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Purpose The aim of this study was to determine the association between smoking and breast cancer after adjusting for smoking misclassification bias and confounders. Methods In this case-control study, 1000 women with breast cancer and 1000 healthy controls were selected. Using a probabilistic bias analysis method, the association between smoking and breast cancer was adjusted for the bias resulting from misclassification of smoking secondary to self-reporting as well as a minimally sufficient adjustment set of confounders derived from a causal directed acyclic graph (cDAG). Population attributable fraction (PAF) for smoking was calculated using Miettinen's formula. Results While the odds ratio (OR) from the conventional logistic regression model between smoking and breast cancer was 0.64 (95% CI: 0.36-1.13), the adjusted ORs from the probabilistic bias analysis were in the ranges of 2.63-2.69 and 1.73-2.83 for non-differential and differential misclassification, respectively. PAF ranges obtained were 1.36-1.72% and 0.62-2.01% using the non-differential bias analysis and differential bias analysis, respectively. Conclusion After misclassification correction for smoking, the non-significant negative-adjusted association between smoking and breast cancer changed to a significant positive-adjusted association.

Background: To investigate the geographical distribution of physical activity (PA) prevalence among adults aged 15–64 years old across Iran provinces using geographic maps. Methods: Data from 4 consecutive national surveys conducted between 2007 and 2010 were pooled to determine the geographical distribution. Prevalence of low PA with 95% confidence interval was estimated by sociodemographic subpopulations over provinces using complex survey design. Results: In total, 119,560 participants (49.9% females) were included in the analyses. The mean (SD) age of participants was 39.5 (14.3) years. The prevalence of the low PA in the pooled 2007–2010 was 35.8% (95% confidence interval, 34.1–37.6). The 3 provinces with the highest prevalence of low PA were Sistan and Baluchestan, Yazd, and Hormozgan. The results of hot spot analysis showed that the Kerman province was a hot spot, and Ilam, Kermanshah, Hamedan, and Markazi were cold spots for low PA. Ilam, Kohgiluyeh and Boyer-Ahmad, and Mazandaran had the highest total PA volume (metabolic equivalent minutes per week). Hot spot analysis showed that Ilam and Khuzestan provinces were hot spots for the total PA volume. Conclusions: The regions with low and high PA are predominately situated in the near center/southeast and west, respectively.

Objective To evaluate the effects of azelnidipine-carboxyl methyl cellulose (AZL-CMC) gel and carboxyl methyl cellulose 2% gel (CMC) on the healing of full-thickness skin wounds of diabetic rats. Methods Fifteen Sprague Dawley male rats were studied. The rats were divided into three groups: AZL-CMC gel-treated, CMC 2% gel-treated, and control group. Wounds were assessed by wound area measurement every 3 days and histopathology samples were collected at 4, 7 and 12 days post wounding to evaluate the healing process using stereological study. Mann-Whitney U-test repeated measurement and non-parametric one-way analysis of variance (ANOVA) were used to analyze the data using SPSS, version 18. Results Numerical density of the fibroblasts of the AZL-CMC gel treated group was 59.17±2.69 (×104/mm3) and higher than the control 22.64±1.34 (×104/mm3) and CMC 2%-treated groups 40.80±5.27 (×104/mm3), respectively, P

Background Osteoporosis is a multifactorial disease hallmarked by the interaction of genetic, nutritional and environmental factors. We aimed to assess the effect of alcohol consumption on the osteoporosis by undertaking a systematic review and meta-analysis. Methods We searched electronic databases including MEDLINE, Scopus, and Web of Science until June 2018. We identified all pertinent observational studies that examined the risk of OSTEOPOROSIS with alcohol use including cohort, case-control and cross-sectional studies. Relative risks (RR) for cohort studies and odds ratios (ORs) for case-control studies were pooled using the random effects model. Risk of bias was assessed using the Newcastle-Ottawa scale. Results From a pool of 3479 studies identified six met the study inclusion criteria (three case control, two cohorts and one cross-sectional study). Compared with abstainers of alcohol, persons consuming 0.5–1 drinks per day had 1.38 times the risk of developing osteoporosis (adjusted RR = 1.38, 95% CI: 0.90–2.12), persons consuming 1–2 drinks per day had 1.34 times the risk of developing OSTEOPOROSIS (adjusted RR = 1.34, 95% CI: 1.11–1.62), and persons consuming two drinks or more per day had 1.63 times the risk of developing osteoporosis (adjusted RR = 1.63, 95% CI: 1.01–2.65). We found a positive association between alcohol consumption and osteoporosis in the case-control studies (adjusted OR = 2.95, 95% CI: 1.78–4.90). Conclusion Our study demonstrates a positive relationship between alcohol consumption and osteoporosis.

