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: 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

OBJECTIVES: Nicotine narrows uterine blood vessels reducing the flow of oxygen and nutrients to the developing fetus. This study examined the effects of fetal exposure to secondhand smoke on neonatal anthropometry. METHODS: This cross sectional study recruited 128 pregnant women in the third trimester of single pregnancies who had no chronic illness, were not active or ex-smokers, and who were willing to participate in the study. Pregnant women who were exposed to secondhand smoke had umbilical cord blood nicotine concentrations of ≥ 1 ng/mL. Neonatal anthropometry was assessed according to the newborn birth weight and length. The independent t-test was used to determine the neonatal difference in mean birth weight and length between the women who were exposed to secondhand smoke, and those who were not exposed. A multiple linear regression analysis was employed to assess the effect of secondhand smoke exposure on birth weight and birth length, controlling for potential confounding variables (weight gain during pregnancy, body mass index, parity, maternal age, and maternal hemoglobin). RESULTS: There were 35 women exposed to secondhand smoke (nicotine ≥ 1 ng/mL). Neonate birth weight and birth length were lower among mothers who were exposed to secondhand smoke. However, only neonate birth weight was significantly reduced by exposure to secondhand smoke (p = 0.005). The mean birth weight of these neonates was 2,916.5 g ± 327.3 g which was 205.6 g less than in unexposed fetuses. CONCLUSION: Exposure of mothers to secondhand smoke during pregnancy reduces fetal development and neonatal weight.
Anthropometry ; Birth Weight ; Blood Vessels ; Body Mass Index ; Chronic Disease ; Confounding Factors (Epidemiology) ; Female ; Fetal Blood ; Fetal Development ; Fetus ; Humans ; Infant, Newborn ; Linear Models ; Maternal Age ; Mothers ; Nicotine ; Oxygen ; Parity ; Parturition ; Pregnancy ; Pregnancy Trimester, Third ; Pregnant Women ; Tobacco Smoke Pollution ; Umbilical Cord

Our study aimed to analyze the clinical characteristics and psychotropic prescription patterns of a history of suicide attempts in South Koreans with bipolar disorder (BD), by using only Korean data from the Research on Asian Psychotropic Prescription Pattern for Bipolar disorder. The patterns of clinical characteristics and psychotropic drug use were compared among 53 patients with a history of suicide attempts and 297 without this history; the potential effects of confounding variables were adjusted with binary logistic analyses for discrete variables and analyses of covariance for continuous variables. After adjusting the effects of age, sex, duration of illness, and enrollment as an outpatient, patients with a history of suicide attempts were characterized by a significantly more prevalent depressive episode, lower prevalent remission state, lower levels of hemoglobin, and more use of antidepressants, anxiolytics, and hypnotics compared to those without lifetime suicide attempt. The inability to plan goal-directed behavior may be an intervening factor in the relationship between suicide attempts and depression in BD. Relatively low hemoglobin levels can be associated with manic episodes in patients with a history of suicide attempts and the use of antidepressants, anxiolytics, or hypnotics can be associated with suicide attempts in BD patients.
Anti-Anxiety Agents ; Antidepressive Agents ; Asian Continental Ancestry Group ; Bipolar Disorder ; Confounding Factors (Epidemiology) ; Depression ; Drug Prescriptions ; Humans ; Hypnotics and Sedatives ; Korea ; Outpatients ; Prescriptions ; Suicide

OBJECTIVE: This study aimed to examine the association between normal-but-low folate levels and cognitive function in the elderly population using a prospective cohort study. METHODS: We analyzed 3,910 participants whose serum folate levels were within the normal reference range (1.5–16.9 ng/mL) at baseline evaluation in the population-based prospective cohort study named the “Korean Longitudinal Study on Cognitive Aging and Dementia.” The association between baseline folate quartile categories and baseline cognitive disorders [mild cognitive impairment (MCI) or dementia] was examined using binary logistic regression analysis adjusting for confounding variables. The risks of incident MCI and dementia associated with the decline of serum folate level during a 4-year follow-up period were examined using multinomial logistic regression analysis. RESULTS: The lowest quartile group of serum folate (≥1.5, ≤5.9 ng/mL) showed a higher risk of cognitive disorders than did the highest quartile group at baseline evaluation (odds ratio 1.314, p=0.012). Over the 4 years of follow-up, the risk of incident dementia was 2.364 times higher among subjects whose serum folate levels declined from the 2nd–4th quartile group to the 1st quartile than among those for whom it did not (p=0.031). CONCLUSION: Normal-but-low serum folate levels were associated with the risk of cognitive disorders in the elderly population, and a decline to normal-but-low serum folate levels was associated with incident dementia. Maintaining serum folate concentration above 5.9 ng/mL may be beneficial for cognitive status.
Aged ; Cognition ; Cognition Disorders ; Cognitive Aging ; Cohort Studies ; Confounding Factors (Epidemiology) ; Dementia ; Folic Acid ; Follow-Up Studies ; Humans ; Logistic Models ; Longitudinal Studies ; Prospective Studies ; Reference Values

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