. This study analyzes the liver fibrosis status and the determinants of its progression in ex-thalassemic patients. The liver fibrosis status of 108 pediatric transfusion-dependent β-thalassemia major patients was evaluated before and one year after allo-HSCT using transient elastography (TE). All patients achieved normal hematopoiesis. In univariate analyses, not in all, but in patients developing significant post-HSCT iron overload or hepatic graft-versus-host disease (GvHD), as well as recipients of bone marrow stem cells (BMSC), significant TE increment occurred. In multivariable analyses, through a model with large effect size (Adj.R2 = 26%, F(3,104) = 13.53, P

Background: Non-communicable diseases (NCDs) are the leading cause of death worldwide, with a disproportionally rising burden among low- and middle-income populations. While preventable risk factors highly contribute to this burden, population-based studies assessing these factors and the health status of these populations, are scarce. Methods: The Khuzestan Comprehensive Health Study (KCHS)—a cross sectional study—was conducted between 2016-2019, including 30,506 Iranians aged 20 to 65 years, from 27 counties of Khuzestan province, southwest of Iran. KCHS aimed to provide a comprehensive health overview by investigating the prevalence and risk factors of NCDs and psychological disorders, along with viral hepatitis as a common communicable disease. Upon registration, 15 mL of blood and anthropometric measurements were obtained from participants. Afterwards, several interviewer-administered questionnaires were completed to gather data on demographics, socioeconomic status, sleep quality, physical activity, lifestyle habits, nutrition, and medical history. Results: The mean ± SD age of participants was 41.7 ± 11.9 years. The majority were female (64.3%), of the Arab ethnicity (49%), married (83%), and urban residents (73.1%). About 70% had an educational level below high school diploma. Overall, 10.8%, 5.2%, and 2.8% of participants had used cigarettes, hookah, and drugs at least once in their lifetime, respectively. While body mass index and serum cholesterol levels were higher in females, blood pressure was higher in males (PConclusion: KCHS assessed many aspects of health in the Khuzestan province. In addition to develop a biobank along with a comprehensive dataset, KCHS will serve as a valuable infrastructure for future research.

AimsTens of millions of people worldwide use opiates but little is known about their potential role in causing cardiovascular diseases. We aimed to study the association of long-term opiate use with cardiovascular mortality and whether this association is independent of the known risk factors.Methods and resultsIn the population-based Golestan Cohort Study—50 045 Iranian participants, 40–75 years, 58% women—we used Cox regression to estimate hazard ratios and 95% confidence intervals (HRs, 95% CIs) for the association of opiate use (at least once a week for a period of 6 months) with cardiovascular mortality, adjusting for potential confounders—i.e. age, sex, education, wealth, residential place, marital status, ethnicity, and tobacco and alcohol use. To show independent association, the models were further adjusted for hypertension, diabetes, waist and hip circumferences, physical activity, fruit/vegetable intake, aspirin and statin use, and history of cardiovascular diseases and cancers. In total, 8487 participants (72.2% men) were opiate users for a median (IQR) of 10 (4–20) years. During 548 940 person-years—median of 11.3 years, >99% success follow-up—3079 cardiovascular deaths occurred, with substantially higher rates in opiate users than non-users (1005 vs. 478 deaths/100 000 person-years). Opiate use was associated with increased cardiovascular mortality, with adjusted HR (95% CI) of 1.63 (1.49–1.79). Overall 10.9% of cardiovascular deaths were attributable to opiate use. The association was independent of the traditional cardiovascular risk factors.ConclusionLong-term opiate use was associated with an increased cardiovascular mortality independent of the traditional risk factors. Further research, particularly on mechanisms of action, is recommended.

