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Purpose of the study: We aim to examine the association between liver function‐related indicators and gallstone disease (GSD) risk. Study design: The subjects who participated in the China Multicenter Physical Examination Cohort (CMPEC) were enrolled. Relative odds ratios (ORs) with 95% CIs and standardized mean differences (SMDs) were applied to investigate the effect of liver function‐related indicators and GSD risk. Moreover, a systematic review and meta‐analysis were conducted until July 2021. Additionally, the results in the CMPEC and the systematic review and meta‐analysis were combined by meta‐analysis. Finally, the results were validated by a cohort study of the UK Biobank (UKB). Results and conclusions: Totally, 369,931 subjects in CMPEC were included in the study. A total of 28 publications were incorporated into the systematic review and meta‐analysis. The pooled analysis suggested that aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), total protein (TP), and low albumin (ALB) were positively associated with the risk of GSD. Meanwhile, GSD present to have higher AST, ALT, gamma‐glutamyl transferase (GGT), total bilirubin (TBil), globulin (G), and ALP levels and relatively lower TP and ALB levels than the healthy participants. These results were consistent when stratified by the study design, geographic background, and study quality. Only the association between ALP and GSD risk was validated in the UKB cohort. This study suggests liver function indicators were associated with GSD risk. The results may provide the basis for exploring the etiology of GSD and may help clinicians identify high‐risk subjects. Trial Registration: PROSPERO (CRD42020179076). [ABSTRACT FROM AUTHOR]

Aim: Depression is one of the most common mental disorders and affects many people around the world. Studies show different and conflicting prevalence rates in Iran. This study aimed to investigate the prevalence and associated risk factors for depression in the Prospective Epidemiological Research Studies of the Iranian Adults (PERSIAN) Guilan cohort study (PGCS). Subject and methods: In this cross-sectional study, the population consisted of 10,520 individuals aged 35–70 years in the PGCS (Sowme'eh Sara, Guilan, Iran), which was conducted in 2014–2017. Demographic, anthropometric, and self-report depression data were used, and statistical analysis was performed using SPSS version 16.0 software. Results: The prevalence of depression was 5.2% in this study and was more prevalent in women than in men (7.3% vs. 2.8%). According to the adjusted analysis, depression was significantly associated with female gender, being divorced, being unemployed, higher educational level, less physical activity, and presence of a chronic disease. Conclusion: Pre-existence of underlying disease is likely to be the greatest risk factor associated with higher prevalence of depression. In light of these findings, there is a need to improve evidence-based and suitable community-based primary and secondary psychological health prevention programs. [ABSTRACT FROM AUTHOR]

Context Nonalcoholic fatty liver disease (NAFLD) is considered the leading cause of chronic liver disease worldwide. To date, no confirmed medication is available for the treatment of NAFLD. Previous studies showed the promising effects of gut microbiome–targeted therapies; however, the results were controversial and the strength of the evidence and their clinical significance remained unclear. Objectives This umbrella study summarizes the results of meta-analyses investigating the effects of probiotics, prebiotics, and synbiotics on liver enzymes in the NAFLD population. Data Source A comprehensive search of the PubMed, Scopus, Web of Science, and Cochrane Library databases was done up to December 20, 2022, to find meta-analyses on randomized control trials reporting the effects of gut microbial therapy on patients with NAFLD. Data Extraction Two independent investigators extracted data on the characteristics of meta-analyses, and any discrepancies were resolved by a third researcher. The AMSTAR2 checklist was used for evaluating the quality of studies. Data Analysis A final total of 15 studies were included in the analysis. Results showed that microbiome-targeted therapies could significantly reduce levels of alanine aminotransferase (ALT; effect size [ES], −10.21; 95% confidence interval [CI], −13.29, −7.14; P < 0.001), aspartate aminotransferase (AST; ES, −8.86; 95%CI, −11.39, −6.32; P < 0.001), and γ-glutamyltransferase (ES, −5.56; 95%CI, −7.92, −3.31; P < 0.001) in patients with NAFLD. Results of subgroup analysis based on intervention showed probiotics could significantly reduce levels of AST (ES, −8.69; 95%CI, −11.01, −6.37; P < 0.001) and ALT (ES, −9.82; 95%CI, −11.59, −8.05; P < 0.001). Synbiotics could significantly reduce levels of AST (ES, −11.40; 95%CI, −13.91, −8.88; P < 0.001) and ALT (ES, −11.87; 95%CI, −13.80, −9.95; P < 0.001). Prebiotics had no significant effects on AST and ALT levels (ES, −2.96; 95%CI, −8.12, 2.18, P = 0.259; and ES, −4.69; 95%CI, −13.53, 4.15, P = 0.299, respectively). Conclusion Gut microbiome–targeted therapies could be a promising therapeutic approach in the improvement of hepatic damage in patients with NAFLD. However, more studies are needed to better determine the best bacterial strains, duration of treatment, and optimum dosage of gut microbiome–targeted therapies in the treatment of the NAFLD population. Systematic Review Registration PROSPERO registration no. CRD42022346998. [ABSTRACT FROM AUTHOR]

