Linear Spline Regression Research Articles

Association of maternal TSH and neonatal metabolism: A large prospective cohort study in China.

Neonatal metabolites are very important in neonatal disease screening, and maternal thyroid hormones play an important role in fetal and neonatal health. Our study aimed to explore the association of maternal thyroid hormones with neonatal metabolites and identify an important time windows. Pregnant women were recruited in Jinan Maternity and Child Care Hospital and followed up until delivery. Multivariate generalized linear regression models (GLMs) and restricted cubic spline (RCS) regression analysis models were used to investigate the associations of maternal TSH and FT4 with neonatal metabolites. In total, 6,653 pairs of mothers and newborns were enrolled in our study. We identified 5 neonatal metabolites, including arginine/ornithine (Arg/Orn), C14:1/C2, C18:1, C3DC+C4OH and C8:1, that were significantly associated with maternal serum TSH during the whole pregnancy (P < 0.05), especially in the first trimester. Moreover, 10 neonatal metabolites were significantly associated with maternal serum FT4 (P < 0.05), most of which had positive correlations with maternal FT4 in the first trimester (P < 0.05). Some neonatal metabolites also had linear or nonlinear dose-effect relationships with maternal serum TSH and FT4 during the whole pregnancy, particularly in the first trimester. Our study, for the first time, provides epidemiological evidence that maternal serum TSH and FT4, especially during the first trimester, are associated with linear or nonlinear variations in neonatal metabolites. Efforts to identify newborn metabolism levels should carefully consider the effects of maternal thyroid function.

Associations between trace level thallium and multiple health effects in rural areas: Chinese Exposure and Response Mapping Program (CERMP)

Thallium (Tl) is a cumulative high toxicant in the environment, but few studies have investigated the comprehensive health effects underlying chronic Tl exposure at trace levels. This study aims to evaluate the liver, kidney, lung and other potential health effects associated with chronic Tl exposure at trace levels in rural areas of China. Urinary Tl concentrations of 2883 adults from rural areas of 12 provinces in China were measured and 2363 participants were involved in the final analysis. Indicators of liver and kidney functions in the serum, as well as the lung function indicators, were determined in the participants. General linear regression and restricted cubic spline regression were combined to study the associations between urinary Tl and health indicators or outcomes. In this study, the detected rate of Tl in the urine of the participants was 97.28 %. When the urinary Tl concentration was ranged at the fourth quintile, the risk of having liver function disorder was 70 % higher [Odds ratio (OR) = 1.70 (95 % confidence intervals (CI): 1.30, 2.22)] in all the participants, whereas the farmers were more likely to have the disorder [OR = 2.08 (95 % CI: 1.49, 2.92)] than the non-farmers [OR = 1.20 (95 % CI: 0.77, 1.88)]. Nonlinear associations between most of the liver health indicators and urinary Tl were identified, of which serum bilirubin was strongly associated with the elevation of urinary Tl when its concentration was >0.40 μg/g creatinine. Besides, urinary Tl was negatively associated with lung health indicators. Our study proposes the safety re-assessment of the current exposure level of Tl in the environment, especially in rural areas of China.

The Implementation of Hierarchical Linear Spline Regression Model to Maternal Mortality Rate Data in Indonesia

Hierarchical spline nonparametric regression analysis is one regression method to identify the correlation pattern among the variables with unidentified curves and nested data structure using a spline truncated regression approach on its function. On the maternal mortality rate, there is a nested data structure between the regional/ city level and provincial level. This study aimed to identify the correlation between the response variable and predictor variable from the maternal mortality rate data in 2020. There are two analyzed levels consisting of the city/ regional level (level-1) with 256 cities/ regencies and the provincial level (level-2). The level-1 predictor variable is total pregnant women taking blood booster supplements and total pregnant women attending K4 antenatal care and the level-2 predictor variable is poverty rates and school enrollment rates. A spline truncated approach has high flexibility and this study employs Maximum Likelihood as its estimator. The finding suggested that if a province has a lower poverty rate than 7.24%, maternal mortality rates tend to increase. If a province has lower enrolment rates than 67.8 %, the maternal mortality rate tends to decrease. If a regency or a city has fewer pregnant women taking blood booster supplements than 2258, maternal mortality rates tend to decrease. If a regency or a city has fewer pregnant women attending K4 antenatal care than 2258, the maternal mortality rate tends to decrease.

