Measurement bias (MB) has been described in causal structures but is still not entirely clear. In practice, the correctness of substitution estimate (SE) of effect is a prerequisite for causal inference, usually based on a bidirectionally non-differential misclassification between the measured exposure and the measured outcome. Based on a directed acyclic graph (DAG), this paper proposes a structure for the single-variable measure, where its MB is derived from the choice of an imperfect, "input/output device-like" measurement system. The MB of the SE is influenced both by the measurement system itself and by factors outside the measurement system: while the independence or dependence mechanism of the measurement system still ensures that the MB of the SE is bidirectionally non-differential; however, the misclassification can be bidirectionally non-differential, unidirectionally differential, or bidirectionally differential resulted from the factors outside the measurement system. In addition, reverse causality should be defined at the level of measurement, where measured exposures can influence measured outcomes and vice versa. Combined with temporal relationships, DAGs help elucidate MB's structures, mechanisms, and directionality.
Humans ; Confounding Factors, Epidemiologic ; Data Interpretation, Statistical ; Bias ; Causality

Controlling unmeasured confounders in non-randomized controlled studies is challenging. Negative control theory is based on the theoretical concept that the test result of negative controls must be negative. Setting appropriate negative control incorporates the specificity of association into population studies for the identification and control of unmeasured confounders. This paper explains the principles to control unmeasured confounders using negative control theory from a statistical perspective. A detailed introduction of derived methods based on negative control theory is also introduced, including adjusted standardized mortality ratio method, calibrating P-value method, generalized difference-in-difference model and double negative control method. The reasonable application of those derived methods is also comprehensively summarized based on representative case studies. Negative control is an important statistical design to identify, revise and control unmeasured confounders and a valuable method for comparative effectiveness research based on real-world data.
Humans ; Confounding Factors, Epidemiologic ; Research Design ; Comparative Effectiveness Research ; Bias

confounding variables.RESULTS: The BMD of the total femur and Ward's triangle were significantly different according to the potassium intake among men (P = 0.031 and P = 0.010, respectively). Women in the top tertile for potassium intake showed higher BMD than those in the bottom tertile at all measurement sites (all P < 0.05). Daily potassium intake was significantly related to a decreased risk of osteoporosis at the lumbar spine in postmenopausal women (odds ratios: 0.68, 95% confidence interval: 0.48-0.96, P trend = 0.031). However, the dietary potassium level was not related to the risk of osteoporosis in men.CONCLUSION: Current findings indicate that higher dietary potassium levels have a favorable effect on bone health and preventing osteoporosis in older Korean women.]]>
Absorptiometry, Photon ; Adult ; Bone Density ; Bone Diseases, Metabolic ; Calcium ; Confounding Factors (Epidemiology) ; Cross-Sectional Studies ; Epidemiology ; Female ; Femur ; Femur Neck ; Hip ; Humans ; Logistic Models ; Male ; Methods ; Nutrition Surveys ; Osteoporosis ; Population Surveillance ; Potassium ; Potassium, Dietary ; Prevalence ; Retrospective Studies ; Spine ; Vitamin D

PURPOSE: To determine the relationship between uterine leiomyoma and female sexual dysfunction (FSD) among premenopausal and postmenopausal women. MATERIALS AND METHODS: The study population consisted of consecutive women who underwent gynecologic screening tests, including transvaginal ultrasound, and completed the questionnaires on FSD. A total of 841 women were included from January 2010 to December 2011. FSD was defined as Female Sexual Function Index (FSFI) ≤26.55. The relationship between uterine leiomyoma and FSD were compared according to menopausal status. RESULTS: In premenopausal group (n=564), there were no differences in the frequency of FSD (55.0% vs. 58.8%, p=0.387) and total FSFI score. However, in postmenopausal group (n=277), women with uterine leiomyoma had a lower frequency of FSD than those without uterine leiomyoma (71.3% vs. 86.4%, p=0.003). This relationship between uterine leiomyoma and lower frequency of FSD in postmenopausal women remained significant after adjusting for confounding variables. CONCLUSION: The relationship between uterine leiomyoma and FSD is different depending on the menopausal status.
Confounding Factors (Epidemiology) ; Dyspareunia ; Female ; Humans ; Leiomyoma ; Mass Screening ; Menopause ; Sexual Behavior ; Ultrasonography

