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1.  The risk of osteoporotic fractures and its associating risk factors according to the FRAX model in the Iranian patients: a follow-up cohort 
The present study is designed to assess the incidence rate of osteoporotic fracture and its risk factors, particularly those used to predict the 10-year risk of osteoporotic fracture in FRAX based on the data gathered through a follow up cohort initiated in 2000.
The present retrospective cohort was conducted on men and women from 40 to 90 years of age enrolled in the IROSTEOPs study. A phone survey was conducted during 2013 and beginning of 2014 to assess the fractures (traumatic/osteoporotic) occurring at the time of inclusion until the date of the telephone survey, its type and mechanism, and the patient’s age at the time of accident. Survival analysis using Kaplan-Meier product-limit method was performed with the time of fracture as the study outcome.
Final study population consisted of 1233 individuals, translated in to 9133 person years. The incidence rate of osteoporotic fracture was reported to be 359.1 cases in every 10,000 person years. The 10-year Kaplan-Meier estimate of any kind of major osteoporotic fractures for all the subcohort population was 10.75%. Osteoporosis (HR = 0.75), Discordance between femoral neck and spine (HR = 1.45), Diabetes (HR = 1.81), IBD (HR = 1.84), immobility more than 90 days (HR = 2.19), and personal history of fracture (HR = 7.75) had a considerable effect on the 10-year risk of major osteoporotic fractures.
Adding new clinical risk factors to FRAX® may help improve fracture prediction in the Iranian population.
PMCID: PMC4209052  PMID: 25349839
Fracture; FRAX; Major osteoporotic fracture
2.  Association between vitamin D receptor gene polymorphisms (Fok1 and Bsm1) and osteoporosis: a systematic review 
Osteoporosis is a health concern characterized by reduced bone mineral density (BMD) and increased risk of fragility fractures. Many studies have investigated the association between genetic variants and osteoporosis. Polymorphism and allelic variations in the vitamin D receptor gene (VDR) have been found to be associated with bone mineral density. However, many studies have not been able to find this association. Literature review was conducted in several databases, including MEDLINE/Pubmed, Scopus, EMBASE, Ebsco, Science Citation Index Expanded, Ovid, Google Scholar, Iran Medex, Magiran and Scientific Information Database (SID) for papers published between 2000 and 2013 describing the association between Fok1 and Bsm1 polymorphisms of the VDR gene and osteoporosis risk. The majority of the revealed papers were conducted on postmenopausal women. Also, more than 50% studies reported significant relation between Fok1, Bsm1 and osteoporosis. Larger and more rigorous analytical studies with consideration of gene-gene and gene-environment interactions are needed to further dissect the mechanisms by which VDR polymorphisms influence osteoporosis.
PMCID: PMC4215021  PMID: 25364703
Osteoporosis; Vitamin D receptor gene; Bone density; Polymorphism; Fok1; Bsm1
3.  Aberrant DNA methylation patterns in diabetic nephropathy 
The aim of this study was to evaluate whether global levels of DNA methylation status were associated with albuminuria and progression of diabetic nephropathy in a case-control study of 123 patients with type 2 diabetes- 53 patients with albuminuria and 70 patients without albuminuria.
The 5-methyl cytosine content was assessed by reverse phase high pressure liquid chromatography (RP-HPLC) of peripheral blood mononuclear cells to determine individual global DNA methylation status in two groups.
Global DNA methylation levels were significantly higher in patients with albuminuria compared with those in normal range of albuminuria (p = 0.01). There were significant differences in global levels of DNA methylation in relation to albuminuria (p = 0.028) and an interesting pattern of increasing global levels of DNA methylation in terms of albuminuria severity.
In patients with micro- and macro albuminuria, we found no significant correlations between global DNA methylation levels and duration of diabetes (p > 0.05). In both sub groups, there were not significant differences between global DNA methylation levels with good and poor glycaemic control (p > 0.05). In addition, in patients with albuminuria, no differences in DNA methylation levels were observed between patients with and without other risk factors including age, gender, hypertension, dyslipidaemia and obesity.
