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Background and Objectives Methods Results Conclusions 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.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.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.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 Methods Results Conclusions 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.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.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.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]

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: 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]

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]

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: 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]

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.

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.

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]

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]

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.

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.

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]

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]

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.

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.

Background: Previous studies have indicated a correlation between maternal imbalances in essential trace elements during pregnancy and the occurrence of spontaneous abortion (SA). Nonetheless, the impact of these elements from both partners and during the preconception period remains unexplored. Objective: This study sought to evaluate the relationship between preconception essential trace elements and spontaneous abortion (SA) based on husband–wife dyads. Methods: This study selected 390 couples with spontaneous abortion (SA) and 390 matched couples with live births from a preconception cohort of 33,687 couples. Urine samples collected prior to pregnancy were analyzed for ten essential trace elements (Se, Cr, Mo, Cu, Zn, Fe, Mn, V, Co, and Ni) using inductively coupled plasma mass spectrometry (ICP-MS). Results: Multivariate conditional logistic regression analysis identified that elevated concentrations of Zn (OR = 0.73) and Ni (OR = 0.69) in couples were associated with a reduced risk of SA, whereas elevated levels of Cr (OR = 1.30) and Mn (OR = 1.39) were linked to an increased risk. Restricted cubic spline models suggested a U-shaped association between couples’ Cu and Co concentrations and SA. Bayesian Kernel Machine Regression further supported a U-shaped relationship between the mixture of ten elements and SA, showing significant protection at the 50th and 55th percentiles compared to the 10th percentile. Additionally, the effects of Cr, Zn, Mn, and Ni on SA varied when the concentrations of the other nine elements were held constant at their 25th, 50th, and 75th percentiles. Stratified analysis revealed that maternal Cu (OR = 0.43) and Fe (OR = 0.63) reduced the risk of SA when paternal Cu and Fe were in the lower quartile. Conversely, maternal Cu (OR = 2.03) and Fe (OR = 1.77) increased the risk of SA when paternal concentrations were in the higher quartile. Similar patterns were observed for Cr, Mn, Co, and Zn. Conclusion: Elevated urinary concentrations of Zn and Ni in couples were associated with a reduced risk of SA, while higher levels of Cr and Mn were linked to an increased risk. Cu, Co, and a mixture of ten essential trace elements exhibited a U-shaped relationship with SA. The impact of certain essential trace elements (Cu, Fe, Cr, Mn, Co, and Zn) on SA in one partner was influenced by their concentrations in the other partner.

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.

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: 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]

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]

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]

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]

Given the global significance of gout and gastric cancer (GC) as major health problems with interrelated impacts, we examined the development of GC in Korean patients with gout. We conducted a nested case–control study using data from 10,174 GC patients and 40,696 control patients from the Korean National Health Insurance Service-National Sample Cohort database. Propensity score matching (1:4) with propensity score overlap-weighted adjustment was used to reduce selection bias and estimate the odds ratio (OR) and 95% confidence intervals (CIs) for the association between gout and GC. An adjusted OR for GC was not significantly higher in patients with gout than in control patients (1.02; 95% CI, 0.93–1.12; p = 0.652). Additionally, no association between gout and GC was observed in subgroup analyses such as sex, age, level of income, region of residence, or Charlson Comorbidity Index score. In conclusion, these results suggest that gout is not a significant independent risk factor for GC among the Korean population. Additional investigation is required to establish a causal association between gout and GC, and to generalize these results to general populations. [ABSTRACT FROM AUTHOR]

Aims: To investigate the association of methylation risk score (MRS) and its interactions with environmental factors with type 2 diabetes mellitus (T2DM) risk. Methods: We conducted a nested case–control study with 241 onset cases and 241 matched controls. Conditional logistic regression models were employed to identify risk CpG sites. Simple and weighted MRSs were constructed based on the methylation levels of ATP‐binding cassette G1 gene, fat mass and obesity associated gene, potassium voltage‐gated channel member 1 gene, and thioredoxin‐interacting protein gene previously associated with T2DM to estimate the association of MRS with T2DM risk. Stratified analyses were used to investigate interactions between MRS and environmental factors. Results: A total of 10 CpG loci were identified from the aforementioned genes to calculate MRS. After controlling for potential confounding factors, taking tertile 1 as reference, the odds ratios (ORs) and 95% confidence intervals (CIs) for T2DM of tertile 3 was 2.39 (1.36–4.20) for simple MRS and 2.59 (1.45–4.63) for weighted MRS. With per SD score increment in MRS, the OR (95% CI) was 1.66 (1.29–2.14) and 1.60 (1.24–2.08) for simple and weighted MRSs, respectively. J‐curved associations were observed between both simple and weighted MRSs and T2DM risks. Additionally, multiplication interactions for smoking and hypertension with simple MRS on the risk of T2DM were found, similarly for smoking and obesity with weighted MRS on the risk of T2DM (all Pinteraction <.05). Conclusion: Elevated simple and weighted MRSs were associated with increased risk of T2DM. Environmental risk factors may influence the association between MRS and T2DM. [ABSTRACT FROM AUTHOR]

