Large-scale Population-based Cohort Research Articles

The Prevalence and Risk Factors of Clostridioides difficile Infection in Inflammatory Bowel Disease: 10-Year South Korean Experience Based on the National Database.

Few studies evaluate the epidemiology and risk factors of Clostridioides difficile infection (CDI) in Asian patients with inflammatory bowel disease (IBD). We investigated the year-end prevalence, cumulative incidence and risk factors of CDI in Asian patients with IBD using a large-scale population-based cohort in Korea. Using the National Health Insurance Service database, we identified patients with IBD and sex- and age-matched controls without IBD between 2008 and 2018. The year-end prevalence and cumulative incidence of CDI were compared among patients with Crohn's disease (CD) and ulcerative colitis (UC) with controls. The risk factors for CDI were evaluated. Among the 54,836 patients with IBD and 109,178 controls, CDI occurred in 293 patients with IBD and 87 controls. The annual year-end prevalence of CDI in patients with IBD increased from 8.6/10,000 persons in 2008 to 22.3/10,000 persons in 2018. The risk of CDI was higher in both patients with CD and UC than that in the matched controls (hazard ratio [HR], 7.285; 95% confidence interval [CI], 5.388-9.851; P < 0.001 and HR, 7.487; 95% CI, 5.796-9.670; P < 0.001, respectively). Among patients with IBD, the risk factors for CDI included older age, female sex, high Charlson comorbidity index score, and IBD-related medications including oral 5-aminosalicylic acid, immunomodulatory agents, biologics, and steroids used for > 90 days. The risk of CDI in Korean patients with IBD was approximately seven times higher than that in controls without IBD, and the annual year-end prevalence of CDI continuously increased from 2008 to 2018.

Frailty status and risk of irritable bowel syndrome in middle-aged and older adults: a large-scale prospective cohort study

Frailty is a public health problem for ageing society, however, evidence is lacking regarding its impact on intestinal functions. We aimed to examine prospective relationships of frailty and pre-frailty in middle-aged and older adults with incident irritable bowel syndrome (IBS) in a large-scale population-based cohort. Participants (aged 37-73 years) free of IBS, coeliac disease, inflammatory bowel disease and any cancer at baseline were included, using data from the UK Biobank (collected 2006-2010, 22 assessment centres). Participants without available primary care data were excluded. Frailty status was assessed using Fried phenotype including fivecriteria (weight loss, exhaustion, low grip strength, low physical activity, slow walking pace). Participants who met at least three criteria were defined as frail, and those who fulfilled one or two criteria were defined as pre-frail. Primary outcome was incident IBS. Cox proportional hazard model was conducted to examine the associated risk of incident IBS. Among 176,423 participants (mean age 56.19 years), 7994 (4.5%) and 78,957 (44.8%) were frail and pre-frail at baseline. During a median of 13.2-year follow-up, 4155 cases of incident IBS were identified. Compared with non-frail individuals, those with frail (HR=1.80, 95% CI: 1.59-2.04) and pre-frail (HR=1.21, 1.14-1.30) showed significantly higher risk of developing IBS after multivariable adjustment (Ptrend < 0.001). Specifically, the positive association was not only observed in older adults (HR=1.69, 1.37-2.08 for frail; 1.24, 1.12-1.39 for pre-frail), but also in middle-aged adults (HR=1.90, 1.62-2.22 for frail; 1.19, 1.10-1.30 for pre-frail), both with Ptrend < 0.001. Further sensitivity analysis and subgroup analysis indicated similar results. Frailty and pre-frailty in middle-aged and older adults are associated with increased risk of incident clinical diagnosis of IBS. National Natural Science Foundation of China (No. 82070550) & National Key Research and Development Program of China (2022YFC2504002, 2022YFC2504003).

