Antibody Titers and the Risk of Infection During the SARS-CoV-2 Omicron Phase in Bizen City, Japan.

BACKGROUND: Understanding the association between the immune response and the risk of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has implications for forthcoming prevention strategies. We evaluated the association between antibody titers and the risk of infection for the general population during the Omicron-dominant phase. METHODS: This was a prospective cohort study of residents or people affiliated with institutions in Bizen City, which included 1899 participants. We measured the titers of antibodies against SARS-CoV-2 repeatedly every 2 months from June 2022 to March 2023. Infection status was obtained from self-reported questionnaires and the official registry. We estimated risk ratios (RRs) for infection within 2 months of the date of each antibody measurement with 95% confidence intervals (CIs) based on antibody titer categories and spline functions. RESULTS: Compared with the <2500 arbitrary unit (AU)/mL category, the 2500-5000, 5000-10 000, and ≥10 000 AU/mL categories had adjusted RRs of 0.81 (95% CI, .61-1.08), 0.51 (95% CI, .36-.72), and 0.41 (95% CI, .31-.54), respectively. The spline function showed a nonlinear relationship between antibody titer and risk. CONCLUSIONS: Higher antibody titers were associated with a lower risk. We demonstrate the usefulness of measuring an antibody titers to determine the appropriate timing for future prevention strategies.

Outdoor playing during preschool was associated with a reduced risk of school-age obesity in Japan.

AIM: This study investigated the association between outdoor play habits during preschool and school-age obesity. METHODS: We conducted a longitudinal cohort study of all children born in Japan during 2 weeks in January and July 2001. We defined outdoor play habits at age 2.5 years (third survey) as exposure, while parent-reported height and weight at age 7 years (seventh survey) were defined as overweight and obesity status using the WHO reference. Logistic regression models were used to estimate odds ratios (ORs) for associations between preschool outdoor play habits and school-age obesity, adjusting for parental and child factors. RESULTS: Of 53 575 children born, 42 812 had data on outdoor play habits at age 2.5 years, with 91% (38 970) having such habits. At age 7 years, 31 743/42 812 (74%) children had height and weight data, with 3249/31 743 (10%) classified as overweight or obesity (BMI SD score ≥1.0). Outdoor play habits were negatively associated with obesity (adjusted OR 0.85, 95% confidence interval (CI): 0.74-0.97). CONCLUSION: Outdoor play habits in early preschool years are associated with a reduced risk of school-age obesity. Parents and caregivers may consider encouraging their children to outdoor play habits at an early age to help prevent obesity later in life.

Regression of Necrotic Lesions after Methotrexate Withdrawal in Patients with Methotrexate-Associated Lymphoproliferative Disorders: A Retrospective CT Study.

This retrospective study investigated whether necrotic lesions detected on a computed tomography (CT) scan are more regressive than non-necrotic lesions after methotrexate withdrawal in patients pathologically diagnosed with methotrexate-associated lymphoproliferative disorders (MTX-LPD). In total, 89 lesions extracted from 24 patients on CT scans were included in the analysis. All patients had been evaluated for the presence of necrosis within lesions via CT scan upon first suspicion of MTX-LPD (baseline CT scan). The percentage lesion size reduction between the baseline and initial follow-up CT scan was calculated. The association between necrosis within lesions and size changes was estimated via linear regression analyses using both crude and adjusted models. Necrosis was significantly more common in extranodal lesions (27 out of 30 lesions, 90%) than in nodal lesions (9 out of 59 lesions, 15%, p<0.001). In the crude model, the regression of necrotic lesions was 58.5% greater than that of non-necrotic lesions; the difference was statistically significant (p<0.001). Additionally, the longest diameter of necrotic lesions at the baseline CT scan was significantly greater than that of non-necrotic lesions (p<0.001). Based on the adjusted model, necrotic lesions showed 49.3% greater regression than non-necrotic lesions (p=0.017). Necrosis detected on a CT scan was found to be an independent predictor of regression after MTX withdrawal in patients with MTX-LPD.

