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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., (Copyright © 2024 The Royal Society for Public Health. Published by Elsevier Ltd. All rights reserved.)

Background: Cervical cancer presents a considerable challenge in South Asia, notably in Nepal, where screening remains limited. Past research in Nepal lacked national representation and a thorough exploration of factors influencing cervical cancer screening, such as educational and socioeconomic disparities. This study aims to measure these gaps and identify associated factors in testing for early detection of cervical cancer among Nepalese women., Methods: Data from the 2019 Nepal Noncommunicable Disease Risk Factors survey (World Health Organization STEPwise approach to noncommunicable risk factor surveillance), involving 2,332 women aged 30 to 69 years, were used. Respondents were asked if they had undergone cervical cancer testing through visual inspection with acetic acid, Pap smear, or human papillomavirus test ever or in the past 5 years. The slope index of inequality (SII) and relative concentration index were used to measure socioeconomic and education-based disparities in cervical cancer test uptake., Results: Only 7.1% [95% confidence interval (CI): 5.1-9.9] Nepalese women had ever undergone cervical cancer testing, whereas 5.1% (95% CI: 3.4-7.5) tested within the last 5 years. The ever uptake of cervical cancer testing was 5.1 percentage points higher (SII: 5.1, 95% CI: -0.1 to 10.2) among women from the richest compared with the poorest households. Education-based disparities were particularly pronounced, with a 13.9 percentage point difference between highly educated urban residents and their uneducated counterparts (SII: 13.9, 95% CI: 5.8-21.9)., Conclusions: Less than one in ten women in Nepal had a cervical cancer testing, primarily favoring higher educated and wealthier individuals., Impact: Targeted early detection and cervical cancer screening interventions are necessary to address these disparities and improve access and uptake., (©2024 American Association for Cancer Research.)

Background: Epidemiological studies have shown inconsistent results regarding the link between smoking and breast cancer risk, despite the biological plausibility of a positive association., Methods: Participants were 166 611 women from nine prospective cohort studies in Japan which launched in 1984-1994 and followed for 8-22 years. Information on smoking and secondhand smoke was obtained through self-administered baseline questionnaires. Breast cancer was defined as code C50 according to the International Classification of Diseases for Oncology, 3rd Edition or the International Classification of Diseases, 10th Revision. After adjusting for several potential confounders, relative risks for breast cancer were calculated in the individual studies according to the current or previous status of active and passive smoking using Cox regression, followed by a summary estimate of hazard ratios using random-effects meta-analyses., Results: Of the 60 441 participants who reported being premenopausal and 106 170 who reported being postmenopausal at baseline, 897 and 1168 developed breast cancer during follow-up, respectively. Compared with never smokers, current smokers had a higher risk of developing breast cancer before the age of 50 years. In addition, ever smokers who started smoking at 30 years of age or younger, or who started smoking before first childbirth, had a higher risk of developing breast cancer before the age of 50 years. No association between adulthood or childhood exposure to secondhand smoke and breast cancer was observed., Conclusion: Smoking may increase the risk of premenopausal breast cancer, and smoking earlier in life might be especially harmful. The impact of secondhand smoke needs further investigation., (© The Author(s) 2024; all rights reserved. Published by Oxford University Press on behalf of the International Epidemiological Association.)

Introduction: Although lung cancer prediction models are widely used to support risk-based screening, their performance outside Western populations remains uncertain. This study aims to evaluate the performance of 11 existing risk prediction models in multiple Asian populations and to refit prediction models for Asians., Methods: In a pooled analysis of 186,458 Asian ever-smokers from 19 prospective cohorts, we assessed calibration (expected-to-observed ratio) and discrimination (area under the receiver operating characteristic curve [AUC]) for each model. In addition, we developed the "Shanghai models" to better refine risk models for Asians on the basis of two well-characterized population-based prospective cohorts and externally validated them in other Asian cohorts., Results: Among the 11 models, the Lung Cancer Death Risk Assessment Tool yielded the highest AUC (AUC [95% confidence interval (CI)] = 0.71 [0.67-0.74] for lung cancer death and 0.69 [0.67-0.72] for lung cancer incidence) and the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial Model had good calibration overall (expected-to-observed ratio [95% CI] = 1.06 [0.90-1.25]). Nevertheless, these models substantially underestimated lung cancer risk among Asians who reported less than 10 smoking pack-years or stopped smoking more than or equal to 20 years ago. The Shanghai models were found to have marginal improvement overall in discrimination (AUC [95% CI] = 0.72 [0.69-0.74] for lung cancer death and 0.70 [0.67-0.72] for lung cancer incidence) but consistently outperformed the selected Western models among low-intensity smokers and long-term quitters., Conclusions: The Shanghai models had comparable performance overall to the best existing models, but they improved much in predicting the lung cancer risk of low-intensity smokers and long-term quitters in Asia., (Copyright © 2023. Published by Elsevier Inc.)