PURPOSE: This study aims to investigate the effects of smoking on the development of placenta-associated syndromes, including preeclampsia, abruptio placentae, and placenta previa, which share the common pathophysiology of vascular compromise of the placenta. METHODS: A total of 966,629 pregnancies identified from the Korean National Insurance Claims Database and the National Health Information Database were analyzed from 2010 to 2014. The adjusted odds ratio and attributable risk of smoking for the development of placenta-associated syndromes, such as preeclampsia, placenta previa, and abruptio placentae, were analyzed. Maternal age, alcohol consumption, exercise habit, and economic status were controlled as confounding variables. A binary logistic regression model was used, and simple and multiple logistic regression analyses were performed. RESULTS: Among 966,629 pregnancies, 11.86% of women were ever smokers. Ever smokers had a higher risk of developing placenta previa (adjusted odds ratio, 1.23; 95% confidence interval [CI], 1.18–1.29; adjusted attributable risk, 18.70%). The adjusted odds ratio of developing placenta-associated syndromes in ever smokers compared to nonsmokers over the age of 35 years with a low economic status was 1.32 (95% CI, 1.18–1.47), with an adjusted attributable risk of 23.95%. CONCLUSION: The risk of developing placenta-associated syndromes, such as preeclampsia, placenta previa, and abruptio placentae, is high in ever smokers. Pregnant ever smokers who are >35 years and belong to the lower one-third of the economic division require special care to prevent the development of placenta-associated syndromes.
Abruptio Placentae ; Alcohol Drinking ; Confounding Factors (Epidemiology) ; Female ; Humans ; Insurance ; Korea ; Logistic Models ; Maternal Age ; Odds Ratio ; Placenta ; Placenta Previa ; Pre-Eclampsia ; Pregnancy ; Smoke ; Smoking

BACKGROUND: Chronic kidney disease (CKD)-mineral and bone disorder (MBD) and fracture risk are both closely related to declining renal function. Controlling hyperphosphatemia with phosphate binders is a basic principle of CKD-MBD treatment. The aim of this study was to identify differences in fracture risk between pre-dialysis CKD patients and end-stage renal disease (ESRD) on dialysis, and to evaluate the effects of phosphate binders on fracture risk in ESRD patients. METHODS: Data from a total of 89,533 CKD patients comprising CKD diagnosis, dialysis, fracture history, and phosphate binder prescription history from 2012 to 2016 were retrieved from the Health Insurance Review and Assessment Service Database. Multivariate Cox regression analyses were performed to identify whether dialysis or phosphate binders were associated with an increased fracture risk. RESULTS: Overall, the rate of fractures in pre-dialysis CKD patients was 74 per 1,000 patient-years, while that in dialysis patients was 84 per 1,000 patient-years. The risk of fracture in ESRD patients was higher than pre-dialysis CKD patients (hazard ratio, 1.16; 95% confidence interval, 1.12–1.21; P < 0.001) after adjusting for confounding variables. In addition, the fracture risk in patients who were not taking phosphate binders was 20.0% higher compared to ESRD patients taking phosphate binders. CONCLUSION: Fractures were more prevalent in ESRD patients on dialysis than pre-dialysis CKD patients. Use of phosphate binders was associated with a lower fracture risk in ESRD patients.
Cohort Studies ; Confounding Factors (Epidemiology) ; Diagnosis ; Dialysis ; Humans ; Hyperphosphatemia ; Insurance, Health ; Kidney Failure, Chronic ; Prescriptions ; Renal Insufficiency, Chronic

BACKGROUND: Several studies have suggested that breastfeeding has a positive effect on long-term obesity, diabetes, hypertension, and hyperlipidemia. This study aimed to examine maternal bone health, muscle mass, and obesity based on breastfeeding duration. METHODS: This study was based on the Korea National Health and Nutrition Examination Survey 2010–2011. We selected 2,027 elderly women by screening survey participants with a history of delivery. Multivariate logistic regression analyses were performed to estimate the odds ratios (ORs) of sarcopenia, osteoporosis, and obesity among four breastfeeding groups. RESULTS: The OR of sarcopenia significantly decreased with increasing breastfeeding duration (OR, 0.27; 95% confidence interval [CI], 0.11–0.65; P for trend <0.001), whereas the OR of obesity significantly increased with increasing breastfeeding duration (OR, 2.56; 95% CI, 1.43–4.60; P for trend=0.009) after adjusting for potential confounding variables. We also found a positive correlation between the duration since last delivery and sarcopenia. CONCLUSION: Our results suggest a negative correlation between prolonged breastfeeding and the prevalence of sarcopenia, and a positive correlation between prolonged breastfeeding and the prevalence of obesity. Further studies are needed to clarify the relationship between breastfeeding and sarcopenia in the future.
Aged ; Breast Feeding ; Confounding Factors (Epidemiology) ; Cross-Sectional Studies ; Female ; Humans ; Hyperlipidemias ; Hypertension ; Korea ; Logistic Models ; Mass Screening ; Nutrition Surveys ; Obesity ; Odds Ratio ; Osteoporosis ; Prevalence ; Sarcopenia