Significance of Continuous Low-Dose Lenvatinib for the Treating of the Patients with Unresectable Thyroid Carcinoma.

The tyrosine kinase inhibitor lenvatinib has been confirmed as an effective treatment option for patients with unresectable thyroid carcinoma. We conducted a retrospective analysis of the significance of the effect of continued lenvatinib treatment for the longest duration possible at a reasonable daily dose and with a minimum discontinuation period in 42 patients with unresectable thyroid carcinoma treated with lenvatinib between 2015 and 2020. A Cox proportional hazard model-based analysis revealed that the overall survival of the patients treated with a <8 mg/day mean dose of lenvatinib was significantly better than that of the patients treated with 8-24 mg/day (hazard ratio [HR] 0.38 for 1.14-4.54 mg/day, and HR 0.01 for 4.56-7.97 mg/day) adjusted for various factors (e.g., sex, age, drug interruption period). The cumulative dose of lenvatinib administered tended to be higher in the patients treated with low doses (< 8 mg/day) than in the patients treated with relatively high doses (8-24 mg/day). Considering its adverse events, the continuation of lenvatinib treatment with an adequate daily dose and drug interruption may help prolong the survival of patients with unresectable thyroid carcinoma.

Designing a test battery for workers' well-being: the first wave of the Tsukuba Salutogenic Occupational Cohort Study.

BACKGROUND: In recent years, there has been a diversification of working styles. The concept of workers' well-being is no longer limited to material wealth, such as how satisfied they are with their wages. Psychological enrichment, encompassing factors like motivation and interpersonal relationships, is also important. This study was established to develop a scale to evaluate the well-being of workers, named the Abundance Index for Workers (AIW). This new concept proposed by the authors comprehensively considers both job-related resources and personal and societal resources. METHODS: This study was carried out as part of the Tsukuba Salutogenic Occupational Cohort Study (T-SOCS). We utilized data from a survey targeting workers affiliated with institutions under the Tsukuba Science City Network, examining aspects of their daily life, work, and mental health. The deviation scores for each survey item were averaged to calculate an overall score. The correlations of the comprehensive score with the Patient Health Questionnaire-9 (PHQ-9) index for depression and the Single-item Presenteeism Question (SPQ) index for presenteeism were analyzed to determine criterion-related validity. RESULTS: The number of participants analyzed was 2,745. Factor analysis categorized the data into three factors: workplace mental health, societal resources, and lifestyle habits. Cronbach's α coefficient was 0.688. There were correlations of -0.363 (p < 0.001) between the total score and SPQ, and -0.558 (p < 0.001) between the total score and PHQ-9, suggesting a degree of criterion-related validity. CONCLUSIONS: In this study, we designed a test battery that assesses workers' well-being based on job-related resources and the richness of societal resources. The internal consistency of this battery was not as high as expected due to the broad scope of well-being. Although it is difficult to evaluate workers' well-being on a single scale, we believe that the AIW functions well as a test battery by combining scales with different attributes, which enables well-being to be captured from as many different perspectives as possible. This tool is designed to assist individuals in evaluating their own well-being and recognizing factors that can enhance it. TRIAL REGISTRATION: Not applicable; this study is not an intervention trial.

EGFR Mutation is a Prognostic Factor in Lung Cancer Patients with Pleural Dissemination Detected During or After Surgery.