Objectives The relationship between reproductive factors and breast cancer (BC) risk has been investigated in previous studies. Considering the discrepancies in the results, the aim of this study was to estimate the causal effect of reproductive factors on BC risk in a case-control study using the double robust approach of targeted maximum likelihood estimation. Methods This is a causal reanalysis of a case-control study done between 2005 and 2008 in Shiraz, Iran, in which 787 confirmed BC cases and 928 controls were enrolled. Targeted maximum likelihood estimation along with super Learner were used to analyze the data, and risk ratio (RR), risk difference (RD), andpopulation attributable fraction (PAF) were reported. Results Our findings did not support parity and age at the first pregnancy as risk factors for BC. The risk of BC was higher among postmenopausal women (RR = 3.3, 95% confidence interval (CI) = (2.3, 4.6)), women with the age at first marriage ≥20 years (RR = 1.6, 95% CI = (1.3, 2.1)), and the history of oral contraceptive (OC) use (RR = 1.6, 95% CI = (1.3, 2.1)) or breastfeeding duration ≤60 months (RR = 1.8, 95% CI = (1.3, 2.5)). The PAF for menopause status, breastfeeding duration, and OC use were 40.3% (95% CI = 39.5, 40.6), 27.3% (95% CI = 23.1, 30.8) and 24.4% (95% CI = 10.5, 35.5), respectively. Conclusions Postmenopausal women, and women with a higher age at first marriage, shorter duration of breastfeeding, and history of OC use are at the higher risk of BC.

Background: Resistin reduces tissue sensitivity to insulin and causes hyperglycemia. Diabetic nephropathy is also a metabolic disorder caused by chronic hyperglycemia that causes kidney dysfunction. Objectives: This study aimed to investigate the relationship between serum resistin and diabetic nephropathy in diabetic patients who referred to Imam Reza Hospital in 2018 - 2019. Methods: This case-control study recruited 30 diabetic patients with nephropathy, 29 non-nephropathy diabetic patients, and 30 healthy controls via convenience sampling. Serum and 24-hour urine samples were taken from each person. After the determination of the glomerular filtration rate, samples were tested in a laboratory. Also, data were analyzed by SPSS software version 23, and P < 0.05 was considered significant. Results: Mean serum resistin was significantly different between the groups (F = 3.600, P = 0.032). Tukey’s follow-up test showed that resistin was critically higher in the diabetic nephropathy group than in the control group and healthy controls. There was a weak inverse relationship between glomerular filtration rate and serum resistin level (r = -0.233, P = 0.031). Conclusions: Levels of resistin may rise in people with diabetes associated with nephropathy. It seems that Serum resistin can be used as a biomarker to assess the severity of diabetes mellitus.

Introduction: Peripheral neuropathy (PN) is among the most prevalent complications of diabetes that can lead to impairment of mobility of diabetic patients. The purpose of the current study was to predict relative factors influencing the occurrence of peripheral neuropathy (PN) in patients with type 2 diabetes. Methods: This was a cohort study on diabetic patients in the Isfahan Province of Iran. The studied population consisted of patients with type 2 diabetes, of ages 18 or older, who were diagnosed as new cases of diabetes from 2007 to 2014, and whose follow-up was completed by the end of 2016. In this study, with regards to the presence of time-varying co-variates, timedependent Cox regression model was employed in order to estimate the Hazard Ratio (HR) of PN in the diabetic patients. Results: Overall, 1874 patients with diabetes participated in the study, of which 839 (44.77%) were men and 1035 (55.23%) were women. During the study period, PN occurred in 17.98% of the patients; the ratio was 17% in women and 19.18% in men. In comparison to the reference group, the adjusted HR of PN in males was equal to 3.66 (95% CI: 1.15-11.67), in housewives was equal to 4.09 (95% CI: 1.02-16.38), and divorced or wife died patients was equal to 3.02 (95% CI: 1.61-5.65). In addition, for each 6 month follow-up of the patients, the adjusted HR of PN increased to 1.19 (95% CI: 1.17-1.22). Conclusions: The adjusted HR of PN in men, in housewives, and elderly people, divorced or wife died patients, with elementary education level were greater than the reference group. Thus, training, screening and diagnostic programs should be carried out with greater sensitivity in patients who are at greater risk for PN.

