Efficacy and Safety of Tofacitinib for Treatment of Moderate to Severe Active Ulcerative Colitis: First Report from Iran.

BACKGROUND: Tofacitinib, a selective inhibitor of JAK/STAT pathway, has recently become available in our region. Here, we examined the safety and efficacy of tofacitinib in active ulcerative colitis (UC). METHODS: In a prospective, non-randomized, placebo-free, 52-week clinical trial defined in two phases of induction and maintenance, adult patients with active UC and no response or loss of response to previous conventional treatments, or anti-TNF were recruited (IRCT20181217042020N2). Patients received 10 mg/BID of tofacitinib for 8 weeks. Clinically responding patients were entered into the maintenance phase and received tofacitinib 5 mg/BID for 44 weeks. Clinical evaluation, biochemical tests and endoscopy at time points of baseline, 8, 24 and 52 weeks were performed. The primary outcome was clinical remission at 8 and 52 weeks. RESULTS: Fifty out of 53 enrolled patients completed the induction phase. Clinical response and clinical remission at 8 weeks occurred in 84% and 9.5%, respectively. Forty-two patients who had clinical response entered the maintenance phase. Clinical remission based on the total Mayo score and the partial Mayo score occurred in 38.9% and 55.3% at 24 weeks and in 61.1% and 72.2% at 52 weeks, respectively. There was significant correlation between the total and partial Mayo score with regard to clinical remission in both 24 and 52 weeks. No serious adverse events, no case of herpes zoster, but two cases of deep vein thrombosis were seen. CONCLUSIONS: Our study showed acceptable efficacy and safety for tofacitinib and suggested a correlation between the total Mayo score with partial Mayo score with regard to clinical remission.

Iranian Registry of Crohn's and Colitis: study profile of first nation-wide inflammatory bowel disease registry in Middle East.

BACKGROUND/AIMS: A recent study revealed increasing incidence and prevalence of inflammatory bowel disease (IBD) in Iran. The Iranian Registry of Crohn's and Colitis (IRCC) was designed recently to answer the needs. We reported the design, methods of data collection, and aims of IRCC in this paper. METHODS: IRCC is a multicenter prospective registry, which is established with collaboration of more than 100 gastroenterologists from different provinces of Iran. Minimum data set for IRCC was defined according to an international consensus on standard set of outcomes for IBD. A pilot feasibility study was performed on 553 IBD patients with a web-based questionnaire. The reliability of questionnaire evaluated by Cronbach's α. RESULTS: All sections of questionnaire had Cronbach's α of more than 0.6. In pilot study, 312 of participants (56.4%) were male and mean age was 38 years (standard deviation=12.8) and 378 patients (68.35%) had ulcerative colitis, 303 subjects (54,7%) had college education and 358 patients (64.74%) were of Fars ethnicity. We found that 68 (12.3%), 44 (7.9%), 13 (2.3%) of participants were smokers, hookah and opium users, respectively. History of appendectomy was reported in 58 of patients (10.48%). The most common medication was 5-aminosalicylate (94.39%). CONCLUSIONS: To the best of our knowledge, IRCC is the first national IBD registry in the Middle East and could become a reliable infrastructure for national and international research on IBD. IRCC will improve the quality of care of IBD patients and provide national information for policy makers to better plan for controlling IBD in Iran.

Prevalence, Awareness, Treatment, Control, and Correlates of Hypertension in the Pars Cohort Study.

BACKGROUND: High blood pressure is an important risk factor for all-cause mortality and cardiovascular mortality and morbidity among Iranians. We aimed to estimate its prevalence, correlates, and its rate of awareness, treatment, and control in South of Iran. METHODS: The Pars Cohort Study (PCS) was launched in a district of Fars province. All residents between 40 and 75 years old in the district were recruited from 2012 to 2014. Hypertension was defined as either systolic/diastolic blood pressure ≥ 140/90 mm Hg or taking medications. Logistic regression was used to identify the correlates of hypertension and awareness and its treatment and control. A total of 9264 participants were recruited. Of the total participants, 46.2% were men. The mean age was 52.6 years (SD: 9.7). RESULTS: Prevalence of hypertension was 26.9%. Of the total 2489 hypertensives, 49.6% were aware and 55.7% were under treatment. Blood pressure was controlled in 69.2% of treated hypertensives. In the adjusted model, female sex and history of cardiovascular disease (CVD) were positively associated with having hypertension, higher awareness, and better treatment and control. Older age, being overweight or obese, and having a history of diabetes were also positively associated with having hypertension and higher awareness and treatment; however, being overweight or obese was associated with poorer hypertension control. Older age and having a history of diabetes did not show a statistically significant association with control. CONCLUSION: Being underweight and higher physical activity were inversely associated with having hypertension but were not associated with awareness, treatment, or control. Prevalence of hypertension is high but the rates of awareness, treatment, and control are not adequate.

Non-high-density lipoprotein fractions are strongly associated with the presence of metabolic syndrome independent of obesity and diabetes: a population-based study among Iranian adults.

