Age at menarche by birth cohort: A pooled analysis of half a million women in Asia.

OBJECTIVES: To evaluate changes in the age at menarche in Asian populations. STUDY DESIGN: Retrospective cohort study. METHODS: We included 548,830 women from six countries in Asia. The data were sourced from 20 cohorts participating in the Asia Cohort Consortium (ACC) and two additional cohort studies: Japan Multi-institutional Collaborative Cohorts (J-MICC), and Japan Nurse Health Study (JNHS) with data on age at menarche. Joinpoint regression was used to evaluate changes in age at menarche by birth year and by country. RESULTS: The study includes data from cohorts in six Asian countries namely, China, Iran, Japan, Korea, Malaysia and Singapore. Birth cohorts ranged from 1873 to 1995. The mean age of menarche was 14.0 years with a standard deviation (SD) of 1.4 years, ranged from 12.6 to 15.5 years. Over 100 years age at menarche showed an overall decrease in all six countries. China showed a mixed pattern of decrease, increase, and subsequent decrease from 1926 to 1960. Iran and Malaysia experienced a sharp decline between about 1985 and 1990, with APC values of -4.48 and -1.24, respectively, while Japan, South Korea, and Singapore exhibited a nearly linear decline since the 1980s, notably with an APC of -3.41 in Singapore from 1993 to 1995. CONCLUSIONS: Overall, we observed a declining age at menarche, while the pace of the change differed by country. Additional long-term observation is needed to examine the contributing factors of differences in trend across Asian countries. The study could serve as a tool to strengthen global health campaigns.

Association between family history with lung cancer incidence and mortality risk in the Asia Cohort Consortium.

Family history of lung cancer (FHLC) has been widely studied but most prospective cohort studies have primarily been conducted in non-Asian countries. We assessed the association between FHLC with risk of lung cancer (LC) incidence and mortality in a population of East Asian individuals. A total of 478,354 participants from 11 population-based cohorts in the Asia Cohort Consortium were included. A Cox proportional hazards regression model was used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). A total of 7,785 LC incident cases were identified. FHLC (any LC subtype) was associated with an increased risk of LC incidence (HR = 1.45, 95% CI = 1.30-1.63). The positive association was observed in men and women (HR = 1.44, 95% CI = 1.26-1.66 in men; HR = 1.47, 95% CI = 1.22-1.79 in women), and in both never-smokers and ever-smokers (HR = 1.43, 95% CI = 1.18-1.73 in never-smokers; HR = 1.46, 95% CI =1.27-1.67 in ever-smokers). FHLC was associated with an increased risk of lung adenocarcinoma (HR = 1.63, 95% CI: 1.36-1. 94), squamous cell carcinoma (HR = 1.88, 95% CI: 1.46-2.44), and other non-small cell LC (HR = 1.94, 95% CI: 1.02-3.68). However, we found no evidence of significant effect modification by sex, smoking status, and ethnic groups. In conclusion, FHLC was associated with increased risk of LC incidence and mortality, and the associations remained consistent regardless of sex, smoking status and ethnic groups among the East Asian population.

A Comparison of Green, Delta, and Monte Carlo Methods to Select an Optimal Approach for Calculating the 95% Confidence Interval of the Population-attributable Fraction: Guidance for Epidemiological Research.

OBJECTIVES: This study aimed to compare the Delta, Greenland, and Monte Carlo methods for estimating 95% confidence intervals (CIs) of the population-attributable fraction (PAF). The objectives were to identify the optimal method and to determine the influence of primary parameters on PAF calculations. METHODS: A dataset was simulated using hypothetical values for primary parameters (population, relative risk [RR], prevalence, and variance of the beta estimator ) involved in PAF calculations. Three methods (Delta, Greenland, and Monte Carlo) were used to estimate the 95% CIs of the PAFs. Perturbation analysis was performed to assess the sensitivity of the PAF to changes in these parameters. An R Shiny application, the "GDM-PAF CI Explorer," was developed to facilitate the analysis and visualization of these computations. RESULTS: No significant differences were observed among the 3 methods when both the RR and p-value were low. The Delta method performed well under conditions of low prevalence or minimal RR, while Greenland's method was effective in scenarios with high prevalence. Meanwhile, the Monte Carlo method calculated 95% CIs of PAFs that were stable overall, though it required intensive computational resources. In a novel approach that utilized perturbation for sensitivity analysis, was identified as the most influential parameter in the estimation of CIs. CONCLUSIONS: This study emphasizes the necessity of a careful approach for comparing 95% CI estimation methods for PAFs and selecting the method that best suits the context. It provides practical guidelines to researchers to increase the reliability and accuracy of epidemiological studies.