To assess the prevalence and correlates of low physical activity among Iranian population aged 15-64 years. We used the data collected in National Surveillance of Risk Factors of Non-Communicable Diseases in Iran, 2011. Physical activity was categorized in 3 levels of low, moderate, and high based on a Persian version of Global Physical Activity Questionnaire. The multistage cluster sampling design was accounted for using complex survey analysis method. The sample included 10016 individuals; 41.7% (n = 4178) were men and 58.3% (n = 5837) were women. The mean (SD) age of participants was 38.8 (14.9) years also, and 69.8% (n = 6991) of the participants were from urban areas. The prevalence of low physical activity in the whole population was estimated to be 44.8% (95% CI: 41.7, 48.1). The odds of lower physical activity in the women were 3 times greater than men (OR = 3.14; 95% CI: 2.64, 3.57); in the wealthiest people was 25% lower than the poorest people (OR = 0.75; 95% CI: 0.60, 0.94). The odds of lower physical activity in the age groups 55-64 years were 44% greater than the youngest age groups 15-24 years (OR = 1.44; 95% CI: 1.23, 1.68). The odds of lower physical activity in the obese participants were 18% greater than normal-weight people (OR = 1.18; 95% CI: 1.01, 1.38).). The odds of lower physical activity in diabetic patients were 30% greater than healthy people (OR: 1.30; 95% CI: 1.07, 1.57). The prevalence of low physical activity in Iran, 2011 was high. The correlates of low physical activity in Iran are different to those of Western populations. The main associated factors with low physical activity were female gender, urban area, low socioeconomic status, obesity, diabetes, and older age. Public health policies should target the groups at highest risk of low physical activity.

Background and Purpose— Standard analytic approaches (eg, logistic regression) fail to adequately control for time-dependent confounding and, therefore, may yield biased estimates of the total effect of the exposure on the outcome. In the present study, we estimate the effect of body mass index, intentional physical activity, HDL (high-density lipoprotein) cholesterol, LDL (low-density lipoprotein) cholesterol, hypertension, and cigarette smoking on the 11-year risk of ischemic stroke by sex using the parametric g-formula to control time-dependent confounders. Methods— Using data from the MESA (Multi-Ethnic Study of Atherosclerosis), we followed 6809 men and women aged 45 to 84 years. We estimated the risk of stroke under 6 hypothetical interventions: maintaining body mass index 2 , maintaining normotension (systolic blood pressure 1.55 mmol/L, maintaining LDL Results— In men, the 11-year risk of ischemic stroke would be reduced by 85% (95% CI, 66–96) for all 6 hypothetical interventions. In women, this same effect was estimated as 55% (95% CI, 6–82). Conclusions— The hypothetical interventions explored in our study resulted in risk reduction in both men and women.

In longitudinal studies, standard analysis may yield biased estimates of exposure effect in the presence of time-varying confounders that are also intermediate variables. We aimed to quantify the relationship between obesity and coronary heart disease (CHD) by appropriately adjusting for time-varying confounders. This study was performed in a subset of participants from the Atherosclerosis Risk in Communities (ARIC) Study (1987-2010), a US study designed to investigate risk factors for atherosclerosis. General obesity was defined as body mass index (weight (kg)/height (m)2) ≥30, and abdominal obesity (AOB) was defined according to either waist circumference (≥102 cm in men and ≥88 cm in women) or waist:hip ratio (≥0.9 in men and ≥0.85 in women). The association of obesity with CHD was estimated by G-estimation and compared with results from accelerated failure-time models using 3 specifications. The first model, which adjusted for baseline covariates, excluding metabolic mediators of obesity, showed increased risk of CHD for all obesity measures. Further adjustment for metabolic mediators in the second model and time-varying variables in the third model produced negligible changes in the hazard ratios. The hazard ratios estimated by G-estimation were 1.15 (95% confidence interval (CI): 0.83, 1.47) for general obesity, 1.65 (95% CI: 1.35, 1.92) for AOB based on waist circumference, and 1.38 (95% CI: 1.13, 1.99) for AOB based on waist:hip ratio, suggesting that AOB increased the risk of CHD. The G-estimated hazard ratios for both measures were further from the null than those derived from standard models.

