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1.  Adenoma detection rates in an opportunistic screening colonoscopy program in Iran, a country with rising colorectal cancer incidence 
BMC Gastroenterology  2014;14(1):196.
Data on the quality of colonoscopies in populations with rising colorectal cancer (CRC) incidence is scarce. We aimed to calculate the adenoma detection rates (ADR), and assess the quality of colonoscopies in an opportunistic screening colonoscopy program in Iran.
All the colonoscopy and pathology reports of asymptomatic adults over age 50 who underwent screening colonoscopy between June 2007 and March 2013 were reviewed. The colonoscopy quality indicators including ADR were calculated, and patient factors associated with the adenoma detection were determined.
A total of 713 asymptomatic adults aged 50 years and older who underwent their first-time screening colonoscopy were included in this study. ADR and advanced-ADR were 33.00% (95% CI: 29.52-36.54) and 13.18% (95% CI: 10.79-15.90), respectively. We observed a significantly higher rate of cecal intubation in patients with fair or better bowel preparation compared to those with poor prep, 90.00% vs. 70.45%, respectively (P < 0.001). Bowel preparation (adjusted OR: 2.49, 95% CI: 1.75-3.55), older age (≥60) (adjusted OR: 1.70, 95% CI: 1.22-2.36), and male gender (adjusted OR: 1.39, 95% CI: 1.01-1.92) were associated with the adenoma detection.
Our ADR in both genders meets and exceeds the recommended colonoscopy quality benchmarks. The polyp and adenoma detection rates in the current study are comparable to those reported from Western countries where the incidence of CRC is traditionally high. These data are in line with the epidemiologic transition of CRC in Iran.
PMCID: PMC4245784  PMID: 25404264
Screening colonoscopy; Colonic polyps; Colon cancers
2.  Characteristics of Colorectal Polyps and Cancer; a Retrospective Review of Colonoscopy Data in Iran 
Early diagnosis and endoscopic resection of adenomatous polyps is the main approach for screening and prevention of colorectal cancer (CRC). We aimed to assess polyp detection rate (PDR) and to characterize demographic, clinical, and pathological features of colorectal polyps in an Iranian population.
We retrospectively analyzed the data from 5427 colonoscopies performed during 2007-2012 at Masoud Clinic, the main endoscopy center associated with Sasan Alborz Biomedical Research Center, in Tehran, Iran.
Our sample included 2928 (54%) women and 2499 (46%) men, with the mean age of 48.3 years (SD=16.1). The most common reasons for colonoscopy included screening in 25.0%, and gastrointestinal bleeding in 15.2%. Cecal intubation was successful in 86% of patients. The quality of bowel preparation was fair to excellent in 78.1% (n=4235) of colonoscopies. Overall PDR was 42.0% (95% CI: 40.6-43.3). The PDR in men (51.1%, 95% CI: 49.1-53.1) was significantly higher than women (34.2%, 95% CI: 32.4-35.9, p<0.001). Polyps were more frequently observed in patients after the 6th decade of life (F=3.2; p=0.004). CRC was detected in 2.9% (73/2499) of men and 1.9% (57/2928) of women (p=0.02). The mean age for patients with cancer was significantly higher than that for individuals with polyps, 60.9 (SD=13.4) year vs. 56.9 (SD=13.7) year, respectively (p=0.001). Almost 82.8% of the lesions were precancerous with tubular type predominance (62.3%) followed by tubulo-villous (10.3%), villous (6.6%), and serrated (3.6%). Hyperplastic/inflammatory polyps comprised 17.2% of lesions.
Distal colon was more prone to develop polyps and cancer than proximal colon in our series. These findings provide a great infrastructure for next preventive programs and have implications for colorectal cancer screening at population-level.