The role of family, school and neighbourhood in explaining inequalities in physical activity trajectories between age 9 and 18

Differentials in physical activity (PA) between social and economic groups has been shown to contribute significantly to social gradients in health and life expectancy, yet relatively little is known about why differentials in PA emerge. This paper uses longitudinal data on a nationally representative sample of 6,216 young people aged between 9 and 18, from Ireland, to measure the role of family, school and neighbourhood level factors in accounting for differentials in PA trajectories between groups of young people, defined by level of maternal education, whilst adjusting for the individual characteristics of the young person (sex, age, personality, body mass index and health-status). Levels of PA fall significantly across the sample between 9 and 18, and the decline in PA is larger for the children of lower educated mothers. We find a clear gradient in PA at each age by maternal education for both males and females. Descriptive analyses found social gradients in the majority of our risk factors. Using multi-level, linear spline regression models to decompose differentials between groups, we find that family-level mechanisms account for the biggest proportion of the differential in PA for both males (50.8%) and females (35.1%). Differences in income across maternal education categories accounted for 24.1% of the differential for males and 14.7% among females, making it the second most effective mechanism in explaining the social patterning of PA. Neighbourhood-level processes resulted in a modest reduction in the same differential, while school level processes had the effect of equalising differences in PA across maternal education groups.

Birth outcomes associated with paternal polybrominated and polychlorinated biphenyl exposure

In 1973–74, a polybrominated biphenyl (PBB) flame retardant mixture was shipped to Michigan livestock feed mills in place of a nutritional supplement and contaminated the food supply. Following the accident, the Michigan PBB Registry was established to study the long-term health effects of halogenated compounds and is now led by a community-academic partnership. PBB exposure is associated with altered DNA methylation in sperm, which may lead to adverse birth outcomes in children whose fathers have increased levels of serum PBB or polychlorinated biphenyl (PCB). Paternal PBB and PCB levels of men enrolled in the Michigan PBB Registry (n = 155) were analyzed against matched offspring birthweight and gestational age (n = 336). Birthweight and gestational age were dichotomized at the 25th percentile and 37 weeks, respectively, and paternal PBB and PCB levels were examined as continuous measures and divided into tertiles. Associations of offspring birthweight and gestational age with paternal PBB and PCB serum concentrations were modeled using multivariable linear spline and log-risk regression, adjusting for family clustering, paternal health and lifestyle factors, maternal PBB, and PCB serum concentrations, sex, and offspring gestational age (for birthweight). Fathers in the middle and upper PBB and PCB tertiles had increased risks for lowest quartile birthweight compared to the first tertile, with adjusted risk ratios (aRR) = 1.67 (95% CI: 0.93, 2.99) and aRR = 2.06 (95% CI: 1.12, 3.79) for PBB, and aRR = 1.47 (95% CI: 0.79, 2.75) and aRR = 1.34 (95% CI: 0.70, 2.54) for PCB, respectively. Elevated paternal PBB levels were not associated with an increased risk for preterm birth, while PCB levels were associated with a small, but not significant, decrease in gestational age, β = -0.37 (95% CI: -0.76, 0.03) weeks per log unit increase PCB. The findings suggest that increased paternal PBB and PCB levels negatively impact offspring birthweight, and paternal PCB levels may negatively impact gestational age.

Waning of antibody levels induced by a 13-valent pneumococcal conjugate vaccine, using a 3 + 0 schedule, within the first year of life among children younger than 5 years in Blantyre, Malawi: an observational, population-level, serosurveillance study

