Corrigendum to "Relationship between growth and food avoidance with food allergy at age 3 years: The Japan Environment and Children's Study (JECS)" [World Allergy Organ J (2023) 100826].

[This corrects the article DOI: 10.1016/j.waojou.2023.100826.].

Relationship between growth and food avoidance with food allergy at age 3 years: The Japan Environment and Children's Study (JECS).

Background: Basic management for food allergy (FA) is eliminating causative food from the diet, which can impact normal growth. This study examined the association between food avoidance and growth failure among children with FA aged 0-3 years using the Japan Environment and Children's Study (JECS) data. Methods: Data on height, weight, and FA history registered were collected using self-administered questionnaires at age 1, 1.5, 2, and 3 years. A general linear model was used to examine whether dietary restriction affected body size. Height, weight, and body mass index (BMI) were adjusted for age in months using standard deviation (SD) scores for each age group by month of measurement. Presence of FA or dietary restriction was used as a binary variable. Results: Of the 38 477 participants included in this analysis, 4070 with FAs had significantly lower SD scores for height and weight at age 3 years. With milk avoidance, significantly lower SD scores for height (male: ß = -0.097 [95%CI: 0.175, -0.019], female: ß = -0.103 [95%CI: 0.204, -0.002]), a significantly lower SD score for weight (male: ß = -0.115[95%CI: 0.187, -0.043], female ß = -0.114[95%CI: 0.203, -0.026]) were observed. Soy avoidance in males marked a lower SD score for height (ß = -0.307 [95%CI: 0.474, -0.140]). Continued food avoidance until age 3 resulted in significantly lower SD score for height and weight regardless of gender. Conclusion: Growth impairment was observed with food avoidance at age 3 years. Growth impairment were more obvious in males than in females. With regards food items, the impact of milk and soy was more significant.

Association between maternal use of spray formulations and offspring urological anomalies: The Japan Environment and Children's Study.

OBJECTIVE: Concerns exist regarding the effects of maternal inhalation of household products on fetal health. This study aimed to clarify the impact of maternal exposure to household products, including spray formulations, on urological anomalies in offspring up to the age of 1 year. METHODS: This study included data from 84 237 children from the Japan Environment and Children's Study, an ongoing nationwide cohort study. Using maternal self-report questionnaires, information on the use of organic solvents, waterproof sprays, insect-repellent sprays, insecticide sprays, and herbicides from implantation until the second or third trimester of pregnancy and data on urological anomalies were collected 1 year after delivery. RESULTS: Urological anomalies occurred in 799 infants. Multivariate logistic regression analysis adjusted for maternal age, pregnancy body mass index, gestational diabetes, pre-existing maternal kidney disease, and preterm birth revealed no association between maternal exposure to organic solvents and the prevalence of offspring urological anomalies. Nevertheless, we observed significant associations between waterproof spray use during pregnancy and urological anomalies in boys (odds ratio [OR]: 1.28, 95% confidence interval [CI]: 1.03-1.59) and between the use of insecticide spray during pregnancy and urological anomalies in girls (OR: 1.48, 95% CI: 0.98-2.22). Sub-analysis revealed significant associations between waterproof spray use during pregnancy and vesicoureteral reflux in boys (OR: 2.14, 95% CI: 1.02-4.49) and between the use of insecticide spray during pregnancy and hydronephrosis in girls (OR: 2.23, 95% CI: 1.11-4.47). CONCLUSION: Spray formulation use during pregnancy might increase the risk of urological anomalies in the offspring.

Pitavastatin Compared with Differential Intervention Trial by Standard Therapy on Cardiovascular Events in Patients with Dyslipidemia on Chronic Hemodialysis (DIALYSIS): A Randomized Controlled Trial.

