Publications by authors named "Mohammad Reza Ostovaneh"

24 Publications

  • Page 1 of 1

Effectiveness of polypill for primary and secondary prevention of cardiovascular diseases (PolyIran): a pragmatic, cluster-randomised trial.

Lancet 2019 08;394(10199):672-683

Digestive Disease Research Center, Digestive Disease Research Institute, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran; Digestive Oncology Research Center, Digestive Disease Research Institute, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran; Liver and Pancreaticobiliary Disease Research Center, Digestive Disease Research Institute, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran. Electronic address:

Background: A fixed-dose combination therapy (polypill strategy) has been proposed as an approach to reduce the burden of cardiovascular disease, especially in low-income and middle-income countries (LMICs). The PolyIran study aimed to assess the effectiveness and safety of a four-component polypill including aspirin, atorvastatin, hydrochlorothiazide, and either enalapril or valsartan for primary and secondary prevention of cardiovascular disease.

Methods: The PolyIran study was a two-group, pragmatic, cluster-randomised trial nested within the Golestan Cohort Study (GCS), a cohort study with 50 045 participants aged 40-75 years from the Golestan province in Iran. Clusters (villages) were randomly allocated (1:1) to either a package of non-pharmacological preventive interventions alone (minimal care group) or together with a once-daily polypill tablet (polypill group). Randomisation was stratified by three districts (Gonbad, Aq-Qala, and Kalaleh), with the village as the unit of randomisation. We used a balanced randomisation algorithm, considering block sizes of 20 and balancing for cluster size or natural log of the cluster size (depending on the skewness within strata). Randomisation was done at a fixed point in time (Jan 18, 2011) by statisticians at the University of Birmingham (Birmingham, UK), independent of the local study team. The non-pharmacological preventive interventions (including educational training about healthy lifestyle-eg, healthy diet with low salt, sugar, and fat content, exercise, weight control, and abstinence from smoking and opium) were delivered by the PolyIran field visit team at months 3 and 6, and then every 6 months thereafter. Two formulations of polypill tablet were used in this study. Participants were first prescribed polypill one (hydrochlorothiazide 12·5 mg, aspirin 81 mg, atorvastatin 20 mg, and enalapril 5 mg). Participants who developed cough during follow-up were switched by a trained study physician to polypill two, which included valsartan 40 mg instead of enalapril 5 mg. Participants were followed up for 60 months. The primary outcome-occurrence of major cardiovascular events (including hospitalisation for acute coronary syndrome, fatal myocardial infarction, sudden death, heart failure, coronary artery revascularisation procedures, and non-fatal and fatal stroke)-was centrally assessed by the GCS follow-up team, who were masked to allocation status. We did intention-to-treat analyses by including all participants who met eligibility criteria in the two study groups. The trial was registered with ClinicalTrials.gov, number NCT01271985.

Findings: Between Feb 22, 2011, and April 15, 2013, we enrolled 6838 individuals into the study-3417 (in 116 clusters) in the minimal care group and 3421 (in 120 clusters) in the polypill group. 1761 (51·5%) of 3421 participants in the polypill group were women, as were 1679 (49·1%) of 3417 participants in the minimal care group. Median adherence to polypill tablets was 80·5% (IQR 48·5-92·2). During follow-up, 301 (8·8%) of 3417 participants in the minimal care group had major cardiovascular events compared with 202 (5·9%) of 3421 participants in the polypill group (adjusted hazard ratio [HR] 0·66, 95% CI 0·55-0·80). We found no statistically significant interaction with the presence (HR 0·61, 95% CI 0·49-0·75) or absence of pre-existing cardiovascular disease (0·80; 0·51-1·12; p=0·19). When restricted to participants in the polypill group with high adherence, the reduction in the risk of major cardiovascular events was even greater compared with the minimal care group (adjusted HR 0·43, 95% CI 0·33-0·55). The frequency of adverse events was similar between the two study groups. 21 intracranial haemorrhages were reported during the 5 years of follow-up-ten participants in the polypill group and 11 participants in the minimal care group. There were 13 physician-confirmed diagnoses of upper gastrointestinal bleeding in the polypill group and nine in the minimal care group.

Interpretation: Use of polypill was effective in preventing major cardiovascular events. Medication adherence was high and adverse event numbers were low. The polypill strategy could be considered as an additional effective component in controlling cardiovascular diseases, especially in LMICs.

Funding: Tehran University of Medical Sciences, Barakat Foundation, and Alborz Darou.
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http://dx.doi.org/10.1016/S0140-6736(19)31791-XDOI Listing
August 2019

Left Ventricular Hypertrophy and Remodeling and Risk of Cognitive Impairment and Dementia: MESA (Multi-Ethnic Study of Atherosclerosis).

Hypertension 2018 03 29;71(3):429-436. Epub 2018 Jan 29.

From the Department of Cardiology (K.M., M.R.O., B.A.V., M.H., K.Y., I.P., J.A.C.L.) and Department of Neurology (R.F.G.), Johns Hopkins University, Baltimore, MD; Department of Medicine, Rutgers New Jersey Medical School, State University of New Jersey, Newark (K.M.); Office of Biostatistics, National Heart, Lung, and Blood Institute, Bethesda, MD (C.W.); Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL (K.L.); Department of Family Medicine, School of Medicine (A.F.), Department of Epidemiology, School of Medicine (A.F.), Department of Global Health, School of Public Health (A.F.), Department of Biostatistics (R.L.M.), and Department of Epidemiology (S.H.), University of Washington, Seattle; Department of Medicine, Columbia University College of Physicians and Surgeons, New York City, NY (S.S.); National Institute of Biomedical Imaging and Bioengineering, National Institutes of Health Clinical Center, Bethesda, MD (D.A.B.); and Department of Internal Medicine, Wake Forest School of Medicine, Winston-Salem, NC (T.M.H.).

