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Background: Amyotrophic lateral sclerosis (ALS) is a rapidly progressing and rare neurodegenerative disease. Therefore, evaluating the risk factors affecting the survival of patients with ALS is crucial. Constipation, a common but overlooked symptom of ALS, can be effectively managed. It is currently unknown whether constipation contributes to the progression and survival of ALS. Objectives: This study aimed to investigate the association between constipation and ALS development and survival using a novel overlap-weighted (OW) method to enhance the robustness and reliability of results. Design: This prospective matching nested case-control (NCC) study was conducted within an ongoing ALS cohort at the Second Hospital of Hebei Medical University. Baseline data were collected from patients meeting the inclusion and exclusion criteria, with constipation as the exposure factor. A 9-month follow-up was conducted, with death as the endpoint event. Methods: We primarily used the OW method in NCC studies to examine the association between constipation and ALS development and survival. Weighted Cox proportional hazards model was used to assess risk factors associated with overall survival. Survival differences between the two groups were analyzed using Kaplan-Meier's plots and log-rank tests. Finally, the bioinformatic analysis explored common pathways between ALS and constipation. Results: Among the 190 patients included, the prevalence of constipation was 50%. Patients with ALS constipation exhibited faster disease progression (p < 0.001), with a positive correlation between constipation severity and progression rate (r = 0.356, p < 0.001). The constipation group had poorer survival before and after OW (log-rank test, p < 0.0001). In the Cox proportional hazards model of 114 patients, constipation was a risk factor for ALS both before (hazard ratio (HR) = 5.840, 95% confidence interval (CI) = 1.504–22.675, p = 0.011) and after (HR = 5.271, 95% CI = 1.241–22.379, p = 0.024) OW. Conclusion: Constipation in individuals with ALS is associated with faster disease progression and reduced survival rates, potentially through the peroxisome proliferator-activated receptor pathway. [ABSTRACT FROM AUTHOR]

Background and Objectives: Associations between the occurrence of early age‐related macular degeneration (AMD) and alterations in retinal layer thicknesses have been reported based on classical processing of optical coherence tomography (OCT) data by noise removal and subsequent image segmentation. However, speckle noise within OCT data itself bears a substantial part of the total information. For this reason, an omics‐type approach was designed for full exploitation of OCT data, which was able to identify signs of early AMD throughout the retina as a whole. Methods: A nested case–control study was designed with 200 early AMD cases and 200 healthy controls. For every participant, within a randomly selected OCT scan and a randomly selected column therein, manual grading was performed for 26 retinal feature positions. At each position, a total of 3792 descriptors were computed, based on nonlinear transformations of OCT data, first‐order neighbourhood statistics and Haralick features. Equivalence and differences between cases and controls were tested for every descriptor at each graded position. Results of multiple testing were expressed in terms of false and true discovery rates controlled by the Benjamini–Yekutieli procedure. Results: In terms of the amount and disparity of true discoveries, overall non‐equivalence of early AMD and healthy groups was found. Strong difference signals were observed at the internal limiting membrane and two central retinal positions, particularly for descriptors emphasising speckle noise. Conclusions: Between retinae of healthy controls and early AMD patients, significant differences were observed at the level of local neighbourhood statistics within the OCT data. Thus, independent evidence was obtained for AMD affecting not only the outer retinal layers but also the retina as a whole, even in the early stages of the disease. Within OCT data, both cartoons and speckle bear essential parts of total information. A constructive, completely documented, traceable and repeatable approach was pursued without invoking artificial intelligence methods. [ABSTRACT FROM AUTHOR]

Background and Objectives: Associations between the occurrence of early age related macular degeneration (AMD) and alterations in retinal layer thicknesses have been reported, based on classical processing of optical coherence tomography (OCT) data by noise removal and subsequent image segmentation. However, speckle noise within OCT data itself bears a substantial part of the total information. For this reason, we designed an omics‐type approach for full exploitation of OCT data, which was able to identify signs of early AMD throughout the retina as a whole. Methods: A nested case‐control study was designed with 200 early AMD cases and 200 healthy controls. For each participant, within a randomly selected OCT scan and a randomly selected column therein, manual grading was performed for 26 retinal feature positions. At every position, a total of 3792 descriptors were computed, based on nonlinear transformations of OCT data, first‐order neighbourhood statistics and Haralick features. Equivalence and differences between cases and controls were tested for each descriptor at every graded position. Results of multiple testing were expressed in terms of false and true discovery rates controlled by the Benjamini–Yekutieli procedure. Results: In terms of the amount and disparity of true discoveries, overall non‐equivalence was found for early AMD and healthy groups. Strong difference signals were observed at the internal limiting membrane and two central retinal positions, particularly for descriptors emphasising speckle noise. Conclusions: Between the retinae of healthy controls and early AMD patients, significant differences were observed at the level of local neighbourhood statistics within OCT data. Thus, independent evidence was obtained for AMD affecting not only the outer retinal layers but the retina as a whole, even in the early stages of the disease. Within OCT data, both cartoon and speckle bear essential parts of the total information. We pursued a constructive, completely documented, traceable and repeatable approach without invoking artificial intelligence methods. [ABSTRACT FROM AUTHOR]

Aims: To investigate immunometabolic associations of CD4+ T cell phenotypes with gestational diabetes mellitus (GDM). Methods: A nested case-control study was conducted comprising 53 pairs of GDM patients and matched controls within a prospective cohort. Metabolomic signatures related to both CD4+ T cell phenotypes and glycemic traits among pregnant women were investigated by weighted gene co-expression network analysis (WGCNA). Multivariable-adjusted generalized linear models were used to explore the associations of CD4+ T cell phenotypes and selected metabolites with GDM. Mediation analysis was conducted to evaluate the mediating effect of selected metabolites on the relationship between CD4+ T cell phenotypes and glycemic traits. Results: Higher levels of Treg cells (OR per SD increment (95%CI): 0.57 (0.34, 0.95), p = 0.031) and increased expression of Foxp3 (OR per SD increment (95%CI): 0.59 (0.35, 0.97), p = 0.039) and GATA3 (OR per SD increment (95%CI): 0.42 (0.25, 0.72), p = 0.002) were correlated with a decreased risk of GDM. Plasma pyruvaldehyde, S-adenosylhomocysteine (SAH), bergapten, and 9-fluorenone mediated the association between Tregs and fasting plasma glucose (FPG), with mediation proportions of 46.9%, 39.6%, 52.4%, and 56.9%, respectively. Conclusions: Treg cells and Foxp3 expressions were inversely associated with GDM risk, with potential metabolic mechanisms involving metabolites such as pyruvaldehyde and SAH. [ABSTRACT FROM AUTHOR]

Background/Objectives: Psoriasis is a chronic inflammatory disease that significantly impacts physical and emotional health. Statins, primarily used as lipid-lowering drugs, have also demonstrated anti-inflammatory effects. While some studies suggest that statins may improve psoriasis symptoms, the findings have been inconsistent. This study aims to investigate the association between prior statin use and the onset of psoriasis in a Korean population, focusing on individuals with dyslipidemia to minimize confounding factors. Methods: Using the Korean Health Insurance database (2002–2019), a nationwide nested case-control study was conducted, enrolling 8285 participants with psoriasis and 33,140 controls, matched 1:4 for sex, age, residence, and income through propensity scoring. Results: Adjusted odds ratios revealed significantly lower risks of psoriasis among short-term statin users (OR = 0.70, 95% CI = 0.66–0.74) and long-term users (OR = 0.77, 95% CI = 0.73–0.82) than in nonusers. This trend was consistent for both lipophilic and hydrophilic statins, and across subgroup analyses. Conclusions: These findings suggest that statins may reduce the incidence of psoriasis. However, further research is needed to assess their effects on psoriasis progression and severity. [ABSTRACT FROM AUTHOR]