Objective To evaluate the effects of azelnidipine-carboxyl methyl cellulose (AZL-CMC) gel and carboxyl methyl cellulose 2% gel (CMC) on the healing of full-thickness skin wounds of diabetic rats. Methods Fifteen Sprague Dawley male rats were studied. The rats were divided into three groups: AZL-CMC gel-treated, CMC 2% gel-treated, and control group. Wounds were assessed by wound area measurement every 3 days and histopathology samples were collected at 4, 7 and 12 days post wounding to evaluate the healing process using stereological study. Mann–Whitney U-test repeated measurement and non-parametric one-way analysis of variance (ANOVA) were used to analyze the data using SPSS, version 18. Results Numerical density of the fibroblasts of the AZL-CMC gel treated group was 59.17±2.69 (×104/mm3) and higher than the control 22.64±1.34 (×104/mm3) and CMC 2%-treated groups 40.80±5.27 (×104/mm3), respectively, P

There is still debate on whether the relationship between blood pressure (BP) and risk of cardiovascular diseases (CVD) in patients with type 2 diabetes (T2D) is linear or not. Since these cardio-metabolic disturbances share interrelated complex pathogenic mechanisms, we aimed to assess the relationship of baseline systolic (SBP)/diastolic pressures with CVD and coronary heart disease (CHD) events in a cohort of Iranians with T2D during a median follow-up of 8.8 years. Of all 1009 eligible participants with T2D with a mean (s.d.) age of 54.4 (11.6) years and free of CVD at baseline, we primarily focused on 260 participants undergoing anti-hypertensive treatment. Multivariate Cox proportional hazard models were used to evaluate hazard ratios (HR) of BP categories for CVD and CHD events. Also, multivariable regression modelling was applied to obtain their risk curve. We detected a J-shaped phenomenon between the continuous baseline BP and risk of CVD events. Considering 130⩽SBP

Background: Adverse effects of excessive body mass reduction among wrestlers dictate minimum weight determination through body composition. Although skinfold equations are essential to estimate body composition in the field setting, they are mostly derived from Western societies and may lack generalizability to other populations. Purpose: Previously published skinfold equations lacked external validity in predicting body density of Iranian wrestlers. We aimed to derive a new anthropometric model specific to young Iranian male wrestlers. Study design: Cross-sectional cohort study. Level of evidence: Level 3. Methods: One hundred twenty-six Iranian male wrestlers with at least 1 year of experience and a mean age of 19 ± 4.0 years underwent underwater weight analysis for body density estimation and anthropometric measurements. The previously published equations were validated, followed by new regression modeling, using multivariable fractional polynomials, with body density as the criterion predicted by common anthropometric variables. The final model was validated throughout the modeling procedure using 1000 bootstrap replications. Results: The mean body fat percentage (%BF) was 12.6% (95% CI, 11.9%-13.4%), lower than that of previous studies. Six previously published equations each had significant deviations from the line of identity (all P < 0.001). The new prediction equation combined subscapular, tricipital, and midaxillary skinfolds and body mass index cubed to predict body density. Conclusion: The development of ethnicity-specific equations, using statistically unbiased and comprehensive validation methods, is imperative for body composition estimation to determine the minimum weight for regulation of health in athletes. Clinical Relevance: Using equations without external validation can bias the prediction of minimum weight, leading to unsafe weight reduction by athletes. Compared with a previous study, much lower mean %BF was found using an ethnicity-specific equation (12.6% vs 15.9%). This difference observed in %BF prediction could affect safe fat reduction in athletes.

Association of subclinical hypothyroidism with type 2 diabetes and its complications has been previously documented. These reports were, however, inconclusive and mainly gathered from Chinese and East Asian populations. In this study, we aimed to determine the prevalence of subclinical hypothyroidism and its relationship with diabetic nephropathy in Iranian individuals with type 2 diabetes, drawn from a white Middle Eastern population with an increasing prevalence of diabetes.In this cross-sectional study, 255 Iranian participants with type 2 diabetes and without history of thyroid disorders were included. Patients with TSH 4.2 mIU/L and normal T4 were classified as having subclinical hypothyroidism. Diabetic nephropathy was diagnosed based on abnormal 24-h urinary albumin or protein measurements (24-h urinary albumin ≥30 mg/day or 24-h urinary protein ≥150 mg/day). Multivariate logistic regression was employed to obtain the OR for the relationship between subclinical hypothyroidism and diabetic nephropathy.We found that subclinical hypothyroidism and diabetic nephropathy were as prevalent as 18.1 and 41.2 %, respectively, among the participants. We also found that subclinical hypothyroidism was independently associated with higher rates of diabetic nephropathy, after multivariable adjustment (OR [95 % CI] 3.23 [1.42-7.37], p = 0.005).We found that the prevalence of subclinical hypothyroidism in Iranian diabetic population was among the highest rates reported to date. Our data supported the independent association of subclinical hypothyroidism with diabetic nephropathy, calling for further investigations to evaluate their longitudinal associations.

