Search

Abstract Objectives The purpose of this study is to develop and refine PPE guidelines that address students’ needs and concerns for the Peer Physical Examination (PPE) guidelines and to assess the feasibility of a Japanese version of such guidelines for managing PPE classes. Method An action research approach was employed. Firstly, we sent a Questionnaire Survey 1 to the 5th and 6th year undergraduate medical students and junior residents to gather participants’ expectations and suggested improvements for PPEs and their opinion about having a set of PPE guidelines. We drafted a set of PPE guidelines with reference to PPE policies overseas by reflecting participants’ needs as identified through Questionnaire Survey 1. We then conducted interviews of 16 participants and revised our guidelines accordingly. Finally, we asked 632 medical students and 191 junior residents to fill out the form for obtaining informed consent (Questionnaire Survey 2) in order to check the feasibility of our PPE guidelines. Result The majority of the participants supported the development of the PPE guidelines. The interviews identified 5 themes relating to participants’ needs and concerns. In a pilot survey, students’ refusal rate for being a model patient varied depending on body region and 74.2% had a desire to be informed of any abnormal findings confidentially. Additionally, the need to take a balance between respecting students’ autonomy and securing model patients was noted. Conclusion Medical students and junior residents generally supported the PPE guidelines. The right to refuse the model patient role and management of incidental findings should be included in the guidelines. In addition, informing students of educational benefits in being a model patient may be necessary to address the shortage of model patients.

BackgroundA systematic review has reported that paternal involvement is beneficial in reducing social, behavioural and psychological problems in children. However, little research has investigated factors associated with the attainment of paternity leave.ObjectiveThe objective of this study was to explore fathers’ perceptions of the factors associated with taking paternity leave.Participants and settingOverall, 21 in-depth interviews were conducted with fathers to obtain information on their perceptions of paternity leave. We also conducted key informant interviews with four supervisors at companies to understand their opinions on paternity leaves and ensure that the implications of this study are relevant at workplaces.MethodsThematic analysis was adopted to analyse the data. Deductive coding was conducted based on previous studies on paternity leave, followed by inductive coding and modification of the initial codes. The final codes were organised based on the social-ecological model.ResultsThemes associated with taking paternity leave included fathers’ career aspirations, fathers’ commitment to supporting infants or mothers, mothers’ or infants’ need for fathers’ involvement, colleagues’ outlook on paternity leaves, fathers’ work schedules or responsibilities, support from relatives, paternity leave policies, and trends toward fathers’ involvement. The supervisors mentioned themes related to paternity leave from the broader perspective of long-term effects and impact on the organisation.ConclusionsThis study revealed fathers’ perceptions regarding the factors associated with taking paternity leave. The results may provide useful information on how to create an environment in which fathers can easily take paternity leave.

Not available.

Objectives As more emphasis is placed on the acquisition of competencies in medical education, portfolios are increasingly being used for evaluation. EPOC2 (E-POrtfolio of Clinical training) is an e-portfolio system developed in Japan and is used by about 800 clinical training hospitals. The study objective is to identify the learning trajectory of junior residents to provide insights into the provision of better postgraduate and undergraduate medical education in Japan.Design Longitudinal cohort study.Setting Hospitals nationwide adopting EPOC2.Participants 7671 residents who participated in clinical training programmes at hospitals adopting EPOC2 between April 2020 and March 2022.Primary outcome measure Formative evaluation scores assessed through self-evaluation by junior residents and evaluations by supervisors/senior physicians at the end of each rotation in each clinical department.Results For all evaluation items, growth trajectories were divided into six groups, each with distinct characteristics based on the specific content of the evaluation form. For example, in the self-evaluation of medical knowledge and problem-solving (B-2), a lower percentage of respondents had adequate scores at the beginning of their training compared with other similar items. Compared with the self-evaluations of the other item groups (ie, forms A1–A4 and B1–B9), the self-evaluation of the item group related to seeing patients (ie, forms C1–C4) differed by showing a group that remained at or below 2 until the end, accounting for 2.8% to 7.0%, possibly indicating the relatively low confidence of the residents for these items.Conclusions Growth trajectories fall into six groups, each with its own characteristics depending on the content of the items. These findings offer valuable insights into the developmental trajectories of junior residents and may highlight opportunities for enhancing their training programmes in Japan. This underscores the usefulness of a nationwide evaluation system, enabling researchers to analyse clinical education outcomes across the country using uniform indicators.

Summary: Background: While Japan provides universal healthcare, immigrants may experience hampered access to healthcare. A comprehensive review of immigrant healthcare access is also lacking. This systematic review aims to examine barriers and facilitators of healthcare access among immigrants in Japan. Methods: We searched for literature published in English and Japanese until January 9, 2024. Studies were included if they assessed factors influencing any stage of immigrants’ healthcare access, such as perceiving needs, seeking, reaching, utilizing healthcare and the consequences of healthcare, as defined by the Levesque framework. We performed a thematic analysis to further identify categories (PROSPERO: CRD42023418554). Findings: After screening 2791 articles, we identified 67 studies (40 quantitative, 23 qualitative, 4 mixed methods) meeting eligibility criteria. Limited healthcare information led immigrants to seek alternative information sources and affected immigrants' perceived healthcare needs. Longer duration of stay improved access to healthcare information. Cultural and healthcare system differences affected healthcare seeking. Reaching and utilizing healthcare were hindered by heavy workloads, undocumented status, financial hardship, and limited insurance but were facilitated by support from family and friends. The healthcare system was often insufficient to support immigrants’ language and cultural needs leading to dissatisfaction and poor compliance. Interpretation: Findings highlight the critical importance of a multidimensional approach to support immigrants in Japan, ranging from improving healthcare information access to creating immigrant-friendly health systems. More research is needed on the healthcare access among vulnerable immigrants, such as undocumented and low-skilled labor immigrants and children. Funding: No specific funding source supported this study.