About 95% of cervical cancers worldwide are caused by human papillomavirus (HPV). Cervical cancer is preventable and curable if it is detected and treated early. We reviewed the latest national cervical cancer indicators, and barriers to HPV vaccination and cervical cancer screening in 21 Asian National Cancer Centers Alliance (ANCCA) member countries. Half (n = 11, 52%) of the countries have introduced HPV vaccination for girls as part of their national vaccination programme, three countries reported coverage of over 90%. Most ANCCA member countries have cervical cancer screening programmes, only five countries reported screening uptake of over 50%. The barriers to HPV vaccination coverage and cervical cancer screening participation have been identified. Ensuring health service accessibility and affordability for women, addressing sociocultural barriers, and strengthening the healthcare system and continuum of care are essential to increase HPV vaccination and cervical cancer screening coverage., Competing Interests: The authors have no conflicts of interest to declare., (© 2023 Published by Elsevier Ltd.)

This study was aimed at investigating differences in antibody titers indicative of the presence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) between those who had experienced symptoms of coronavirus disease 2019 (COVID-19) and those who had not. We used data from a cross-sectional survey conducted at the National Cancer Center, Japan, of 434 individuals with no previous COVID-19 infection. The participants self-reported symptoms from the start of 2020. A generalized linear model was used to compare the mean SARS-CoV-2-specific IgG nucleocapsid protein (N-IgG) titer with estimated confidence intervals according to the onset of symptoms indicative of COVID-19. We observed a tendency toward an association between higher mean N-IgG titers and occurrence of high fever within the past 8 months (P = 0.053). The mean N-IgG titer was higher in those with prior symptoms (P = 0.03) and those with over three symptoms (P < 0.01) than in those without symptoms. The mean N-IgG titer was higher in those with symptoms and those with more symptoms that might indicate COVID-19 relative to those without symptoms, suggesting that transient but contained SARS-CoV-2 infection had occurred.

The study aimed to evaluate the association between green tea and coffee consumption and the risk of kidney cancer using data from a large prospective cohort study in Japan (the Japan Public Health Center-based Prospective Study: JPHC Study). A total of 102,463 participants aged 40-69 were followed during 1,916,421 person-years (mean follow-up period, 19 years). A total of 286 cases of kidney cancer (199 in men, 87 in women) were identified. Cox proportional hazards regression models were used to estimate hazard ratios (HRs) and 95% confidence intervals (95% CIs) while adjusting for potential confounders. No statistically significant association between green tea intake and kidney cancer risk was found in the total population. Among women who consumed more than five cups of green tea per day, a statistically significant decreased risk was shown with a HR of 0.45 (95% CI: 0.23-0.89), compared to women who rarely consumed green tea. For coffee consumption, the association of kidney cancer risk was not statistically significant. This large prospective cohort study indicated green tea intake may be inversely associated with kidney cancer risk in Japanese adults, particularly in Japanese women., (© 2022. The Author(s).)

Background: This study was performed to investigate the association between body mass index (BMI) and gastric cancer in East and Southeast Asia where most of gastric cancer is non-cardia gastric cancer., Methods: On the basis of 8,997 gastric cancer cases among the Asia Cohort Consortium participants from China, Japan, Korea, and Singapore (N = 538,835), we assessed gastric cancer risk according to BMI by calculating hazard ratios (HR) and 95% confidence intervals (CI) using the Cox proportional hazard regression model., Results: A U-shaped associations between BMI and gastric cancer risk were observed. Gastric cancer risks in underweight group (&lt;18.5 kg/m2) and in obesity group (≥27.5 kg/m2) were higher than reference BMI group (23-24.9 kg/m2; HR, 1.15; 95% CI, 1.05-1.25 for underweight; HR, 1.12; 95% CI, 1.03-1.22 for obesity, respectively). The associations of underweight and obesity with gastric cancer risk were consistent in the analyses for non-cardia gastric cancer, intestinal-type gastric cancer, and late-onset gastric cancer. No significant association of underweight and obesity with the risk of cardia gastric cancer, diffuse-type gastric cancer, and early-onset gastric cancer was observed. In addition, we found that the U-shaped association between BMI and gastric cancer risk remained in nonsmokers, while only underweight was related to increased gastric cancer risk in smokers., Conclusions: BMI has a U-shaped association with gastric cancer risk in East and Southeast Asian population, especially for the non-cardia gastric cancer, intestinal-type gastric cancer, and late-onset gastric cancer., Impact: Future studies with consideration of anatomic location and histology of gastric cancer are needed to establish the association of underweight as well as obesity with gastric cancer risk., (©2022 American Association for Cancer Research.)