Hospitalization among adults with chronic kidney disease: results from the KoreaN cohort study for Outcomes in patients With Chronic Kidney Disease (KNOW-CKD) study.

Background: Chronic kidney disease (CKD) patients are hospitalized for various conditions. Hospitalization increases the readmission rate and mortality rate, seriously deteriorating patients' quality of life. Consequently, it is crucial to analyze the reasons for hospitalization in CKD patients from a broader perspective according to CKD grade. Methods: This is a prospective cohort study of CKD patients entitled the KoreaN Cohort Study for Outcomes in Patients With Chronic Kidney Disease (KNOW-CKD). A total of 2,238 patients were examined, and the reasons for hospitalization were classified into 16 disease categories. The incidence rate ratio (IRR) according to CKD stage was compared using negative bimodal regression analysis. Results: The all-cause hospitalization incidence was 184.96 per 1,000 person-years. The most common reason for hospitalization was circulatory system disease, followed by infection and digestive system disease. Among hospitalizations for acute kidney injury, endocrine-nutrition-metabolic-related illness, blood-related disease, and diseases of the nervous system and sensory organs, IRR increased as CKD grade advanced. The incidence of ophthalmologic surgery during hospitalization increased according to the CKD stage. The IRR of KNOW-CKD patients was 6.19 (95% confidence interval, 5.92-6.48; p < 0.001) compared with the general population. Conclusion: This in-depth analysis of hospitalizations among CKD patients confirmed that CKD patients were hospitalized for various reasons, such as metabolic, ophthalmic, and hematologic diseases. Early detection and intervention regarding causative diseases of CKD are important to reduce the hospitalization burden and improve patients' quality of life.

Body Mass Index and Risk of Colorectal Cancer Incidence and Mortality in Asia.

Importance: The global burden of obesity is increasing, as are colorectal cancer (CRC) incidence and mortality. Objectives: To assess the association between body mass index (BMI) and risks of incident CRC and CRC-related death in the Asian population. Design, Setting, and Participants: This cohort study includes data pooled from 17 prospective cohort studies included in The Asia Cohort Consortium. Cohort enrollment was conducted from January 1, 1984, to December 31, 2002. Median follow-up time was 15.2 years (IQR, 12.1-19.2 years). Data were analyzed from January 15, 2023, through January 15, 2024. Exposure: Body mass index, calculated as weight in kilograms divided by height in meters squared. Main Outcomes and Measures: The primary outcomes were CRC incidence and CRC-related mortality. The risk of events is reported as adjusted hazard ratios (AHRs) and 95% CIs for incident CRC and death from CRC using the Cox proportional hazards regression model. Results: To assess the risk of incident CRC, 619 981 participants (mean [SD] age, 53.8 [10.1] years; 52.0% female; 11 900 diagnosed incident CRC cases) were included in the study, and to assess CRC-related mortality, 650 195 participants (mean [SD] age, 53.5 [10.2] years; 51.9% female; 4550 identified CRC deaths) were included in the study. A positive association between BMI and risk of CRC was observed among participants with a BMI greater than 25.0 to 27.5 (AHR, 1.09 [95% CI, 1.03-1.16]), greater than 27.5 to 30.0 (AHR, 1.19 [95% CI, 1.11-1.29]), and greater than 30.0 (AHR, 1.32 [95% CI, 1.19-1.46]) compared with those with a BMI greater than 23.0 to 25.0 (P < .001 for trend), and BMI was associated with a greater increase in risk for colon cancer than for rectal cancer. A similar association between BMI and CRC-related death risk was observed among participants with a BMI greater than 27.5 (BMI >27.5-30.0: AHR, 1.18 [95% CI, 1.04-1.34]; BMI >30.0: AHR, 1.38 [95% CI, 1.18-1.62]; P < .001 for trend) and was present among men with a BMI greater than 30.0 (AHR, 1.87 [95% CI, 1.49-2.34]; P < .001 for trend) but not among women (P = .15 for trend) (P = .02 for heterogeneity). Conclusions and Relevance: In this cohort study that included a pooled analysis of 17 cohort studies comprising participants across Asia, a positive association between BMI and CRC incidence and related mortality was found. The risk was greater among men and participants with colon cancer. These findings may have implications to better understand the burden of obesity on CRC incidence and related deaths in the Asian population.