Background: Smoking poses a significant risk for colorectal cancer (CRC), considered the third leading reason for cancer-related deaths worldwide. However, there has been limited research on the relationship between smoking and CRC in the Eastern Mediterranean Regional Office (EMRO). Therefore, a meta-analysis was conducted to combine available data and gain a comprehensive understanding of the relationship between smoking and CRC in EMRO. Methods: Two independent researchers searched PubMed, Scopus, and Web of Science until December 2022. The included studies were checked for risk of bias administering the Newcastle-Ottawa scale. Heterogeneity was evaluated using I2 statistics and the Cochrane test. Publication bias was determined through funnel plot analysis and Egger's regression test. Additionally, a meta-regression analysis explored the impact of a country's Human Development Index (HDI) on the relationship between smoking and CRC. Results: The final analysis included 26 studies, revealing a significant association between smoking and CRC (OR = 1.40; 95% CI: 1.11 - 1.78; P = 0.004). Moreover, smoking had a more pronounced adverse effect on CRC in countries with higher HDIs compared to those with lower HDIs (OR = 1.30; 95% CI: 0.99 - 1.71; P = 0.054). Conclusions: Our findings underscore the importance of implementing smoking cessation programs and policies in EMRO countries, as they demonstrate a positive relationship between smoking and the risk of CRC. Furthermore, the results suggest that a country's level of human development may influence the association between smoking and CRC. Further research is needed to investigate this potential connection and develop targeted public health interventions. [ABSTRACT FROM AUTHOR]

The incidence of microbial resistance is growing, and new rescue regimens are needed to treat Helicobacter pylori (H. pylori) infection. This study aimed to evaluate levofloxacin-based quadruple therapies' efficacy, safety, and tolerability in eradicating H. pylori. In a randomized, double-blind clinical trial, 220 patients with dyspepsia and H. pylori infection were randomly assigned to receive either bismuth subcitrate 240 mg, pantoprazole 20 mg, amoxicillin 1000 mg twice a day, and levofloxacin 500 mg daily for seven days (BPAL-7) or ten days (BPAL-10). The eradication of H. pylori was evaluated two months after the end of treatment, and adverse drug reactions (ADRs) were assessed during the intervention. According to intention-to-treat and per-protocol, the eradication rate was significantly lower in the BPAL-7 regimen at 49.1% (95% CI: 39.3–57.8) and 47.6% (95% CI: 39.7–58.4), respectively, compared to the BPAL-10 regimen at 62.7% (95% CI: 53.6–72.8) and 62.4% (95% CI: 55.1–72.8), respectively. The ADR incidence was not statistically significant between the groups of BPAL-7 (33.6%) and BPAL-10 (36.7%). Although the ADRs were negligible in both groups, these regimens could not be an ideal alternative therapy for H. pylori because of their low eradication rates compared to standard regimens. Trial Registration. The study was reviewed and approved by the Iranian Registry of Clinical Trials (IRCT201406141155N19). [ABSTRACT FROM AUTHOR]

Objective Nonalcoholic fatty liver disease (NAFLD) is an emerging global chronic liver disease encompassing a wide spectrum of disorders ranging from simple steatosis to nonalcoholic steatohepatitis, fibrosis, cirrhosis, and hepatocellular carcinoma. Considering the strong association between NAFLD and insulin resistance, and the vital role of insulin-like growth factor 1 (IGF1) in IR, we hypothesized that IGF1 gene polymorphism might be associated with NAFLD. Methods A total of 302 subjects, including 149 patients with biopsy-proven NAFLD and 153 controls, were enrolled in this case-control study. All the subjects were genotyped for the rs5742612 polymorphism of the IGF1 gene using the polymerase chain reaction-restriction fragment length polymorphism method. Results The distribution of IGF1 rs5742612 genotypes and alleles differed significantly between the cases with NAFLD and controls. The IGF1 rs5742612 CC genotype compared with the TT genotype or the TT+TC genotype occurred more frequently in the cases than the controls and the differences remained significant after adjustment for confounding factors such as age and body mass index (P  = .011, OR = 2.71, 95%CI = 1.16-5.85; and P  = .032, OR = 2.29, 95% CI = 1.10-5.24, respectively). Conclusion For the first time, this study uncovered that the IGF1 rs5742612 CC genotype compared with the TT genotype or the TT+TC genotype had a 2.71-fold or 2.29-fold increased risk for NAFLD, respectively. [ABSTRACT FROM AUTHOR]