COVID-19 due to novel Coronavirus was first reported in Wuhan, China. Nowadays, the Islamic Republic of Iran stands among countries with high COVID-19 prevalence and high burden of disease. Since the medical resources are limited, we aimed to identify the risk factors for patients developing critical conditions. This can help to improve resource management and treatment outcomes. In this retrospective study, we included 12,677 patients who were from 26 hospitals, supervised by Tehran University of Medical Sciences with signs and symptoms of COVID-19, until April 12. University integrated IT system was adopted to collect the data. We performed Logistic regression to evaluate the association between death in COVID-19 positive patients and other variables. Cough, respiratory distress and fever were the most common symptoms in our patients, respectively. Cancer, chronic lung diseases and chronic neurologic diseases were the strongest risk factors for death in COVID-19 patients.

Aim The mechanisms linking body mass index to cardiovascular disease are still not clearly defined. The purpose of this study was to find out how much of the effect of central and general adiposity on cardiovascular disease is mediated through blood pressure, cholesterol, and glucose, and how much is independent of these factors. Methods and results The study population included participants, aged ≥30 years, free of cardiovascular disease at baseline with median follow-up of 13.9 years. The total effects were broken down into natural direct and indirect effects using the inverse odds weighting method in the context of survival models. Systolic blood pressure, total serum cholesterol, and fasting plasma glucose as the primary measure of blood glucose were used as mediators. Blood pressure and cholesterol with indirect hazard ratios of 1.09 (95% confidence interval: 1.006–1.18) and 1.35 (95% confidence interval: 1.12–1.62) were the most important mediators for overweight-cardiovascular disease and obesity-cardiovascular disease relationships, respectively. The proportion mediated of overweight was 22% (6–47%) for blood pressure, 18% (5–37%) for blood glucose, and 20% (7–43%) for cholesterol. The same measure for obesity was 65% (35–91%) for cholesterol. For central adiposity, blood pressure, glucose, and cholesterol were the most important mediators with proportion mediated of 36% (17–72%), 23% (9–48%), and 21% (8–45%), respectively. Conclusions The findings of this study show that proper control of cardiometabolic risk factors of blood pressure, blood glucose, and dyslipidemia in an adult population can be effective to significantly reduce the effects of general and abdominal adiposity on cardiovascular diseases.

The current study was performed to evaluate the effect of Albusite gel on the healing process of excisional wounds in diabetic and control rats. Fifty-two Sprague Dawley male rats were used to evaluate the effects of Albusite Gel (synthetic gel) on the healing of full-thickness skin wounds. The control group (n = 2 6) and study group (n = 26) were divided into two groups (n = 13). Wounds were assessed by wound measurements and collection of samples at 9 (A, C) and 21 days (B, D) post-wounding to evaluate the healing process. Variables of interest were gross and microscopic histopathological characteristics were reflective of wound healing. Topical Albusite gel was applied for wound A and B, once a day. Each rat was anesthetized and a round full thickness excisional wound with 150 cm2 area was performed on the right dorsolateral side of each rat. There was little difference between the case and control groups. Wound healing processes and wound closure in the intervention group began sooner and completed more quickly respectively, but both of them did not show a statistically significant difference (p>0.05). The healing of Albusite treated wound was better than the control wounds grossly. The study wounds were biopsied at days 9 and 21, so this might not show different effects of the Albusite gel group in appropriate time. Therefore, further studies are recommended with more sample size and less biopsy interval.

Vitamin D is shown to be a potent immunomodulator. Considering the potential role of low serum vitamin D levels in autoimmune disorder, we evaluated the association between Hashimoto's thyroiditis (HT) (with subclinical or overt hypothyroidism) and serum 25-hydroxyvitamin D (25OHD) levels in an Iranian population.A total number of 86 individuals were enrolled. The case group included 41 patients with hypothyroid HT (overt or subclinical). The control group comprised 45 healthy euthyroid persons. Serum 25OHD levels were measured in all subjects.control ratio of geometric means of 25OHD levels was 0.66 (95 % CI: 0.49-0.90; P = 0.008). There was a significant inverse association between serum 25OHD levels and HT (OR: 0.81 for 5 ng/ml increase in 25OHD level, 95 % CI: 0.68-0.96; P = 0.018). This association remained significant after adjustment for potential confounding factors including age, sex and BMI.Our study suggested that higher serum 25OHD levels was associated with decreased risk of HT so that each 5 ng/ml increase in the serum 25OHD levels results in 19 % decrease in odds of HT.