Depression amongst medical students is a crucial matter. Grit, which is a potentially modifiable psychological factor, has been inversely linked to depressive symptoms. However, it remains unclear how grit is associated with depression. This study aims to examine the relationship between grit and depressive symptoms and to further investigate the potential effect modification by academic performance on the association between grit and depression among medical students. We focus on the total grit score and its subscales, namely perseverance of effort and consistency of interest. A cross-sectional study was conducted using data from second-year medical students at Tokyo Medical and Dental University in Japan from 2020 to 2023. The participants responded to questionnaire surveys comprising the Center for Epidemiologic Studies Depression Scale and the Short Grit Scale. Linear regression analysis was performed to assess the association between grit and depressive symptoms. We also tested for effect modification by first-year Grade Point Average (GPA) on the association between grit and depression. The total grit score and its subscales, perseverance of effort and consistency of interest, were all inversely associated with depressive symptoms (b = −4.7 [95%CI − 6.7 to − 2.6], b = −3.7 [95%CI − 5.3 to − 2.1], b = −1.8 [95%CI − 3.5 to − 0.2], respectively). While the interaction term for the total grit score and GPA was not significant, the interaction term for perseverance of effort and GPA was significant, indicating that the association between perseverance of effort and depression was stronger among the higher-achieving students. The interaction term for consistency of interest and GPA was also significant, indicating that the association was stronger among the lower-achieving students. We reveal a novel aspect of the association between grit and depressive symptoms in light of academic performance. The findings will contribute to future research on depression amongst medical students.

Abstract Background Most Japanese medical schools likely continue to rely on peer physical examination (PPE) as a tool to for teaching physical examination skills to students. However, the attitudes of medical students in Japan toward PPEs have not be identified. Therefore, we evaluated students’ attitudes toward PPE in a Japanese medical school as a preparation for developing a PPE policy tailored to the context of Japanese culture. Methods We conducted a mixed-methods study with an explanatory sequential approach, in which qualitative data were used to interpret the quantitative findings. Surveys and interviews were conducted with medical students and junior residents at a Japanese university. A total of 63 medical students and 50 junior residents responded to the questionnaire. We interviewed 16 participants to reach theoretical saturation and investigated the attitudes of medical students toward PPE and the themes emerging from the interview data, providing detailed descriptions of the quantitative findings. Results Female participants were significantly more likely than male participants to report varying degrees of resistance to being a model patient during PPE (male: 59.7%, female: 87%, p

IntroductionCOVID-19 have changed our lifestyle and little is known how our lifestyle associated with flourishing during COVID-19. This study examined the association between lifestyle, including sleep time, drinking, and smoking, and flourishing during the COVID-19 pandemic in Japan.MethodsWe used the population-based study, Utsunomiya COVID-19 seROprevalence Neighborhood Association (U-CORONA) survey conducted in November 2021 to examine the association between lifestyle such as sleeping time, drinking and smoking, and flourishing (n = 473). Flourishing was assessed with the flourishing index, a 10-item multidimensional scale with five domains. Multivariate linear regression analysis was performed adjusted for sex, age, income, and education.ResultsWe found that the flourishing index was significantly lower in the group that slept less than 6 h than in the group that slept 6–8 h (coef = −0.49, SE = 0.17, p < 0.01). We also found that drinking once to several times/week showed higher flourishing than those who almost never drink (coef = 0.57, SE = 0.19, p < 0.01). Smoking was not associated with flourishing.DiscussionSleep duration and drinking habit, but not smoking, may be important for flourishing during the COVID-19 pandemic.

ABSTRACTIntroduction The COVID-19 pandemic had an additional negative impact on the mental health of healthcare workers, including residents. Previous studies revealed that grit, which is an individual trait to achieve long-term goals unrelated to intelligence quotient, is not only positively associated with academic achievement and career success but also negatively correlated with depression. This study aimed to examine the association between grit and depressive symptoms among residents at the time of job start during the coronavirus disease 2019 (COVID-19) pandemic in Japan.Materials and methods This cross-sectional study used data from all post-graduate year 1 residents from March 2020 to April 2022 at Tokyo Medical and Dental University, Tokyo, Japan. Grit was measured by the Japanese version of Grit-S. The resident’s depressive symptoms were assessed using the Center for Epidemiologic Studies Depression Scale. The association of interest was examined using logistic regression analysis.Results Among 221 residents, 28 (12.7%) have depressive symptoms. One unit increase in Grit-S score after adjusting for age, sex, graduated university, and sleeping hours was associated with lower odds of having depressive symptoms by 63% (odds ratio [OR]: 0.37; 95% confidence interval [CI]: 0.19–0.74). Further, the perseverance of effort subscale score was associated with lower odds of having depressive symptoms after covariate adjustment (OR: 0.43; 95% CI: 0.22–0.84).Conclusions Higher grit scores were associated with lower odds of having depressive symptoms among residents at the timing of job start during the COVID-19 pandemic. Regular mental health assessment is particularly important for residents with low grit scores at entry.

Objective There is a need for public health strategies to address the negative psychological consequences of the COVID-19 pandemic, and the role of residential green exposure has gained prominence, particularly in the context of the ‘new normal’ and the prevailing ‘stay-at-home’ policies. This study aimed to evaluate the association between residential greenness and severe psychological distress during the COVID-19 pandemic in Japan. We also investigated the association stratified by ‘stay-at-home’ status, a proxy for exposure to residential greenness.Methods and analysis We used data from a population-based cohort study conducted in Utsunomiya City, Japan. Residential greenness was measured by the normalised difference vegetation index (NDVI) averaged over circular buffers around residence. Severe psychological distress was defined as a Kessler Psychological Distress Scale (K6) score ≥13. ‘Stay-at-home’ status was categorised as either ‘not stay-at-home’ (individuals working outside the home or self-employed) or ‘stay-at-home’ (working from home or not working), based on the working status. Logistic regression analysis was performed to examine the association between residential greenness and severe psychological distress.Results A total of 615 participants were analysed. Among the ‘stay-at-home’ group, an IQR increase in NDVI was inversely associated with severe psychological distress (100 m buffer: OR=0.27, 95% CI 0.10 to 0.77; 250 m buffer: OR=0.26, 95% CI 0.10 to 0.69; 500 m buffer: OR=0.33, 95% CI 0.11 to 0.95). However, no significant association was observed for the ‘not stay-at-home’ group.Conclusion Residential greenness was a protective factor for severe psychological distress among the ‘stay-at-home’ group, who were assumed to have spent more time in their residence.