These data may be helpful in further studies to develop novel biomarkers and new strategies for clinical care of patients at risk of diabetic nephropathy.
PMCID: PMC4099150  PMID: 25028646
Type 2 diabetes; Diabetic nephropathy; Albuminuria; Global DNA methylation; Epigenetic
4.  Predictive factors of diabetic complications: a possible link between family history of diabetes and diabetic retinopathy 
The aim of this study was assessment of predictive factors of diabetic retinopathy.
A cross-sectional study was designed by recruiting 1228 type 2 diabetic patients from a diabetes referral clinic over a six-month period (from July to December, 2012). Diabetes risk factors, complications, laboratory results have been recorded.
Of the 1228 diabetic patients (54% women, mean age 58.48 ± 9.94 years), prevalence of diabetes retinopathy was 26.6%. There were significant associations between retinopathy and family history of diabetes (p = 0.04), hypertension (p = 0.0001), diabetic duration (p = 0.0001), poor glycemic control (p = 0.0001) and age of onset of diabetes (p = 0.0001). However, no significant associations were found between retinopathy with dyslipidemia and obesity. In logistic regression model, poor glycemic control (p = 0.014), hypertension (p = 0.0001), duration of diabetes (p = 0.0001) and family history of diabetes (p = 0.012) independently predicted retinopathy after adjustment for age and sex.
Diabetic complications are resulting from an interaction from genes and environmental factors. A family history of diabetes is pointing toward a possible genetic and epigenetic basis for diabetic retinopathy. Our findings suggest the role of epigenetic modifications and metabolic memory in diabetic retinopathy in subjects with family history of diabetes.
PMCID: PMC4031909  PMID: 24860795
Diabetic retinopathy; Epigenetic; Family history of diabetes
5.  Knowledge translation in Iranian universities: need for serious interventions 
The aim of this study was to assess the status of knowledge translation (KT) in Iranian medical science universities in order to assess the strengths and weaknesses of the most important organizations responsible for producing knowledge in the country.
The KT activities were assessed qualitatively and quantitatively in nine universities using the Self-Assessment Tool for Research Institutes.
The strengths and weaknesses of universities were determined using seven main themes: priority setting; research quality and timeliness; researchers’ KT capacities; interaction with research users; the facilities and prerequisites of KT; the processes and regulations supporting KT; and promoting and evaluating the use of evidence.
The quantitative and qualitative results showed that the Iranian universities did not have an appropriate context for KT. There were significant shortcomings in supportive regulations, facilities for KT activities, and the level of interaction between the researchers and research users.
The shortcomings in KT were mostly in the area of stewardship and policymaking (macro level), followed by planning and implementation at the universities. In order to strengthen KT in Iran, it should occupy a prominent and focused role in the strategies of the country’s health research system.
PMCID: PMC3835863  PMID: 24225146
6.  Goiter Frequency Is More Strongly Associated with Gastric Adenocarcinoma than Urine Iodine Level 
Journal of Gastric Cancer  2013;13(2):106-110.
We designed our study to evaluate the hypothesis that gastric cancer is correlated with iodine deficiency or thyroid dysfunction.
Materials and Methods
We investigated the total body iodine reserve, thyroid function status and autoimmune disorder in 40 recently diagnosed gastric adenocarcinoma cases versus 80 healthy controls. The participants came from a region with high gastric cancer rate but sufficient iodine supply due to salt iodination. The investigation included urine iodine level, thyroid gland clinical and ultrasonographic examination, and thyroid function tests.
Goiter was detected more frequently in the case group (P=0.001); such a finding, however, was not true for lower than normal urine iodine levels. The free T3 mean level was significantly lower in the case group compared to the control group (P=0.005).
