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Background: To provide seamless nutritional support from early adulthood to late adulthood in Japan, this study aimed to identify aging-related changes in protein and fat intake and meal types. Methods: Birth cohort analysis was conducted in this study. The protein intake, protein-to-energy ratio, fat intake, and fat-to-energy ratio in men and women from their 20s to 60s in 2001 was calculated using the data of the National Health and Nutrition Survey in Japan between 2001 and 2019 (n = 139,876, 47.0% men, mean age: 54.9 and 55.4 years for men and women, respectively). The intakes were calculated for every subsequent year, the aging-related changes were identified by age group, and the 99 food groups were classified into staple-focused meal types through factor analysis. The weighted average component value per 1 g of each food group was calculated, multiplied by the food weight, and totaled to determine the mean intake by meal type and to confirm the aging-related changes. The year when the slope changed before and after was identified through Joinpoint regression analysis. Results: The protein intake, protein-to-energy ratio, fat intake, and fat-to-energy ratio initially declined or remained unchanged with aging in almost all generations (20s to 60s in 2001) but began to increase after 8–15 years. The food groups were classified into rice, noodle, and bread types. The protein and fat intake from the noodle type initially showed a decreasing trend but began to increase with aging after 8–15 years in almost all generations in both sexes (p < 0.05 for difference in slope). Conclusions: The increase of protein intake and protein-to-energy ratio and fat intake and fat-to-energy ratio over time observed among Japanese adults may be related to the increased intake of food groups from noodle type meals. Thus, considering the type of staple food (i.e., rice, noodles, or bread) and its combination with other foods when adhering to a balanced diet is necessary.

Background Dental caries are a common non-communicable disease among children. As a public health measure at the prefectural level, school-based fluoride mouth-rinse (S-FMR) program, medical/dental expense subsidy policies, and other factors may reduce the incidence of dental caries and tooth loss. Prefectures focusing on promoting oral health policies may promote both, but the interaction effect of implementing both subsidy policies and S-FMR at the prefectural level on caries prevention has not yet been examined. Methods We conducted an ecological study using two-wave panel data, prefecture-level aggregated data in Japan for 2016 and 2018. Coefficient and 95% confidence intervals (CI) were calculated for the dependent variables for oral health using mixed-effects linear regression analysis adjusted for possible confounders. Two dependent variables were used; the standardized claim ratio (SCR) of deciduous tooth extraction and 12-year-olds’ decayed, missing, or filled permanent teeth (DMFT). Four independent variables were S-FMR, the SCR of dental sealants, prefectural income per person, and subsidy policy in three models: co-payment until children enter elementary school (n = 23), no co-payment until children enter elementary school (n = 7), and co-payment continuing beyond elementary school (n = 17). The effects of six interaction terms, each representing a unique pairing from the four independent variables, were individually calculated. Results S-FMR was negatively associated with the SCR of deciduous tooth extractions and DMFT (coefficient = -0.11, 95% CI -0.20; -0.01 and coefficient = -0.003, 95% CI -0.005; -0.001, respectively). No co-payment until children enter elementary school was positively associated with the SCR of deciduous tooth extraction compared to co-payment until children enter elementary school(coefficient = 11.42, 95% CI 3.29; 19.55). SCR of dental sealants was positively associated with the SCR of deciduous tooth extractions (coefficient = 0.12, 95% CI 0.06; 0.19) but negatively associated with DMFT (coefficient = -0.001, 95% CI -0.003; -0.0001). Per capita prefectural income was positively associated with the SCR of deciduous tooth extractions(coefficient = 0.01, 95% CI 0.001; 0.02). No interaction was found between S-FMR and the subsidy policy at both outcomes. Conclusion High S-FMR utilization and no co-payment until children enter elementary school were associated with fewer deciduous tooth extractions. Also, S-FMR and dental sealant were associated with decreased DMFT.

Background: We aimed to clarify whether differences in food group intake according to household income have changed over the last decade in Japanese people aged 20 years or older. Methods: This cross-sectional study was based on the 2010, 2014, and 2018 National Health and Nutrition Surveys in Japan. Food intake was assessed using a 1-day semi-weighed household dietary record. The participants were categorized into three groups based on their income. The mean of each food intake according to the income group was estimated by adjusting for age, occupation, and number of participants from the same household. The significance of the interaction terms between income and survey year was evaluated to assess the change in income-related differences in food intake over time. Results: Cereal intake was lower in the middle- and the highest-income groups than in the lowest-income group, regardless of sex, and the interaction between income and year was nonsignificant for cereal intake. In the former two surveys, vegetable intake was higher among the highest-income women, while in the 2018 survey, the vegetable intake decreased in the women in the middle- and the highest-income groups. The interaction between income and year was significant for vegetable intake among the women. For other foods, the differences in intake among the income groups did not significantly change over time. Conclusion: The tendency for lower cereal intake in the higher-income groups was consistent over time in both the sexes, and the tendency for higher vegetable intake in the highest income women disappeared over time.

Abstract Background A gap has been reported between healthcare professionals’ (hereafter “professionals”) recognition of preschool children’s diets and parents’ perception of concern. This study investigated the gap between the concerns reported by professionals and parents’ perceptions regarding health and dietary habits by age (18 months and 3 years) and gender in Japan. Methods The study design consisted of a cross-sectional, multilevel survey. The request letters were sent to all households with target children with the cooperation of local governments. After obtaining written informed consent from parents, questionnaires were distributed to them. The survey included 30 items on children's concerns about health and dietary habits. At the health checkup, parents indicated whether they were concerned in response to each item, and responded child’s height and weight and birth height and weight. Next, the professionals provided counseling to the parents at a health checkup. After that, the professionals noted their concerns in response to the same 30 items as those given to parents. The participation rates were 82.9% (18 months) and 82.8% (3 years). Data of 239 persons for 18 months and 223 persons for 3 years old were analyzed. In the statistical analysis, the items that were judged as concerning by professionals but not by parents were identified; likewise, the items that were of concern to parents but not to professionals were identified. Sensitivity, false negative rate, specificity, false positive rate, and Youden index were calculated to analyze the discordance rate for each item. Results Many parents in this study were concerned about the issues that professionals did not consider to be concerning. Moreover, the parents worried about more issues for 3-year-olds than for 18-month-olds. The items for which ≥ 10 professionals indicated concerns and with higher discordance between the professionals and parents for both boys and girls were “picky eating” for 18-month-olds and “inconsistent amount of food” for 3-year-olds. Conclusions The concerns that professionals have with respect to children's diets and the things that parents worry about show gaps. It might be necessary to provide professional counseling for parents to develop a correct understanding of their children’s dietary habits.