Objective To clarify the reasons for consultation, advice sought by frontline physicians and relationship between the patient’s pathology and the type of advice provided to guide the future development of telecritical care services.Design Secondary analysis of transcripts of telephone calls originally recorded for quality control purposes was conducted using a thematic content analysis. The calls were conducted between December 2019 and April 2021 (total cases: 70; total time: ~15 hour).Settings Intensivists provided consultation services to frontline physicians at secondary care institutions in the Kansai and Chubu regions.Participants Non-intensive care frontline physicians working in five secondary care institutions in the Kansai and Chubu regions and intensivists providing a consultation service (n=26).Interventions Not applicable.Primary and secondary outcome measures The main outcome was the themes emerging from the language used during telephone and video consultations, indicating the gap filled by the telecritical care service.Findings We analysed 70 cases and approximately 15 hours of anonymised audio data. We identified the following reasons for consultation: ‘lack of competence in treatment and diagnostic testing’ and ‘lack of access to consultation in their own hospital’. Frontline physicians most often sought advice related to ‘treatment’, followed by ‘patient triage and transfer’, ‘diagnosis’ and ‘diagnostic testing and evaluation’. Regarding the relationship between the patient’s pathology and type of advice provided, the most commonly sought advice by frontline physicians varied based on the patient’s pathology.Conclusion This study explored the characteristics of 70 telecritical sessions and identified the reasons for and nature of the consultations. These findings can be used to guide the future provision and scale up of telecritical services.

BackgroundIn Japan, people have rich access to 24-h convenience stores where they can buy sweets, juice and fluoride hygiene products, among others. However, the association between the number of convenience stores in a neighbourhood and caries in elementary school children status has not been studied. This study aimed to investigate this particular association.MethodsData were derived from a population-based longitudinal cohort study (A-CHILD study) of elementary school children from first-grade to fourth-grade in Adachi City, Tokyo. Caregivers were asked to complete a questionnaire in 2015, 2016, and 2018. A total of 3,136 caregivers provided a valid response. We analysed the association using multilevel Poisson regression.ResultsThe mean number of caries among children in school districts with low, middle, and high number of convenience stores was 0.31 (SD: 0.81), 0.21 (SD: 0.69), and 0.16 (SD: 0.58). After covariate adjustment, children in the school districts with high and middle number of convenience stores had 44% (mean ratio 0.56, 95% CI: 0.31, 0.998) and 31% (mean ratio 0.69, 95% CI: 0.42, 1.13) fewer caries in their permanent teeth, respectively, than children in the school districts with low number of convenience stores. We also found dose–response relationship (p for trend: 0.042).ConclusionHigher number of convenience stores in a school district was associated with fewer caries in permanent teeth among elementary school children. Further study elucidating the mechanism on this protective association is warranted.

Abstract Background Information communication technology (ICT) is crucial to modern communication and information sharing. Effective interprofessional collaboration is essential in the care of elderly people. However, little is known about the effects of ICT on care provision for elderly people in a home setting. This retrospective cohort study examines the impact of interprofessional collaboration using ICT on the health outcomes of elderly home care patients. Methods The Team® mobile application promotes cooperation in local medical health care. It enables providers to obtain and share patient information within a single, cloud‐based platform. We collected and analyzed data from 554 patients from Nagaoka (Niigata prefecture, Japan) who received home care services from 2015 to 2020. We calculated the cumulative hazard ratio (HR) of death or admission to a hospital or nursing home for patients whose information was shared among different professions using the platform, and for those whose information was not shared. We used a Cox proportional hazards model, adjusted for covariates, and applied propensity score matching. Results The average age of the study population was 83.5 years; the median follow‐up period was 579.0 days. The risk of death or admission to a hospital or nursing home significantly decreased in the information‐shared group, compared with the control group (adjusted HR: 0.47 [p

Abstract Background Arthrogryposis, renal dysfunction, and cholestasis syndrome (ARCS) is a rare autosomal recessive disorder caused by mutations in VPS33B (ARCS1) and VIPAS39 (ARCS2). As per literature, most patients with ARCS died of persistent infections and bleeding by the age of 1 year. We report the first Japanese cases with ARCS1 and ARCS2 who presented with mild phenotypes and were diagnosed via genetic testing. Case presentation Case 1: A 6-year-old boy born to nonconsanguineous Japanese parents presented with jaundice and normal serum gamma-glutamyl transferase (GGT) levels, proteinuria, bilateral nerve deafness, motor delay, failure to thrive, and persistent pruritus. After cochlear implantation for deafness at the age of 2 years, despite a normal platelet count and prothrombin time-international normalized ratio, the patient presented with persistent bleeding that required hematoma removal. Although he did not show any obvious signs of arthrogryposis, he was suspected to have ARCS based on other symptoms. Compound heterozygous mutations in VPS33B were identified using targeted next-generation sequencing (NGS), which resulted in no protein expression. Case 2: A 7-month-old boy, the younger brother of case 1, presented with bilateral deafness, renal tubular dysfunction, failure to thrive, and mild cholestasis. He had the same mutations that were identified in his brother’s VPS33B. Case 3: A 24-year-old man born to nonconsanguineous Japanese parents was suspected to have progressive familial intrahepatic cholestasis 1 (PFIC1) in his childhood on the basis of low GGT cholestasis, renal tubular dysfunction, sensory deafness, mental retardation, and persistent itching. A liver biopsy performed at the age of 16 years showed findings that were consistent with PFIC1. He developed anemia owing to intraperitoneal hemorrhage from a peripheral intrahepatic artery the day after the biopsy, and transcatheter arterial embolization was required. ARCS2 was diagnosed using targeted NGS, which identified novel compound heterozygous mutations in VIPAS39. Conclusions The first Japanese cases of ARCS1 and ARCS2 diagnosed using genetic tests were reported in this study. These cases are milder than those previously reported. For patients with ARCS, invasive procedures should be performed with meticulous care to prevent bleeding.