PMCID: PMC4119671  PMID: 25093062
Colon Cancer; Colonoscopy; Colonic Polyps
3.  Gastroesophageal Reflux Disease and overall and Cause-specific Mortality: A Prospective Study of 50000 Individuals 
Only a few studies in Western countries have investigated the association between gastroesophageal reflux disease (GERD) and mortality at the general population level and they have shown mixed results. This study investigated the association between GERD symptoms and overall and cause-specific mortality in a large prospective population-based study in Golestan Province, Iran.
Baseline data on frequency, onset time, and patient-perceived severity of GERD symptoms were available for 50001 participants in the Golestan Cohort Study (GCS). We identified 3107 deaths (including 1146 circulatory and 470 cancer-related) with an average follow-up of 6.4 years and calculated hazard ratios (HR) and 95% confidence intervals (CI) adjusted for multiple potential confounders.
Severe daily symptoms (defined as symptoms interfering with daily work or causing nighttime awakenings on a daily bases, reported by 4.3% of participants) were associated with cancer mortality (HR 1.48, 95% CI: 1.04-2.05). This increase was too small to noticeably affect overall mortality. Mortality was not associated with onset time or frequency of GERD and was not increased with mild to moderate symptoms.
We have observed an association with GERD and increased cancer mortality in a small group of individuals that had severe symptoms. Most patients with mild to moderate GERD can be re-assured that their symptoms are not associated with increased mortality.
PMCID: PMC4034667  PMID: 24872865
Cardiovascular disease; Esophageal cancer; Gastroesophageal reflux disease; Mortality
4.  Determinants of Gastroesophageal Reflux Disease, Including Hookah Smoking and Opium Use– A Cross-Sectional Analysis of 50,000 Individuals 
PLoS ONE  2014;9(2):e89256.
Gastroesophageal reflux disease (GERD) is a common cause of discomfort and morbidity worldwide. However, information on determinants of GERD from large-scale studies in low- to medium-income countries is limited. We investigated the factors associated with different measures of GERD symptoms, including frequency, patient-perceived severity, and onset time.
We performed a cross-sectional analysis of the baseline data from a population-based cohort study of ∼50,000 individuals in in Golestan Province, Iran. GERD symptoms in this study included regurgitation and/or heartburn.
Approximately 20% of participants reported at least weekly symptoms. Daily symptoms were less commonly reported by men, those of Turkmen ethnicity, and nass chewers. On the other hand, age, body mass index, alcohol drinking, cigarette smoking, opium use, lower socioeconomic status, and lower physical activity were associated with daily symptoms. Most of these factors showed similar associations with severe symptoms. Women with higher BMI and waist to hip ratio were more likely to report frequent and severe GERD symptoms. Hookah smoking (OR 1.34, 95% CI 1.02–1.75) and opium use (OR 1.70, 95% CI 1.55–1.87) were associated with severe symptoms, whereas nass chewing had an inverse association (OR 0.87, 95% CI 0.76–0.99). After exclusion of cigarette smokers, hookah smoking was still positively associated and nass chewing was inversely associated with GERD symptoms (all frequencies combined).
GERD is common in this population. The associations of hookah and opium use and inverse association of nass use with GERD symptoms are reported for the first time. Further studies are required to investigate the nature of these associations. Other determinants of GERD were mostly comparable to those reported elsewhere.
PMCID: PMC3931722  PMID: 24586635
5.  Oral Nitrate Reductase Activity Is Not Associated with Development of Non-Alcoholic Fatty Liver Disease (NAFLD) and Non-Alcoholic Steatohepatitis (NASH): A Pilot Study 
NAFLD/NASH is a manifestation of metabolic syndrome and is associated with obesity/overweight. Not all obese/overweight individuals develop NASH. Gastro-esophageal reflux disease (GERD) is considered a gastrointestinal manifestation of the metabolic syndrome and is associated with obesity/overweight. Again not all obese/overweight individuals develop GERD. Recent data show association of dietary nitrate content and oral nitrate reductase activity (NRA) with GERD. Nitrates need to be converted to nitrite (done in human beings by nitrate reductase of oral bacteria exclusively) to be active in metabolic pathways.