Background: Professional breastfeeding support contributes to maternal and child health. However, the influence of the current coronavirus disease 2019 (COVID-19) pandemic on breastfeeding support has not been carefully examined. Therefore, we assessed maternal breastfeeding intention and professional breastfeeding support before and during the pandemic. We further examined the association of compliance with World Health Organization (WHO) recommendations for professional breastfeeding support with exclusive breastfeeding during the pandemic., Methods: This cross-sectional, internet-based, questionnaire study analyzed data from 484 healthy women with live singleton births between 15 October 2019 and 25 October 2020 in Japan. A delivery before 5 March 2020 was classified as a before-pandemic delivery ( n  = 135), and a delivery after 6 March 2020 was a during-pandemic delivery ( n  = 349). Among the ten breastfeeding support steps recommended by the WHO, we assessed the five steps that are measurable by maternal self-report and would likely exhibit variability. Receipt of a free formula sample or invitation to a free sample campaign by the time of survey was also asked. Infant feeding status at the time of the survey was measured among women with infants younger than 5 months, which was a subgroup of mothers who delivered during the pandemic. Mothers were asked what was given to infants during the 24 h before the survey and when nothing other than breast milk was given, the status was classified as exclusive breastfeeding., Results: While 82.2% of women with a delivery before the pandemic intended to breastfeed, the rate was 75.6% during the pandemic ( p  = 0.120). The average number of breastfeeding support steps received was 3.24 before the pandemic but it was 3.01 during the pandemic ( p  = 0.069). In particular, rooming-in was less frequent (39.3% before vs. 27.8% during the pandemic, p  = 0.014). Among mothers with infants younger than 5 months who had a delivery during the pandemic ( n  = 189), only 37.0% ( n  = 70) reported exclusively breastfeeding during the 24 h before completing the survey. Multiple logistic regression analysis indicated that receiving support for all five steps was positively associated with exclusive breastfeeding during the 24 h before the survey (adjusted odds ratio 4.51; 95% CI [1.50-13.61]). Receipt of a free formula sample or invitation to a free sample campaign was negatively associated with exclusive breastfeeding (adjusted odds ratio 0.43; 95% CI [0.19-0.98]). Other factors related to non-exclusive breastfeeding were older maternal age, lower education level, primiparity, and no breastfeeding intention., Conclusions: The pandemic weakened breastfeeding support for healthy women in Japan; however, support practice that adhered to WHO recommendations appeared to be effective during the pandemic., Competing Interests: The authors declare there are no competing interests., (©2022 Nanishi et al.)

The eligibility of COVID-19 vaccines has been expanded to children aged 12 and above in several countries including Japan, and there is a plan to further lower the age. This study aimed to assess factors related to parental COVID-19 vaccine hesitancy. A nationwide internet-based cross-sectional study was conducted between May 25 and June 3, 2021 in Japan. The target population was parents of children aged 3-14 years who resided in Japan, and agreed to answer the online questionnaire. Parental COVID-19 vaccine hesitancy (their intention to vaccinate their child) and related factors were analyzed using logistic regression models. Interaction effects of gender of parents and their level of social relationship satisfaction related to parental vaccine hesitancy was tested using log likelihood ratio test (LRT). Social media as the most trusted information source increased parental vaccine hesitancy compared to those who trusted official information (Adjusted Odds Ratio: aOR 2.80, 95% CI 1.53-5.12). Being a mother and low perceived risk of infection also increased parental vaccine hesitancy compared to father (aOR 2.43, 95% CI 1.57-3.74) and those with higher perceived risk of infection (aOR 1.55, 95% CI 1.04-2.32) respectively. People with lower satisfaction to social relationships tended to be more hesitant to vaccinate their child among mothers in contrast to fathers who showed constant intention to vaccinate their child regardless of the level of satisfaction to social relationship (LRT p = 0.021). Our findings suggest that dissemination of targeted information about COVID-19 vaccine by considering means of communication, gender and people who are isolated during measures of social distancing may help to increase parental vaccine acceptance., Competing Interests: The authors have declared that no competing interests exist.

Background: Body mass index (BMI) is inversely associated with lung cancer risk, while residual confounding by smoking or weight change is controversial. Evidence on height and lung cancer is scarce., Methods: We investigated the associations between anthropometrics, BMI, and height, and incidence of lung cancer among 92,098 study subjects (44,158 men and 47,940 women) in the Japan Public Health Center-based Prospective Study. Cox proportional hazards regression was performed with adjustment for potential confounders and by cancer subtypes and smoking status. Information on weight and height was self-reported at baseline, and validated using measured health check-up data., Results: During follow-up between 1990 and 2013 (average, 19.1 years), a total of 2,152 lung cancer cases were newly diagnosed. In a multivariate regression model, lower BMI was positively associated with overall lung cancer risk [<19 kg/m 2 HR = 1.48; 95% confidence interval (CI) = 1.18-1.85 and 19-22.9 kg/m 2 ; HR = 1.19; 95% CI = 1.05-1.35; P trend = <0.001] in men. The risk estimate was also elevated for adenocarcinoma in the BMI <19 kg/m 2 category and for squamous cell carcinoma among men in the 19-22.9 kg/m 2 BMI category. An association was also observed between low BMI, weight decrease, and squamous cell carcinoma in women. No significant associations were observed for other weight categories, height, weight change and lung cancer, adenocarcinoma, squamous and small cell carcinoma., Conclusions: Our prospective study suggests that lower BMI may be associated with an increased risk of smoking-related lung cancer in Japan, irrespective of gender., Impact: This study highlights the association between lower BMI and the risk of lung cancer in men., (©2021 American Association for Cancer Research.)

Associations of coffee and tea consumption with lung cancer risk have been inconsistent, and most lung cancer cases investigated were smokers. Included in this study were over 1.1 million participants from 17 prospective cohorts. Cox regression analyses were conducted to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). Potential effect modifications by sex, smoking, race, cancer subtype and coffee type were assessed. After a median 8.6 years of follow-up, 20 280 incident lung cancer cases were identified. Compared with noncoffee and nontea consumption, HRs (95% CIs) associated with exclusive coffee drinkers (≥2 cups/d) among current, former and never smokers were 1.30 (1.15-1.47), 1.49 (1.27-1.74) and 1.35 (1.15-1.58), respectively. Corresponding HRs for exclusive tea drinkers (≥2 cups/d) were 1.16 (1.02-1.32), 1.10 (0.92-1.32) and 1.37 (1.17-1.61). In general, the coffee and tea associations did not differ significantly by sex, race or histologic subtype. Our findings suggest that higher consumption of coffee or tea is associated with increased lung cancer risk. However, these findings should not be assumed to be causal because of the likelihood of residual confounding by smoking, including passive smoking, and change of coffee and tea consumption after study enrolment., (© 2020 UICC.)

