Risk of acute kidney injury following contrast-enhanced CT or MRI in a cohort of 3061 hospitalized children in China.

OBJECTIVES: To compare the risk of acute kidney injury (AKI) between hospitalized children who received intravenous contrast media for imaging examinations and those who did not. METHODS: This retrospective cohort study enrolled patients aged 0-18 years with serum creatinine levels before and after imaging examinations from 2015 to 2020 at Beijing Children's Hospital. Participants were classified into an exposure group or a control group. Log-binomial regression analysis was used to estimate the adjusted risk ratio (aRR) value for the association between exposure to contrast media and consequential AKI. After which, inverse probability treatment weighting was used to reduce systematic differences in baseline characteristics among the groups. Moreover, subgroup and sensitivity analyses were performed. Finally, multivariate logistic regression analysis was performed to identify risk factors for pediatric AKI. RESULTS: In total, 3061 pediatric patients were included in the analyses (median age, 4.5 [IQR, 1.3-8.9] years, 1760 males). According the KDIGO definition of AKI, the incidence of AKI in the exposure group, and the control group were 7.4% and 6.5%, respectively; furthermore, the aRR was 1.35 (95% CI: 1.31-1.39). In patients underwent CT, the risk of AKI in the exposure group of contrast media increased compared with the control group and the aRR was 1.39 (95% CI: 1.09-1.78). However, it is not observed in patients underwent MRI (aRR: 1.36; 95% CI: 0.96-1.95). According to our subgroup analysis of pediatric patients aged ≥ 2 years (aRR: 1.38; 95% CI: 1.05-1.82) and sensitivity analysis (aRR: 1.32, 95% CI: 1.08-1.61), the risk of AKI in the exposure group was greater than that in the control group. An increased risk to exposure to contrast media was seen in females (aRR: 1.41, 95% CI: 1.05-1.89) rather than males (aRR: 1.30, 95% CI: 0.99-1.70). According to the multivariate logistic regression analyses, the baseline eGFR (OR: 1.02; 95% CI: 1.01-1.03) and comorbidities (OR: 2.97; 95% CI: 1.89-4.65) were risk factors, while age (OR: 0.87; 95% CI: 0.84-0.91) was a protective factor against AKI. CONCLUSION: The evidence from the present study suggested that the increased risk of AKI in hospitalized children induced by intravascular contrast should not be ignored.

Indirect estimation of pediatric reference interval via density graph deep embedded clustering.

Establishing reference intervals (RIs) for pediatric patients is crucial in clinical decision-making, and there is a critical gap of pediatric RIs in China. However, the direct sampling technique for establishing RIs is resource-intensive and ethically challenging. Indirect estimation methods, such as unsupervised clustering algorithms, have emerged as potential alternatives for predicting reference intervals. This study introduces deep graph clustering methods into indirect estimation of pediatric reference intervals. Specifically, we propose a Density Graph Deep Embedded Clustering (DGDEC) algorithm, which incorporates a density feature extractor to enhance sample representation and provides additional perspectives for distinguishing different levels of health status among populations. Additionally, we construct an adjacency matrix by computing the similarity between samples after feature enhancement. The DGDEC algorithm leverages the adjacency matrix to capture the interrelationships between patients and divides patients into different groups, thereby estimating reference intervals for the potential healthy population. The experimental results demonstrate that when compared to other indirect estimation techniques, our method ensures the predicted pediatric reference intervals in different age and gender groups are closer to the true values while maintaining good generalization performance. Additionally, through ablation experiments, our study confirms that the similarity between patients and the multi-scale density features of samples can effectively describe the potential health status of patients.

Evaluation of glomerular filtration rate estimation equations based on serum creatinine in healthy Chinese children and adolescents: a nationwide cross-sectional study.

BACKGROUND: Several equations for glomerular filtration rate (GFR) estimation based on serum creatinine (SCr) have been proposed for children, but most were developed among patients with kidney disease. The association between SCr and GFR may be distorted by kidney dysfunction and thus not applicable to healthy children. This study aimed to evaluate the applicability of existing SCr-based GFR estimation equations in healthy Chinese children. METHODS: GFR estimation equations that developed in healthy children were mainly analysed, including the Flanders Metadata (FM), simple height-independent (Simple), full age spectrum (FAS) and FAS-height equations. The FM equation assumed that GFR is proportional to the ratio of height to SCr. The Simple, FAS and FAS-height equations assumed that the ratio of GFR to population mean is equal to the reciprocal ratio of SCr to population mean (denoted by Q). Estimated GFR were calculated using data of SCr, age, sex and height collected from 12 208 healthy Chinese children aged 3 months to <20 years. The performance of GFR estimation equations was evaluated by the sex and age distribution of the estimated GFR and the deviation from the measured GFR reported by other literatures. RESULTS: The FM and Simple equations performed well in their applicable age of 1 month to 14 years, but presented undesirable sex difference after adolescence. The FAS and FAS-height equations showed reasonable development trend of estimated GFR throughout childhood, and the FAS equation had higher consistency than the FAS-height equation compared with measured GFR in healthy children. The GFR estimated by the FAS equation increased with age before 2 years, and reached the adult level thereafter without important sex difference. CONCLUSIONS: The FAS equation is applicable to healthy Chinese children.

