Mohammad Reza Ostovaneh

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

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.

SEROPREVALENCE OF HEPATITIS B SURFACE ANTIGEN AND ANTI HEPATITIS C ANTIBODY IN ZAHEDAN CITY, IRAN: A POPULATION-BASED STUDY

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.

Comparing omeprazole with fluoxetine for treatment of patients with heartburn and normal endoscopy who failed once daily proton pump inhibitors: Double-blind placebo-controlled trial

Patients with heartburn but without esophageal erosion respond less well to proton pump inhibitors (PPIs). There is a growing body of evidence implicating the role of psychological comorbidities in producing reflux symptoms. Pain modulators improve symptoms in patients with other functional gastrointestinal disorders. We aimed to compare the efficacy of fluoxetine with omeprazole and placebo to achieve symptomatic relief in patients with heartburn and normal endoscopy who failed once daily PPIs.

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

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.

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

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. Liver Transpl 20:1462‐1467, 2014.

A novel approach for selecting combination clinical markers of pathology applied to a large retrospective cohort of surgically resected pancreatic cysts

Objective: Our objective was to develop an approach for selecting combinatorial markers of pathology from diverse clinical data types. We demonstrate this approach on the problem of pancreatic cyst classification. Materials and Methods: We analyzed 1026 patients with surgically resected pancreatic cysts, comprising 584 intraductal papillary mucinous neoplasms, 332 serous cystadenomas, 78 mucinous cystic neoplasms, and 42 solid-pseudopapillary neoplasms. To derive optimal markers for cyst classification from the preoperative clinical and radiological data, we developed a statistical approach for combining any number of categorical, dichotomous, or continuous-valued clinical parameters into individual predictors of pathology. The approach is unbiased and statistically rigorous. Millions of feature combinations were tested using 10-fold cross-validation, and the most informative features were validated in an independent cohort of 130 patients with surgically resected pancreatic cysts. Results: We identified combinatorial clinical markers that classified serous cystadenomas with 95% sensitivity and 83% specificity; solid-pseudopapillary neoplasms with 89% sensitivity and 86% specificity; mucinous cystic neoplasms with 91% sensitivity and 83% specificity; and intraductal papillary mucinous neoplasms with 94% sensitivity and 90% specificity. No individual features were as accurate as the combination markers. We further validated these combinatorial markers on an independent cohort of 130 pancreatic cysts, and achieved high and well-balanced accuracies. Overall sensitivity and specificity for identifying patients requiring surgical resection was 84% and 81%, respectively. Conclusions: Our approach identified combinatorial markers for pancreatic cyst classification that had improved performance relative to the individual features they comprise. In principle, this approach can be applied to any clinical dataset comprising dichotomous, categorical, and continuous-valued parameters.

Cohort Profile: Golestan Hepatitis B Cohort Study-A Prospective Long Term Study in Northern Iran

There are overwhelming reports and descriptions about celiac associated disorders. Although there is a clear genetic association between celiac disease (CD) and some gastrointestinal disorders, there are controversial reports claiming an association between CD and Helicobacter pylori (H. pylori) infection. Different studies indicated the possible association between lymphocytic gastritis and both CD and H. pylori infection, although this evidence is not consistently accepted. Also it was shown that an increase in intraepithelial lymphocytes count is associated with both H. pylori infection and celiac disease. Therefore the following questions may raise: how far is this infection actually related to CD?, which are the underlying patho-mechanisms for these associations? what are the clinical implications? what is the management? and what would be the role of gluten free diet in treating these conditions? PubMed (PubMed Central), Ovid, ISI of web knowledge, and Google scholar were searched for full text articles published between 1985 and 2015. The associated keywords were used, and papers described particularly the impact of pathological and clinical correlation between CD and H. pylori infection were identified. In this review we tried to answer the above questions and discussed some of the recent developments in the pathological and clinical aspects of CD and H. pylori infection.

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

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.

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

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.

Immune responses to hepatitis B immunization 10-18 years after primary vaccination: a population-based cohort study.

We evaluated the immune response to neonatal HBV immunization in children of infected parents 10–18 years after primary vaccination. Healthy individuals immunized with an infantile course of three doses of HBV vaccine were tested for persistence of anti‐HB surface antibody (HBsAb). Those with an HBsAb level of <10 IU/mL received a booster dose of the vaccine with subsequent doses to those without protective titres. HBsAb concentrations were determined 4 weeks after each dose of the booster vaccine. The data were analysed separately for three age groups: 10–11, 12–14 and 15–18 years old. A total of 541 healthy individuals were studied. The highest seroprotection rate of 48% was observed in the youngest vaccinees (10–11 years old). This declined to 26.5% in the oldest (15–18 years old) group (P = 0.008). The youngest vaccinees showed the highest rate of anamnestic immune responses (96%). However, 25% of oldest individuals failed to mount an anamnestic immune response in challenge with a booster dose of the vaccine (P = 0.005), suggesting waning immunity with increasing age. Age (OR: 0.80; P = 0.01) and prebooster HBsAb levels (OR: 0.37; P = 0.01) identified responders to first booster doses of the vaccine by logistic regression analysis. The majority of high‐risk vaccinees showed anamnestic immune response 10–11 years after primary immunization. However, we found a significant proportion (25%) of older individuals with no anamnetic response, which suggests a waning of immune memory. Detailed long‐term follow‐up studies are necessary to determine the risk of natural infection among these individuals before a booster schedule can be recommended.