To assess the relation between NASH/NAFLD and oral NRA.
Oral NRA was measured in individuals with NASH (compatible abdominal ultrasound and two elevated ALT/AST levels over six months) and was compared with that of those without NASH. Oral NRA was measured according to a previously reported protocol.
Eleven NASH patients and twelve controls were enrolled. Mean oral NRA activity were 2.82 vs. 3.51 μg nitrite-N formed per person per minute for cases and controls respectively (p=0.46).
According to our data, oral nitrite production is not different between individual swith and without NASH.
PMCID: PMC4005477  PMID: 24829701
NASH; NAFLD; GERD; Nitrate Reductase Activity; Oral Bacterial Flora
6.  Serum Cystatin-C Is Not Superior to Serum Creatinine in Predicting Glomerular Filtration Rate in Cirrhotic Patients 
Assessment of glomerular filtration rate (GFR) by common creatininebased methods is potentially inaccurate in patients with cirrhosis. Cirrhotic patients have several underlying conditions that contribute to falsely low serum creatinine concentrations, even in the presence of moderate to severe renal impairment. Therefore creatinine-based methods usually overestimate true GFR in these patients. Cystatin-C is a low molecular weight protein and an endogenous marker of GFR. We compared the accuracy of plasma cystatin-C and creatinine in assessing renal function in cirrhotic patients.
We serially enrolled cirrhotic patients with stable renal function admitted in our ward if they met the inclusion criteria and consented to participate. Child-Pugh (CP) score was calculated for all patients. GFR was calculated using serum creatinine, serum cystatin-C, and 99m TC-DTPA clearance with the last one serving as the gold standard. The area under curve (AUC) on receiveroperating characteristic curves (ROC) were used to assess the diagnostic accuracy of each calculated GFR with that measured by DTPA.
Fourty-eight patients were enrolled (32 males, 66.7%). Nine were in class-A, 20 in class-B and 19 in class-C of CP. Cystatin-C did not perform well in predicting the true GFR, while serum creatinine performed relatively accurately at GFR<80ml/min (AUC=0.764, p=0.004). Serum creatinine at a cutoff of 1.4 mg/dl was 20% sensitive & 92% specific and with at a cutoff of 0.9 mg/dl was 77%sensitive & 72% specific for diagnosis of impaired renal function. Cystatin-C could not predict GFR effectively even after stratification for CP score, gender, and BMI. Serum creatinine could predict GFR<65ml/min in females (ROC curve AUC=0.844, p=0.045). In those with BMI>20 kg/m2 a GFR<80 ml/min could also be predicted by serum creatinine (ROC curve AUC=0.739, p=0.034). It also could predict GFR<80ml/min in patients with CP class A & B (ROC curve AUC=0.795, p=0.01), but not in patients with CP class C.
Neither serum creatinine nor Cystatin-C are good predictors of GFR in cirrhotic patients, although serum creatinine seems to perform better in selected subgroups.
PMCID: PMC3990151  PMID: 24829693
Creatinine; Cystatin-C; Glomerular filtration rate (GFR); Cirrhosis
7.  Cyclosporine-A Versus Prednisolone for Induction of Remission in Auto-immune Hepatitis: Interim Analysis Report of a Randomized Controlled Trial 
Corticosteroids are used to induce remission in auto-immune hepatitis. They are not universally effective; therefore, alternative treatments are needed. In this study Cysclosporine-A has been compared with prednisolone as an alternative treatment in a randomized controlled trial. This paper is an interim analysis of an ongoing clinical trial.
Sixteen years and older consenting patients were enrolled. Group-A received prednisolone and group-B cyclosporine-A according to a preset protocol and followed at regular intervals for 48 weeks. Final assessment was done at week 48. Primary outcome was response rate as defined below. “Complete response” was defined as achieving AST and ALT in the normal range and absence of any clinical signs of deterioration, and partial response was defined as a decrease in AST and ALT by less than half of their original values but not to within normal limit. Non-responding ones at week eight were switched to the other arm.
