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[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.

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.

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.

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., This is the first report on nationwide survival data and pathological criteria of superficial head and neck cancer. Transoral surgery for superficial head and neck cancer was safe and offered highly curative minimally invasive treatment preserving organs and their function. Subepithelial invasion was clinically useful predictor of recurrence after transoral surgery.

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.

Globally, a decreasing incidence of male esophageal squamous cell carcinoma (ESCC) has been observed in recent decades. We evaluated the determinants of esophageal distinct iodine‐unstained lesions (DIULs), high‐cancer‐risk lesions and ESCC, among 3858 Japanese alcohol‐dependent men (40‐79 years) who underwent chromoendoscopic screening between 2003 and 2018. The initial screening detected DIULs ≥ 5 mm in 541 patients (dysplasia in 319 and SCC in 129) and multiple DIULs in 640. The detection rates for DIULs and chronic atrophic gastritis (CAG), pack‐years, and the mean corpuscular volume (MCV) decreased over the course of the study period, while the detection of hiatal hernia and/or columnar‐lined esophagus (HH/CLE) and the carriers of inactive heterozygous aldehyde dehydrogenase‐2 (ALDH2, rs671) increased. Multiple logistic regression analyses showed that an older age, larger number of pack‐years, smaller body mass index, larger MCV, presence of a slow‐metabolizing alcohol dehydrogenase‐1B genotype (rs1229984), presence of an inactive heterozygous ALDH2 genotype, and more advanced degree of CAG increased the odds ratios (ORs) for DIULs, while the 2008‐2013 and 2014‐2018 screening periods had lower ORs for DIULs than the 2003‐2007 screening period. The presence of HH/CLE decreased the OR for multiple DIULs and was associated with a more proximal location of ESCC. In conclusion, the detection of DIULs in an alcohol‐dependent population decreased between 2003 and 2018. In addition to reported determinants of ESCC, CAG and HH/CLE were associated with the risk of DIULs. Enigmatically, however, the decline in the detection of DIULs was not adequately explained by these factors and warrants further research., The detection of large or multiple esophageal iodine‐unstained lesions including cancer decreased between 2003 and 2018 in an alcohol‐dependent population. In addition to reported determinants of esophageal cancer, chronic atrophic gastritis and hiatal hernia/columnar‐lined esophagus were associated with the risk of these lesions. Enigmatically, however, the declining trend in these lesions was not adequately explained by these factors and warrants further research.

Background Prospectively collected long-term data of patients undergoing endoscopic resection for superficial esophageal squamous cell carcinoma (ESCC) are limited. The aim of this study was to determine the prospectively collected long-term outcomes of endoscopic resection for ESCC as a secondary analysis of the Japan Esophageal Cohort (JEC) study. Methods Patients who underwent endoscopic resection of intramucosal ESCC at 16 institutions between September 2005 and May 2010 were enrolled in the JEC study. All patients underwent endoscopic examination with iodine staining at 3 and 6 months after resection, and every 6 months thereafter. We investigated clinical courses after endoscopic resection, survival rates, and cumulative incidence of metachronous ESCC. Results 330 patients (mean age 67.0 years) with 396 lesions (mean size 20.4 mm) were included in the analysis. Lesions were diagnosed as high-grade intraepithelial neoplasia in 17.4 % and as squamous cell carcinoma in 82.6 % (limited to epithelium in 28.4 %, to lamina propria in 55.4 %, and to muscularis mucosa in 16.2 %). En bloc resection was achieved in 291 (73.5 %). The median follow-up period was 49.4 months. Local recurrences occurred in 13 patients (3.9 %) and were treated by endoscopic procedures. Lymph node metastasis occurred in two patients (0.6 %) after endoscopic resection. The 5-year overall, disease-specific, and metastasis-free survival rates were 95.1 %, 99.1 %, and 94.6 %, respectively. The 5-year cumulative incidence rate of metachronous ESCC was 25.7 %. Conclusions Our study demonstrated that endoscopic resection is an effective treatment for intramucosal ESCC, with favorable long-term outcomes.

Background Second primary head and neck cancers after endoscopic resection of esophageal squamous cell carcinoma adversely affect patients’ outcomes and the quality of life; however, an adequate surveillance schedule remains unclear. Methods We analyzed 330 patients with early esophageal squamous cell carcinoma who underwent endoscopic resection and were registered in the multicenter cohort study to evaluate adequate surveillance for detection of second primary head and neck cancers. Gastrointestinal endoscopists examined the head and neck regions after 3–6 months of endoscopic resection for esophageal squamous cell carcinoma and subsequently every 6 months. An otolaryngologist also examined the head and neck regions at the time of endoscopic resection for esophageal squamous cell carcinoma and at 12 months intervals thereafter. Results During the median follow-up period of 49.4 months (1.3–81.2 months), 33 second primary head and neck cancers were newly detected in 20 patients (6%). The tumor site was as follows: 22 lesions in the hypopharynx, eight lesions in the oropharynx, two lesions in larynx and one lesion in the oral cavity. The 2-year cumulative incidence rate of second primary head and neck cancers was 3.7%. Among them, 17 patients with 29 lesions were treated by transoral surgery. One patient with two synchronous lesions was treated by radiotherapy. Two lesions in two patients were not detected after biopsy. All patients were cured with preserved laryngeal function. Conclusions Surveillance by gastrointestinal endoscopy every 6 months and surveillance by an otolaryngologist every 12 months could detect second primary head and neck cancers at an early stage, thereby facilitating minimally invasive treatment.