BACKGROUND: Primary lung tumors are sometimes resected when either pleural dissemination (PD) or malignant pleural effusion (MPE) exists. This study clarified the prognostic factors for non-small cell lung cancer (NSCLC) with either PD and MPE, or both, detected during or after surgery. PATIENTS AND METHODS: We examined patients with NSCLC from a multicenter database who had either PD, MPE, or both, detected during or after surgery between 2005 and 2015. Hazard ratios and 95% confidence intervals were estimated using the Cox proportional hazards model adjusted for potential confounding factors. RESULTS: Among 9463 registered patients, PD, MPE, or both, were found in 114 patients with NSCLC during or after surgery. Primary tumor resection and exploratory thoracotomy were performed in 65 and 49 patients, respectively. In univariate analysis, adenocarcinoma, clinically undetected lymph node metastasis (c-N0 or unknown), EGFR mutation, and combination of chemotherapy or tyrosine kinase inhibitors after surgery were better prognostic factors for overall survival (OS), whereas in the multivariate analysis, adenocarcinoma, clinically undetected lymph node metastasis, and EGFR mutation were favorable independent prognostic factors in OS. Additionally, limited to patients with EGFR mutation, patients with primary lung tumor resection showed a significantly better 5-year OS than those with exploratory thoracotomy (86.4 vs. 44.8%; p < 0.001). CONCLUSION: Our findings show that surgical resection of primary tumors could improve the prognosis of patients with PD, MPE, or both, detected during or after surgery when the tumors harbor an EGFR mutation.

Association between handwashing and gargling education for children and prevention of respiratory tract infections: a longitudinal Japanese children population-based study.

PURPOSE: A longitudinal study was conducted to examine the effects of handwashing and gargling education for children on the prevention of respiratory tract infections (RTIs) in children in Japan. METHODS: The study included 38,554 children born in 2010 who were enrolled in a longitudinal study. Information on children's hygiene education regarding handwashing and gargling was collected in a survey at the age of 3.5 years. Based on parents' reports of doctors' diagnoses, airway infections and influenza events in the 12-month duration before the survey were evaluated for RTIs at the ages of 4.5 and 9 years. Poisson regression with robust variance was performed to examine the effects of hygiene education on RTIs prevention. The supplementary analysis was stratified by household income. RESULTS: Children were categorized into different groups: 38% in the handwashing and gargling group, 29% in the handwashing group, 0.1% in the gargling group, and 9.7% in the no-education group. Exclusions were made for non-respondent children (23%) and those in the gargling group. Hygiene education was associated with decreased influenza at the age of 4.5 years in the handwashing (adjusted RR [aRR] = 0.8; 95% CI, 0.8-0.9) and handwashing and gargling groups (aRR = 0.8; 95% CI, 0.8-0.9) compared with no education. However, no preventive effects on airway infections at the age of 4.5 and 9, influenza at the age of 9, or hospitalization between the ages of 3.5 and 9 years were detected. Handwashing and gargling could significantly prevent influenza in low-income households (aRR = 0.7; 95% CI, 0.6-0.8).     Conclusions: Gargling education was widespread and mostly combined with handwashing education in Japan. Hygiene education significantly affected prevention of influenza infections at the age of 4.5 years, especially in low-income households. WHAT IS KNOWN: • Previous intervention studies showed handwashing and gargling are effective in preventing respiratory tract infections. WHAT IS NEW: • We conducted a longitudinal study on handwashing and gargling education in Japanese children and found that handwashing and gargling were widely practiced together. • Handwashing and gargling education were related to a reduction in influenza, particularly in low-income households.

Obesity, overweight, and severe prognosis in COVID-19 patients in Japan.

INTRODUCTION: Obesity (i.e., body mass index [BMI] of 30 kg/m2 or more) is one of the risk factors for severe COVID-19, but the findings may not be directly applicable to Asians, who have a different cutoff point for defining obesity. We thus examined the association between obesity/overweight (BMI of 25 kg/m2 or more and less than 30 kg/m2) and the risk of COVID-19 severity. METHODS: The study population included COVID-19 patients who had been enrolled in the registry of the Okayama City Public Health Center in Okayama, Japan, between March 2020 and June 2022. We included 27 820 patients who had information on BMI and prognosis, and we conducted Poisson regression analysis with robust error variance to estimate risk ratios (RRs) with 95% confidence intervals (CIs) for severe outcomes. RESULTS: Obesity and overweight were associated with the increased risk of severe COVID-19 in all age categories. The RRs (95% CI) for COVID-19 induced respiratory failure compared to the normal weight category were 1.57 (1.31-1.88) for overweight and 2.45 (1.90-3.15) for obesity. CONCLUSIONS: Both obesity and overweight were associated with increased risk of severe COVID-19. This study suggests the importance of the overweight category to predict the risk of severe COVID-19 in Asians.