Background: Little is known about the health harms associated with low-intensity smoking in Asians who, on average, smoke fewer cigarettes and start smoking at a later age than their Western counterparts., Methods: In this pooled analysis of 738 013 Asians from 16 prospective cohorts, we quantified the associations of low-intensity (<5 cigarettes/day) and late initiation (≥35 years) of smoking with mortality outcomes. HRs and 95% CIs were estimated for each cohort by Cox regression. Cohort-specific HRs were pooled using random-effects meta-analysis., Findings: During a mean follow-up of 11.3 years, 92 068 deaths were ascertained. Compared with never smokers, current smokers who consumed <5 cigarettes/day or started smoking after age 35 years had a 16%-41% increased risk of all-cause, cardiovascular disease (CVD), respiratory disease mortality and a >twofold risk of lung cancer mortality. Furthermore, current smokers who started smoking after age 35 and smoked <5 cigarettes/day had significantly elevated risks of all-cause (HRs (95% CIs)=1.14 (1.05 to 1.23)), CVD (1.27 (1.08 to 1.49)) and respiratory disease (1.54 (1.17 to 2.01)) mortality. Even smokers who smoked <5 cigarettes/day but quit smoking before the age of 45 years had a 16% elevated risk of all-cause mortality; however, the risk declined further with increasing duration of abstinence., Conclusions: Our study showed that smokers who smoked a small number of cigarettes or started smoking later in life also experienced significantly elevated all-cause and major cause-specific mortality but benefited from cessation. There is no safe way to smoke-not smoking is always the best choice., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Body fatness and weight gain are considered probable causes of gastric cancer, specifically in the cardia region. However, limited evidence is available in Asia, where the burden of gastric cancer is high. The objective of this study was to determine an association between body-mass index (BMI) and gastric cancer risk using a large population prospective cohort., Methods: 92,056 subjects enrolled in the Japan Public Health Center-based prospective Study who reported their height and weight were followed up until the end of 2013. A Cox proportional hazards model was used to estimate the risk for gastric cancer and its subsite based on baseline BMI. A subgroup analysis was conducted taking account of Helicobacter pylori (H. pylori) infection and atrophic gastritis status., Results: 2,860 gastric cancer cases (2,047 men, 813 women), 307 proximal gastric cancer cases (244 men, 63 women), and 1967 distal gastric cancer cases (1,405 men, 562 women) were found during the follow-up period. Among men, baseline BMI ≥ 27 kg/m 2 increased the risk of overall gastric cancer (hazards ratio (HR) 1.23, 95% confidence interval (CI) 1.00-1.53). For both sexes, U-shaped increase in the risk was observed for proximal gastric cancer. Subgroup analysis showed a statistically significant association between the risk of proximal gastric cancer and BMI ≥ 27 kg/m 2 among those who were atrophic gastritis positive, H. pylori antibody positive, and those who tested positive to either or both atrophic gastritis and H. pylori antibody., Conclusion: Our result suggests that gastric cancer risk increases for men with BMI ≥ 27 kg/m 2 ., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Although empirical data suggest a possible link between female reproductive events and risk of nonfatal accidents and suicidal behaviors, evidence to determine these effects on mortality is scarce. This study investigated the association between female reproductive factors and the risk of external causes of death among middle-aged Japanese women. We used a population-based cohort study consisting of 71 698 women residing in 11 public health center areas across Japan between 1990 and 1994. Multivariable-adjusted Cox proportional hazard regression models were used to estimate hazard ratios (HRs) of the risk of all external causes, suicide, and accidents according to female reproductive factors at the baseline survey. During 1 028 583 person-years of follow-up for 49 279 eligible subjects (average 20.9 years), we identified 328 deaths by all injuries. Among parous women, ever versus never breastfeeding [0.67 (95% CI: 0.49-0.92)] was associated with a decreased risk of all injuries. Risk of suicide was inversely associated with ever versus never parity [0.53 (95% CI: 0.32-0.88)]. A lower risk of death by accidents was seen in ever breastfeeding [0.63 (95% CI: 0.40-0.97)] compared to never breastfeeding. This study suggests that parity and breastfeeding are associated with reduced risk of death by all external causes, suicide and/or accidents among Japanese women.

Household air pollution (HAP) is of public health concern with ~3 billion people worldwide (including >15 million in the US) exposed. HAP from coal use is a human lung carcinogen, yet the epidemiological evidence on carcinogenicity of HAP from biomass use, primarily wood, is not conclusive. To robustly assess biomass's carcinogenic potential, prospective studies of individuals experiencing a variety of HAP exposures are needed. We have built a global consortium of 13 prospective cohorts (HAPCO: Household Air Pollution Consortium) that have site- and disease-specific mortality and solid fuel use data, for a combined sample size of 587,257 participants and 57,483 deaths. HAPCO provides a novel opportunity to assess the association of HAP with lung cancer death while controlling for important confounders such as tobacco and outdoor air pollution exposures. HAPCO is also uniquely positioned to determine the risks associated with cancers other than lung as well as non-malignant respiratory and cardiometabolic outcomes, for which prospective epidemiologic research is limited. HAPCO will facilitate research to address public health concerns associated with HAP-attributed exposures by enabling investigators to evaluate sex-specific and smoking status-specific effects under various exposure scenarios., Competing Interests: Conflicts of Interest: The authors declare no conflict of interest.