Abstract The development of multiple squamous cell carcinomas (SCC) in the upper aerodigestive tract, which includes the oral cavity, pharynx, larynx, and esophagus, is explained by field cancerization and is associated with alcohol consumption and cigarette smoking. We reviewed the association between alcohol consumption, multiple Lugol‐voiding lesions, and field cancerization, mainly based on the Japan Esophageal Cohort study. The Japan Esophageal Cohort study is a prospective cohort study that enrolled patients with esophageal SCC after endoscopic resection. Enrolled patients received surveillance by gastrointestinal endoscopy every 6 months and surveillance by an otolaryngologist every 12 months. The Japan Esophageal Cohort study showed that esophageal SCC and head and neck SCC that developed after endoscopic resection for esophageal SCC were associated with genetic polymorphisms related to alcohol metabolism. They were also associated with Lugol‐voiding lesions grade in the background esophageal mucosa, the score of the health risk appraisal model for predicting the risk of esophageal SCC, macrocytosis, and score on alcohol use disorders identification test. The standardized incidence ratio of head and neck SCC in patients with esophageal SCC after endoscopic resection was extremely high compared to the general population. Drinking and smoking cessation is strongly recommended to reduce the risk of metachronous esophageal SCC after treatment of esophageal SCC. Risk factors for field cancerization provide opportunities for early diagnosis and minimally invasive treatment. Lifestyle guidance of alcohol consumption and cigarette smoking for esophageal precancerous conditions, which are endoscopically visualized as multiple Lugol‐voiding lesions, may play a pivotal role in decreasing the incidence and mortality of esophageal SCC.

Background: Prioritization for novel coronavirus disease 2019 (COVID-19)-related health policies usually considers age and certain other characteristics, but sex is rarely included, despite the higher risk of severe disease in men. The aim of this study was to compare the impact of sex and age on the severity of COVID-19 by estimating the age difference in years for which the risk for men versus women is the same. Methods: We analyzed 23,414 Japanese COVID-19 inpatients aged 20–89 years (13,360 men and 10,054 women). We graded the severity of COVID-19 (0 to 5) according to the most intensive treatment required during hospitalization. The risk of grade 2/3/4/5 (non-invasive positive pressure ventilation/invasive mechanical ventilation/extracorporeal membrane oxygenation/death), grade 3/4/5, and separately grade 5 was analyzed using a multiple logistic regression model. Results: The odds ratio (OR) of grades 2/3/4/5, 3/4/5 (primary outcome), and 5 for men relative to women was 2.76 (95% CI, 2.44–3.12), 2.78 (95% CI, 2.42–3.19), and 2.60 (95% CI, 2.23–3.03), respectively, after adjustment for age and date of admission. These risks for men were equivalent to those for women 14.1 (95% CI, 12.3–15.8), 11.2 (95% CI, 9.7–12.8), and 7.5 (95% CI, 6.3–8.7) years older, respectively. Conclusion: The risks of worse COVID-19 prognosis (grades 3/4/5) in men were equivalent to those of women 11.2 years older. Reanalyzing data extracted from four previous studies also revealed a large impact of sex difference on the severity of COVID-19. We should pay more attention to sex differences to predict the risk of COVID-19 severity and to formulate public health policy accordingly.

Background and Aims: Multiple developments of squamous dysplasia and squamous cell carcinoma (SCC) in the upper aerodigestive tract have been explained by field cancerization phenomenon and were associated with alcohol and cigarette use. Second primary SCC development after curative treatment impairs patients’ quality of life and survival; however, how these consumption and cessation affect field cancerization is still unknown. Methods: This is a multicenter cohort study including 331 patients with superficial esophageal SCC (ESCC) treated endoscopically and pooled data from 1022 healthy subjects for comparison. Physiological condition in the background esophageal mucosa was classified into 3 groups based on the number of Lugol-voiding lesions (LVLs) per endoscopic view: grade A, 0; grade B, 1–9; or grade C, ≥10 LVLs. Lifestyle surveys were conducted using a self-administered questionnaire. Patients were counseled on the need for alcohol and smoking cessation by physicians and were endoscopically surveyed every 6 months. Results: LVL grades were positively associated with alcohol drinking intensity, flushing reactions, smoking, and high-temperature food and were negatively associated with eating green and yellow vegetables and fruit. Second primary ESCC and head/neck SCC were significantly more prevalent in the grade C LVL (cumulative 5-y incidences 47.1%, 95% confidence interval [CI] = 38.0–57.2 and 13.3%, 95% CI = 8.1–21.5, respectively). Alcohol and smoking cessation significantly reduced the development of second primary ESCC (adjusted hazard ratios 0.47, 95% = CI 0.26–0.85 and 0.49, 95% CI = 0.26–0.91, respectively). Conclusion: Alcohol drinking, smoking, flushing reaction, and high-temperature food were closely associated with field cancerization, and cessation of alcohol and smoking significantly reduced the risk of development of second primary cancer. UMIN Clinical Trials Registry ID:UMIN000001676.