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. Multi variable 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 ofCOVID-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. [ABSTRACT FROM AUTHOR]

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Nonalcoholic fatty liver disease (NAFLD) is the most common cause of liver disease worldwide. If this disease is not appropriately controlled, it can eventually cause chronic liver damage, including cirrhosis and hepatocellular carcinoma. Accordingly, the adoption of appropriate interventions to control NAFLD is important for any healthcare system. The aim of the present systematic review and meta-analysis was to clarify the effect of vitamin D supplementation on NAFLD. PubMed, Scopus, Science Direct, ISI Web of Science, and Google Scholar were systematically searched up to March 2019 to find clinical trials that examined the effects of vitamin D supplementation on liver enzyme levels in NAFLD patients. Means for liver enzymes and potential sources of heterogeneity were extracted. A subgroup analysis was performed to detect potential sources of interstudy heterogeneity. Nine trials (10 arms) comprising 467 participants were eligible for meta-analysis. The results from a pooled analysis did not reveal a significant effect of vitamin D intake on alanine aminotransferase (−2.88 U/L; 95% CI, −6.03 to 0.27; I2 = 85%), aspartate aminotransferase (−0.10 U/L; 95% CI, −1.18 to 0.97; I2 = 26%), and γ-glutamyltransferase levels (0.12 U/L; 95% CI, −5.94 to 6.18; I2 = 38%). The meta-analysis suggested a significant reduction in alkaline phosphatase (−13.79 U/L; 95% CI, −22.13 to −5.45; I2 = 72%) following vitamin D supplementation. This effect was robust in the subgroup in which > 3,000 IU/day vitamin D was administered (−19.74 U/L; 95% CI, −25.36 to −14.12; I2 = 0.0%). The present meta-analysis does not suggest the efficacy of vitamin D supplementation on NAFLD treatment. [ABSTRACT FROM AUTHOR]

Background: Socioeconomic-related inequality in oral hygiene behaviors in Iran is poorly understood. This study aims to measure and decompose socioeconomic-related inequalities in oral hygiene behaviors among middle-aged and elderly adults in Iran. Methods: A cross-sectional analysis was performed using data from the Prospective Epidemiological Research Studies in IrAN (PERSIAN), a large national cohort study. A total of 130,016 individuals aged 35 years and above from 17 cohort centers in Iran were included in the study. The normalized concentration index (Cn) was used to measure the magnitude of inequality in oral hygiene behaviors, i.e. brushing at least twice and flossing once daily, among middle-aged and elderly Iranian adults included in the cohort centers. Decomposition analysis was performed to quantify the contribution of each determinant to the observed inequality in oral hygiene behaviors. Results: Totally, 65.5% of middle-aged and elderly adults brushed their teeth twice a day or more, 7.6% flossed at least once a day and 3.48% had both habits. The estimated Cn of the two habits combined, i.e. tooth brushing and dental flossing, for all provinces taken part in the PERSIAN cohort study was 0.399 (95% confidence interval [CI]: 0.383 to 0.417), indicating that the prevalence of the two habits combined is more concentrated among individuals with higher socioeconomic status. Inequality in oral hygiene behaviors was pro-rich in all cohort centers. The decomposition results suggested socioeconomic status as the main factor contributing to the overall inequality, followed by the level of education, and the province of residence. Conclusion: A low prevalence of oral hygiene behaviors among middle-aged and elderly Iranian adults was observed. There was also a pro-rich inequality in oral hygiene behaviors among middle-aged and elderly adults in all cohort centers. These results suggest an urgent need for targeted policy interventions to increase the prevalence of preventive oral hygiene behaviors among the poor and less-educated middle-aged and elderly adults in Iran. [ABSTRACT FROM AUTHOR]

