The condition of critically ill patients changes rapidly, involving pathological changes in multiple systems and organs throughout the body. Exploring the causal relationship of mechanisms can further reveal etiology, treatment, and prognosis of diseases. However, traditional prospective studies in the field of critical care are still subject to numerous limitations. As an emerging research method, Mendelian randomization (MR) analysis uses genetic variation to provide causal evidence for instrumental variables, which is expected to provide clues in critical diseases. This article systematically describes the research progresson the application of MR analysis in critical care medicine from four aspects: the principle of MR analysis, the difference between MR analysis and randomized controlled trial (RCT), the use of MR analysis in the field of critical illness, and the possible methods of application, aiming to provide possible directions for the research in this field.
Humans ; Mendelian Randomization Analysis/methods* ; Genetic Variation ; Causality ; Research Design

Community-acquired pneumonia (CAP) is the third leading cause of death worldwide and one of the most commonly infectious diseases. Its epidemiological characteristics vary with host and immune status, and corresponding pathogen spectrums migrate over time and space distribution. Meanwhile, with the outbreak of COVID-19, some unconventional treatment strategies are on the rise. This article reviewed the epidemiological characteristics, pathogen spectrum and treatment direction of CAP in China over the years, and aimed to provide guidance for the diagnosis and treatment of CAP in clinical practice.
Humans ; COVID-19 ; Pneumonia/diagnosis* ; Community-Acquired Infections/drug therapy* ; Causality ; Risk Factors

Childhood obesity is a global public health problem, which can not only endangers children's health, but also might be an important cause of chronic diseases in adulthood. In recent years, with the in-depth development of precision medicine research, more and more research evidences have shown that there are interactions between environmental factors, such as early intrauterine environment, children's diet, physical activity and children's gene factor on the incidence of childhood obesity, which can result in or inhibit the incidence and development of childhood obesity. This paper summarizes the progress in research in this field to reveal the effects and potential mechanisms of genetic factors and environmental factors on the incidence of childhood obesity in order to provide reference for the precise prevention and control of childhood obesity under different genetic backgrounds.
Child ; Humans ; Pediatric Obesity/genetics* ; Diet ; Causality ; Exercise ; Public Health

International research on healthy life expectancy (HALE) focuses on inequality of socioeconomic status and individual natural attributes. With the acceleration of population ageing and the increase in average life expectancy, the extension of unhealthy life expectancy and the increase of social and economic burden caused by diseases have gradually attracted the attention of countries around the world. Therefore, the evaluation of disease factors affecting HALE is a meaningful direction in the future. This study introduces the development process and commonly used measurement methods of HALE. According to the definition of health from the Global Burden of Disease Study and World Health Organization, physical and mental diseases such as cardiovascular and cerebrovascular diseases, chronic respiratory diseases, diabetes, malignant tumors and depression were selected to summarize the impact of these diseases and pre-disease states on HALE. It is expected to provide a theoretical basis for the formulation of relevant public health policies and the improvement of quality of life in China.
Humans ; Healthy Life Expectancy ; Quality of Life ; Life Expectancy ; Causality ; Social Class

Objective: To explore the causal effects of the serum Vitamin D levels on the risk of systemic lupus erythematosus (SLE). Methods: A two-sample Mendelian randomization (MR) study was performed to infer the causality. Three Genome-wide association studies (GWAS) for circulating Vitamin D levels, including 25-hydroxyvitamin D [25(OH)D], 25-hydroxyvitamin D₃ [25(OH)D₃] and C3-epimer of 25-hydroxyvitamin D₃ [C3-epi-25(OH)D₃] published in 2020, and one GWAS for SLE published in 2015 were utilized to analyze the causal effects of the serum Vitamin D levels on the risk of SLE. MR analyses were conducted using the inverse-variance weighted method (IVW), weighted median, MR-Egger methods, MR-pleiotropy residual sum and outlier (MR-PRESSO) method. Results: 34, 29 and 6 SNPs were respectively selected as instrumental variables to analyze the causal association of total 25 (OH) D level, 25 (OH) D₃ level and C3-epi-25 (OH) D₃ level with the risk of SLE. The MR results showed that each standard deviation decrease in the level of 25(OH)D₃ would result in 14.2% higher risk of SLE (OR, 0.858; 95%CI, 0.753-0.978; P=0.022). The levels of 25(OH)D and C3-epi-25(OH)D₃ had null associations with risk of SLE (OR, 0.849; 95%CI, 0.653-1.104; P=0.222; OR, 0.904; 95%CI, 0.695-1.176; P=0.452). Conclusion: This study have identified a causal effect of 25(OH)D₃ on increased risk of SLE. These findings highlighted the significance of active monitoring and prevention of SLE in population of low Vitamin D levels.
Humans ; Genome-Wide Association Study ; Vitamin D ; Lupus Erythematosus, Systemic/complications* ; Vitamins ; Causality ; Mendelian Randomization Analysis/methods* ; Polymorphism, Single Nucleotide

