Clinical Phenotype and Disease Course of Inflammatory Bowel Disease in Iran: Results of the Iranian Registry of Crohn's and Colitis (IRCC).

BACKGROUND: Data on the epidemiology of inflammatory bowel disease (IBD) in the Middle East are scarce. We aimed to describe the clinical phenotype, disease course, and medication usage of IBD cases from Iran in the Middle East. METHODS: We conducted a cross-sectional study of registered IBD patients in the Iranian Registry of Crohn's and Colitis (IRCC) from 2017 until 2022. We collected information on demographic characteristics, past medical history, family history, disease extent and location, extra-intestinal manifestations, IBD medications, and activity using the IBD-control-8 questionnaire and the Manitoba IBD index, admissions history, history of colon cancer, and IBD-related surgeries. RESULTS: In total, 9746 patients with ulcerative colitis (UC) (n=7793), and Crohn's disease (CD) (n=1953) were reported. The UC to CD ratio was 3.99. The median age at diagnosis was 29.2 (IQR: 22.6,37.6) and 27.6 (IQR: 20.6,37.6) for patients with UC and CD, respectively. The male-to-female ratio was 1.28 in CD patients. A positive family history was observed in 17.9% of UC patients. The majority of UC patients had pancolitis (47%). Ileocolonic involvement was the most common type of involvement in CD patients (43.7%), and the prevalence of stricturing behavior was 4.6%. A prevalence of 0.3% was observed for colorectal cancer among patients with UC. Moreover,15.2% of UC patients and 38.4% of CD patients had been treated with anti-tumor necrosis factor (anti-TNF). CONCLUSION: In this national registry-based study, there are significant differences in some clinical phenotypes such as the prevalence of extra-intestinal manifestations and treatment strategies such as biological use in different geographical locations.

Iranian Consensus Guideline for Pharmacotherapy with Biologics and Small Molecules Drugs in Adults with Inflammatory Bowel Diseases.

Background: Pharmacotherapy with biologics and small molecules, as the more effective therapies for moderate to severe ulcerative colitis (UC) and Crohn's disease (CD), is complex. Choosing the best methods for their utilization in order to induce and maintain remission are critical for practicing gastroenterologists. We aimed to develop an Iranian consensus on the management of inflammatory bowel disease (IBD) patients with biologics and small molecules. Methods: A Delphi consensus was undertaken by experts who performed a literature summary and voting process. Quality of evidence was assessed using the Grading and Recommendations Assessment, Development, and Evaluation; and an additional risk of bias-protocol. Results: Following an extensive search of the literature, 219 studies were used to determine the quality of the evidence. After three rounds of voting, consensus (defined as≥80% agreement) was reached for 87 statements. Conclusion: We considered different aspects of pharmacotherapy in this consensus. This guideline, along with clinical judgment, can be used to optimize management of IBD patients.

Mini Review: The Impact of Climate Change on Gastrointestinal Health.

Global warming and climate change are important worldwide issues which are a major human health threat. Climate change can affect the gastrointestinal (GI) system in many ways. Increased rainfall events and flooding may be associated with increased GI infections and hepatitis. Climate change could cause changes in gut microbiota, which may impact the pattern of GI diseases. The stress of access to essential needs such as clean water and food, the effects of forced migration, and natural disasters could increase brain-gut axis disorders. The association between air pollution and GI disorders is another challenging issue. There is a lot to do personally and professionally as gastroenterologists regarding climate change.

Colorectal Cancer Screening Pilot Project in Tehran-Iran, a Feasibility Study.

BACKGROUND: Colorectal cancer (CRC) is the third most common cancer in Iran, where there is no organised CRC-screening programme. This study aimed to evaluate feasibility of CRC screening using a qualitative fecal immunochemical test (FIT) among Iranian average-risk adults. METHODS: In this feasibility study, 7039 individuals aged 50-75 years were invited by community health workers (CHWs) in southern Tehran and its suburban districts between April 2018 and November 2019. The CHWs performed a qualitative FIT with cut-off level 50 ng Hb/mL buffer and referred those with positive-FIT for colonoscopy to the endoscopy center of Shariati hospital in Tehran. Outcomes included acceptance rate, FIT positivity rate, colonoscopy compliance, detection rates and positive predictive values (PPVs) with 95% confidence interval for CRC and advanced adenomas (AAs). RESULTS: Acceptance rate at initial invitation was 71.7%. From 4974 average-risk adults (1600 males and 3374 females) who were offered FIT, 96.8% (n=4813) provided valid samples, of whom 471 (9.8%) tested positive. Among FIT-positive participants, 150 (31.8%) underwent colonoscopy; CRC was detected in 2.0% (n=3) and adenomas in 27.3% (n=41). Detection rate of CRC and AAs per 1000-FIT-screened participants was 0.6 (0.1-1.8) [males: 0.7 (0.01-3.6), females: 0.6 (0.07-2.0)] and 4.2 (2.5-6.4) [males: 5.9 (2.6-11.0), females: 3.4 (1.7-6.0)], respectively. PPVs were 2.0% (0.4-5.7) for CRC and 13.3% (8.3-19.8) for AAs. There was no association between gender and the studied outcomes. CONCLUSION: Our results partially support the feasibility of scaling up organized CRC-screening through the existing healthcare system in Iran; it remains to be discussed carefully to ensure the capacity of healthcare system for adequate colonoscopy services.