Aim To elucidate associations among liver disease, lipid profile, body mass index (BMI), ketonuria, and meal skipping under the influence of alcohol dehydrogenase-1B (ADH1B; rs1229984) and aldehyde dehydrogenase-2 (ALDH2; rs671) genotypes in men with alcohol dependence. Methods We investigated the associations among these variables in 1768 Japanese men with alcohol dependence. Serum lipid levels were followed up after abstinence. Results The slow-metabolizing ADH1B Arg/Arg genotype and inactive ALDH2 Glu/Lys genotype increased the age- and drinking-adjusted odds ratio or regression coefficient for fatty liver, ketonuria, and serum high-density-lipoprotein cholesterol levels (HDL-C), and decreased these for cirrhosis and serum triglyceride levels (TG). The ADH1B Arg/Arg genotype increased the adjusted regression coefficient for BMI and non-HDL-C. In addition to the positive interlinkage among fatty liver, BMI, and atherogenic dyslipidemia, positive associations were observed of fatty liver with ketonuria and meal skipping, of cirrhosis with the BMI, and of ketonuria with non-HDL-C. Negative associations were observed of cirrhosis with fatty liver, TG, non-HDL-C, and HDL-C, and of ketonuria with BMI and TG. Overall, after admission for 4 or 6 weeks, the TG and HDL-C decreased, and the serum low-density lipoprotein cholesterol levels increased. However, there was no change of the serum low-density lipoprotein in the patients with cirrhosis or of the serum TG in those with fatty liver. Conclusions These associations and the alterations in lipid profile after abstinence serve as useful information for a better understanding of the clinical features of men with alcohol dependence.

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.

OBJECTIVE This study sought to evaluate the impacts of interactions between the alcohol dehydrogenase-1B (rs1229984) genotype and the aldehyde dehydrogenase-2 (rs671) genotype on alcohol flushing, alcohol reeking on the day after drinking, and the age distribution in alcohol-dependent patients. METHODS The study subjects were 4107 Japanese alcohol-dependent men who underwent alcohol dehydrogenase-1B and aldehyde dehydrogenase-2 genotyping: 4051 patients were asked about their current or former tendency to experience facial flushing after drinking a glass of beer, and 969 patients were asked about whether they had ever been told that they reeked of alcohol more than 12 hours after they had stopped drinking. RESULTS Current, former, and never flushing were reported in 3.5, 14.9, and 81.5%, respectively, of the subject, and alcohol reeking after more than 12 hours in 36.1% of the subjects. The fast-metabolizing ADH1B*2(+) genotype (*1/*2 or *2/*2) and the inactive ALDH2*2(+) genotype (*1/*2 or *2/*2) affected the multivariate odds ratios for current or former flushing [odds ratio, 95% confidence interval = 2.27 (1.79-2.86) and 23.0 (18.6-28.5), respectively, vs. *2(-) genotype] and for alcohol reeking [0.39 (0.29-0.52) and 1.56 (1.09-2.25), respectively, vs. *2(-) genotype]. An age-dependent decrease in the ADH1B*2(-) and ALDH2*2(-) combination from 32.3% in the 30-39-year age group to 12.5% in the 70-79-year age group and an age-dependent increase in the ADH1B*2(+) and ALDH2*2(-) combination from 52.5% in the 30-39-year age group to 70.5% in the 70-79-year age group were observed (P < 0.0001 for trend). The frequencies of the ADH1B*2(-) and ALDH2*2(+) combination (4.7-6.2%) and the ADH1B*2(+) and ALDH2*2(+) combination (8.9-12.0%) did not change markedly with increasing age. CONCLUSION Interactions between the alcohol dehydrogenase-1B and aldehyde dehydrogenase-2 genotypes modified alcohol flushing, alcohol reeking on the day after drinking, and the age distribution. These findings support the protective roles of the ADH1B*2(+) and ALDH2*2(+) genotypes against the development of alcohol dependence.

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

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, Comparison of detection rates of esophageal squamous cell carcinoma (ESCC) and gastric adenocarcinoma (GA) according to age groups and ALDH2 genotype between the 1993‐2007 screening period and the 2008‐2018 screening period in Japanese alcohol‐dependent men. The detection rates for ESCC and GA were consistently lower during the 2008‐2018 study period than during the 1993‐2007 study period regardless of age groups and ALDH2 genotype.

Background and aim Although an inverse relationship between current smoking and the development of ulcerative colitis (UC) has been shown in North America and Europe, evidence is limited in Asian countries, where the incidence of UC is rapidly increasing. This Japanese case-control study examined the association between active and passive smoking and risk of UC. Methods A self-administered questionnaire was used to obtain information on smoking and potential confounding factors in 384 cases with a diagnosis of UC within the past four years and 665 controls. Results Compared with having never smoked, having ever smoked was associated with an increased risk of UC (adjusted odds ratio [OR] = 1.70, 95% confidence interval [CI]: 1.23-2.37). No association was observed between current smoking and risk of UC, but former smokers had a significant elevation in risk (adjusted OR = 2.40, 95% CI: 1.67-3.45). There was a positive dose-response relationship with pack-years smoked (P for trend = 0.006). Among never smokers, passive smoking exposure at home was significantly associated with an increased risk of UC (adjusted OR = 1.90, 95% CI: 1.30-2.79). A significant dose-response gradient was also observed between pack-years of passive smoking at home and risk of UC (P for trend = 0.0003). Conclusions We confirmed that former smoking elevated the risk of UC, whereas an inverse association between current smoking and the risk of UC did not reach a statistically significant level. Passive smoking may be associated with an increased risk of UC.