Serum sex hormone-binding globulin is a mediator of the association between intrahepatic lipid content and type 2 diabetes: the Maastricht Study

Aims/hypothesisSerum sex hormone-binding globulin (SHBG) has been proposed to act as a hepatokine that contributes to the extrahepatic complications observed in non-alcoholic fatty liver disease (NAFLD). However, it remains uncertain whether serum SHBG mediates the association between intrahepatic lipids (IHL) and type 2 diabetes. Therefore, we studied whether, and to what extent, serum SHBG mediates the association between IHL content and type 2 diabetes.MethodsWe used cross-sectional data from the Maastricht Study (n=1554), a population-based cohort study with oversampling of individuals with type 2 diabetes. Type 2 diabetes status was assessed by oral glucose tolerance test, and IHL content was measured using 3T Dixon MRI. Mediation analyses were performed to assess the role of serum SHBG in mediating the association between IHL content and type 2 diabetes.ResultsIHL content was significantly associated with type 2 diabetes in women and men (OR 1.08 [95% CI 1.04, 1.14] and OR 1.12 [95% CI 1.08, 1.17], respectively). Serum SHBG significantly mediated the association between IHL content and type 2 diabetes. The contribution of serum SHBG was higher in women (OR 1.04 [95% CI 1.02, 1.07]; proportion mediated 50.9% [95% CI 26.7, 81.3]) than in men (OR 1.02 [95% CI 1.01, 1.03]; proportion mediated 17.2% [95% CI 9.6, 27.6]). Repeat analyses with proxies of type 2 diabetes and adjustment for covariates did not substantially affect the results.Conclusions/interpretationIn this large-scale population-based cohort study, serum SHBG was found to be a mediator of the association between IHL content and type 2 diabetes. These findings extend our understanding of the potential mechanisms by which NAFLD is a risk factor for type 2 diabetes, and further elaborate on the role of SHBG as a hepatokine.Graphical abstract

Association between acetabular dysplasia and sagittal spino-pelvic alignment in a population-based cohort in Japan

The relationship between acetabular dysplasia and spino-pelvic alignment remains unclear. The aim of this study was to clarify the association between acetabular dysplasia and spino-pelvic alignment, based on a large-scale population-based cohort in Japan. From the third survey of the Research on Osteoarthritis/Osteoporosis Against Disability (ROAD) study, 1,481 participants (491 men and 990 women; mean age, 65.3 years) were analyzed. Center-edge (CE) angle and spino-pelvic parameters (lumbar lordosis, LL; sacral slope, SS; pelvic tilt, PT; pelvic incidence, PI) were measured radiographically. Acetabular dysplasia was defined as a CE angle < 20°, and associations between acetabular dysplasia and spino-pelvic parameters were assessed. The group with acetabular dysplasia had significantly higher age, higher percentage of female, higher SS and higher PI than the group without acetabular dysplasia in a univariate analysis. On the other hand, acetabular dysplasia was not significantly associated with spino-pelvic parameters in a multiple logistic regression analysis that include age, sex, SS and PI as explanatory variables; however, PI demonstrated a positive odds ratio (odds ratio, 1.02; 95% CI 1.00–1.04). In conclusion, acetabular dysplasia was not significantly associated with spino-pelvic parameters, but higher PI may be an associated factor for acetabular dysplasia.

Siblings and Early Childhood Development: Evidence from a Population-Based Cohort in Preschoolers from Shanghai.

(1) Background: The current study aims to investigate the association between the presence of a sibling and early childhood development (ECD). (2) Methods: Data were obtained from a large-scale population-based cohort in Shanghai. Children were followed from three to six years old. Based on birth order, the sample was divided into four groups: single child, younger child, elder child, and single-elder transfer (transfer from single-child to elder-child). Psychosocial well-being and school readiness were assessed with the total difficulties score from the Strengths and Difficulties Questionnaire (SDQ) and the overall development score from the early Human Capability Index (eHCI), respectively. A multilevel model was conducted to evaluate the main effect of each sibling group and the group × age interaction effect on psychosocial well-being and school readiness. (3) Results: Across all measures, children in the younger child group presented with lower psychosocial problems (β = −0.96, 95% CI: −1.44, −0.48, p < 0.001) and higher school readiness scores (β = 1.56, 95% CI: 0.61, 2.51, p = 0.001). No significant difference, or marginally significant difference, was found between the elder group and the single-child group. Compared to the single-child group, the single-elder transfer group presented with slower development on both psychosocial well-being (Age × Group: β = 0.37, 95% CI: 0.18, 0.56, p < 0.001) and school readiness (Age × Group: β = −0.75, 95% CI: −1.10, −0.40, p < 0.001). The sibling-ECD effects did not differ between children from families of low versus high socioeconomic status. (4) Conclusion: The current study suggested the presence of a sibling was not associated with worse development outcomes in general. Rather, children with an elder sibling are more likely to present with better ECD.