Helicobacter pylori (H. pylori), an established risk factor for gastric cancer, is suggested to also play a role in the development of pancreatic cancer; however, the association remains inconclusive. We examined this association among Japanese men and women. H. pylori and atrophic gastritis (AG) status were determined serologically, using blood sample collected during health checkups. A total of 20,116 subjects enrolled in the Japan Public Health Center-based Prospective Study Cohort II with available data on H. pylori seropositivity (anti-H. pylori) and AG were followed until the end of 2010. Cox proportional hazards models were used to calculate the hazard ratios (HR) and 95% confidence intervals (CI), using the information from the baseline survey. During 320,470 person-years of follow-up, 119 cases of pancreatic cancer were identified. No statically significant increase or decrease in pancreatic cancer risk was observed for H. pylori and AG status, independently or in combination. In a multivariable-adjusted model, we observed a non-significant decrease in the risk among those who had AG but were anti-H. pylori seronegative (HR 0.57, 95% CI 0.31-1.03). In a stratified analysis, we observed a statistically significant increased risk of pancreatic cancer for AG+ (HR 3.64, 95% CI 1.37-9.66), and AG+/anti-H. pylori- or AG+/anti-H. pylori+ (HR 5.21, 95% CI 1.14-23.87) among current smokers. Non-smokers in all categories of AG and anti-H. pylori showed a non-statistical decrease in the risk. There was no statistically significant interaction between H. pylori infection, AG status, and smoking status. Our findings suggest H. pylori seropositivity and AG, individually or in combination, are not associated with the risk of pancreatic cancer in a general Japanese population. Among current smokers, pancreatic cancer risk increased with AG, regardless of H. pylori infection status.

Purpose: We investigated the association between reproductive history and mortality from all and major causes among Japanese women., Methods: A large-scale population-based cohort study in Japan included 40,149 eligible women aged 40-69 years in 1990-1994. A total of 4788 deaths were reported during follow-up (average 20.9 years). A Cox proportional hazards regression model was used to estimate the hazard ratios (HRs) and 95% confidence intervals (95% CI) for all-cause and major causes of mortality, adjusting for potential confounders., Results: Inverse associations with all-cause mortality were found in parous women (0.74 [0.67-0.82]), women with two or three births compared with a single birth (2 births: 0.88 [0.78-0.99]; 3 births: 0.83 [0.74-0.94]), parous women who breastfed (0.81 [0.75-0.87]), women who were older at menopause (0.88 [0.80-0.97]; p-trend: <0.01), and women who had a longer fertility span (0.85 [0.76-0.95]; p-trend: <0.01). A positive association was seen between all-cause mortality and later age at first birth (≥30 years) than early childbearing (≤22 years)., Conclusions: Our study suggests that parous, two or three births, breastfeeding, late age at menopause, and longer reproductive span are associated with lower risk of all-cause of mortality., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: With an increasing burden of non-communicable disease in Nepal and limited progress towards universal health coverage, country- and disease-specific estimates of financial hardship related to healthcare costs need to be evaluated to protect the population effectively from healthcare-related financial burden., Objectives: To estimate the cost and economic burden of illness and to assess the inequality in the financial burden due to catastrophic health expenditure from 1995 to 2010 in Nepal., Methods: This study used nationally representative Nepal Living Standards Surveys conducted in 1995 and 2010. A Bayesian two-stage hurdle model was used to estimate average cost of illness and Bayesian logistic regression models were used to estimate the disease-specific incidence of catastrophic health payment and impoverishment. The concentration curve and index were estimated by disease category to examine inequality in healthcare-related financial hardship., Findings: Inflation-adjusted mean out-of-pocket (OOP) payments for chronic illness and injury increased by 4.6% and 7.3%, respectively, while the cost of recent acute illness declined by 1.5% between 1995 and 2010. Injury showed the highest incidence of catastrophic expenditure (30.7% in 1995 and 22.4% in 2010) followed by chronic illness (12.0% in 1995 and 9.6% in 2010) and recent acute illness (21.1% in 1995 and 7.8% in 2010). Asthma, diabetes, heart conditions, malaria, jaundice and parasitic illnesses showed increased catastrophic health expenditure over time. Impoverishment due to injury declined most (by 12% change in average annual rate) followed by recent acute illness (9.7%) and chronic illness (9.6%) in 15 years. Inequality analysis indicated that poorer populations with recent acute illness suffered more catastrophic health expenditure in both sample years, while wealthier households with injury and chronic illnesses suffered more catastrophic health expenditure in 2010., Conclusion: To minimize the economic burden of illness, several approaches need to be adopted, including social health insurance complemented with an upgraded community-based health insurance system, subsidy program expansion for diseases with high economic burden and third party liability motor insurance to reduce the economic burden of injury.