In Japan, dietary habits have greatly changed since the coronavirus disease (COVID-19) outbreak, we examined factors related to dietary changes. An online cross-sectional questionnaire survey was conducted in November 2020 among 6000 Japanese adults (aged 20–64 years) registered with a research company and gathered data on demographics, socioeconomic factors, medical history, COVID-19 status of the respondent’s family and neighbors, fear of COVID-19, and changes in lifestyle and dietary habits since the COVID-19 outbreak. To the question “Have you made healthier changes to your dietary habits compared with the dietary habits before the spread of COVID-19 (1 year ago, November 2019)?”, 1215 (20.3%), 491 (8.2%), and 4294 (71.6%) participants answered that their dietary habits were healthier, unhealthier, and unchanged, respectively. Healthier and unhealthier dietary habits were associated with greater fear of COVID-19, altered exercise and sleep times, and smoking. Unhealthy habits were positively associated with living alone, decreasing household income, colleagues with COVID-19, stress, and weight loss/gain. Annual household income, changing household income, COVID-19 in friends, health literacy, exercise frequency, weight loss, and starting smoking were positively associated with healthier dietary changes. The generalizability of these results and strategies to inculcate healthy diets in this “new normal” should be investigated.

Macrocytosis is associated with an increased risk of squamous cell carcinoma (SCC) arising in the esophagus in men. The aim of this study was to evaluate the association between macrocytosis and metachronous SCC of the esophagus after endoscopic resection (ER) of early esophageal SCC in men. The study group comprised 278 men with early esophageal SCC after ER. The main study variables were as follows: (1) cumulative incidence and total number of metachronous SCC of the esophagus according to the presence or absence of macrocytosis (mean corpuscular volume ≥ 106 fl) and (2) predictors of metachronous SCC of the esophagus as assessed with a multivariate Cox proportional-hazards model. The median follow-up was 50.3 months. Macrocytosis was associated with a higher 2-year cumulative incidence of metachronous SCC of the esophagus (without macrocytosis vs. with macrocytosis: 11.4% vs. 38.1%, p = 0.002). Macrocytosis was also associated with a higher total number of metachronous SCC of the esophagus per 100 person-years (without macrocytosis vs. with macrocytosis: 7.7 vs. 31.5 per 100 person-years, p

This study aimed to estimate the distribution of usual intakes in protein, sodium, potassium, and calcium by age group and assessed whether proportions of deficiencies/excesses of each nutrient would occur more in older age via a comparison with the dietary reference intakes for the Japanese population (DRIs_J). A cross-sectional analysis was conducted using a database of the 2-day nutrient intake of 361 Japanese people aged 65–90 years. The AGEVAR MODE was used to estimate usual intake. Percentile curves using estimated distribution by sex and age and usual nutrient intake were compared to those of the DRIs_J. The usual intake of protein (male and female) and potassium and calcium (female) were lower with older age. Within-individual variance of protein in female (p = 0.037) and calcium in male (p = 0.008) subjects were considerably lower with older age. The proportion of deficiencies in protein (male and female), potassium (female), and calcium (female) were higher with older age. However, the proportion of people with excess salt (converted from sodium, male and female) did not differ by age. The variances found herein could be important for enhancing the understanding of differences in dietary intake by age.

Objective: To identify the relationship between preschool children’s dietary diversity and parents’ care behaviours related to their diet including contents of foods and snacks, mealtime practice and parent–child communication. Design: Cross-sectional study. Data were extracted from the National Nutrition Survey on Preschool Children in 2015 by Japan’s Ministry of Health, Labour and Welfare. Setting: The distribution of food diversity score (FDS) (maximum of eight points) was confirmed. The participants were divided into higher (≥4 points) and lower (≤3 points) food diversity groups. A comparison between the two groups examined parents’ socio-economic status, children’s health and living conditions, and parental care concerning children’s diets (thirteen items). A multiple regression analysis was performed relating FDS to the factors of parental socio-economic status and child health, and a logistic regression analysis was conducted to identify factors of parental care related to the higher food diversity group. Participants: 2143 persons from households with children aged 2–6 years. Results: Parental care concerning children’s diets was the factor most strongly associated with children’s FDS. Those factors most strongly associated with higher food diversity were nutritional balance of foods (OR: 1·76; 95 % CI 1·44, 2·16; P < 0 0001), snack contents (OR: 1·41; 95 % CI 1·07, 1·86; P = 0·014) and regular mealtimes (OR: 1·30; 95 % CI 1·08, 1·55; P = 0·005). Conclusions: The findings indicate the importance of parents paying attention to the contents of children’s foods and snacks, ensuring that children eat regularly, and increasing the diversity of their diets.

Background: The aim of this study was to identify associations between smoking status and the severity of COVID-19 using a large-scale data registry of hospitalized COVID-19 patients in Japan (COVIREGI-JP) and to explore the reasons for the inconsistent results previously reported on this subject. Methods: The analysis included 17,702 COVID-19 inpatients aged 20-89 years (10,279 men and 7,423 women). We graded the severity of COVID-19 (grade 0 to 5) according to the most intensive treatment required during hospitalization. Associations of smoking status with severe grade 3/4/5 (invasive mechanical ventilation/extracorporeal membrane oxygenation/death) and separately with grade 5 (death) were analyzed using multiple logistic regression with grade 0 (no oxygen) as the control group. Results were expressed as odds ratios (OR) and 95% confidence intervals (CI) adjusted for age and other factors considering the potential intermediate effects of comorbidities. Findings: Among men, former smoking significantly increased the risk of grade 3/4/5 and grade 5, with age-adjusted ORs (95% CI) of 1·50 (1·18-1·90) and 1·65 (1·23-2·21), respectively. An additional adjustment for comorbidities weakened these ORs to 1·29 (1·00-1·66) and 1.41 (1·01-1·95), respectively. Similar results were seen for women. Current smoking did not significantly increase the risk of grade 3/4/5 and grade 5 in either sex. Interpretation: Smoking cessation should be recommended even if the observed relationship between current smoking and the severity of COVID-19 is null because current smoking increases the risks of future comorbidities due to different diseases that increase the risk of severe COVID-19. Funding Information: This research was funded by the Health and Labour Sciences Research grant (19HA1003, 20CA2031) and the National Center for Global Health and Medicine (20A-3002). Declaration of Interests: All authors report no conflict of interest. Ethics Approval Statement: This study was approved by the National Center for Global Health and Medicine (NCGM) ethics review (NCGM-G-003494-0).