Gastric and colorectal cancer incidence attributable to dietary factors in Korea.

Background: Dietary factors play a role in the etiology of gastrointestinal cancer. We aimed to estimate the burden of gastric and colorectal cancer that can be attributable to dietary factors in adults aged 20 years and older in Korea in 2018. Methods: Dietary intakes in 2000 were estimated using data from the 2001, 2005, and 2007-2018 Korea National Health and Nutrition Examination Survey (KNHANES). For counterfactual scenarios, the optimal level of intake suggested by the Global Burden of Disease (GBD) study was used if it was available. Otherwise, the average intake values of reference groups among published studies globally were used. Relative risks (RRs) were pooled through dose-response meta-analyses of Korean studies. Results: In Korea in 2018, an estimated 18.6% of gastric cancer cases and 34.9% of colorectal cancer cases were attributed to the combined effect of evaluated dietary factors. High intake of salted vegetables accounted for 16.0% of gastric cancer cases, followed by salted fish at 2.4%. Low intakes of whole grains (16.6%) and milk (13.7%) were leading contributors to colorectal cancer cases, followed by high intakes of processed meat (3.1%) and red meat (5.9%), and a low intake of dietary fiber (0.5%). Conclusions: These results suggest that a considerable proportion of gastric and colorectal cancer incidence might be preventable by healthy dietary habits in Korea. However, further research is needed to confirm the associations between dietary factors and gastric and colorectal cancers in Korea and to formulate and apply effective cancer prevention strategies to Koreans.

Selenium levels and their association with thyroid autoimmunity and severe preeclampsia in pregnancy: Insights from a prospective ideal breast milk cohort study.

Objective: This study aimed to assess selenium status in South Korean pregnant women and its impact on maternal thyroid function and pregnancy outcomes. Methods: 'Ideal Breast Milk (IBM) Cohort Study' included 367 pregnant women out of 442 participants and categorized into three groups based on plasma selenium levels: deficient (< 70 µg/L), suboptimal (70-99 µg/L), and optimal (≥ 100 µg/L). During the second or third trimester, various blood parameters, including selenium, thyroid-stimulating hormone, free T4, free T3, and anti-thyroid peroxidase antibody levels, were measured. Thyroid parenchymal echogenicity was assessed as another surrogate marker for thyroid autoimmunity using ultrasonography. Results: The median plasma selenium was 98.8 (range: 46.7-206.4) µg/L, and 30 individuals (8%) were categorized as deficient, while 164 (45%) were classified in the suboptimal group. Selenium deficiency was associated with markers of autoimmune thyroiditis, including positive anti-thyroid peroxidase antibody results (13.3 (deficient) vs 4.6 (optimal) %, P = 0.031) and thyroid parenchymal heterogeneity on ultrasound (33.3 (deficient) vs 14.6 (suboptimal) vs 17.3 (optimal) %, P = 0.042), independently of gestational age. The incidence of severe preeclampsia was higher in the group not taking selenium supplements, particularly among those with twin pregnancies, compared to the group taking selenium supplements (0 (selenium supplement) vs 9.0 (no supplement) %, P = 0.015). Conclusion: Pregnant women experience mild selenium deficiency, which can lead to significant health issues including maternal thyroid autoimmunity and obstetrical complications during pregnancy. Guidelines for appropriate selenium intake according to the stage of pregnancy and the number of fetuses are needed.

Thyroid cancer-specific mortality during 2005-2018 in Korea, aftermath of the overdiagnosis issue: a nationwide population-based cohort study.