Over 80% of perinatal mortality in Japan is due to stillbirths after 22 weeks of gestation, with one in 300 families experiencing fetal loss every year. This study aimed to assess causes and risk factors for singleton stillbirth in Japan. A retrospective cross-sectional study was conducted using the Japan Society of Obstetrics and Gynecology Perinatal Database from January 2013 to December 2014. A total of 379,211 births including 2,133 stillbirths were analyzed. Causes of death were classified into eight categories. A multi-level Poisson regression model was used to assess the relationship between stillbirth and key covariates. Causes of death were unknown in 25-40% of stillbirths across gestational age. Placental abnormality accounted for the largest proportion of known causes, followed by umbilical cord abnormality. Stillbirth risk was increased among small-for-gestational-age infants (adjusted relative risk [ARR]: 3.78, 95% confidence interval [CI]: 3.31-4.32) and nulliparous women (ARR: 1.19, 95% CI: 1.05-1.35). Maternal underweight, pregnancy-induced hypertension and oligohydramnios showed a protective effect. Our finding suggests that stillbirths occurring among women with known complications are likely already being prevented. Further reduction in stillbirths must target small-sized fetuses and nulliparous women. Improved recording of the causal pathways of stillbirths is also needed.

Background: The influence of body mass index (BMI) change during adulthood on the development of oesophageal squamous-cell carcinoma (ESCC) is unknown., Methods: Based on the Japan Public Health Center-based Prospective Study, we enrolled 103 238 participants from 1990 to 1994. Anthropometric data at age 20 years, baseline, and 5- and/or 10-year follow-up surveys were collected by questionnaire. The effect of BMI change between age 20 years and baseline on ESCC risk was estimated by Cox proportional hazards regression models. The updated BMI was taken into account by fitting a simple linear regression model for each individual, where the slope was incorporated into regressions as a time-varying variable., Results: After excluding the first 5 years of observation, we identified 342 newly diagnosed ESCC cases. An increase in BMI during adulthood was linked with a decreased risk of ESCC development, with each 1% increase per 5 years corresponding to a 15% decrease in ESCC risk (95% confidence interval 9-21%). Identical estimates were obtained from time-dependent models. The importance of BMI change was not modified by gender, smoking, or alcohol drinking but confined to participants assessed as non-overweight at baseline., Conclusions: An increase in BMI during adulthood is associated with a lower risk of developing ESCC among non-overweight subjects.

Evidence regarding stress as a risk factor for cancer onset is inconsistent. In this study, based on the Japan Public Health Center-based Prospective Study, we enrolled 101,708 participants aged 40-69 years from 1990-1994. The self-reported perceived stress level was collected at baseline and updated through 5-year follow-up. The association between perceived stress and cancer risk was measured by Cox proportional hazards regression model, adjusted for all known confounders. During follow-up (mean = 17.8 years), we identified 17,161 cancer cases. We found no association between baseline perceived stress level and cancer incidence. However, by taking account of the dynamic changes in perceived stress, time-varying analyses revealed a slightly (4-6%) increased overall cancer risk for subjects under elevated perceived stress levels compared to the 'low stress level' group. Analyses concerning long-term perceived stress level showed that individuals with constantly high perceived stress level had an 11% (95% confidence interval 1-22%) excess risk for cancer compared to subjects with persistently low stress levels. This association was confined to men (20% excess risk), and was particularly strong among smokers, alcohol drinkers, obese subjects, and subjects without family history of cancer. Therefore, we concluded high perceived stress level might contribute to excess overall cancer incidence among men.

Background: Japan has entered the era of super-ageing and advanced health transition, which is increasingly putting pressure on the sustainability of its health system. The level and pace of this health transition might vary across regions within Japan and concern is growing about increasing regional variations in disease burden. The Global Burden of Diseases, Injuries, and Risk Factors Study 2015 (GBD 2015) provides a comprehensive, comparable framework. We used data from GBD 2015 with the aim to quantify the burden of disease and injuries, and to attribute risk factors in Japan at a subnational, prefecture-level., Methods: We used data from GBD 2015 for 315 causes and 79 risk factors of death, disease, and injury incidence and prevalence to measure the burden of diseases and injuries in Japan and in the 47 Japanese prefectures from 1990 to 2015. We extracted data from GBD 2015 to assess mortality, causes of death, years of life lost (YLLs), years lived with disability (YLDs), disability-adjusted life-years (DALYs), life expectancy, and healthy life expectancy (HALE) in Japan and its 47 prefectures. We split extracted data by prefecture and applied GBD methods to generate estimates of burden, and attributable burden due to known risk factors. We examined the prefecture-level relationships of common health system inputs (eg, health expenditure and workforces) to the GBD outputs in 2015 to address underlying determinants of regional health variations., Findings: Life expectancy at birth in Japan increased by 4·2 years from 79·0 years (95% uncertainty interval [UI] 79·0 to 79·0) to 83·2 years (83·1 to 83·2) between 1990 and 2015. However, the gaps between prefectures with the lowest and highest life expectancies and HALE have widened, from 2·5 to 3·1 years and from 2·3 to 2·7 years, respectively, from 1990 to 2015. Although overall age-standardised death rates decreased by 29·0% (28·7 to 29·3) from 1990 to 2015, the rates of mortality decline in this period substantially varied across the prefectures, ranging from -32·4% (-34·8 to -30·0) to -22·0% (-20·4 to -20·1). During the same time period, the rate of age-standardised DALYs was reduced overall by 19·8% (17·9 to 22·0). The reduction in rates of age-standardised YLDs was very small by 3·5% (2·6 to 4·3). The pace of reduction in mortality and DALYs in many leading causes has largely levelled off since 2005. Known risk factors accounted for 34·5% (32·4 to 36·9) of DALYs; the two leading behavioural risk factors were unhealthy diets and tobacco smoking in 2015. The common health system inputs were not associated with age-standardised death and DALY rates in 2015., Interpretation: Japan has been successful overall in reducing mortality and disability from most major diseases. However, progress has slowed down and health variations between prefectures is growing. In view of the limited association between the prefecture-level health system inputs and health outcomes, the potential sources of regional variations, including subnational health system performance, urgently need assessment., Funding: Bill & Melinda Gates Foundation, Japan Ministry of Education, Science, Sports and Culture, Japan Ministry of Health, Labour and Welfare, AXA CR Fixed Income Fund and AXA Research Fund., (Copyright © 2017 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC-ND 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