Background: Hepatitis B (HBV) and hepatitis C(HCV) are viral infections which attack the liver and can cause both acute and chronic diseases. Objectives: The aim of this study was to investigate the knowledge, risk factors, and prevalence of hepatitis B and C infections among high-risk populations of Guilan province, North of Iran. Methods: The current cross-sectional study was conducted on three high-risk groups, including nurses, municipal workers and barbers as well as the control group from the general population. Results: A total of 3391 subjects were recruited for this study. The results of the ANOVA test showed that knowledge about HBV and HCV and their components are statistically different among the groups (P value < 0.05). The overall prevalence of HBV surface antigen (HBsAg) positivity was zero in nurses, barbers, and municipal workers, and 0.5% in general population (95% CI 0.14% to 0.86%). The overall prevalence of HCV infection was zero in nurses and barbers, 0.5% in municipal workers (95% CI 0.03% to 0.97%), and 0.2% in the general population (95% CI 0.02% to 0.38%). Conclusions: Regarding the low prevalence of HBV and HCV infection in high-risk groups, it seems that mandatory vaccination has had a significant role in recruiting or obtaining work permits. However, given the low level of knowledge, it was suggested that authorities should pay more attention in general education and specialized courses for high-risk groups. [ABSTRACT FROM AUTHOR]

BACKGROUND Helicobacter pylori (H. pylori) infection is a major casual factor in any peptic diseases. Clarithromycin as one of the drugs recommended for the infection eradication regimen has shown different levels of resistance. The present study is comparing the effectiveness of clarithromycin- and gemifloxacin - based quadruple regimens in H. pylori eradication. METHODS This was a prospective double blind randomized clinical trial on patients with clear indication of H. pylori eradication. The patients were randomly divided into two groups: "BPAC group" treated with bismuth subcitrate (240 mg), pantoprazole (20 mg), amoxicillin (1 gr), and clarithromycin (500 mg), all twice daily, and the "BPAG group" treated with bismuth subcitrate, pantoprazole, and amoxicillin with same doses as "BPAC group" and gemifloxacin (320 mg daily) all for 10 days. Three months after the end of therapy, 14C-Urea breath test was performed to confirm the eradication. All the patients were assessed for compliance and drug side effects. Based on per-protocol (PP) and intention-to-treat (ITT) methods, data were analyzed and a P value<0.05 was considered as statistically significant. This project has been registered in the Iranian registry of clinical trials (IRCT). RESULTS Three patients were excluded from the survey and finally, 179 patients (89 patients in BPAC group and 90 patients in BPAG group) including 71(39.66%) men with the mean age of 46.4±12.3 years completed the treatment period. The incidence of side effects between the two study groups did not differ significantly. The success rate of BPAC regimen eradication was remarkably greater than BPAG regimen (ITT analysis; 89% vs 77%, respectively; CI 95%: 1.072-5.507, P<0.015 and PP analysis; 91% vs 77.8% respectively; CI 95%: P<0.015). There was no significant relationship between the demographic features and the eradication results. CONCLUSION The results showed that gemifloxacin is not a good alternative for clarithromycin in H. pylori eradication regimens in our region. [ABSTRACT FROM AUTHOR]

Context: Non-alcoholic fatty liver disease (NAFLD) is progressing considerably worldwide. Identifying the risk factors of NAFLD is a critical step in preventing its progression. Methods: In November 2022, two independent researchers studied seven databases, including PubMed, ISI/WoS, ProQuest, Scopus, SID, Magiran, and Google Scholar, and reference list of relevant articles, searching studies that assessed NAFLD risk factors in the Iranian adult population. Heterogeneity between studies was assessed by Cochran's test and its composition using I² statistics. A random-effects model was used when heterogeneity was observed; otherwise, a fixed-effects model was applied. Egger's regression test and Trim-and-Fill analysis were used to assess publication bias. Comprehensive Meta-analysis software (version 3) was used for the analyses of the present study. Results: The results of this study showed significant associations between NAFLD with age (n = 15, odds ratio (OR) = 2.12,95% CI: 1.79 - 2.51), body mass index (n = 46, OR= 5.00,95% CI: 3.34 - 7.49), waist circumference (n = 20, OR = 6.37,95% CI: 3.25 -12.48), waist-to-hip ratio (n = 17, OR = 4.72, 95% CI: 3.93 - 5.66), total cholesterol (n = 39, OR = 1.80, 95% CI: 1.52 - 2.13), high-density lipoprotein (n = 37, OR = 0.53, 95% CI: 0.44-0.65), low-density lipoprotein (n = 31, OR = 1.68, 95% CI: 1.38 - 2.05), triglyceride (n = 31, OR = 3.21, 95% CI: 2.67-3.87), alanine aminotransferase (n = 26, OR = 4.06,95% CI: 2.94 - 5.62), aspartate aminotransferase (n = 27, OR = 2.16,95% CI: 1.50-3.12), hypertension (n =13, OR = 2.53,95% CI: 2.32 - 2.77), systolic blood pressure (n = 13, OR = 1.83,95% CI: 1.53 - 2.18), diastolic blood pressure (n = 14, OR=1.80,95% CI: 1.48-2.20), fasting blood sugar (n = 31, OR=2.91,95% CI: 2.11-4.01), homeostatic model assessment for insulin resistance (n = 5, OR = 1.92,95% CI: 1.48 - 2.59), diabetes mellitus (n =15, OR = 3.04,95% CI: 2.46-3.75), metabolic syndrome (n = 10, OR = 3.56,95% CI: 2.79 - 4.55), and physical activity (n = 11, OR= 0.32, 95% CI: 0.24-0.43) (P< 0.05). Conclusions: In conclusion, several factors are significantly associated with NAFLD. However, anthropometric indices had the strongest relationship with NAFLD in the Iranian adult population. [ABSTRACT FROM AUTHOR]