Limited information exists on the longitudinal association between the left ventricular (LV) structure and function and future cognitive impairment and dementia in a large population without clinically recognized cardiovascular disease at baseline. The aim of the present study was to investigate the association between cardiac structure and function and risk of dementia and cognitive impairment in the MESA (Multi-Ethnic Study of Atherosclerosis) cohort. Measures of LV structure and function were determined using magnetic resonance imaging at baseline in 4999 participants free of clinically diagnosed cardiovascular disease and dementia. Probable incident clinical dementia was ascertained from hospitalization discharge records. Cognitive function was evaluated using tests addressing global cognitive function, processing speed, and memory. Associations of measures of LV structure and function with the incidence of clinically diagnosed dementia and cognitive performance were evaluated using Cox proportional hazard regression models adjusted for demographics, cardiovascular risk factors, and cardiovascular events. During a median follow-up of 12 years, 130 probable incident dementia cases were documented. Higher LV mass index (hazard ratio, 1.01; 95% confidence interval, 1.00-1.02) and LV mass-to-volume ratio (hazard ratio, 2.37; 95% confidence interval, 1.25-4.43) were independently associated with incident dementia and impaired cognitive function. Measures of LV function were not associated with risk of dementia or cognitive impairment. In conclusion, in a multiethnic cohort of participants without clinically detected cardiovascular disease and dementia at baseline, LV hypertrophy and concentric remodeling were independently associated with incident dementia and cognitive impairment.
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http://dx.doi.org/10.1161/HYPERTENSIONAHA.117.10289DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5812794PMC
March 2018

Pancreatic Tuberculosis in an Immunocompetent Patient: A Case Report and Review of the Literature.

Middle East J Dig Dis 2017 Oct;9(4):239-241

Department of Internal Medicine, Amir Alam Hospital, Tehran University of Medical Sciences, Tehran, Iran.

Pancreatic tuberculosis is extremely rare and its clinical and radiological findings are similar to those of pancreatic malignancy. The diagnosis of pancreatic tuberculosis is not usually made prior to surgery. Here, we report a case of pancreatic tuberculosis, presented with abdominal pain and weight loss. Abdominal computed tomography (CT) showed a 62 mm × 32 mm septate solid-cystic mass in the pancreatic head area with extension into the hilum of the liver. There was no evidence of inflammation or pancreatitis. Endoscopic ultrasound-fine needle aspiration (EUSFNA) could not yield the diagnosis. Exploratory laparotomy and further pathological evaluation suggested pancreatic tuberculosis. Response to antituberculosis treatment confirmed the diagnosis. Finally, previous case reports and case studies of pancreatic tuberculosis in the literature are fully investigated.
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http://dx.doi.org/10.15171/mejdd.2017.80DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5726338PMC
October 2017

Reliability Analysis of a Newly Developed Questionnaire for Quality Control of Follow-up Visits in PolyIran Study.

Arch Iran Med 2016 Aug;19(8):551-5

Digestive Disease Research Center, Digestive Disease Research Institute, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran.

Background: The PolyIran study is a large-scale pragmatic cluster randomized controlled trial of fixed-dose combination therapy (Polypill) for prevention of cardiovascular diseases (CVD) in Iran. The PolyIran Quality Control Program (PIQCP) including a new questionnaire was developed to assess the quality of data collection during follow-up visits. The aim of this study was to assess the inter-rater reliability of PIQCP questionnaire.

Methods: The study was conducted in 26 (11%) randomly selected clusters (from a total of 236 PolyIran clusters). All participants within these 26 clusters were enrolled. The quality scores were measured according to the PIQCP guidelines by two independent raters. The intraclass correlation coefficients (ICC) were measured. In addition, the quality scores were categorized into good (70%) and poor (<70%). The kappa coefficient was used to assess inter-rater agreement for this categorical quality scores.

Results: A total number of 945 PolyIran participants were enrolled of which, 501 (53%) were from intervention arm. In 934 participants (98.8%), the quality score could be successfully identified by both raters. The ICC (95%CI) of the overall quality scores was 0.985 (0.983-0.987). It was 0.976 (0.972-0.980) and 0.988 (0.986-0.990) in intervention and control arms, respectively. We found excellent agreement between the two raters in identifying participants with good and poor quality scores (kappa = 0.988, P < 0.001). The kappa values were 0.972 (P < 0.001) and 1.000 (P < 0.001) in intervention and control arms, respectively.

Discussion: Our results suggested that the PIQCP questionnaire is a reliable tool for assessing quality of data collection in PolyIran follow-up visits. Using this measure will help us in efficient monitoring of the PolyIran follow-ups and may ensure high quality data.
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http://dx.doi.org/0161908/AIM.006DOI Listing
August 2016

Opium use, cigarette smoking, and alcohol consumption in relation to pancreatic cancer.

Medicine (Baltimore) 2016 Jul;95(28):e3922

Digestive Oncology Research Center, Digestive Diseases Research Institute, Tehran University of Medical Sciences, Tehran, Iran Digestive Disease Research Center, Digestive Diseases Research Institute, Tehran University of Medical Sciences, Tehran, Iran Department of Public Health Analysis, School of Community Health and Policy, Morgan State University, Baltimore, MD Liver and Pancreatobiliary Diseases Research Center, Digestive Diseases Research Institute, Tehran University of Medical Sciences Gastrointestinal and Liver Disease Research Center, Firoozgar Hospital, Iran University of Medical Sciences Sasan Alborz Biomedical Research Center, Masoud Gastroenterology and Hepatology Clinic, Tehran, Iran Division of Gastroenterology and Hepatology, The Sol Goldman Pancreatic Cancer Research Center, The Johns Hopkins Medical Institutions, Baltimore, MD American Cancer Society, Atlanta, GA Institute for Transitional Epidemiology and the Tisch Cancer Institute, Mount Sinai School of Medicine, New York, NY.

