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Background: While previous literature suggests that multimorbidity is linked to a higher risk of mortality, evidence is scarce among individuals in middle adulthood. We aimed to examine the association between physical multimorbidity and all-cause mortality among individuals aged 40–64 years at baseline in Japan. Methods: Data were obtained from two cohort studies, the Japan Public Health Center-based Prospective Study (JPHC) and the Japan Epidemiology Collaboration on Occupational Health Study (J-ECOH). The study participants were 144,774 individuals aged 40–64 years at baseline who were followed up for a maximum of 29 and 10 years in the JPHC and J-ECOH, respectively. Multimorbidity was defined as the presence of ≥ 2 of 10 morbidities or conditions based on self-reported information. A Cox proportional hazards model was used to examine the association in relation to all-cause mortality. We calculated pooled hazard ratios (HR) and corresponding 95% confidence intervals (CI) using a random-effects meta-analysis model. Cause-specific analysis was performed using the JPHC dataset, which provided a sufficient number of events for mortality due to physical disorders, mental disorders/suicide, and unintentional injuries. Results: During a follow-up of 2,304,375 person-years in the JPHC and 311,637 person-years in the J-ECOH, 23,611 and 275 deaths were recorded, respectively. Participants with vs. without physical multimorbidity at baseline were more likely to die prematurely in both cohorts with a pooled HR of 1.61 (95%CI = 1.29–2.01). Cause-specific analyses among the JPHC participants revealed that physical multimorbidity at baseline was linked with mortality due to physical disorders, mortality due to mental disorders/suicide, and mortality due to unintentional injuries. Conclusions: Physical multimorbidity in middle adulthood is associated with an increased risk of all-cause mortality in Japan. [ABSTRACT FROM AUTHOR]

Aim: Driving cessation is strongly associated with adverse health outcomes in older adults. Although numerous studies have focused on driving skill interventions for safe driving, the effects of interventions on car accidents remain unclear. We designed a randomized controlled trial to examine the effects of driving skill training on the prevention of car accidents among community‐dwelling older adults using on‐road training. Methods: A total of 1408 community‐dwelling older drivers aged ≥65 years participated in the randomized controlled trial with blinded endpoint assessment. Participants randomized to the intervention group (n = 697) underwent four sessions, with 200 min re‐training focused on the problem of driving in the older people. Controls (n = 697) received one classroom education session. On‐road driving performance was assessed by certified driving school instructors in a driving school. The primary endpoint is an incident car accident, which will be detected based on the Japanese national car accident report data, after 24 months. Discussion: This study has the potential to provide the first evidence of the effectiveness of on‐road driving skill training regarding the prevention of car accidents. If our trial results show a lower number of car accidents due to driving skill training, this kind of intervention will provide an effective method for maintaining safe driving. These results will be disseminated to the appropriate national transportation agencies to improve or modify safe driving policies and possibly extend the validity of driver's licenses for older adults. Trial Registration: UMIN‐CTR (identification number: UMIN000034709). Registered 31 October 2018. Geriatr Gerontol Int 2024; 24: 1218–1222. [ABSTRACT FROM AUTHOR]

Background: QRS morphology can change during ventricular arrhythmias (VAs) with the appearance of bundle branch block (BBB). Methods: We retrospectively investigated 195 consecutive patients who underwent an initial ablation of VA. The study inclusion criteria were VAs that were successfully ablated in the outflow tract (OT) and in whom right bundle branch block (RBBB) was induced by catheter manipulation close to the His bundle area during sinus rhythm, before any radiofrequency application. We analyzed the QRS morphology of the VAs with and without RBBB during sinus beats. Results: Twenty‐four patients (age 59 ± 17 years, female 14) developed RBBB at some point during their procedure. The successful ablation sites of the VAs were the right ventricular outflow tract (RVOT) in 12 patients, pulmonary artery in one, left coronary cusp in five, right coronary cusp in three, right‐left cusp junction in two, and great cardiac vein in two. QRS‐morphology change was observed in five (20%) cases. The successful ablation sites in that group were the left coronary cusp in three cases, right coronary cusp in one, and RVOT septum in one. The QRS duration of the VAs increased during RBBB. Conclusions: There are some cases of OT‐VAs in which the QRS waveform changes with the appearance of catheter induced RBBB. We need to be aware that when QRS morphology changes during an OT‐VA ablation, it does not necessarily mean that the origin or exit of the VA has changed. [ABSTRACT FROM AUTHOR]