Background: Japan’s historically low immigration rate and monolingual culture makes it a particularly interesting setting for clarifying non-national medical care. Our study objective was to examine disease patterns and outcome differences between Japanese and non-Japanese patients in a rapidly globalizing nation. Methods: A secondary data analysis of 325 non-Japanese and 13,370 Japanese patients requiring tertiary care or intensive-care unit or high-care unit admission to the emergency department at the Tokyo Medical and Dental University medical hospital from 2010 through 2019 was conducted. Multivariable linear and logistic regressions models were applied to examine differences in percentage of diagnosis, mortality rates, and length of stay, stratified by Glasgow Coma Scale (GCS) scores to consider the impact of language barriers. Sex and age were adjusted. Results: Non-Japanese patients had more anaphylaxis, burns, and infectious disease, but less cardiovascular diagnoses prior to adjustment. After adjustment, there were significantly more anaphylaxis (adjusted odds ratio [aOR] 2.7; 95% confidence interval [CI], 1.7–4.4) and infectious disease diagnoses (aOR 2.2; 95% CI, 1.3–3.7), and marginally more burn diagnoses (aOR 2.3; 95% CI, 0.96–5.3) than Japanese patients. Regardless of GCS scores, there were no significant differences between non-Japanese and Japanese patient length of stay for anaphylaxis, burn, and infectious disease after covariate adjustment. Conclusion: There were more non-Japanese patients diagnosed with anaphylaxis, burns, and infectious disease, but no notable patient care differences for length of stay. Further prevention efforts are needed against anaphylaxis, burns, and infectious disease for non-Japanese tourists or residents.

ObjectiveAdolescents with prediabetes are at high risk of developing type 2 diabetes in later life. It is necessary to identify risk factors for prediabetes in adolescents. This study aimed to examine the association between skipping breakfast and prediabetes among adolescents in Japan.Study designWe used the population-based cross-sectional data of eighth grade in junior high school students from the Adachi Child Health Impact of Living Difficulty (A-CHILD) study conducted in Adachi City, Tokyo, Japan, in 2016, 2018, and 2020. Skipping breakfast was assessed using self-reported questionnaires (N=1510). Prediabetes was defined as hemoglobin A1c (HbA1c) levels of 5.6-6.4%. The association between skipping breakfast and prediabetes was evaluated using multivariate logistic regression analysis. Stratified analysis was also performed using BMI, 1 SD or more, or less than 1SD, as overweight was defined as 1SD or more.ResultsStudents who skipped breakfast were 16.4% (n=248). The prevalence of prediabetes was 3.8% (n=58). Skipping breakfast exhibited a significant association with prediabetes (OR:1.95, 95% CI: 1.03 to 3.69) after adjusting for sex, annual household income, family history of diabetes mellitus, BMI, and survey year. Stratified analysis showed stronger association among students with overweight (BMI ≥1SD) (OR=4.31, 95% CI 1.06-17.58), while non-sigificant among students without overweight (BMI

OBJECTIVES:. The antimicrobial stewardship program (ASP) is an important quality improvement initiative that is recommended in the ICU. However, the shortage of infectious disease physicians in Japan has led to the need for simpler methods for implementing ASPs. We investigated whether antibiotic time-outs (ATOs) during multidisciplinary rounds as part of an ASP can improve patient survival and reduce the number of days of therapy (DOT) with antibiotics. DESIGN:. Single-center controlled before-and-after study. SETTING:. Medical/surgical ICU in a tertiary university medical center in Tokyo, Japan. PATIENTS:. All patients 16 years old or older admitted consecutively in the ICU between October 2016 and March 2020. INTERVENTIONS:. An intensivist-driven ICU multidisciplinary round was introduced in October 2016, and ATOs with ICU rounds were implemented in June 2018. ATOs were conducted 3, 7, and 14 days after initiation of antibiotics. MEASUREMENTS AND MAIN RESULTS:. The primary outcome was the subdistribution hazard ratio (SHR) of survival to hospital discharge compared between multidisciplinary rounds (phase 1) and ATO during multidisciplinary rounds (phase 2) using the multivariable Fine-Gray model. The secondary outcomes were the SHR of survival to ICU discharge and the trends in the DOT with IV antibiotics per 1,000 patient-days between October 2016 and March 2020 by using interrupted time-series analysis. The number of patients in phases 1 and 2 was 777 and 796, respectively. The group that underwent ATO during multidisciplinary rounds showed a significant increase in the survival to hospital discharge in comparison with the multidisciplinary round-only group (SHR, 1.13; 95% CI, 1.02–1.25); however, the SHR of survival to ICU discharge showed no significant intergroup difference. The DOT with total IV antibiotics decreased after ATO implementation (change in intercept, –178.26; 95% CI, –317.74 to –38.78; change in slope, –7.00; 95% CI, –15.77 to 1.78). CONCLUSIONS:. ATOs during multidisciplinary rounds are associated with improved patient survival and reduced DOT.

ObjectivesIncreased levels of stress have been reported among parents due to the factors associated with the COVID-19 pandemic. Although social support is known as a protective factor for the stressors, restrictions due to the pandemic could influence the provision and forms of social support. To date, few qualitative studies have examined the stressors and coping strategies in detail. In particular, the role of social support for single mothers during the pandemic remains largely unclear. The purpose of this study is to explore the stressors and coping strategies of single parents during the COVID-19 pandemic, with a focus on social support as a coping strategy.MethodsIn-depth interviews with 20 single mothers were conducted in Japan between October and November 2021. Data were deductively coded using thematic coding based on codes related to stressors and coping strategies, focusing on social support as a coping strategy.ResultsMost interviewees recognized additional stressors after the COVID-19 outbreak. Five stressors were mentioned by the participants: (1) fear of infection, (2) financial concerns, (3) stress caused by interactions with their children, (4) restrictions on childcare facilities, and (5) stress related to staying at home. The major coping strategies were (1) informal social support from family, friends, and coworkers, (2) formal social support from municipalities or nonprofit organizations, and (3) self-coping strategies.ConclusionSingle mothers in Japan recognized additional stressors after the COVID-19 outbreak. Our results support the importance of both formal and informal social support for single mothers, either in-person or online, to cope with stress during the pandemic.

