BackgroundControl 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 FindingsWe 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/SignificanceHospital 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.
Background Recent studies have suggested that opium use may increase mortality from cancer and cardiovascular diseases. However, no comprehensive study of opium use and mortality from respiratory diseases has been published. We aimed to study the association between opium use and mortality from respiratory disease using prospectively collected data. Methods We used data from the Golestan Cohort Study (GCS), a prospective cohort study in northeastern Iran, with detailed, validated data on opium use and several other exposures. A total of 50,045 adults were enrolled from 2004 to 2008, and followed annually until June 2015, with a follow-up success rate of 99%. We used Cox proportional hazard regression models to evaluate the association between opium use and outcomes of interest. Results During the follow-up period 331 deaths from respiratory disease were reported (85 due to respiratory malignancies and 246 due to nonmalignant etiologies). Opium use was associated with an increased risk of death from any respiratory disease (adjusted hazard ratio (HR) 95% CI; 3.13 (2.42-4.04)). The association was dose-dependent with a HR of 3.84 (2.61-5.67) for the highest quintile of cumulative opium use vs. never use (Ptrend<0.001). The hazard ratios (95% CI) for the associations between opium use and malignant and nonmalignant causes of respiratory mortality were 1.96 (1.18-3.25) and 3.71 (2.76-4.96), respectively. Conclusion Long-term opium use is associated with increased mortality from both malignant and nonmalignant respiratory diseases.
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