Association between Coffee Consumption and Risk of Prostate Cancer in Japanese Men: A Population-Based Cohort Study in Japan.

Although numerous epidemiological studies have examined whether coffee consumption is associated with prostate cancer risk, the results remain controversial. Moreover, there are few studies in Asian populations. Therefore, we investigated the association between coffee consumption and the risk of prostate cancer in a large-scale prospective population-based cohort study in Japan. Study subjects were 48,222 men (40-69 years) who completed a questionnaire that included questions about their coffee consumption in 1990 for Cohort I and 1993 for Cohort II and were followed up until December 31, 2015. Newly diagnosed cases were classified into localized and advanced using information on local staging, the Gleason score, and degree of differentiation. Hazard ratios (HR) and 95% confidential intervals (95% CI) were estimated using Cox regression analysis. A total of 1,617 participants were newly diagnosed with prostate cancer during a mean follow-up period of 18.8 years. Of these, 1,099 and 461 patients had localized and advanced cancer, respectively. There was no association between coffee intake and prostate cancer risk. Comparison between the highest and lowest category of coffee consumption produced HRs of 1.08 (95% CI, 0.90-1.30), 1.08 (95% CI, 0.84-1.38), and 1.00 (95% CI, 0.67-1.47) for risk of total, localized, and advanced cancer, respectively. The same results were obtained even when we limited the analysis to patients with subjective symptoms. Our findings suggest that coffee consumption has no impact on prostate cancer risk in Japanese men. Coffee has no protective effects against prostate cancer among Japanese men.

Combined effects of host genetics and diet on human gut microbiota and incident disease in a single population cohort.

Human genetic variation affects the gut microbiota through a complex combination of environmental and host factors. Here we characterize genetic variations associated with microbial abundances in a single large-scale population-based cohort of 5,959 genotyped individuals with matched gut microbial metagenomes, and dietary and health records (prevalent and follow-up). We identified 567 independent SNP-taxon associations. Variants at the LCT locus associated with Bifidobacterium and other taxa, but they differed according to dairy intake. Furthermore, levels of Faecalicatena lactaris associated with ABO, and suggested preferential utilization of secreted blood antigens as energy source in the gut. Enterococcus faecalis levels associated with variants in the MED13L locus, which has been linked to colorectal cancer. Mendelian randomization analysis indicated a potential causal effect of Morganella on major depressive disorder, consistent with observational incident disease analysis. Overall, we identify and characterize the intricate nature of host-microbiota interactions and their association with disease.

Population study of the gut microbiome: associations with diet, lifestyle, and cardiometabolic disease

BackgroundThe human gut harbors trillions of microbes that play dynamic roles in health. While the microbiome contributes to many cardiometabolic traits by modulating host inflammation and metabolism, there is an incomplete understanding regarding the extent that and mechanisms by which individual microbes impact risk and development of cardiovascular disease (CVD). The Framingham Heart Study (FHS) is a multi-generational observational study following participants over decades to identify risk factors for CVD by correlating genetic and phenotypic factors with clinical outcomes. As a large-scale population-based cohort with extensive clinical phenotyping, FHS provides a rich landscape to explore the relationships between the gut microbiome and cardiometabolic traits.MethodsWe performed 16S rRNA gene sequencing on stool from 1423 participants of the FHS Generation 3, OMNI2, and New Offspring Spouse cohorts. Data processing and taxonomic assignment were performed with the 16S bioBakery workflow using the UPARSE pipeline. We conducted statistical analyses to investigate trends in overall microbiome composition and diversity in relation to disease states and systematically examined taxonomic associations with a variety of clinical traits, disease phenotypes, clinical blood markers, and medications.ResultsWe demonstrate that overall microbial diversity decreases with increasing 10-year CVD risk and body mass index measures. We link lifestyle factors, especially diet and exercise, to microbial diversity. Our association analyses reveal both known and unreported microbial associations with CVD and diabetes, related prescription medications, as well as many anthropometric and blood test measurements. In particular, we observe a set of microbial species that demonstrate significant associations with CVD risk, metabolic syndrome, and type 2 diabetes as well as a number of shared associations between microbial species and cardiometabolic subphenotypes.ConclusionsThe identification of significant microbial taxa associated with prevalent CVD and diabetes, as well as risk for developing CVD, adds to increasing evidence that the microbiome may contribute to CVD pathogenesis. Our findings support new hypothesis generation around shared microbe-mediated mechanisms that influence metabolic syndrome, diabetes, and CVD risk. Further investigation of the gut microbiomes of CVD patients in a targeted manner may elucidate microbial mechanisms with diagnostic and therapeutic implications.