BackgroundCatheter-related thrombosis (CRT) is a common complication for patients who receive central venous catheter (CVC) placement. This study investigated the risk factors for CRT and developed a nomogram for CRT prediction among cancer patients.MethodsThis nested case-control study was conducted in the Third Affiliated Hospital of Kunming Medical University between January 2019 and February 2021. Univariable and multivariable logistic regression analyses were used to identify the risk factors for CRT. A nomogram was developed to predict CRT. Receiver operating curves (ROC), calibration curves, and decision curves were used to evaluate the performance of the nomogram in the training and validation sets.ResultsA total of 4,691 cancer patients were included in this study. Among them, 355 (7.57%) had CRT, and 70% of CRTs occurred in the first week of insertion. Among the 3,284 patients in the training set, the multivariable analysis showed that nine characteristics were independently associated with CRT, and a nomogram was constructed based on the multivariable analysis. The ROC analysis indicated good discrimination in the training set (area under the curve [AUC] = 0.832, 95% CI: 0.802–0.862) and the testing set (AUC = 0.827, 95% CI: 0.783–0.871) for the CRT nomogram. The calibration curves showed good calibration abilities, and the decision curves indicated the clinical usefulness of the prediction nomograms.ConclusionThe validated nomogram accurately predicts CRT occurrence in cancer patients. This model may assist clinicians in developing treatment plans for each patient.

Objective: Colorectal cancer (CRC) incidence has been increasing worldwide over time. This study investigated whether drinking was associated with CRC risk. Methods: We designed a case-control study nested in a mass CRC screening program in Quzhou, China. Cases were newly diagnosed CRC in 2020–2022. Controls were randomly sampled using frequency match. Drinking variables included drinking status, frequency, duration, and others. Logistic regressions were used to estimate odds ratio (OR) and 95 % confidence interval (CI). Results: The crude OR (cOR) (95 % CI) of drinking between 153 cases and 650 controls was 1.46 (0.99, 2.16) in current drinkers, 3.31 (1.44, 7.60) in former drinkers, 1.82 (1.21, 2.74) in drinking 6–7 days/week, and 3.48 (1.29, 9.37) in drinking 1–19 years. Stratifying by sex, all drinking variables in women but not all in men were consistently associated with CRC risk. The adjusted OR (aOR) (95 % CI) was 1.01 (0.59, 1.74) in current drinking men, 2.27 (0.78, 6.64) in former drinking men, and 4.24 (1.61, 11.13) in current drinking women. The aOR (95 % CI) of drinking whisky was 0.19 (0.04, 0.83), 1.89 (0.86, 4.17), 2.25 (1.05, 4.83), and 1.82 (0.85, 3.92) in men drinking ≤0.5, >0.5–≤1.0, >1.0–≤1.5, and >1.5 Liter/week (Ptrend = 0.011), and 3.80 (1.03, 14.00) and 9.92 (2.01, 49.00) in women drinking ≤0.5 and >0.5 Liter/week (Ptrend = 0.001), respectively. Conclusions: There was sex difference in drinking associated with increased risk of CRC which association was stronger in women than that in men. Men’s association between drinking whisky and CRC risk was J-shaped.