In the presence of non-adherence, intention-to-treat analysis preserves randomization, but does not lead to a valid comparison of outcome between the assigned groups. Using a reanalysis of Diabetes Prevention Program, this study aimed to estimate the causal effect of treatment with intensive lifestyle intervention or metformin vs. placebo on blood pressure and lipid profile using G-estimation after accounting for non-adherence.The Diabetes Prevention Program randomized 3,052 pre-diabetic individuals to metformin (N = 1015), placebo (N = 1014), or an intensive lifestyle intervention (N = 1023). G-estimation was used to estimate the causal effect of intensive lifestyle intervention or metformin vs. placebo on blood pressure and lipid profile in 2,973 patients who had adherence data. For comparison, we also performed the standard intention-to-treat analysis.The G-estimation results showed that intensive lifestyle substantially improves systolic and diastolic blood pressure and lipid profile. The G-estimates of the effects of metformin vs. placebo as well as intensive lifestyle intervention vs. metformin on blood pressure and lipid profile were also stronger than the intention-to-treat effect estimates.G-estimation suggests that intensive lifestyle modification improves known risk factors for cardiovascular disease, including systolic blood pressure, diastolic blood pressure, triglyceride, and HDL levels more than what standard ITT analysis suggests. Adherence to the assigned treatment should be measured in all randomized trials, and G-estimation should be the standard analysis of randomized trials with substantial non-adherence.

The relation of Two single nucleotide polymorphisms (SNPs) at the adiponectin locus (+45T/G and +276G/T) with coronary artery disease (CAD) is controversial. The aim of the present study was to evaluate the genetic influence of the adiponectin gene polymorphisms in the development of CAD among patients with Type 2 diabetes (T2D). The adiponectin genotypes were detected by polymerase chain reaction and restriction analysis (PCR-RFLP) in our patients. Two adiponectin gene (ADIPOQ) SNPs (i.e. SNPs +45TG and +276GT) were genotyped in 114 Type 2 diabetic subjects with CAD, and 127 Type 2 diabetic patients without CAD. Demographic and anthropometric data along with plasma biochemistry including lipids, glycemic indices, and adiponectin were collected. There was a significant difference in the distribution of genotypes of +45T/G and +276G/T between CAD and non-CAD individuals (P 0.05). Based on our results SNP+276GT is associated with decreased risk of CAD after adjustment for potential confounding factors [adjusted OR = 0.39 (95%CI: 0.22-0.68); P = 0.001]. Similar findings were not observed for the +45TG SNP. Two haplotypes 45T-276T and 45G-276T were associated with a decreased risk of CAD [adjusted OR = 0.47 (95% CI: 0.32-0.94); P = 0.03 and adjusted OR = 0.33 (95% CI: 0.13-0.83); P = 0.02 respectively]. No significant difference was observed between HOMA-IR, BMI, waist circumference, history of hypertension, HbA1C, and lipid concentrations regarding the two SNPs. In conclusion, these findings suggest that T allele of +276GT SNP is significantly associated with decreased risk of CAD in T2D Patients. Also Haplotype analysis showed that two haplotypes 45T-276T and 45G-276T were associated with a decreased risk of CAD.

ObjectivesDiet and nutrition might play an important role in the aetiology of metabolic syndrome (MetS). Most studies that examine the effects of food intake on MetS have used conventional statistical analyses which usually investigate only a limited number of food items and are subject to sparse data bias. This study was undertaken with the goal of investigating the concurrent effect of numerous food items and related nutrients on the incidence of MetS using Bayesian multilevel modelling which can control for sparse data bias.DesignProspective cohort study.SettingThis prospective study was a subcohort of the Tehran Lipid and Glucose Study. We analysed dietary intake as well as pertinent covariates for cohort members in the fourth (2008–2011) and fifth (2011–2014) follow-up examinations. We fitted Bayesian multilevel model and compared the results with two logistic regression models: (1) full model which included all variables and (2) reduced model through backward selection of dietary variables.Participants3616 healthy Iranian adults, aged ≥20 years.Primary and secondary outcome measuresIncident cases of MetS.ResultsBayesian multilevel approach produced results that were more precise and biologically plausible compared with conventional logistic regression models. The OR and 95% confidence limits for the effects of the four foods comparing the Bayesian multilevel with the full conventional model were as follows: (1) noodle soup (1.20 (0.67 to 2.14) vs 1.91 (0.65 to 5.64)), (2) beans (0.96 (0.5 to 1.85) vs 0.55 (0.03 to 11.41)), (3) turnip (1.23 (0.68 to 2.23) vs 2.48 (0.82 to 7.52)) and (4) eggplant (1.01 (0.51 to 2.00) vs 1 09 396 (0.152×10–6to 768×1012)). For most food items, the Bayesian multilevel analysis gave narrower confidence limits than both logistic regression models, and hence provided the highest precision.ConclusionsThis study demonstrates that conventional regression methods do not perform well and might even be biased when assessing highly correlated exposures such as food items in dietary epidemiological studies. Despite the complexity of the Bayesian multilevel models and their inherent assumptions, this approach performs superior to conventional statistical models in studies that examine multiple nutritional exposures that are highly correlated.