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

Objective: To determine the causal association between long-term Nitrogen dioxide (NO₂) exposure and the risk of cardiovascular hospitalization. Methods: Based on a sub-cohort of a community-based prospective cohort study, a total of 36 271 participants were recruited from 35 communities randomly selected in Guangzhou in 2015. The annual average exposure of NO₂, demographic characteristics, lifestyle factors, and information on the causes of hospitalization was collected. We applied marginal structural Cox models to investigate the effect of NO₂ on cardiovascular hospitalization. Demographic and behavioral factors also stratified results. Results: The mean age of participants in the present study was (50.9±17.8) years, and the cardiovascular admission rate was 8.7%, with 203 822 person-years of follow-up. The annual mean NO₂ concentration was 48.7 μg/m³ during 2015-2020. For each 10 μg/m³ increase in NO₂ concentrations, the HRs (95%CIs) of total cardiovascular hospitalization, cardiovascular hospitalization, and cerebrovascular hospitalization were 1.33 (1.16-1.52), 1.36 (1.16-1.60) and 1.25 (1.00-1.55), respectively. Participants who were never married/married, with secondary education, high exercise frequency, or non-smokers/current smokers may be more susceptible than their counterparts. Conclusion: Long-term exposure to NO₂ significantly increased hospitalization risk for cardiovascular disease.
Humans ; Adult ; Middle Aged ; Aged ; Nitrogen Dioxide ; Prospective Studies ; Cardiovascular Diseases/epidemiology* ; Causality ; Hospitalization

BACKGROUND: A Japanese woman in her early twenties had committed suicide, jumped from a 25-meter high bridge into a lake. She had been suffering from severe dysmenorrhea and general fatigue monthly. RESULTS: A forensic autopsy revealed indications of a bicorporeal uterus, obstructed hemi-vagina, and ipsilateral renal agenesis, which lead to a diagnosis of obstructed hemi-vagina and ipsilateral renal anomaly (OHVIRA) syndrome. On the right side of the uterus, an enclosed cavity composed of black clots was observed. Histological findings suggested that her endometrium was in the early proliferative phase, implying that she was in the menstrual phase just before her death. She may have been suffering from severe lower abdominal pain from the increased pressure of the closed uterus cavity. CONCLUSIONS This case indicates that dysmenorrhea from undiagnosed OHVIRA syndrome can possibly lead to a suicide attempt. In Japan, because suicide was the leading cause of death for people aged 15 to 39 in 2019, preventive measures for suicide should be promoted. The present case also suggests that intervention for dysmenorrhea may prevent this in adolescent woman.
Adult ; Causality ; Dysmenorrhea/etiology* ; Female ; Humans ; Kidney ; Syndrome ; Vagina ; Young Adult

Estimating the actual real-world effectiveness of the vaccine is an essential part of the post-marketing evaluation. This regression discontinuity design (RDD) using observational data is designed to quantify the effect of an intervention when eligibility for the intervention is based on a defined cutoff as age, making it suited to estimate vaccine effects. This approach can avoid the high cost and ethical issues; overcome difficulties in the organization and practice process in randomized controlled trials, which leads to a higher level of causal inference evidence and more realistic results. Here, we describe key features of RDD in general, and then specific scenarios, with examples, to illustrate that RDD are an essential tool for advancing our understanding of vaccine effects.
Causality ; Humans ; Vaccine Efficacy ; Vaccines

Among kinds of methods for causal inference in observational studies, the propensity score (PS) method to control measured confounding is more widely used. PS method usually consists of two critical steps: first, estimating the propensity score, followed by calculating the causal parameters of interest by regression, weighting, matching, and stratification. Unlike the traditional dichotomous treatment, the generalized propensity scoring estimator used for continuous treatment has been proposed in recent years. Many methods have been developed to estimate the generalized propensity score or even estimate the balancing weight directly. This paper introduces the existing estimators from both the model-based and balance-based perspectives.
Causality ; Computer Simulation ; Humans ; Propensity Score ; Research Design