BACKGROUND: Thyroid cancer (TC) has underwent notable changes in its diagnosis and treatments following the concerns regarding overdiagnosis and overtreatment. However, there is little research on evaluating the effects of these alterations on TC-specific mortality. MATERIALS AND METHODS: This population-based cohort study included 434 228 patients with TC using Korean National Health Insurance Service-National Health Information Database. The age-standardized and sex-standardized mortality rates of TC per 1000 person-years were calculated considering the number of patients diagnosed with TC in 2013 per our database to evaluate the TC-specific mortality trends according to the year of TC diagnosis. RESULTS: The authors enrolled 434 228 patients with TC, including 352 678 women and 81 550 men, with a mean age of 48.6±12.5 years and a median follow-up duration of 7.4 (interquartile range: 4.5-10.1) years. TC incidence increased from 2005 to 2012, with a standardized rate of 91.9 per 100 000 people in 2012, decreased rapidly to 50.6 in 2015, and remained stable until 2018. However, TC-specific age-standardized and sex-standardized mortality rates decreased from 1.94 per 1000 person-years in 2005 to 0.76 per 1000 person-years in 2013 and then increased to 2.70 per 1000 person-years in 2018. The TC-specific age-standardized and sex-standardized mortality rates of patients who had undergone hemithyroidectomy or subtotal thyroidectomy remained steady during 2005-2018, but increased in patients who had undergone total thyroidectomy or not undergone thyroidectomy between 2013 and 2018. CONCLUSIONS: The TC-specific mortality rates among patients with TC diagnosed since 2015 have increased, in contrast to the significant decline in TC incidence during the same period. This underscores the importance of appropriate diagnosis and treatment in patients with TC at high-risk of progression, simultaneously emphasizing efforts to reduce overdiagnosis and overtreatment in those with low-risk TC.

Diabetes and gastric cancer incidence and mortality in the Asia Cohort Consortium: A pooled analysis of more than a half million participants.

BACKGROUND: Evidence suggests a possible link between diabetes and gastric cancer risk, but the findings remain inconclusive, with limited studies in the Asian population. We aimed to assess the impact of diabetes and diabetes duration on the development of gastric cancer overall, by anatomical and histological subtypes. METHODS: A pooled analysis was conducted using 12 prospective studies included in the Asia Cohort Consortium. Among 558 981 participants (median age 52), after a median follow-up of 14.9 years and 10.5 years, 8556 incident primary gastric cancers and 8058 gastric cancer deaths occurred, respectively. Cox proportional hazard regression models were used to estimate study-specific hazard ratios (HRs) and 95% confidence intervals (CIs) and pooled using random-effects meta-analyses. RESULTS: Diabetes was associated with an increased incidence of overall gastric cancer (HR 1.15, 95% CI 1.06-1.25). The risk association did not differ significantly by sex (women vs men: HR 1.31, 95% CI 1.07-1.60 vs 1.12, 1.01-1.23), anatomical subsites (noncardia vs cardia: 1.14, 1.02-1.28 vs 1.17, 0.77-1.78) and histological subtypes (intestinal vs diffuse: 1.22, 1.02-1.46 vs 1.00, 0.62-1.61). Gastric cancer risk increased significantly during the first decade following diabetes diagnosis (HR 4.70, 95% CI 3.77-5.86), and decreased with time (nonlinear p < .01). Positive associations between diabetes and gastric cancer mortality were observed (HR 1.15, 95% CI 1.03-1.28) but attenuated after a 2-year time lag. CONCLUSION: Diabetes was associated with an increased gastric cancer incidence regardless of sex, anatomical subsite, or subtypes of gastric cancer. The risk of gastric cancer was particularly high during the first decade following diabetes diagnosis.

Family history and gastric cancer incidence and mortality in Asia: a pooled analysis of more than half a million participants.

BACKGROUND: The family history of gastric cancer holds important implications for cancer surveillance and prevention, yet existing evidence predominantly comes from case-control studies. We aimed to investigate the association between family history of gastric cancer and gastric cancer risk overall and by various subtypes in Asians in a prospective study. METHODS: We included 12 prospective cohorts with 550,508 participants in the Asia Cohort Consortium. Cox proportional hazard regression was used to estimate study-specific adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for the association between family history of gastric cancer and gastric cancer incidence and mortality, then pooled using random-effects meta-analyses. Stratified analyses were performed for the anatomical subsites and histological subtypes. RESULTS: During the mean follow-up of 15.6 years, 2258 incident gastric cancers and 5194 gastric cancer deaths occurred. The risk of incident gastric cancer was higher in individuals with a family history of gastric cancer (HR 1.44, 95% CI 1.32-1.58), similarly in males (1.44, 1.31-1.59) and females (1.45, 1.23-1.70). Family history of gastric cancer was associated with both cardia (HR 1.26, 95% CI 1.00-1.60) and non-cardia subsites (1.49, 1.35-1.65), and with intestinal- (1.48, 1.30-1.70) and diffuse-type (1.59, 1.35-1.87) gastric cancer incidence. Positive associations were also found for gastric cancer mortality (HR 1.30, 95% CI 1.19-1.41). CONCLUSIONS: In this largest prospective study to date on family history and gastric cancer, a familial background of gastric cancer increased the risk of gastric cancer in the Asian population. Targeted education, screening, and intervention in these high-risk groups may reduce the burden of gastric cancer.