BackgroundMany diabetic individuals use prescription and non-prescription opioids and opiates. We aimed to investigate the joint effect of diabetes and opiate use on all-cause and cause-specific mortality.MethodsGolestan Cohort study is a prospective population-based study in Iran. A total of 50 045 people—aged 40–75, 28 811 women, 8487 opiate users, 3548 diabetic patients—were followed during a median of 11.1 years, with over 99% success follow-up. Hazard ratio and 95% confidence intervals (HRs, 95% CIs), and preventable death attributable to each risk factor, were calculated.ResultsAfter 533 309 person-years, 7060 deaths occurred: 4178 (10.8%) of non-diabetic non-opiate users, 757 (25.3%) diabetic non-users, 1906 (24.0%) non-diabetic opiate users and 219 (39.8%) diabetic opiate users. Compared with non-diabetic non-users, HRs (95% CIs) for all-cause mortality were 2.17 (2.00–2.35) in diabetic non-opiate users, 1.63 (1.53–1.74) in non-diabetic opiate users and 2.76 (2.40–3.17) in diabetic opiate users. Among those who both had diabetes and used opiates, 63.8% (95% CI: 58.3%–68.5%) of all deaths were attributable to these risk factors, compared with 53.9% (95% CI: 50%–57.4%) in people who only had diabetes and 38.7% (95% CI: 34.6%–42.5%) in non-diabetic opiate users. Diabetes was more strongly associated with cardiovascular than cancer mortality. The risk of early mortality in known cases of diabetes did not depend on whether they started opiate use before or after their diagnosis.ConclusionsUsing opiates is detrimental to the health of diabetic patients. Public awareness about the health effects of opiates, and improvement of diabetes care especially among individuals with or at risk of opiate use, are necessary.

BACKGROUND Measuring serum alanine aminotransferase (ALT) enzyme is a routine clinical test commonly used to evaluate abnormalities in the body in general, and in the liver function in particular. Higher ALT levels are associated with some metabolic disorders. The upper limit normal (ULN) is considered as a reliable threshold for the definition of high ALT. OBJECTIVES: To assess the existing evidence on the ULN for ALT in the general population. DATA SOURCE: PubMed (Medline), EMBASE, Scopus, and Web of Science (ISI) were searched using a specified search strategy. ELIGIBILITY CRITERIA: We collected documents published from 1980 to 2018 in the English language, focusing on human samples at the population level and extracted the data after qualitative evaluation. METHODS We conducted this study in accordance with the recommendations of the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) statement. We used specific search terms and their combinations to find documents from relevant databases. We used a snowballing approach to find documents not captured in the main phase of the search. Two authors separately conducted the search, screened the articles, and selected documents that were qualified for data extraction based on the defined inclusion criteria. Finally, data extraction was conducted by two authors using PRISMA checklist. Reported ULNs for ALT and 95% confidence intervals (CIs) were documented in previously developed datasheets. RESULTS Out of 15242 studies, 47 articles were included for data extraction and analysis. Data were sparse and lacked the consistency to precisely estimate ULN for serum ALT. The ULN of ALT was significantly diverse across various geographical locations and sexes. The lowest value of ULN for ALT was 19 IU/L in Chinese children (age range: 7 to < 10 years), and the highest value of ULN for ALT was 55 IU/L in children from Ghana aged < 5 years. LIMITATIONS: The main limitation of the current systematic review was the scarcity of the reported measures for ULN of ALT. CONCLUSION Based on the results of the current systematic review, it is suggested that the normal range of ALT be redefined, but this redefinition should be done according to the localized data. In order to redefine the ULN for ALT, regional differences, methods used in ALT measurements, and ULN determination should be considered.