The higher prevalence of goiter rather than low levels of urinary iodine in gastric adenocarcinoma cases suggests that goiter, perhaps due to protracted but currently adjusted iodine deficiency, is more likely to be associated with gastric adenocarcinoma compared to the existing iodine deficiency itself.
PMCID: PMC3705130  PMID: 23844325
Stomach neoplasms; Goiter; Iodine; Thyroid function tests; Autoimmune diseases
7.  Estimating the avoidable burden of certain modifiable risk factors in osteoporotic hip fracture using Generalized Impact Fraction (GIF) model in Iran 
The number of hip fractures, the most common complication of osteoporosis, has increased rapidly over the past decades. The goal of this study is to estimate the avoidable burden of certain modifiable risk factor of the condition using the Generalized Impact Fraction (GIF) model, which has been suggested and used by epidemiologists to overcome the drawbacks associated with the use of Attributable Fraction index. In addition to preventing a risk factor or the avoidable fraction of burden, this index can also calculate the change in the burden, when a risk factor is altered.
International databases were searched through PubMed, CINAHLD, Embase using OVID and Google scholar. National resources were searched through IranDoc, IranMedex, SID and Journal sites. Other resources include abstract books and articles sent to the IOF congress. The following search strategy was used: (“Osteoporotic fracture” OR “Fragility Hip fracture” OR “Calcium” OR “vitamin D” OR “BMI” OR “lean body weight” OR “Physical activity” OR “exercise” OR “Smoke”) AND (“prevalence” OR “incidence” OR “relative risk”) and limited to “humans.”
With regards to different scenarios already explained in modifying the studied risk factors, the greatest impact in reducing the prevalence of risk factors on osteoporotic hip fractures, was seen in low serum vitamin D levels, low physical activity and low intake of calcium and vitamin D, respectively. According to the fact that interventions for low serum vitamin D and low intake of calcium and vitamin D, are related to each other, it can be concluded that implementing interventions to change these two risk factors, in the easy, moderate and difficult scenarios, would result in approximately a 5%, 11% and 17% decrease in the burden of osteoporotic hip fractures, respectively. The addition of interventions addressing low physical activity in the easy, moderate and difficult scenarios, an 8%, 21% and 35% reduction in the burden of osteoporotic hip fractures would be reported, respectively.
Improving serum vitamin D levels, recommending the consumption of calcium and vitamin D supplementations and advocating physical activity are the most effective interventions to reduce the risk of osteoporotic hip fractures.
PMCID: PMC3598997  PMID: 23497489
Osteoporotic fracture; Fragility hip fracture; Calcium; Vitamin D; BMI; Physical activity; Smoke; Prevalence; Incidence
8.  Modifiable Risk of Breast Cancer in Northeast Iran: Hope for the Future. A Case-Control Study 
Breast Care  2011;6(6):453-456.
Breast cancer is the most common cancer in women. Its prevalence is increasing annually by 2%. The determination of modifiable risk factors has been the subject of various studies. The aim of this study was to determine risk factors of breast cancer in women in Golestan Province.
Patients and Methods
This case-control study was conducted among women with breast cancer recorded in the cancer registry system between 2004 and 2006 (n = 134), and their age-matched healthy neighbors (n = 133). Data were statistically analyzed.
Age at marriage, menarche and pregnancy, breast feeding, positive family history, marital status, and educational level were not significantly correlated with risk of breast cancer, but age at menopause (< 46.6 years) was significantly correlated (95% confidence interval 1.15–7.37; p = 0.021). Live births, still births, and infant deaths were not significantly different between the 2 groups. For other variables, such as smoking history, no odds ratio was calculated.
Results show that there is no significant correlation between variables and risk of breast cancer in our population, except for age at menopause. A large cohort study is recommended.