Birth order and prosociality in the early adolescent brain

Birth order is a crucial environmental factor for child development. For example, later-born children are relatively unlikely to feel secure due to sibling competition or diluted parental resources. The positive effect of being earlier-born on cognitive intelligence is well-established. However, whether birth order is linked to social behavior remains controversial, and the neural correlates of birth order effects in adolescence when social cognition develops remain unknown. Here, we explored the birth order effect on prosociality using a large-scale population-based adolescent cohort. Next, since the amygdala is a key region for sociality and environmental stress, we examined amygdala substrates of the association between birth order and prosociality using a subset neuroimaging cohort. We found enhanced prosociality in later-born adolescents (N = 3160), and observed the mediating role of larger amygdala volume (N = 208) and amygdala-prefrontal functional connectivity with sex-selective effects (N = 183). We found that birth order, a non-genetic environmental factor, affects adolescent social development via different neural substrates. Our findings may indicate the later-born people’s adaptive survival strategy in stressful environments.

The association between obesity and quality of life: a retrospective analysis of a large-scale population-based cohort study

BackgroundThe relationship between obesity and health-related quality of life (HRQoL) may be confounded by factors such as multimorbidity. The aim of the study was to explore this relationship, controlling for long-term conditions and other health, lifestyle and demographic factors in a general adult population. There was specific interest in the impact of high weight status, measured by body mass index (BMI) levels (obesity, morbid obesity) compared with individuals of normal weight.MethodsHealth, lifestyle and demographic data were collected from 64,631 individuals aged 16 years and over registered in the Yorkshire Health Study; a long-term cohort study. Data were collected in 2 waves: from patients attending GP surgeries in the South Yorkshire region; and using online recruitment across the entire Yorkshire and Humber area. Univariable and multivariable regression methods were utilised to identify factors associated with HRQoL as measured by the EQ-5D summary score. Long-term conditions were tested as both covariates and mediating factors on the causal pathway between obesity and HRQoL.ResultsIncreasing levels of obesity are associated with reduced HRQoL, although this difference is negligible between those of normal weight and those who are overweight. Individuals with obesity and morbid obesity score 4.9 and 11.3 percentage points less on the EQ-5D summary scale respectively than those of normal weight. Concurrent physical, and particularly mental health-related long-term conditions are substantively related to HRQoL: those with 3 or more reported mental or physical health conditions score 29.8 and 14.6 percentage points less on the EQ-5D summary scale respectively than those with fewer conditions. Long-term conditions can be conceptualised as lying on the causal path between obesity and HRQoL, but there is weak evidence for a partial mediating relationship only.ConclusionsTo conclude, in agreement with the established literature we have found a clear inverse relationship between increasing weight status and decreasing HRQoL and confirmed the mediating role of long-term conditions in the reduction of HRQoL in people with obesity. Nevertheless, a high BMI remains independently related to HRQoL, suggesting that ‘healthy people with obesity’ may be in transition to an unhealthy future.

Association between sugar and starch intakes and type 2 diabetes risk in middle-aged adults in a prospective cohort study.

