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

BACKGROUND: Idiopathic scoliosis (IS) affects patients' quality of life, yet there have been few reports of its morphology and epidemiological study in the southeast region of China. The aim of this study is to access the curve characteristics, prevalence, and factors associated with IS in Chaozhou city. METHODS: A cross-sectional study was performed in 2018, in which scoliosis screening was conducted among 5497 primary school students in Chaozhou city. Then, a case-control study based on the screening involving 2547 children was followed for the exploration of the associated factors. The questionnaires covering demographic characteristics, postural habits, cognition and self-sensation of scoliosis, and physical conditions were addressed for the investigation. ORs with 95%CIs were calculated based on logistic regression analysis to evaluate the factors associated with scoliosis. RESULTS: The prevalence of IS among primary school students was 6.15% in Chaozhou city, with 4.04% for males and 8.71% for females. The average Cobb angle was 15° (range 8 to 37°). Multiple logistic regression analysis suggested that female (OR=2.45), BMI (OR=0.67), having myopia (OR=1.49), self-sensation of scoliosis with symptoms (OR=5.52), insufficient sleep time (OR=2.65, 3.33), and less exercise time (OR=7.09, 7.29) were significantly associated with IS. CONCLUSIONS The prevalence of IS among primary school students in Chaozhou was at an average level, and it was significantly higher in females than in males. Lower body mass, having myopia, insufficient sleep time, and lower physical activity were associated with IS.
Case-Control Studies ; Child ; China/epidemiology* ; Cross-Sectional Studies ; Epidemiologic Studies ; Female ; Humans ; Male ; Myopia/complications* ; Risk Factors ; Schools ; Scoliosis/physiopathology* ; Students

BACKGROUND: Given the important repercussions that sociodemographic factors can have on physical activity, especially in the field of leisure, and cardiometabolic risk, it seems relevant to analyze the implications of these variables on the relationship between physical activity in leisure time (LTPA) and cardiometabolic risk. In this sense, the present study aims to verify the moderating role of biologic and socioeconomic factors in the relationship between LTPA and cardiometabolic risk in adolescents in southern Brazil. METHODS: Cross-sectional study that included 1596 adolescents selected at random (58.2% girls), aged between 10 and 17 years. LTPA, biological and socioeconomic factors were assessed using a self-reported questionnaire and the cardiometabolic risk score (total cholesterol/HDL-c ratio, triglycerides, fasting glucose, systolic blood pressure, and waist circumference, considering the participant's age and sex) was included as an outcome. Associations and moderations were tested by multiple linear regression models. RESULTS: It was observed a positive interaction of LTPA and sex (p = 0.048) and LTPA and school system (p = 0.037), and negative interaction of LTPA and skin color (p = 0.040), indicating that these factors were moderators in the relationship between LTPA and clustered cardiometabolic risk score (cMetS) in adolescents. A reduction in cardiometabolic risk was observed according to the increase in weekly minutes of LTPA among boys, non-white adolescents, and students from municipal schools. CONCLUSIONS The association between LTPA and cardiometabolic risk was moderated by sex, skin color, and school system in adolescents from southern Brazil.
Adolescent ; Age Factors ; Brazil/epidemiology* ; Cardiometabolic Risk Factors ; Child ; Cross-Sectional Studies ; Effect Modifier, Epidemiologic ; Exercise ; Female ; Humans ; Leisure Activities ; Male ; Sex Factors ; Skin Pigmentation ; Socioeconomic Factors

Some patients with type 1 and type 2 diabetes mellitus (DM) present with cognitive dysfunctions. The pathophysiology underlying this complication is not well understood. Type 1 DM has been associated with a decrease in the speed of information processing, psychomotor efficiency, attention, mental flexibility, and visual perception. Longitudinal epidemiological studies of type 1 DM have indicated that chronic hyperglycemia and microvascular disease, rather than repeated severe hypoglycemia, are associated with the pathogenesis of DM-related cognitive dysfunction. However, severe hypoglycemic episodes may contribute to cognitive dysfunction in high-risk patients with DM. Type 2 DM has been associated with memory deficits, decreased psychomotor speed, and reduced frontal lobe/executive function. In type 2 DM, chronic hyperglycemia, long duration of DM, presence of vascular risk factors (e.g., hypertension and obesity), and microvascular and macrovascular complications are associated with the increased risk of developing cognitive dysfunction. The pathophysiology of cognitive dysfunction in individuals with DM include the following: (1) role of hyperglycemia, (2) role of vascular disease, (3) role of hypoglycemia, and (4) role of insulin resistance and amyloid. Recently, some investigators have proposed that type 3 DM is correlated to sporadic Alzheimer’s disease. The molecular and biochemical consequences of insulin and insulin-like growth factor resistance in the brain compromise neuronal survival, energy production, gene expression, plasticity, and white matter integrity. If patients claim that their performance is worsening or if they ask about the effects of DM on functioning, screening and assessment are recommended.
Amyloid ; Automatic Data Processing ; Brain ; Cognition ; Dementia ; Diabetes Mellitus ; Diabetes Mellitus, Type 2 ; Epidemiologic Studies ; Gene Expression ; Humans ; Hyperglycemia ; Hypertension ; Hypoglycemia ; Insulin ; Insulin Resistance ; Mass Screening ; Memory Disorders ; Neurons ; Plastics ; Pliability ; Research Personnel ; Risk Factors ; Vascular Diseases ; Visual Perception ; White Matter