Background And Aims: Although several studies have suggested opium as a risk factor for cancers of the esophagus, stomach, larynx, lung, and bladder, no previous study has examined the association of opium with pancreatic cancer. We aimed to study the association between opium use and risk of pancreatic cancer in Iran, using a case-control design. We also studied the association of cigarette smoking and alcohol consumption with pancreatic cancer, for which little information was available from this population.

Methods: Cases and controls were selected from patients who were referred to 4 endoscopic ultrasound centers in Tehran, Iran. We recruited 316 histopathologically (all adenocarcinoma) and 41 clinically diagnosed incident cases of pancreatic cancer, as well as 328 controls from those with a normal pancreas in enodosonography from January 2011 to January 2015. We used logistic regression models to calculate odds ratios (ORs) and 95% confidence intervals (CIs).

Results: After adjustment for potential confounders, opium use (OR 1.91; 95% CI 1.06-3.43) and alcohol consumption (OR 4.16; 95% CI 1.86-9.31) were significantly associated with an increased risk of pancreatic cancer. We did not find an association between ever tobacco smoking and pancreatic cancer risk (OR 0.93; 95% CI 0.62-1.39).

Conclusion: In our study, opium use and alcohol consumption were associated with an increased risk of pancreatic cancer, whereas cigarette smoking was not.
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http://dx.doi.org/10.1097/MD.0000000000003922DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4956779PMC
July 2016

Predictive Value of Pupillary Response to Mydriatic Agents for Diagnosis of Retinopathy of Prematurity.

J Ophthalmic Vis Res 2015 Oct-Dec;10(4):417-23

Department of Cardiology, Johns Hopkins University, Baltimore, Maryland, USA.

Purpose: To evaluate the feasibility of screening for retinopathy of prematurity (ROP) by assessing the pupillary response to mydriatics.

Methods: This observational case series included 134 eyes of 67 premature infants with birth weight less than 2,000 grams and gestational age less than 33 weeks. A composite eye drop composed of phenylephrine 1%, tetracaine and tropicamide 0.5% was applied 3 times within 5-minute intervals and pupil diameters were measured. The eyes were examined by experienced ROP specialists using an indirect ophthalmoscope. Zone and stage of ROP, presence of plus disease and need for treatment were recorded. The relationship between the pupillary response to mydriatics, and presence and severity of ROP was evaluated. Logistic regression was used for statistical analysis.

Results: According to receiver operating characteristic (ROC) curve analysis, final pupil diameter after mydriatic administration was found the most accurate factor among other factors to recognize ROP zone I from zones II and III (Area under ROC: 0.92 [95%CI: 0.85-0.98]). The best cutoff value for final pupil diameter was 5.6 mm, because it could differentiate involvement of zone I from zones II and III with sensitivity of 80% and specificity of 100%.

Conclusion: Response of the pupil to mydriatic eye drops may be useful as a less invasive method for rough estimation of ROP in high risk babies who need emergent attention; however, it cannot be considered as a screening test due to its low sensitivity.
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http://dx.doi.org/10.4103/2008-322X.176892DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4795391PMC
April 2016

Nonalcoholic Fatty Liver: The Association with Metabolic Abnormalities, Body Mass Index and Central Obesity--A Population-Based Study.

Metab Syndr Relat Disord 2015 Sep 4;13(7):304-11. Epub 2015 Jun 4.

2 Liver and Pancreatobiliary Diseases Research Center, Digestive Diseases Research Institute, Tehran University of Medical Sciences , Tehran, Iran .

Background: To assess the prevalence of nonalcoholic fatty liver (NAFL) in Iran and to evaluate correlates of NAFL in categories of body mass index (BMI).

Methods: Using a cluster random sampling approach, 7723 subjects over 18 years of age underwent abdominal ultrasonography, laboratory evaluations, blood pressure, and anthropometric measurements and were interviewed to obtain baseline characteristics. Prevalence of NAFL according to BMI and waist to hip ratio and its association with metabolic abnormalities in categories of BMI were assessed in multivariate analysis.

Results: The overall prevalence of NAFL was 35.2% [95% confidence interval (CI) 34.1-36.3]. A significant number of subjects with BMI < 30 had NAFL [22.1% (CI 21.0-23.2)]. Waist to hip ratio for 38.2% (CI 35.6-40.8) of the subjects with NAFL, and BMI < 30 was higher than normal values. The odds ratio for association of NAFL and dyslipidemias were higher in subjects with BMI < 30 versus those with BMI ≥ 30: (1) hypertriglyceridemia: 2.21 vs. 1.57, P = 0.006; (2) lower high-density lipoprotein: 1.29 versus 0.98, P = 0.046. Higher low-density lipoprotein also revealed greater association with NAFL in subjects with BMI < 25 than those with BMI ≥ 25 (odds ratio 1.84 vs. 1.1, P = 0.015).

Conclusions: NAFL shows stronger association with central obesity compared to high BMI. NAFL has stronger association with dyslipidemias in subjects with low compared with high BMI.
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http://dx.doi.org/10.1089/met.2014.0131DOI Listing
September 2015

Cohort profile: golestan hepatitis B cohort study- a prospective long term study in northern iran ​.

Middle East J Dig Dis 2014 Oct;6(4):186-94

Liver and Pancreatobiliary Diseases Research Center, Digestive Disease Research Institute, Shariati Hospital, Tehran university of Medical Sciences, Tehran, Iran.