Background: An increase in extreme heat events has been reported along with global warming. Heat exposure in ambient temperature is associated with all-cause diabetes mortality and all-cause hospitalization in diabetic patients. However, the association between heat exposure and hospitalization for hyperglycemic emergencies, such as diabetic ketoacidosis (DKA), hyperosmolar hyperglycemic state (HHS), and hypoglycemia is unclear. The objective of our study is to clarify the impact of heat exposure on the hospitalization for DKA, HHS, and hypoglycemia. Methods: Data of daily hospitalizations for hyperglycemic emergencies (i.e., DKA or HHS) and hypoglycemia was extracted from a nationwide administrative database in Japan and linked with temperature in each prefecture in Japan during 2012–2019. We applied distributed lag non-linear model to evaluate the non-linear and lagged effects of heat exposure on hospitalization for hyperglycemic emergencies. Results: The pooled relative risk for hyperglycemic emergencies of heat effect (the 90th percentile of temperature with reference to the 75th percentile of temperature) and extreme heat effect (the 99th percentile of temperature with reference to the 75th percentile of temperature) over 0–3 lag days was 1.27 (95 %CI: 1.16–1.39) and 1.64 (95 %CI: 1.38–1.93), respectively. The pooled relative risk for heat effect on hospitalization for hypoglycemia and extreme heat effect over 0–3 lag days was 1.33 (95 %CI: 1.17–1.52) and 1.65 (95 %CI: 1.29–2.10), respectively. These associations were consistent by type of hyperglycemic emergencies and type of diabetes and were generally consistent by regions. Discussion: Heat exposure was associated with hospitalizations for DKA, HHS and hypoglycemia. These results may be useful to guide preventive actions for the risk of fatal hyperglycemic emergencies and hypoglycemia.

Keiji Kawatani et al. developed a panel of Down syndrome (DS) isogenic astrocytes derived from iPSCs to observe the consequence of DS on astrocyte precursor proliferation, differentiation, and gene expression. Their results suggest a dose-dependent effect of DYRK1A and PIGP on DS-derived astrocyte precursor proliferation, and represent a valuable resource and cellular model for future DS research.

Abstract Clinical outcomes of pulmonary arterial hypertension (PAH) may be improved using targeted delivery system. We investigated the efficacy of ONO1301 (prostacyclin agonist) nanospheres (ONONS) in Sugen5416/hypoxia rat models of PAH. The rats were injected with saline (control) or ONONS (n = 10, each) on days 21 and 28, respectively. Hepatocyte growth factor (HGF)-expressing fibroblasts and inflammatory cytokines were measured. Cardiac performance was assessed and targeted delivery was monitored in vivo, using Texas red-labeled nanoparticles. Compared with control, HGF-expressing fibroblasts and HGF expression levels were significantly higher in the ONONS group, while the levels of interleukin-6, interleukin-1β, transforming growth factor-β, and platelet-derived growth factor were lower. Histological assessment revealed significant amelioration of the percent medial wall thickness in pulmonary vasculature of rats in the ONONS group. Rats in the ONONS group showed decreased proliferating cell nuclear antigen-positive smooth muscle cells and improved right ventricle pressure/left ventricle pressure. No difference was seen in the accumulation of Texas red-labeled nanoparticles in the brain, heart, liver, and spleen between PAH and normal rats. However, a significant area of nanoparticles was detected in the lungs of PAH rats. ONONS effectively ameliorated PAH, with selective delivery to the damaged lung.

IntroductionPrior studies have shown that children who are the only child are more likely to be overweight compared to their peers with siblings, regardless of whether they are the oldest, in the middle, or youngest. The study objective was to clarify whether there is an association between the length of the only-child period and the risk of overweight in firstborns who experienced an only-child period during early childhood before their siblings were born.MethodsA total of 7,576 first-born boys and 7,229 first-born girls were examined from a nationwide longitudinal survey in Japan. The length of the only-child period was determined by “birth interval”; i.e., the interval between the birth of the index child and the birth of the second child. It was categorized as short (

Abstract Individuals with Down syndrome (DS) commonly show unique pathological phenotypes throughout their life span. Besides the specific effects of dosage-sensitive genes on chromosome 21, recent studies have demonstrated that the gain of a chromosome exerts an adverse impact on cell physiology, regardless of the karyotype. Although dysregulated transcription and perturbed protein homeostasis are observed in common in human fibroblasts with trisomy 21, 18, and 13, whether and how this aneuploidy-associated stress acts on other cell lineages and affects the pathophysiology are unknown. Here, we investigated cellular stress responses in human trisomy 21 and 13 neurons differentiated from patient-derived induced pluripotent stem cells. Neurons of both trisomies showed increased vulnerability to apoptotic cell death, accompanied by dysregulated protein homeostasis and upregulation of the endoplasmic reticulum stress pathway. In addition, misfolded protein aggregates, comprising various types of neurodegenerative disease-related proteins, were abnormally accumulated in trisomic neurons. Intriguingly, treatment with sodium 4-phenylbutyrate, a chemical chaperone, successfully decreased the formation of protein aggregates and prevented the progression of cell apoptosis in trisomic neurons. These results suggest that aneuploidy-associated stress might be a therapeutic target for the neurodegenerative phenotypes in DS.

IntroductionPrevious studies have shown that paternal absence leads to earlier pubertal timing among girls in high-income countries. Despite the low divorce rate in Japan, paternal separation is commonly seen due to a unique corporation system, tanshin funin, where employees relocate with their spouses and children. We examined paternal separation, including paternal absence (due to divorce or paternal death) and paternal tanshin funin, during early childhood as a predictor of earlier girl’s pubertal development, assessed as age at peak height velocity (PHV).MethodsThis study examined 15 214 girls from a longitudinal survey conducted in Japan from 2001 to 2016 by the Ministry of Health, Labor and Welfare. Paternal separation was determined by the occurrence through annual surveys conducted at ages 0.5 to 4.5 years. Outcome was defined as age at PHV between ages 6 to 15 years. We conducted linear regression, adjusted for potential confounders and other covariates.ResultsContinuous father cohabitation was seen in 88.7% of households, while paternal separation was experienced 1-2, 3-4 and 5 times (always) among 7.4%, 2.8% and 1.1% of households, respectively. Girls who confronted continuous paternal separation (5 times) experienced 0.42 years earlier [95% confidence interval (CI): -0.75, -0.10] age at PHV compared to their peers who always lived with their fathers.ConclusionGirls who experienced paternal separation throughout ages 0.5 to 4.5 years experienced PHV earlier.