Is the Tradeoff between Folic Acid or/and Multivitamin Supplementation against Birth Defects in Early Pregnancy Reconsidered? Evidence Based on a Chinese Birth Cohort Study.

BACKGROUND: Several studies have reported conflicting results on the association between maternal exposure to folic acid (FA) and/or multivitamin (MV) supplements and the risk of birth defects (BDs), especially for different subtypes of BDs. The present study aimed to identify the association between maternal exposure to FA or/and MV and BDs in offspring. METHODS: In the Chinese Birth Cohort Study initiated from 20 November 2017, 120,652 pregnant women completed follow-up until 20 August 2021. The participants were classified into four groups: without exposure to FA and MV, exposure to only FA, exposure to only MV, and exposure to FA and MV. Birth defects were coded by the International Classification of Diseases (ICD)-10. In order to explore the structural relationship between maternal FA or MV supplements and BDs, directed acyclic graphs were drawn. Then, an inverse probability treatment weighting was utilized to reduce the systematic differences in the baseline characteristics among the different groups. Lastly, a two-level mixed-effect log binomial regression analysis was used to estimate the relative risk (RR) value of the different subtypes of BDs under different exposures to FA and/or MV. RESULTS: Compared with the maternal group without exposure to FA and MV, the RR values of nervous system defects, face, ear, and neck defects, limb defects, and CHDs in the maternal group with only FA supplementation were less than 1.0, but they were not statistically significant. The RR values of genitourinary defects, abnormal chromosomes, and oral clefts were more than 1.0, and they were also not statistically significant. However, the risk of genitourinary defects (RR: 3.22, 95% CI: 1.42-7.29) and chromosomal abnormalities (RR: 2.57, 95% CI: 1.16-5.73) in the maternal group with only MV supplementation increased more than those in the maternal group without exposure to FA and MV. In addition, the RR values of all subtypes of BDs in the maternal group with exposure to FA and MV were closer to 1.0 than those in maternal group with exposure to only MV, but they were not statistically significant. CONCLUSIONS: It was indicated that the simultaneous supplementation of FA and MV in early pregnancy may have an interaction for the prevention of BDs and may have inconsistent effects for different subtypes of BDs. At the same time, excessive FA supplementation in pregnant women may increase the risk of BDs in their offspring. Although the mechanism is not clear, this evidence reminded us that more trade-offs are necessary for formulating strategies for the prevention of BDs with FA and/or MV supplementation in early pregnancy.

Chinese pediatric and adolescent reference intervals of vitamin E based on real-world physical examination data.

OBJECTIVES: To establish the reference interval (RI) of vitamin E for Chinese children and adolescents. MATERIALS AND METHODS: Serum tocopherol samples were examined using high performance liquid chromatography in third-party clinical laboratory institutions. Using real-world data from multi-center clinical laboratory institutions in China, the distribution parameters of vitamin E levels were described and the RI was calculated using three algorithms. RESULTS: A total of 756,766 cases were included in the analysis, including 435,561 males and 321,205 females. The median of vitamin E in infants younger than 4 years of age initially increased but subsequently decreased; while its levels in children between 4 and 11 years of age remained relatively stable despite progressing in age (approximately 7.4-7.8 mg/L). After the start of puberty, the difference, relative to sex, gradually became apparent, and the median vitamin E levels in females was higher than in males. The differences of vitamin E levels between different regions and samples in different seasons had no clinical significance. The RI of vitamin E for children aged 0-18 years in China was 4.5-11.1 mg/L based on expectation-maximization algorithm. The RI established by the Hoffmann method was 4.6-12.8 mg/L. CONCLUSION: The age- and sex-specific RIs of vitamin E were established by an indirect approach. The RIs established by EM algorithms could be used as an alternative to establish RIs based on real-world data.