PMCID: PMC3290010  PMID: 22419899
Breast cancer; Risk factors; Golestan; Case-control study
9.  The Role of IL-6 for Predicting Neonatal Sepsis: A Systematic Review and Meta-Analysis 
Iranian Journal of Pediatrics  2011;21(4):411-417.
Neonatal sepsis (NS) is a common and life-threatening disorder in infants. Previous studies showed that interleukin-6 (IL-6) may be a valid non-invasive and rapid method for diagnosis of NS. We conducted this review to assess the validity of IL-6 for predicting NS.
This was a systematic review with meta-analysis. Embase, Medline and Web of Science databases were searched between January 1990 and December 2009. The search terms used were “cytokine”, “neonate”, “sepsis” and “interleukin-6". We used standard methods recommended for meta analyses of diagnostic test evaluations. The analysis was based on a summary ROC (SROC) curve. Meta-regression analysis was used to assess the effects of some confounding factors on the results of meta-analysis. Potential presence of publication bias was tested using funnel plots and the Egger test.
Meta-analysis was performed on 13 publications including 353 infants with sepsis and 691 control infants. The pooled sensitivity and specificity of IL-6 was 0.79 and 0.84, respectively. The maximum joint sensitivity and specificity (i.e., the Q value) in SROC curve was 0.82 and the area under curve (AUC) was 0.89 (95% CI: 0.84-0.94). Meta-regression analysis showed that the diagnostic accuracy of IL-6 was not affected by confounding variables. The evaluation of publication bias showed that the Egger test was not significant (P=0.07).
IL-6 seems to be a valid marker for predicting NS. It may be considered for early diagnosis of sepsis in neonatal care units.
PMCID: PMC3446138  PMID: 23056824
Interlukin-6; Cytokines; Sepsis; Neonate; Meta-analysis
10.  Effects of Vitamin E and Zinc Supplementation on Antioxidants in Beta thalassemia major Patients 
Iranian Journal of Pediatrics  2011;21(1):8-14.
In beta thalassemic patients, tissue damage occurs due to oxidative stress and it happens because of the accumulation of iron in the body. This study was conducted to determine the effect of zinc and vitamin E supplementation on antioxidant status in beta-thalassemic major patients.
This double blind randomized clinical trial was carried out on 120 beta thalassemic patients older than 18 years. Patients were randomly categorized in four groups. Zinc (50mg/day) and vitamin E (400mg/day) supplements were administered for former and latter group, respectively. In the third group both supplements were administered in similar doses. The fourth (control) group received no supplement. The effect of supplementations on serum zinc and vitamin E, superoxide dismutase (SOD), glutathione peroxidase (GPX), total antioxidant capacity (TAC) and body mass index (BMI) were measured at the beginning and the end of the study.
Serum zinc levels in group 1 and 3 were significantly increased (P<0.007 and P<0.005, respectively). Serum vitamin E levels in group 2 and 3 were also increased significantly (P<0.001). Mean GPX activity in group1, 2 and 3 decreased significantly (P<0.015, P<0.032 and P<0.029, respectively). Mean SOD activity and TAC did not show significant change after supplementation. BMI had significant increase in all treated groups (P<0.001).
Our results suggest that beta thalassemic patients have enhanced oxidative stress and administration of selective antioxidants may preclude oxidative damage.
PMCID: PMC3446117  PMID: 23056757
Vitamin E; Zinc; Glutathione Peroxidase; Superoxide Dismutase; Body Mass Index; Antioxidants
11.  Incidence of Childhood Cancers in Golestan Province of Iran 
Iranian Journal of Pediatrics  2010;20(3):335-342.
This paper presents the incidence rates of childhood cancers using the data obtained from Golestan population based cancer registry (GPCR) between 2004 and 2006.
GPCR registers only primary cancers based on standard protocols of the international association of cancer registries (IACR). We collect data on newly diagnosed (incident) cancer cases from all public and private diagnostic and therapeutic centers of the whole province. CanReg-4 software was used for data entry and analysis.