INTRODUCTION: Statin has been reported to reduce cardiovascular events. However, the comparative efficacy of statin with standard therapy on cardiovascular events has not been sufficiently reported in patients on chronic hemodialysis. Thus, this study aimed to compare the effects of pitavastatin and standard therapy on mortality and cardiovascular events in chronic hemodialysis patients with dyslipidemia in Japan. METHODS: Patients on chronic hemodialysis with dyslipidemia were randomized into pitavastatin-administered (pitavastatin group) or dietary therapy as standard therapy (control) group. Primary outcomes are all-cause mortality and myocardial infarction; secondary outcomes are cardiac arrest and fatal myocardial infarction. The composite outcomes included the incidence of coronary intervention, stroke, fracture, and hospitalization due to heart failure and unstable angina. The clinical outcome analyses used a logistic regression model to categorize the variables. A p value of <0.05 was considered statistically significant. RESULTS: This study included 848 patients (422 in the control group and 426 in the pitavastatin group) from 79 health facilities. The mean age of the patients was 60.1±10.3 years, and the dialysis period was 7.2±7.6 years. The mean observation period was 36.5 months. The low-density lipoprotein cholesterol level was significantly lower than the baseline value in the pitavastatin group after 12 months of trial (79.8±26.1 vs. 107.8±25.5 mg/dL, p < 0.001). Moreover, the total number of deaths was 85, of which 50 occurred in the control group and 35 in the pitavastatin group. In an analysis adjusted for confounding factors due to participant attributes, there was a significant difference between the control group and the pitavastatin group in the primary and composite endpoints (p = 0.007 and p = 0.022, respectively). CONCLUSION: Our study has demonstrated that aggressive intervention with pitavastatin is more effective than the standard (dietary) therapy for improving the clinical outcomes in patients with dyslipidemia on chronic hemodialysis.

Smart Gene™ as an effective non-invasive point-of-care test to detect Helicobacter pylori clarithromycin-resistant mutation.

BACKGROUND AND AIM: Smart Gene™ was developed based on the concept of point-of-care genetic testing. We evaluated the detection performance of a reagent for Helicobacter pylori (H. pylori) clarithromycin (CAM)-resistant mutation assessment and determined the association between the results of Smart Gene™ and those of eradication therapy for H. pylori. METHODS: In 2020, the present study was conducted on participants of the H. pylori test and treat project in Saga Prefecture. The submitted stool samples were measured for H. pylori gene and CAM-resistant mutation by Smart Gene™, and the results were compared with real-time polymerase chain reaction (PCR) and sequencing analysis. Finally, the results of the eradication therapy were examined for each result of Smart Gene™. RESULTS: Stool samples were obtained from 139 patients who were tested positive by stool antigen test and were analyzed. The H. pylori detection rate was 95.7% by Smart Gene™, 92.8% by real-time PCR (P < 0.01), and 89.2% by sequencing analysis (P = 0.06). The overall concordance rate for CAM-resistant mutation between Smart Gene™ and sequencing analysis was 96.7%. Moreover, 35 of 48 students with CAM-resistant mutation and 33 of the 35 students with a mutation without CAM resistance succeeded in CAM-containing triple therapy, and the success rate was significantly higher for the mutation without CAM resistance (P = 0.012). CONCLUSIONS: The detection performance of Smart Gene™ was comparable with that of real-time PCR and sequencing analysis. It is expected that the success rate of eradication would be further improved by using the reagent.

Effects of Screen Viewing Time on Sleep Duration and Bedtime in Children Aged 1 and 3 Years: Japan Environment and Children's Study.

This study aimed to clarify the effects of television/digital versatile disc (TV/DVD) viewing time and portable electronic device (PED) usage time on sleep duration and bedtime and the difference between the effects of TV/DVD and PED on sleep. The effect of TV/DVD viewing time or PED usage time on sleep duration and bedtime was analyzed using a multiple logistic regression analysis adjusted for covariates. A total of 74,525 participants were included in the analysis, using data from Japan Environment and Children's Study. TV/DVD viewing was not associated with short sleep duration, but PED usage was associated with short sleep duration. In addition, the risk of short sleep duration increased as PED usage time increased. We also investigated the effects of sleep habits at age 1 year on sleep at age 3 years. This study showed that late bedtime at age 1 year posed a significant risk of late bedtime at age 3 years. In summary, particular caution should be paid to PED use from a child's health perspective, and sleep habits should be focused on bedtime from the age of 1 year.

Early Developmental Signs in Children with Autism Spectrum Disorder: Results from the Japan Environment and Children's Study.