Thirty-nine patients were enrolled (24 group-A, 9 male). Mean AST and ALT at baseline were higher in group-B, but other variables were comparable. At week 12, 34.8% and 64.3% of group-A and B had achieved AST and ALT in the normal range (less than 40 IU/L) respectively ( p=0.081). Corresponding figures at week 48 were 50.0% and 47.6% ( p=0.62 & 0.48 respectively). At week 12, 86.9% and 85.7% of patients had AST and ALT levels less than twice upper normal limit in groups-A and B respectively ( p=0.54 & 0.42).Corresponding figures at week 48 were 90.0% for both groups. There was one treatment failure in group-B which did not respond to prednisolone either. Serious adverse events (death and liver transplantation) occurred in group-A only. Serum creatinine did not change during the study period in either group.
According to our data, Cyclosporine-A is as effective as prednisolone for induction of remission in AIH. Adverse events and serious adverse events were more common with prednisolone.
PMCID: PMC3990153  PMID: 24829691
Auto-immune hepatitis; Cyclosporine-A; Prednisolone; Randomized controlled trial; Remission; Adverse effect
8.  Probiotic vs. Placebo in Irritable Bowel Syndrome:A Randomized Controlled Trial 
This study assesses the potential effect of Lactobacillus reuteri as a single strain probiotic preparation (Biogaia®) on irritable bowel syndrome (IBS).
Patients diagnosed with IBS who fulfilled Rome III criteria and consented to participate in this study were randomized to receive either the probiotic or an identical placebo once daily for four weeks. Patients used a questionnaire to record any symptoms and adverse reactions over a one-week run-in period and during the final two weeks of intervention. For each group, we calculated the differences between mean scores of the variables and compared the results between groups.
Frequency of defecation increased in the Biogaia® group and decreased in the placebo group meaningfully. But There were no significant difference in the two groups in other terms of bloating, sense of urgency for defecation, abdominal pain, stool shape, quality of defecation, sense of incomplete evacuation, and treatment satisfaction.
The frequency of defecation increased in the Biogaia® group and decreased in the placebo group, however this study did not classify patients according to diarrhea or constipated subgroups, the efficacy of this drug is not clear. Hence Lactobacillus reuteri was not better than placebo in controlling IBS symptoms in this study. However, considering the significant placebo effect in IBS patients, it may be necessary to conduct studies with larger numbers of participants to better assess the possible beneficial effects of Biogaia.
PMCID: PMC3990144  PMID: 24829677
Irritable Bowel Syndrome; Probiotic; Lactobacillus Reuteri
9.  Treatment of Gastro-Esophageal Reflux Disease May Improve Surgical Outcomes for Chronic Otitis Media 
This study has been designed to investigate the clinical association between gastro esophageal reflux disease (GERD) and chronic otitis media (COM) in adults and also the role of GERD treatment on the outcome of COM surgery.
In a randomized clinical trial, 58 patients with COM who were candidates for surgery were evaluated for GERD and divided in two groups; GERD positive (case) and GERD negative (control) patients. The GERD positive patients were randomized to either receiving medical treatment for GERD or not prior to surgery. The surgical outcomes were assessed at 3 and 6 months after COM surgery in the three groups.
Fifty-eight (26 males) patients were enrolled. Forty-two (72.4%) of these had GERD according to a validated questionnaire. Three months after surgery auditory recovery in GERD negative patients was significantly higher [16(100%)] than those suffering from GERD [28 out of 42 (66.7%)], p=0.008. The figures remained similar at six months follow up as well (100 % vs. 72.5% in GERD negative and positive patients respectively, p=0.002).In the GERD-positive group, 8 of 18 (44.4%) patients who did not receive GERD treatment before tympanomastoidectomy recovered after three months whereas, while 20 of 24 (83.3%) patients who received GERD treatment recovered during this time (p<0.001). At six months 44.4% of non-treated GERD patients had auditory recovery as compared to 95.5 % of those treated for GERD (p<0.01).