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., A comparison in the ability to detect diabetic retinopathy between fasting plasma glucose and HbA1c levels in a longitudinal study.

Background The collection of weighed food records (WFR) is a gold standard for dietary assessment. However, what a person eats changes every day, and it is practically difficult to weigh foods and drinks daily and calculate their nutrient contents. The validity of 24-hour dietary recall with the use of a portable camera (24hR-camera) was examined by comparison with the WFR.Methods The study subjects were recruited from 30 male adults who were fathers of university students and cooked rarely. For the validation of the 24hR-camera, we compared it and the WFR. The digital photographs were taken by the subjects of all food consumed during a day and a 24-h recall questionnaire was conducted by a registered dietitian who was trained on the survey methodology. An estimate of the amount of food consumed was made using a food atlas and the photographs taken by the subjects. For validation, comparison was made between the calculations, by both methods, of the levels of food group and nutrient. Results Correlation coefficients between the two methods were 0.7 or higher in most food groups but were low in food groups that are difficult to see, such as oils, fats, condiments, and spices. The intake of vegetables was significantly lower for the 24hR-camera method compared to the WFR method. For other food groups, except for algae, of which intake amount (in weight base) is very low, the percentages of mean difference between 24hR-camera and WFR s were -22.1% to 5.5%, with no significant differences between the methods. The correlation coefficients between the two methods were 0.774 for energy, and 0.855, 0.769, and 0.763 for the three major nutrients, proteins, lipids, and carbohydrates, respectively, demonstrating high correlation with coefficients greater than 0.75. The correlation coefficients between the two methods were 0.583 and 0.560 for salt and potassium intake, respectively, but no significant differences in intake were observed. Conclusions The method of 24-hR-canera satisfactorily estimated the intake of energy and major nutrients (except salt and potassium) in Japanese males, and was confirmed as a useful method for dietary assessment.

Background: Multiple development of dysplastic squamous epithelium and squamous cell carcinoma (SCC) in the esophagus and head/neck region was associated with alcohol and cigarette use and have been explained by field cancerization phenomenon. Second primary cancer developed after curative treatment have harmful effect on patients’ quality of life and survival, however, until recently there have been no evidence-based assessment of the effects of these consumption and cessation on field cancerization. Methods: We conducted a multicentre cohort study at 16 hospitals in Japan. Patients with superficial esophageal SCC (ESCCs) who treated by endoscopic resection were registered. Dysplastic squamous epithelium in the background esophageal mucosa was evaluated by Lugol chromoendoscopy and 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, ³10 LVLs. Lifestyle surveys were conducted using a self-administered questionnaire. Patients were counselled on the need for ceasing alcohol and cigarette consumption by physicians, and were evaluated endoscopical surveillance every 6 months. This study conforms to the STROBE guidelines Findings: Between September 12, 2005 and April 9, 2010, 331 patients with superficial ESCCs were registered. Pooled data from 1,022 healthy subjects were used for comparison. Grades of LVL were positively associated with alcohol drinking intensity, flushing reactions, smoking, high-temperature food and negatively with eating green/yellow vegetables and fruit. Secondary ESCCs and HNSCCs were significantly more prevalent in the grade C LVL group (cumulative 5-y incidences 47.1%, 95% confidence interval [CI], 38.0 to 57.2, and 13.3%, 95% CI, 8.1 to 21.5, respectively). Ceasing alcohol and cigarette use significantly reduced the development of secondary ESCCs (adjusted hazard ratios 0.47, 95% CI, 0.26 to 0.85 and 0.49, 95% CI, 0.26 to 0.91, respectively) Interpretation: Alcohol and cigarette use were closely associated with field cancerization and cessation of them significantly reduced the risk of development of second primary cancer. Funding Statement: Grant from National Cancer Center Research and Development Fund 36 by the Ministry of Health, Labour and Welfare of Japan. Declaration of Interests: The authors declared no conflict of interest. Ethics Approval Statement: This study was approved by the institutional review board at each hospital, and we obtained written informed consent from all patients. (UMIN Clinical Trials Registry ID:UMIN000001676).

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 HbA 1 c ≥ 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.

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

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.