Although several environmental factors may increase the risk of nervous system anomalies, the association between exposure to particulate matter with an aerodynamic diameter of ≤ 2.5 μm (PM2.5) and nervous system anomalies is not completely understood. This study aimed to examine the association between expoure to PM2.5 and nervous system anomalies, including specific phenotypes during preconception and early pregnancy and determine the crucial time windows. We conducted a nested case-control study from the Taiwan Maternal and Child Health Database between 2004 and 2017. We applied satellite-based models with a 1 km resolution to estimate the weekly average PM2.5 from 13 weeks before conception to the first 8 weeks of pregnancy. We used conditional logistic regression with distributed lag nonlinear models (DLNMs) to assess the effects of weekly average PM2.5 on the risk of nervous system anomalies and exposure-response relationships. We identified 12,383 incident nervous system anomalies cases in 2,571,300 participants. A 10 µg/m³ increase in PM2.5 concentrations from a reference value of 25 µg/m³ was associated with higher risk of nervous system anomalies (adjusted odds ratio [aOR]: 1.21; 95% confidence incidence [CI]: 1.18, 1.25) and encephalocele (aOR: 1.56; 95% CI: 1.33, 1.84) from 13 weeks before conception to the first 8 weeks of gestation. Anencephaly showed a significant association with PM2.5 exposure during the 13 weeks before conception (aOR: 1.48; 95% CI: 1.02, 2.51). In DLNMs, the risk of nervous system anomalies was elevated each week from 8 to 11 weeks before conception to 1–8 weeks of gestation. Our findings suggest that exposure to PM2.5 during preconception and early pregnancy may increase the risk of nervous system anomalies in offspring, particularly neural tube defects such as anencephaly and encephalocele. [ABSTRACT FROM AUTHOR]

Abstract Background Organic phosphate flame retardants (OPFRs) and phthalate acid esters (PAEs) are common endocrine-disrupting chemicals that cause metabolic disorders. This study aimed to assess the association between joint exposure to OPFRs and PAEs during early pregnancy in women with gestational diabetes mellitus (GDM). Methods Seven OPFRs and five PAEs were detected in the urine of 65 GDM patients and 100 controls using gas chromatography-tandem triple quadrupole mass spectrometry (GC-MS). The association of OPFRs and PAEs with GDM was assessed using logistic regression, weighted quantile sum (WQS) regression, and Bayesian kernel machine regression (BKMR) models. Results Levels of dibutyl phthalate (DBP), di-2-ethylhexyl phthalate (DEHP), diethyl phthalate (DEP), dimethyl phthalate (DMP), tris (2-butoxyethyl) phosphate (TBEP), tributyl phosphate (TBP), tris (2-chloroethyl) phosphate (TCEP), tris (1,3-dichloro-2-propyl) phosphate (TDCPP), tri-ortho-cresyl phosphate (TOCP), and triphenyl phosphate (TPHP) increased in the GDM group, and the OPFRs and PAEs, except for BBP and TMCP, were associated with GDM in the logistic regression analysis. In the WQS model, the mixture of OPFRs and PAEs was significantly positively associated with GDM (OR = 3.29, 95%CI = 1.27–8.51, P = 0.014), with TDCPP having the highest WQS index weight. BKMR analysis reinforced these results, showing that the overall association of joint exposure to the OPFRs and PAEs with GDM increased at exposure levels of the 55th to 75th percentiles. Independent exposure to TDCPP (OR = 1.42, 95%CI = 1.09–1.86, P = 0.011) and TBEP (OR = 1.29, 95%CI = 1.04–1.60, P = 0.023) were associated with an increased risk of GDM. Conclusions Environmental exposure to OPFRs and PAEs is significantly associated with GDM. These findings provide evidence for the adverse effects of exposure to OPFRs and PAEs on the health of pregnant women.

Abstract Background Breast cancer (BC) is the most common cancer in women and incidence rates are increasing; metabolomics may be a promising approach for identifying the drivers of the increasing trends that cannot be explained by changes in known BC risk factors. Methods We conducted a nested case–control study (median followup 6.3 years) within the New York site of the Breast Cancer Family Registry (BCFR) (n = 40 cases and 70 age-matched controls). We conducted a metabolome-wide association study using untargeted metabolomics coupling hydrophilic interaction liquid chromatography (HILIC) and C18 chromatography with high-resolution mass spectrometry (LC-HRMS) to identify BC-related metabolic features. Results We found eight metabolic features associated with BC risk. For the four metabolites negatively associated with risk, the adjusted odds ratios (ORs) ranged from 0.31 (95% confidence interval (CI): 0.14, 0.66) (L-Histidine) to 0.65 (95% CI: 0.43, 0.98) (N-Acetylgalactosamine), and for the four metabolites positively associated with risk, ORs ranged from 1.61 (95% CI: 1.04, 2.51, (m/z: 101.5813, RT: 90.4, 1,3-dibutyl-1-nitrosourea, a potential carcinogen)) to 2.20 (95% CI: 1.15, 4.23) (11-cis-Eicosenic acid). These results were no longer statistically significant after adjusting for multiple comparisons. Adding the BC-related metabolic features to a model, including age, the Breast and Ovarian Analysis of Disease Incidence and Carrier Estimation Algorithm (BOADICEA) risk score improved the accuracy of BC prediction from an area under the curve (AUC) of 66% to 83%. Conclusions If replicated in larger prospective cohorts, these findings offer promising new ways to identify exposures related to BC and improve BC risk prediction.

Background and Objectives: Malnutrition is associated with a higher risk of osteoporosis. We aim to assess the relationship between serum albumin with geriatric nutritional risk index and osteopenia in Chinese elderly men. Methods and Study Design: This is a nested case-control study from a prospective cohort enrolled 1109 individuals who were followed for seven years. Demographic data, medical history, signs and symptoms, and laboratory parameters were collected and analysed. Nutritional status and Geriatric Nutritional Risk Index (GNRI) were assessed. The nutrition-related indexes predictive value for osteopenia development was analyzed through multivariate Cox regression analysis and by creating a receiver operating characteristic curve (ROC), calculating the area under the curve (AUC). Kaplan-Meier (K-M) method was further used to find the nutritional status level in the elderly men. Results: The ALB and GNRI correlated with the risk of osteopenia in Chinese elderly men. After adjusting for all covariates, people with higher ALB level (HR: 0.821; 95% CI: 0.790-0.852) and higher GNRI score (HR: 0.889; 95% CI: 0.869-0.908) had a smaller risk of osteopenia. ROC analysis showed that the AUC for ALB was 0.729 (p<0.05) and for the GNRI score was 0.731 (p<0.05). K-M curve indicated a significant difference in ALB level (p<0.001) and GNRI score (p<0.001) in the respective subgroups. Conclusions: This study found that lower ALB level and lower GNRI score are associated with a higher prevalence of osteopenia among elderly men in China. [ABSTRACT FROM AUTHOR]

Objectives: Schizophrenia is associated with an increased risk of suicide. Few studies have investigated the risk of suicide across different ages, likely due to limitations around sample size. Methods: From the National Health Insurance Research Database in Taiwan, this study identified 195,787 patients with schizophrenia from January 1, 2000, to December 31, 2019. During the study period, 3848 patients died from suicide. We calculated the standardized mortality ratio (SMR) for suicide stratified by age. In this age‐stratified, nested case–control study, risk set sampling was used to match each case with 4 living controls by age, sex, and the year of the first diagnosis with schizophrenia. Conditional logistic regression was used for estimating age‐stratified risk profiles. Results: The SMR was the highest in the <25 years age group (52.8) and inversely correlated with age. Unemployment was associated with an increased risk of suicide in the 25 to 34, 35 to 44, 45 to 54, and 55 to 64 years age groups. Depressive and sleep disorders before suicide were more common among suicide cases with schizophrenia than among controls across all age groups. Drug‐induced and alcohol‐induced mental disorders were significantly associated with suicide but were observed only in the age group younger than 54. Heart disease, pneumonia, and moderate or severe renal disease were risk factors for suicide in the age groups less than 65. Conclusions: The risk factors for suicide differ by age. This study's findings can be used to optimize health‐care interventions for preventing suicide in patients with schizophrenia. [ABSTRACT FROM AUTHOR]