An association between female reproductive factors, exogenous hormone use, and pancreatic cancer risk has long been suggested in laboratory settings, but epidemiological findings remain mixed and inconclusive. Studies carried out on Asian populations are also limited. In this study, 45 617 women aged 40-69 years were followed for an average of 18.4 years in the Japan Public Health Center-based prospective cohort and 211 pancreatic cases were identified as of 31 December 2011. We applied multivariate-adjusted Cox proportional hazards regression models using age as a time-scale to assess the association between female reproductive factors (menstrual status, menarche age, menopause age, number of births, age at first birth, total years of fertility, history of breastfeeding) and exogenous hormone use with the incidence of pancreatic cancer through hazard ratios and confidence intervals. No significant associations were found between our examined female reproductive factors and pancreatic cancer incidence. The use of exogenous hormones was found to be associated with an increased risk of pancreatic cancer in a multivariate-adjusted model (hazard ratio: 1.47; 95%; confidence interval: 1.00-2.14) in the Japanese female population. Our results suggest that exogenous hormones may play a role in the formation of pancreatic cancer, and further prospective studies are warranted for clarification.

Purpose: Epidemiological studies have suggested a protective effect of dietary fiber intake on breast cancer risk while the results have been inconsistent. Our study aimed to investigate the association between dietary fiber intake and breast cancer risk and to explore whether this association is modified by reproductive factors and hormone receptor status of the tumor., Methods: A total of 44,444 women aged 45 to 74 years from the Japan Public Health Center-based Prospective Study were included in analyses. Dietary intake assessment was performed using a validated 138-item food frequency questionnaire (FFQ). Hazard ratios (HRs) and 95% confidence intervals (CIs) for breast cancer incidence were calculated by multivariate Cox proportional hazards regression models., Results: During 624,423 person-years of follow-up period, 681 breast cancer cases were identified. After adjusting for major confounders for breast cancer risk, inverse trends were observed but statistically non-significant. Extremely high intake of fiber was associated with decreased risk of breast cancer but this should be interpreted with caution due to limited statistical power. In stratified analyses by menopausal and hormone receptor status, null associations were observed except for ER-PR- status., Conclusions: Our findings suggest that extreme high fiber intake may be associated with decreased risk of breast cancer but the level of dietary fiber intake among Japanese population might not be sufficient to examine the association between dietary fiber intake and breast cancer risk.