Hepatitis B virus (HBV) infection is the most common cause of end stage liver disease in Iran and in Golestan province. Large-scale population-based prospective cohort studies with long term follow-up are the method of choice to accurately understand the natural course of HBV infection. To date, several studies of HBV epidemiology, natural history, progression to cirrhosis and association with HCC have been reported from other countries. However, few of these are prospective and fewer still are population-based. Moreover, the underlying molecular mechanisms and immunogenetic determinants of the outcome of HBV infection especially in low and middle income countries remains largely unknown. Therefore, the hepatitis B cohort study (HBCS), nested as part of the Golestan Cohort Study (GCS), Golestan, Iran was established in 2008 with the objective to prospectively investigate the natural course of chronic hepatitis B with reference to its epidemiology, viral/host genetic interactions, clinical features and outcome in the Middle East where genotype D HBV accounts for >90% of infections. In 2008, a baseline measurement of HBV surface antigen (HBsAg) was performed on stored serum samples of all GCS participants. A sub-cohort of 3,505 individuals were found to be HBsAg positive and were enrolled in the Golestan HBCS. In 2011, all first degree relatives of HBsAg positive subjects including their children and spouses were invited for HBV serology screening and those who were positive for HBsAg were also included in the Golestan HBCS.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4208926PMC
October 2014

Polypill for the prevention of cardiovascular disease (PolyIran): study design and rationale for a pragmatic cluster randomized controlled trial.

Eur J Prev Cardiol 2015 Dec 17;22(12):1609-17. Epub 2014 Sep 17.

Digestive Disease Research Institute, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran

Background: The complexity of treatment regimens, costs and pill burden decrease the medication adherence and contribute to shortfall in cardiovascular preventive drug coverage. The polypill, a fixed dose combination pill of established drugs, is expected to increase adherence and reduce the costs whilst preventing major cardiovascular events (MCVE).

Design And Methods: The PolyIran trial is a pragmatic cluster randomized trial nested within the Golestan Cohort Study (GCS). Subjects were randomized to either non-pharmacological preventive interventions alone (minimal care arm) or together with a polypill (polypill arm) comprising hydrochlorothiazide, aspirin, atorvastatin and either enalapril or valsartan. This study benefits from the infrastructure of the primary health care system in Iran and the interventions are delivered by the local auxiliary health workers (Behvarz) to the participants. The primary outcome of the study is the occurrence of first MCVE within five years defined as non-fatal and fatal myocardial infarction, unstable angina, sudden death, heart failure, coronary artery revascularization procedures, and non-fatal and fatal stroke.

Trial Status: From February 2011 to April 2013, 8410 individuals (236 clusters) attended the eligibility assessment. Of those, 3421 in the polypill arm and 3417 in the minimal care arm were eligible. The study is ongoing.

Conclusion: The infrastructure of GCS and the primary health care system in Iran enabled the conduct of this pragmatic large-scale trial. If the polypill strategy proves effective, it may be implemented to prevent cardiovascular disease in developing countries.
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http://dx.doi.org/10.1177/2047487314550803DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5836725PMC
December 2015

Liver transplant patients have a risk of progression similar to that of sporadic patients with branch duct intraductal papillary mucinous neoplasms.

Liver Transpl 2014 Dec;20(12):1462-7

Division of Gastroenterology and Hepatology, The Sol Goldman Pancreatic Cancer Research Center, The Johns Hopkins Medical Institutions, Baltimore, MD; Division of Surgery, The Sol Goldman Pancreatic Cancer Research Center, The Johns Hopkins Medical Institutions, Baltimore, MD.

Intraductal papillary mucinous neoplasms (IPMNs) have malignant potential and can progress from low- to high-grade dysplasia to invasive adenocarcinoma. The management of patients with IPMNs is dependent on their risk of malignant progression, with surgical resection recommended for patients with branch-duct IPMN (BD-IPMN) who develop high-risk features. There is increasing evidence that liver transplant (LT) patients are at increased risk of extrahepatic malignancy. However, there are few data regarding the risk of progression of BD-IPMNs in LT recipients. The aim of this study was to determine whether LT recipients with BD-IPMNs are at higher risk of developing high-risk features than patients with BD-IPMNs who did not receive a transplant. Consecutive patients who underwent an LT with BD-IPMNs were included. Patients with BD-IPMNs with no history of immunosuppression were used as controls. Progression of the BD-IPMNs was defined as development of a high-risk feature (jaundice, dilated main pancreatic duct, mural nodule, cytology suspicious or diagnostic for malignancy, cyst diameter ≥3 cm). Twenty-three LT patients with BD-IPMN were compared with 274 control patients. The median length of follow-up was 53.7 and 24.0 months in LT and control groups, respectively. Four (17.4%) LT patients and 45 (16.4%) controls developed high-risk features (P = 0.99). In multivariate analysis, progression of BD-IPMNs was associated with age at diagnosis but not with LT. There was no statistically significant difference in the risk of developing high-risk features between the LT and the control groups.
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http://dx.doi.org/10.1002/lt.23983DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4322915PMC
December 2014

Impact of microscopic duodenitis on symptomatic response to Helicobacter pylori eradication in functional dyspepsia.

Dig Dis Sci 2015 Jan 8;60(1):163-7. Epub 2014 Aug 8.

Division of Gastroenterology, Department of Internal Medicine, Amir Alam Hospital, Tehran University of Medical Sciences, North Sa'adi Street, 13145-784, Tehran, Iran.

Background And Aim: There is no consensus regarding the benefit of eradicating Helicobacter pylori (H. pylori) infection in patients with functional dyspepsia (FD). We intended to compare the symptom response to H. pylori eradication in FD patients in presence or absence of microscopic duodenitis (MD).