Diabetes is associated with increased liver cancer incidence and mortality in adults: A report from Asia Cohort Consortium.

There has been growing evidence suggesting that diabetes may be associated with increased liver cancer risk. However, studies conducted in Asian countries are limited. This project considered data of 968,738 adults pooled from 20 cohort studies of Asia Cohort Consortium to examine the association between baseline diabetes and liver cancer incidence and mortality. Cox proportional hazard model and competing risk approach was used for pooled data. Two-stage meta-analysis across studies was also done. There were 839,194 subjects with valid data regarding liver cancer incidence (5654 liver cancer cases [48.29/100,000 person-years]), follow-up time and baseline diabetes (44,781 with diabetes [5.3%]). There were 747,198 subjects with valid data regarding liver cancer mortality (5020 liver cancer deaths [44.03/100,000 person-years]), follow-up time and baseline diabetes (43,243 with diabetes [5.8%]). Hazard ratio (HR) (95% confidence interval [95%CI]) of liver cancer diagnosis in those with vs. without baseline diabetes was 1.97 (1.79, 2.16) (p < .0001) after adjusting for baseline age, gender, body mass index, tobacco smoking, alcohol use, and heterogeneity across studies (n = 586,072; events = 4620). Baseline diabetes was associated with increased cumulative incidence of death due to liver cancer (adjusted HR (95%CI) = 1.97 (1.79, 2.18); p < .0001) (n = 595,193; events = 4110). A two-stage meta-analytic approach showed similar results. This paper adds important population-based evidence to current literature regarding the increased incidence and mortality of liver cancer in adults with diabetes. The analysis of data pooled from 20 studies of different Asian countries and the meta-analysis across studies with large number of subjects makes the results robust.

SCORE and SCORE2 in East Asian Population: A Performance Comparison.

Background: Systematic COronary Risk Evaluation 2 (SCORE2) and SCORE2-Older Persons (OP) models have been proposed as new cardiovascular risk evaluation tools. Objectives: This study evaluated the performance of SCORE/SCORE-OP and SCORE2/SCORE2-OP in the East Asian population by using population-based cohort data from the National Health Insurance Service (NHIS) Health Screening Cohort of Korea. Methods: A total of 324,384 NHIS examinees from 2004 to 2005 were divided into 5 age groups: 40-49 years, 50-59 years, 60-69 years,70-79 years, and more than 80 years. The examinees had their predicted cardiovascular disease risks calculated by using SCORE, SCORE2, SCORE-OP, and SCORE2-OP models. The low-risk model was applied on the basis of the cohort's observed event rates. The observed and predicted cardiovascular risks were compared. Results: A total of 324,384 subjects were included (mean age 51.4 ± 7.3 years; women, 37.9% for the SCORE/SCORE2 group and mean age 73.0 ± 2.8 years; women, 47.5% for the SCORE/SCORE2-OP group). Over a median follow-up of 9 years, cardiovascular events occurred in 15.0% and 28.9% in SCORE/SCORE2 and SCORE/SCORE2-OP groups, respectively. The SCORE/SCORE-OP model underestimated cardiovascular disease risk in young men (aged 40-49 years) and women (aged 40-59 years) and overestimated it in older age groups. In contrast, SCORE2/SCORE2-OP invariably overestimated the risk in all age groups and sexes. SCORE2/SCORE2-OP showed no improvement in Harrell's concordance index (C-index) compared with SCORE/SCORE-OP. Calibration plots favored SCORE2 over SCORE but not SCORE2-OP over SCORE-OP. Conclusions: Both SCORE2/SCORE2-OP and SCORE/SCORE-OP overestimated cardiovascular disease risk with low performance. SCORE2/SCORE2-OP showed slight improvement over older versions, but modifications are necessary for the East Asian population.

Association of female reproductive and hormonal factors with gallbladder cancer risk in Asia: A pooled analysis of the Asia Cohort Consortium.