Dyssynergic Defecation: A Comprehensive Review on Diagnosis and Management.

About one-third of chronically constipated patients have an evacuation disorder, and dyssynergic defecation is a common cause of the evacuation disorder. In dyssynergic defecation, the coordination between abdominal and pelvic floor muscles during defecation is disrupted and patients cannot produce a normal bowel movement. The etiology of dyssynergic defecation is still unknown. Although a detailed history taking and a careful examination including digital rectal examination could be useful, other modalities such as anorectal manometry and balloon expulsion test are necessary for the diagnosis. Biofeedback therapy is one of the most effective and safe treatments. Here, we provide an overview of dyssynergic defecation as well as how to diagnose and manage this condition.

Comparison of Disease Phenotype and Course among Elderly- and Early-Onset Inflammatory Bowel Diseases in the Middle East.

BACKGROUND: It is unknown if the clinical manifestations and phenotype of disease are comparable between early- and elderly-onset 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 10048 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.

SARS-CoV-2 Seroprevalence Among Health Care Workers in Major Private and Public Hospitals With COVID-19 Patient's Referral in Tehran, Iran.

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.

xsGastrointestinal symptoms are associated with a lower risk of hospitalization and mortality and Outcomes in COVID-19.

BACKGROUND: We aimed to find the association between gastrointestinal (GI) and respiratory symptoms with mortality and hospitalization among COVID-19 patients. METHODS: We analyzed the registered data of COVID-19 patients from February 20, 2020, to March 10, 2021. Depending on the patients' disease symptoms, four categories were defined: patients with only GI symptoms, patients with only respiratory symptoms, patients with both symptoms, and patients with other symptoms. Logistic regression analysis was used to assess the association of groups with outcomes. RESULTS: A total of 42,964 patients from 23 hospitals were included, of which 26.5% patients had at least one or more GI symptoms. Of total patients, 51.58% patients were hospitalized among which 22.8% had at least one or more GI symptoms. GI symptoms significantly decreased the odds of mortality (OR 0.72, 95% CI 0.56-0.92), but respiratory symptoms increased the odds for mortality (1.36: 1.24-1.50), compared with patients with other symptoms. Moreover, the odds ratio of patients who had both respiratory and GI symptoms increased (1.52: 1.31-1.78) compared with patients with other symptoms. The same results were observed for hospitalization as the outcome. CONCLUSIONS: Our study showed that the presence of GI symptoms in COVID-19 at the time of admission was associated with a lower odds of hospitalization and mortality; however, this association had higher odds for respiratory symptoms.

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

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

Outcomes of COVID-19 in Patients with Inflammatory Bowel Disease: Comparison with Household Members and the Role of IBD Medications.

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: 2.02- 16.07, 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.

Clinical Phenotype and Disease Course of Inflammatory Bowel Disease: A Comparison Between Sporadic and Familial Cases.

BACKGROUND: The role of genetic and environmental factors in inflammatory bowel disease's (IBD) clinical course is not fully clear. We aimed to assess the clinical phenotype, disease course, and prognosis of familial IBD in comparison with sporadic cases. METHODS: We conducted a prospective national matched case-control study of registered IBD patients in the Iranian Registry of Crohn's and Colitis (IRCC) recruited from 2017 until 2020. Sporadic and familial IBD patients were matched based on age, sex, and disease duration. Data on demographics, past medical disease, family history of IBD, disease type, clinical phenotype, extraintestinal manifestations, IBD medications, IBD activity using the IBD-control-8 questionnaire and the Manitoba IBD index, emergency visits in the past 12 months, admissions in the past 3 months, history of colon cancer, IBD-related surgeries, and aggressive phenotype were gathered. Variable distributions were compared between sporadic and familial cases. RESULTS: Overall, 5231 patients with ulcerative colitis (UC, 18.3% familial) and 1438 patients with Crohn's disease (CD, 16.7% familial) were registered in the IRCC. Age at diagnosis was similar between familial and sporadic cases. After matching, 3523 UC patients and 908 CD patients were enrolled in the study. Extraintestinal manifestations, UC extent, CD location and behavior, anti-TNF use, disease activity, colon cancer, IBD-related surgeries and the aggressive phenotype were similar between these sporadic and familial cases. CONCLUSIONS: The prevalence of familial UC and CD cases in Iran was more similar to western countries, and family history did not show a predictive value for disease phenotype, course, and outcomes in our study.

Colonoscopy Complications in an Iranian Teaching Hospital.