Kidney stones pose a significant healthcare burden worldwide. Dyslipidemia is a risk factor for kidney stones, but the relationship between remnant cholesterol (RC) and kidney stone risk is unknown. We aimed to investigate the association between RC and the risk of incident kidney stones. We conducted a nested case-control study based on data from Shanghai Kidney Stone Cohort conducted in Shanghai from December 2018 to February 2023. Propensity score matching was used to select 2550 incident kidney stone cases and 7650 controls from a total of 60,158 adults. Baseline fasting plasma samples were collected to measure RC, which was calculated as total cholesterol minus high-density lipoproteins cholesterol and low-density lipoproteins cholesterol. Multivariable conditional logistic regression and a restricted cubic spline were used to estimate the association between tertiles of RC and kidney stone risk. Subgroup and sensitivity analyses were also performed. The baseline RC of incident kidney stone cases and controls were 0.58 (0.57) and 0.54 (0.55), respectively. Incident kidney stones had much higher baseline RC levels than controls (P < 0.001). Higher baseline RC levels were significantly associated with increased kidney stone risk after adjustment for potential confounders (highest vs. lowest tertile: OR 1.16, 95% CI 1.04–1.30; per 1 mmol/L increase: OR 1.16, 95% CI 1.07–1.26). Restricted cubic spline showed a significant positive and linear dose-response relationship between RC and the risk of developing kidney stones (P-overall = 0.005, P-nonlinear = 0.482). Sensitivity analyses yielded consistent results. Elevated RC levels are associated with a greater risk of incident kidney stones in Chinese adults. [ABSTRACT FROM AUTHOR]

Background: Recent studies have increasingly shown the connection between gut microbiome and gestational diabetes mellitus (GDM). However, no studies have explored the relationship between the gut virome and GDM, and the underlying mechanism remains unknown. Methods: We performed a nested case-control study within a follow-up cohort, enrolling 51 patients with GDM and 51 healthy controls. Shotgun metagenomics sequencing was used to explore gut virome profiles during early pregnancy. Results: Diversity analysis revealed no difference in the overall gut virome composition between two groups, however, we found greater abundance of Escherichia phage SH2026Stx1 (Q = 0.23), Enterobacteria phage mEp043 c-1 (Q = 0.21), crAssphage cr50_1 (Q = 0.21), Enterobacteria phage phi80 (Q = 0.21), and Escherichia phage HK106 (Q = 0.23) in GDM patients. Cross-kingdom correlation analysis showed the negative correlation between the gut bacterium Eubacterium eligens and three bacteriophages (Escherichia phage SH2026Stx1 , Enterobacteria phage mEp043 c-1 , and Escherichia phage HK106) in GDM group (r < 0, P < 0.05). Based on gut microbial features and clinical indicators, we constructed a new prediction model using random forest method for GDM with good predictive performance (AUC of 0.893, 95% CI : 0.736 ∼ 0.990). Conclusion: This study is the first to investigate the relationship between the gut virome and GDM as well as the cross-kingdom correlation between gut viruses and bacteria in GDM. Our findings could enhance strategies for preventing and treating GDM from the perspective of gut microbiome, offering valuable insights into its pathogenesis. [ABSTRACT FROM AUTHOR]

Objective: Ischemic stroke-associated pneumonia (iSAP) affects about 10% of acute ischemic stroke patients during hospitalization. Current prediction scales for iSAP are insufficient. Identifying early biomarkers for stroke-associated pneumonia is crucial for improving patient outcomes. This study aimed to investigate the predictive value of euthyroid sick syndrome (ESS) for iSAP in acute-stage of ischemic stroke patients. Methods: We studied 1767 acute ischemic stroke patients within one week of symptom onset, categorizing them into an infection group (iSAP, n=376) and control group (control, n=1391). COX regression analysis was used to identify the potential risk and protected factors. Kaplan-Meier time-event curves and Log-Rank tests were performed to differentiate infection time in patients with ESS or normal T3 group. Results: The iSAP group had higher rates of risk factors like older age, atrial fibrillation, COPD, and ESS, along with elevated levels of WBC, CRP,and FT4 levels (all P < 0.001). Conversely, iSAP patients had lower GCS scores, eGFR, TSH, T3, FT3 (all P < 0.001) and T4 levels (P = 0.005) upon admission. No significant differences were observed in sex, smoking history, hypertension, diabetes, or LDL-C levels (P > 0.05). COX regression analysis identified age, KWST scores, leukocyte count, CRP, and ESS (all P < 0.001) as significantly correlated with iSAP. ROC analysis revealed ESS as a predictor with sensitivity of 35.64% and specificity of 87.92% for SAP prediction, like atrial fibrillation and higher than COPD and eGFR. Conclusion: ESS at admission predicts a higher risk of stroke-associated pneumonia in acute-stage of ischemic stroke. [ABSTRACT FROM AUTHOR]

Background: Breast cancer (BC) is the most common cancer in women and incidence rates are increasing; metabolomics may be a promising approach for identifying the drivers of the increasing trends that cannot be explained by changes in known BC risk factors. Methods: We conducted a nested case–control study (median followup 6.3 years) within the New York site of the Breast Cancer Family Registry (BCFR) (n = 40 cases and 70 age-matched controls). We conducted a metabolome-wide association study using untargeted metabolomics coupling hydrophilic interaction liquid chromatography (HILIC) and C18 chromatography with high-resolution mass spectrometry (LC-HRMS) to identify BC-related metabolic features. Results: We found eight metabolic features associated with BC risk. For the four metabolites negatively associated with risk, the adjusted odds ratios (ORs) ranged from 0.31 (95% confidence interval (CI): 0.14, 0.66) (L-Histidine) to 0.65 (95% CI: 0.43, 0.98) (N-Acetylgalactosamine), and for the four metabolites positively associated with risk, ORs ranged from 1.61 (95% CI: 1.04, 2.51, (m/z: 101.5813, RT: 90.4, 1,3-dibutyl-1-nitrosourea, a potential carcinogen)) to 2.20 (95% CI: 1.15, 4.23) (11-cis-Eicosenic acid). These results were no longer statistically significant after adjusting for multiple comparisons. Adding the BC-related metabolic features to a model, including age, the Breast and Ovarian Analysis of Disease Incidence and Carrier Estimation Algorithm (BOADICEA) risk score improved the accuracy of BC prediction from an area under the curve (AUC) of 66% to 83%. Conclusions: If replicated in larger prospective cohorts, these findings offer promising new ways to identify exposures related to BC and improve BC risk prediction. [ABSTRACT FROM AUTHOR]

This study aimed to investigate the impact of sexual partners' HIV serostatus awareness on the HIV acquisition among men who have sex with men (MSM) in Guangzhou, China. A nested case–control study was conducted based on a prospective cohort of MSM in Guangzhou. Within the cohort, individuals who underwent HIV seroconversion were identified as the case group, and each case was matched with four controls from the non-seroconverted participants. Information regarding the awareness of sexual partners' HIV serostatus over the preceding 6 months was gathered. Of the 161 participants, 36.0% were aware of the HIV serostatus of all their sexual partners. The practice of engaging in condomless anal sex with partners of unknown HIV serostatus and being aware of the HIV serostatus of only some casual partners were positively correlated with an elevated risk of acquiring HIV. Conversely, being fully aware of the HIV serostatus of all sexual partners, including regular ones, was associated with a diminished risk of HIV incidence. Regular communication with sexual partners regarding HIV testing outcomes, honest disclosure of one's own HIV serostatus, and refusal of sexual contact with partners of unknown HIV serostatus can potentially mitigate the risk of acquiring HIV among MSM. [ABSTRACT FROM AUTHOR]

Background: Sepsis constitutes a condition that involves life-threatening organ dysfunction induced by severe infection. This nested case–control study investigated risk factors for severe sepsis and whether antipsychotic use is associated with severe sepsis risk in patients with schizophrenia, a topic that has not been comprehensively explored in previous studies. Methods: We selected 39,432 patients with schizophrenia aged between 15 and 65 years from Taiwan's Psychiatric Inpatient Medical Claims database for the period 2000–2012. The case group comprised patients with severe sepsis after their first psychiatric admission (n = 1382). The case and control groups were randomly matched (1:4) by age, sex and first psychiatric admission (year) and finally comprised 1382 and 5528 individuals, respectively. We employed multivariable conditional logistic regression to identify (1) risk factors (physical illnesses and nonpsychiatric medications) and (2) antipsychotic–severe sepsis associations. Results: Higher numbers of psychiatric admissions and physical illnesses such as delirium, cerebrovascular disease and cancer were significantly associated with a higher risk of severe sepsis. Furthermore, severe sepsis was associated with the use of antithrombotic agents, systemic corticosteroids and agents targeting the renin–angiotensin system. Clozapine (adjusted risk ratio = 1.65) and quetiapine (adjusted risk ratio = 1.59) use were associated with an increased risk of severe sepsis. The use of more than one antipsychotic drug could further increase this risk. Conclusion: Several physical illnesses and nonpsychiatric medications increase the risk of severe sepsis in patients with schizophrenia. Specifically, clozapine or quetiapine use significantly increased the risk of severe sepsis in these patients. [ABSTRACT FROM AUTHOR]