Regional differences in the contribution of smoking, dietary and cooking behaviours to airflow obstruction in China: A population-based case-control study.

BACKGROUND AND OBJECTIVE: The major contributing risk factors to airflow obstruction (AO) in China remain largely unknown. We examined the environmental and lifestyle risk factors of unrecognized AO in the baseline of a population-based cohort drawn from 115 urban and rural communities across 12 provinces in China. METHODS: Amongst 46,285 adults recruited from 2005 to 2009, 3686 were identified with AO on spirometry (defined by the ratio of forced expiratory volume in the first second to forced vital capacity <0.7) and without known chronic lung disease. These cases were age- and sex-matched to 11,129 controls with normal spirometry and no chronic lung disease from the same community. Conditional multivariable adjusted OR and population attributable fraction (PAF) were calculated for each identified risk factor and their combined effect. RESULTS: Compared to controls, smoking initiation age <20 years (OR 1.22 [95% CI 1.01-1.48]), smoking duration ≥40 years (OR 1.82 [1.50-2.22]), low vegetables (OR 1.86 [1.67-2.07]) and fruits (OR 1.14 [1.02-1.29]) intake, cooking with biomass fuels (OR 2.54 [2.32-2.78]) and poor kitchen ventilation (OR 1.37 [1.19-1.58]) were significantly associated with elevated risks of unrecognized AO. The combined effect of these lifestyle factors significantly elevated the odds by 25 fold (18.6-34.3). The addition of prior tuberculosis and low socioeconomic status further increased the odds to 40.1 (28.2-57.0) and the PAF to 66.7% (51.1-78.1). CONCLUSION: Smoking, unhealthy diet, biomass cooking fuels and low socioeconomic status are strongly associated with AO. Addressing these risk factors could substantially reduce the burden of AO in China.

Reference intervals of 14 biochemical markers for children and adolescence in China: the PRINCE study.

OBJECTIVES: The Pediatric Reference Intervals in China (PRINCE) was initiated to establish the reference intervals (RIs) of Chinese children, as well as to make it possible to compare the variability of biochemical markers among countries internationally. METHODS: Healthy participants, aged up to 20 years, from 11 provinces across China, were enrolled in PRINCE and according to a standard screening procedure, that included a questionnaire survey, physical examinations and laboratory tests. Fasting venous blood specimens were collected. All serum specimens were analyzed with Cobas C702 in the center laboratory, i.e. clinical laboratory of Beijing Children's Hospital, with certified qualification (ISO15189). The nonparametric method recommended by Clinical Laboratory Standards Institute guidelines, was used to calculate the age- and sex-specified RIs. RESULTS: Among the 15,150 participants enrolled, 12,352 children (6,093 males and 6,259 females) were included to calculate RIs. The RIs for total protein, albumin, globulin, calcium, phosphate, potassium, sodium, chlorine, alkaline phosphatase, γ-glutamyl transpeptadase, alanine aminotransferase, aspartate aminotransferase, creatinine and urea were established by age- or sex-partitions. Most biochemical markers displayed larger variability and higher dispersion during the periods between 28 days and 1 year old, and included 4-6 age partitions commonly during 1 to <20 years old. In addition, differences of RIs between sexes usually occurs around the initiation of puberty at 12-13 years old. CONCLUSIONS: The age- and sex-specified RIs of 14 biochemical markers in PRINCE study can provide a solid reference, which will be transferred into relevant RIs for other clinical laboratory's platforms according to the CLSI guidelines.

Age and sex specific reference intervals of 13 hematological analytes in Chinese children and adolescents aged from 28 days up to 20 years: the PRINCE study.

OBJECTIVES: Pediatric Reference Intervals in China (PRINCE) is a nationwide initiative that aims to establish and validate harmonized reference intervals (RIs) for Chinese children and adolescents, in which 15,150 healthy volunteers aged up to 20 years were recruited from 11 centers to establish RIs and 7,557 children and adolescents were enrolled from 21 centers to validate RIs. METHODS: The complete blood cell counts (CBC) of venous whole blood were measured by hematology analyzers through Sysmex systems in different centers. Age- and sex-specific RIs were calculated according to the guidelines. RESULTS: Unlike adults with certain levels of analyte concentrations, hematological parameters of children changed through growth and development. Red blood cell counts, hemoglobin, and hematocrit increased with age, and revealed higher concentrations in boys than girls after puberty. White blood cell counts and platelet counts showed significant higher levels than adults before 2 years of age, and then gradually decreased without distinct sex differences. In addition, lymphocyte counts decreased with age while neutrophil counts showed an opposite trend. The lower and upper limits of pediatric RIs of CBC were different from those of adults. CONCLUSIONS: The validation of RIs indicated that the PRINCE study provided a version of RIs suitable for most of regions in China. This first harmonized pediatric RIs of CBC across China provided a robust database to understand the dynamic changes of hematologic parameters from birth to adolescence, and will contribute to clinical diagnosis and prognosis evaluation for pediatric patients as well.