Abstract Background A seroepidemiological study was conducted on a random sample of households in Utsunomiya City, Tochigi Prefecture, Greater Tokyo, Japan, to assess the seroprevalence of SARS‐CoV‐2. Methods The level of IgG antibodies in the blood of the recruited subjects was assessed using chemiluminescence immunoassay analysis. In addition, the population‐based prevalence of SARS‐CoV‐2 was estimated. Results Three positive afebrile cases were confirmed. The estimated unweighted prevalence and weighted prevalence of SARS‐CoV‐2 infection were 0.40% and 1.23%, respectively. Conclusions This study suggests that the prevalence of SARS‐CoV‐2 may have been underestimated. Wider testing strategies may lead to revealing more SARS‐CoV‐2 cases.

BackgroundThe Japanese healthcare system currently faces numerous challenges, including a super-aging society and an excessive burden on medical workers; therefore, the need for innovative solutions from healthcare ventures to tackle these issues has increased. Meanwhile, as physicians play important roles in healthcare ventures, the need for Japanese physician entrepreneurs is more important than ever. Given the lack of research examining barriers to physicians starting ventures and what skills, knowledge, and surrounding environments act as facilitators, this study aimed to identify the facilitators and barriers faced by physicians to start ventures.MethodsBetween September and November 2019 and in May 2021, qualitative interviews were conducted with 33 participants, which included eight physician entrepreneurs; two administrative officers at the Ministry of Health, Labour and Welfare and the Ministry of Economy, Trade and Industry; three faculty members at Tokyo Medical and Dental University (in-depth interviews); and 20 medical students (focus group discussions). The interviews were deductively coded based on the social ecological model. The inductive approach was applied to coding any knowledge necessary to start a business. We conducted member checking with three physician entrepreneurs and seven medical students to improve our results' credibility.ResultsThe factors influencing a physician's decision to launch a new business include their willingness to contribute to society, the unique environment in which an individual is placed while in medical school and afterward, negative aspects of the lack of diversity in physicians' careers, the financial stability provided by a medical license, and self-efficacy.ConclusionsOur study revealed facilitators and barriers to physicians' entrepreneurial ventures. Knowledge about these factors might be useful in supporting physicians to launch or become involved in healthcare ventures.

BackgroundInterprofessional education (IPE) is crucial in dentistry, medicine, and nursing. However, scant mixed methods studies have compared the IPE outcomes across these disciplines to develop evidence-based IPE. This study explored the differences in the readiness of dental, medical, and nursing students for interprofessional learning before and after IPE workshops and elucidated reasons for this disparity.MethodsData were obtained from dental, medical, and nursing students who participated in IPE workshops conducted at Tokyo Medical and Dental University in Japan in 2019 and 2020. The participants filled the validated Japanese version of the Readiness for Interprofessional Learning Scale (RIPLS) before and after attending the workshops (n = 378). Paired t-tests were performed to assess differences between the pre- and post- workshop RIPLS scores. Welch's t-tests were deployed to evaluate interdisciplinary differences in their scores. Qualitative analyses were conducted using an explanatory sequential design with focus group discussions (FGDs) held with 17 dental students to explain the quantitative results.ResultsTotal RIPLS scores increased significantly for every discipline after the workshops (p < 0.001). Dental students scored significantly lower pre- and post- workshop aggregates than medical and nursing students, respectively (p < 0.001). The FGDs yielded three principal themes in the explanations tendered by dental students on their lower scores: 1) dental students rarely felt the need for interprofessional collaborations, 2) dentists often worked without the need for interprofessional collaborations, and 3) dental students believed their contribution to the workshop was insufficient.ConclusionsThe results revealed divergences in the readiness of dental, medical, and nursing students for interprofessional learning, and the study illuminated possible reasons for these disparities. These outcomes will help develop evidence-based IPE by indicating approaches to place a higher value on interprofessional collaborations in educational environments, ameliorate the awareness of educators, and enhance the workshop facilitation style.

ObjectiveKawasaki disease (KD) is a systemic vasculitis in childhood that can lead to coronary artery lesions (CALs). Although early diagnosis and treatment is important for preventing KD patients from development of CALs, diagnosis depends on the clinical features of KD. We studied the usefulness of leucine-rich alpha-2-glycoprotein 1 (LRG1) and angiotensinogen (AGT), previously reported as KD-related proteins, for KD diagnosis and estimation of intravenous immunoglobulin (IVIG) efficacy.MethodsWe undertook a prospective cohort study with patients having two or more KD symptoms in multiple centers in Japan, between July 2017 and February 2019.ResultsTwo hundred forty-two patients were included. In multivariable analysis, one unit increase in LRG1 was associated with higher odds of KD diagnosis (Odds ratio [OR] 1.02 [95% confidence interval (CI) 1.001-1.03]). Double-positivity for AGT (≥ 26 μg/mL) and LRG1 (≥ 123.5 μg/mL) was an independent biomarker for KD diagnosis in both the total cohort and the subgroup of patients with two to four KD symptoms (OR 5.01 [95% CI 1.86-13.50] and 3.71 [95% CI 1.23-11.16], respectively). There was no association between LRG1/AGT and IVIG efficacy.ConclusionDouble-positivity for LRG1 and AGT is an biomarker for KD diagnosis, especially useful in diagnosing incomplete KD from non-KD. Future studies with larger cohorts should seek to determine whether LRG1 and AGT are valuable as definitive data referred at the diagnosis of KD and for estimating the risk of CALs.

BackgroundChildren who are exposed to natural disasters are at greater risk of developing mental and behavior problems. Prior studies have suggested that positive parenting practices could prevent child mental and behavior problems among those who were exposed to natural disasters. Parent–child interaction increases oxytocin level in parents and infants; however, studies assessing the change in oxytocin level after positive parent-child interaction and its effect on child behavior problems among preadolescents who were exposed to natural disasters are lacking. This study investigated whether playful interaction stimulated oxytocin levels in 34 mother–child dyads who experienced the 2011 Great East Japan Earthquake in Kesennuma City in Miyagi Prefecture, Japan, and the effect of the maternal oxytocin changes on child behavior problems.MethodsParticipants were recruited in 2012 after the Great East Japan Earthquake. Annual surveys were conducted from 2012 to 2017. Salivary oxytocin level was assessed before and after the playful interaction in 2015. Behavior problems were evaluated by caregivers, using the Child Behavior Checklist (CBCL) in 2017. Fixed effect regression analyses were conducted to determine the effect of playful mother–child interaction on oxytocin level by comparing the change in the 10 min after the interaction with the change in the 10 min before the interaction. We also examined the effect of maternal oxytocin changes before and after the playful interaction on the onset of child behavior problems in 2017.ResultsA significant increase in maternal oxytocin level was detected following playful interaction, especially among mothers of first-born boys (2.63 pg/mg protein. 95% CI: 0.45, 4.81). Maternal psychological distress and trauma were also negatively associated with an increase of oxytocin levels. The increase in maternal oxytocin level was significantly associated with lower externalizing problem score of children 2 years later.ConclusionOur results might suggest a rational for potential preventive intervention for child behavior problems through playful mother–child interaction after natural disasters.