Objective: This study aimed to explore the association between major depressive disorder (MDD) and suicide risk in patients with dementia. Methods: A cohort of 625,218 individuals aged ≥ 40 years with dementia was identified from Taiwan’s National Health Insurance Research Database (NHIRD) between 2007 and 2018. After excluding prevalent cases in 2007, a nested case-control study enrolling 1,256 suicide cases and 5,022 matched controls was conducted. The frequencies of MDD-related outpatient or inpatient visits over a 7-year period preceding the event dates were calculated and analyzed for association using conditional logistic regression. Results: Dementia comorbid with MDD was associated with increased suicide risk (adjusted OR [AOR]: 2.67), particularly in individuals with ≤ 1.0 MDD episodes per year (AOR: 2.85). A similar association was observed only in individuals aged ≥ 65 years and males, with a pronounced risk of suicide in those experiencing ≤ 1.0 MDD episodes per year (AOR: 3.08 for individuals aged ≥ 65 years; AOR: 3.28 for males). Conversely, the risk increase was evident with > 1.0 MDD episodes per year in those aged < 65 years (AOR: 3.04) and females (AOR: 2.45). Conclusion: MDD is associated with suicide risk in patients with dementia. The strength of this association possibly varies with age and gender.

Abstract Background Gastric cancer is the fourth most common cancer and highly prevalent in South Korea. As one of the predictors of gastric cancer, we focused on health utilization patterns and expenditures, as the surrogate variables of health conditions. This nested case-control study aimed to identify the association between health expenditure trajectory and incidence of gastric cancer. Methods Data from the National Health Insurance Service Senior Cohort of South Korea were used. Individuals diagnosed with gastric cancer (N = 14,873) were matched to a non-diagnosed group (N = 44,619) in a 1:3 ratio using a nested case-control design. A latent class trajectory analysis was performed to identify the patterns of health expenditure among the matched participants. Furthermore, conditional logistic regression analysis was conducted to examine the relationship between healthcare expenditure trajectories and gastric cancer incidence. Results Seven distinct health expenditure trajectories for five years were identified; consistently lowest (13.8%), rapidly increasing (5.9%), gradually increasing (13.8%), consistently second-highest (21.4%), middle-low (18.8%), gradually decreasing (13.1%), and consistently highest (13.2%). Compared to the middle-low group, individuals in the rapidly increasing [odds ratio (OR) = 2.11, 95% confidence interval (CI); 1.94–2.30], consistently lowest (OR = 1.40, 95% CI; 1.30–1.51), and gradually increasing (OR = 1.26, 95% CI; 1.17–1.35) groups exhibited a higher risk of developing gastric cancer. Conclusions Our findings suggest that health expenditure trajectories are predictors of gastric cancer. Potential risk groups can be identified by monitoring health expenditures.

Abstract Background Bladder cancer (BC) and Renal cell carcinoma (RCC) are the most common urogenital cancers among both sexes, with a yearly global incidence of around 500 000 each. Both BC and RCC have been linked to diabetes. Poor glycemic control (malglycemia) is a serious consequence of diabetes and a possible consequence of systemic treatments used in BC and RCC. The objective of this study was to investigate the prevalence of diabetes and use of hospital-based care for malglycemia in people with BC or RCC. Methods This Swedish retrospective population-based register study used national health-data registers for longitudinal data on cancer incidence covering 15 years, use of hospital-based health care, and filled prescriptions of outpatient medications. Study endpoints included co-prevalence of diabetes in individuals with BC/RCC, healthcare resource utilization due to malglycemia, use of systemic corticosteroids, and changes in diabetes management for people with concomitant type 2 diabetes. Results We identified 36,620 and 15,581 individuals diagnosed with BC and RCC, respectively, between 2006 and 2019. The proportion of individuals registered with diabetes was 24% in BC and 23% in RCC. An association between BC/RCC and poor glycemic control was found, although the number of malglycemic events in hospital-based care were few (65/59 per 1000 individuals with diabetes and BC/RCC respectively with at least one event). An earlier switch to insulin-based diabetes management was observed in BC/RCC compared to matched individuals with type 2 diabetes but no cancer. The results also indicated an association between steroid treatment and poor glycemic control, and that systemic corticosteroids were more common among people with BC/RCC compared to diabetes controls. Conclusion The high prevalence of diabetes and increased use of systemic corticosteroid treatment observed in this large national study highlights the need for specific clinical management, risk-assessment, and monitoring of individuals with BC/RCC and diabetes.

Background: Gastric cancer is the fourth most common cancer and highly prevalent in South Korea. As one of the predictors of gastric cancer, we focused on health utilization patterns and expenditures, as the surrogate variables of health conditions. This nested case-control study aimed to identify the association between health expenditure trajectory and incidence of gastric cancer. Methods: Data from the National Health Insurance Service Senior Cohort of South Korea were used. Individuals diagnosed with gastric cancer (N = 14,873) were matched to a non-diagnosed group (N = 44,619) in a 1:3 ratio using a nested case-control design. A latent class trajectory analysis was performed to identify the patterns of health expenditure among the matched participants. Furthermore, conditional logistic regression analysis was conducted to examine the relationship between healthcare expenditure trajectories and gastric cancer incidence. Results: Seven distinct health expenditure trajectories for five years were identified; consistently lowest (13.8%), rapidly increasing (5.9%), gradually increasing (13.8%), consistently second-highest (21.4%), middle-low (18.8%), gradually decreasing (13.1%), and consistently highest (13.2%). Compared to the middle-low group, individuals in the rapidly increasing [odds ratio (OR) = 2.11, 95% confidence interval (CI); 1.94–2.30], consistently lowest (OR = 1.40, 95% CI; 1.30–1.51), and gradually increasing (OR = 1.26, 95% CI; 1.17–1.35) groups exhibited a higher risk of developing gastric cancer. Conclusions: Our findings suggest that health expenditure trajectories are predictors of gastric cancer. Potential risk groups can be identified by monitoring health expenditures. [ABSTRACT FROM AUTHOR]

BackgroundMethodsResultsConclusionMedium-chain fatty acids (MCFAs) and docosahexaenoic acid (DHA) could affect the occurrence of mild cognitive impairment (MCI). β-hydroxybutyrate (BHB), mitochondrial DNA copy number (mtDNAcn) and mitochondrial DNA (mtDNA) deletions might be their potential mechanisms. This study aimed to explore the relationship between MCFAs, DHA and MCI, and potential mechanisms.This study used data from Tianjin Elderly Nutrition and Cognition (TENC) cohort study, 120 individuals were identified with new onset MCI during follow-up, 120 individuals without MCI were selected by 1:1 matching sex, age, and education levels as the control group from TENC. Conditional logistic regression analysis and mediation effect analysis were used to explore their relationship.Higher serum octanoic acid levels (OR: 0.633, 95% CI: 0.520, 0.769), higher serum DHA levels (OR: 0.962, 95% CI: 0.942, 0.981), and more mtDNAcn (OR: 0.436, 95% CI: 0.240, 0.794) were associated with lower MCI risk, while more mtDNA deletions was associated with higher MCI risk (OR: 8.833, 95% CI: 3.909, 19.960). Mediation analysis suggested that BHB and mtDNAcn, in series, have mediation roles in the association between octanoic acid and MCI risk, and mtDNA deletions have mediation roles in the association between DHA and MCI risk.Higher serum octanoic acid and DHA levels were associated with lower MCI risk. Octanoic acid could affect the incidence of MCI through BHB, then mitochondria function, or through mitochondria function, or directly. Serum DHA level could affect the incidence of MCI through mitochondria function, or directly. [ABSTRACT FROM AUTHOR]