We aimed to investigate the association between sugar or starch intake and the risk of type 2 diabetes (T2D) in middle-aged Japanese adults. Participants comprised 27,797 men and 36,880 women aged 45-75 years with no history of diabetes and critical illness before the second survey in the Japan Public Health Center-based Prospective Study. We calculated sugar (total sugar, total fructose, and sugar subtypes) and starch intakes (% energy/d) using a validated 147-item food frequency questionnaire, to estimate the average dietary intake over the previous year. T2D onset was defined by validated self-reports. ORs adjusted for potential confounders were estimated using multiple logistic regression with categorical and cubic spline models. During the 5-year follow-up, 690 men and 500 women were identified with T2D. In women, the quartiles of total sugar or total fructose intakes were not significantly associated with T2D risk; however, the spline curves showed an increased risk at extremely high intake levels (ORs [95% CI]: 1.88 [1.07-3.31] at 30% energy/d for total sugar and 1.87 [1.10-3.16] at 14% energy/d for total fructose). Starch intake was positively associated with T2D risk among women in the categorical and spline models (ORs [95% CI]: 1.55 [1.13-2.12] at 50% energy/d). In men, sugar and starch intakes were not associated with T2D risk. In this large-scale population-based cohort study, starch intake was associated with an increased T2D risk in Japanese women. An increased risk with extremely high intake of total sugar or total fructose among women cannot be disregarded.

U-Shaped Effect of Blood Pressure on Structural OCT Metrics and Retinal Perfusion in Ophthalmologically Healthy Subjects.

PurposeWe wanted to investigate the association of blood pressure (BP) status with the ganglion cell-inner plexiform layer (GCIPL) and retinal nerve fiber layer (RNFL) thickness of nonglaucomatous eyes and to elucidate whether this effect is related to vascular metrics proxying retinal perfusion.MethodsFor this case-control study, we prospectively included 96 eyes of 96 healthy subjects (age 50–65) from a large-scale population-based cohort in the northern Netherlands (n = 167,000) and allocated them to four groups (low BP, normal BP [controls], treated arterial hypertension [AHT], untreated AHT). We measured macular GCIPL and RNFL (mRNFL) and peripapillary RNFL (pRNFL) thicknesses with optical coherence tomography (OCT). We estimated retinal blood flow (RBF), retinal vascular resistance (RVR), and autoregulatory reserve (AR) from quantitative OCT-angiography, fundus imaging, BP, and intraocular pressure. We compared structural and vascular metrics across groups and performed mediation analysis.ResultsCompared to controls, GCIPL was thinner in the low BP group (P = 0.013), treated hypertensives (P = 0.007), and untreated hypertensives (P = 0.007). Treated hypertensives exhibited the thinnest mRNFL (P = 0.001), temporal pRNFL (P = 0.045), and inferior pRNFL (P = 0.034). The association of GCIPL thickness with BP was mediated by RBF within the combined low BP group and controls (P = 0.003), by RVR and AR within the combined treated hypertensives and controls (P = 0.001, P = 0.032), and by RVR within the combined untreated antihypertensives and controls (P = 0.022).ConclusionsInner retinal thinning was associated with both tails of the BP distribution and with ineffective autoregulation. Longitudinal studies could clarify whether these defects can explain the reported glaucomatous predisposition of these population groups.

Development and validation of a new diabetes index for the risk classification of present and new-onset diabetes: multicohort study

In this study, we aimed to propose a novel diabetes index for the risk classification based on machine learning techniques with a high accuracy for diabetes mellitus. Upon analyzing their demographic and biochemical data, we classified the 2013–16 Korea National Health and Nutrition Examination Survey (KNHANES), the 2017–18 KNHANES, and the Korean Genome and Epidemiology Study (KoGES), as the derivation, internal validation, and external validation sets, respectively. We constructed a new diabetes index using logistic regression (LR) and calculated the probability of diabetes in the validation sets. We used the area under the receiver operating characteristic curve (AUROC) and Cox regression analysis to measure the performance of the internal and external validation sets, respectively. We constructed a gender-specific diabetes prediction model, having a resultant AUROC of 0.93 and 0.94 for men and women, respectively. Based on this probability, we classified participants into five groups and analyzed cumulative incidence from the KoGES dataset. Group 5 demonstrated significantly worse outcomes than those in other groups. Our novel model for predicting diabetes, based on two large-scale population-based cohort studies, showed high sensitivity and selectivity. Therefore, our diabetes index can be used to classify individuals at high risk of diabetes.