Assessment of evidence on reported non-genetic risk factors of congenital heart defects: the updated umbrella review.

BACKGROUND: Congenital heart defect (CHD) is the leading cause of birth defects globally, which results in a great disease burden. It is still imperative to detect the risk factors of CHD. This umbrella review aimed to comprehensively summarize the evidence and grade the evidence of the associations between non-genetic risk factors and CHD. METHODS: Databases including Medline, Embase, Web of Science, Cochrane Library, and four Chinese databases were searched from inception to 18 Jan 2022. The reference lists of systematic reviews (SR) and meta-analyses (MA) were screened, which aimed to explore the non-genetic risk factors of CHD. Subsequently, titles and abstracts of identified records and full texts of selected SR/MA were screened by two independent reviewers based on predefined eligibility criteria. A priori developed extraction form was used to abstract relative data following the PRISMA 2020 and MOOSE guidelines. The risk of bias was assessed with the AMSTAR2 instrument. Data were synthesized using fixed-effects and random-effects meta-analyses, respectively. Finally, the evidence on the association of non-genetic risk factors and CHD was graded using Ioannidis's five-class evidence grade. RESULTS: A total of 56 SRs, encompassing 369 MAs, were identified. The risk factors included relative factors on air pollution, reproductive-related factors, parental age and BMI, parental life habits, working and dwelling environment, maternal drug exposure, and maternal disease. Based on AMSTAR2 criteria, only 16% (9/56) of SRs were classified as "Moderate". One hundred and two traceable positive association MAs involving 949 component individual studies were included in further analysis and grading of evidence. Family genetic history, number of abortions, maternal obesity, especially moderate or severe obesity, decoration materials, harmful chemicals, noise during pregnancy, folic acid supplementation, SSRIs, SNRIs, any antidepressants in the first trimester, maternal DM (including both PGDM and GDM), and gestational hypertension were convincing and highly suggestive factors for CHD. After sensitivity analyses based on cohort studies, some grades of evidence changed. CONCLUSION: The present umbrella review will provide evidence-based information for women of childbearing age before or during pregnancy to prevent CHD. In addition, sensitivity analysis based on cohort studies showed the changed evidence levels. Therefore, future SR/MA should concern the sensitivity analysis based on prospective birth cohort studies and case-control studies.

Comparison of reference distributions acquired by direct and indirect sampling techniques: exemplified with the Pediatric Reference Interval in China (PRINCE) study.

BACKGROUND: Our study aimed to compare the reference distributions of serum creatinine and urea obtained by direct sampling technique and two indirect sampling techniques including the Gaussian Mixture Model (GMM) and the Self-Organizing Map (SOM) clustering based on clinical laboratory records, so that the feasibility as well as the potential limitations of indirect sampling techniques could be clarified. METHODS: The direct sampling technique was used in the Pediatric Reference Interval in China (PRINCE) study, in which 15,150 healthy volunteers aged 0 to 19 years were recruited from 11 provinces across China from January 2017 to December 2018. The indirect sampling techniques were used in the Laboratory Information System (LIS) database of Beijing Children's Hospital, in which 164,710 outpatients were included for partitioning of potential healthy individuals by GMM or SOM from January to December 2016. The reference distributions of creatinine and urea that were established by the PRINCE study and the LIS database were compared. RESULTS: The density curves of creatinine and urea based on the PRINCE data and the GMM and SOM partitioned LIS data showed a large overlap. However, deviations were found in reference intervals among the three populations. CONCLUSIONS: Both GMM and SOM can identify potential healthy individuals from the LIS data. The performance of GMM is consistent and stable. However, GMM relies on Gaussian fitting, and thus is not suitable for skewed data. SOM is applicable for high-dimensional data, and is adaptable to data distribution. But it is susceptible to sample size and outlier detection strategy.

Continuous reference intervals for 21 biochemical and hematological analytes in healthy Chinese children and adolescents: The PRINCE study.