Despite growing interest in the preventive effects of statins, as lipid-lowering agents, on migraine attacks, comprehensive nationwide studies comparing migraine likelihood between statin users and controls are lacking. Our nested case–control study within the Korean National Health Insurance Service-Health Screening Cohort (2002–2019) investigated this association using 38,957 migraine patients and 155,828 controls, considering migraine subtypes (with/without aura) and statin types (lipophilic vs. hydrophilic). Using propensity score matching and adjusting for confounders, statin use was linked to reduced migraine likelihood overall (odds ratio (OR) 0.93), particularly for migraines with aura (OR 0.75) and without aura (OR 0.94). Lipophilic statins were effective for both subtypes, while hydrophilic statins mainly reduced the likelihood of migraines without aura. Subgroup analyses showed consistent benefits across demographics, but varied effectiveness based on weight, smoking, alcohol use, hemoglobin levels, and dyslipidemia history. In summary, this nationwide cohort study suggests that statin use may reduce migraine likelihood among Korean adults across diverse demographics and clinical profiles, but varied effectiveness based on certain lifestyle and comorbidity factors underscores the importance of considering individual patient profiles when assessing the potential benefits of statin therapy for migraine prevention. [ABSTRACT FROM AUTHOR]

To explore the association between gabapentin use and the risk of dementia in patients with chronic pain, considering the rising concerns of dementia in an aging population and the potential cognitive impacts of chronic pain management. A nested case-control study utilizing data from a longitudinal health insurance database. The study is based on a longitudinal health insurance database spanning 2000–2019 in Taiwan. A total of 201,492 patients aged 50 years and older diagnosed with chronic pain between 2001 and 2017 were included. The study focused on individuals with chronic pain, excluding those diagnosed with dementia a year before or after their chronic pain diagnosis. Analysis of gabapentin prescription history was conducted, considering the cumulative dose from the chronic pain diagnosis date to the dementia diagnosis date or equivalent period for controls. Data included demographics, gabapentin prescription history, and comorbidities. Logistic regression was used to estimate odds ratios for dementia risk. No significant difference in the risk of dementia was found between low and high cumulative doses of gabapentin. The adjusted odds ratio for dementia risk associated with gabapentin use was 0.91 (95 % C.I. 0.83–1.01), indicating no substantial increase in risk. Long-term Gabapentin therapy for chronic pain is not associated with a differential risk of dementia across dosage levels, irrespective of age or gender. Further study into its potential cognitive impacts is essential. • Rising global dementia prevalence is drawing attention to chronic pain as a potential risk factor often managed by gabapentin. • Taiwanese health insurance database spanning 2000-2019 assessed dementia risk in gabapentin-using chronic pain. • The study showed that gabapentin use not linked to higher dementia risk. • No elevated dementia risk was found across varying dosage levels or among different age and gender subgroups. [ABSTRACT FROM AUTHOR]

STUDY QUESTION Is the mode of conception (natural, subfertility and non-IVF, and IVF) associated with the risk of Type 1 diabetes mellitus among offspring? SUMMARY ANSWER The risk of Type 1 diabetes in offspring does not differ among natural, subfertility and non-IVF, and IVF conceptions. WHAT IS KNOWN ALREADY Evidence has shown that children born through IVF have an increased risk of impaired metabolic function. STUDY DESIGN, SIZE, DURATION A population-based, nested case–control study was carried out, including 769 children with and 3110 children without Type 1 diabetes mellitus within the prospective cohort of 2 228 073 eligible parent-child triads between 1 January 2004 and 31 December 2017. PARTICIPANTS/MATERIALS, SETTING, METHODS Using registry data from Taiwan, the mode of conception was divided into three categories: natural conception, subfertility, and non-IVF (indicating infertility diagnosis but no IVF-facilitated conception), and IVF conception. The diagnosis of Type 1 diabetes mellitus was determined according to the International Classification of Diseases, 9th or 10th Revision, Clinical Modification. Each case was matched to four controls randomly selected after matching for child age and sex, residential township, and calendar date of Type 1 diabetes mellitus occurrence. MAIN RESULTS AND THE ROLE OF CHANCE Based on 14.3 million person-years of follow-up (median, 10 years), the incidence rates of Type 1 diabetes were 5.33, 5.61, and 4.74 per 100 000 person-years for natural, subfertility and non-IVF, and IVF conceptions, respectively. Compared with natural conception, no significant differences in the risk of Type 1 diabetes were observed for subfertility and non-IVF conception (adjusted odds ratio, 1.04 [95% CI, 0.85–1.27]) and IVF conception (adjusted odds ratio, 1.00 [95% CI, 0.50–2.03]). In addition, there were no significant differences in the risk of Type 1 diabetes according to infertility source (male/female/both) and embryo type (fresh/frozen). LIMITATIONS, REASONS FOR CAUTION Although the population-level data from Taiwanese registries was used, a limited number of exposed cases was included. We showed risk of Type 1 diabetes was not associated with infertility source or embryo type; however, caution with interpretation is required owing to the limited number of exposed events after the stratification. The exclusion criterion regarding parents' history of diabetes mellitus was only applicable after 1997, and this might have caused residual confounding. WIDER IMPLICATIONS OF THE FINDINGS It has been reported that children born to parents who conceived through IVF had worse metabolic profiles than those who conceived naturally. Considering the findings of the present and previous studies, poor metabolic profiles may not be sufficient to develop Type 1 diabetes mellitus during childhood. STUDY FUNDING/COMPETING INTEREST(S) This study was supported by grants from Shin Kong Wu Ho-Su Memorial Hospital (No. 109GB006-1). The funders had no role in considering the study design or in the collection, analysis, interpretation of data, writing of the report, or decision to submit the article for publication. The authors have no competing interests to disclose. TRIAL REGISTRATION NUMBER N/A. [ABSTRACT FROM AUTHOR]

Background: Limited studies have investigated the association between statin therapy and poor glycemic control, especially in the Chinese diabetic population. Methods: Two prospective diabetes cohorts were drawn from the Kailuan Cohort. In Cohort 1, linear regression models were used to evaluate the association between statin therapy and glycated hemoglobin (HbA1c) level change. In Cohort 2, new user design and conditional logistic models were used to assess associations between statin initiation and poor glycemic control which was a composite outcome comprised of hypoglycemic agent escalation and new-onset hyperglycemia. Results: Among 11,755 diabetic patients with medication information, 1400 statin users and 1767 statin nonusers with repeated HbA1c measurements were included in Cohort 1 (mean age: 64.6 ± 10.0 years). After a median follow-up of 3.02 (1.44, 5.00) years, statin therapy was associated with higher HbA1c levels (β: 0.20%; 95%CI: 0.05% to 0.34%). In Cohort 2, 1319 pairs of matched cases/controls were included (mean age: 61.6 ± 9.75 years). After a median follow-up of 4.87 (2.51, 8.42) years, poor glycemic control occurred in 43.0% of statin new users and 31.8% of statin nonusers (OR: 1.69; 95% CI: 1.32 to 2.17; P < 0.001). The statin-associated poor glycemic control risk was significantly higher among patients with lower body mass index (Pint = 0.089). Furthermore, a nonlinear association was observed between statin therapy duration and poor glycemic control (P = 0.003). Conclusions: Among Chinese diabetic adults, statin therapy was associated with a higher level of HbA1c, and a higher risk of hypoglycemic agent escalation and new-onset hyperglycemia, especially among those who had lower body mass index levels and longer statin therapy duration. [ABSTRACT FROM AUTHOR]

Background: Gut microbiota may influence the development of acute pancreatitis (AP), a serious gastrointestinal disease with high morbidity and mortality. This study aimed to identify a causal link by investigating the relationship between gut microbiota and AP. Methods: Mendelian randomization (MR) and a nested case-control study were used to explore associations between gut microbiota composition and AP. 16S rRNA sequencing, random forest modelling (RF), support vector machine (SVM), and Kaplan-Meier survival analysis was applied to identify significant gut microbiota and their correlation with hospitalization duration in AP patients. Results: Bidirectional MR results confirmed a causal link between specific gut microbiota and AP (15 and 8 microbial taxa identified via forward and reverse MR, respectively). The 16S rRNA sequencing analysis demonstrated a pronounced difference in gut microbiota composition between cases and controls. Notably, after a comprehensive evaluation of the results of RF and SVM, Bacteroides plebeius (B. plebeius) was found to play a significant role in influencing the hospital status. Using a receiver operating characteristic (ROC) curve, the predictive power (0.757) of B. plebeius. Kaplan-Meier survival analysis offered further insight that patients with an elevated abundance of B. plebeius experienced prolonged hospital stays. Conclusion: Combining MR with nested case-control studies provided a detailed characterization of interactions between gut microbiota and AP. B. plebeius was identified as a significant contributor, suggesting its role as both a precursor and consequence of AP dynamics. The findings highlight the multifactorial nature of AP and its complex relationship with the gut microbiota. This study lays the groundwork for future therapeutic interventions targeting microbial dynamics in AP treatment. [ABSTRACT FROM AUTHOR]