The female predominance of gallbladder cancer (GBC) has led to a hypothesis regarding the hormone-related aetiology of GBC. We aimed to investigate the association between female reproductive factors and GBC risk, considering birth cohorts of Asian women. We conducted a pooled analysis of 331,323 women from 12 cohorts across 4 countries (China, Japan, Korea, and Singapore) in the Asia Cohort Consortium. Cox proportional hazard models were used to estimate the hazard ratios (HRs) and corresponding 95% confidence intervals (CIs) to assess the association between reproductive factors (age at menarche, parity, age at first delivery, breastfeeding, and age at menopause) and GBC risk. We observed that a later age at menarche was associated with an increased risk of GBC (HR 1.4, 95% CI 1.16-1.70 for 17 years and older vs. 13-14 years), especially among the cohort born in 1940 and later (HR 2.5, 95% CI 1.50-4.35). Among the cohort born before 1940, women with a later age at first delivery showed an increased risk of GBC (HR 1.56, 95% CI 1.08-2.24 for 31 years of age and older vs. 20 years of age and younger). Other reproductive factors did not show a clear association with GBC risk. Later ages at menarche and at first delivery were associated with a higher risk of GBC, and these associations varied by birth cohort.

Association Between Orthostatic Hypertension and Frailty Among Older Patients With Hypertension.

BACKGROUND: Frailty frequently coexists with hypertension in older patients. We aimed to evaluate the association between frailty and positional change in blood pressure, especially orthostatic hypertension. METHODS: Participants were recruited from 12 University hospitals in South Korea. Using a digital device, trained research nurses measured blood pressure in the supine and standing positions. Physical frailty was evaluated using the Korean version of the FRAIL questionnaire, gait speed, and handgrip strength. Orthostatic hypertension was defined as a ≥20-mm Hg increase in systolic blood pressure within 3 minutes of standing and upright systolic blood pressure of ≥140 mm Hg. RESULTS: We analyzed the data of 2065 participants who had been enrolled until December 31, 2022. The mean age was 73.2±5.6 years, and 52.0% were female. The mean blood pressure was 137.1±14.9/75.1±9.7 mm Hg. Among the participants, 1886 (91.3%) showed normal response after standing, but 94 (4.6%) had orthostatic hypertension, and 85 (4.1%) had orthostatic hypotension. Orthostatic hypertension was associated with female sex, obesity, cognitive function, physical frailty, and lower quality of life. In the multivariable analysis, body mass index and frailty status were independently associated with orthostatic hypertension. CONCLUSIONS: Orthostatic hypertension is associated with physical frailty, cognitive impairment, and low quality of life in older patients with hypertension. Therefore, evaluation of orthostatic blood pressure changes to confirm orthostatic hypertension or hypotension in frail older adults will serve as an important diagnostic procedure in vulnerable patients. Further studies are required to identify the underlying mechanisms of this association.

Characteristics According to Frailty Status Among Older Korean Patients With Hypertension.

BACKGROUND: As the prevalence of hypertension increases with age and the proportion of the older population is also on the rise, research on the characteristics of older hypertensive patients and the importance of frailty is necessary. This study aimed to identify clinical characteristics of older hypertension in Korea and to investigate these characteristics based on frailty status. METHODS: The HOW to Optimize eLDerly systolic BP (HOWOLD-BP) is a prospective, multicenter, open-label, randomized clinical trial that aims to compare intensive (target systolic blood pressure [SBP] ≤ 130 mmHg) with standard (target SBP ≤ 140 mmHg) treatment to reduce cardiovascular events in older hypertensive Korean patients aged ≥ 65 years. Data were analyzed through a screening assessment of 2,085 patients recruited from 11 university hospitals. Demographic, functional (physical and cognitive), medical history, laboratory data, quality of life, and medication history of antihypertensive drugs were assessed. RESULTS: The mean age was 73.2 years (standard deviation ± 5.60), and 48.0% (n = 1,001) were male. Prevalent conditions included dyslipidemia (66.5%), obesity (body mass index ≥ 25 kg/m², 53.6%), and diabetes (28.9%). Dizziness and orthostatic hypotension were self-reported by 1.6% (n = 33) and 1.2% (n = 24), respectively. The majority of patients were on two antihypertensive drugs (48.4%), while 27.5% (n = 574) and 20.8% (n = 433) were on 1 and 3 antihypertensive medications, respectively. Frail to pre-frail patients were older and also tended to have dependent instrumental activities of daily living, slower gait speed, weaker grip strength, lower quality of life, and lower cognitive function. The frail to pre-frail group reported more dizziness (2.6% vs. 1.2%, P < 0.001) and had concerning clinical factors, including lower glomerular filtration rate, more comorbidities such as diabetes, stroke, and a history of admission. Frail to pre-frail older hypertensive patients used slightly more antihypertensive medications than robust older hypertensive patients (1.95 vs. 2.06, P = 0.003). Pre-frail to frail patients often chose beta-blockers as a third medication over diuretics. CONCLUSION: This study described the general clinical characteristics of older hypertensive patients in Korea. Frail hypertensive patients face challenges in achieving positive clinical outcomes because of multifactorial causes: they are older, have more morbidities, decreased function, lower quality of life and cognitive function, and take more antihypertensive medications. Therefore, it is essential to comprehensively evaluate and monitor disease-related or drug-related adverse events more frequently during regular check-ups, which is necessary for pre-frail to frail older patients with hypertension. TRIAL REGISTRATION: Clinical Research Information Service Identifier: KCT0003787.