OBJECTIVE: To investigate the epidemiology of sepsis in Korea and identify risk factors for death in sepsis.METHODS: We conducted a longitudinal, population-based epidemiological study of sepsis in Korea from 2005 to 2012 using the National Health Insurance Service-National Sample Cohort, a population-based cohort representing 2.2% of the Korean population. The primary objective was to assess the incidence, mortality and cost of sepsis. The secondary objective was to identify the risk factors for death in sepsis. Claim records of admitted adult patients (aged ≥15 years) were analyzed. Sepsis was defined as 1) bacterial or fungal infection or the conditions they often complicate, 2) prescription of intravenous antibiotics, and 3) presence of any organ dysfunction. Comorbidities were defined using the Charlson/Deyo method. Risk factors for 6-month mortality were assessed using multivariable logistic regression.RESULTS: A total of 22,882 cases were identified. Both incidence and 6-month mortality increased from 265.7 (95% confidence interval [CI], 254.7 to 277.1) to 453.1 (95% CI, 439.0 to 467.5) per 100,000 person-years (P-trend <0.001) and from 26.5% (95% CI, 24.4% to 28.8%) to 30.1% (95% CI, 28.4% to 31.9%), respectively. After standardization, the increasing trend of incidence was slower but still significant (P-trend <0.001), while that for mortality was not (P-trend 0.883). The average cost increased by 75.5% (P-trend <0.001). Multivariable logistic regression identified various risk factors for mortality.CONCLUSION: The burden of sepsis in Korea was high and is expected to increase considering the aging population. Proactive measures to curtail this increase should be sought and implemented.
Adult ; Aging ; Anti-Bacterial Agents ; Cohort Studies ; Comorbidity ; Epidemiologic Studies ; Epidemiology ; Humans ; Incidence ; Korea ; Logistic Models ; Methods ; Mortality ; National Health Programs ; Prescriptions ; Risk Factors ; Sepsis

PURPOSE: This study aimed to investigate the molecular epidemiology of a methicillin-resistant Staphylococcus aureus (MRSA) outbreak at a newborn nursery and neonatal intensive care unit (NICU).METHODS: During the outbreak, from August to September 2017, MRSA isolates collected from neonates and medical staff underwent genotyping and screened for virulence factors. Antibiotic susceptibilities were tested.RESULTS: During the study period, 41 neonates were admitted at the nursery (n=27) and NICU (n=14). Of these, 7 had MRSA infections (skin infection [n=6] and sepsis [n=1]) and 4 were colonized with MRSA. Associated medical staff (n=32) were screened; three were nasal MRSA carriers. Staphylococcal chromosomal cassette mec (SCCmec) type II, sequence type (ST) 89, spa type t375 was found to be the skin infection outbreak causing strain, with multi-drug resistance including low-level mupirocin resistance. SCCmec type IVa, ST 72, and a novel spa type designated t17879, was the cause of MRSA sepsis. Many different types of MRSA were colonized on the neonates; however, SCCmec type IVa, ST 72, spa type t664 was colonized in both neonates and a NICU nurse. All MRSA isolates from colonized infants were positive for the Panton-Valentine leukocidin (PVL) toxin gene.CONCLUSIONS: The strain causing an outbreak of skin infections had multi-drug resistance. Also, MRSA colonized in the neonates were found to carry the PVL toxin gene. Because different strains are present during an outbreak, molecular epidemiologic studies are important to identify the outbreak strain and colonized strains which aid in effective control and prevention of future MRSA outbreaks.
Colon ; Disease Outbreaks ; Drug Resistance, Multiple ; Epidemiologic Studies ; Humans ; Infant ; Infant, Newborn ; Intensive Care, Neonatal ; Leukocidins ; Medical Staff ; Methicillin Resistance ; Methicillin-Resistant Staphylococcus aureus ; Molecular Epidemiology ; Mupirocin ; Nurseries ; Sepsis ; Skin ; Virulence Factors