Objectives Oxidative stress is considered one of the etiologic factors involved in ulcerative colitis (UC), yet there is limited epidemiologic information regarding the relationship between antioxidant intake and the risk of UC. The aim of the present case-control study in Japan was to examine the association between intake of green and yellow vegetables, other vegetables, fruit, vitamin C, vitamin E, retinol, alpha-carotene, beta-carotene, and cryptoxanthin and UC risk. Methods A total of 384 cases within 4 y of diagnosis with UC and 665 controls were included in the study. Data on dietary intake and confounders were obtained using a self-reported questionnaire. Information on dietary factors was collected using a 169-item semiquantitative food-frequency questionnaire. Adjustment was made for sex, age, pack-y of smoking, alcohol consumption, history of appendicitis, family history of UC, education level, and body mass index. Results Higher intake levels of other vegetables, vitamin C, and retinol were independently associated with a reduced risk of UC. The adjusted odds ratio between extreme quartiles was 0.51 (95% confidence interval [CI], 0.34−0.76; P for trend ≤ 0.001) for other vegetables, 0.45 (95% CI, 0.30−0.69, P for trend ≤ 0.001) for vitamin C, and 0.64 (95% CI, 0.43−0.95, P for trend = 0.04) for retinol. There were no associations between intake of green and yellow vegetables, fruit, vitamin E, alpha-carotene, beta-carotene, or cryptoxanthin and UC risk (P for trend = 0.29, 0.56, 0.89, 0.20, 0.69, and 0.22, respectively). Conclusions Intake of other vegetables, vitamin C, and retinol was inversely associated with UC risk.

Objective The 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. Methods Case 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. Results Current 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. Conclusion Although 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.

Genetic polymorphisms of alcohol dehydrogenase-1B (ADH1B; rs1229984, His48Arg) and aldehyde dehydrogenase-2 (ALDH2; rs671, Glu504Lys) affect body weight, body fat, and lipid metabolism in individuals with alcohol dependence, and the aim of this study was to identify their determinants in relation to the development of fatty liver. We evaluated associations between the presence of fatty liver and ADH1B and ALDH2 genotypes and other factors in 1604 Japanese men who had been admitted for treatment of alcohol dependence. Fatty liver was diagnosed when ultrasonography showed both hepatorenal contrast and liver brightness. Age-adjusted usual alcohol intake did not differ according to ADH1B or ALDH2 genotypes. A multivariate analysis showed that the adjusted odds ratio (OR, 95% confidence interval) of slow-metabolizing ADH1B Arg/Arg carriers was 1.61 (1.27–2.03) for fatty liver and 1.82 (1.37–2.41) for fatty liver with deep attenuation in comparison with the ADH1B His/Arg or His/His carriers, and that the OR of inactive heterozygous ALDH2 Glu/Lys carriers was 1.43 (1.08–1.91) for fatty liver and 1.84 (1.31–2.59) for fatty liver with deep attenuation in comparison with the ALDH2 Glu/Glu carriers. Younger age, shorter interval between the last drink and the ultrasound examination, larger body mass index, and absence of cirrhosis were identified as other positive determinants for fatty liver. The ADH1B Arg/Arg genotype and the ALDH2 Glu/Lys genotype were positive determinants of fatty liver in the subjects. These results suggest that slow ethanol and acetaldehyde metabolism accelerates the development of alcoholic fatty liver in heavy drinkers.

AIM To determine whether the presence of columnar-lined esophagus (CLE) is associated with the presence of esophageal varices (EVs) in male Japanese alcoholics. METHODS The subjects were 1614 Japanese alcohol-dependent men (≥ 40 years of age) who had undergone upper gastrointestinal endoscopic screening. Digitalized records of high-quality endoscopic images that included the squamocolumnar junction and esophagogastric junction were retrospectively jointly reviewed by four expert endoscopists for the purpose of diagnosing CLE. The authors investigated whether and to what extent there were associations between the presence of CLE and the presence of EVs, especially in the group with liver cirrhosis (LC). RESULTS CLE ≥ 5 mm in length was found in 355 subjects (≥ 30 mm in 6 of them), LC without EVs in 152 subjects, LC with EVs in 174 subjects, and EVs without LC in 6 subjects. Advanced EVs, i.e., nodular, large or coiled forms, red color sign, or post-treatment, were found in 88 subjects. The incidence of CLE ≥ 5 mm decreased in the following order (P < 0.0001): 23.3% in the group without EVs, 17.4% in the group with small and straight EVs, and 5.7% in the group with advanced EVs. The multivariate ORs (95%CI) for EVs and advanced EVs in the group with LC were lower when CLE ≥ 5mm was present [0.46 (0.23-0.93) and 0.24 (0.08-0.74), respectively, vs 0-4 mm CLE]. CONCLUSION The presence of CLE in male Japanese alcoholics was negatively associated with the presence of EVs.

Soft palatal melanosis can be detected by visual inspection during routine physical examination or even personally in a mirror. The aim of this study was to evaluate the association between squamous cell neoplasia in the upper aerodigestive tract (UAT) and soft palatal melanosis. We reviewed digitized records of high‐quality endoscopic images of the soft palate of 1786 Japanese alcoholic men who underwent endoscopic screening. Soft palatal melanosis was observed in 381 (21.3%) of the subjects (distinct, 6.3%). Older age, an inactive heterozygous aldehyde dehydrogenase‐2 genotype, smoking, and a high mean corpuscular volume were positively associated with the presence of soft palatal melanosis. The age‐adjusted odds ratio (95% confidence interval) for UAT neoplasia was 1.92 (1.40–2.64) in the group with melanosis and 2.51 (1.55–4.06) in the group with distinct melanosis, compared with the melanosis‐free group. A multivariate analysis showed that the presence of soft palatal melanosis was independently associated with a high risk of UAT neoplasia. We calculated the individual number of risk factors out of four easily identifiable and significant factors: age ≥55 years, current/former alcohol flushing, mean corpuscular volume ≥106 fL, and distinct soft palatal melanosis. Compared with the risk‐factor‐free condition, the odds ratio (95% confidence interval) values of UAT neoplasia for one, two, three, and four risk factors were 1.49 (0.97–2.30), 3.14 (2.02–4.88), 4.80 (2.71–8.51), and 7.80 (2.17–28.1), respectively. The presence of soft palatal melanosis provides a simple new strategy for identifying heavy drinkers with a high risk for UAT neoplasia.