Pneumococcal conjugate vaccines (PCVs) induce serotype-specific IgG antibodies, effectively reducing vaccine-serotype carriage and invasive pneumococcal disease (IPD). IgG production wanes approximately 1 month after vaccination in absence of serotype-specific exposure. With uncertainty surrrounding correlate of protection (CoP) estimates and with persistent vaccine-serotype carriage and vaccine-serotype IPD after PCV13 introduction, we aimed to profile population-level immunogenicity among children younger than 5 years in Blantyre, Malawi. For this serosurveillance study, we used a random subset of samples from a prospective population-based serosurvey in Blantyre, Malawi, done between Dec 16, 2016, and June 27, 2018. Sample selection was based on age category optimisation among children younger than 5 years, adequate sample volume, and available budget. We measured serotype-specific IgGs against the 13 vaccine serotypes (1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, and 23F) and two non-vaccine serotypes (12F and 33F), as well as IgGs against three pneumococcal proteins (PsaA, NanA, and Ply), using ELISA and a direct-binding electrochemiluminescence-based multiplex assay. We estimated population-level, serotype-specific immunogenicity profiles using a linear spline regression model. Analyses included samples stratified to 20 3-month age strata (eg, age <3 months to 57-59 months). We evaluated 638 plasma samples: 556 primary samples and 82 unique secondary samples (each linked to one primary sample). Immunogenicity profiles revealed a consistent pattern among vaccine serotypes except serotype 3: a vaccine-induced IgG peak followed by waning to a nadir and subsequent increase in titre. For serotype 3, we observed no apparent vaccine-induced increase. Heterogeneity in parameters included age range at post-vaccination nadir (from 11·2 months [19A] to 27·3 months [7F]). The age at peak IgG titre ranged from 2·69 months (5) to 6·64 months (14). Titres dropped below CoPs against IPD among nine vaccine serotypes (1, 3, 4, 5, 6B, 7F, 9V, 18C, and 23F) and below CoPs against carriage for ten vaccine serotypes (1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F, and 23F). Increasing antibody concentrations among older children and seroincident events were consistent with ongoing vaccine-serotype exposure. A 3 + 0 PCV13 schedule with high uptake has not led to sustained population-level antibody immunity beyond the first year of life. Indeed, post-vaccine antibody concentrations dropped below putative CoPs for several vaccine serotypes, potentially contributing to persistent vaccine-serotype carriage and residual vaccine-serotype IPD in Malawi and other similar settings. Policy decisions should consider alternative vaccine strategies, including a booster dose, to achieve sustained vaccine-induced antibody titres, and thus control. Bill & Melinda Gates Foundation, Wellcome UK, and National Institute for Health and Care Research.

Modeling non-linear relationships in epidemiological data: The application and interpretation of spline models.

Traditional methods to deal with non-linearity in regression analysis often result in loss of information or compromised interpretability of the results. A recommended but underutilized method for modeling non-linear associations in regression models is spline functions. We explain spline functions in a non-mathematical way and illustrate the application and interpretation to an empirical data example. Using data from the Amsterdam Growth and Health Longitudinal Study, we examined the non-linear relationship between the sum of four skinfolds and VO2max, which are measures of body fat and cardiorespiratory fitness, respectively. We compared traditional methods (i.e., quadratic regression and categorization) to spline methods [1- and 3-knot linear spline (LSP) models and a 3-knot restricted cubic spline (RCS) model] in terms of the interpretability of the results and their explained variance (). The spline models fitted the data better than the traditional methods. Increasing the number of knots in the LSP model increased the explained variance (from for the 1-knot model to for the 3-knot model). The RCS model fitted the data best (), but results in regression coefficients that are harder to interpret. Spline functions should be considered more often as they are flexible and can be applied in commonly used regression analysis. RCS regression is generally recommended for prediction research (i.e., to obtain the predicted outcome for a specific exposure value), whereas LSP regression is recommended if one is interested in the effects in a population.

Mediation Effect of Body Mass Index on the Association of Urinary Nickel Exposure with Serum Lipid Profiles.

The objective of this study was to determine the relationship of urinary nickel (U-Ni) exposure to serum lipid profiles and the mediation effect of body mass index (BMI) in a US general population. We analyzed the cross-sectional data from 3517 participants in the National Health and Nutrition Examination Survey (NHANES) (2017-March 2020). Multivariable linear regression and restricted cubic spline (RCS) regression were conducted to explore the association of U-Ni with four serum lipids and four lipids-derived indicators. Mediation analysis was performed to examine the effect of BMI on the relationship between U-Ni levels and serum lipid profiles. Compared with the lowest quartile, the β with 95% confidence intervals (CIs) in the highest quartile were − 12.83 (− 19.42, − 6.25) for total cholesterol (TC) (P for trend < 0.001), − 12.76 (− 19.78, − 5.74) for non-high-density lipoprotein cholesterol (non-HDL-C) (P for trend = 0.001) and − 0.29 (− 0.51, − 0.07) for TC/HDL-C (P for trend = 0.007) in the fully adjusted model. RCS plots showed the linear association of log2-transformed U-Ni levels with TC, non-HDL-C and TC/HDL-C (P for nonlinearity = 0.294, 0.152, and 0.087, respectively). Besides, BMI decreased monotonically in correlation with increasing U-Ni levels (P for trend < 0.001). Mediation analysis revealed that BMI significantly mediated the relationship of U-Ni to TC, non-HDL-C and TC/HDL-C with mediated proportions of 11.17%, 22.20% and 36.44%, respectively. In summary, our findings suggest that BMI mediates the negative association of U-Ni with TC, non-HDL-C, and TC/HDL-C in the US general population.Supplementary InformationThe online version contains supplementary material available at 10.1007/s12011-022-03375-4.