Our data show that the effect of GERD on the outcome of COM surgery may be considerable. On the other hand, treating COM patients for GERD medically for two months before tympanoplasty improves the surgical outcomes. Therefore, we suggest that COM patients be evaluated for GERD before undergoing tympanoplasty and if GERD is present, they be treated medically for a couple of months before undergoing surgery.
PMCID: PMC3990123  PMID: 24829661
Tympanomastoidectomy; Treatment; GERD; Chronic otitis media; Outcome
10.  Diagnostic Accuracy of Age and Alarm Symptoms for Upper GI Malignancy in Patients with Dyspepsia in a GI Clinic: A 7-Year Cross-Sectional Study 
PLoS ONE  2012;7(6):e39173.
We investigated whether using demographic characteristics and alarm symptoms can accurately predict cancer in patients with dyspepsia in Iran, where upper GI cancers and H. pylori infection are common.
All consecutive patients referred to a tertiary gastroenterology clinic in Tehran, Iran, from 2002 to 2009 were invited to participate in this study. Each patient completed a standard questionnaire and underwent upper gastrointestinal endoscopy. Alarm symptoms included in the questionnaire were weight loss, dysphagia, GI bleeding, and persistent vomiting. We used logistic regression models to estimate the diagnostic value of each variable in combination with other ones, and to develop a risk-prediction model.
A total of 2,847 patients with dyspepsia participated in this study, of whom 87 (3.1%) had upper GI malignancy. Patients reporting at least one of the alarm symptoms constituted 66.7% of cancer patients compared to 38.9% in patients without cancer (p<0.001). Esophageal or gastric cancers in patients with dyspepsia was associated with older age, being male, and symptoms of weight loss and vomiting. Each single predictor had low sensitivity and specificity. Using a combination of age, alarm symptoms, and smoking, we built a risk-prediction model that distinguished between high-risk and low-risk individuals with an area under the ROC curve of 0.85 and acceptable calibration.
None of the predictors demonstrated high diagnostic accuracy. While our risk-prediction model had reasonable accuracy, some cancer cases would have remained undiagnosed. Therefore, where available, low cost endoscopy may be preferable for dyspeptic older patient or those with history of weight loss.
PMCID: PMC3374763  PMID: 22720064
11.  Inflammatory Bowel Disease 
Inflammatory bowel disease (IBD) is the term used for a group of diseases with yet unknown etiology, prevalence of which is increasing almost everywhere in the world. The disease was almost non-existent four decades ago in the east, including the middle-east, while now a days it is seen more and more. In addition to the increasing prevalence, our knowledge about its pathogenesis, clinical course, diagnosis, and treatment has changed dramatically over the past couple of decades. This has changed our concept of this group of diseases, their diagnosis, treatment, and treatment goals. Considering the vast literature on the subject, it is timely to review major topics in IBD with a look on the regional progress and knowledge as well. This essay is aimed to cover this task.
PMCID: PMC4017691  PMID: 24829639
Inflammatory bowel disease; Ulcerative colitis; Crohn’s disease; Iran
12.  Clinical Features and Long Term Outcome of 102 Treated Autoimmune Hepatitis Patients 
Hepatitis Monthly  2012;12(2):92-99.
There is limited data on the natural history of autoimmune hepatitis (AIH) and on the long-term follow-up of AIH patients who have been referred for regular medical attention.
We evaluated the clinical presentation and natural history of AIH in a large cohort of type I AIH patients from Iran.