Background: Bladder cancer (BC) and Renal cell carcinoma (RCC) are the most common urogenital cancers among both sexes, with a yearly global incidence of around 500 000 each. Both BC and RCC have been linked to diabetes. Poor glycemic control (malglycemia) is a serious consequence of diabetes and a possible consequence of systemic treatments used in BC and RCC. The objective of this study was to investigate the prevalence of diabetes and use of hospital-based care for malglycemia in people with BC or RCC. Methods: This Swedish retrospective population-based register study used national health-data registers for longitudinal data on cancer incidence covering 15 years, use of hospital-based health care, and filled prescriptions of outpatient medications. Study endpoints included co-prevalence of diabetes in individuals with BC/RCC, healthcare resource utilization due to malglycemia, use of systemic corticosteroids, and changes in diabetes management for people with concomitant type 2 diabetes. Results: We identified 36,620 and 15,581 individuals diagnosed with BC and RCC, respectively, between 2006 and 2019. The proportion of individuals registered with diabetes was 24% in BC and 23% in RCC. An association between BC/RCC and poor glycemic control was found, although the number of malglycemic events in hospital-based care were few (65/59 per 1000 individuals with diabetes and BC/RCC respectively with at least one event). An earlier switch to insulin-based diabetes management was observed in BC/RCC compared to matched individuals with type 2 diabetes but no cancer. The results also indicated an association between steroid treatment and poor glycemic control, and that systemic corticosteroids were more common among people with BC/RCC compared to diabetes controls. Conclusion: The high prevalence of diabetes and increased use of systemic corticosteroid treatment observed in this large national study highlights the need for specific clinical management, risk-assessment, and monitoring of individuals with BC/RCC and diabetes. [ABSTRACT FROM AUTHOR]

Background: There is little evidence regarding risk prediction for surgical site infection (SSI) after lower third molar (L3M) surgery. Methods: We conducted a nested case–control study to develop a multivariable logistic model for predicting the risk of SSI after L3M surgery. Data were obtained from Hokkaido University Hospital from April 2013 to March 2020. Multiple imputation was applied for the missing values. We conducted decision tree (DT) analysis to evaluate the combinations of factors affecting SSI risk. Results: We identified 648 patients. The final model retained the available distal space (Pell & Gregory II [p = 0.05], Pell & Gregory III [p < 0.01]), depth (Pell & Gregory B [p < 0.01], Pell & Gregory C [p < 0.01]), surgeon's experience (3–10 years [p = 0.25], <3 years [p < 0.01]), and simultaneous extraction of both L3M [p < 0.01]; the concordance‐statistic was 0.72. The DT analysis demonstrated that patients with Pell and Gregory B or C and simultaneous extraction of both L3M had the highest risk of SSI. Conclusions: We developed a model for predicting SSI after L3M surgery with adequate predictive metrics in a single center. This model will make the SSI risk prediction more accessible. [ABSTRACT FROM AUTHOR]

Simple Summary: Using data from the Korean National Health Insurance Service—National Sample Cohort database, we evaluated whether patient-specific factors such as age, sex, income, residence, and the presence of comorbidities influence the relationship between gastric cancer (GC) and the likelihood of developing osteoporosis. Our study, with 1:4 propensity score matching and a stratified Cox proportional hazards model, showed that the hazard ratio of osteoporosis for the GC group was 1.13 (95%CI, 1.03–1.24) compared to that for the control group. In addition, subgroup analysis showed that age < 65 years, male sex, and a Charlson Comorbidity Index of 0 were risk factors for osteoporosis. Gastric cancer (GC) survivors may be more likely to develop osteoporosis. However, few studies on the relationship between GC and osteoporosis have been conducted on large patient populations. We aimed to determine the incidence of osteoporosis and identify related factors by comparing patients with GC and matched controls using the Korean National Health Insurance Service—National Sample Cohort (KNHIS-NSC). This study included 9078 patients with GC and 36,312 controls (1:4 propensity score-matched for sex, age, residence, and income). The hazard ratio (HR) for osteoporosis was significantly greater for GC patients than for controls according to Charlson Comorbidity Index (CCI) score-adjusted models (adjusted HR = 1.13). Kaplan–Meier analysis revealed that the cumulative incidence of osteoporosis during the follow-up period commencing from the index date was significantly greater in GC patients than in the controls (p = 0.0087). A positive correlation of osteoporosis with GC was detected for those aged < 65 years, males, and those with CCI scores = 0. In conclusion, the study findings suggest that men with GC aged < 65 years may be at an increased risk for osteoporosis. Research into additional risk factors and the optimal timing of interventions are needed to prevent fractures and minimize bone loss in GC survivors. [ABSTRACT FROM AUTHOR]

ABSTRACTAlthough previous studies have shown no increased mortality risk after the primary series of COVID-19 mRNA vaccines, reports on booster doses are lacking. This study aimed to evaluate mortality risk after the mRNA vaccine boosters in addition to the primary series. This nested case-control study included two age-specific cohorts (18–64 and ≥65 years as of February 1, 2021) in two municipalities. All deaths were identified and matched five controls for each case at each date of death (index date) with risk set sampling according to municipality, age, and sex. The adjusted odds ratios (aORs) and 95% confidence intervals (CIs) for mRNA vaccines (first to fifth doses) were estimated by comparing with no vaccination within 21 and 42 days before the index date using a conditional logistic regression model. The 18–64-years cohort comprised 431 cases (mean age, 57.0 years; men, 58.2%) and 2,155 controls (mean age, 56.0; men, 58.2%), whereas the ≥65-years cohort comprised 12,166 cases (84.0; 50.2%) and 60,830 controls (84.0, 50.2%). The aORs (95% CI) in 0–21 days after the third and fourth doses in the 18–64-years cohort were 0.62 (0.24, 1.62) and 0.38 (0.08, 1.84), respectively. The aORs (95% CI) after the third to fifth doses in the ≥65 years cohort were 0.36 (0.31, 0.43), 0.30 (0.25, 0.37), and 0.26 (0.20, 0.33), respectively. In conclusion, booster doses of mRNA vaccines do not increase mortality risk. These findings could help subsequent vaccine campaigns and alleviate vaccine hesitancy.

Background: Environmental pollution has emerged as a significant determinant in ovarian cancer prognosis. However, limited evidence exists regarding the correlations between heavy metals and ovarian cancer prognosis. Objective: To elucidate the relationship between urinary heavy metals and their mixtures with overall survival (OS) of advanced high-grade serous ovarian cancer (HGSOC). Methods: Within the Ovarian Cancer Follow-Up Study, we conducted a nested case-control study. A sum of 159 deceased patients and an equal number of alive patients were included, matched by sample date, body mass index, and age at diagnosis. Urinary concentrations of five heavy metals were quantified: arsenic (As), cadmium (Cd), chromium (Cr), mercury (Hg), and lead (Pb). Conditional logistic regression models were employed to calculate odds ratios (ORs) and their 95 % confidence intervals (CIs). To elucidate joint effects, we utilized quantile g-computation and Bayesian kernel machine regression models. Results: For the multivariable adjusted conditional logistic regression model, significant associations were found between high urinary levels of As (OR=1.99, 95 %CI: 1.05–3.79), Cd (OR=2.56, 95 %CI: 1.29–5.05), Hg (OR=2.24, 95 %CI: 1.09–4.62), and Pb (OR=3.80, 95 %CI: 1.75–8.27) and worse OS of HGSOC, comparing the highest tertile to the lowest. Analysis of joint effects showed that elevated concentrations of heavy metal mixtures were related to poor OS of HGSOC. Pb exhibited the highest contribution to the overall association within the metal mixtures. Conclusions: High urinary heavy metal concentrations were linked to worse OS of HGSOC. Future research is necessary to validate our findings.