Aim Food security and sufficient nutrient intake are critical to longevity and active aging. The present study aimed to elucidate physical and social factors related to dietary variety among single-living older adults in Japanese communities. Methods The cross-sectional survey with a self-administrated questionnaire was carried out for all older adults living alone aged 65 years and older in three cities of Japan during 2014. Dietary variety score (DVS) was determined by counting the number of 10 food groups consumed at least once in 2 days using a food frequency questionnaire. Using the data of 704 men and 1366 women, the sex-specific association of low DVS (

Objective To document the clinical features and associated pure-tone audiometry data in patients with enlargement of the vestibular aqueduct (EVA), and to identify risk factors for fluctuating hearing loss (HL) and vertigo/dizziness in EVA patients. Methods In this nationwide survey in Japan, a first survey sheet was mailed to 662 board-certified otolaryngology departments to identify the ones treating EVA patients. A second survey sheet, which contained solicited clinical information and the results of the hearing tests, was mailed to all facilities that reported treating EVA cases. We analyzed clinical information, including age at the time of the most recent evaluation, gender, EVA side, age at onset, initial symptoms, precipitating factors, and etiology from survey responses, and assessed 4-frequency (500, 1000, 2000, and 4000 Hz) pure-tone average (PTA) from accompanying pure-tone audiometry data. A multivariate logistic regression analysis was utilized to identify the possible risk factors for fluctuating HL and vertigo/dizziness. Results In total, 513 hospitals (response rate, 77.5%) responded to the first survey, and 113 reported treating patients with EVA. Seventy-nine out of the 113 hospitals (response rate 69.9%) responded to the second survey, and the data of 380 EVA patients were registered and analyzed. Of the 380 patients, 221 (58.2%) were female, suggesting female preponderance. The patient age ranged from 0 to 73 years (mean, 16.7 years; median, 13 years; interquartile range, 6–24 years). EVA was bilateral in 91.1% of the patients (346/380). The most prevalent initial symptom was HL (341/380), followed by vertigo/dizziness/imbalance (34/380). Sudden HL occurred secondary to head trauma in 5.3% of the patients and upper respiratory infection in 5.0%. Pure-tone audiometry showed profound HL (PTA >91 dB) in 316 (52.0%) of the 608 ears in the 304 patients tested, and asymmetric HL, defined as >10 dB, in 147 (48.4%) of the 304 patients. The mean PTA was 83.7 dB (median, 91.3 dB; interquartile range, 71.3–103.8 dB), and the severity in PTA did not correlate with age. Multivariate logistic regression identified age ≥10 years (compared to age of 0–9 years), bilateral HL (compared to unilateral HL/normal hearing), a history of head trauma, and Pendred syndrome (compared to the other EVA-associated disorders) as significant risk factors for fluctuating HL and/or vertigo/dizziness. Conclusion The present nationwide survey of 380 EVA patients provided a more precise description of the clinical features, including risk factors for fluctuating HL and vertigo/dizziness.

Background Sensitization to Staphylococcus aureus enterotoxin (SE) is a known risk factor for asthma susceptibility and severity. However, how SE sensitization is involved in asthma, particularly nonatopic asthma and/or late-onset asthma, remains uncertain. Objective To clarify the involvement of SE sensitization in nonatopic and/or late-onset asthma and its association with a polymorphism of the cysteinyl leukotriene receptor 1 gene ( CysLTR1 ), which was examined because CysLT signaling is closely associated with late-onset eosinophilic asthma. Methods We assessed associations between sensitization to SE (A and/or B) and clinical indexes in 224 patients with asthma (mean age, 62.3 years; 171 women) from a cohort of the Kinki Hokuriku Airway Disease Conference, particularly those with nonatopic asthma (not sensitized to common aeroallergens) and/or late-onset asthma. Associations between SE sensitization and CysLTR1 polymorphism (rs2806489), a potential regulatory variant for atopic predisposition in women, were also assessed in a sex-stratified manner. Results A total of 105 patients (47%) with asthma were sensitized to SE. Among patients with nonatopic asthma (n = 67) or with late-onset asthma (n = 124), those sensitized to SE had significantly higher serum total IgE and periostin levels than those not sensitized. In nonatopic patients, a rapid decrease in forced expiratory volume in 1 second was associated with SE sensitization. In women with asthma, rs2806489 was associated with sensitization to SEB and age at asthma onset. Conclusion SE sensitization contributes to T H 2 inflammation in nonatopic and/or late-onset asthma. In women with asthma, the CysLTR1 variant might be associated with sensitization to SEB and age at asthma onset.

Background The combination of the fast-metabolizing alcohol dehydrogenase-1B (ADH1B*2 allele) and inactive heterozygous aldehyde dehydrogenase-2 (ALDH2*1/*2) increases susceptibility to macrocytic anemia and leukocytopenia in alcoholics due to severe acetaldehydemia. More than half of Japanese drinkers with esophageal cancer have this genotype combination. Methods To assess the recovery of hematologic abnormalities after drinking cessation, changes in blood erythrocyte indices and leukocyte count during 8-week hospital stay were evaluated in 925 Japanese alcoholic men. We used four categories in ascending order for high blood acetaldehyde exposure from drinking: A, ADH1B*1/*1 plus ALDH2*1/*1; B, ADH1B*2 plus ALDH2*1/*1; C, ADH1B*1/*1 plus ALDH2*1/*2; and D, ADH1B*2 plus ALDH2*1/*2. Results Mean values of hemoglobin and hematocrit were the lowest, and those of mean corpuscular volume (MCV) were markedly the highest in the D group on admission, and returning toward normal after abstinence, but the inter-group differences remained significant throughout the 8 weeks. The mean leukocyte count was the lowest in the D group on admission, but increased during 4-week abstinence when the inter-group differences were no longer significant. Frequencies of MCV ≥110 fl (50.5%), hemoglobin levels

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.”