BACKGROUND: Cigarette smoking increases the risk of atherosclerosis, which often develops as vascular calcification on radiologic examinations. This study evaluated the relationship between smoking-related factors and incidental abdominal aorta calcification (AAC) detected by computed tomography (CT) among middle-aged and elderly men. METHODS: We assessed the abdominal CT findings of 218 men aged 40 to 81 years who underwent health checkups. The associations between smoking factors and AAC were analyzed using logistic regression analysis to adjust for confounding variables such as age, lifestyle factors, and chronic diseases. RESULTS: Adjusting for confounding variables, the risk of AAC was significantly increased in association with smoking for at least 20 years (adjusted odds ratio [AOR], 5.22; 95% confidence interval [CI], 1.82–14.93), smoking 10+ pack-years (10–20 pack-years: AOR, 4.54; 95% CI, 1.07–5.68; >20 pack-years: AOR, 5.28; 95% CI, 2.10–13.31), and a history of smoking (former smoker: AOR, 2.10; 95% CI, 1.07–5.68; current smoker: AOR, 5.05; 95% CI, 2.08–12.26). In terms of the daily smoking amount, even a low smoking level increased the risk of AAC. CONCLUSION: These findings suggest that smoking for 20+ years, smoking 10+ pack-years, and even a low level of smoking daily increases the likelihood of developing AAC. Clinicians should recommend that patients quit smoking and stress the importance of smoking duration when promoting health in middle-aged and elderly patients.
Aged ; Aorta, Abdominal ; Atherosclerosis ; Chronic Disease ; Confounding Factors (Epidemiology) ; Humans ; Life Style ; Logistic Models ; Male ; Odds Ratio ; Smoke ; Smoking ; Tomography, X-Ray Computed ; Vascular Calcification

BACKGROUND: Cancer survivors are at a higher risk of primary cancer recurrence and development of second primary cancer. In both cases, early disease detection is crucial. This cross-sectional study assessed cancer screening participation rates according to cancer history. METHODS: Data were obtained from the 2010–2012 Korea National Health and Nutrition Examination Survey for 12,500 participants. Of these, 624 cancer survivors were enrolled in this study. Sampling weights were applied to maintain the representativeness of the Korean adult population. RESULTS: Overall 2-year cancer screening rates prior to the survey in male and female cancer survivors were 59.9% and 73.7%, respectively, while opportunistic cancer screening rates were 33.5% and 52.1%, respectively. The odds ratios (95% confidence interval) of the overall cancer screening among the cancer survivors, compared to others, were 1.16 (0.79–1.72) in male and 1.78 (1.20–2.63) in female participants, after the adjustment for confounding variables. The odds ratios (95% confidence interval) for opportunistic cancer screening and National Cancer Screening Program among cancer survivors were 1.56 (1.07–2.27) and 0.80 (0.53–1.21) in males and 2.05 (1.46–2.88) and 0.66 (0.46–0.95) in females. CONCLUSION: Female cancer survivors showed a higher rate of overall and opportunistic cancer screening than did the male cancer survivors. Further efforts are required to improve cancer screening among male cancer survivors.
Adult ; Confounding Factors (Epidemiology) ; Cross-Sectional Studies ; Diagnosis ; Early Detection of Cancer ; Female ; Humans ; Korea ; Male ; Mass Screening ; Neoplasms, Second Primary ; Nutrition Surveys ; Odds Ratio ; Recurrence ; Survivors ; Weights and Measures

BACKGROUND: Exposure to secondhand smoke (SHS) has been shown to cause health problems. Recent studies demonstrated an association of SHS with depression and poor mental health. The urinary cotinine concentration (Ucot) is an objective indicator of exposure to SHS. In this study, we evaluated the association between depression and Ucot in adult non-smokers adults in Korea. METHODS: We analyzed the data of 3,417 adults, aged ≥19 years, who participated in the seventh Korea National Health and Nutrition Examination Survey (2016). The eligible subjects were non-smokers. Depression was evaluated using the Patient Health Questionnaire-9 (PHQ-9). The subjects were dichotomized into two groups: the high depressive symptom group (PHQ-9 ≥10 [n=185]) and the low depressive symptom group (PHQ-9 <10 [n=3,232]). The demographic, socioeconomic, and clinical characteristics of the subjects were retrieved from the survey data. Ucot was dichotomized into high-Ucot (≥10 ng/mL) and low-Ucot (<10 ng/mL). The Ucot and other characteristics were compared between the two groups. To adjust for confounding variables, we conducted a logistic regression analysis and determined the difference in Ucot between the two groups. RESULTS: After adjusting for confounders, the high depressive symptom group was found to be associated with high-Ucot (odds ratio, 1.824; 95% confidence interval, 1.020–3.262). Sex, education, socioeconomic status, marital status, occupational status, limitation of activity, and the presence of an underlying diseases (diabetes and dyslipidemia) had a significant effect on depression. CONCLUSIONS: This concluded that depression was associated with high urine cotinine level in adult non-smokers.
Adult ; Confounding Factors (Epidemiology) ; Cotinine ; Depression ; Education ; Employment ; Humans ; Korea ; Logistic Models ; Marital Status ; Mental Health ; Nutrition Surveys ; Social Class ; Tobacco ; Tobacco Smoke Pollution