BackgroundGrowing evidence suggests that intervention for smoking cessation enhances alcohol abstinence in treatment settings for alcohol dependence. However, research in this field is rare in Asians.MethodWe prospectively investigated the association of smoking status with drinking status using 9 surveys mailed during a 12-month period in 198 Japanese alcohol-dependent men (70 never/ex-smokers and 128 smokers) who admitted for the first time and completed a 3-month inpatient program for simultaneous alcohol abstinence and smoking cessation.ResultsNonsmoking during the first month after discharge and at the end of follow-up was reported in 28.9% and 25.0% of the baseline smokers, respectively. Kaplan-Meier estimates showed that a 12-month alcohol abstinence and heavy-drinking-free status were more frequent among never/ex-smokers (45.1% and 59.8%, respectively) and baseline smokers who quit smoking during the first month after discharge (59.0% and 60.8%, respectively), compared with sustained smokers (30.0% and 41.2%, respectively). Among the baseline smokers, the multivariate odds ratio (95% confidence interval) for smoking cessation during the first month were 2.77 (1.01-7.61) for alcohol abstinence during the period and 2.50 (1.00-6.25) for use of varenicline, a smoking cessation agent, during the inpatient program. After adjusting for age, drinking profile, lifestyle, family history of heavy or problem drinking, lifetime episodes of other major psychiatric disorders, and medications at discharge, the multivariate hazard ratios (HRs) for drinking lapse were 0.57 (0.37-0.89) for the never/ex-smoking and 0.41 (0.23-0.75) for new smoking cessation groups, respectively, compared with sustained smoking, while the corresponding HRs for heavy-drinking lapse were 0.55 (0.33-0.90) and 0.47 (0.25-0.88), respectively. The HR for drinking lapse was 0.63 (0.42-0.95) for the nonsmoking group (vs. smoking) during the observation period, while the HR for heavy-drinking lapse was 0.58 (0.37-0.91) for the nonsmoking group (vs. smoking) during the observation period. Other significant variables that worsened drinking outcomes were higher daily alcohol intake prior to hospitalization, family history of heavy or problem drinking and psychiatric medications at discharge.ConclusionNonsmoking was associated with better outcomes on the drinking status of Japanese alcohol-dependent men, and a smoking cessation program may be recommended to be integrated into alcohol abstinence programs.

Objectives To determine national medium-term trends in dental visits during three COVID-19 emergency declaration periods in Japan and to analyse how these trends varied according to prefectural emergency measures and COVID-19 incidence.Design and setting A retrospective observational study of Japan’s dental claims from January 2017 to December 2021.Data sources Data from a monthly report by the Health Insurance Claims Review and Reimbursement Services (HICRRS) in Japan. HICRRS handles the claims of employer-based health insurance.Data analysis We determined the number of monthly dental claims nationwide from January 2017 to December 2021 and the percentage change in the number of monthly dental claims based on the difference in the COVID-19 alert level between the three emergency declaration periods in 2020–2021 and the corresponding periods in 2019. Results were analysed using descriptive statistics, multiple regression model, graphical figures, and narrative synthesis.Outcome measures The main outcome was the change in the number of dental visits between the emergency declaration periods in 2020–2021 and the corresponding periods in 2019. We also assessed the difference in the number of dental visits based on the COVID-19 alert level.Results The data set included a total of 736 946 088 dental claims. Until the end of 2021, the greatest decrease in monthly dental claims was in April 2020, which was 22.3% lower than that in April 2019. As indicated by the coefficient in the regression model, the percentage change in monthly dental claims decreased by 5.01% (95% CI −8.27 to –1.74) depending on the difference between the prefectures designated as being under special precautions and other prefectures.Conclusions The decrease in dental visits was greater during the first state of emergency, ie, April–May 2020, and in prefectures designated as being under special precautions. Further efforts to promote appropriate dental visits at different alert levels are necessary.

Abstract Background The collection of weighed food records (WFR) is a gold standard for dietary assessment. We propose using the 24-h recall method combined with a portable camera and a food atlas (24hR-camera). This combination overcomes the disadvantages of the 24-h dietary recall method. Our study examined the validity of the 24hR-camera method against WFR by comparing the results. Methods Study subjects were 30 Japanese males, aged 31–58 years, who rarely cook and reside in the Tokyo metropolitan area. For validation, we compared the estimated food intake (24hR-camera method) and weighed food intake (WFR method). The 24hR-camera method uses digital photographs of all food consumed during a day, taken by the subjects, and a 24-h recall questionnaire conducted by a registered dietitian, who estimates food intake by comparing the participant’s photographs with food atlas photographs. The WFR method involves a registered dietitian weighing each food item prepared for the subject to consume and any leftovers. Food intake was calculated for each food group and nutrient using the 24hR-camera vs. weighed methods. Results Correlation coefficients between the estimated vs. weighed food intake were 0.7 or higher in most food groups but were low in food groups, such as oils, fats, condiments, and spices. The estimated intake of vegetables was significantly lower for the 24hR-camera method compared to the WFR method. For other food groups, the percentages of the mean difference between estimated vs. weighed food intake were -22.1% to 5.5%, with no significant differences between the methods (except for algae, which had a very low estimated intake). The correlation coefficients between the two methods were 0.774 for energy, and 0.855, 0.769, and 0.763 for the macronutrients, proteins, lipids, and carbohydrates, respectively, demonstrating high correlation coefficients: greater than 0.75. The correlation coefficients between the estimated vs. weighed for salt equivalents and potassium intake were 0.583 and 0.560, respectively, but no significant differences in intake were observed. Conclusions The 24hR-camera method satisfactorily estimated the intake of energy and macronutrients (except salt equivalents and potassium) in Japanese males and was confirmed as a useful method for dietary assessment.