Breast-Milk Rubidium and Other Trace Elements are Associated with Neurocognitive Development in Infants at Age of 8 Months

BackgroundTrace elements may affect neurodevelopment. There is a lack of data on breast-milk rubidium (Rb) in relation to neurodevelopment in infants. The associations of copper (Cu), zinc (Zn) and strontium (Sr) with neurodevelopment in infants remain uncertain. ObjectivesWe sought to evaluate the associations of breast-milk Rb (primary exposure), Cu, Zn, and Sr with neurodevelopment in infants at age 8 months. MethodsThe study cohort included 117 breastfed infants. Breast-milk samples were collected at 42 days and 8 months postpartum. Breast-milk Rb, Zn, Cu, and Sr were measured by inductively coupled plasma mass spectrometer. Neurodevelopment was assessed at age 8 months. The primary outcomes were attention and working memory scores, as evaluated by the A-not-B task. Other outcomes included the Mental Development Index (MDI) and Psychomotor Development Index (PDI) as evaluated by the Bayley Scale of Infant Development III. Generalized linear models and restricted cubic spline regression were used to assess the associations between trace elements and neurodevelopment indices. Bonferroni correction was conducted on all data presented. ResultsA nonlinear association was observed between breast-milk Rb at 42 days and infant’s attention at age 8 months (nonlinearity P = 0.037). Positive associations were observed with infant MDI scores and breast-milk Rb at 42 days (β = 4.46; P = 0.06) and 8 months (β = 3.79; P = 0.009) postpartum. Breast-milk Zn at 42 days was positively associated with infant’s attention (β = 0.31; P = 0.039). Sr at 42 days was positively correlated with attention (β = 0.18; P = 0.043) and MDI scores (β = 2.18; P = 0.015) at 8 months. Inverted U-shape associations were observed for breast-milk Cu at 42 days with infant attention and PDI scores. All associations were not significant after correction for multiple tests. ConclusionsOur data suggest that Rb, Zn, Cu, and Sr in breast milk at certain concentrations are associated with neurodevelopment in breastfed infants. Further studies are warranted to validate the findings.

Relationships Between 25-Hydroxyvitamin D, Parathyroid Hormone, and Bone Mass in 4-Year-Old Children in Dhaka, Bangladesh

ObjectivesElevated serum parathyroid hormone (PTH) concentration was incidentally observed in a high proportion of children in a study in Dhaka, Bangladesh. We explored potential correlates of elevated PTH by estimating the association of PTH with 25-hydroxyvitamin D (25(OH)D) and associations of 25(OH)D and PTH with bone outcomes.MethodsData were obtained from the BONe and mUScle health in Kids study (BONUSKids; NCT03537443). Total-body less head (TBLH) bone mineral content (BMC) and areal bone mineral density (aBMD) were measured by dual-energy X-ray absorptiometry (DXA). Serum PTH and 25(OH)D were analyzed by chemiluminescent immunoassay and liquid chromatography-tandem mass spectrometry, respectively. BONUSKids participants (n = 642) with DXA, PTH and 25(OH)D data at 4 years were included. Associations between 25(OH)D, PTH and bone outcomes were estimated using unadjusted linear and two-phase linear spline regression models. Model fit was compared using AIC.ResultsAmong the 534 children who met inclusion criteria, 43% were vitamin D deficient (< 30nmol/L) and 30% had PTH > 6.9pmol/L. A non-linear inverse relationship was observed between 25(OH)D and PTH. Model fit was optimized with an inflection point at 25nmol/L, above which the association attenuated (< 25nmol/L: −0.16pmol/L per 1nmol/L change in 25(OH)D [95%CI −0.23, −0.10]; ≥ 25nmol/L: –0.02pmol/L [95% CI −0.04, −0.008]. 25(OH)D was positively linearly associated with TBLH BMC (0.39g per 1nmol/L change in 25(OH)D [95%CI 0.10: 0.69]) and aBMD (0.0004g/cm2 per 1nmol/L change in 25(OH)D [95% CI 0.0002, 0.0006]). There was no significant association between PTH and TBLH BMC. The non-linear association between PTH and TBLH aBMD was negative at PTH > 4pmol/L (< 4pmol/L: 0.002g/cm2 per 1pmol/L change in PTH [95% CI –0.006, 0.01], ≥ 4pmol/L: −0.002g/cm2 [95% CI −0.0038, −0.0002]).ConclusionsThe non-linear inverse association of PTH with 25(OH)D supports the hypothesis that vitamin D deficiency contributed to elevated PTH in this population. Although 25(OH)D was associated with bone outcomes, the magnitude of the association was similar at 25(OH)D concentrations below and above 25nmol/L. PTH was inconsistently associated with bone outcomes, suggesting single measurements of PTH may not be a useful marker of bone health in this setting.Funding SourcesCanadian Institutes of Health Research.