Background: It is unknown if the clinical manifestations and phenotype of disease are comparable between early- and elderlyonset inflammatory bowel disease (IBD). We aimed to seek differences in disease phenotype, course, complications, and treatment between early- and elderly-onset IBD patients. Methods: This retrospective cohort study on registered IBD patients in the Iranian Registry of Crohn's and Colitis (IRCC) compared demographics, disease phenotype, disease activity, IBD-related surgery and medications between early- and elderly-onset IBD. A generalized linear regression model was used to investigate the relative risk of age at diagnosis adjusted for gender and disease duration for the outcomes. Results: From 10 048 IBD patients, 749 with early-onset (7.5%), and 472 (4.7%) elderly-onset IBD were enrolled: 855 (63.1%) ulcerative colitis (UC) and 366 (26.9%) Crohn's disease (CD). Left-sided colitis was more frequent among elderly-onset UC patients (P < 0.001). Ileum and ileocolonic locations were the most common types in elderly-onset and early-onset CD patients, respectively. In comparison with elderly-onset UC, early-onset cases more often used prednisolone (22.1% vs. 11.4%, P = 0.001), immunomodulators (44.9% vs 25.2%, P < 0.001) and anti-tumor necrosis factors (TNF) (20.1% vs 11.9%, P = 0.002). Elderly-onset UC patients had 0.7 times lower risk of aggressive phenotype (95%CI:0.6-0.9, P = 0.005). Early-onset CD was associated with higher use of prednisolone (27.7% vs 8.1%, P < 0.001), immunomodulators (58.7% vs 41.8%, P = 0.005) and anti-TNF (49.6% vs 35.4%, P = 0.006). Conclusion: Early-onset IBD was associated with a more aggressive phenotype and higher prednisolone, immunomodulators, and anti-TNF use. [ABSTRACT FROM AUTHOR]

Background: Most data on the effect of inflammatory bowel disease (IBD) and its treatments on coronavirus disease 2019 (COVID-19) outcomes have not had non-IBD comparators. Hence, we aimed to describe COVID-19 outcomes in IBD compared to non-IBD patients. Methods: We conducted a prospective cohort study of registered IBD patients with confirmed COVID-19 from six provinces in Iran from February to April 2020. Proven COVID-19 patients were followed up at four weeks and the frequency of outcomes was assessed. Multivariable logistic regression was used to assess associations between demographics, clinical characteristics and COVID-19 outcomes. Results: Overall, 2159 IBD patients and 4721 household members were enrolled, with 84 (3.9%) and 49 (1.1%) participants having confirmed COVID-19, respectively. Household spread of COVID-19 was not common in this cohort (1.2%). While hospitalization was significantly more frequent in IBD patients compared with non-IBD household members (27.1% vs. 6.0%, P = 0.002), there was no significant difference in the frequency of severe cases. Age and presence of IBD were positively associated with hospitalization in IBD compared with non-IBD household members (OR: 1.06, 95% CI: 1.03-1.10; OR: 5.7, 95% CI: 2.0216.07, respectively). Age, presence of new gastrointestinal symptoms, and 5-aminosalicylic acid (5-ASA) use were associated with higher hospitalization rate in IBD patients (OR: 1.13, 95% CI: 1.05-1.23; OR: 6.49, 95% CI: 1.87-22.54; OR: 6.22, 95% CI: 1.90-20.36, respectively). Anti-tumor necrosis factor (TNF) was not associated with more severe outcomes. Conclusion: Age, presence of new gastrointestinal symptoms and use of 5-ASA were associated with increased hospitalization rate among IBD patients, while anti-TNF therapy had no statistical association. [ABSTRACT FROM AUTHOR]