OBJECTIVES: Critical gaps have existed in pediatric reference intervals in China. In this study, we presented the sex and age distributions of 21 laboratory analytes from childhood to adolescence, and established the corresponding continuous reference intervals based on direct samples. METHODS: We used the data from the Pediatric Reference Intervals in China (PRINCE), which is a nation-wide cross-sectional study enrolling 15,150 healthy children and adolescents aged 0 - <20 years from 11 centers across China. Blood samples were collected and analyzed by trained staff following standard operating procedures. Biochemical tests were performed with Cobas C702 at the central laboratory, and hematological tests were performed with Sysmex XE, XN, or XS that satisfy the national standards at each participating center. Children younger than 3 months were excluded due to high neonatal variability and insufficient samples. Continuous reference intervals were calculated using the generalized additive models for location, shape, and scale, and were validated among another 387 healthy volunteers. RESULTS: We provided pediatric continuous reference intervals for 21 commonly used biochemical and hematological analytes in China, and depicted the changes in analyte concentrations from 3 months to 20 years. The out-of-range values for all analytes were less than 10%, indicating a well applicability of the continuous reference intervals to the general pediatric population. CONCLUSIONS: This is the first comprehensive report of continuous reference intervals based on healthy Chinese children, reflecting the complex dynamic trends of analytes from infancy to adulthood. Applying continuous reference intervals to clinical practice would not only improve the laboratory test result interpretation, but also help better clinical decision making.

The Role of Serum Calcium Levels in Pediatric Dyslipidemia: Are There Any?

Background: No previous study explored the association between serum calcium levels and dyslipidemia in children. This study aimed to explore this relationship in children, based on a multicenter cross-sectional study population in China. Methods: Cross-sectional data was derived from the Pediatric Reference Intervals in China (PRINCE) study conducted between 2017 and 2018 involving 5,252 males and 5,427 females with a mean age of 10.0 ± 4.6 years. Multivariable logistic regression models were applied to calculate odds ratios (ORs), with 95% confidence intervals (CIs), for dyslipidemia of each serum calcium level and albumin-corrected calcium levels, which were sorted into quartiles. The restricted cubic spline model was fitted for the dose-response analysis. An L-shaped dose-response relation between calcium levels and the probability of dyslipidemia was found after the adjustment for multiple potential confounding factors, p for non-linear < 0.001. Results: Using the middle category of calcium level as the reference, multivariable-adjusted ORs and 95% CIs of the lowest and the highest quartile categories were 0.96 (0.82-1.12) and 1.29 (1.12-1.48), respectively, for total serum calcium levels and 1.06 (0.91-1.23) and 1.39 (1.21-1.60) for albumin-corrected calcium levels. Conclusions: Individuals with higher levels of serum calcium were associated with increased risk of dyslipidemia in a sample of a healthy Chinese pediatric population. The association between serum calcium levels and dyslipidemia needs to be examined prospectively in future studies.

Fruit, vegetable, and legume intake and the risk of all-cause, cardiovascular, and cancer mortality: A prospective study.

BACKGROUND & AIMS: Although fruits and vegetable consumption has been shown to be associated with lower risks of mortality, cancers, and cardiovascular disease (CVD), there are limited data from China on the shape of the association. This study aimed to quantify the relationship between levels of fruit, vegetable, and legume consumption with the risk of major CVD, CVD mortality, cancer incidence, cancer mortality, and all-cause mortality. METHODS: In the baseline survey, participants attended 1 of 115 (45 urban and 70 rural) communities from 12 provinces to complete a standardized questionnaire, and undergo a physical examination between 2005 and 2009, and were followed up till 2017 (for the current analysis). Diet was assessed through in-person interviews by using validated food-frequency questionnaires. The clinical outcomes were adjudicated centrally by trained physicians using standardized definitions. Cox frailty models were used to explore the associations between fruit, vegetable, and legume consumption with the risk of all-cause, CVD, and cancer mortality. RESULTS: A total of 41 243 participants were eligible for inclusion in the analyses. The average combined average daily intake of fruit, vegetable, and legume was 2.97 [standard deviation (SD) 1.22] servings per day. During a median follow-up of 8.9 years [interquartile range (IQR) 6.7-9.9 years], we recorded 1893 major CVDs, 794 cancer events, and 1324 deaths, with 411 CVD deaths and 429 cancer deaths. In the models adjusted for age, sex, and center (random effect), a higher total intake of fruit, vegetable, and legume was inversely associated with CVD mortality, cancer incidence, cancer mortality, and all-cause mortality. After adjusting for additional covariates, the associations were evidently attenuated and only the association with all-cause mortality (hazard ratio [HR] trend 0.92, 95% CI 0.86-0.98, p trend = 0.021) remained significant, with a non-significant trend for major CVD (HR trend 1.02, 95% CI 0.97-1.08, p trend = 0.449), CVD mortality (HR trend 0.94, 95% CI 0.84-1.06, p trend = 0.301), cancer incidence (HR trend 0.97, 95% CI 0.89-1.06, p trend = 0.540), or cancer mortality (HR trend 0.92, 95% CI 0.82-1.04, p trend = 0.174). Compared with the reference group, the risk of all-cause mortality was the lowest for four to five servings of total daily intake of fruit, vegetable, and legume (HR 0.73, 95% CI 0.55-0.97), and did not show a further decrease for the higher intake group. Separately, fruit intake was associated with a lower risk of all-cause mortality (HR trend 0.92, 95% CI 0.86-0.99, p trend = 0.020) and legume intake was associated with a lower risk of major CVD (HR trend 0.95, 95% CI 0.90-0.99, p trend = 0.028) and all-cause mortality (HR trend 0.94, 95% CI 0.89-0.99, p trend = 0.020) in the fully adjusted models. CONCLUSIONS: This prospective study suggests that Chinese people with daily consumption of four to five servings (equivalent to 500-625 g/day) of fruit, vegetable, and legume demonstrated the lowest mortality, which conveys an encouraging message to the public that lifestyle modification to increase fruit, vegetable, and legume intakes may have greater beneficial effects on reducing all-cause mortality.

