Drinking maté, common in southern South America, may increase the risk of esophageal squamous cell carcinoma (ESCC). In 2006, we found high but variable polycyclic aromatic hydrocarbon (PAH) content in commercial yerba maté samples from eight Brazilian brands. The PAH content of new samples from the same brands, purchased in 2008, and four brands from a single manufacturer processed in different ways, obtained in 2010, were quantified to determine whether PAH concentration was still high, PAH content variation was brand specific, and whether processing method affects PAH content of commercial yerba maté. Concentrations of individual PAHs were quantified using gas chromatography/mass spectrometry with deuterated PAHs as internal standards. Median total PAH concentration was 1500 ng/g (range: 625 to 3710 ng/g) and 1090 ng/g (621 to 1990 ng/g) in 2008 and 2010 samples, respectively. Comparing 2006 and 2008 samples, some brands had high PAH concentrations in both years, while PAH concentration changed considerably in others. Benzo[a]pyrene concentrations ranged from 11.9 to 99.3 ng/g and 5.11 to 21.0 ng/g in 2008 and 2010 samples, respectively. The 2010 sample processed without touching smoke had the lowest benzo[a]pyrene content. These results support previous findings of very high total and carcinogenic PAH concentrations in yerba maté, perhaps contributing to the high incidence of ESCC in southern South America. The large PAH content variation by brand, batch and processing method suggests it may be possible to reduce the content of carcinogenic PAHs in commercial yerba maté, making it a healthier beverage.

Background

Identifying people at higher risk of having squamous dysplasia, the precursor lesion for esophageal squamous cell carcinoma (ESCC), would allow targeted endoscopic screening.

Methods

We used multivariate logistic regression models to predict ESCC and dysplasia as outcomes. The ESCC model was based on data from the Golestan Case-Control Study (total n=871; cases=300), and the dysplasia model was based on data from a cohort of subjects from a GI clinic in Northeast Iran (total n=724; cases=26). In each of these analyses, we fit a model including all risk factors known in this region to be associated with ESCC. Individual risks were calculated using the linear combination of estimated regression coefficients and individual-specific values for covariates. We used cross-validation to determine the area under the curve (AUC) and to find the optimal cut points for each of the models.

Results

The model had an area under the curve of 0.77 (95% CI: 0.74–0.80) to predict ESCC with 74% sensitivity and 70.4% specificity for the optimum cut point. The area under the curve was 0.71 (95% CI: 0.64–0.79) for dysplasia diagnosis, and the classification table optimized at 61.5% sensitivity and 69.5% specificity. In this population, the positive and negative predictive values for diagnosis of dysplasia were 6.8% and 97.8%, respectively.

Conclusion

Our models were able to discriminate between ESCC cases and controls in about 77%, and between individuals with and without squamous dysplasia in about 70% of the cases. Using risk factors to predict individual risk of ESCC or squamous dysplasia still has limited application in clinical practice, but such models may be suitable for selecting high risk individuals in research studies, or increasing the pretest probability for other screening strategies.

Background

Although for asymptomatic hepatic hemangiomas, conservative management is generally recommended, factors affecting disease course are still not very well understood.

Aim

To determine disease characteristics of cavernous hemangioma and factors affecting its progression in patients from a general hepatology clinic in Tehran, Iran.

Methods

We reviewed medical records of 198 patients with cavernous hemangioma of the liver visiting a large private hepatology clinic in Tehran from 1997 to 2007. Of a total of 198 cases, 129 could be followed up for a period of 3.2±2.5 years, and 80 of these had 1 to 5 repeat sonographies.

Results

Patients were between 27 and 84 years old (mean age 44.3±10.9), and 131 (66.2%) were female. Thirty-six patients (18.2%) had giant hemangiomas. Abdominal pain was the primary reason for evaluation in 100 (50.5%) patients. Abdominal pain at the beginning of follow-up was significantly associated with having irritable bowel syndrome (OR=8.3; 95%CI: 3.1-28.7) or other GI diseases (OR=3.9; 95%CI: 2.6-10.2), but not with hemangioma size, number or location. During follow-up, having a single giant lesion at the time of diagnosis, adjusted for age, sex and presence of IBS, was a strong predictor of persistent pain during follow-up (OR=11.1; 95%CI: 3.2-38.6). In repeat sonographies, 35% showed increased size, which was significantly associated only with having a single lesion (p=0.04).