Risk Factors for Gallstones and Cholecystectomy: A Large-Scale Population-Based Prospective Cohort Study in Japan

Introduction: Studies investigating the risk of gallstones in the Japanese population are sparse. To our knowledge, this is the first prospective cohort study assessing risk factors of gallstones in Japan. Methods: A nationwide population-based prospective cohort of 112,109 men and women, aged 40–69 years, self-completed questionnaires at baseline regarding exposures to potential risk factors, between 1990 and 1994. The occurrence of gallstones and cholecystectomy for gallstones were ascertained from another questionnaire after 10 years. Odds ratios and the 95% confidence intervals were calculated using the multivariate logistic regression. Results: During the 10-year follow-up, 3,092 (5.0%) participants developed gallstones and 729 (1.2%) participants required cholecystectomy. Increasing age, high body mass index, and diabetes mellitus were associated with the risk of gallstones in both sexes. In men, weight gain or loss of >5 kg over the follow-up period and stress were associated with risk of gallstones, whereas alcohol intake was inversely associated with the risk. In women, weight gain of >5 kg during the follow-up period, smoking, menopause, and lipid-lowering drugs were associated with risk of gallstones, whereas late onset of menarche was inversely associated with risk of gallstones. The risk of cholecystectomy broadly reflected the risk of gallstones for both sexes respectively. Conclusion: Risk factors for both gallstones and cholecystectomy for gallstones are multifactorial and differ between men and women. Novel findings in this study include an inverse association between late onset of menarche and gallstones, and an association between self-reported stress in men and gallstones.

Red blood cell folate, high-risk human papillomavirus risk and cervical intraepithelial neoplasia development: A large Chinese community-based cohort study of cervical screening.

10547 Background: Although low folate status has been implicated in cervical carcinogenesis, large-scale population-based prospective cohort studies controlling for high-risk types of human papillomavirus (hrHPV) infection are lacking. The aim of this study is to evaluate the associations of red blood cell (RBC) folate, hrHPV infection risk and cervical intraepithelial neoplasia (CIN) development. Methods: In this prospective, population-based cohort study, we analyzed the cross-sectional data of 2304 women from a large cervical cancer screening program of 40,000 women aged 19-65 years in the Chinese rural area from 2014-2015. We conducted a nested case-control study including 35 CIN1 progression cases and 105 CIN1 regression controls. A logistic regression model was used to evaluate the associations of RBC folate and hrHPV infection risk and CIN1 development. Results: The median RBC folate concentration decreased gradually with cervical lesion severity. The risks of CIN 1 and CIN2 or worse (CIN 2+) in the 1st quartile of RBC folate concentration were significantly higher than those in the 4th quartile (Odds Ratio [OR], 2.27; 95% confidence interval [CI], 1.71-3.01 and OR, 2.33; 95% CI,1.52-3.56; respectively). We did not observe a significant relationship between hrHPV infection and CIN1 risk in the unadjusted and adjusted models, however, a statistically significant association was observed for CIN2+. Interestingly, RBC folate concentration was not associated with hrHPV infection among women with CIN1 or CIN2+. After full adjustment for potential confounders, a highly significant inverse linear relation between RBC folate concentration and CIN2+ was observed ( P-overall＜0.001, P-nonlinearity = 0.969). We further observed a positive additive interaction between RBC folate concentration and hrHPV infection on the risk of CIN2+ ( P-interaction＜0.01). Moreover, during the 21-month follow-up, CIN1 progression risk was significantly higher in the lowest RBC folate quartile (1st quartile compared with 4th quartile: OR, 3.86; 95% CI,1.01-14.76). Conclusions: Our findings indicates that RBC folate is inversely associated with the risk of higher-grade CIN and CIN1 progression in the Chinese rural population, either with or without hrHPV infection. Therefore, improving folate status has the potential to prevent higher-grade CIN and cervical cancer among women in the areas without mandatory folic acid food fortification. Clinical trial information: ChiCTR-ROC-15006479 .

Alcohol consumption and breast cancer risk in Japan: A pooled analysis of eight population-based cohort studies.