BackgroundRecent studies have increasingly shown the connection between gut microbiome and gestational diabetes mellitus (GDM). However, no studies have explored the relationship between the gut virome and GDM, and the underlying mechanism remains unknown.MethodsWe performed a nested case-control study within a follow-up cohort, enrolling 51 patients with GDM and 51 healthy controls. Shotgun metagenomics sequencing was used to explore gut virome profiles during early pregnancy.ResultsDiversity analysis revealed no difference in the overall gut virome composition between two groups, however, we found greater abundance of Escherichia phage SH2026Stx1 (Q = 0.23), Enterobacteria phage mEp043 c-1 (Q = 0.21), crAssphage cr50_1 (Q = 0.21), Enterobacteria phage phi80 (Q = 0.21), and Escherichia phage HK106 (Q = 0.23) in GDM patients. Cross-kingdom correlation analysis showed the negative correlation between the gut bacterium Eubacterium eligens and three bacteriophages (Escherichia phage SH2026Stx1, Enterobacteria phage mEp043 c-1, and Escherichia phage HK106) in GDM group (r < 0, P < 0.05). Based on gut microbial features and clinical indicators, we constructed a new prediction model using random forest method for GDM with good predictive performance (AUC of 0.893, 95% CI: 0.736 ∼ 0.990).ConclusionThis study is the first to investigate the relationship between the gut virome and GDM as well as the cross-kingdom correlation between gut viruses and bacteria in GDM. Our findings could enhance strategies for preventing and treating GDM from the perspective of gut microbiome, offering valuable insights into its pathogenesis.

ObjectiveIschemic stroke-associated pneumonia (iSAP) affects about 10% of acute ischemic stroke patients during hospitalization. Current prediction scales for iSAP are insufficient. Identifying early biomarkers for stroke-associated pneumonia is crucial for improving patient outcomes. This study aimed to investigate the predictive value of euthyroid sick syndrome (ESS) for iSAP in acute-stage of ischemic stroke patients.MethodsWe studied 1767 acute ischemic stroke patients within one week of symptom onset, categorizing them into an infection group (iSAP, n=376) and control group (control, n=1391). COX regression analysis was used to identify the potential risk and protected factors. Kaplan-Meier time-event curves and Log-Rank tests were performed to differentiate infection time in patients with ESS or normal T3 group.ResultsThe iSAP group had higher rates of risk factors like older age, atrial fibrillation, COPD, and ESS, along with elevated levels of WBC, CRP,and FT4 levels (all P < 0.001). Conversely, iSAP patients had lower GCS scores, eGFR, TSH, T3, FT3 (all P < 0.001) and T4 levels (P = 0.005) upon admission. No significant differences were observed in sex, smoking history, hypertension, diabetes, or LDL-C levels (P > 0.05). COX regression analysis identified age, KWST scores, leukocyte count, CRP, and ESS (all P < 0.001) as significantly correlated with iSAP. ROC analysis revealed ESS as a predictor with sensitivity of 35.64% and specificity of 87.92% for SAP prediction, like atrial fibrillation and higher than COPD and eGFR.ConclusionESS at admission predicts a higher risk of stroke-associated pneumonia in acute-stage of ischemic stroke.

Abstract OPFRs are emerging environmental pollutants with reproductive and endocrine toxicity. This study aimed to examine the association between environmental exposure to OPFRs during early pregnancy and GDM. This nested case–control study was based on a birth cohort that was constructed at a maternal and child health hospital, including 74 cases of GDM among 512 pregnant women. The OPFRs, including TBP, TBEP, TCEP, TDCPP, TMCP, TOCP, and TPHP during 10–14 weeks of pregnancy were determined using GC–MS. The association between the OPFRs and GDM was assessed using WQS and BKMR models. The levels of OPFRs were significantly elevated in GDM patients (60) compared with the controls (90). The WQS analysis showed that mixtures of the OPFRs were significantly associated with GDM (OR 1.370, 95% CI 1.036–1.810, P = 0.027), and TBP, TPHP, and TMCP were the major contributors to the mixed exposure effect. In the BKMR model, individual exposure to TBP, TPHP, and TMCP, and the interaction of TMCP with TBP and TPHP were significantly associated with GDM. Environmental exposure to OPFRs is positively associated with GDM. These findings provide evidence for the adverse effects of OPFR exposure on the health of pregnant women.

ObjectiveTo design a prospective nested case-control study based on a city-wide birth cohort of Shanghai， so as to understand their health status and explore the influencing factors of birth defects.MethodsBased on the birth registration covering the entire city of Shanghai， the nested case-control study of children with severe birth defects was designed. Children born with severe birth defects were selected as the case group， and healthy children were matched as the control group. Basic information， health status， maternal pregnancy history， and survival outcome of children both in the case group and the control group were collected through medical history review and home visits. The logistic regression model was used for multivariate analysis.ResultsA total of 18 875 infants born between January 1， 2011， and December 31， 2021， were included， among which 11 500 （60.93%） were children with severe birth defects and 7 375 （39.07%） were healthy children. The logistic regression model analysis showed that being male （OR=1.20， 95%CI：1.13‒1.29）， non-Shanghai residency （OR=1.16， 95%CI： 1.06‒1.25）， multiple births （OR=8.41， 95%CI：6.25‒11.30）， artificial insemination （OR=2.31， 95%CI：1.34‒3.99）， in vitro fertilization （IVF） （OR=1.85， 95%CI：1.44‒2.38）， maternal exposure to radiation （OR=1.83， 95%CI：1.07‒3.14）， maternal illness during pregnancy （OR=1.61， 95%CI：1.49‒1.74）， experiencing a traumatic event during pregnancy （OR=2.34， 95%CI：1.88‒2.92）， paternal chemical exposure （OR=1.88， 95%CI：1.32‒2.69）， paternal radiation exposure （OR=1.65， 95%CI： 1.18‒2.33）， family history of birth defects （OR=8.18， 95%CI： 3.96‒16.89）， being overweight before pregnancy （OR=1.16， 95%CI： 1.07‒1.27）， being obese before pregnancy （OR=1.15， 95%CI：1.03‒1.30）， and being excessively obese before pregnancy （OR=1.52， 95%CI：1.26‒1.83） were risk factors for the occurrence of birth defects. Analysis by type of birth defect found that prematurity was a risk factor for cardiac malformations and cheilopalatoschisis （OR=27.87， 95%CI： 20.84‒37.27）， especially ranking first in cardiac malformations.ConclusionAfter controlling for influencing factors， maternal overweight， obesity， and excessive obesity before pregnancy， artificial insemination， and IVF are independent risk factors for the occurrence of birth defects. Choosing a healthy lifestyle， improving physical and mental health during pregnancy， and controlling BMI during pregnancy are beneficial in reducing the risk of birth defects.

Abstract Background Nested case–control (NCC) designs are efficient for developing and validating prediction models that use expensive or difficult-to-obtain predictors, especially when the outcome is rare. Previous research has focused on how to develop prediction models in this sampling design, but little attention has been given to model validation in this context. We therefore aimed to systematically characterize the key elements for the correct evaluation of the performance of prediction models in NCC data. Methods We proposed how to correctly evaluate prediction models in NCC data, by adjusting performance metrics with sampling weights to account for the NCC sampling. We included in this study the C-index, threshold-based metrics, Observed-to-expected events ratio (O/E ratio), calibration slope, and decision curve analysis. We illustrated the proposed metrics with a validation of the Breast and Ovarian Analysis of Disease Incidence and Carrier Estimation Algorithm (BOADICEA version 5) in data from the population-based Rotterdam study. We compared the metrics obtained in the full cohort with those obtained in NCC datasets sampled from the Rotterdam study, with and without a matched design. Results Performance metrics without weight adjustment were biased: the unweighted C-index in NCC datasets was 0.61 (0.58–0.63) for the unmatched design, while the C-index in the full cohort and the weighted C-index in the NCC datasets were similar: 0.65 (0.62–0.69) and 0.65 (0.61–0.69), respectively. The unweighted O/E ratio was 18.38 (17.67–19.06) in the NCC datasets, while it was 1.69 (1.42–1.93) in the full cohort and its weighted version in the NCC datasets was 1.68 (1.53–1.84). Similarly, weighted adjustments of threshold-based metrics and net benefit for decision curves were unbiased estimates of the corresponding metrics in the full cohort, while the corresponding unweighted metrics were biased. In the matched design, the bias of the unweighted metrics was larger, but it could also be compensated by the weight adjustment. Conclusions Nested case–control studies are an efficient solution for evaluating the performance of prediction models that use expensive or difficult-to-obtain biomarkers, especially when the outcome is rare, but the performance metrics need to be adjusted to the sampling procedure.