Risk Factors for Infertility in Korean Women.

BACKGROUND: Female infertility is a crucial problem with significant implications for individuals and society. In this study, we explore risk factors for infertility in Korean women. METHODS: A total of 986 female patients who visited six major infertility clinics in Korea were recruited from April to December 2014. Fertile age-matched controls were selected from two nationwide survey study participants. Conditional logistic regression after age-matching was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) of each risk factor for infertility. RESULTS: Women with a body mass index (BMI) < 18.5 kg/m² had 1.35 times higher odds of infertility (OR, 1.35; 95% CI, 1.03-1.77), while those with a BMI ≥ 25.0 kg/m² had even higher odds (OR, 2.06; 95% CI, 1.61-2.64) compared to women with a normal BMI (18.5 kg/m² ≤ BMI < 25 kg/m²). Ever-smokers exhibited 4.94 times higher odds of infertility compared to never-smokers (95% CI, 3.45-8.85). Concerning alcohol consumption, women who consumed ≥ 7 glasses at a time showed 3.13 times significantly higher odds of infertility than those who consumed ≤ 4 glasses at a time (95% CI, 1.79-5.48). Lastly, women with thyroid disease demonstrated 1.44 times higher odds of infertility compared to women without thyroid disease (95% CI, 1.00-2.08). CONCLUSION: Female infertility in Korea was associated with underweight, obesity, smoking, alcohol consumption, and thyroid disease.

Active Surveillance for Low-Risk Thyroid Cancers: A Review of Current Practice Guidelines.

The indolent nature and favorable outcomes associated with papillary thyroid microcarcinoma have prompted numerous prospective studies on active surveillance (AS) and its adoption as an alternative to immediate surgery in managing low-risk thyroid cancer. This article reviews the current status of AS, as outlined in various international practice guidelines. AS is typically recommended for tumors that measure 1 cm or less in diameter and do not exhibit aggressive subtypes on cytology, extrathyroidal extension, lymph node metastasis, or distant metastasis. To determine the most appropriate candidates for AS, factors such as tumor size, location, multiplicity, and ultrasound findings are considered, along with patient characteristics like medical condition, age, and family history. Moreover, shared decision-making, which includes patient-reported outcomes such as quality of life and cost-effectiveness, is essential. During AS, patients undergo regular ultrasound examinations to monitor for signs of disease progression, including tumor growth, extrathyroidal extension, or lymph node metastasis. In conclusion, while AS is a feasible and reliable approach for managing lowrisk thyroid cancer, it requires careful patient selection, effective communication for shared decision-making, standardized follow-up protocols, and a clear definition of disease progression.

Association between reproductive factors with lung cancer incidence and mortality: A pooled analysis of over 308,000 females in the Asia cohort consortium.