The pathogenesis of diabetic nephropathy, mainly characterized by macroalbuminuria, is still poorly understood, but it is reported that transforming growth factor-beta (TGF-beta) plays a key role. In vitro evidence suggests that administration of oxidized LDL (ox-LDL) can lead to upregulation of TGF-beta by human glomerular mesangial cells. This study aimed to evaluate the association between macroalbuminuria, ox-LDL, and TGF-beta in diabetic patients. A total of 77 type 2 diabetic patients with macroalbuminuria (albumin excretion rate: AERor = 300 mg/24 h) and 66 patients with normoalbuminuria (AERor = 30 mg/24 h) were recruited. Fasting blood samples were obtained and serum levels of ox-LDL and TGF-beta were determined. Ox-LDL and TGF-beta were significantly higher in patients with macroalbuminuria than in those with normoalbuminuria (98.93 + or - 3.99 vs. 72.45 + or - 2.48 U/l; P0.001 and 6.46 + or - 0.74 vs. 2.49 + or - 0.39 ng/ml; P0.001, respectively). In patients with macroalbuminuria, there was a significant correlation between Ox-LDL and TGF-beta (r = 0.376; P0.01). AER was significantly correlated to ox-LDL (r = 0.302; P0.05) and TGF-beta (r = 0.306; P0.05) in macroalbuminuric patients. This association remained significant after adjustment for potential confounders. Adjustment for TGF-beta (ox-LDL), attenuated the association of ox-LDL (TGF-beta) with AER. In conclusion, this study demonstrated the association of TGF-beta and ox-LDL with albuminuria in macroalbuminuric type 2 diabetic patients, and suggested that this relationship is highly mediated through the correlation between TGF-beta and ox-LDL.

Exercise-induced bronchospasm (EIB) is a clinical syndrome that affects 8-20% of the general population and 11-50% of athletes. Although a variety of testing protocols for the diagnosis of EIB have been pursued, the optimal algorithm still is lacking. The aim of this study was to determine the prevalence of EIB among students of Tehran University of Medical Sciences and to find out whether self-reported symptoms are sufficient to establish the diagnosis of EIB. A total of 463 students completed an EIB symptoms-specific questionnaire, followed by a 9-minute exercise test. Spirometric measurements were performed before, and 6 and 15 minutes after exercise. In our study, decrements of >15% in forced expiratory volume in 1 second or 25% in peak expiratory flow or forced expiratory flow at 25-75% from baseline values were defined as positive indications of EIB. The overall prevalence of EIB was 10.8% (15.94% in men versus 8.62% in women; p = 0.02). There was no significant difference between the students with and without EIB regarding body mass index, family income, and allergy frequency. The frequency of at least two out of the four symptoms of coughing, wheezing, shortness of breathing, and chest pain/discomfort among students with EIB was significantly higher than those without EIB (26.5% versus 15.1%, respectively; p = 0.04). The sensitivity and specificity of self-reported symptoms for EIB diagnosis were 26.5 and 84.9%, respectively. Although among all determinants proposed for EIB, respiratory symptoms are closely related to the disease, diagnosis based on only these symptoms is not recommended because of high false positive and false negative results.