Methods: Patients with dyspepsia, normal upper gastrointestinal endoscopy and no psychological comorbidity according to the 12-item General Health Questionnaire underwent duodenal biopsy sampling. Of those, subjects with positive rapid urease test and H. pylori colonization in Wright-Giemsa staining were included in the study and evaluated histologically for presence of MD. All patients received sequential H. pylori eradication therapy and underwent urea breath test 4 weeks after the completion of the treatment to confirm the H. pylori eradication. The severity of dyspepsia was assessed using the Leeds Dyspepsia Questionnaire (LDQ) at baseline, 3rd and 6th months after the H. pylori infection was eradicated.

Results: Thirty seven patients were included in the study [mean age: 34.9 (8.1), 54.05 % female]. MD was observed in 16 (43.2 %) of the subjects. The mean LDQ score in patients with MD decreased from 12.5 (4.1) at baseline to 4.3 (2.1) at 3rd month and 2.6 (1.9) at 6th month. In patients without microscopic duodenitis, the mean LDQ score decreased from 10.6 (5.2) at baseline to 6.8 (4.1) and 6.2 (3.8) at 3rd and 6th months, respectively. The improvement in severity of symptoms in presence of MD was significantly greater than when it was absent (P < 0.001).

Conclusion: FD patients with MD achieved greater symptomatic response with H. pylori eradication than those without microscopic duodenitis.
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http://dx.doi.org/10.1007/s10620-014-3285-1DOI Listing
January 2015

Noninvasive measurement of liver fibrosis using transient elastography in pediatric patients with major thalassemia who are candidates for hematopoietic stem cell transplantation.

Biol Blood Marrow Transplant 2014 Dec 25;20(12):1912-7. Epub 2014 Jul 25.

Liver and Pancreatobiliary Diseases Research Center, Digestive Diseases Research Institute, Tehran University of Medical Sciences, Tehran, Iran. Electronic address:

Although liver biopsy is an invasive procedure, it remains the gold standard technique for the evaluation of hepatic fibrosis in different patients, including those with major thalassemia (MT). Recently, noninvasive imaging techniques, such as transient elastography, have emerged. We investigated the effectiveness of TE, in comparison to liver biopsy, for the evaluation of liver fibrosis in pediatric patients with MT who were candidates for hematopoietic stem cell transplantation (HSCT). Eighty-three pediatric MT patients (48 boys and 35 girls), who were candidates for HSCT, were included in this study. The median age was 8 years. Liver stiffness was assessed for all patients, before transplantation, using both TE, measured in kilopascals (kPa) and liver biopsy, based on the Metavir score. The diagnostic accuracy of TE and liver biopsy were estimated using linear discriminated analysis (the area under the receiver operating characteristic curves [AUROCs]). The median TE score was 4.3 kPa (range, 3.5 to 5.2). The TE value did not differ among patients with different ferritin levels (P = .53). TE increased proportionally to Metavir fibrosis stages (P < .001) and the necro-inflammatory grade (P < .001). The TE score also correlated to liver iron content (P < .001), liver size (P < .003), and Lucarelli risk classification (LRC) (P < .001). ROC curve analysis revealed moderate accuracy of the TE score for the diagnosis of fibrosis (AUROC = 73%) and for distinguishing individuals with a LRC III from those classified as I and II (AUROC = 82%). The TE score was also superior to Fibrosis-4 (AUROC = 61%) for the assessment of liver fibrosis and LRC differentiation. The results of this study demonstrated that TE can be a valuable method for assessing liver fibrosis and differentiating LRC III from the other 2 classes in pediatric patients with MT who have been selected for HSCT.
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http://dx.doi.org/10.1016/j.bbmt.2014.07.025DOI Listing
December 2014

Prevalence of metabolic syndrome in Amol and Zahedan, Iran: a population based study.

Arch Iran Med 2014 Jul;17(7):477-82

Digestive Diseases Research Institute (DDRI), Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran.

Purpose: So far, a variety of prevalence rates have been reported for the metabolic syndrome (MetS) according to several definitions. The aim of this study was to assess the prevalence of MetS in Iran according to two definitions and compare the characteristics of the subjects who met the MetS criteria according to the different definitions.

Methods: Participants were recruited from family registries of public health centers. After obtaining demographic and clinical data, the subjects underwent anthropometric measurements and laboratory evaluations. MetS was defined according to the NCEP-ATPIII and IDF criteria. The subjects were then categorized into 3 groups: 1) Healthy non-MetS subjects based on either definition, 2) Individuals with MetS according to only one of the definitions, and 3) Individuals who met both NCEP-ATPIII and IDF criteria for MetS.

Results: Totally, 5826 subjects in Amol and 2243 subjects in Zahedan were enrolled in the study. The weighted prevalence of MetS according to the NCEP-ATPIII and IDF criteria was 27.8% and 26.9% in Amol and 12% and 11.8% in Zahedan, respectively. Overall, 18.9% of the subjects fulfilled both criteria for MetS. However, a considerable proportion (8.5%) met the MetS criteria according to only one definition but not both.

Conclusions: MetS is increasingly prevalent in Iran as well as other parts of the world. Due to non-uniform definitions of MetS, some of the subjects who meet MetS according to one set of criteria might be considered healthy according to another definition and consequently would not receive the preventive health services.
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http://dx.doi.org/0141707/AIM.006DOI Listing
July 2014

Diagnostic value of fecal calprotectin in patient with ulcerative colitis.

Middle East J Dig Dis 2013 Apr;5(2):76-80

Digestive Diseases Research Center, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran.

Background: Ulcerative colitis (UC) is characterized by recurrent episodes of inflammation limited to the mucosal layer of the colon. Calprotectin is a zinc and calcium binding protein derived from neutrophils and monocytes. It is easily detectable in tissue samples, body fluids, and stools, which makes it a potentially valuable marker of inflammation. The aim of the current study is to evaluate the value of fecal calprotectin (FC) as a marker of disease activity in patients with UC.