Autism spectrum disorder (ASD) is a developmental disability in early childhood. Early identification and intervention in children with ASD are essential for children and their families. This study aimed to identify the earliest signs of ASD. Using a large cohort including data from 104,062 fetal records in the Japan Environment and Children's Study, we examined the Ages and Stages Questionnaires® (ASQ-3TM) scores of children with and without ASD. The ASQ-3 comprises five domains: communication, gross motor, fine motor, problem solving, and personal-social. The ASQ-3 scores were obtained at ages 6 months, 1 year, and 3 years. There were 64,501 children with available ASQ-3 data. The number of children diagnosed with ASD was 188 (0.29%) at 3 years of age. The highest relative risk (RR) for any domain below the monitoring score at 6 months was in the communication (RR 1.90, 95% CI 1.29-2.78, p = 0.0041), followed by fine motor (RR 1.50, 95% CI 1.28-1.76, p < 0.0001) domain. A low ASQ-3 score in the communication domain at 6 months was related to an ASD diagnosis at 3 years of age. The ASQ-3 score at 6 months can contribute to the early identification of and intervention for ASD.

Association between maternal insecticide use and otitis media in one-year-old children in the Japan Environment and Children's Study.

Otitis media (OM) is common among young children and is related to hearing loss. We investigated the association between maternal insecticide use, from conception to the first and second/third trimesters, and OM events in children in the first year of age. Data from Japan Environment and Children's Study were used in this prospective cohort study. Characteristics of patients with and without history of OM during the first year of age were compared. The association between history of OM in the first year and insecticide use was evaluated using logistic regression analysis. The study enrolled 98,255 infants. There was no significant difference in the frequency of insecticide use between groups. Insecticide use of more than once a week from conception to the first trimester significantly increased the occurrence of OM in children in the first year (odds ratio [OR] = 1.30, 95% confidence interval [CI] 1.01-1.67). The association between OM in the first year and insecticide use from conception to the first trimester was only significant in the group without daycare attendance (OR 1.76, 95% CI 1.30-2.38). Maternal insecticide use more than once a week from conception to the first trimester significantly increased OM risk in offspring without daycare attendance.

Prevalence estimates of Helicobacter species infection in pancreatic and biliary tract cancers.

BACKGROUND: Helicobacter pylori infection is a well-established risk factor for gastric cancer and has been linked to other gastrointestinal diseases, including pancreatic and biliary tract cancers; however, the relevance of enterohepatic non-H. pylori helicobacters to the pathophysiology of these diseases remains unclear. MATERIALS AND METHODS: We estimated the prevalence of two enterohepatic non-H. pylori helicobacters (Helicobacter hepaticus and Helicobacter bilis) in the framework of a hospital-based case-control study involving 121 patients with biliary tract cancer, pancreatic cancer, or other gastrointestinal diseases. Bile and blood samples were collected from the patients undergoing endoscopic retrograde cholangiopancreatography. The presence of H. bilis, H. hepaticus, and other Helicobacter spp. was examined using bacterial culture, PCR-based detection, and serological tests. RESULTS: Culture of Helicobacter spp. from biliary brush samples was unsuccessful. Approximately 13.0% (15/115) of the bile samples collected from patients with a variety of gastrointestinal cancers, including pancreatic and biliary tract cancers, tested positive for one of the enterohepatic non-H. pylori helicobacter species as determined by PCR. Specifically, H. bilis and H. hepaticus DNA were detected in 11 and 4 bile samples, respectively. Approximately 20%-40% of the patients tested positive for serum non-H. pylori helicobacter IgG antibodies. The seroprevalence of H. bilis and H. hepaticus in the patients without evidence of H. pylori infection appeared to be higher in the pancreatic cancer group than in the control group. CONCLUSION: Our findings suggest a role for Helicobacter spp., especially H. bilis and H. hepaticus, in the etiology of pancreatic and biliary tract cancers.

Lifetime incidence risk for gastric cancer in the Helicobacter pylori-infected and uninfected population in Japan: A Monte Carlo simulation study.