Abstract Head and neck cancers, especially in hypopharynx and oropharynx, are often detected at advanced stage with poor prognosis. Narrow band imaging enables detection of superficial cancers and transoral surgery is performed with curative intent. However, pathological evaluation and real‐world safety and clinical outcomes have not been clearly understood. The aim of this nationwide multicenter study was to investigate the safety and efficacy of transoral surgery for superficial head and neck cancer. We collected the patients with superficial head and neck squamous cell carcinoma who were treated by transoral surgery from 27 hospitals in Japan. Central pathology review was undertaken on all of the resected specimens. The primary objective was effectiveness of transoral surgery, and the secondary objective was safety including incidence and severity of adverse events. Among the 568 patients, a total of 662 lesions were primarily treated by 575 sessions of transoral surgery. The median tumor diameter was 12 mm (range 1–75) endoscopically. Among the lesions, 57.4% were diagnosed as squamous cell carcinoma in situ. The median procedure time was 48 minutes (range 2–357). Adverse events occurred in 12.7%. Life‐threatening complications occurred in 0.5%, but there were no treatment‐related deaths. During a median follow‐up period of 46.1 months (range 1–113), the 3‐year overall survival rate, relapse‐free survival rate, cause‐specific survival rate, and larynx‐preservation survival rate were 88.1%, 84.4%, 99.6%, and 87.5%, respectively. Transoral surgery for superficial head and neck cancer offers effective minimally invasive treatment. Clinical trials registry number: UMIN000008276.

Background: Improving the specific health checkups participation rate is an essential task nationwide; however, studies on measures to accomplish this are limited. This study aimed to examine the influence of ophthalmic checkups on the specific health checkups’ participation rate. Methods: We conducted a postal questionnaire survey on 1,741 countrywide municipalities in Japan from January to February 2019. The questionnaire specifically addressed health checkup participation rates of 2017, health checkups formats (group, individual, or both), simultaneous cancer screenings, simultaneous ophthalmic checkups, and the state of implementation of ophthalmic checkups. We used multiple linear regression analyses to calculate the partial regression coefficients (βs) and their 95% confidential intervals (CIs) to identify the influence of simultaneous ophthalmic checkups on specific health checkup participation rates. Results: There was a significant association between specific health checkup participation rates and simultaneous ophthalmic checkups (β: +2.5%; 95% CI, 1.3–3.8) after adjusting for covariates. The fundus photos of all applicants, fundus photos with restrictions, and ophthalmology consultation for all applicants were associated with a significant increase in the specific health checkup participation rate (β: +2.8%, 95% CI, 1.2–4.4; β: +2.0%, 95% CI, 0.2–3.9; β: +7.4%, 95% CI, 1.2–13.6 respectively). Conclusions: Our results suggest that additional simultaneous ophthalmic checkups as specific health checkups could increase the specific health checkup participation rate.

Abstract Background Birthweight has been declining consistently for more than 30 years in Japan. This rapid rise in low birthweight is one of the worst among the countries of the Organization for Economic Co-operation and Development. We examined potential determinants of birthweight decline in Japan. Methods We used population-based birth certificate data from vital statistics records and retrieved 40,968,266 birth certificates of neonates born between 1980 and 2004. We analyzed time trends using linear regression analysis in examining whether the decline in birthweight could be explained by obstetrical variables such as gestational age and multiple gestations. Results From 1980 to 2004, we observed a decline in mean birthweight with a yearly effect of − 8.07 g, which became steeper after 1985, persisted until 1999, and plateaued thereafter. After adjusting for gestational age, gender, birth order, multiple gestations, and fathers’ age, the yearly effect between 1980 and 2004 persisted at − 5.13 g. Conclusion Recent decreases in birthweight among Japanese neonates were not fully explained by trends in gestational age, gender, birth order, multiple gestations, and fathers’ age. Thus, additional factors such as pre-pregnancy maternal body mass index (BMI) and maternal diet should be considered. Reducing the rate of induced deliveries and improving the BMI or diet of young women should be a public health priority.

Background: It is uncertain whether health counselling after community-based health checkups for high-risk individuals of lifestyle-related disease enhances their referral to physicians. Methods: We performed a clustered randomized controlled trial of untreated high-risk individuals aged 40 to 74 years who were screened from the annual health checkup in 2014 and 2015 under the national health insurance in 43 municipalities around Japan, assigning 21 intervention and 22 usual care municipalities. The high-risk conditions were severe forms of hypertension, diabetes, dyslipidemia (for men), and proteinuria. For the intervention group, the theory-based health counselling was performed to enhance referrals to physicians, while each municipality performed its own standard counselling for the usual care group. Data on clinical visits and risk factors were collected systematically and anonymously from the databases of health insurance qualification, health insurance claims, and annual health checkups. Hypotheses are that the cumulative proportion of seeing physicians (clinical visits) is higher in the intervention than the usual care groups, and that those in the intervention group have lower cumulative incidence of composite outcomes associated with lifestyle-related diseases. Results: The numbers of subjects for the analyses were 8,977 in the intervention group and 6,733 in the usual care group. Among them, 6,758 had hypertension, 2,147 had diabetes, 2,861 had dyslipidemia, and 1,221 had proteinuria in the intervention group, with corresponding numbers of 4,833, 1,517, 2,262, and 845, respectively, in the usual care group. There were no material differences in mean levels and proportions of major cardiovascular risk factors between the two groups. Conclusions: We expect to provide scientific evidence on the effectiveness of health counselling.