Methods: Seventy three eligible subjects underwent ileocolonoscopy and multiple biopsies were obtained from different parts of the colon and terminal ileum. All patients underwent blood and stool sampling as well as an interview to assess the disease severity utilizing ulcerative colitis activity index (UCAI), subjectively. The diagnostic value of the FC in comparison with Mayo disease activity index as the gold standard technique, was then evaluated.

Results: Mean FC level increased linearly according to Mayo disease activity index (r=0.44, p<0.001) and was significantly different between levels of Mayo disease activity index (p=0.003). In multivariate analysis, Mayo disease activity index, positive CRP and ESR were associated with FC level. FC level > 21.4 ng/ml was able to discriminate between active and inactive phases of UC according to Mayo disease activity index>2 with 72.3% sensitivity and 73.1% specificity. The combination of FC > 21.4 ng/ml and UCAI score of 7 had a 46.8% sensitivity and 88% specificity to diagnose Mayo disease activity index >2. Furthermore, FC level <21.4 ng/ml in combination with UCAI score of <3 showed a highly considerable specificity of 98% to discriminate the remission phase of UC (Mayo disease activity index <2), although with a low sensitivity (31%).

Conclusion: FC appears to be a non-invasive biomarker with moderate accuracy to discriminate the active phase of inflammatory bowel disease (IBD). The value of FC especially in combination with UCAI is highly considerable to rule out the Mayo disease activity index >2.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3990145PMC
April 2013

Screening colonoscopy in first-degree relatives of patients with colorectal cancer.

Arch Iran Med 2014 Feb;17(2):115-7

Digestive Disease Research Institute, Tehran University of Medical Sciences, Tehran, Iran.

Background: Colorectal cancer (CRC), one of the most important causes of morbidity and mortality, has earned the attention of healthcare systems widely. Screening programs are designed to detect patients at risk as effectively as possible. One of the major CRC risk factors is having a family member with diagnosed CRC.

Aim: To investigate the association between presence of polyps on colonoscopy and family history of CRC.

Methods: This was a retrospective cohort study in which the data was collected from colonoscopy reports of patients with/without familial history of CRC in Masoud private clinic, Tehran, Iran from October 1, 2011 to October 1, 2012. The association between presence of colorectal polyps on colonoscopy and family history of CRC was then assessed.

Results: A total of 210 patients were included in the study, constituting two groups with/without familial history of CRC with a 1:1 ratio (105 subjects in each group). Compared to subjects with a negative family history of CRC, a 2.7-fold (CI 95%: 1.2-6.24) fold increase was observed in those with a positive family history to have colorectal polyps. In multivariate regression analysis, family history of CRC was the only independent variable associated with presence of colorectal polyps (odds ratio: 3.12, CI 95%:1.22-8).

Conclusion: A positive family history of CRC is a risk factor for colorectal polyps.
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http://dx.doi.org/014172/AIM.006DOI Listing
February 2014

Tissue hypoxia in pathogenesis of ulcerative colitis: should we change all our beliefs?

Scand J Gastroenterol 2013 Dec 18;48(12):1487-8. Epub 2013 Oct 18.

Department of Gastroenterology, Amira'lam Hospital, Faculty of Medicine, Tehran University of Medical Science , Tehran , Iran.

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http://dx.doi.org/10.3109/00365521.2013.845798DOI Listing
December 2013

Transient elastography in hepatitis C virus-infected patients with beta-thalassemia for assessment of fibrosis.

Hepatol Res 2013 Dec 12;43(12):1276-83. Epub 2013 Mar 12.

Digestive Diseases Research Institute, Shariati Hospital, Tehran, Iran.

Aim: We sought to evaluate the performance of transient elastography (TE) for the assessment of liver fibrosis in chronic hepatitis C (CHC) patients with beta-thalassemia.

Methods: Seventy-six CHC patients with beta-thalassemia underwent TE, liver biopsy, T2 -weighted magnetic resonance imaging (MRI) for the assessment of liver iron content (LIC) and laboratory evaluation. The accuracy of TE and its correlation with the other variables was assessed.

Results: TE values increased proportional to fibrosis stage (r = 0.404, P < 0.001), but was independent of T2 -weighted MRI-LIC (r = 0.064, P = 0.581). In multivariate analysis, fibrosis stage was still associated with the log-transformed TE score(standardized β = 0.42 for F4 stage of METAVIR, P = 0.001). No correlation was noted between LIC and TE score (standardized β = 0.064, P = 0.512). The area under the receiver operating characteristic curve for prediction of cirrhosis was 80% (95% confidence interval, 59-100%). A cut-off TE score of 11 had a sensitivity of 78% and specificity of 88.1% for diagnosing cirrhosis. The best cut-off values for "TE-FIB-4 cirrhosis score" comprising TE and FIB-4 and "TE-APRI cirrhosis score" combining TE with aspartate aminotransferase-to-platelet ratio index (APRI) both had 87.5% sensitivity and 91.04% specificity for the diagnosis of cirrhosis.

Conclusion: Regardless of LIC, TE alone or when combined with FIB-4 or APRI, is a diagnostic tool with moderate to high accuracy to evaluate liver fibrosis in CHC patients with beta-thalassemia. However, because splenectomy in a proportion of our subjects might have affected the platelet count, the scores utilizing APRI and FIB-4 should be interpreted cautiously.
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http://dx.doi.org/10.1111/hepr.12088DOI Listing
December 2013

Na(+)-H+ exchange inhibition attenuates ischemic injury in rat random pattern skin flap: the role of mitochondrial ATP-sensitive potassium channels.

Eur J Pharmacol 2013 Jan 2;698(1-3):330-4. Epub 2012 Nov 2.