Patients and Methods
Between 1997 and 2008, 102 patients were enrolled in the study. Patients were diagnosed using the International Autoimmune Hepatitis Group criteria and were followed up for an average of 60 months. Clinical and biochemical data were gathered from all the patients at both the beginning and the end of the follow-up period. Liver biopsy was performed in all patients before treatment, and the biopsies were performed in 28 patients after treatment.
Biochemical remission was achieved by 80 (79.4%) patients. Of these, 53 (66.5%) showed near-normal liver histology or liver function test results and sonogram. The remaining 27 (33.5%) patients also achieved clinical and biochemical remission, but developed compensated cirrhosis. After a period of remission, 24 patients (32.5%) relapsed. Among the 22 (21.6%) patients who showed ultimate treatment failure, 6 underwent orthotopic liver transplantation and 3 died of liver failure while awaiting a transplant. Sixteen (72.7%) of the 22 patients who did not respond to therapy were non-compliant with medications and had irregular follow-up. The overall 10-year survival rate in the cohort was 96%.
Long-term survival in AIH patients is very good. Prompt diagnosis and appropriate first-line and salvage therapy that includes close follow-up will make liver transplantation a rare necessity in the treatment of this disease.
PMCID: PMC3321327  PMID: 22509185
Hepatitis; Autoimmune; Natural History; Liver Cirrhosis; Hepatitis, Chronic; Iran
13.  Eosinophilic Gastroenteritis: A Case Series from Iran 
Eosinophilic gastroenteritis (EG) is a rare inflammatory disorder of the gastrointestinal (GI) tract. There have been several case series of patients with EG from the western world and East Asia. However, there has not been a report of patients with EG from the Middle East region. The aim of this study is to describe clinical characteristics and treatment response in a series of EG patients from Iran.
We retrospectively reviewed charts with a diagnosis of EG from 1997 to 2010 at Shariati Hospital and the private clinics of the authors. Clinical characteristics of the patients were evaluated, and the treatment response and relapse rate were assessed.
Twenty-two patients (9 male) with EG were identified. Mean age of the patients was 45.1±15.5 (range: 27-75) years. Median duration between symptom onset and diagnosis was 12 (range 1- 48) months. Twenty (90%) patients had mucosal involvement, one (5%) had muscular involvement and one (5%) had subserosal involvement.
Patients were followed for a median duration of 36.5 (range 4-123) months. Two patients had spontaneous remission with supportive care. The remaining 20 patients responded well to oral corticosteroid treatments. The relapse rate was 33%. Episodes of relapse were successfully controlled with a repeat course of corticosteroids. Two patients with several relapses required maintenance treatment with azathioprine.
The clinical characteristics and treatment responses of EG patients from Iran are similar to reports from other parts of the world. Patients need to undergo close follow up after treatment to detect early signs of relapse.
PMCID: PMC4154914  PMID: 25197542
Eosinophilic gastroenteritis; Esophagus; Small intestine; Eosinophils
14.  Socio-economic status and oesophageal cancer: results from a population-based case–control study in a high-risk area 
Background Cancer registries in the 1970s showed that parts of Golestan Province in Iran had the highest rate of oesophageal squamous cell carcinoma (OSCC) in the world. More recent studies have shown that while rates are still high, they are approximately half of what they were before, which might be attributable to improved socio-economic status (SES) and living conditions in this area. We examined a wide range of SES indicators to investigate the association between different SES components and risk of OSCC in the region.
Methods Data were obtained from a population-based case–control study conducted between 2003 and 2007 with 300 histologically proven OSCC cases and 571 matched neighbourhood controls. We used conditional logistic regression to compare cases and controls for individual SES indicators, for a composite wealth score constructed using multiple correspondence analysis, and for factors obtained from factors analysis.
Results We found that various dimensions of SES, such as education, wealth and being married were all inversely related to OSCC. The strongest inverse association was found with education. Compared with no education, the adjusted odds ratios (95% confidence intervals) for primary education and high school or beyond were 0.52 (0.27–0.98) and 0.20 (0.06–0.65), respectively.