Helicobacter pylori (H. pylori) infection is considered the leading cause of gastric cancer. Gastric cancer is currently a common cancer with high incidence and mortality rates, but it is expected that the incidence rate will gradually decrease as the H. pylori infection prevalence decreases in the future. When evaluating the effectiveness of gastric cancer prevention strategies, it is essential to note the differences in long-term cumulative risks between H. pylori-infected and uninfected populations, but this has not yet been precisely evaluated. In our study, we aimed to estimate the cumulative incidence risks of developing gastric cancer from birth to 85 years among H. pylori-infected and uninfected populations by using population-based cancer registry data and birth year-specific H. pylori infection prevalence rates. Death from gastric cancer and other causes of death were considered in the estimations of the adjusted cumulative incidence risks stratified by sex and H. pylori infection status. After performing 5000 Monte Carlo simulations with repeated random sampling using observed cancer incidence in selected three prefectures (Fukui, Nagasaki, Yamagata) of prefectural population-based cancer registry in Japan, the mean adjusted cumulative incidence risk for gastric cancer in the H. pylori-infected population was 17.0% for males and 7.7% for females and 1.0% for males and 0.5% for females in the uninfected population. These results calculated with Japanese cancer registry data may be useful in considering and evaluating future prevention strategies for gastric cancer in Japan.

Association between house renovation during pregnancy and wheezing in the first year of life: The Japan environment and children's study.

BACKGROUND: Wheezing is a common symptom in infants, which may occasionally develop into asthma. There are many factors related to infant wheezing, including anatomical features, viral infections, and passive smoking. There are only a few reports on the association between renovation and pregnancy worldwide, and reports on this association are inadequate in Japan. This study aimed to examine the association between house renovation and new construction during pregnancy and wheezing in infants during the first year of life using data from the Japan Environment and Children's Study (JECS). METHODS: Data of pregnant women registered in JECS were collected using self-administered questionnaires during the second/third trimester and 1 month after delivery. Childbirth records were completed by the doctors. Similarly, wheezing in infants was evaluated using self-administered questionnaires 1 year after birth. Logistic regression analysis was used to determine the primary outcome. RESULTS: In total, 75,731 infants, excluding those with unknown gender, who were not singleton infants, and who relocated during pregnancy and the first month of life, were examined in this study. Renovation during pregnancy increased the prevalence of wheezing (odds ratio [OR]: 1.33, 95% confidence interval [CI]: 1.20-1.48) and recurrent wheezing (OR: 1.22, 95% CI: 1.00-1.48) in the first year of life. The relationship between new construction during pregnancy and wheezing in infants was insignificant (OR: 0.98, 95% CI: 0.90-1.06). CONCLUSIONS: Renovation during pregnancy may be a risk factor for wheezing in infants, and should be avoided.

Emotional and behavioral problems in pediatric patients with migraine and tension-type headache.

OBJECTIVE: This study aimed to investigate the associations between psychopathological characteristics of children and adolescents with primary headache, as measured by the Strengths and Difficulties Questionnaire (SDQ), and treatment outcomes. METHODS: A cohort study was conducted on 124 pediatric patients with primary headache. At the first consultation, the SDQ was completed by the parents. The analysis of treatment efficacy was conducted on 90 patients with a follow-up period of at least one year. Treatment responders were defined as those who showed 50% reduction in the headache frequency. First, an analysis of the SDQ total scores and five subscales, among the migraine and tension-type headache groups, was conducted for 124 participants. Second, the association between the SDQ scores and treatment outcomes in the groups with periods of improvement of less than three months and three months or more were analyzed in 90 patients. RESULTS: Migraine patients displayed more difficulties than strengths in terms of the total score (p = .004) and in the emotional symptoms subscale (p = .012) compared with tension-type headache patients. Migraine patients who required more than three months to show improvement displayed more peer problems (p = .020), while tension-type headache patients who required more than three months to show improvement displayed fewer conduct problems (p = .007). CONCLUSION: Evaluation of patient characteristics using the SDQ at first consultation can predict the treatment outcome. Moreover, it can help provide appropriate initial treatment and improve outcome of primary headache in children.

Gut microbiota changes related to Helicobacter pylori eradication with vonoprazan containing triple therapy among adolescents: a prospective multicenter study.