BACKGROUND: Non-HDL-C as a valuable predictor of premature atherosclerosis, coronary events like first Myocardial infarction and cardiovascular mortality has a high accuracy of measurement both in fasting and non-fasting individuals. Metabolic syndrome (MetS) can promote the development of diabetes mellitus, endothelial dysfunction and atherosclerosis. A common pathway for cross linking of metabolic abnormalities and non-HDL-C has been suggested. In this study we aimed to describe the potential association between non-HDL cholesterol fractions and metabolic syndrome. METHODS: Data of third national surveillance of the risk factors of non-communicable diseases (SuRFNCD-2007) were analyzed. We defined metabolic syndrome (MetS) according to the Adult Treatment Panel III (ATPIII) and International Diabetes Federation (IDF) criteria for 2125 subjects aging 25-64 years. The receiver operating characteristic (ROC) curves were used to determine the optimal cut-points for the diagnosis of MetS. The curves were depicted for non-high-density lipoprotein cholesterol (non-HDL-C) and difference of total non-HDL-C and LDL-C (Differential cholesterol or Diff-C) as predictors of MetS. Logistic regression was also performed in a complex sample analysis scheme. RESULTS: The area under the curve (AUC) with 95% Confidence intervals of total non-HDL-C was computed. Values were 0.693 (0.670-0.715) for IDF-defined MetS and 0.719 (0.697-0.740) for ATPIII criteria. The optimal non-HDL-C cut-point we recommend for both criteria is 153.50 mg/dl (sensitivity: 75.7%, specificity: 57.2%, with ATPIII; sensitivity: 73.2%, specificity: 57.1%, with IDF). Using IDF criteria, the accuracy of predictors were greater in non-diabetic subjects. AUC of Diff-C in DM (-) vs. DM (+) were 0.786 (0.765-0.807) vs. 0.627(0.549-0.705). Adults with high non-HDL-C were 4.42 times more likely to have ATPIII-defined MetS (≥190 vs. < 190 mg/dL). Elevated Diff-C corresponded to increased risk of the MetS (ORs: 10.71 and 26.29 for IDF and ATP III criteria, respectively. All P-values <0.001). CONCLUSIONS: A significant robust association exists between non-HDL-C and MetS whether applying conventional or new thresholds.

Emerging Epidemic of Inflammatory Bowel Disease in a Middle Income Country: A Nation-wide Study from Iran.

BACKGROUND: The burden of inflammatory bowel disease (IBD) hasn't been reported in Iran. We aimed to estimate the prevalence and incidence of IBD and its trend in Iran at national and subnational level from 1990 to 2012. METHODS: We conducted a systematic review of English and Persian databases about the epidemiology of IBD. We also collected outpatient data from 17 provinces of Iran using almost all public and private referral gastroenterology clinics. Prevalence and incidence rate was calculated at national and subnational levels. The Kriging method was used to extrapolate provinces with missing data and GPR model to calculate time trends of rates at subnational level. RESULTS: We found 16 case series, two population-based studies, and two review articles. We collected 11,000 IBD cases from outpatient databases. Among them, 9,269 (84.26%) had ulcerative colitis (UC), 1,646 (14.96%) had Crohn's disease (CD), and 85 had intermediate colitis (IC). A total of 5,452 (49.56%) patients were male. Mean age at diagnosis was 32.80 years (CI: 13 - 61) for UC and 29.98 years (CI: 11 - 58) for CD. Annual incidences of IBD, UC, and CD in 2012 were 3.11, 2.70, and 0.41 per 100,000 subjects respectively. Prevalence of IBD, UC, and CD in 2012 were 40.67, 35.52, and 5.03 per 100,000 subjects respectively. The incidence of UC and CD showed a significant increase during the study period (P for trend < 0.05). CONCLUSIONS: The incidence and prevalence of IBD are increasing in Iran. Establishing a national IBD registry seems necessary for comprehensive care of IBD patients in Iran.

Cardiovascular disease mortality and years of life lost attributable to non-optimal systolic blood pressure and hypertension in northeastern Iran.

BACKGROUND: High blood pressure is the second most important risk factor of cardiovascular diseases (CVDs) in Iran. It is imperative to estimate the burden of CVDs that can be averted if high blood pressure is controlled at the population level. The aim of the current study was to estimate the avertable CVD mortality in the setting of Golestan Cohort Study (GCS). METHODS: Over 50,000 participants were recruited and followed for a median of 7 years. The exposures of interest in this study were non-optimal systolic blood pressure (SBP) and hypertension measured at baseline. Deaths by cause have been precisely recorded. The Population Attributable Fraction (PAF) of deaths and Years of Life Lost (YLLs) due to CVDs attributable to exposures of interest were calculated. RESULTS: Overall, 223 deaths due to ischemic heart disease (IHD), 207 deaths due to cerebrovascular accidents (CVA), and 460 deaths due to all CVDs could be averted if the SBP of all subjects in the study were optimal. Similarly, 5,560 YLLs due to IHD, 4,771 YLLs due to CVA, and 11,135 YLLs due to CVDs could be prevented if SBP were optimal. In all age groups, the avertable deaths and YLLs were higher due to IHD compared with CVA. Deaths and YLLs attributable to non-optimal SBP in women were less than men. CONCLUSIONS: A very large proportion of CVD deaths can be averted if blood pressure is controlled in Iran. Effective interventions in primary and secondary health care setting are mandatory to be implemented as early as possible.