Background: Phthalates (PAEs) are endocrine-disrupting chemicals ubiquitously found in the environment. This study aimed to examine the association between exposure of PAEs and subfecundity in preconception couples. Methods: This is a nested case-control study based on preconception cohort. Preconception couples with intention to conceive were enrolled and followed up until a clinically confirmed pregnancy or 12 menstrual cycles of preparation for conception. A total of 107 couples with subfecundity- time to pregnancy (TTP) more than 12 menstrual cycles, and 144 couples ≤12 cycles were included in the analysis. The levels of PAE metabolites in one spot urine samples were detected and compared between the groups. The weighted quantile sum (WQS) regression model and Bayesian kernel machine regression (BKMR) model were used to examine the joint effects of couples’ exposure to PAEs on subfecundity. Results: Using the multivariate binary logistic regression model, compared to the lowest quartile of urinary ∑PAEs concentration group, both preconception females (aOR=2.42, 95% CI: 1.10–5.30, p=0.027) and males (aOR=2.99, 95% CI: 1.36–6.58, p=0.006) in the highest quartile group had an increased risk of subfecundity, and a dose-response relationship was observed between PAEs and the risk of subfecundity. The WQS analyses found that co-exposure to PAE mixture was a risk factor for subfecundity in preconception female (aOR=1.76, 95% CI: 1.38–2.26, p

Background: Children with allergic rhinitis (AR) have substantially more acute rhinosinusitis than children without AR. We evaluated whether intranasal corticosteroids (INCS), second-generation antihistamines (SGH), and/or intranasal antihistamines (INH) for AR affect acute rhinosinusitis in children with AR aged 2–18 years. Methods: By using the National Health Research Institutes Database 2005 of Taiwan, a cohort of patients with AR aged 2–18 years treated with AR medications between 2002 and 2018 was made, within which a nested case–control study was performed. Risk settings for acute rhinosinusitis cases matched controls for age, sex, and comorbidities. Current users of INCS, INH, and/or SGH were compared with remote and recent users of any AR medications and current users of INCS with and without SGH were compared with current users of SGH. Results: Current users of SGH and/or INCS had a higher risk of acute rhinosinusitis than remote users of AR drugs, and current users of SGH had a higher risk of acute rhinosinusitis than recent users; however, no difference in the risk of acute rhinosinusitis was found between current users of INCS and recent users of AR drugs. Current users of INCS with and without SGH had a lower risk of acute rhinosinusitis than current users of SGH alone. Conclusions: Treatment of INCS with and without SGH diminished the risk of acute rhinosinusitis compared with treatment using SGH alone. Adequate INCS treatment for patients with AR is important to reduce the incidence of acute rhinosinusitis.

Abstract Background The therapeutic efficacy of renin-angiotensin system inhibitors (RASi) in elderly patients with hypertension and at risk of fractures has been in the limelight because of accumulating evidence that localized RAS activation in bone tissue leads to osteoclastic bone resorption, resulting in osteoporosis. This study set out to investigate the association between RASi use and fracture incidence in a large cohort. Methods We employed a nested case–control design to investigate the association between RASi use and newly developed fractures. A case was defined as a patient newly diagnosed with a fracture between January 2004 and December 2015. We selected 1,049 cases and controls using 1:1 propensity score matching. Conditional logistic regression analysis was conducted to estimate the association between RASi exposure and fracture incidence. Results Overall, RASi usage was significantly associated with lower odds for fracture incidence (ever-users vs never-users: OR, 0.73; 95% CI, 0.59–0.91). We found that ARB-only users experienced fewer fractures than RASi-never users (OR, 0.65; 95% CI, 0.49–0.86), whereas ACEi-only users or ARB/ACEi-ever users did not. In subgroup analysis, RASi-ever users without cerebrovascular disease, those with a BMI exceeding 23, and statin exposure had significantly lower ORs. Conclusions The present study established a significant association between RASi use and reduced fracture incidence, thus highlighting the potential clinical utility of RASi use as a preventive strategy in elderly patients at risk for osteoporotic fractures.

The aim of this study is to clarify the role of physical activity level and physical function on cognitive function of the elderly. A nested case–control investigation from a middle-aged and elderly cognitive health cohort was conducted. 103 mild cognitive impairment (MCI) patients were selected for the purpose of the study and matched 1:1 according to age and sex. Handgrip strength, gait speed and 5-time chair stand test were used to evaluate physical function. The physical activity scale for the elderly (PASE) was used to assess physical activity level. The Montreal cognitive assessment (MoCA) was used to quickly screen the mild cognitive impairment of the subjects. Body composition was estimated by bioelectrical impedance analysis. The total score of MoCA and the scores of different cognitive domains in two groups were different, handgrip strength was lower in the MCI group. Multivariate logistic regression model results showed that handgrip strength decreased could increase the risk of MCI(OR = 3.008, 95%CI: 1.421,6.369), higher PASE score was correlated with lower risk of MCI (OR = 0.402, 95%CI: 0.168,0.966). After combining body composition indices, handgrip strength and PASE score remained significantly associated with the occurrence of MCI, and there is an interaction. Logistic regression models were used for receiver operating characteristic curve analysis, all models demonstrate a good level of predictive performance for MCI. Physical activity level and physical function are associated with mild cognitive impairment. Higher physical activity level, normal handgrip strength are correlated with lower risk of MCI.