Associations between diabetes self-management and microvascular complications in patients with type 2 diabetes Fatemeh Mehravar,1 Mohammad Ali Mansournia,2 Kourosh Holakouie-Naieni,2 Ensie Nasli-Esfahani,3 Nasrin Mansournia,4 and Amir Almasi-Hashiani5 Abstract OBJECTIVES: Diabetes is a major public health problem that is approaching epidemic proportions globally. Diabetes self-management can reduce complications and mortality in type 2 diabetic patients. The purpose of this study was to examine associations between diabetes self-management and microvascular complications in patients with type 2 diabetes. METHODS: In this cross-sectional study, 562 Iranian patients older than 30 years of age with type 2 diabetes who received treatment at the Diabetes Research Center of the Endocrinology and Metabolism Research Institute of the Tehran University of Medical Sciences were identified. The participants were enrolled and completed questionnaires between January and April 2014. Patients’ diabetes self-management was assessed as an independent variable by using the Diabetes Self-Management Questionnaire translated into Persian. The outcomes were the microvascular complications of diabetes (retinopathy, nephropathy, and neuropathy), identified from the clinical records of each patient. A multiple logistic regression model was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) between diabetes self-management and the microvascular complications of type 2 diabetes, adjusting for potential confounders. RESULTS: After adjusting for potential confounders, a significant association was found between the diabetes self-management sum scale and neuropathy (adjusted OR, 0.64; 95% CI, 0.45 to 0.92, p=0.01). Additionally, weak evidence was found of an association between the sum scale score of diabetes self-management and nephropathy (adjusted OR, 0.71; 95% CI, 0.47 to 1.05, p=0.09). CONCLUSIONS: Among patients with type 2 diabetes, a lower diabetes self-management score was associated with higher rates of nephropathy and neuropathy. Keywords: Diabetes self-management, Type 2 diabetes, Microvascular complications, Neuropathy, Retinopathy, Nephropathy

Background: A previous analysis of the Osteoarthritis Initiative study reported a dose-response relationship between physical activity and improved physical function in adults with knee osteoarthritis, using conventional statistical methods. These methods are subject to bias when confounders are affected by prior exposure. Methods: We used baseline and 1-, 2-, and 3-year follow-up data from the Osteoarthritis Initiative study of 2545 US adults with knee osteoarthritis recruited between 2004 and 2006 from 4 clinical sites. Physical activity was measured using the Physical Activity Scale for the Elderly, and outcomes were functional performance measured by the timed 20-meter walk test and self-reported knee pain measured by the Western Ontario and McMaster Universities Osteoarthritis Index. We estimated the effect of physical activity on each outcome using inverse probability-weighted (IPW) estimators of marginal structural models. For each outcome, we fitted 2 separate IPW models adjusting for concurrent or lagged confounders. Results: The mean differences in walking speed for the second, third, and fourth quartiles of physical activity relative to the first were 0.48 (95% confidence interval = -0.12 to 1.08), 0.45 (-0.23 to 1.13), and 0.46 (-0.29 to 1.22) meters/min based on the IPW model adjusting for concurrent confounders. When adjusting for lagged confounders, the results were 1.35 (0.64 to 2.07), 1.33 (0.54 to 2.14), and 1.26 (0.40 to 2.12). Both IPW models indicated that physical activity did not affect knee pain. Conclusions: Physical activity has no effect on knee pain and may have either a very small effect or no effect on functional performance in adults with knee osteoarthritis. Knee osteoarthritis is a leading cause of pain and disability in the elderly.1 There is no cure for osteoarthritis, and treatment is generally aimed at reducing pain and maintaining function.2 Several systematic reviews of randomized trials have demonstrated that exercise programs reduce pain and disability in the short term in patients with knee osteoarthritis.3–5 However, prospective observational studies are needed to evaluate the long-term effects of lifestyle physical activity among people with knee osteoarthritis. Using generalized estimating equations (GEE) to estimate a linear model, Dunlop et al 6 evaluated the effect of physical activity on subsequent 1-year functional performance in adults with knee osteoarthritis using 2-year follow-up data from the Osteoarthritis Initiative. The authors adjusted for the potential confounders available only at baseline, as well as the concurrent values of time-dependent confounders, and reported a dose-response relationship between physical activity and improved performance. However, standard methods for analysis of longitudinal data may lead to biased estimates when exposure affects a confounder, or when exposure is affected by prior outcome and affects future outcome.7–9 Both of these conditions are possible in the Osteoarthritis Initiative data, eg, physical activity may affect body mass index as a potential confounder and may also affect as well as be affected by functional performance. Marginal structural models overcome this problem by using inverse probability weighting.10,11 The aim of this study was to estimate the effect of physical activity on functional performance and knee pain in the Osteoarthritis Initiative cohort using inverse probability-weighted (IPW) estimators of marginal structural models.