Although alcohol consumption is reported to increase the incidence of breast cancer in European studies, evidence for an association between alcohol and breast cancer in Asian populations is insufficient. We conducted a pooled analysis of eight large-scale population-based prospective cohort studies in Japan to evaluate the association between alcohol (both frequency and amount) and breast cancer risk with categorization by menopausal status at baseline and at diagnosis. Estimated hazard ratios (HR) and 95% confidence intervals were calculated in the individual cohorts and combined using random-effects models. Among 158 164 subjects with 2 369 252 person-years of follow-up, 2208 breast cancer cases were newly diagnosed. Alcohol consumption had a significant association with a higher risk of breast cancer in both women who were premenopausal at baseline (regular drinker compared to nondrinker: HR 1.37, 1.04-1.81, ≥23 g/d compared to 0 g/d: HR 1.74, 1.25-2.43, P for trend per frequency category: P = .017) and those who were premenopausal at diagnosis (≥23 g/d compared to 0 g/d: HR 1.89, 1.04-3.43, P for trend per frequency category: P = .032). In contrast, no significant association was seen in women who were postmenopausal at baseline or at diagnosis, despite a substantial number of subjects and long follow-up period. Our results revealed that frequent and high alcohol consumption are both risk factors for Asian premenopausal breast cancer, similarly to previous studies in Western countries. The lack of a clear association in postmenopausal women in our study warrants larger investigation in Asia.

Anxiety and depression predispose individuals to an autoimmune bullous diseases- bullous pemphigoid: A large-scale population-based cohort study

The association of bullous pemphigoid (BP) with anxiety and anxiety-depression comorbidity is yet to be established. We aimed to evaluate the bidirectional association of BP with anxiety, depression, and anxiety-depression comorbidity, and to delineate the epidemiological features of patients with BP and the aforementioned psychiatric comorbidities. A population-based cohort study was performed to assess the risk of anxiety, depression, and anxiety-depression comorbidity among patients with BP (n = 3924) relative to age-, sex- and ethnicity-matched control subjects (n = 19,280). A case-control design was additionally adopted to estimate the odds of BP in individuals with a preexisting diagnosis of these three psychiatric conditions. Adjusted hazard ratios (HRs) and adjusted odds ratios (ORs) were estimated by Cox regression and logistic regression, respectively. A history of anxiety (OR, 1.17; 95% CI, 1.04–1.31), depression (OR, 1.26; 95% CI, 1.15–1.38), and anxiety-depression comorbidity (OR, 1.19; 95% CI, 1.04–1.35) was associated with subsequent development of BP. In the cohort study design, patients with BP were found to be at an increased overall risk of depression (HR, 1.17; 95% CI, 1.01–1.35), while female BP patients had an increased risk of depression (HR, 1.19; 95% CI, 1.00–1.42) and anxiety (HR, 1.29; 95% CI, 1.00–1.67). Patients with comorbid BP and depression exhibited a 19% increased all-cause mortality rate (HR, 1.19; 95% CI, 1.08–1.31), whereas patients with BP and anxiety-depression comorbidity were less adherent to long-term topical corticosteroid treatment and less frequently managed by adjuvant agents. In conclusion, a history of anxiety, depression, and anxiety-depression comorbidity predisposes individuals to BP, whereas patients with BP are at an increased risk of depression. Clinicians managing patients with anxiety and depression should take the increased risk of BP into consideration, and patients with BP should be monitored for depression.

Intake of Vegetables and Fruits and the Risk of Cataract Incidence in a Japanese Population: The Japan Public Health Center-Based Prospective Study.