Juvenile Hemochromatosis, Genetic Study and Long-term Follow up after Therapy.

BACKGROUND Hereditary hemochromatosis (HH) is a very rare disease in Iran and reported cases are all negative for HFE mutation. We report a family affected by severe juvenile hemochromatosis (JH) with a detailed molecular study of the family members. METHODS We studied a pedigree with siblings affected by juvenile HH and followed them for 3 years. Microsatellite and gene sequencing analysis was performed for all family members. RESULTS Two siblings (the proband and his sister, aged 26 and 30 years, respectively) were found to have clinical findings of JH. The proband's brother, who presented with hyperpigmentation, died of probable JH at the age of 24 years. Gene sequencing analysis showed that the proband has a homozygote c.265T>C (p.C89R) HJV mutation + a heterozygote c.884T>C (p.V295A) mutation of HFE. The affected proband's sister presented with the same HJV c.265T>C (p.C89R) homozygote mutation. In addition, we found the HJV c.98-6C>G polymorphic variant in both the sister and proband (homozygote). Sequencing of hepcidin (HAMP), TfR2, and FPN revealed no mutation. CONCLUSION We have shown that molecular analysis of the HH related gene is a powerful tool for reliable diagnosis of JH and, in conjunction with magnetic resonance imaging (MRI) and noninvasive liver stiffness measurement by elastography, is adequate tool for management and follow up of HH.

Opium use and risk of mortality from digestive diseases: a prospective cohort study.

OBJECTIVES: Opium use, particularly in low doses, is a common practice among adults in northeastern Iran. We aimed to investigate the association between opium use and subsequent mortality from disorders of the digestive tract. METHODS: We used data from the Golestan Cohort Study, a prospective cohort study in northeastern Iran, with detailed, validated data on opium use and several other exposures. A total of 50,045 adults were enrolled during a 4-year period (2004-2008) and followed annually until December 2012, with a follow-up success rate of 99%. We used Cox proportional hazard regression models to evaluate the association between opium use and outcomes of interest. RESULTS: In all, 8,487 (17%) participants reported opium use, with a mean duration of 12.7 years. During the follow-up period 474 deaths from digestive diseases were reported (387 due to gastrointestinal cancers and 87 due to nonmalignant etiologies). Opium use was associated with an increased risk of death from any digestive disease (adjusted hazard ratio (HR)=1.55, 95% confidence interval (CI)=1.24-1.93). The association was dose dependent, with a HR of 2.21 (1.57-3.31) for the highest quintile of cumulative opium use vs. no use (Ptrend=0.037). The HRs (95% CI) for the associations between opium use and malignant and nonmalignant causes of digestive mortality were 1.38 (1.07-1.76) and 2.60 (1.57-4.31), respectively. Increased risks were seen both for smoking opium and for ingestion of opium. CONCLUSIONS: Long-term opium use, even in low doses, is associated with increased risk of death from both malignant and nonmalignant digestive diseases.

Prevalence, awareness and risk factors of hypertension in a large cohort of Iranian adult population.

BACKGROUND: There is considerable variation in hypertension prevalence and awareness, and their correlates, across different geographic locations and ethnic groups. We performed this cross-sectional analysis on data from the Golestan Cohort Study (GCS). METHODS: Enrollment in this study occurred in 2004-2008, and included 50,045 healthy individuals from Golestan Province in northeastern Iran. Hypertension was defined as a SBP at least 140 mmHg, a DBP at least 90 mmHg, a prior diagnosis of hypertension, or the use of antihypertensive drugs. Potential correlates of hypertension and its awareness were analyzed by logistic regression adjusted for sex, age, BMI, place of residence, literacy, ethnicity, physical activity, smoking, black and green tea consumption and wealth score. RESULTS: Of the total cohort participants, 21,350 (42.7%) were hypertensive. Age-standardized prevalence of hypertension, using the 2001 WHO standard world population, was 41.8% (95% confidence interval: 38.3-45.2%). Hypertension was directly associated with female sex, increased BMI, Turkmen ethnicity, and lack of physical activity, and inversely associated with drinking black tea and wealth score. Among hypertensive patients, 46.2% were aware of their disease, 17.6% were receiving antihypertensive medication, and 32.1% of the treated patients had controlled hypertension. Hypertension awareness was greater among women, the elderly, overweight and obese patients, and those with a higher wealth score. CONCLUSION: Hypertension is highly prevalent in rural Iran, many of the affected individuals are unaware of their disease, and the rate of control by antihypertensive medications is low. Increasing hypertension awareness and access to health services, especially among less privileged residents are recommended.