Recent evidence has demonstrated a strong interplay and multifaceted relationship between non-alcoholic fatty liver disease (NAFLD) and cardiovascular disease (CVD). CVD is the major cause of death in patients with NAFLD. NAFLD also has strong associations with diabetes and metabolic syndrome. In this comprehensive review, we aimed to overview the primary environmental and genetic risk factors of NAFLD, and CVD and also focus on the genetic aspects of these two disorders. NAFLD and CVD are both heterogeneous diseases with common genetic and molecular pathways. We have searched for the latest published articles regarding this matter and tried to provide an overview of recent insights into the genetic aspects of NAFLD and CVD. The common genetic and molecular pathways involved in NAFLD and CVD are insulin resistance (IR), subclinical inflammation, oxidative stress, and atherogenic dyslipidemia. According to an investigation, the exact associations between genomic characteristics of NAFLD and CVD and casual relationships are not fully determined. Different gene polymorphisms have been identified as the genetic components of the NAFLDCVD association. Some of the most documented ones of these gene polymorphisms are patatin-like phospholipase domain-containing protein 3 (PNPLA3), transmembrane 6 superfamily member 2 (TM6SF2), hydroxysteroid 17-beta dehydrogenase 13 (HSD17B13), adiponectin-encoding gene (ADIPOQ), apolipoprotein C3 (APOC3), peroxisome proliferator-activated receptors (PPAR), leptin receptor (LEPR), sterol regulatory element-binding proteins (SREBP), tumor necrosis factor-alpha (TNF-α), microsomal triglyceride transfer protein (MTTP), manganese superoxide dismutase (MnSOD), membrane-bound O-acyltransferase domain-containing 7 (MBOAT7), and mutation in DYRK1B that substitutes cysteine for arginine at position 102 in kinase-like domain. Further cohort studies with a significant sample size using advanced genomic assessments and next-generation sequencing techniques are needed to shed more light on genetic associations between NAFLD and CVD.

PurposeNon-alcoholic fatty liver disease (NAFLD) is the most common cause of liver disease worldwide. The purpose of this study is to assess the possible association between habitual intake of allium vegetables and NAFLD risk.Design/methodology/approachIn this study, 196 cases of NAFLD and 803 age-matched controls were enrolled from the same clinic. Dietary intakes were assessed using a validated food frequency questionnaire. Consumption of allium vegetables, including raw garlic and onions, were calculated and considered as grams/day in all participants.FindingsParticipants in the highest tertile of allium vegetable intake had 64% lower risk of NAFLD compared with those in the lowest tertile of the allium vegetables intake (odds ratio [OR]: 0.35; 95% confidence interval [CI]: 0.23-0.51;p< 0.001). After controlling for potential confounders, there was no significant change in this inverse association (OR: 0.36; 95% CI: 0.22-0.56;p< 0.001).Originality/valueThis study for the first time showed that higher consumption of allium vegetables was associated with lower risk of NAFLD. The results did not change when the authors adjusted the analysis for the known risk factors of the disease, which indicate the independency of the association.

We conducted a population-based prospective study to assess prevalence and incidence rates of cardiovascular diseases (CVDs) and obesity-related metabolic disorders, and to evaluate predictive ability of various CVD risk assessment tools, in a population not represented in existing CVD cohorts. We enrolled 5,799 participants in Amol, a city in northern Iran, in 2009–2010, and carried out first repeated measurement (RM) after seven years (2016–2017). For all participants, demographic, anthropometric, laboratory, hepatobiliary imaging, and electrocardiography data have been collected in the enrollment and the first RM. At least two more RM phases, with 7-year intervals, are considered for a comprehensive evaluation of participants (commencing in 2023 and 2030). After enrollment, all participants have been and will be followed up annually for 20 years, both actively and passively. We adopted a multidisciplinary approach to overcome barriers to participation, and achieved a 7-year follow-up success rate of 93.0% with active follow-up of 5,394 participants aged 18–90 years. Of 160 deceased participants, 69 cases (43.1%) died due to CVDs during seven years. The study outcomes offer an evidence base for future researches, and inform policies regarding non-communicable diseases in Iran.