Currently, it is unclear whether treating Helicobacter pylori (H. pylori) infection is safe among adolescents. This study aimed to evaluate the safety of H. pylori eradication therapy by examining gut microbiota changes in adolescents 3 months after the therapy. H. pylori-infected adolescents were enrolled in this study. Their stool samples were collected at the following three time points: before treatment, 1-2 days after completion of treatment, and time of eradication successful judgment. We assessed the relative abundance, alpha-diversity, and beta-diversity of the gut microbiota and adverse events. The number of isolated Actinobacteria decreased immediately after eradication therapy in the 16 students included in the study, and it returned to pretreatment condition at the eradication judgment point. There was no change in the relative abundance at genus level. The alpha-diversity was lost immediately after eradication therapy; however, it recovered at the time of eradication judgment, and it was restored to pretreatment condition. Meanwhile, none of the participants experienced serious adverse events. H. pylori eradication therapy is safe for adolescents with respect to gut microbiota changes associated with H. pylori eradication therapy. Therefore, further long-term evaluations of gut microbiota changes following eradication therapy are warranted.

An approach to exploring associations between hospital structural measures and patient satisfaction by distance-based analysis.

BACKGROUND: Patient satisfaction studies have explored domains of patient satisfaction, the determinants of domains, and score differences of domains by patient/hospital structural measures but reports on the structure of patient satisfaction with respect to similarities among domains are scarce. This study is to explore by distance-based analysis whether similarities among patient-satisfaction domains are influenced by hospital structural measures, and to design a model evaluating relationships between the structure of patient satisfaction and hospital structural measures. METHODS: The Hospital Consumer Assessment of Healthcare Providers and Systems 2012 survey scores and their structural measures from the Hospital Compare website reported adjusted percentages of scale for each hospital. Contingency tables of nine measures and their ratings were designed based on hospital structural measures, followed by three different distance-based analyses - clustering, correspondence analysis, and ordinal multidimensional scaling - for robustness to identify homogenous groups with respect to similarities. RESULTS: Of 4,677 hospitals, 3,711 (79.3%) met the inclusion criteria and were analyzed. The measures were divided into three groups plus cleanliness. Certain combinations of these groups were shown to be dependent on hospital structural measures. High value ratings for communication and low value ratings for medication explanation, quietness and staff responsiveness were not influenced by hospital structural measures, but the varied-ratings domain group similarities, including items such as global evaluation and pain management, were affected by hospital structural measures. CONCLUSIONS: Distance-based analysis can reveal the hidden structure of patient satisfaction. This study suggests that hospital structural measures including hospital size, the ability to provide acute surgical treatment, and hospital interest in improving medical care quality are factors which may influence the structure of patient satisfaction.

A nationwide questionnaire survey on accidental magnet ingestion in children in Japan.

AIM: The aim is to investigate the actual situation of accidental ingestion of magnets in children in Japan and the clinical features of the resulting gastrointestinal damage. METHODS: We developed a questionnaire and sent it to 496 board-certified training hospitals nationwide. Information was collected on the number of children with accidental magnet intake from 2015 to 2017, witnesses of magnet intake, number and type of magnets, presence or absence of gastrointestinal injury, treatment, etc RESULTS: The number of cases of accidental ingestion of magnets within the study period was 104, with a median age of 2 years. About half of the incidents were unwitnessed. There were 33 cases of accidental ingestion of multiple magnets. Among them, oesophagogastroduodenoscopy was performed in 4 children and surgery in 10, and significantly invasive treatment was required in comparison with single-magnet ingestion. Gastrointestinal injury was observed in 11 cases, 10 of which were caused by multiple-magnet ingestion. All 10 of these patients underwent surgical treatment. There was no mortality. CONCLUSION: The incidence of accidental magnet ingestion in Japan is estimated to be 50-70 per year. Unwitnessed cases are not uncommon. Multiple magnet ingestion often causes gastrointestinal injury. Many cases of gastrointestinal injury are caused by ingestion of magnetic toys.

Gastrointestinal adverse reactions reduce the success rate of Helicobacter pylori eradication therapy: A multicenter prospective cohort study.