Background Misdiagnoses are associated with various cognitive biases, which are difficult to reduce even if physicians think about clinical cases deliberately. We propose a new "2-Dimensional Approach" that combines two perspectives in diagnostic reasoning: organs (brain, heart, lung, intestine/liver, kidney) and systems (metabolic, endocrine, blood/tumor, infection, immune, circulatory, nervous systems). Systems involve throughout the whole body and can be pathogenesis of diseases. As a result of diseases, organs show abnormal vital signs and symptoms. We investigated: (1) whether each individual resident has a bias for either organs or systems when they diagnose clinical cases, and (2) whether the 2D Approach can reduce such a bias. Methods We randomly assigned PGY1 residents (n=105) to either the 2D Approach group (n=45) or a control group (n=60). After attending either a lecture on the 2D Approach or a non-related lecture, residents were asked to diagnose two clinical cases. We divided each diagnosis into one of the two categories, either "organs" or "systems". We investigated whether each resident would diagnose the two cases into the same category, either organs or systems (i.e., a bias for either organs or systems). Results The participants in the control group tended to diagnose the two cases into the same category, either organs or systems (OR: 5.63, 95% CI: 1.62-21.7, p=0.0030, Fisher's exact test). In the 2D Approach group, the category of diagnoses for the two cases were not related to each other (OR: 2.14, 95% CI: 0.50-9.81, p=0.33). Conclusion There is a bias for either organs or systems when residents diagnose clinical cases, suggesting that organs and systems are different perspectives in diagnostic reasoning. By combining these 2 different perspectives in a 2-dimensional matrix, the 2D Approach reduces this bias.

The aim of this study was to examine the relationship between parental anxiety (father-only, mother-only, or both) and infant weight change. We performed a secondary data analysis among 551 children in the Avon Longitudinal Study of Parents and Children, a birth cohort with weight measurements collected prospectively at 4, 8, and 12 months of age. Paternal and maternal anxiety symptoms were based on the eight-item anxiety subscale of the Crown-Crisp Experiential Index. Scores in the top 15% at 8 weeks postpartum were classified as high anxiety. Generalized Estimating Equations were employed to estimate the joint association between parental anxiety and change in child weight-for-age z-score. Children who had fathers, but not mothers, with anxiety showed a 0.15 (95% CI: 0.01, 0.29) greater increase in weight-for-age z-score than children with neither parent anxious. This result suggests that paternal anxiety, not maternal anxiety, was associated with increases in child weight gain in the first year of life. Public health practitioners and clinicians should consider the use of robust measures of both maternal and paternal anxiety in the postpartum period, in addition to the suggested screening for postpartum depression. Given the limitations of the study, this study should be considered preliminary and hypothesis generating.

Abstract Eukaryotic genomes are organised into complex higher-order structures within the nucleus, and the three-dimensional arrangement of chromosomes is functionally important for global gene regulation. The existence of supernumerary chromosome 21 in Down syndrome may perturb the nuclear architecture at different levels, which is normally optimised to maintain the physiological balance of gene expression. However, it has not been clearly elucidated whether and how aberrant configuration of chromosomes affects gene activities. To investigate the effects of trisomy 21 on nuclear organisation and gene expression, we performed three-dimensional fluorescent imaging analysis of chromosome-edited human induced pluripotent stem cells (iPSCs), which enabled identification of the parental origin of the three copies of chromosome 21. We found that two copies of maternal chromosomes resulting from meiotic nondisjunction had a higher tendency to form an adjacent pair and were located relatively distant from the nuclear membrane, suggesting the conserved interaction between these homologous chromosomes. Transcriptional profiling of parental-origin-specific corrected disomy 21 iPSC lines indicated upregulated expression of the maternal alleles for a group of genes, which was accompanied by a fluctuating expression pattern. These results suggest the unique effects of a pair of maternal chromosomes in trisomy 21, which may contribute to the pathological phenotype.

BACKGROUND:Although leprosy is portrayed as a disappearing disease, leprosy affected persons in India are still suffering massively. Even further, nearly 60% of the world's newly detected cases are appearing from India alone. The problem has exacerbated due to the drastic decrease of global funding after India's official declaration of 'elimination', which did not foster the actual pain of patients beyond prevalence. Leprosy patients have hardships in their lives due to disabilities, stigma and poverty; thus, they require sustained, continuous care even after release from treatment. Yet, current interventions mostly have a vertical, short-term approach, not showing much progress in lightening the burden of leprosy. In contrast, Little Flower Hospital Community (LFHC) in India has been remarkably providing holistic care for thousands of leprosy patients for 35 years. However, there has not been any research conducted to uncover the underlying factors of this longstanding leprosy control model. Therefore, this research explores the in-depth contextual attributes of this hospital community that has been able to successfully provide sustainable care for a long time even without excessive external funds. METHODS AND FINDINGS:This qualitative research used a grounded theory approach, involving 28 in-depth interviews of 11 patients, 13 workers, and 4 board members from the hospital. The interview data were inductively analyzed to examine the contextual factors of the hospital's sustainability. Open coding, axial coding and selective coding were conducted, and Glaser's Six C's model was used to create a theoretical model of the sustainability of LFHC. The fundamental cause of the sustainability was the leprosy patients' strong craving for life with dignity, despite the isolation from the society. The desire resulted in a bottom-up formation of a 'consumer-provider cooperative', where patients mutually support each other with basic treatment learned from experience. The profits earned from the patients' occupational efforts such as dairy farming, cover the costs needed to manage the hospital community, which contributes to economical sustainability. Social sustainability was established through the holistic care including psychosocial, educational, medical, and residential support. The wholesome care socially rehabilitated the patients to be included in the society with satisfaction, social justice and social cohesion. The main limitation of this study is that this study cannot be generalized due to the nature of Grounded Theory based study. CONCLUSIONS:This study investigated the determinants that made LFHC sustainable, and the findings suggested the importance of forming a cooperative community and implementing social rehabilitation for sustainable leprosy control. More exploration on transferring this model to other leprosy colonies will have great impact in maintaining sustainable care for leprosy patients. Furthermore, this research may highlight the importance of sustainable development in policies targeting neglected tropical diseases beyond leprosy as well.