Conclusions The strong association of SES with OSCC after adjustment for known risk factors implies the presence of yet unidentified risk factors that are correlated with our SES measures; identification of these factors could be the target of future studies. Our results also emphasize the importance of using multiple SES measures in epidemiological studies.
PMCID: PMC2720396  PMID: 19416955
Oesophageal cancer; socio-economic status; case–control; epidemiology; Iran; factor analysis; correspondence analysis
15.  Overlapping gastroesophageal reflux disease and irritable bowel syndrome: Increased dysfunctional symptoms 
AIM: To investigate the association of gastroesophageal reflux disease (GERD) and irritable bowel syndrome (IBS) in Iranian patients and examine the prevalence of functional symptoms of the gastrointestinal tract in patients presenting with either IBS, GERD or both.
METHODS: Six thousand four hundred and seventy six patients presented to the Gastro-intestinal (GI) clinic with symptoms of functional dysfunction of GI tract, 1419 patients (62.0% women, 38.0% men; mean age: 37.4 ± 11.5 years) met Rome II or Rome III criteria (depending on the year of diagnosis) for IBS. 2658 patients were diagnosed with GERD based on clinical presentation and endoscopic findings. We assessed other functional symptoms (epigastric pain, nausea, vomiting, belching, constipation and diarrhea) in patients suffering from GERD, IBS or both.
RESULTS: Among IBS subjects, 63.6% (69.0% women, 31.0% men; mean age: 36.4 ± 10.3 years) also had GERD, whereas 34.7% of the non-IBS patients had GERD [odds ratio (OR) = 3.2, 95% confidence interval (CI): 2.9-3.7, P < 0.0001]. Among patients with GERD, 33.9% of subjects met Rome criteria compared to 13.5% of non-GERD patients (OR = 3.6, 95% CI: 3.1-4.3, P < 0.0001). Prevalence of all functional symptoms was higher in overlapping GERD and IBS subjects, when compared with their prevalence in the IBS subjects without GERD or GERD only subjects (P < 0.05).
CONCLUSION: This finding shows that in overlapping GERD and IBS, other functional abnormalities of the GI tract are also highly prevalent, suggesting a common underlying dysfunction.
PMCID: PMC2839176  PMID: 20222167
Gastro-esophageal reflux disease; Irritable bowel syndrome; Helicobacter pylori; Gastro-intestinal dysfunction; Endoscopy
16.  Capture-recapture method for assessing publication bias 
Publication bias is an important factor that may result in selection bias and lead to overestimation of the intervention effect. In this study, the focus was on using capture-recapture method as a statistical procedure which may possibly be a practical means for measuring the amount of publication bias.
A systematic review was conducted to estimate the duration of protection provided by hepatitis B vaccine by measuring the anamnestic immune response to booster doses of vaccine and retrieved studies from three separate sources of electronic databases, reference lists of the studies, and conference databases as well as contact with experts and manufacturers. Capture-recapture and some conventional methods such as funnel plot, Begg test, Egger test, and trim and fill method were employed for assessing publication bias.
Based on capture-recapture method, completeness of the overall search results was 87.2% [95% CI: 84.6% to 89.0%] and log-linear model suggested 5 [95% CI: 4.2 to 6.2] missing studies. The funnel plot was asymmetric while Begg and Egger tests results were statistically insignificant and trill and fill approach made no change in pooled effect.
Capture-recapture method may be a useful practical approach for estimating the number of missing studies which are not usually detected by search strategy. As a result, use of capture-recapture method as an alternative approach could be suggested for estimating the extent of publication bias based on overlapping information rather than mirror image of extreme values on funnel plot.
PMCID: PMC3082794  PMID: 21526067
Meta-Analysis; Publication Bias; Review Literature; Capture-Recapture
17.  Crohn's Disease and Early Exposure to Domestic Refrigeration 
PLoS ONE  2009;4(1):e4288.