Background: The National Nutrition Survey on Preschool Children, Japan (NNSPC) provides fundamental information for policy making for child nutrition. However, the response rate and background characteristics of subjects are unclear. Here, we examined response rate and sociodemographic factors related with response to the survey and evaluated the magnitude of bias due to selective response in the survey estimates of the NNSPC. Methods: This study was based on two national surveys conducted in 2015: the NNSPC and the Comprehensive Survey of Living Conditions (CSLC). Because potential survey participants of the NNSPC were children aged

Abstract Background Esophageal squamous cell carcinoma (ESCC), head and neck SCC (HNSCC), and gastric adenocarcinoma (GA) are frequently detected at an early stage using endoscopic screening in Japanese alcohol‐dependent men. Methods We performed endoscopic screening with esophageal iodine staining and oropharyngolaryngeal inspection in 7582 Japanese alcohol‐dependent men (40‐79 years) during 1993‐2018, and retrospectively investigated their initial screening results. Results The 2008‐2018 screening showed lower detection rates for ESCC (2.6% vs 4.0%, P = .0009) and GA (0.5% vs 1.4%, P

Abstract Background Parents often have concerns about the food habits of their young children. Cooking is a frequent behavior related to dietary activities at home. We hypothesized that “a parent cooking meals together with young children might alleviate dietary concerns.” The aim of this study was to identify the relationship between parental cooking practices (e.g., cooking meals together with the child) and diet-related concerns. Methods Data were extracted from the “National nutrition survey on preschool children” conducted among nation-wide households with toddlers and preschoolers in 2015 by the Ministry of Health, Labour and Welfare of Japan. Parents were classified into two groups comprising those who cooked meals together with their children and those who did not. The following variables were compared: taking too much time to eat (slow eaters), “picky” eating (eating only certain foods), inconsistent food intake (eating too much or too little), playing with food/utensils while eating, preferring sweetened beverages and snacks over meals, eating too fast to chew well, not swallowing food, disinterested in eating, and spitting out food. The associations between parent–child cooking meals together and the concerns pertaining to the child’s dietary habits and food intake were analyzed and compared between the two groups. Results The concerns of “picky eating” and “playing with food/utensils while eating” were lower, while “eating too much” was higher in the parent-cooking together group. The intake frequency of fish, soybeans/soy products, vegetables, and milk among children were higher in the “cooking together” group than among those in the “not cooking together” group. Children in the “cooking together” group consumed a significantly greater variety of foods than those in the “not cooking together” group. Conclusions Cooking a meal together with a child may be related to the parent’s lower concerns about the dietary habits of the child, including “picky eating” and “playing with food/utensils while eating,” but may also be related to the higher concerns of “eating too much.”

Abstract Aims The relationship between HbA1c and diabetic retinopathy is expected to differ between different races. In this study, we verified which of HbA1c and fasting plasma glucose (FPG) is more effective for detecting the diabetic retinopathy longitudinally in a Japanese population. Materials and Methods The study subjects underwent health examinations twice (including eye test and questionnaire of lifestyle and health) in 2008‐2009 (baseline) and in 2012‐2013 (4‐year follow‐up). Both non‐DM and DM patients at baseline were included as the participants. Of these participants, who had not been diagnosed with retinopathy at the baseline survey (n = 2427; 2150 men and 277 women) had eye fundus photographs taken four years later (follow‐up survey). The odds ratios of incidence of retinopathy according to the eight groups of FPG and HbA1c were estimated using multiple logistic regression analysis adjusted for sex and age. Receiver operator characteristic analysis was used to evaluate each value associated with the presence or absence of retinopathy. Results The odds ratios (95% confidence intervals) of incidence of retinopathy by HbA1c level categories, in ascending order, were 1.0 (ref.), 5.66 (1.14‐28.26), 1.69 (0.24‐12.04), 3.03 (0.50‐18.28), 1.04 (0.09‐11.59), 4.73 (0.78‐28.69), 4.12 (0.74‐22.85) and 24.47 (5.61‐106.75). For both FPG and HbA1c levels, the odds ratio for the development of retinopathy increased linearly with the increases in the levels FPG and HbA1c, and no clear threshold was observed. The AUC values (SE) for FPG and HbA1c were almost the same, at 0.750 (0.046) and 0.732 (0.048). Conclusions It was clarified that the higher the level of FPG and HbA1c was, the higher the incidence of retinopathy after 4 years was. There was no clear threshold. The detection ability of the incidence of retinopathy was almost the same between FPG and HbA1c, suggesting it is possible to detect the risk of retinopathy by HbA1c only.

ObjectiveThe risk of alcohol dependence (AD) in Japanese men and women was evaluated according to combinations of alcohol flushing and aldehyde dehydrogenase-2 (ALDH2, rs671) and alcohol dehydrogenase-1B (ADH1B, rs1229984) genotypes, all of which are known to determine AD susceptibility in Asians. Previous studies have focused on men, since women account for a smaller proportion of AD subjects.MethodsCase control studies were conducted between 3721 male and 335 female AD Japanese and 610 male and 406 female controls who were asked about their current or former tendency to experience facial flushing after drinking a glass of beer and underwent ALDH2 and ADH1B genotyping. The time at which alcohol-induced facial flushing tendencies had disappeared in former-flushing AD subjects was also evaluated.ResultsCurrent alcohol flushing, the inactive ALDH2*1/*2 genotype, and the fast-metabolizing ADH1B*2 allele were less frequently found in the AD groups. Although alcohol flushing was strongly influenced by the ALDH2 and ADH1B genotypes, multiple logistic model showed that never or former flushing and the genotype combinations were independent strong risk factors of AD in men and women. Never or former flushing (vs. current flushing) markedly increased the odds ratios of AD in carriers of each of the ALDH2 and ADH1B genotype combinations. The temporal profiles for drinking and flushing in former-flushing AD subjects revealed that the flushing response disappeared soon after or before the start of habitual drinking during young adulthood, regardless of the ALDH2 genotype.ConclusionAlthough alcohol flushing is influenced by the ALDH2 and ADH1B genotypes, constitutional or acquired flushing tolerance is an independent susceptibility trait for AD. The combination of the alcohol flushing status and the ALDH2 and ADH1B genotypes can provide a better new strategy for AD risk assessment than the alcohol flushing status alone or the genotypes alone in Asian men and women.