Cosinor-rhythmometry for 24-h urinary sodium, potassium, creatinine excretion in the Chinese adult population.

BACKGROUND: The low accuracy of equations predicting 24-h urinary sodium excretion using a single spot urine sample contributed to the misclassification of individual sodium intake levels. The application of single spot urine sample is limited by a lack of representativity of urinary sodium excretion, possibly due to the circadian rhythm in urinary excretion. This study aimed to explore the circadian rhythm, characteristics, and parameters in a healthy young adult Chinese population as a theoretical foundation for developing new approaches. METHODS: Eighty-five participants (mean age 32.4 years) completed the 24-h urine collection by successively collecting each of the single-voided specimens within 24 h. The concentrations of the urinary sodium, potassium, and creatinine for each voided specimen were measured. Cosinor analysis was applied to explore the circadian rhythm of the urinary sodium, potassium, and creatinine excretion. The excretion per hour was computed for analyzing the change over time with repeated-measures analysis of variance and a cubic spline model. RESULTS: The metabolism of urinary sodium, potassium, and creatinine showed different patterns of circadian rhythm, although the urinary sodium excretion showed non-significant parameters in the cosinor model. A significant circadian rhythm of urinary creatinine excretion was observed, while the circadian rhythm of sodium was less significant than that of potassium. The circadian rhythm of urinary sodium and creatinine excretion showed synchronization to some extent, which had a nocturnal peak and fell to the lowest around noon to afternoon. In contrast, the peak of potassium was observed in the morning and dropped to the lowest point in the evening. The hourly urinary excretion followed a similar circadian rhythm. CONCLUSION: It is necessary to consider the circadian rhythm of urinary sodium, potassium, and creatinine excretion in adults while exploring the estimation model for 24-h urinary sodium excretion using spot urine.

The Impact of Study-at-Home During the COVID-19 Pandemic on Myopia Progression in Chinese Children.

Background: To assess the impact of study-at-home during the COVID-19 pandemic on myopia development in Chinese schoolchildren. Methods: This historical cohort involved two groups with a total of 154 children. The exposed group was formed from 77 children aged 8 to 10 years who studied at home in the 7-month period during the COVID-19 pandemic (follow-up period: January - August 2020) and did not study at home in the 7-month period before the COVID-19 outbreak (baseline period: July 2019 - January 2020). Seventy-seven children who did not undergo study-at-home (baseline period: 7 months in 2015, follow-up period: 7 months in 2016) were included in the control group. Cycloplegic refraction, axial length and uncorrected visual acuity were measured 3 times. The questionnaire mainly focused on collecting visual habits. Results: Myopia progression was similar between the two groups in the baseline period. However, in the follow-up period the exposed group had a greater change in refraction toward myopia (-0.83 ± 0.56 D) than the control group (-0.28 ± 0.54 D; p < 0.001). In addition, the exposed group exhibited a significantly greater change in refraction toward myopia in the follow-up period (-0.83 ± 0.56 D) than in the baseline period (-0.33 ± 0.46 D; p < 0.001). Difference-in-difference analysis indicated that study-at-home accelerated the change in refraction toward myopia (t = -0.567; p < 0.001). Conclusions: During the COVID-19 pandemic study-at-home accelerated the change of refraction toward myopia in children.