Summary This study was designed to evaluate the relation between dysplastic squamous epithelium in the esophageal mucosa and the development of metachronous secondary primary malignancies (mSPM) other than esophagus after endoscopic resection (ER) in patients with early esophageal squamous cell carcinoma (SCC). We studied 330 patients with early esophageal SCC who underwent ER as a post hoc analysis of a prospective multicenter cohort study (UMIN Clinical Trials Registry ID UMIN000001676). Lugol-voiding lesions (LVL) were graded into 3 categories (A = no lesion; B = 1 to 9 lesions; C ≥ 10 lesions). The following variables were studied: (i) the incidences of mSPM other than esophagus; (ii) the standardized incidence ratios (SIRs) of mSPM; (iii) the cumulative incidence and total number of mSPM other than esophagus; and (iv) predictors of mSPM other than esophagus on analysis with a multivariate Cox proportional-hazards model. After a median follow-up of 46.6 months, mSPM other than esophagus was diagnosed in a total of 73 patients (90 lesions). Among the 106 patients in group C, 37 patients had mSPM (51 lesions), including head and neck cancer in 14 patients (24 lesions) and gastric cancer in 12 patients (16 lesions). The SIR of mSPM was 3.61 in this study subjects. An increase in the LVL grade (A to B to C) was associated with a progressive increase in the cumulative incidence rate of mSPM other than esophagus (P = 0.017 for A vs. C, P = 0.023 for B vs. C). An increase in the LVL grade (A to B to C) was also associated with a progressive increase in the total number of mSPM other than esophagus per 100 person-years (primary events, relative risk [RR] = 1.66 and 3.24 for grades B and C, respectively, vs. A, P = 0.002 for trend; all events, RR = 1.81 and 4.66 for grades B and C, respectively, vs. A, P

ObjectiveTo calculate the incidence of hospitalisation due to acute respiratory failure, pneumonia, acute respiratory distress syndrome (ARDS), febrile seizures and encephalitis/encephalopathy among influenza-positive patients in Japan, where point-of-care tests are routinely used to diagnose influenza.DesignA cross-sectional study using routinely collected data.SettingJapanese clinics and hospitals between 2012 and 2016.ParticipantsJapanese patients aged 0–74 years diagnosed with influenza by a rapid test in employment-related health insurance records.Primary outcome measuresIncidence of hospitalisation per 100 000 influenza-positive episodes.ResultsWe included over 16 million influenza-positive episodes, 1.0% of whom were hospitalised. Of these, 3361 were acute respiratory failure, 27 253 pneumonia, 18 ARDS, 2603 febrile seizure and 159 encephalitis/encephalopathy. The percentage of hospitalisations by age was 2.96% of patients aged 0–1 years, 0.77% aged 2–5, 0.51% aged 6–12, 0.78% aged 13–18, 1.36% aged 19–44, 1.19% aged 45–64, and 2.21% aged 65–74. The incidence of hospitalisations from these five complications combined was highest in influenza-positive patients aged 0–1 years (943 per 100 000) compared with 307 in those aged 2–5 years and 271 in those aged 65–74 years. For pneumonia, the incidence was highest for influenza-positive patients aged 0–5 years and 65 years or more. There were statistically significant decreasing trends over the years in the incidence of all-cause hospitalisations, pneumonia and febrile seizures.ConclusionsJapanese administrative data revealed that 1.0% of influenza-positive patients aged under 75 years were hospitalised. Male patients had a higher incidence of pulmonary complications and febrile seizures. Children aged 0–5 years and adults aged 65–74 years were at high risk of being admitted to hospital for pneumonia.

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.

4027 Background: In patients with resectable esophageal squamous cell carcinoma (SCC), the outcomes of chemoradiotherapy (CRT) for good responders after three courses of induction chemotherapy (IC) with docetaxel, cisplatin, and 5–fluorouracil (DCF chemotherapy) were unclear. Methods: Patients with clinical stage IB–III (UICC 7th) resectable esophageal SCC were eligible. IC included docetaxel 75 mg/m2 on day 1, cisplatin 75 mg/m2 on day 1, and 5–fluorouracil 750 mg/m2 on days 1–5, repeated every 3 weeks for 3 cycles. The response was evaluated after 2 and 3 courses of IC. Patients were considered to have a “remarkable response (RR)” if an endoscopic examination with a central review showed shrinking of the primary lesion equivalent to T1 and the short axis of the metastatic lymph nodes were all < 1 cm on computed tomography—in other words, down staging to T1N0M0 stage IA. Patients were considered to have a “poor response (POR)” if they had progressive disease or no signs of reduction. Patients who did not achieve RR or POR were deemed to have “limited partial response (LPR)”. CRT was administered to patients who achieved RR, and surgery was performed in patients who achieved LPR or POR. CRT included cisplatin 75 mg/m2 on day 1 and 5–fluorouracil 1000 mg/m2 on days 1–4, repeated every 4 weeks for 2 cycles. Radiotherapy was administered as 50.4 Gy in 28 fractions. The primary endpoint was a 1–year progression free survival (PFS) for RR followed by CRT. Results: A total of 92 patients were enrolled. Two patients with non–SCC (n = 1) and distant metastasis (n = 1) were excluded. Therefore, 90 patients were included in the analysis group. Although 1 patient could not continue IC due to renal failure, the remaining 89 patients completed 3 courses of IC. The response after IC were RR in 58.4% (52/89), LPR in 41.6% (37/89), and POR in 0.0% (0/89). Three patients who achieved RR underwent surgery owing to renal dysfunction (n = 1), curative irradiation difficulty due to intestinal malrotation (n = 1), and CRT refusal (n = 1). Six patients who achieved LPR underwent CRT owing to surgery refusal (n = 3), unresectable tumors (n = 2), and respiratory dysfunction due to emphysema (n = 1). The complete response rate for RR followed by CRT was 89.8%. During the median follow–up period of 33 months (range: 1–85), the 1 and 3–years overall survival (OS) for the analysis group were 96.6% and 74.1%, respectively. The 1 and 3–years organ preservation survival for the analysis group were 56.8% and 45.3%, respectively. The 1 and 3–years OS for RR followed by CRT (n = 49) vs. LPR followed by surgery (n = 31) were 100% vs. 93.1% and 83.7% vs. 62.8%, respectively (p = 0.06). The 1 and 3–years PFS for RR followed by CRT were 89.8% and 70.0%, respectively. Conclusions: Three courses of DCF chemotherapy followed by CRT is an effective treatment for patients with resectable esophageal SCC who respond to the IC regimen. Clinical trial information: 8086.