Previous studies have investigated the association between reproductive factors and lung cancer risk; however, findings have been inconsistent. In order to assess this association among Asian women, a total of 308,949 female participants from 11 prospective cohorts and four Asian countries (Japan, Korea, China, and Singapore) were included. Cox proportional hazards regression models were used to estimate the hazard ratios (HR) and 95% confidence intervals (CIs). A total of 3,119 primary lung cancer cases and 2247 lung cancer deaths were identified with a mean follow-up of 16.4 years. Parous women had a lower risk of lung cancer incidence and mortality as compared with nulliparous women, with HRs of 0.82 (95% CI = 0.70-0.96) and 0.78 (95% CI = 0.65-0.94). The protective association of parity and lung cancer incidence was greater among ever-smokers (HR = 0.66, 95% CI = 0.49-0.87) than in never-smokers (HR = 0.90, 95% CI = 0.74-1.09) (P-interaction = 0.029). Compared with age at first delivery ≤20 years, older age at first delivery (21-25, ≥26 years) was associated with a lower risk of lung cancer incidence and mortality. Women who ever used hormone replacements had a higher likelihood of developing non-small cell lung cancer (HR = 1.31, 95% CI = 1.02-1.68), compared to those who never used hormone replacements. Future studies are needed to assess the underlying mechanisms, the relationships within these female reproductive factors, and the potential changes in smoking habits over time.

Group I pharmaceuticals of IARC and associated cancer risks: systematic review and meta-analysis.

We aimed to summarize the cancer risk among patients with indication of group I pharmaceuticals as stated in monographs presented by the International Agency for Research on Cancer working groups. Following the PRISMA guidelines, a comprehensive literature search was conducted using the PubMed database. Pharmaceuticals with few studies on cancer risk were identified in systematic reviews; those with two or more studies were subjected to meta-analysis. For the meta-analysis, a random-effects model was used to calculate the summary relative risks (SRRs) and 95% confidence intervals (95% CIs). Heterogeneity across studies was presented using the Higgins I square value from Cochran's Q test. Among the 12 group I pharmaceuticals selected, three involved a single study [etoposide, thiotepa, and mustargen + oncovin + procarbazine + prednisone (MOPP)], seven had two or more studies [busulfan, cyclosporine, azathioprine, cyclophosphamide, methoxsalen + ultraviolet (UV) radiation therapy, melphalan, and chlorambucil], and two did not have any studies [etoposide + bleomycin + cisplatin and treosulfan]. Cyclosporine and azathioprine reported increased skin cancer risk (SRR = 1.32, 95% CI 1.07-1.62; SRR = 1.56, 95% CI 1.25-1.93) compared to non-use. Cyclophosphamide increased bladder and hematologic cancer risk (SRR = 2.87, 95% CI 1.32-6.23; SRR = 2.43, 95% CI 1.65-3.58). Busulfan increased hematologic cancer risk (SRR = 6.71, 95% CI 2.49-18.08); melphalan was associated with hematologic cancer (SRR = 4.43, 95% CI 1.30-15.15). In the systematic review, methoxsalen + UV and MOPP were associated with an increased risk of skin and lung cancer, respectively. Our results can enhance persistent surveillance of group I pharmaceutical use, establish novel clinical strategies for patients with indications, and provide evidence for re-categorizing current group I pharmaceuticals into other groups.

Differential patterns of reproductive and lifestyle risk factors for breast cancer according to birth cohorts among women in China, Japan and Korea.

BACKGROUND: The birth cohort effect has been suggested to influence the rate of breast cancer incidence and the trends of associated reproductive and lifestyle factors. We conducted a cohort study to determine whether a differential pattern of associations exists between certain factors and breast cancer risk based on birth cohorts. METHODS: This was a cohort study using pooled data from 12 cohort studies. We analysed associations between reproductive (menarche age, menopause age, parity and age at first delivery) and lifestyle (smoking and alcohol consumption) factors and breast cancer risk. We obtained hazard ratios (HRs) with 95% confidence intervals (CIs) using the Cox proportional hazard regression analysis on the 1920s, 1930s, 1940s and 1950s birth cohorts. RESULTS: Parity was found to lower the risk of breast cancer in the older but not in the younger birth cohort, whereas lifestyle factors showed associations with breast cancer risk only among the participants born in the 1950s. In the younger birth cohort group, the effect size was lower for parous women compared to the other cohort groups (HR [95% CI] 0.86 [0.66-1.13] compared to 0.60 [0.49-0.73], 0.46 [0.38-0.56] and 0.62 [0.51-0.77]). Meanwhile, a higher effect size was found for smoking (1.45 [1.14-1.84] compared to 1.25 [0.99-1.58], 1.06 [0.85-1.32] and 0.86 [0.69-1.08]) and alcohol consumption (1.22 [1.01-1.48] compared to 1.10 [0.90-1.33], 1.15 [0.96-1.38], and 1.07 [0.91-1.26]). CONCLUSION: We observed different associations of parity, smoking and alcohol consumption with breast cancer risk across various birth cohorts.