Examining the association between vaccine reactogenicity and antibody titer dynamics after the third dose of BNT162b2 vaccine using a mixed-effects model.

BACKGROUND: To mitigate the COVID-19 pandemic, many countries have recommended the use of booster vaccinations. The relationship between the degree of adverse vaccine reactions and elevated antibody titers is of interest; however, no studies have investigated the temporal changes in antibody titers based on repeated measurements after a third dose of the BNT162b2 vaccine. METHODS: This prospective longitudinal cohort study was conducted with 62 healthcare workers who received a third dose of the BNT162b2 at Okayama University Hospital, Japan. Venous blood draw and fingertip whole blood test sample collection were conducted at the early (3-13 days) and 1-month time points; only FWT sample collection was conducted at the 2-month time point. Information on adverse reactions within 1 week after vaccination was also obtained. The association between fever of 37.5 °C or higher and antibody titers after the third dose of BNT162b2 was examined using a mixed-effects model and Poisson regression with robust variance. RESULTS: A trend toward higher antibody titers in the early period after vaccination was observed in the febrile individuals, but the differences were not significant at 1 and 2 months post-vaccination (the partial regression coefficient for fever was 8094.3 [-1910.2, 18,098.8] at 1 month after vaccination, and 1764.1 [-4133.9, 7662.1] at 2 months after vaccination in the adjusted models). CONCLUSION: The findings suggest that the presence of fever after the third vaccine does not predict a sustained elevation in serum antibody titers.

Breastfeeding at 6 months of age had a positive impact on overweight and obesity in Japanese adolescents at 15 years of age.

AIM: A number of studies have indicated the potential benefits that breastfeeding has on reducing childhood obesity, but few studies have evaluated the effect on adolescent obesity. We examined the association between breastfeeding and overweight or obesity at 15 years of age using data from a large nationwide longitudinal study launched by the Japanese Government in 2001. METHODS: We analysed data for 26 164 participants with known infant feeding practices at 6 months of age, namely the duration of breastfeeding or formula feeding. Overweight or obesity at 15 years of age were calculated based on the subject's self-reported height and weight. Multinomial logistic regression analysis adjusted the data for child factors, namely sex, siblings, birth weight and physical activity clubs and the maternal factors of age, educational attainment and smoking status. RESULTS: Formula feeding was associated with an increased risk of overweight or obesity at 15 years of age. The adjusted odds ratios (95% confidence intervals) were 0.99 (0.89-1.09) for partial breastfeeding and 1.23 (1.02-1.48) for formula feeding, when exclusive breastfeeding was the reference category. CONCLUSION: Breastfeeding during infancy had potential benefits for overweight or obesity among 15-year-old adolescents. Our results provide further evidence of the importance of breastfeeding.

Childcare and Child Development in Japan.

For decades, the notion has persisted in developed countries that exclusive care by the mothers is best for the development of children up to 3 years of age. To examine the veracity of this "myth of the first three years" in Japan, we examined the effects of childcare facility use for children younger than 3 years on their development using the cohorts of the Longitudinal Survey of Newborns in the 21st Century conducted in Japan. Of the 47,015 respondents to the survey, we studied the children of 5,508 mothers with university/professional education to evaluate the relationships between primary early (< 2.5 years) childcare providers during weekday daytime hours and specific development indices for the ages of 2.5, 5.5, and 8 years. At the age of 2.5 and 5.5 years, children attending childcare facilities were judged as having more advanced developmental behaviors by their parents, such as being able to compose a two-word sentence (adjusted odds ratio [aOR]: 0.22) or to express emotions (aOR: 0.81), compared with those cared for by mothers. However, at the age of 8 years, children who attended childcare facilities as infants < 2.5 years showed more aggressive behavior in interrupting people (aOR: 1.20) and causing disturbances in public (aOR: 1.26) than those cared for by mothers (after adjustment for numerous child and parental factors). Although these results are generally consistent with previous studies, issues potentially involved with problem behavior such as quality of childcare require further investigation, as does the case of children of mothers with more modest educational attainment.