BACKGROUND/OBJECTIVES: This study aimed to examine the association of Japanese schoolchildren’s involvement in at-home meal preparation with food intake and cooking skill. SUBJECTS/METHODS: We included 1,207 fifth-grade children aged 10-11 years and one parent of each child. A cross-sectional survey was used to collect data on involvement in at-home meal preparation. Correspondence analysis was used to classify involvement in at-home meal preparation into three groups: food-related activities (cooking only or with other activities such as shopping, table-setting, clean up, and dishwashing), non-food-related activities (table-setting and/or clean up), and no (helping) activities. Food intake was assessed using a food frequency questionnaire. Logistic regression models were used to examine involvement in at-home meal preparation associations. RESULTS: The sample consisted of 1,207 fifth-grade children. Vegetable intake was lower in the no (helping) activities group than the food-related activities group (95% CI; boys: 1.2, 5.1, girls: 2.0, 8.9). Fewer children in the non-food-related activities group reported they were able to make a portion of their meals compared with the food-related activities group (95% CI; boys: 1.6, 3.5; girls: 1.5, 3.2). CONCLUSIONS: Children in the food-related activities group showed more favorable food intake and cooking skills than children in the no (helping) activities or non-food-related activities group.

Background: Previously we showed that air-flow limitation, GG genotype of IL4RA rs8832, and A allele of ADAM33 T_2 rs2280090 were independent risks of adult asthma patients with both exacerbations and type 2-high endotype (Sunadome, et al. ATS2016). Meanwhile, little is known about risks of asthma exacerbations in type 2-low patients. Aims: To determine clinical and genetic risks that may contribute to exacerbations in asthma patients with type 2-low endotype. Methods: This is a follow-up study of asthmatics on inhaled corticosteroids treatment who were enrolled in the Kinki Hokuriku Airway disease Conference multicenter study. Associations between asthma exacerbations requiring systemic corticosteroids during the 2 years of follow-up and clinical and genetic factors were examined in patients with type 2-low endotype. Type 2-low endotype was defined as serum periostin of ORMDL3 rs7216389, IL4RA rs8832 and CDHR3 rs6967330 were assessed. Results: Among 134 type 2-low patients (106 females, average age 61.6 years), 33 had one or more exacerbations during subsequent 2 years. Multivariate analysis showed that female [Odds ratio (95% confidence interval); 7.9 (1.6-66.7), p = 0.02], body mass index [1.2 (1.1-1.5), p = 0.008], recent exacerbations [10.5 (2.5-56.0), p = 0.003], ORMDL3 rs7216389 TT genotype [3.5 (1.2-11.5), p = 0.03] and IL4RA rs8832 GG genotype [0.03 (0.001-0.024), p = 0.007] were associated with exacerbations in patients with type 2-low endotype. CDHR3 rs6967330 was unrelated to exacerbations in type 2-low patients. Conclusions: Clinical and genetic risks of asthma exacerbations may be different between type 2-high and type 2-low patients.

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.

Aims: Alcoholic ketosis and ketoacidosis are metabolic abnormalities often diagnosed in alcoholics in emergency departments. We attempted to identify determinants or factors associated with alcoholic ketosis. Methods: The subjects of this cross-sectional survey were 1588 Japanese alcoholic men (≥40 years) who came to an addiction center within 14 days of their last drink. Results: The results of the dipstick urinalyses revealed a prevalence of ketosis of 34.0% (±, 21.5%; +, 8.9%; and 2+/3+; 3.6%) in the alcoholics. Higher urine ketone levels were associated with higher serum total bilirubin, aspartate transaminase (AST), alanine transaminase and gamma-glutamyl transpeptidase levels. A multivariate analysis by the proportional odds model showed that the odds ratio (95% confidence interval) for an increase in ketosis by one category was 0.94 (0.84–1.06) per 10-year increase in age, 0.93 (0.89–0.97) per 1-day increase in interval since the last drink, 1.78 (1.41–2.26) in the presence of slow-metabolizing alcohol dehydrogenase-1B ( ADH1B\*1/\*1 ), 1.61 (1.10–2.36) and 1.30 (1.03–1.65) when the beverage of choice was whiskey and shochu, respectively (distilled no-carbohydrate beverages vs. the other beverages), 2.05 (1.27–3.32) in the presence of hypoglycemia