Experimental Medicine Research Center, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.

Necrosis of distal portion of skin flaps due to ischemia still remains a problem in plastic surgery. Following ischemia, a cascade of deleterious events including over-activity of Na(+)-H(+) Exchanger (NHE) takes place. In present study we evaluated the effect of the potent NHE inhibitor, 5-(N-ethyl-N-isopropyl) amiloride (EIPA) on ischemic tissue injury in a skin flap model, and investigated the role of mitochondrial ATP-sensitive K(+) channels (K(ATP)) in this phenomenon. Seventy-eight rats were randomly divided into thirteen treatment groups (6 rats each). Four groups received different doses of EIPA in the flap. EIPA/GLY group received an effective dose of a K(ATP) channel blocker, glibenclamide (GLY, 0.3mg/kg) intraperitoneally (i.p.) 30 min before raising the flap, and a local effective dose of EIPA (0.1mM) immediately after raising the flap. EIPA/diazoxide group (EIPA/DIA) received a sub-effective dose of diazoxide (7.5mg/kg i.p.) 30 min before raising the flap and a local sub-effective dose of EIPA (0.075 mM). EIPA 0.1 and 0.2mM significantly increased flap survival area compared to control group (56.01 ± 6.1%, P<0.001). The protective effect of EIPA (0.1mM) was abolished by administration of glibenclamide (0.3mg/kg i.p.). Co-administration of a sub-effective dose of EIPA (0.075 mM), with a sub-effective dose of diazoxide (7.5mg/kg i.p.) significantly improved flap survival (P<0.05). We demonstrated that the NHE inhibitor, EIPA can increase random pattern skin flap survival. Administration of diazoxide potentiates this effect, while glibenclamide abolishes that, implicating that the protective effect of EIPA is mediated through mitochondrial-K(ATP) channels.
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http://dx.doi.org/10.1016/j.ejphar.2012.10.022DOI Listing
January 2013

Seroprevalence of hepatitis B surface antigen and anti hepatitis C antibody in zahedan city, iran: a population-based study.

Hepat Mon 2012 Sep 30;12(9):e6618. Epub 2012 Sep 30.

Health Promotion Research Center, Zahedan University of Medical Sciences, Zahedan, IR Iran.

Background: There have been studies regarding the prevalence of hepatitis B surface antigen (HBsAg) and anti-hepatitis C antibody (HCVAb) in Iran. However, the majority of these have reported a variety of rates, depending on their study population, which limits the generalizability of their results to the general population. On the other hand, cultural diversity in the different provinces of Iran also necessitates the performing separate population-based studies in the various regions.

Objectives: To evaluate the population-based prevalence of HBsAg and HCVAb and their correlates in Zahedan City, Iran.

Patients And Methods: Included in this study were 2587 individuals, using a random and cluster sampling approach. The participants were drawn from the Family Registry of the public health centers in Zahedan City, Iran, from 2008 to 2009. Following data collection from the interviews, subjects were assessed for seropositivity of HBsAg and HCVAb. We then calculated the prevalence of HBsAg and HCVAb, and evaluated these viral markers for an association with; age, sex and potential risk factors.

Results: Weighted seroprevalence of HBsAg and HCVAb was 2.5% (CI 95% : 1.9 to 3.3 %) and 0.5% (CI 95% : 0.27 to 0.9 %), respectively. Prevalence of HBsAg increased significantly with age (P value < 0.001), but this was not true for HCVAb (P value: 0.67). We observed no sex dominance in the prevalence of HBsAg (3.2% and 2.2% for males and females, respectively, P value: 0.15) or HCVAb (0.4% and 0.7% for males and females, respectively, P value: 0.27). In a multivariate regression analysis, every additional year in age resulted in a 2% increment in the odds of HBsAg seropositivity. HBsAg was also three times more prevalent among married, than single subjects (with a P value reaching toward significance: 0.065) in multivariate analysis. Prevalence of HCVAb did not differ with respect to any of the potential risk factors.

Conclusions: This is the first population-based study on the prevalence of HCVAb and one of the few population based studies on HBsAg in Zahedan City. We detected lower prevalence rates of HBsAg and HCVAb than in previous studies conducted in Zahedan City. In addition to improvements in social awareness and general health elements, we think that the observed low prevalence rates have been achieved due to the efficiency of mass vaccination projects, implemented against HBV infection in Iran.
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http://dx.doi.org/10.5812/hepatmon.6618DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3475139PMC
September 2012

Predictors of mental and physical health in non-cirrhotic patients with viral hepatitis: a case control study.

J Psychosom Res 2012 Sep 16;73(3):218-24. Epub 2012 Jul 16.

Digestive Disease Research Institute (DDRI), Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran.

Objective: To identify independent predictors of mental and physical health in patients with viral hepatitis.

Methods: Hepatitis C (HCV) and hepatitis B (HBV) infected patients, and community control subjects with equal age and sex distribution were recruited. All subjects filled in personal characteristics questionnaire, Hospital Anxiety and Depression Scale (HADS), Iowa Fatigue Scale (IFS), and Medical Outcomes Survey Short Form-12 (SF-12). All patients had measurement of routine laboratory values, and some had recent liver biopsy. Regression analyses were used to identify predictors of physical and mental health.

Results: One hundred eighty nine subjects (162 males, 27 females, for each group N=63) with mean (±SD) age of 39±11years were included. Anxiety and depression were important predictors of SF-12 (and its subscales MCS and PCS) and IFS scores, whereas IFS scores independently predicted HADS, PCS, MCS, and SF-12 scores. After controlling for confounders, HCV infection was independently associated with impairment of physical health. Moreover, creatinine showed an inverse strong relation with fatigue. Genotype 3a of HCV was independently associated with depressed and anxious states, whereas higher inflammation grade was significantly related to depression. Marital status, non-psychiatric comorbidities, and history of alcohol abuse also predicted health scores in the patients. Adjusted R(2)s for linear models were 0.571 to 0.709, whereas areas under the receiver operating characteristic (ROC) curve for logistic models were 0.90 to 0.93.

