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

BACKGROUND: Shift work is associated with a higher risk of cardiovascular diseases. Here, we sought to assess the relationship between shift work and plasma homocysteine levels. Determining the correlations between shift work and homocysteine levels may provide a better understanding of the mechanisms underlying cardiovascular diseases. METHODS: This study was performed using data from routine health examinations of steel workers in 2017. In total, 431 male workers (70 daytime workers and 361 shift workers) employed on a rolling departure schedule were recruited. Plasma homocysteine levels > 15 μmol/L were considered elevated. The χ2, analysis of variance, and multiple logistic regression analyses were used to examine the association between shift work and plasma homocysteine levels. RESULTS: In comparison to daytime workers, the odds ratio (OR) of hyperhomocysteinemia in individuals with < 10 years of shift work was 1.14 (95% confidence interval [CI]: 0.64–2.03), compared to 2.01 (95% CI: 1.14–3.54) for workers with ≥ 10 years of experience. After adjusting for confounding variables, the adjusted OR for shift workers with < 10 years of experience was 0.95 (95% CI: 0.50–1.80), compared to 2.00 (95% CI: 1.07–3.74) for workers with ≥ 10 years of experience. CONCLUSIONS: The risk of hyperhomocysteinemia was significantly higher in shift workers compared to those working normal daytime hours, particularly among long-term shift workers.
Appointments and Schedules ; Cardiovascular Diseases ; Confounding Factors (Epidemiology) ; Homocysteine ; Humans ; Hyperhomocysteinemia ; Logistic Models ; Male ; Odds Ratio ; Plasma ; Steel

OBJECTIVES: The purpose of this study was to investigate the association between the components of metabolic syndrome (MetS) (waist circumference, hyperglycemia, hypertriglyceridemia, low levels of high-density lipoprotein cholesterol, and hypertension) and periodontitis in Korean adults aged 35–79 years. METHODS: In this study, data from the Sixth Korean National Health and Nutrition Examination Survey (KNHANES, 2013–2015) were analyzed. Among the 22,948 participants of the Sixth KNHANES, 8,314 participants, who were aged 35–79 years and had completed all systemic and oral health examinations and questionnaires, were included in this study. Confounding variables associated with the demographics and socioeconomic status and systemic and oral health-related behaviors were age, gender, household income, the educational level, smoking and drinking habits, the physical activity status, and frequency of daily toothbrushing. The independent variables were components of MetS, and the dependent variable was periodontitis. RESULTS: Periodontitis was diagnosed in 37.0% of the participants. The incidence of periodontitis among participants with MetS was 47.9%. The incidences of periodontitis among participants with three, four, and five components of MetS were 44.8%, 50.0%, and 56.2%, respectively. The odds ratio (OR) for periodontitis among participants with MetS was 1.43 (95% confidence interval [CI]: 1.27–1.61). The participants with three, four, and five components of MetS showed a significantly higher OR for periodontitis than those with no components of MetS (three components, OR=1.18, 95% CI: 1.02–1.36; four components, OR=1.34, 95% CI: 1.14–1.59; five components, OR=1.68, 95% CI: 1.29–2.20). CONCLUSIONS: A higher number of components of MetS augments the OR of periodontitis.
Adult ; Cholesterol ; Confounding Factors (Epidemiology) ; Demography ; Drinking ; Epidemiology ; Family Characteristics ; Humans ; Hyperglycemia ; Hypertriglyceridemia ; Incidence ; Lipoproteins ; Motor Activity ; Nutrition Surveys ; Odds Ratio ; Oral Health ; Periodontitis ; Smoke ; Smoking ; Social Class ; Toothbrushing

PURPOSE: This study examined the changes in the nutrient intake and the prevalences of obesity and metabolic syndrome according to the eating alone behavior in middle-aged men and women. METHODS: The data from the 2013 ~ 2017 Korean National Health and Nutrition Examination Survey were analyzed. A total of 7,728 adults (3,404 male, 4,324 female) aged 40 ~ 64 years old were included. The subjects were classified into three groups according to the number of times eating alone per day (0, 1 ~ 2, and 3 times/day). Dietary data were collected by a 1-day 24-h recall. The nutrient intakes were compared among the three groups. Survey logistic regression analyses were conducted to examine the association of the eating alone behavior with obesity and metabolic syndrome, adjusting for the related confounding variables. RESULTS: In men, eating alone was associated significantly with a lower intake of potassium (p-for-trend = 0.048) and lower intake of calories from protein (p-for-trend = 0.04). In women, the proportion of subjects consuming energy less than 75% of the estimated energy requirement (p = 0.001) and less than the estimated adequate requirement of riboflavin (p < 0.001) differed significantly according to the eating alone behavior. The eating alone behavior was positively associated with an increased risk of developing metabolic syndrome (p-for-trend = 0.033), increased blood pressure (p-for-trend < 0.001), and increased waist circumference (p-for-trend = 0.004). On the other hand, in women, however, the eating alone behavior was associated with a decreased risks of developing obesity (p-for-trend = 0.02). No association was found between the eating alone behavior and the risk of metabolic syndrome in women. CONCLUSION: These results suggest that the eating alone behavior is a risk factor for the development of metabolic syndrome in middle-aged Korean men.
Adult ; Blood Pressure ; Confounding Factors (Epidemiology) ; Eating ; Female ; Hand ; Humans ; Logistic Models ; Male ; Nutrition Surveys ; Obesity ; Potassium ; Prevalence ; Riboflavin ; Risk Factors ; Waist Circumference

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

OBJECTIVE: In this study, we evaluated the prevalence of allergic disease in offsprings delivered via the delivery modes of vaginal delivery vs. planned Cesarean section vs. Cesarean section with labor. METHODS: This study included 175 mother-neonate pairs from Severance Hospital who were enrolled in the Cohort for Childhood Origin of Asthma and allergic diseases study. Information regarding prenatal environmental factors, delivery, and diagnosis of allergic diseases was obtained from a questionnaire and medical record review. Patients with at least 3 years of follow-up data were included in this study. Results were adjusted for sex, birth weight, gestational age at birth, season of birth, neonatal intensive care unit admission, parity, breastfeeding, and maternal factors. RESULTS: A total of 175 offsprings were eligible for analysis. Among the subjects, 52.0% were delivered by vaginal delivery, 34.3% by planned Cesarean section, and 16.6% by Cesarean section with labor. Fifty-nine offsprings (33.7%) were diagnosed with allergic disease at a median age of 1 year (range 0.5–3 years). The prevalence of allergic disease was not associated with delivery mode after adjusting for confounding variables. Time period from membrane rupture to delivery, duration of the active phase, and the beginning of the pelvic division prior to Cesarean section were not associated with allergic disease development in offsprings. CONCLUSION: Cesarean section, irrespective of the occurrence of labor before surgery, did not increase the prevalence of allergic disease in infants up to 3 years of age.
Asthma ; Birth Weight ; Breast Feeding ; Cesarean Section* ; Cohort Studies ; Confounding Factors (Epidemiology) ; Diagnosis ; Female ; Follow-Up Studies ; Gestational Age ; Humans ; Infant ; Infant, Newborn ; Intensive Care, Neonatal ; Medical Records ; Membranes ; Parity ; Parturition ; Pregnancy ; Prevalence* ; Rupture ; Seasons

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