We aimed to evaluate the accuracy of glaucoma screening using fundus photography combined with optical coherence tomography and determine the agreement between ophthalmologists and ophthalmology residents. We used a comprehensive ophthalmologic examination dataset obtained from 503 cases (1006 eyes). Of the 1006 eyes, 132 had a confirmed glaucoma diagnosis. Overall, 24 doctors, comprising two groups (ophthalmologists and ophthalmology residents, 12 individuals/group), analyzed the data presented in three screening strategies as follows: (1) fundus photography alone, (2) fundus photography + optical coherence tomography, and (3) fundus photography + optical coherence tomography + comprehensive examination. We investigated the diagnostic accuracy (sensitivity and specificity). The respective sensitivity and specificity values for the diagnostic accuracy obtained by 24 doctors, 12 ophthalmologists, and 12 ophthalmology residents were as follows: (1) fundus photography: sensitivity, 55.4%, 55.4%, and 55.4%; specificity, 91.8%, 94.0%, and 89.6%; (2) fundus photography + OCT: sensitivity, 80.0%, 82.3%, and 77.8%; specificity, 91.7%, 92.9%, and 90.6%; and (3) fundus photography + OCT + comprehensive examination: sensitivity 78.4%, 79.8%, and 77.1%; specificity, 92.7%, 94.0%, and 91.3%. The diagnostic accuracy of glaucoma screening significantly increased with optical coherence tomography. Following its addition, ophthalmologists could more effectively improve the diagnostic accuracy than ophthalmology residents. Screening accuracy is improved when optical coherence tomography is added to fundus photography.

Abstract Background Data on the long-term risks of non-AIDS defining cancers (NADCs) are limited, especially in Asians. The incidence of NADCs may correlate with the epidemiological trend of cancers or oncogenic infection in each country, and thus the target cancers would be different between Western and Asian countries. We aimed to elucidate the incidence of NADCs and its predictive factors in Asian HIV-infected patients. Methods Subjects were HIV-infected patients (n = 1001) periodically followed-up for 9 years on average. NADCs were diagnosed by histopathology and/ or imaging findings. Standardized incidence ratios (SIR) were calculated as the ratio of the observed to expected number of NADCs for comparison with an age-and sex-matched general population. Cox’s proportional hazards model was used to estimate hazard ratios (HR). Results During the median follow-up of 9 years, the 10-year cumulative incidence of NADCs was 6.4%.At NADC diagnosis, half of patients presented at age 40–59 years and with advanced tumor stage. Compared with the age-and sex-matched general population, HIV-infected patients are at increased risk for liver cancer (SIR, 4.7), colon cancer (SIR, 2.1), and stomach cancer (SIR, 1.8). In multivariate analysis, a predictive model for NADCs was developed that included age group (40–49, 50–59, 60–69, and ≥ 70 years), smoker, HIV infection through blood transmission, and injection drug use (IDU), and HBV co-infection. The c-statistic for the NADCs predictive model was 0.8 (95%CI, 0.8–0.9, P

Abstract Background Health personnel must provide continuous support in response to problematic results from health checks of infants and toddlers (hereinafter “infant[s]”). Among this support, it is important for health personnel to provide nutritional guidance to families as a collaborative effort between the staff from multiple disciplines and community organizations. This study aimed to clarify the factors affecting collaboration with community organizations in providing nutritional guidance to families following health checks for infants in Japan. Methods The design of this study consisted of a cross-sectional, multilevel survey. A self-administered questionnaire was mailed to all municipalities (1741 towns and cities) in Japan to be completed by the person responsible for nutrition advice. The research was performed in August 2015. We obtained 988 valid responses (response rate of 56.7%). To identify the factors that affect the collaboration with community organizations in providing nutritional guidance, we determined how municipalities responded to infants needing support (five items), how municipalities evaluated health guidance (five items), the number of distributed maternal and child health handbooks, and the number of infants who received follow-up evaluations. Results The results of multivariate analyses showed that the factors related to successful community collaboration in providing nutritional guidance included holding a multi-professional staff meeting after health checks (post-conference; odds ratio [OR], 2.34; P = 0.001); following up children suspected of having developmental and mental disabilities or delays before entering elementary school (OR, 1.77; P = 0.0004); and considering dental caries data from dental checkups in providing health guidance (OR, 1.56; P = 0.003). Conclusions Holding a multi-professional meeting after infant health checks (post-conference) was strongly associated with community collaboration in providing nutritional guidance for infants.

Type-2/eosinophilic inflammation plays a pivotal role in asthma. The identification of severe type-2/eosinophilic asthma is important for improving the management of patients with asthma. Therefore, efforts to develop non-invasive biomarkers for type-2/eosinophilic airway inflammation have been made during this decade. Currently, fraction of exhaled nitric oxide (FeNO) and serum periostin levels are considered markers of type-2/eosinophilic inflammation in asthma. However, a single-marker approach has limited the ability to diagnose severe type-2/eosinophilic asthma accurately and predict disease outcomes precisely. The present article reviews the utility of FeNO and serum periostin levels in a single-marker approach and in a multiple-marker approach in identifying patients with severe type-2/eosinophilic asthma. Furthermore, based on a sub-analysis of the Kinki Hokuriku Airway disease Conference (KiHAC), geno-endo-phenotypes of patients were stratified into four groups according to the FeNO and serum periostin levels.

Introduction. The relationship between HbA1c and diabetic retinopathy is expected to differ between different races. This study was designed to verify whether HbA1c or fasting plasma glucose (FPG) is more effective in detecting diabetic retinopathy in a Japanese population. Materials and Methods. The study subjects underwent health examinations between 2008 and 2009 with fasting. Of these participants, we analyzed the data for 2,921 Japanese men who had undergone an ophthalmologic examination. Retinopathy was classified into 7 categories according to a simplified diabetic retinopathy scale. The odds ratios of retinopathy according to the eight groups of FPG and HbA1c were estimated using multiple logistic regression analysis adjusted for age. Receiver operator characteristic analysis was used to evaluate each value associated with the presence or absence of retinopathy. Results and Discussion. The odds ratios (95% CI) of retinopathy for HbA1c level categories, in ascending order, were 1.0 (ref.), 0.88 (0.28-2.75), 1.27 (0.44-3.69), 1.52 (0.48-4.79), 1.89 (0.52-6.85), 2.70 (0.66-11.10), 4.10 (0.80-21.00), and 6.34 (2.37-16.97) where the odds ratios significantly increased with HbA1c≥6.8%. The area under the curve (SE) for FPG and HbA1c was almost the same, at 0.668 (0.043) and 0.680 (0.043), respectively. Conclusions. It was clarified that the higher the level of HbA1c, the higher the prevalence of retinopathy, and there was no clear threshold. The detection ability of retinopathy was almost the same, suggesting that it is possible to detect the risk of retinopathy by HbA1c only.