Background: Globally, more than two billion people are estimated to be deficient in key vitamins and minerals, particularly iodine, iron and zinc. The majority of these people live in low-income settings and are typically deficient in more than one micronutrient. However, micronutrient deficiency among breastfeeding mothers and their infants also remains an issue in high-income settings, specifically among women who avoid meat and/or milk, women who may lack sufficient supplies of vitamin B12 and vitamin D, and/or women who are iron-deficient. Young children, pregnant and lactating women are particularly vulnerable to micronutrient deficiencies. They not only have a relatively greater need for vitamins and minerals because of their physiological state, but are also more susceptible to the harmful consequences of deficiencies. Multiple-micronutrient supplementation might be an option to solve these problems., Objectives: The objective of this review was to evaluate the effects of multiple-micronutrient supplementation in breastfeeding mothers on maternal and infant outcomes., Search Methods: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (30 September 2015) and reference lists of retrieved studies., Selection Criteria: Randomised controlled trials of multiple-micronutrient supplementation of three or more micronutrients versus placebo, no supplementation or supplementation with two or fewer micronutrients, irrespective of dosage of micronutrients, in breastfeeding mothers., Data Collection and Analysis: Two review authors independently assessed trials for inclusion and risk of bias, extracted data and checked them for accuracy., Main Results: We found no studies that compared multiple-micronutrient supplementation (with three or more micronutrients) versus supplementation with two or fewer micronutrients.Two small studies (involving a total of 52 women) were included. One study compared multiple micronutrients with placebo and the other study compared multiple micronutrients with a group who received no supplementation. The studies were carried out in Brazil (36 adolescent mothers) and the USA (16 women) and included women with a low socioeconomic status. A lack of information in the study reports meant that risk of bias could not be adequately assessed (unclear risk of bias for many domains). There were no quantitative data for any of this review's outcomes so meta-analysis was not possible.Neither of the studies reported on the primary outcomes of interest in this review: maternal morbidity (febrile illness, respiratory tract infection, diarrhoea), adverse effects of micronutrients within three days of receiving the supplement, infant mortality (defined as a child dying before completing the first year of age).One study reported qualitatively on maternal anaemia (a secondary outcome of this review) - the study found that multiple-micronutrient supplementation was effective for recuperating from anaemia but there were no data for inclusion in our analyses. Maternal satisfaction was not reported in the included studies. Similarly, none of this review's infant secondary outcomes were reported in the included studies: clinical micronutrient deficiency; morbidity episodes (febrile illness, respiratory tract infection, diarrhoea, other), adverse effects of micronutrients within three days of receiving the supplement., Authors' Conclusions: We found no evidence to quantitatively assess the effectiveness of multiple-micronutrient supplementation in improving health outcomes in mother and baby. The results of this review are limited by the small numbers of studies available, small sample sizes and the studies not reporting on the outcomes of interest in this review. There is no evidence to evaluate potential adverse effects of multiple-micronutrient supplements, particularly excess dosages.There is a need for high-quality studies to assess the effectiveness and safety of multiple-micronutrient supplementation for breastfeeding women for improving outcomes for the mother and her baby. Further research should focus on whether multiple-micronutrient supplementation during lactation compared with none, a placebo or supplementation with fewer than two micronutrients is beneficial to maternal and infant health outcomes. Future studies should collect data on outcomes beyond micronutrient concentrations, for example: maternal and infant morbidity, adverse effects, maternal satisfaction, the risks of excess supplementation, and potential adverse interactions between the micronutrients and the other outcomes. This would help to bridge the gap between research on intermediary outcomes and health outcomes in order to develop sound policy in this field. Future studies could more precisely assess a variety of multiple-micronutrient combinations and different dosages and look at how these affect maternal and infant health outcomes. Larger studies with longer follow-up would improve the quality of studies and provide stronger evidence. In most of the included studies, bias could not be adequately assessed due to lack of information, therefore attention should be given to adequate methods of randomisation and allocation concealment, adequate methods of blinding of the participants, providers and the outcome assessors to improve the methodological quality of studies in this field.

Limited and inconsistent studies exist on the association between the intake of fish, n - 3 polyunsaturated fatty acids (PUFA) and n - 6 PUFA and breast cancer. Fish and n - 3 PUFA support various body functions and are thought to reduce the carcinogenesis risk while n - 6 PUFA may have a positive association with cancer risk. We examined the association between intake of fish, n - 3 PUFA [including eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), docosapentaenoic acid (DPA) and alpha-linolenic acid (ALA)] and n - 6 PUFA and breast cancer with subanalyses on estrogen (ER) and progesterone receptor (PR) status. We investigated 38,234 Japanese women aged 45-74 years from the Japan Public Health Center-based prospective study (JPHC study), and during 14.1 years of follow-up time, 556 breast cancer cases were newly diagnosed. Breast cancer risk was not associated with the intake of total fish, n - 3 PUFA and n - 6 PUFA when analyzed in totality through multivariable Cox proportional hazards regression models with age as the time scale. Intake of total n - 6 was positively associated with the development of ER+PR+ tumors [multivariable-adjusted HR Q4 vs. Q1  = 2.94 (95% CI: 1.26-6.89; ptrend  = 0.02)]. Intake of EPA was associated with a decreased breast cancer risk for ER+PR+ tumors [multivariable-adjusted HR Q2 vs. Q1  = 0.47 (95% CI: 0.25-0.89; ptrend =0.47)]. While the overall association between the intake of total fish, n - 3 PUFA and n - 6 PUFA and breast cancer risk is null, for ER+PR+ tumors, a positive association was seen between n - 6 intake and breast cancer, and a marginally significant inverse association was observed for EPA intake., (© 2015 UICC.)

Objectives: We investigated the prevalence, awareness, treatment, and control of hypertension and associated risk factors in the Bangladeshi adult population., Methods: The data for this study were extracted from the nationally-representative 2011 Bangladesh Demographic and Health Survey. Socio-demographic profiles, height, weight, blood pressure measurements, and management were recorded from 7876 adults aged 35 years or older. Multilevel logistic regression models were used to identify the risk factors for hypertension awareness, treatment, and control., Results: Overall, age-standardized prevalence of prehypertension and hypertension were 27.1 and 24.4%, respectively. Among patients with hypertension, 50.1% were aware of their condition, 41.2% were in treatment, but only 31.4% had controlled hypertension. There was a wide disparity in hypertension management between the poor and the wealthy households. Rich households were more likely to be aware of their hypertension [odds ratio (OR) 1.92, 95% confidence interval (CI) 0.97-3.79, P = 0.06], receiving treatment (OR 3.34, 95% CI 1.55-7.18, P < 0.001) and controlling their condition (OR 2.88, 95% CI 1.28-6.46, P = 0.01), as compared to the poor residents. Participants who had lower education were less likely to be aware of, in treatment for, and in control of their condition., Conclusion: One in four adults had hypertension in Bangladesh, and awareness and treatment of hypertension are quite low. Improvements in detection and treatment strategies are needed to prevent the growing disease burden associated with hypertension.