OPFRs are emerging environmental pollutants with reproductive and endocrine toxicity. This study aimed to examine the association between environmental exposure to OPFRs during early pregnancy and GDM. This nested case–control study was based on a birth cohort that was constructed at a maternal and child health hospital, including 74 cases of GDM among 512 pregnant women. The OPFRs, including TBP, TBEP, TCEP, TDCPP, TMCP, TOCP, and TPHP during 10–14 weeks of pregnancy were determined using GC–MS. The association between the OPFRs and GDM was assessed using WQS and BKMR models. The levels of OPFRs were significantly elevated in GDM patients (60) compared with the controls (90). The WQS analysis showed that mixtures of the OPFRs were significantly associated with GDM (OR 1.370, 95% CI 1.036–1.810, P = 0.027), and TBP, TPHP, and TMCP were the major contributors to the mixed exposure effect. In the BKMR model, individual exposure to TBP, TPHP, and TMCP, and the interaction of TMCP with TBP and TPHP were significantly associated with GDM. Environmental exposure to OPFRs is positively associated with GDM. These findings provide evidence for the adverse effects of OPFR exposure on the health of pregnant women. [ABSTRACT FROM AUTHOR]

Sjögren syndrome (SS) is a long-lasting inflammatory autoimmune disease that may cause diverse manifestations, particularly osteoporosis. Though usage of Chinese herbal medicine (CHM) can safely manage autoimmune disease and treatment-related symptoms, the relation between CHM use and osteoporosis risk in SS persons is not yet recognized. With that in mind, this population-level nested case-control study aimed to compare the risk of osteoporosis with and without CHM use. Potential subjects aged 20–70 years, diagnosed with SS between 2001 and 2010, were retrieved from a national health claims database. Those diagnosed with osteoporosis after SS were identified and randomly matched to those without osteoporosis. We capitalize on the conditional logistic regression to estimate osteoporosis risk following CHM use. A total of 1240 osteoporosis cases were detected and randomly matched to 1240 controls at a ratio of 1:1. Those receiving conventional care plus CHM had a substantially lower chance of osteoporosis than those without CHM. Prolonged use of CHM, especially for one year or more, markedly dwindled sequent osteoporosis risk by 71%. Integrating CHM into standard care may favor the improvement of bone function, but further well-designed randomized controlled trials to investigate the possible mechanism are needed. [ABSTRACT FROM AUTHOR]

Background: Nested case–control (NCC) designs are efficient for developing and validating prediction models that use expensive or difficult-to-obtain predictors, especially when the outcome is rare. Previous research has focused on how to develop prediction models in this sampling design, but little attention has been given to model validation in this context. We therefore aimed to systematically characterize the key elements for the correct evaluation of the performance of prediction models in NCC data. Methods: We proposed how to correctly evaluate prediction models in NCC data, by adjusting performance metrics with sampling weights to account for the NCC sampling. We included in this study the C-index, threshold-based metrics, Observed-to-expected events ratio (O/E ratio), calibration slope, and decision curve analysis. We illustrated the proposed metrics with a validation of the Breast and Ovarian Analysis of Disease Incidence and Carrier Estimation Algorithm (BOADICEA version 5) in data from the population-based Rotterdam study. We compared the metrics obtained in the full cohort with those obtained in NCC datasets sampled from the Rotterdam study, with and without a matched design. Results: Performance metrics without weight adjustment were biased: the unweighted C-index in NCC datasets was 0.61 (0.58–0.63) for the unmatched design, while the C-index in the full cohort and the weighted C-index in the NCC datasets were similar: 0.65 (0.62–0.69) and 0.65 (0.61–0.69), respectively. The unweighted O/E ratio was 18.38 (17.67–19.06) in the NCC datasets, while it was 1.69 (1.42–1.93) in the full cohort and its weighted version in the NCC datasets was 1.68 (1.53–1.84). Similarly, weighted adjustments of threshold-based metrics and net benefit for decision curves were unbiased estimates of the corresponding metrics in the full cohort, while the corresponding unweighted metrics were biased. In the matched design, the bias of the unweighted metrics was larger, but it could also be compensated by the weight adjustment. Conclusions: Nested case–control studies are an efficient solution for evaluating the performance of prediction models that use expensive or difficult-to-obtain biomarkers, especially when the outcome is rare, but the performance metrics need to be adjusted to the sampling procedure. [ABSTRACT FROM AUTHOR]

The aim of this study was to examine associations between serum folate levels and risk of disabling dementia that required care under the national insurance (disabling dementia). We performed a nested case–control study in a community-based cohort, the Circulatory Risk in Communities Study, involving 13,934 Japanese individuals aged 40–84 years at the baseline period of 1984–2005. Serum folate was measured in 578 cases of incident disabling dementia, and in 1,156 controls whose age (±1 years), sex, area of residence, and baseline year were matched with the cases. The diagnosis of disabling dementia was performed by attending physicians under the National Long-Term Care Insurance System in Japan. Conditional odds ratios of disabling dementia according to quintiles of serum folate were calculated using conditional logistic regression models. After a 20.8-year follow-up, serum folate was inversely associated with risk of disabling dementia. The respective multivariable odds ratios (95% CIs) were 0.71 (0.51–0.99), 0.76 (0.54–1.06), 0.70 (0.49–1.00), and 0.62 (0.43–0.90) for persons with the second, third, fourth, and highest quintiles of serum folate as compared with the lowest quintile (P for trend = 0.03). A similar association was observed for dementia with or without stroke. In this nested case–control study with a long follow-up, low serum folate levels were associated with an increased risk of disabling dementia among Japanese individuals. [ABSTRACT FROM AUTHOR]

Objective: The aim of the study is to predict employees' long-term sick leave due to psychiatric disorders using the national psychological stress screening program. Methods: University employees who took long-term psychiatric sick leave in 2016-2018 were assigned as cases. Those who were present at work and matched for sex, age, and occupation type were assigned as controls. Answers in a 57-item questionnaire were analyzed by multivariable regression, and a prediction model was developed. It was validated in cases and matched controls in 2019. Results: Six items were identified as independent predictors by multivariable regression and included in a prediction model. The area under the receiver-operating characteristics curve was 0.768 (95% confidence interval: 0.723-0.813). This finding was similar to that in the validation sample. Conclusions: The performance of the prediction model was modest and the national Stress Check Program should be further refined. [ABSTRACT FROM AUTHOR]

Growing research has proposed that rheumatoid arthritis (RA) and chronic periodontitis (CP) share similar pathophysiological mechanisms involving inflammation and tissue destruction. However, the potential correlation of CP as a contributing factor for the occurrence of RA warrants validation in the Korean population, where both diseases are prevalent, especially considering the increasingly aging demographic in Korea. This study examined 5139 RA cases and 509,727 matched controls from a Korean national cohort dataset (2002–2019) by carefully employing propensity score matching to ensure comparability between groups. Baseline characteristics were compared using standardized differences, and logistic regression was employed to estimate the impact of CP history on RA likelihood while controlling for covariates. We fully examined medical records documenting CP occurrences within the two-year period leading up to the index date, conducting comprehensive subgroup analyses. While a 1-year history of CP did not show a significant association with likelihood of RA, a 2-year history of CP increased RA likelihood by 12%, particularly among older adults, females, rural residents, and those with certain comorbidities such as hypercholesterolemia. Interestingly, this association persisted even among individuals with non-smoking habits, normal weight, and infrequent alcohol consumption. These findings suggest that chronic CP exposure for at least 2 years may independently elevate RA risk in Korean adults. The association in certain subgroups appears to suggest a predisposition toward genetic susceptibilities over lifestyle and environmental factors. Predicting RA in CP patients may be challenging, emphasizing the importance of regular RA screening, especially in high-risk subgroups. [ABSTRACT FROM AUTHOR]