Socio-economic inequalities in glycaemic control in recently diagnosed adults with type 1 and type 2 diabetes.

It is unclear whether socio-economic status (SES) is associated with glycaemic control in people with recently diagnosed diabetes. The aim was to investigate whether SES is related to haemoglobin A1c (HbA1c) during the first year after diagnosis in people with type 1 and type 2 diabetes and if metabolic, quality of care or mental factors may explain the association. In the German Diabetes Study, people with type 1 (n=274, median age 36 [25th; 75th percentile: 28; 48] years) and type 2 diabetes (n=424, 54 [47; 60] years) underwent detailed metabolic characterisation within the first year after diagnosis. SES was documented using a standardised questionnaire. Associations between SES and HbA1c were assessed using multivariable linear regression and restricted cubic spline regression analyses. Additional covariables were patient characteristics, laboratory measurements, health behaviour, quality of care and depression variables. Models were separately fitted for diabetes type, SES and its dimensions (income, education, occupation). Higher SES score was associated with lower HbA1c (-0.7mmol/mol per unit increase in SES, 95% CI: -1.1; -0.2mmol/mol [-0.1%, 95% CI: -0.1; 0.0%]) in people with type 1 diabetes. Included covariates did not attenuate this association. In people with type 2 diabetes, effect estimates were close to zero indicating no relevant difference. Socio-economic inequalities in HbA1c already exist during the first year after diagnosis in people with type 1 diabetes. The absence of association between glycaemic control and SES in type 2 diabetes could be due to the lower complexity of diabetes therapy compared to type 1 diabetes.

Associations of urinary and dietary cadmium with urinary 8-oxo-7,8-dihydro-2′-deoxyguanosine and blood biochemical parameters

Cadmium is a heavy metal with established adverse effects on human health, namely on bone, liver and kidney function and the cardiovascular system. We assessed cadmium exposure and its correlation with biomarkers of toxicity. We recruited 137 non-smoking blood donors without a history of chronic disease or cancer who resided in the Northern Italy province of Reggio Emilia (mean age 47 years, range 30–60 years) in the 2017–2019 period. We used a semi-quantitative food frequency questionnaire to estimate dietary cadmium intake and urine samples to assess concentrations of urinary cadmium and 8-oxo-7,8-dihydro-2′-deoxyguanosine (8-oxodG). Median urinary cadmium and 8-oxodG concentrations were 0.21 μg/L (interquartile range (IQR): 0.11–0.34 μg/L) and 3.21 μg/g creatinine (IQR: 2.21–4.80 μg/g creatinine), respectively, while median dietary cadmium intake was 6.16 μg/day (IQR: 5.22–7.93 μg/day). We used multivariable linear and spline regression models to estimate mean differences exposure concentrations. Dietary and urinary cadmium were positively correlated, and both were positively and linearly correlated with 8-oxodG. We found a positive association of urinary cadmium with blood alanine aminotransferase (ALT), total cholesterol, low-density lipoprotein (LDL)-cholesterol and thyroid-stimulating hormone (TSH) concentrations. We also observed a positive association with triglycerides, in both linear (beta regression coefficient = 77.03, 95% confidence interval 32.27–121.78) and non-linear spline regression analyses. Despite the positive correlation between dietary and urinary cadmium estimates, dietary cadmium intake showed inconsistent results with the study endpoints and generally weaker associations, suggesting a decreased capacity to reflect actual cadmium exposure. Overall, these findings suggest that even low levels of cadmium exposure may adversely alter hematological and biochemical variables and induce oxidative stress.