BACKGROUND: The screening and treatment of Helicobacter pylori infection for all junior high students in Saga Prefecture, Japan, were started in 2016. The present study aims to evaluate the influence of adverse reactions on the success of the eradication therapy. METHODS: From 2017 to 2019, 25,006 third-grade junior high school students were tested for urinary anti-H. pylori antibodies. Positive cases were confirmed by H. pylori stool antigen tests. Of the 531 students who were found to be H. pylori-positive, 390 (358 in first-line and 32 in second-line therapy) underwent eradication therapy, and 274 (242 in first-line and 32 in second-line) students actually completed a self-reported form to rate stool consistency (based on the Bristol Stool Scale), the maximum number of bowel movements, and abdominal symptoms during the 7 days of treatment. RESULTS: Among the 274 students, the total of primary and secondary eradication success rates was 87% (95% confidential interval: 82.9-90.1) in intention-to-treat analysis. On days 4, 5, and 6, stool consistency was looser in the primary eradication failure group than in the success group (p < .05). Looser stool consistencies were observed in male students with abdominal pain compared to those who did not experience pain (p < .05). Abdominal pain and diarrhea were detected in 28.5% and 42.7% of the subjects, respectively. The overall incidence of other adverse events was low (n = 8/274, 2.9%), and only two students discontinued treatment because of adverse events. CONCLUSIONS: Softening of the stool was related to the eradication failure in the junior high school students, especially in males with abdominal pain. Adverse effects did not induce discontinuation of the eradication treatment.

Assessment of a novel method to detect clarithromycin-resistant Helicobacter pylori using a stool antigen test reagent.

BACKGROUND: The resistance rate of Helicobacter pylori to clarithromycin (CAM) is high among infected children in Japan. Therefore, a new method for detecting CAM-resistant H. pylori using a minimally invasive technique is strongly desired. We aimed to investigate the clinical usefulness of our newly developed nested polymerase chain reaction-quenching probe (Nested PCR-QP) method using stool specimens. METHODS: We first evaluated our method using a residual solution of the H. pylori stool antigen test for adolescents. Then, we evaluated our method using culture testing for adults. RESULTS: Among 57 middle school students with H. pylori, the Nested PCR-QP test results of 53 (90.3%) were able to be analyzed. A total of 28 students had CAM resistance mutations. We found a genetic mutation in 28 students and no mutation in 23 students, and these results were consistent with those of PCR-direct sequencing. In the 23 adults who were diagnosed with H. pylori infection using the rapid urease test and culture testing, we were able to use Nested PCR-QP for analyzing 21 adults who tested positive in the stool H. pylori antigen test. The results obtained for all 21 adults were consistent with those obtained via the drug susceptibility test. CONCLUSIONS: Our novel method could be useful for non-invasively detecting CAM resistance mutations in H. pylori. This may help select a drug to reduce eradication failure rates against H. pylori. Trial registration This study was registered with the University Hospital Medical Information Network Clinical Trials Registry (no. UMIN000030632, https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000034977 ) on 29 December 2017.

Genome-wide association meta-analysis identifies GP2 gene risk variants for pancreatic cancer.

Pancreatic cancer is the fourth leading cause of cancer-related deaths in Japan. To identify risk loci, we perform a meta-analysis of three genome-wide association studies comprising 2,039 pancreatic cancer patients and 32,592 controls in the Japanese population. Here, we identify 3 (13q12.2, 13q22.1, and 16p12.3) genome-wide significant loci (P < 5.0 × 10-8), of which 16p12.3 has not been reported in the Western population. The lead single nucleotide polymorphism (SNP) at 16p12.3 is rs78193826 (odds ratio = 1.46, 95% confidence interval = 1.29-1.66, P = 4.28 × 10-9), an Asian-specific, nonsynonymous glycoprotein 2 (GP2) gene variant. Associations between selected GP2 gene variants and pancreatic cancer are replicated in 10,822 additional cases and controls of East Asian origin. Functional analyses using cell lines provide supporting evidence of the effect of rs78193826 on KRAS activity. These findings suggest that GP2 gene variants are probably associated with pancreatic cancer susceptibility in populations of East Asian ancestry.