Can statistical adjustment guided by causal inference improve the accuracy of effect estimation? A simulation and empirical research based on meta-analyses of case-control studies.

BACKGROUND: Statistical adjustment is often considered to control confounding bias in observational studies, especially case-control studies. However, different adjustment strategies may affect the estimation of odds ratios (ORs), and in turn affect the results of their pooled analyses. Our study is aimed to investigate how to deal with the statistical adjustment in case-control studies to improve the validity of meta-analyses. METHODS: Three types of adjustment strategies were evaluated including insufficient adjustment (not all preset confounders were adjusted), full adjustment (all confounders were adjusted under the guidance of causal inference), and improper adjustment (covariates other than confounders were adjusted). We carried out a series of Monte Carlo simulation experiments based on predesigned scenarios, and assessed the accuracy of effect estimations from meta-analyses of case-control studies by combining ORs calculated according to different adjustment strategies. Then we used the data from an empirical review to illustrate the replicability of the simulation results. RESULTS: For all scenarios with different strength of causal relations, combining ORs that were comprehensively adjusted for confounders would get the most precise effect estimation. By contrast, combining ORs that were not sufficiently adjusted for confounders or improperly adjusted for mediators or colliders would easily introduce bias in causal interpretation, especially when the true effect of exposure on outcome was weak or none. The findings of the simulation experiments were further verified by the empirical research. CONCLUSIONS: Statistical adjustment guided by causal inference are recommended for effect estimation. Therefore, when conducting meta-analyses of case-control studies, the causal relationship formulated by exposure, outcome, and covariates should be firstly understood through a directed acyclic graph, and then reasonable original ORs could be extracted and combined by suitable methods.

Age-dependent changes of total and differential white blood cell counts in children.

BACKGROUND: Total and differential white blood cell counts are important for the diagnostic evaluation of suspected diseases. To facilitate the interpretation of total and differential white blood cell counts in pediatric patients, the present study investigated age-dependent changes in total and differential white blood cell counts in healthy reference children. METHODS: Data were obtained from the Pediatric Reference Intervals in China study (PRINCE), which aims to establish and verify pediatric reference intervals for Chinese children based on a nationwide multicenter cross-sectional study from January 2017 to December 2018. Quantile curves were calculated using the generalized additive models for location, shape, and scale method. The 2.5th, 50th, and 97.5th quantile curves were calculated for both total and differential white blood counts. Percents of stacked area charts were used to demonstrate the proportions of differential white blood cells. All statistical analyses were performed using R software. RESULTS: Both 50th and 97.5th quantiles of total white blood cell count and monocyte count were highest at birth, then rapidly decreased in the first 6 months of life; relatively slow reduction continued until 2 years of age. The lymphocyte count was low during infancy and increased to its highest level at 6 months of age; it then exhibited moderate and continuous reduction until approximately 9 years of age. The pattern of neutrophil count changed with age in a manner opposite to that of lymphocyte count. Besides, there were two inter-sections of lymphocyte count and neutrophil count during infancy and at approximately 5 years of age, based on locally weighted regression (LOESS) analysis. There were no apparent age-related changes in eosinophil or basophil counts. CONCLUSION: These data regarding age-related changes in total and differential white blood cell counts can be used to assess the health of pediatric patients and guide clinical decisions.

Comparison of four algorithms on establishing continuous reference intervals for pediatric analytes with age-dependent trend.

BACKGROUND: Continuous reference intervals (RIs) allow for more precise consideration of the dynamic changes of physiological development, which can provide new strategies for the presentation of laboratory test results. Our study aimed to establish continuous RIs using four different simulation methods so that the applicability of different methods could be further understood. METHODS: The data of alkaline phosphatase (ALP) and serum creatinine (Cr) were obtained from the Pediatric Reference Interval in China study (PRINCE), in which healthy children aged 0-19 years were recruited. The improved non-parametric method, the radial smoothing method, the General Additive Model for Location Scale and Shape (GAMLSS), and Lambda-Median-Sigma (LMS) were used to develop continuous RIs. The accuracy and goodness of fit of the continuous RIs were evaluated based on the out of range (OOR) and Akaike Information Criterion (AIC) results. RESULTS: Samples from 11,517 and 11,544 participants were used to estimate the continuous RIs of ALP and Cr, respectively. Time frames were partitioned to fulfill the following two criteria: sample size = 120 in each subgroup and mean difference = 2 between adjacent time frames. Cubic spline or penalized spline was used for curve smoothing. The RIs estimated by the four methods approximately overlapped. However, more obvious edge effects were shown in the curves fit by the non-parametric methods than the semi-parametric method, which may be attributed to insufficient sample size. The OOR values of all four methods were smaller than 10%. CONCLUSIONS: All four methods could be used to establish continuous RIs. GAMLSS and LMS are more reliable than the other two methods for dealing with edge effects.