Fine Particulate Matter and Diabetes Prevalence in Okayama, Japan.

Many studies have shown an association between long-term exposure to particulate matter having an aerodynamic diameter of 2.5 µm or less (PM2.5) and diabetes mellitus (DM), but few studies have focused on Asian subjects. We thus examined the association between long-term exposure to PM2.5 and DM prevalence in Okayama City, Japan. We included 76,591 participants who had received basic health checkups in 2006 and 2007. We assigned the census-level modeled PM2.5 data from 2006 and 2007 to each participant and defined DM using treatment status and the blood testing. PM2.5 was associated with DM prevalence, and the prevalence ratio (95% confidence interval) was 1.10 (1.00-1.20) following each interquartile range increase (2.1 µg/m3) in PM2.5. This finding is consistent with previous results and suggests that long-term exposure to PM2.5 is associated with an increased prevalence of DM in Okayama City, Japan, where the PM2.5 level is lower than in other cities in Asian countries.

Does Participation in the Setouchi Triennale Foster Social Capital? : A Cross-Sectional Study.

This study examined whether participation in an art project was associated with higher social capital (SC). We conducted a questionnaire survey from November 2021 to March 2022 among residents aged 20 years or older of Naoshima, an island in Kagawa Prefecture, Japan. Before the survey, the Setouchi Triennale had been held on Naoshima four times, starting in 2010. We calculated propensity scores for Triennale participation and performed propensity score matching. We then compared cognitive and structural SC by Triennale participation and found significant differences, respectively. We adopted a conditional ordered logistic regression analysis with propensity score matching for cognitive or structural SC, and found adjusted odd ratios of 2.913 (95%CI, 1.846-4.596) for cognitive SC and 4.535 (95%CI, 2.839-7.244) for structural SC. Our findings suggest that Triennale participation enhanced the cognitive aspect of SC while also building structural SC.

Participation in the Setouchi Triennale and the Health of Residents in Naoshima: A Cross-Sectional Study.

Arts festivals have become increasingly popular in various parts of Japan in recent years. The purpose of this study was to investigate the relationships between arts festival activities participation at the Setouchi Triennale and the health of residents in the town of Naoshima. This was a cross-sectional study. Questionnaires were distributed to all residents of Naoshima who were 20 years old or older (n=2,588). We analyzed responses from 708 people. The associations between arts festival activities participation and health (measured by self-rated health) were analyzed using logistic regression analysis as the primary outcome. Kessler's psychological distress scale scores were also analyzed in the same manner as the primary outcome. The participating group had an adjusted odds ratio of 1.86 (95% confidence interval: 1.03-3.33) for higher self-rated health compared with those who did not participate. Kessler's psychological distress scale results showed that the participating group had an adjusted odds ratio of 3.23 (95% confidence interval: 1.19-8.81) for lower psychological distress compared with those who did not participate. In conclusion, arts festival activities participation was associated with higher self-rated health and lower psychological distress. However, caution must be taken in regard to generalizability and causality when interpreting these results.

Review of a Series of Surveys on Adverse Reactions to the COVID-19 mRNA-1273 Vaccine at Okayama University.

This paper presents the results of a series of surveys conducted from July 2021 to March 2023 to investigate the post-vaccination adverse reactions to the mRNA-1273 (Moderna) vaccine among faculty, staff, and students at Okayama University. These studies complement the official surveys conducted by the Ministry of Health, Labour and Welfare (MHLW) and provide a more representative picture of adverse reactions in the general population including large numbers of healthy young people. Pain, swelling, redness at the injection site, fever, headache, and malaise were the main adverse reactions reported. The proportion of adverse reactions was generally higher after the second vaccination and decreased with each additional vaccination. No statistically significant differences in the adverse reactions were found for males and females and those with/without a history of allergy, but a lower proportion of fever was observed in older participants and those with underlying medical conditions. We also evaluated the association between adverse reactions and antibody titers after the third vaccination and found no significant differences in antibody levels one month after vaccination. This series of studies highlights the importance of conducting surveys in diverse populations to provide a more representative picture of post-vaccination adverse reactions during a pandemic.