Growth Rate Estimation of Rabi Pulse Production of Odisha by Using Spline Regression Technique

Pulses are considered to be important crop for ensuring nutritional security in Odisha. Proper estimation of growth rate in production of pulse crops allows for more effective cropping system planning and formulation of the agricultural policy of the state. To capture any abrupt changes and the variation in data in different phases of a long time period, spline regression technique is used as it can fit different models in different segments of the time period as necessary without losing the continuity of the model. The present study deals with the estimation of growth rate of area, yield and production of all rabi pulses in Odisha by using best fit spline regression model. To fit the spline regression model, the entire period of study is divided into different segments based on the scatter plot diagram which is further confirmed by testing the significance of change in coefficient of variation between the consecutive segments by chi square test. The regression model found to be suitable from the study of scatter plot of data are linear, compound, logarithmic, power, quadratic and cubic model. The best fit model is selected on the basis of error assumption test and model fit statistics such as R2, adjusted R2 and Mean Absolute Percentage error (MAPE). The respective selected best fit model is used for the estimation of growth rates of area, yield and production of rabi pulses in Odisha for each segment and the whole period of study. Among the spline regression models, the respective linear spline regression model is found to be best fit for area, yield and production of rabi pulses and are used for growth rate estimation of these variables. It is found that though the growth rate in area and yield of rabi pulses are not significant, the growth rate of production is found to be significant for the whole period of study which shows that the interaction effect of area and yield on production seems to dominate.

Vitamin D mediates the association between acrylamide hemoglobin biomarkers and obesity.

Mediation analysis aims to discover the role of intermediate variables from exposure to disease. The current study was performed to evaluate how vitamin D mediates the association between acrylamide hemoglobin biomarkers and obesity. Data were collected on 10,377 adults participating in the National Health and Nutrition Examination Survey (NHANES) 2003-2006 and 2013-2014 aged ≥ 18years. Obesity was assessed through body mass index and abdominal circumference measurements. Generalized linear and restricted cubic spline (RCS) regression were used to estimate the association between vitamin D and acrylamide hemoglobin biomarkers, and the mediation effect of vitamin D was also discussed. After adjusting for potentially confounding factors, vitamin D had strong negative associations with serum concentrations of acrylamide hemoglobin adducts (HbAA, HbGA, and HbAA + HbGA). The RCS plots demonstrated that vitamin D was inversely and nonlinearly associated with HbAA and HbAA + HbGA while inversely and linearly associated with HbGA, and also a striking difference when vitamin D was lower than 60nmol/L. Mediation analysis suggested that a negative correlation between acrylamide and obesity was mediated by vitamin D. The current studyis expected toofferafresh perspective on reducing the toxicity of acrylamide.

Associations between plasma kynurenines and cognitive function in individuals with normal glucose metabolism, prediabetes and type 2 diabetes: the Maastricht Study

Aims/hypothesisStudies investigating associations between kynurenines and cognitive function have generally been small, restricted to clinical samples or have found inconsistent results, and associations in the general adult population, and in individuals with type 2 diabetes in particular, are not clear. Therefore, the aim of the present study was to investigate cross-sectional associations between plasma kynurenines and cognitive function in a cohort of middle-aged participants with normal glucose metabolism, prediabetes (defined as impaired fasting glucose and/or impaired glucose tolerance) and type 2 diabetes.MethodsPlasma kynurenines were quantified in 2358 participants aged 61 ± 8 years. Cross-sectional associations of kynurenines with cognitive impairment and cognitive domain scores were investigated using logistic, multiple linear and restricted cubic spline regression analyses adjusted for several confounders.ResultsEffect modification by glucose metabolism status was found for several associations with cognitive impairment, hence analyses were stratified. In individuals with prediabetes, 3-hydroxykynurenine (OR per SD 0.59 [95% CI 0.37, 0.94]) and 3-hydroxyanthranilic acid (0.67 [0.47, 0.96]) were associated with lower odds of cognitive impairment after full adjustment. In individuals with type 2 diabetes, kynurenine (0.80 [0.66, 0.98]), 3-hydroxykynurenine (0.82 [0.68, 0.99]), kynurenic acid (0.81 [0.68, 0.96]), xanthurenic acid (0.73 [0.61, 0.87]) and 3-hydroxyanthranilic acid (0.73 [0.60, 0.87]) were all associated with lower odds of cognitive impairment. Kynurenic acid (β per SD 0.07 [95% CI 0.02, 0.13]) and xanthurenic acid (0.06 [0.01, 0.11]) were also associated with better executive function/attention. No associations were observed in individuals with normal glucose metabolism.Conclusions/interpretationSeveral kynurenines were cross-sectionally associated with lower odds of cognitive impairment and better cognitive functioning in type 2 diabetes, while less widespread associations were seen in prediabetes. Low levels of kynurenines might be involved in the pathway of type 2 diabetes and cognitive decline but this needs further studies.Graphical abstract