Publisher Copyright: © 2022 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license Background: Combating viral hepatitis is part of the UN Sustainable Development Goals (SDGs), and WHO has put forth hepatitis B elimination targets in its Global Health Sector Strategy on Viral Hepatitis (WHO-GHSS) and Interim Guidance for Country Validation of Viral Hepatitis Elimination (WHO Interim Guidance). We estimated the global, regional, and national prevalence of hepatitis B virus (HBV), as well as mortality and disability-adjusted life-years (DALYs) due to HBV, as part of the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019. This included estimates for 194 WHO member states, for which we compared our estimates to WHO elimination targets. Methods: The primary data sources were population-based serosurveys, claims and hospital discharges, cancer registries, vital registration systems, and published case series. We estimated chronic HBV infection and the burden of HBV-related diseases, defined as an aggregate of cirrhosis due to hepatitis B, liver cancer due to hepatitis B, and acute hepatitis B. We used DisMod-MR 2.1, a Bayesian mixed-effects meta-regression tool, to estimate the prevalence of chronic HBV infection, cirrhosis, and aetiological proportions of cirrhosis. We used mortality-to-incidence ratios modelled with spatiotemporal Gaussian process regression to estimate the incidence of liver cancer. We used the Cause of Death Ensemble modelling (CODEm) model, a tool that selects models and covariates on the basis of out-of-sample performance, to estimate mortality due to cirrhosis, liver cancer, and acute hepatitis B. Findings: In 2019, the estimated global, all-age prevalence of chronic HBV infection was 4·1% (95% uncertainty interval [UI] 3·7 to 4·5), corresponding to 316 million (284 to 351) infected people. There was a 31·3% (29·0 to 33·9) decline in all-age prevalence between 1990 and 2019, with a more marked decline of 76·8% (76·2 to 77·5) in prevalence in children younger than 5 years. HBV-related diseases resulted in 555 000 global deaths (487 000 to 630 000) in 2019. The number of HBV-related deaths increased between 1990 and 2019 (by 5·9% [–5·6 to 19·2]) and between 2015 and 2019 (by 2·9% [–5·9 to 11·3]). By contrast, all-age and age-standardised death rates due to HBV-related diseases decreased during these periods. We compared estimates for 2019 in 194 WHO locations to WHO-GHSS 2020 targets, and found that four countries achieved a 10% reduction in deaths, 15 countries achieved a 30% reduction in new cases, and 147 countries achieved a 1% prevalence in children younger than 5 years. As of 2019, 68 of 194 countries had already achieved the 2030 target proposed in WHO Interim Guidance of an all-age HBV-related death rate of four per 100 000. Interpretation: The prevalence of chronic HBV infection declined over time, particularly in children younger than 5 years, since the introduction of hepatitis B vaccination. HBV-related death rates also decreased, but HBV-related death counts increased as a result of population growth, ageing, and cohort effects. By 2019, many countries had met the interim seroprevalence target for children younger than 5 years, but few countries had met the WHO-GHSS interim targets for deaths and new cases. Progress according to all indicators must be accelerated to meet 2030 targets, and there are marked disparities in burden and progress across the world. HBV interventions, such as vaccination, testing, and treatment, must be strategically supported and scaled up to achieve elimination. Funding: Bill & Melinda Gates Foundation.

We aimed to study the correlation of adiponectin level with insulin resistance (IR), carotid intima-media thickness (cIMT), and various obesity indices especially visceral adipose tissue (VAT) thickness, and visceral adiposity index (VAI), in patients with NAFLD (n = 41), T2D (n = 22), NAFLD + T2D (n = 41), and healthy subjects (n = 20). Results showed the median level of adiponectin in patients with NAFLD (2.97 ��g/mL) and ones with NAFLD + T2D (3.21 ��g/mL) is significantly lower rather than in controls (4.39 ��g/mL). Moreover, VAI is the only predictor for adiponectin concentration in the combination of patient groups and also in all participants independent of IR and other obesity indices. Adiponectin level had also a positive correlation with cIMT and IR in NAFLD patients. Interestingly, lower level of adiponectin was associated with the presence of T2D, NAFLD, and NAFLD + T2D independent of IR and obesity indices. Collectively, it seems that VAI reflecting visceral adipose tissue function is a possible predictor of adiponectin level.