The increasing risk of glucose intolerance and diabetes associated with aging is well established. However, it is difficult to determine whether changes in glucose metabolism result from biological aging itself or due to various environmental factors that occur during the aging process. Many epidemiologic studies have shown that plasma glucose levels after oral glucose tolerance test rise consecutively for every decade of age, but many of these studies also demonstrated the effects of environmental factors including obesity and exercise. In some studies, the development of insulin resistance and insulin secretion defects due to biological aging itself have also been identified as major etiologic factors of glucose intolerance. However, the rate of diabetes development due to these factors is expected to be very slow and largely preventable by addressing environmental risk factors.
Aging ; Blood Glucose ; Carbohydrate Metabolism ; Epidemiologic Studies ; Glucose Intolerance ; Glucose Tolerance Test ; Glucose ; Incretins ; Insulin ; Insulin Resistance ; Metabolism ; Obesity ; Risk Factors

BACKGROUND: Colon cancer is one of the main causes of mortality. Early adenomatous colon polyp is a precursor of colon cancer through the ‘adenomacarcinoma sequence.’ Epidemiological studies suggest that the neutrophil to lymphocyte ratio can be one of useful inflammatory markers in clinical settings. This study aimed to evaluate the association between neutrophil to lymphocyte ratio and development of early adenomatous colon polyps.METHODS: This cross-sectional study retrospectively examined 960 middle-aged and elderly individuals aged ≥45 years who underwent colonoscopy in a health examination program. Multivariate logistic regression was used to analyze the association between neutrophil to lymphocyte ratio and development of early adenomatous colon polyps.RESULTS: Among the 960 subjects, the prevalence of early adenomatous polyps was 20.7% (n=199). The mean age, body mass index, number of current smokers, white blood cell count, triglyceride level, and number of subjects receiving hypolipidemic drugs were higher in the group with early adenomatous polyps than in the multivariate analysis, the odds ratio (95% confidence interval) for the development of early adenomatous polyps was 1.23 (1.01–1.50) with neutrophil to lymphocyte ratio increment after adjusting the confounding variables (P=0.037).CONCLUSION: We found that the neutrophil to lymphocyte ratio was associated with the development of early adenomatous colon polyps among middle-aged and elderly individuals. Accordingly, this result suggests that regular monitoring of early adenomatous colon polyps may be useful among individuals with a higher neutrophil to lymphocyte ratio.
Adenomatous Polyps ; Aged ; Body Mass Index ; Colon ; Colonic Neoplasms ; Colonic Polyps ; Colonoscopy ; Confounding Factors (Epidemiology) ; Cross-Sectional Studies ; Epidemiologic Studies ; Humans ; Hypolipidemic Agents ; Korea ; Leukocyte Count ; Logistic Models ; Lymphocytes ; Middle Aged ; Mortality ; Multivariate Analysis ; Neutrophils ; Odds Ratio ; Polyps ; Prevalence ; Retrospective Studies ; Triglycerides

BACKGROUND: Several contradictory studies exist on the relationship between raising grandchildren and the grandparent's health. The present study identified the association between raising grandchildren and depression among Korean grandparents.METHODS: The wave 1 (2006) and wave 2 (2008) databases of the Korean longitudinal study on aging (KLoSA) were analyzed. T-test and chi-square test were used to compare the demographics and health condition variable between the two groups based on the presence or absence of raising grandchildren. Logistic regression analysis, including demographics and health conditions, was conducted to identify the relationship between depression and raising grandchildren. Depression was assessed using the Center for Epidemiologic Studies Depression scale (CES-D-10).RESULTS: In all, 4,784 participants (4,636: not raising grandchildren; 148: raising grandchildren) were examined. Significantly lower CES-D-10 scores (3.34 vs. 4.35, P<0.001), and therefore, lower depression (25% vs. 39.9%, P<0.001) was found among grandparents raising grandchildren than those who did not raise grandchildren. After adjusting the confounding variables through logistic regression analysis, the odds ratio of depression when raising grandchildren was 0.57 (95% confidence interval=0.37–0.89), which indicates significant relevance.CONCLUSION: The results show lower depressive symptoms among grandparents raising grandchildren. Even after adjusting the variables, the results presented a lower risk of depression among them.
Adult ; Aging ; Confounding Factors (Epidemiology) ; Demography ; Depression ; Epidemiologic Studies ; Grandparents ; Humans ; Logistic Models ; Longitudinal Studies ; Odds Ratio