Conclusion

Many symptoms in hepatic hemangioma are attributable to accompanying GI diseases. Patients with a single giant lesion are more likely to have persistent pain, and single lesions are more likely to grow in size.

Background

Control selection is a major challenge in epidemiologic case-control studies. The aim of our study was to evaluate using hospital versus neighborhood control groups in studying risk factors of esophageal squamous cell carcinoma (ESCC).

Methodology/Principal Findings

We compared the results of two different case-control studies of ESCC conducted in the same region by a single research group. Case definition and enrollment were the same in the two studies, but control selection differed. In the first study, we selected two age- and sex-matched controls from inpatient subjects in hospitals, while for the second we selected two age- and sex-matched controls from each subject's neighborhood of residence. We used the test of heterogeneity to compare the results of the two studies. We found no significant differences in exposure data for tobacco-related variables such as cigarette smoking, chewing Nass (a tobacco product) and hookah (water pipe) usage, but the frequency of opium usage was significantly different between hospital and neighborhood controls. Consequently, the inference drawn for the association between ESCC and tobacco use did not differ between the studies, but it did for opium use. In the study using neighborhood controls, opium use was associated with a significantly increased risk of ESCC (adjusted OR 1.77, 95% CI 1.17–2.68), while in the study using hospital controls, this was not the case (OR 1.09, 95% CI 0.63–1.87). Comparing the prevalence of opium consumption in the two control groups and a cohort enrolled from the same geographic area suggested that the neighborhood controls were more representative of the study base population for this exposure.

Conclusions/Significance

Hospital and neighborhood controls did not lead us to the same conclusion for a major hypothesized risk factor for ESCC in this population. Our results show that control group selection is critical in drawing appropriate conclusions in observational studies.

The rising epidemic of diabetes imposes a substantial economic burden on the Middle East. Using baseline data from a population based cohort study, we aimed to identify the correlates of diabetes mellitus (DM) in a mainly rural population from Iran. Between 2004 and 2007, 50044 adults between 30 and 87 years old from Golestan Province located in Northeast Iran were enrolled in the Golestan Cohort Study. Demographic and health-related information was collected using questionnaires. Individuals' body sizes at ages 15 and 30 were assessed by validated pictograms ranging from 1 (very lean) to 7 in men and 9 in women. DM diagnosis was based on the self-report of a physician's diagnosis. The accuracy of self-reported DM was evaluated in a subcohort of 3811 individuals using fasting plasma glucose level and medical records. Poisson regression with robust variance estimator was used to estimate prevalence ratios (PR's). The prevalence of self-reported DM standardized to the national and world population was 5.7% and 6.2%, respectively. Self-reported DM had 61.5% sensitivity and 97.6% specificity. Socioeconomic status was inversely associated with DM prevalence. Green tea and opium consumption increased the prevalence of DM. Obesity at all ages and extreme leanness in childhood increased diabetes prevalence. Being obese throughout life doubled DM prevalence in women (PR: 2.1; 95% CI: 1.8, 2.4). These findings emphasize the importance of improving DM awareness, improving general living conditions, and early lifestyle modifications in diabetes prevention.

Background

Verbal autopsy (VA) is one method to obtain valid estimates of causes of death in the absence of valid medical records. We tested the reliability and validity of a VA questionnaire developed for a cohort study in Golestan Province in northeastern Iran.

Method

A modified version of the WHO adult verbal autopsy was used to assess the cause of death in the first 219 Golestan Cohort Study (GCS) subjects who died. The GCS cause of death was determined by two internists who independently reviewed all available medical records. Two other internists (“reviewers”) independently reviewed only the VA answers and classified the cause of death into one of nine general categories; they repeated this evaluation one month later. The reliability of the VA was measured by calculating intra-reviewer and inter-reviewer kappa statistics. The validity of the VA was measured using the GCS cause of death as the gold standard.

Results

VA showed both good validity (sensitivity, specificity, PPV, and NPV all above 0.81) and reliability (kappa>0.75) in determining the general cause of death independent of sex and place of residence. The overall multi-rater agreement across four reviews was 0.84 (95%CI: 0.78–0.89). The results for identifying specific cancer deaths were also promising, especially for upper GI cancers (kappa = 0.95). The multi-rater agreement in cancer subgroup was 0.93 (95%CI: 0.85–0.99).

Conclusions

VA seems to have good reliability and validity for determining the cause of death in a large-scale adult follow up study in a predominantly rural area of a middle-income country.

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.