BACKGROUND: Colonoscopy is generally a safe procedure with a limited number of adverse events. Few studies have addressed the rate of adverse events in teaching hospitals. This study aimed to investigate the rate of complications after colonoscopy performed by gastroenterology fellows in a teaching hospital in Tehran. METHODS: A historical cohort study was carried out to link the colonoscopy reports and the hospital information system to identify serious adverse events leading to unplanned hospitalization, unplanned procedures or interventions (e.g. surgery), prolongation of existing hospitalization, or death within 30 days after colonoscopy. RESULTS: We included 9928 colonoscopies (mean age of the patients 53.0±15.9 years, 52.3% men) in this study. In-hospital patients comprised (34.8%) of the procedures. The indications of colonoscopy included 7137 diagnostic (71.9%), and 2519 screening (25.4%) reasons. Colorectal polyps were found in 2005 (20.2%) patients. Major complications were seen in 17 patients (0.2%), including serious bleeding in seven patients, cardiopulmonary complications in five patients, perforation in four patients, and sepsis in one patient. CONCLUSION: Serious adverse events after colonoscopy are relatively rare. The rate of complications does not appear to be higher in an academic teaching hospital when performed by fellows under supervision.

High-dose Intravenous Vitamin C in Early Stages of Severe Acute Respiratory Syndrome Coronavirus 2 Infection: A Double-blind, Randomized, Controlled Clinical Trial.

Objective: Based on previous studies in the sepsis population, Vitamin C could prevent injuries when administered in high doses and before the damage is established. This study aimed to evaluate the protective potentials of high-dose Vitamin C in the progression of coronavirus disease 2019 (COVID-19). Methods: A double-blind, placebo-controlled clinical trial was conducted. Patients with moderate-to-severe disease severity based on the World Health Organization definition were enrolled and received 12 g/d Vitamin C (high-dose intravenous Vitamin C [HDIVC]) or placebo for 4 days. Sequential Organ Failure Assessment (SOFA) score as a primary outcome, National Early Warning Score, Ordinal Scale of Clinical Improvement, and cytokine storm biomarkers were recorded on days 0, 3, and 5. Survival was also assessed on day 28 after enrollment. Findings: Seventy-four patients (37 patients in each group) were enrolled from April 5, 2020, to November 19, 2020, and all patients completed follow-up. A lower increase in SOFA score during the first 3 days of treatment (+0.026 vs. +0.204) and a higher decrease in this parameter in the last 2 days (-0.462 vs. -0.036) were observed in the treatment group. However, these differences did not reach a significance level (P = 0.57 and 0.12, respectively). Other indices of clinical and biological improvement, length of hospitalization, and intensive care unit admission days were the same between the two groups. Treatment did not affect the 28-day mortality. Conclusion: Among patients with moderate-to-severe disease of COVID-19, the use of HDIVC plus standard care resulted in no significant difference in SOFA score or 28-day mortality compared to the standard care alone.

A case of COVID-19 with concomitant infection with hepatitis A.

Symptoms of COVID-19 ranging from mild to severe and pulmonary manifestations are the most common. However, liver injury is not rare as there might be a reciprocal influence between COVID-19 and hepatic disease. While high levels of liver enzymes are associated with an increased prevalence of severe complications, the search for other etiologies of hepatic disease should be not be ignored. We report a case of COVID-19 that presented with acute fulminant hepatitis A (HAV) without a previous history.

Evaluation of the effect of sofosbuvir and daclatasvir in hospitalized COVID-19 patients: a randomized double-blind clinical trial (DISCOVER).

BACKGROUND: The combination of sofosbuvir and daclatasvir has shown preliminary efficacy for hospitalized patients with COVID-19 in four open-label studies with small sample sizes. This larger trial aimed to assess if the addition of sofosbuvir/daclatasvir to standard care improved clinical outcomes in hospitalized patients with COVID-19. METHODS: This was a placebo-controlled, double-blind, randomized clinical trial in adults hospitalized with COVID-19 at 19 hospitals in Iran. Patients were randomized to oral sofosbuvir/daclatasvir 400/60 mg once-daily or placebo in addition to standard of care. Patients were included if they had positive PCR or diagnostic chest CT, O2 saturation <95% and compatible symptoms. The primary outcome was hospital discharge within 10 days of randomization. Secondary outcomes included mortality and time to clinical events. The trial is registered on the Iran Registry of Clinical Trials under IRCT20200624047908N1. RESULTS: Between July and October 2020, 1083 patients were randomized to either the sofosbuvir/daclatasvir arm (n = 541) or the placebo arm (n = 542). No significant difference was observed in the primary outcome of hospital discharge within 10 days, which was achieved by 415/541 (77%) in the sofosbuvir/daclatasvir arm and 411/542 (76%) in the placebo arm [risk ratio (RR) 1.01, 95% CI 0.95-1.08, P = 0.734]. In-hospital mortality was 60/541 (11%) in the sofosbuvir/daclatasvir arm versus 55/542 (10%) in the placebo arm (RR 1.09, 95% CI 0.77-1.54, P = 0.615). No differences were observed in time to hospital discharge or time to in-hospital mortality. CONCLUSIONS: We observed no significant effect of sofosbuvir/daclatasvir versus placebo on hospital discharge or survival in hospitalized COVID-19 patients.

Susceptibility of Patients with Inflammatory Bowel Disease to COVID-19 Compared with Their Households.

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.