BackgroundThe presence of large or multiple esophageal distinct iodine-unstained lesions (DIULs) is a strong predictor of field cancerization in the upper aerodigestive tract. Several risk factors for DIULs, including genetic polymorphisms of alcohol and aldehyde dehydrogenases (ADH1B, rs1229984; ALDH2, rs671), have been demonstrated in Japanese alcohol-dependent men. However, few evaluations of alcohol-dependent women have been conducted in this field.MethodsUsing multiple logistic regression models, we investigated the results of screening using esophageal iodine staining and the identification of determinants for esophageal DIULs in 472 Japanese alcohol-dependent women.ResultsDIULs ≥5 mm, multiple DILUs, and both characteristics were observed in 35 (7.4%), 31 (6.6%), and 16 (3.4%) patients, respectively. DIULs ≥5 mm were histologically diagnosed as low-grade intraepithelial neoplasia in 26 patients and superficial squamous cell carcinoma in 9 patients. Although the inactive heterozygous ALDH2*1/*2 genotype was more common (33.3% vs. 11.4%, p = 0.002) in the group with DIULs ≥5 mm than in the group without DIULs ≥5 mm, no significant differences in the results of a questionnaire asking about current and past facial flushing after a glass of beer were seen between the groups with and without DIULs ≥5 mm. When individuals with current or former flushing were assumed to have inactive ALDH2, the sensitivity and specificity of current or former flushing to identify the presence of inactive ALDH2 were 50.0% and 93.5%, respectively; these values were previously reported to be 88% and 92%, respectively, in a Japanese general female population. The low sensitivity in the present study suggests that a lack of alcohol flushing may play a crucial role in the development of alcohol dependence in women with inactive ALDH2. No significant differences in age, usual alcohol consumption, or smoking habits were observed according to ADH1B and ALDH2 genotypes. Multiple logistic regression analyses showed that the slow-metabolizing ADH1B*1/*1 genotype (odds ratio [95% confidence interval], 12.5 [4.82-32.4] and 9.89 [3.50-27.9]), the inactive heterozygous ALDH2*1/*2 genotype (2.94 [1.18-7.38] and 3.79 [1.40-10.3]), a lower body mass index per -1 kg/m2 (1.17 [1.02-1.35] and 1.38 [1.14-1.67]), and a mean corpuscular volume ≥106 fl (3.70 [1.56-8.81] and 3.27 [1.24-8.64]) increased the risk of DIULs ≥5 mm and multiple DIULs, respectively. The combination of ADH1B*1/*1 and ALDH2*1/*2 markedly increased the risk of esophageal DIULs ≥5 mm (39.3 [10.6-146]).ConclusionsJapanese alcohol-dependent women shared several common risk factors for esophageal squamous cell neoplasia with alcohol-dependent men, but with considerably different magnitudes.

ObjectiveTo examine the possibility of diagnosing the double burden of malnutrition using estimated deviation values in low- and lower-middle-income countries.MethodsA modified version of the Japanese Diagnostic Tool was used. Data on 194 countries were analyzed, including data from the United Nations International Children's Fund, World Health Organization and World Bank. After conducting a Box-Cox transformation, deviation values were calculated. The degree to which the values deviated relative to a deviation cutoff value of 50 was assessed. Focusing on countries with low- and middle-income economic levels, we examined the utility of this tool to show characteristic nutritional problems in each country.ResultsThe deviation values had normal, distorted, bimodal, or trimodal distributions. In the lower-middle-income countries, almost all countries had values ranging from 40 to 60 for education and water environments (urban and rural), and the differences were minimal. However, different causes of noncommunicable disease-related deaths were considered, and the primary cause appeared to be related to lifestyle factors, particularly alcohol consumption and tobacco smoking. In comparison, the deviation values related to death among low-income countries also appeared to be related to differences in education and sanitation in urban and rural areas.ConclusionThe study results can help to determine the status of nutritional inequalities and plan country-specific strategies to reduce the double burden of malnutrition.

Alcohol consumption combined with inactive aldehyde dehydrogenase-2 (ALDH2) and the presence of multiple esophageal Lugol-voiding lesions (LVLs; dysplasia) are strong predictors for multiple development of esophageal squamous cell carcinoma (ESCC) in East Asians. We invented a health risk appraisal (HRA) model for predicting the risk of ESCC based on drinking, smoking, dietary habits, and alcohol flushing, i.e., past or present facial flushing after drinking a glass of beer, a surrogate marker for inactive ALDH2.Prospective follow-up examinations (median follow-up time, 50.3 months) were performed in 278 Japanese men after endoscopic mucosectomy for early ESCC (UMIN Clinical Trials Registry ID: UMIN000001676).Sixty-four subjects developed metachronous ESCC. A receiver operating characteristic curve showed that HRA scores ≥12 best predicted the development of metachronous ESCC. The ESCC detection rate per 100 person-years was 9.8 in the high-HRA-score group (n = 104) and 4.5 in the low-HRA-score group (n = 174), and the risk of development of metachronous ESCC was higher in the high-HRA-score group than in the low-HRA-score group (adjusted hazard ratio: 2.00 [95% CI: 1.12-3.30]). Multiple LVLs was a very strong predictor of the development of metachronous SCC, but high HRA scores predicted it independently. The cumulative incidences of metachronous ESCC decreased after drinking cessation in the high-HRA-score drinker group (adjusted hazard ratio: 0.37 [0.14-0.97]).Both the HRA model that included alcohol flushing and the multiple LVL grade predicted the development of metachronous ESCC in Japanese men after endoscopic mucosectomy for ESCC. Drinking cessation in the high-HRA-score drinker group reduced the rate of metachronous ESCC.