Dose–response effect of postprocedural elevated cardiac troponin level on adverse clinical outcomes following adult noncardiac surgery: a systematic review protocol of prospective studies

IntroductionMyocardial injury after noncardiac surgery has been recognised as an important complication associated with short-term and long-term morbidity and mortality. However, whether a higher level of postoperative cardiac troponin (cTn)...

Correlation of Caesarean Section Rates to Maternal and Neonatal Mortality in the Eastern Mediterranean Region; A Population-Based Ecological Study

Purpose: This study aims to explore the relationship between population-level caesarean section rates (CSRs) with maternal and neonatal mortality rates (MMR, NMR) in the Eastern Mediterranean Region (EMR). Design: A populationbased ecological study was performed with data obtained from the World Health Organization, Global Health Observatory database, 2015, United Nations Inter-agency Group for Child Mortality Estimation (UN-IGME) and the United Nations Maternal Mortality Estimation Inter-Agency Group (UN-MMEIG) 2015). Mean ± standard deviation (SD), range, median and Interquartile range (IQR) were used to describe the quantitative data. We performed multivariate logistic regression analysis to explore the effect (a) of (a) Antenatal clinic visits (ANC %), (b), Skilled Birth Attendance (SBA) rate (% of deliveries attended by SBA), (c) Total Health Expenditure (THE) per capita and (d) Female Literacy Rate (FLR%) on the studied relationship. Spline linear regression was used to find the most predictive variable for MMR, and the NMR. Statistical significance was accepted at P&lt;0.05. Results: The mean CSR was 21.20±13.38, (1.8-52). The CSR of &lt;10% was linked with the highest NMR and MMR, 33.0 (24.0-39.0) and 390.5(329.5-648.0) respectively. The most predictable variables for NMR and MMR were SBA % [B=-0.875; p&lt; .001; R2=0.766 and adjusted R2=0.754] and FLR (F=15-24) [B=0.877; P&lt;0.001; R2=0.77 and adjusted R2=0.758] respectively. Conclusions: We found a statistically significant inverse relationship between CSRs and maternal and neonatal mortality in MSs with &lt;10% of CSR. The improved mortality rates in MSs with &gt;15% of CSR were significantly linked with better socioeconomic and healthcare variables than higher CSRs. Keywords: Caesarean Section, Maternal and Neonatal Mortality, Eastern Mediterranean Region.

Association between parental socioeconomic status and offspring overweight/obesity from the China Family Panel Studies: a longitudinal survey

ObjectiveTo examine the association between parental socioeconomic status (SES) and the risk of offspring overweight/obesity and the changes of the association that occur as children grow older.DesignWe used data from...

Psychological health in preschool children with underweight, overweight or obesity: a regional cohort study

ObjectiveTo examine if underweight (UW), overweight (OW) or obesity (OB), or body mass index (BMI) expressed as its SD score (BMI SDS), were associated with psychological difficulties in preschool children.DesignRegional...

Optimal cut-off value of elevated cardiac troponin concentrations for myocardial injury predicts clinical outcomes in adult patients with COVID-19: a dose–response analysis protocol for systematic review

IntroductionAcute myocardial injury in patients with COVID-19 infection has been recognised as one important complication associated with in-hospital mortality. The potential dose–response effect of cardiac troponin (cTn) concentrations on adverse...