BackgroundAlthough the consumption of vegetables and fruits is reported to influence the risk of cataract, no prospective study of this association from Asia has yet appeared. Here, we investigated the association between vegetable and fruit intake and cataract incidence in a large-scale population-based prospective cohort study in Japan.MethodsThis study included 32,387 men and 39,333 women aged 45–74 years who had no past history of cataract and had completed a dietary questionnaire of the Japan Public Health Center-based Prospective Cohort Study. The incidence of cataract was evaluated after 5-year follow-up. We used multiple logistic regression analyses to estimate the sex-specific odds ratios (ORs), with adjustment for confounding factors.ResultsWe identified 1,836 incident cataracts in 594 men and 1,242 women. In men, the OR for cataract was decreased with higher intake of vegetables (ORQ5 vs Q1, 0.77; 95% confidence interval [CI], 0.59–1.01; Ptrend across quartile categories = 0.03) and cruciferous vegetables (ORQ5 vs Q1, 0.74; 95% CI, 0.57–0.96; Ptrend = 0.02). In contrast, the OR for cataract was increased with higher intake of vegetables among women (ORQ5 vs Q1, 1.28; 95% CI, 1.06–1.53; Ptrend = 0.01). Green and yellow vegetable and fruit intake were not associated with cataract in either sex.ConclusionsThis study suggests that vegetables may reduce the risk of cataract in men, but not in women.

Development and Validation of a New Risk Prediction Model for New-Onset Diabetes: Multicohort Study

Background: In this study, we aimed to propose a novel risk prediction model based on machine learning techniques with a high accuracy for diabetes mellitus. Methods: Upon analyzing their demographic and biochemical data, we classified the 2013–16 Korea National Health and Nutrition Examination Survey (KNHANES), the 2017–18 KNHANES, and the Korean Genome and Epidemiology Study (KoGES), as the derivation, internal validation, and external validation sets, respectively. We constructed a new diabetes index using logistic regression (LR) and calculated the probability of diabetes in the validation sets. We used the area under the receiver operating characteristic curve (AUROC) and Cox regression analysis to measure the performance of the internal and external validation sets, respectively. Findings: Based on literature review, we identified candidate risk factors, of which 20 were selected using backward stepwise LR. We constructed a gender-specific diabetes prediction model, having a resultant AUROC of 0.93 and 0.94 for men and women, respectively. Thereafter, we calculated the probability of diabetes in non-diabetic KoGES subjects at baseline. Based on this probability, we classified participants into five groups and analyzed cumulative incidence from the KoGES dataset. Group 5 demonstrated significantly worse outcomes than those in other groups. Interpretation: Our novel model for predicting diabetes, based on two large-scale population-based cohort studies, showed high sensitivity and selectivity. Therefore, our prediction model can be used to classify individuals at high risk of diabetes, in whom lifestyle modifications may be employed for the prevention of the disease. Funding Statement: This research was supported by the Basic Science Research Program, through the National Research Foundation of Korea (NRF), and funded by the Ministry of Education (2020R1C1C1004999 to C.M.O). Declaration of Interests: The authors declare no conflict of interest. Ethics Approval Statement: The Institutional Review Board of Gwangju Institute of Science and Technology (South Korea) approved the study protocol (IRB No. 20200414-EX-01-02). All research procedures were performed in accordance to the relevant guidelines and regulations. All participants volunteered and provided written informed consent prior to enrolment, and their records were anonymized before being accessed by the authors.

Patients with pemphigus are at an increased risk of developing rheumatoid arthritis: a large-scale cohort study

Data regarding the association between pemphigus and rheumatoid arthritis (RA) is inconclusive and yet to be firmly established. In the current study, we aimed to evaluate the risk of developing RA during the course of pemphigus. A large-scale population-based longitudinal cohort study was conducted to evaluate the hazard ratio (HR) of RA among 1985 patients with pemphigus relative to 9874 age-, sex-, and ethnicity-matched control subjects. A multivariate Cox regression model was utilized. The incidence of RA was 1.07 (95% CI, 0.62–1.72) and 0.36 (95% CI, 0.24–0.52) per 1000 person-years among patients with pemphigus and controls, respectively. The lifetime prevalence of RA was 2.3% (95% CI, 1.7–3.1%) among cases and 1.8% (95% CI, 1.5–2.0%) among controls. Patients with pemphigus were more than twice as likely to develop RA as compared to control subjects (adjusted HR, 2.54; 95% confidence interval [CI], 1.31–4.92). The increased risk was robust to a sensitivity analysis that included only cases managed by pemphigus-related systemic medications (adjusted HR, 2.56; 95% CI, 1.30–5.05). In conclusion, pemphigus is associated with an increased risk of RA. Physicians treating patients with pemphigus should be aware of this possible association. Further research is required to better understand the mechanism underlying this association.