Association between Radon Hot Spring Bathing and Health Conditions: A Cross-Sectional Study in Misasa, Japan.

No epidemiological studies have examined the health effects of daily bathing in radon hot springs. In this cross-sectional study, we investigated the associations between radon hot spring bathing and health conditions. The target population was 5,250 adults ≥ 20 years old in the town of Misasa, Japan. We collected information about the participants' bathing habits and alleviation of a variety of disease symptoms, and their self-rated health (SRH). Unadjusted and adjusted odds ratios (ORs) and 95% confidence intervals (CI) were calculated. In both the adjusted and unadjusted models of hypertension, significant associations between the > 1×/week hot spring bathing and the alleviation of hypertension symptoms were observed compared to the group whose hot spring bathing was <1×/week: adjusted model, OR 5.40 (95%CI: 1.98-14.74); unadjusted model, 3.67 (1.50-8.99) and for gastroenteritis: adjusted model, 9.18 (1.15-72.96); unadjusted model, 7.62 (1.59-36.49). Compared to the no-bathing group, higher SRH was significantly associated with both bathing < 1×/week: unadjusted model, 2.27 (1.53-3.37) and > 1×/week: adjusted model, 1.91 (1.15-3.19). These findings suggest that bathing in radon hot springs is associated with higher SRH and the alleviation of hypertension and gastroenteritis.

Outcomes of solitary postoperative recurrence of esophageal squamous cell carcinoma diagnosed with FDG-PET/CT and treated with definitive radiation therapy.

BACKGROUND: Surgical resection of esophageal cancer is frequently performed to achieve a complete cure. However, the postoperative recurrence rate is 36.8-42.5%, leading to poor prognosis. Radiation therapy has been used to treat recurrences; solitary recurrence has been proposed as a prognostic factor for radiation therapy, though its significance is unclear. 18F-fluorodeoxyglucose positron emission tomography is a highly accurate diagnostic modality for esophageal cancer. This retrospective study aimed to analyze the outcomes of solitary postoperative recurrences of esophageal squamous cell carcinoma diagnosed with 18F-fluorodeoxyglucose positron emission tomography and treated with definitive radiation therapy. METHODS: We examined 27 patients who underwent definitive radiation therapy for single or multiple postoperative recurrences of esophageal squamous cell carcinoma between May 2015 and April 2021. 18F-fluorodeoxyglucose positron emission tomography/computed tomography was performed within 3 months before the commencement of radiation therapy. Kaplan-Meier, univariate, and multivariate analyses were performed to examine the overall survival and identify potential prognostic factors. RESULTS: The 1-, 2-, and 3-year overall survival rates were 85.2%, 62.6%, and 47.3%, respectively, and solitary recurrence was the only significant factor associated with overall survival (P = 0.003). The 1-, 2-, and 3-year overall survival rates in patients with solitary recurrence were 91.7%, 80.2%, and 80.2%, respectively, and in patients with multiple recurrences they were 80.0%, 50.3%, and 25.1%, respectively. Multivariate analysis also showed solitary recurrence as a significant factor for overall survival. CONCLUSIONS: When diagnosed with 18F-fluorodeoxyglucose positron emission tomography/computed tomography, solitary recurrence appears to have a more favorable prognosis than multiple recurrences.

Candidemia in patients with head and neck cancer: mortality and a novel risk factor.