Totally 5076 cancer cases (all ages) were diagnosed in GPCR between 2004 and 2006. Of these, 139 (2.74 %) were children (aged 0–14 years) with mean (±SD) age of 8.06 (±4.48) years. The age standardized incidence rates for childhood cancer were 119.8 and 78.3 per 1000000 person-years in male and female children, respectively. Leukemia was the most common childhood cancer in Golestan province of Iran. Lymphomas and central nervous system tumors were the second and third ones, respectively.
The incidence rates of childhood cancers were relatively high in Golestan province of Iran. So, controlling of childhood cancers should be mentioned as an important issue in health policy making in this area.
PMCID: PMC3446043  PMID: 23056726
Childhood; Cancer; Population; Cancer registry; Iran
12.  Maternal Folate and Vitamin B12 Status and Neural Tube Defects in Northern Iran: A Case Control Study 
Iranian Journal of Pediatrics  2010;20(2):167-173.
This study was conducted to determine the serum level of folic acid and vitamin B12 in neural tube defects pregnancies (NTD) and healthy controls in Northern Iran.
This case-control study was performed on women with neural tube defects pregnancies and controls with unaffected pregnancies in Northern Iran during 2006. Twenty three pregnant women whose pregnancies were diagnosed as NTD by a second-trimester ultrasonographic examination were recruited as cases. The control group (n=23) consisted of women who were selected among socio-economic status (SES) matched women who had a normal targeted ultrasound during the second trimester with documented normal fet al outcome. Fetal NTD was suspected with targeted second-trimester ultrasound during the 16th week of gestation and confirmed with high maternal serum α-fetoprotein levels. Folate, vitamin B12, homocysteine and alpha fetoprotein were evaluated after target ultrasonography.
Serum alpha fetoprotein level (mean±SD) in cases and controls was 120.2±64.1 and 50±33.5 iu/ml, respectively (P<0.05). The mean±SD folate in cases and controls was 8.4±4.2 versus 9.3±4.2 ng/ml, respectively. This difference was not significant. Folate deficiency was found in 30.4% of the cases and 13% of the controls (OR=2.9, 95%: 0.54–19.8). Vitamin B12 deficiency was found in 13% of cases and 17.7% of the controls (OR=0.7, 95%: 0.1-4.9).
This study showed that the probability of having a newborn with NTDs in maternal folate deficiency is three times higher than with normal folate in Northern Iran.
PMCID: PMC3446032  PMID: 23056699
Neural tube defects; Folic acid deficiency; Vitamin B12; Pregnancy; Iran
13.  Inoperable esophageal cancer and outcome of palliative care 
AIM: To determine the outcome of esophageal cancer patients referred for palliative care, in Gorgan and Gonbad gastrointestinal clinics, northeast of Iran.
METHODS: This cross-sectional study was done on inoperable esophageal cancer cases referred to gastrointestinal clinics in Gorgan and Gonbad city (2005-2006). Demographic data were collected during the procedure and cases were followed up every one month. Improvement proportion was calculated with 95% confidence interval, to determine the rate of improvement. Survival analysis and Kaplan-Meier methods were used to estimate the duration of palliative care effectiveness.
RESULTS: We recruited 39 cases into the study. Squamous cell carcinoma was the most prevalent (92.3%). The middle third of the esophagus was involved predominantly (51.3%). Dilation was the most preferred method (89.7%) and stenting was done in 4 cases. Decreasing dysphagia score was not related to palliation method or pathology type of carcinoma. Age of the patients was significantly related to the improvement of dysphagia score. Mean survival time was 137.6 d and median was 103 d.
CONCLUSION: Results of this study showed a low survival rate after palliative care in esophageal cancer cases despite dysphagia scores’ improvement after dilating or stenting.
PMCID: PMC2719235  PMID: 18595139
Esophageal cancer; Palliative care; Survival; Dysphagia; Iran

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