Elevated serum triglyceride (TG) and high-density-lipoprotein cholesterol (HDL-C) levels are common in drinkers. The fast-metabolizing alcohol dehydrogenase-1B encoded by the ADH1B*2 allele (vs. ADH1B*1/*1 genotype) and inactive aldehyde dehydrogenase-2 encoded by the ALDH2*2 allele (vs. ALDH2*1/*1 genotype) modify ethanol metabolism and are prevalent (≈90% and ≈40%, respectively) in East Asians. We attempted to evaluate the associations between the ADH1B and ALDH2 genotypes and lipid levels in alcoholics.The population consisted of 1806 Japanese alcoholic men (≥40 years) who had undergone ADH1B and ALDH2 genotyping and whose serum TG, total cholesterol, and HDL-C levels in the fasting state had been measured within 3 days after admission.High serum levels of TG (≥150 mg/dl), HDL-C (>80 mg/dl), and low-density-lipoprotein cholesterol (LDL-C calculated by the Friedewald formula ≥140 mg/dl) were observed in 24.3%, 16.8%, and 15.6%, respectively, of the subjects. Diabetes, cirrhosis, smoking, and body mass index (BMI) affected the serum lipid levels. Multivariate analysis revealed that the presence of the ADH1B*2 allele and the active ALDH2*1/*1 genotype increased the odds ratio (OR; 95% confidence interval) for a high TG level (2.22 [1.67-2.94] and 1.39 [0.99-1.96], respectively), and decreased the OR for a high HDL-C level (0.37 [0.28-0.49] and 0.51 [0.37-0.69], respectively). The presence of the ADH1B*2 allele decreased the OR for a high LDL-C level (0.60 [0.45-0.80]). The ADH1B*2 plus ALDH2*1/*1 combination yielded the highest ORs for high TG levels and lowest OR for a high HDL-C level. The genotype effects were more prominent in relation to the higher levels of TG (≥220 mg/dl) and HDL-C (≥100 mg/dl).The fast-metabolizing ADH1B and active ALDH2, and especially a combination of the two were strongly associated with higher serum TG levels and lower serum HDL-C levels of alcoholics. The fast-metabolizing ADH1B was associated with lower serum LDL-C levels.

BACKGROUND: Recent reports on Propionibacterium acnes (P. acnes) suggest that this bacterium is prevalent in the prostate, is associated with acute and chronic prostatic inflammation, and might have a role in prostate carcinogenesis. METHODS: To evaluate the pathogenic role of this indigenous bacterium, we screened for the bacterium in radical prostatectomy specimens using enzyme immunohistochemistry with a novel P. acnes-specific monoclonal antibody (PAL antibody), together with an anti-nuclear factor-kappa B (NF-κB) antibody. We examined formalin-fixed and paraffin-embedded tissue sections of radical prostatectomy specimens from 28 patients with prostate cancer and 18 age-matched control patients with bladder cancer, but without prostate cancer. RESULTS: Immunohistochemistry with the PAL antibody revealed small round bodies within some non-cancerous glandular epithelium and stromal macrophages in most prostate samples. Prostate cancer samples had higher frequencies of either cytoplasmic P. acnes or nuclear NF-κB expression of glandular epithelium and higher numbers of stromal macrophages with P. acnes than control samples. These parameters were also higher in the peripheral zone than in the transitional zone of the prostate, especially in prostate cancer samples. Nuclear NF-κB expression was more frequent in glands with P. acnes than in glands without P. acnes. The number of stromal macrophages with the bacterium correlated with the grade of chronic inflammation in both the PZ and TZ areas and with the grade of acute inflammation in the TZ area. CONCLUSIONS: Immunohistochemical analysis with a novel monoclonal antibody for detecting P. acnes in the prostate suggested that intraepithelial P. acnes infection in non-cancerous prostate glands and inflammation caused by the bacterium may contribute to the development of prostate cancer.

BackgroundEvidence regarding the mortality rate after administration of the pandemic influenza A (H1N1) 2009 vaccine on patients with underlying diseases is currently scarce. We conducted a case-control study in Japan to compare the mortality rates of patients with idiopathic interstitial pneumonia after the vaccines were administered and were not administered.MethodsBetween October 2009 and March 2010, we collected clinical records in Japan and conducted a 1:1 matched case-control study. Patients with idiopathic interstitial pneumonia who died during this period were considered case patients, and those who survived were considered control patients. We determined and compared the proportion of each group that received the pandemic influenza A (H1N1) 2009 vaccine and estimated the odds ratio. Finally, we conducted simulations that compensated for the shortcomings of the study associated with adjusted severity of idiopathic interstitial pneumonia.ResultsThe case and control groups each comprised of 75 patients with idiopathic interstitial pneumonia. The proportion of patients who received the pandemic influenza A (H1N1) 2009 vaccine was 30.7% and 38.7% for the case and control groups, respectively. During that winter, the crude conditional odds ratio of mortality was 0.63 (95% confidence interval, 0.25-1.47) and the adjusted conditional odds ratio was 1.18 (95% confidence interval, 0.33-4.49); neither was significant. The simulation study showed more accurate conditional odds ratios of 0.63-0.71.ConclusionsIn our study, we detected no evidence that the influenza A (H1N1) 2009 vaccine increased the mortality rate of patients with idiopathic interstitial pneumonia. The results, however, are limited by the small sample size and low statistical power. A larger-scale study is required.