BACKGROUND:Group-based trajectory modeling is a useful tool for categorizing students' academic trajectories and their determinants. Using insights gained from the analyses, we can identify students at risk for poor academic performance and monitor them to provide support. To date, studies investigating the associations between demographic factors and academic performance trajectories among medical students are scarce. The study objective was to examine the associations between demographic factors and academic performance trajectories in medical students using group-based trajectory modeling. METHODS:Participants included all medical students admitted to Tokyo Medical and Dental University in Japan in 2013 and 2014 (n = 202). Academic performance was evaluated by biannual grade point average (GPA) scores in preclinical years. We used group-based trajectory modeling to categorize students into GPA trajectories. Multinomial logistic regression was used to examine the association between the odds of being in a certain GPA trajectory group and demographic factors such as high school type, high school geographical area, admission test type, high school graduation year, whether the student was a biology major, and sex. RESULTS:Students' GPA trajectories were classified into four trajectory groups as well as another group that consisted of students who withdrew or repeated years. We found that students whose high school geographical area was outside the National Capital Region were 7.2 times more likely to withdraw or repeat years in comparison with students whose school was inside the National Capital Region (OR: 7.21, 95% CI: 1.87, 27.76). In addition, admission test type, high school graduation year, and sex were associated with GPA trajectories. CONCLUSIONS:High school geographical area, admission test type, high school graduation year, and sex were associated with GPA trajectories. These findings provide important insights into identifying students at risk for poor academic performance and strategies for monitoring them to provide adequate and timely support.

Chromosomal aneuploidy and specific gene mutations are recognized early hallmarks of many oncogenic processes. However, the net effect of these abnormalities has generally not been explored. We focused on transient myeloproliferative disorder (TMD) in Down syndrome, which is characteristically associated with somatic mutations in GATA1. To better understand functional interplay between trisomy 21 and GATA1 mutations in hematopoiesis, we constructed cellular disease models using human induced pluripotent stem cells (iPSCs) and genome-editing technologies. Comparative analysis of these engineered iPSCs demonstrated that trisomy 21 perturbed hematopoietic development through the enhanced production of early hematopoietic progenitors and the upregulation of mutated GATA1, resulting in the accelerated production of aberrantly differentiated cells. These effects were mediated by dosage alterations of RUNX1, ETS2, and ERG, which are located in a critical 4-Mb region of chromosome 21. Our study provides insight into the genetic synergy that contributes to multi-step leukemogenesis.

Chromosome abnormalities induces profound alterations in gene expression, leading to various disease phenotypes. Recent studies on yeast and mammalian cells have demonstrated that aneuploidy exerts detrimental effects on organismal growth and development, regardless of the karyotype, suggesting that aneuploidy-associated stress plays an important role in disease pathogenesis. However, whether and how this effect alters cellular homeostasis and long-term features of human disease are not fully understood. Here, we aimed to investigate cellular stress responses in human trisomy syndromes, using fibroblasts and induced pluripotent stem cells (iPSCs). Dermal fibroblasts derived from patients with trisomy 21, 18 and 13 showed a severe impairment of cell proliferation and enhanced premature senescence. These phenomena were accompanied by perturbation of protein homeostasis, leading to the accumulation of protein aggregates. We found that treatment with sodium 4-phenylbutyrate (4-PBA), a chemical chaperone, decreased the protein aggregates in trisomy fibroblasts. Notably, 4-PBA treatment successfully prevented the progression of premature senescence in secondary fibroblasts derived from trisomy 21 iPSCs. Our study reveals aneuploidy-associated stress as a potential therapeutic target for human trisomies, including Down syndrome.

Background: People with intellectual disabilities (IDs) and their caregivers face difficulties during the COVID-19 pandemic. However, limited studies have comprehensively investigated their challenges, especially in Japan. We aimed to clarify the concerns and needs of people with IDs and their caregivers during the COVID-19 pandemic in Japan. Method: From March to August 2021, 27 in-depth interviews were conducted with principal caregivers of people with moderate to profound IDs in Japan. We then transcribed the interviews and conducted deductive coding using predetermined codes focused on their daily life difficulties. Inductive coding was used to ensure that no important themes were overlooked. Results: We found four concerns and four needs among people with IDs and their caregivers as significant themes. Conclusions: Our results provide useful information for supporting people with IDs and their caregivers, especially among those who need medical or social care in accordance with the infection control and social-distancing policies.

We recently found a constitutively active mutant of natriuretic peptide receptor 2 (caNPR2; V883M), which synthesizes larger amounts of cyclic guanosine monophosphate (cGMP) intracellularly without any ligand stimulation than existing drugs. The aim of this study was to investigate the therapeutic effects of gene transduction using caNPR2 for pulmonary arterial hypertension (PAH). In vitro gene transduction into human pulmonary arterial smooth muscle cells using Sendai virus (SeV) vectors carrying caNPR2 induced 10,000-fold increases in the synthesis of cGMP without ligand stimulation, and the proliferation of caNPR2-expressing cells was significantly attenuated. The PAH model rats generated by hypoxia and the administration of SU5416 were then treated with SeV vectors through a direct injection into the left pulmonary artery. Right ventricular systolic pressure was significantly decreased 2 weeks after the treatment, while systemic blood pressure remained unchanged. Histological analyses revealed that the medial wall thickness and occlusion rate of pulmonary arterioles were significantly improved in caNPR2-treated lungs. Neither the systemic integration of virus vectors nor side effects were observed. The massive stimulation of cGMP synthesis by gene therapy with caNPR2 was safe and effective in a PAH rat model and, thus, has potential as a novel therapy for patients with severe progressive PAH.