The household economic burden of non-communicable diseases in 18 countries.

Background: Non-communicable diseases (NCDs) are the leading cause of death globally. In 2014, the United Nations committed to reducing premature mortality from NCDs, including by reducing the burden of healthcare costs. Since 2014, the Prospective Urban and Rural Epidemiology (PURE) Study has been collecting health expenditure data from households with NCDs in 18 countries. Methods: Using data from the PURE Study, we estimated risk of catastrophic health spending and impoverishment among households with at least one person with NCDs (cardiovascular disease, diabetes, kidney disease, cancer and respiratory diseases; n=17 435), with hypertension only (a leading risk factor for NCDs; n=11 831) or with neither (n=22 654) by country income group: high-income countries (Canada and Sweden), upper middle income countries (UMICs: Brazil, Chile, Malaysia, Poland, South Africa and Turkey), lower middle income countries (LMICs: the Philippines, Colombia, India, Iran and the Occupied Palestinian Territory) and low-income countries (LICs: Bangladesh, Pakistan, Zimbabwe and Tanzania) and China. Results: The prevalence of catastrophic spending and impoverishment is highest among households with NCDs in LMICs and China. After adjusting for covariates that might drive health expenditure, the absolute risk of catastrophic spending is higher in households with NCDs compared with no NCDs in LMICs (risk difference=1.71%; 95% CI 0.75 to 2.67), UMICs (0.82%; 95% CI 0.37 to 1.27) and China (7.52%; 95% CI 5.88 to 9.16). A similar pattern is observed in UMICs and China for impoverishment. A high proportion of those with NCDs in LICs, especially women (38.7% compared with 12.6% in men), reported not taking medication due to costs. Conclusions: Our findings show that financial protection from healthcare costs for people with NCDs is inadequate, particularly in LMICs and China. While the burden of NCD care may appear greatest in LMICs and China, the burden in LICs may be masked by care foregone due to costs. The high proportion of women reporting foregone care due to cost may in part explain gender inequality in treatment of NCDs.

Validating the Performance of 5 Risk Scores for Major Adverse Cardiac Events in Patients Who Achieved Complete Revascularization After Percutaneous Coronary Intervention.

BACKGROUND: Risk scores, like the Synergy Between Percutaneous Coronary Intervention With Taxus and Cardiac Surgery (SYNTAX) score (SS), clinical SS, logistic SS (core model and extended model [LSSextended]), Age, Creatinine, and Ejection Fraction (ACEF) score, and modified ACEF score, are predictive for major adverse cardiac events (MACE; including all-cause mortality, myocardial infarction [MI], and revascularization) in patients who have undergone percutaneous coronary intervention (PCI). However, few studies have validated the performance of these scores in complete revascularization (CR) patients. We aimed to compare the performance of previous risk scores in patients who achieved CR after PCI. METHODS: All patients (N = 10,724) who underwent PCI at Fuwai Hospital in 2013 were screened, and those who achieved CR after PCI were enrolled. Risk scores were calculated by experienced cardiologists blinded to the clinical outcomes. Discrimination of risk scores was assessed according to the area under the receiver operating characteristic curve (AUC). RESULTS: Fifty-one percent (5375/10,724) of patients who underwent PCI achieved CR. At a mean follow-up of 2.4 years, the mortality, MI, revascularization, and MACE rates were 1.2%, 1.0%, 6.3%, and 7.7%, respectively. SS was not predictive for mortality (AUC, 0.51; 95% confidence interval [CI], 0.44-0.59). All scores involving clinical variables, especially modified ACEF score (AUC, 0.73; 95% CI, 0.66-0.79), could predict mortality. LSSextended was the most accurate for MI (AUC, 0.68; 95% CI, 0.61-0.75). SS and LSSextended were predictive for revascularization, with marginally significant AUCs (SS, 0.54; LSSextended, 0.55). No score was particularly accurate for predicting MACE, with AUCs ranging from 0.51 (ACEF score) to 0.58 (LSSextended). CONCLUSIONS: In CR patients, risk scores involving clinical variables might help to predict mortality; however, no risk scores showed helpful discrimination for MACE.