Conclusion: In viral hepatitis patients, besides mental and medical comorbidities, marital status, and alcohol abuse, HCV infection itself is associated with impaired physical and possibly mental health.
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http://dx.doi.org/10.1016/j.jpsychores.2012.06.006DOI Listing
September 2012

Impact of Helicobacter pylori infection and microscopic duodenal histopathological changes on clinical symptoms of patients with functional dyspepsia.

Dig Dis Sci 2012 Apr 12;57(4):967-72. Epub 2011 Nov 12.

Department of Internal Medicine, Amir-Alam Hospital, School of Medicine, Tehran University of Medical Sciences, North Sa'adi Street, 13145-784 Tehran, Iran.

Aim: To evaluate the microscopic histopathological changes in duodenal tissue and its relationship to the severity of symptoms in patients with functional dyspepsia while taking the effect of Helicobacter pylori (H. pylori) infection into account.

Methods: Several gastric and duodenal biopsy specimens were obtained in 217 patients with functional dyspepsia and were evaluated for H. pylori infection and histopathological changes. Severity of symptoms was assessed by Leeds Dyspepsia Questionnaire (LDQ) and its relationship to histopathological changes and H. pylori infection status was assessed.

Results: Helicobacter pylori infection was associated with presence and severity of microscopic duodenitis (p < 0.001). In H. pylori-infected patients, the presence of microscopic duodenitis was independent of microscopic gastritis (p = 0.74). Severity of dyspepsia symptoms was not higher in H. pylori-infected patients than non-infected patients (p = 0.15), but in the presence of H. pylori infection and microscopic gastritis, microscopic duodenitis significantly worsened the LDQ symptom severity score (p < 0.001). In multivariate analysis, the odds of experiencing severe symptoms in patients with severe microscopic duodenitis was 2.22 times greater than in individuals with very mild, mild, or moderate duodenitis.

Conclusions: Microscopic duodenitis in H. pylori-infected patients may play a major role in producing and aggravating symptoms in FD patients and may be a determinant factor to consider in whether to treat H. pylori infection in functional dyspepsia.
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http://dx.doi.org/10.1007/s10620-011-1960-zDOI Listing
April 2012

Lithium decreased endothelium-mediated, but not nonadrenergic noncholinergic, relaxation of guinea pig corpus cavernosum in vitro: a role for nitrergic system.

Fundam Clin Pharmacol 2011 Apr;25(2):191-9

Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, P.O. Box 13145-784, Tehran, Iran.

Lithium causes erectile dysfunction in patients but its mechanism is yet unknown. The aim of our study was to verify the effect of acute lithium administration on the nonadrenergic noncholinergic (NANC)- and endothelium-mediated relaxation of guinea pig isolated corpus cavernosum. Although lithium (0.5, 1, and 5mm) had no effect on the neurogenic relaxations, it significantly (P<0.001) attenuated the relaxant responses to acetylcholine in a concentration-dependent manner. Combination of low concentration of lithium (0.5mm) with either 0.1 or 1μm l-NAME significantly (P<0.001) reduced the endothelium-mediated relaxation. Although the Nitric oxide (NO) precursor l-arginine at 1mm did not alter the relaxant responses to acetylcholine in control strips, it improved the inhibition by lithium (1mm) of relaxant responses to acetylcholine. Sodium nitroprusside (SNP; 10nm-1mm) produced similar concentration-dependent relaxations in both groups. Our experiments indicated that lithium can result in impairment of the NO-mediated endothelium-dependent but not NANC relaxation of guinea pig corpus cavernosum.
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http://dx.doi.org/10.1111/j.1472-8206.2010.00825.xDOI Listing
April 2011

Teapot ureterocystoplasty and ureteral Mitrofanoff channel for bilateral megaureters: technical points and surgical results of neurogenic bladder.

J Urol 2010 Mar 22;183(3):1168-74. Epub 2010 Jan 22.

Pediatric Urology Research Center, Department of Urology, Tehran University of Medical Sciences, Tehran, Iran.

Purpose: We present the long-term results of simultaneous "teapot" ureterocystoplasty and ureteral Mitrofanoff in patients with bilateral megaureters due to neurogenic bladder, and compare urodynamic results before and after the procedure.

Materials And Methods: We treated 13 children (mean age 7.3 years) with end stage neurogenic bladder and refluxing megaureters (mean diameter 5.5 cm) with simultaneous teapot ureterocystoplasty and Mitrofanoff appendicovesicostomy between April 1995 and May 2001. The larger ureter was used for teapot bladder augmentation while keeping its distal 2 cm tubularized. The Mitrofanoff channel was then created using the opposite ureter.

Results: Followup ranged from 109 to 169 months (median 121). At the end of the followup period all patients were dry with clean intermittent catheterization and/or voiding. No repeat augmentation was needed and there were no bladder calculi during followup. Median postoperative bladder capacity was 430 ml (IQR 380 to 477), which was increased significantly compared to preoperative evaluations (210 ml, IQR 181 to 230, p = 0.001). During followup bladder compliance also improved significantly (p = 0.001) and serum creatinine level decreased (p = 0.021).

Conclusions: Although neurogenic bladder and high grade reflux are poor prognostic factors for ureterocystoplasty, the present modification resulted in enduring bladder augmentation with no calculus formation. Bladders remained compliant with good capacity, presumably because sufficient tissue and blood supply were provided for the augmented flap.
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http://dx.doi.org/10.1016/j.juro.2009.11.052DOI Listing
March 2010