PURPOSE: Candidemia is a bloodstream infection (BSI) by Candida spp. and is associated with high mortality. However, there have been few reports about BSI in head and neck cancer (HNC). We aimed to evaluate the impact of candidemia in patients with HNC and compared it with bacteremia. STUDY DESIGN: A multicenter retrospective study. METHODS: We retrospectively analyzed 83 BSI episodes in HNC (2011 to 2020) and divided them into the candidemia and bacteremia groups. We then compared the survival rate and risk factors for candidemia between the groups. RESULTS: The overall cumulative incidence (risk) of candidemia in BSI was 12 out of 83 episodes (14.5%). The 1-year mortality for the bacteremia and candidemia groups was 33.3% and 58.3%, respectively (log-rank p = 0.041). Broad-spectrum antibiotics (odds ratio [OR]: 29.5; 95% confidence interval [CI], 2.49-350), mucositis (OR 11.0; 95% CI, 1.52-80.1), and malignant wounds (OR 79.5; 95% CI 1.33-4737) were significant risk factors for candidemia in HNC. CONCLUSIONS: Candidemia causes high mortality in patients with HNC. To our knowledge, malignant wounds have not been previously reported as a risk factor for candidemia. For early diagnosis and treatment of candidemia, risk factors should be considered, and antifungal therapy started earlier.

Timing of REGEN-COV administration and progression to severe COVID-19.

INTRODUCTION: Several clinical trials have demonstrated that REGEN-COV (casirivimab and imdevimab) decreases the risk of hospitalization and death among COVID-19 patients. However, these trials did not evaluate the optimal timing of its administration, and evidence is limited regarding the relationship between the timing of administration and progression to severe COVID-19 among patients who receive REGEN-COV in a real-world setting. We examined the association between the timing of REGEN-COV administration and progression to severe COVID-19 among patients who received REGEN-COV in Japan. METHODS: We included a total of 342 COVID-19 patients (37 hospitals) who received REGEN-COV between July 19 and September 30, 2021. We calculated the difference between the date of symptom onset and the date of administration as an indicator of the timing of REGEN-COV administration and determined progression to severe COVID-19 after REGEN-COV administration. We conducted a logistic regression analysis, adjusting for potential confounders. RESULTS: The proportion of cases progressing to severe COVID-19 increased daily from symptom onset and sharply increased from day 5 of onset. The early administration (days 0-4) decreased the risk of progression to severity compared with late administration (after day 5), with an adjusted odds ratio of 0.29 (95% confidence interval: 0.11-0.56). CONCLUSIONS: The early administration of REGEN-COV was associated with a decreased risk of progression to severe COVID-19 when the delta variant was dominant. The present epidemiological findings indicate that this monoclonal antibody therapy should be implemented very early in the clinical course probably even for emerging variants such as omicron BA.2.

Association of nighttime sleep with behaviors in Japanese early childhood.

BACKGROUND: Preschool children in Asian countries, including Japan, sleep for a shorter duration at night than those in Europe and the USA. We examined the effects of the nighttime sleep duration on behavioral development in early childhood in Japan. METHODS: We used data from a large Japanese nationwide, population-based, longitudinal survey that began in 2001. We restricted the study participants to children born after 37 gestational weeks, with a birth weight ≥ 2500 g and singleton births (n = 41 890). The nighttime sleep duration was examined at 2.5 years old. Responses to survey questions regarding age-appropriate behavior at 5.5 years old were used as indicators of behavioral development. We conducted logistic regression analyses with adjustment for confounding factors, with ≥11 h of nighttime sleep as the reference group. RESULTS: The odds ratios for children who had ≤9 h of nighttime sleep, which was associated with being unable to listen with fidgeting and being unable to remain patient, were 1.26 (95% confidence interval, 1.14-1.39) and 1.27 (1.16-1.38), respectively. Children who had an irregular nighttime sleep duration were associated with age-appropriate behavioral inabilities. These results were similar in children who usually and sometimes took naps to those before stratification by the frequency of napping. CONCLUSION: A short nighttime sleep duration especially affects hyperactivity and impulsivity. An irregular nighttime sleep duration increases the inability to perform overall age-appropriate behaviors more than a short sleep duration. Ensuring a regular and sufficient nighttime sleep duration in early childhood is important for healthy behavioral development.