Environmental risk factors playing a causative role in Crohn's Disease (CD) remain largely unknown. Recently, it has been suggested that refrigerated food could be involved in disease development. We thus conducted a pilot case control study to explore the association of CD with the exposure to domestic refrigeration in childhood.
Methodology/Principal Findings
Using a standard questionnaire we interviewed 199 CD cases and 207 age-matched patients with irritable bowel syndrome (IBS) as controls. Cases and controls were followed by the same gastroenterologists of tertiary referral clinics in Tehran, Iran. The questionnaire focused on the date of the first acquisition of home refrigerator and freezer. Data were analysed by a multivariate logistic model. The current age was in average 34 years in CD cases and the percentage of females in the case and control groups were respectively 48.3% and 63.7%. Patients were exposed earlier than controls to the refrigerator (X2 = 9.9, df = 3, P = 0.04) and refrigerator exposure at birth was found to be a risk factor for CD (OR = 2.08 (95% CI: 1.01–4.29), P = 0.05). Comparable results were obtained looking for the exposure to freezer at home. Finally, among the other recorded items reflecting the hygiene and comfort at home, we also found personal television, car and washing machine associated with CD.
This study supports the opinion that CD is associated with exposure to domestic refrigeration, among other household factors, during childhood.
PMCID: PMC2629547  PMID: 19177167
18.  Prospective Acid Reflux Study of Iran (PARSI): Methodology and study design 
BMC Gastroenterology  2007;7:42.
Gastroesophageal reflux disease is a common and chronic disorder but long term, prospective studies of the fate of patients seeking medical advice are scarce. This is especially prominent when looking at non-erosive reflux disease (NERD) patients.
We designed a prospective cohort to assess the long term outcome of GERD patients referring to gastroenterologists. Consecutive consenting patients, 15 years of age and older, presenting with symptoms suggestive of GERD referring to our outpatient clinics undergo a 30 minute interview. Upper gastrointestinal endoscopy is performed for them with protocol biopsies and blood samples are drawn. Patients are then treated according to a set protocol and followed regularly either in person or by telephone for at least 10 years.
Our data show that such a study is feasible and follow-ups, which are the main concern, can be done in a fairly reliable way to collect data. The results of this study will help to clarify the course of various subgroups of GERD patients after coming to medical attention and their response to treatment considering different variables. In addition, the basic symptoms and biological database will fuel further molecular epidemiologic studies.
PMCID: PMC2212633  PMID: 18028533
19.  Opium use and mortality in Golestan Cohort Study: prospective cohort study of 50 000 adults in Iran 
Objectives To investigate the association between opium use and subsequent risk of death.
Design Prospective cohort study.
Setting The Golestan Cohort Study in north-eastern Iran collected detailed validated data on opium use and other exposures at baseline. Participants were enrolled between January 2004 and June 2008 and were followed to May 2011, with a follow-up success rate of over 99%.
Participants 50 045 participants aged 40-75 at baseline.
Main outcomes Mortality, all cause and major subcategories.
Results 17% (n=8487) of the participants reported opium use, with a mean duration of 12.7 years. During the follow-up period 2145 deaths were reported. The adjusted hazard ratio for all cause mortality associated with ever use of opium was 1.86 (95% confidence interval 1.68 to 2.06). Opium consumption was significantly associated with increased risks of deaths from several causes including circulatory diseases (hazard ratio 1.81) and cancer (1.61). The strongest associations were seen with deaths from asthma, tuberculosis, and chronic obstructive pulmonary disease (11.0, 6.22, and 5.44, respectively). After exclusion of people who self prescribed opium after the onset of major chronic illnesses, the associations remained strong with a dose-response relation.
Conclusion Opium users have an increased risk of death from multiple causes compared with non-users. Increased risks were also seen in people who used low amounts of opium for a long period and those who had no major illness before use.
PMCID: PMC3328545  PMID: 22511302

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