Abstract Background Some medical conditions may increase the risk of developing pulmonary tuberculosis (PTB); however, no systematic study on PTB-associated comorbidities and comorbidity clusters has been undertaken. Methods A nested case-control study was conducted from 2013 to 2017 using multi-source big data. We defined cases as patients with incident PTB, and we matched each case with four event-free controls using propensity score matching (PSM). Comorbidities diagnosed prior to PTB were defined with the International Classification of Diseases-10 (ICD-10). The longitudinal relationships between multimorbidity burden and PTB were analyzed using a generalized estimating equation. The associations between PTB and 30 comorbidities were examined using conditional logistic regression, and the comorbidity clusters were identified using network analysis. Results A total of 4265 cases and 17,060 controls were enrolled during the study period. A total of 849 (19.91%) cases and 1141 (6.69%) controls were multimorbid before the index date. Having 1, 2, and ≥ 3 comorbidities was associated with an increased risk of PTB (aOR 2.85–5.16). Fourteen out of thirty comorbidities were significantly associated with PTB (aOR 1.28–7.27), and the associations differed by sex and age. Network analysis identified three major clusters, mainly in the respiratory, circulatory, and endocrine/metabolic systems, in PTB cases. Conclusions Certain comorbidities involving multiple systems may significantly increase the risk of PTB. Enhanced awareness and surveillance of comorbidity are warranted to ensure early prevention and timely control of PTB.

Purpose: Following the withdrawal of propacetamol in Europe owing to safety issues, the regulatory authority of South Korea requested a post-marketing surveillance study to investigate its safety profile. Materials and Methods: We conducted nested case-control and case-time-control (CTC) analyses of cases and controls identified for outcomes of interest, including anaphylaxis, thrombosis, and Stevens--Johnson syndrome (SJS), using the claims database of South Korea, 2010--2019. Risk-set sampling was used to match each case with up to 10 controls for age, sex, cohort entry date, and follow-up duration. Exposure to anaphylaxis, thrombosis, and SJS was assessed within 7, 90, and 30 days of the index date, respectively. We calculated odds ratios (OR) with 95% confidence intervals (CIs) using conditional logistic regression to assess the risk of outcomes associated with propacetamol. Results: We identified cases of anaphylaxis (n=61), thrombosis (n=95), and SJS (n=1) and matched them to controls (173, 268, and 4, respectively). In the nested case-control analysis, the ORs for anaphylaxis and SJS were inestimable given the small number of propacetamol users during the risk period; meanwhile, the OR for thrombosis was 1.60 (95% CI 0.71--3.62). In the CTC design, the effect estimate was only estimated for thrombosis (OR 0.56, 95% CI 0.09--3.47). Conclusion: In both nested case-control and CTC analyses, propacetamol was not associated with an increased risk of anaphylaxis, thrombosis, or SJS. The findings from this study, which used routinely collected clinical data, provide reassuring real-world evidence regarding the safety of propacetamol in a nationwide population to support regulatory decision-making. [ABSTRACT FROM AUTHOR]

The high proportion of people with HIV (PWH) in the 2022–2023 mpox outbreak has raised questions surrounding the association between HIV and mpox. The objectives of this study were to evaluate the association between engagement in HIV-associated healthcare and mpox diagnosis, as well as to characterize cases of mpox among PWH. The DC Cohort is a longitudinal cohort of PWH in Washington, DC. We conducted a 5:1 (controls:cases) nested case-cohort study on male participants, matching age and care site. Cases were participants with an identified mpox diagnosis. Conditional logistic regression was used to assess the impact of indicators of engagement in HIV-associated healthcare on mpox diagnosis. We identified 70 cases of mpox in DC Cohort participants randomly matched to 323 controls, for a total of 393 participants included in the analysis. Study participants were primarily non-Hispanic Black (72.3%) with a median age of 41 (IQR: 36, 50). There was no association between engagement in care and mpox diagnosis; however, low CD4 was associated with increased odds of mpox diagnosis (aOR: 4.60 (95% CI: 1.23, 17.11)). Among a cohort of PWH, engagement in care was not associated with mpox diagnosis, suggesting that the overrepresentation of PWH among mpox cases is not due to surveillance bias. [ABSTRACT FROM AUTHOR]