This study examines the possibility that interaction through social network platforms can serve as an informal means of developing intercultural competence among international students in higher education settings. Japanese students studying in the United States at a university in the Northwestern US were invited to participate in a mixed-method study involving interviews about their social network use and interactions, and a structured questionnaire measure of intercultural competence development. Overall, the results indicate that those in the top tertile of intercultural competence development tended to describe more proactive social ways and benefits of interacting with potential sources of support over social media, whereas those in the bottom tertile tended to describe the importance and use of social media for passive consumption of information. The implications for the incorporation of social network platforms into higher-education programs for internationalisation and intercultural competence development are discussed.

Background: Deltoid muscle detachment and atrophy have been reported to occur after shoulder surgery. Purpose: To investigate the 2-year changes in deltoid muscle structure and function after arthroscopic rotator cuff repair (ARCR) using magnetic resonance imaging (MRI) and electrophysical examination. Study Design: Case series; Level of evidence, 4. Methods: A total of 72 patients (72 shoulders) who underwent ARCR between 2015 and 2020 were enrolled. Whole deltoid muscle volume and regional (anterior, lateral, and posterior) muscle thicknesses were determined on T2-weighted MRI scans of both shoulders taken preoperatively and at 1, 3, 6, 12, and 24 months postoperatively, and their correlations with compound muscle action potentials (CMAPs), shoulder abduction muscle strength, and Constant scores were investigated. Comparison between groups was performed using paired or Student t tests, and the relationship between deltoid muscle volume and various factors was determined using Pearson correlation analysis. Results: The volume of the deltoid muscle on the affected side decreased from 44,369 ± 12,371 mm3 preoperatively to 38,139 ± 10,615 mm3 at 1 month postoperatively (P <.05), representing a 14% decrease. The deltoid muscle volume of the contralateral side also significantly decreased during the same time frame, from 43,278 ± 12,248 to 40,273 ± 11,464 mm3 (P <.05), representing a 7% decrease at 1 month postoperatively. Subsequently, the deltoid muscle volume on both sides recovered to preoperative levels at 12 months and was maintained at 24 months. Only the thickness of the anterior part of the deltoid was markedly decreased, from 13.9 ± 3.7 mm preoperatively to 12.0 ± 3.2 mm at 1 month postoperatively (P <.05), representing a 14% reduction. The CMAP amplitude showed a significant decrease at 1 month postoperatively; however, no significant difference was observed after 12 months when compared with the preoperative values or the values on the contralateral side. Positive correlations were found between deltoid muscle volume and CMAP amplitude at 24 months as well as between deltoid muscle volume and shoulder abduction muscle strength (R 2 = 0.698; P <.05) and Constant score (R 2 = 0.133; P <.05). Conclusion: Our study demonstrated that the early structural and functional decline of the deltoid muscle after ARCR was fully recovered within 1 year, confirming that this procedure does not negatively affect the deltoid muscle. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of this study is to examine the synergistic effect of adverse childhood experiences (ACEs) and economic challenges on suicide risk, under the coronavirus disease 2019 (COVID-19) pandemic, using a prospective population-based cohort study. Design/methodology/approach: Participants included 435 adults (aged from 18 to 92 years, mean = 53.8) from the Utsunomiya COVID-19 seROprevalence Neighborhood Association (U-CORONA) study, a population-based longitudinal study in Utsunomiya city, Japan. The baseline survey was conducted in June 2020, between the first and the second wave of the COVID-19 pandemic in Japan. ACEs were assessed using 13 items, and economic challenges due to the COVID-19 were assessed using one item. In the follow-up study, conducted in October 2020 between the second and the third wave of the COVID-19 pandemic in Japan, suicide risk was assessed using six items from the Mini-International Neuropsychiatric Interview via a self-reported questionnaire. Findings: This study found positive independent association between ACEs and economic challenges due to COVID-19 and suicide risk. Synergistic effects were also found: the participants with one ACE and economic challenges and those with 2+ ACEs and economic challenges were more likely to be at higher risk of suicide compared to those without ACEs and economic challenges. Originality/value: The findings suggest that adults with a higher number of ACEs, in addition to severe economic challenges, were more likely to be at risk for suicide during the COVID-19 pandemic. [ABSTRACT FROM AUTHOR]

Objectives This study aimed to investigate the association between falls and social frailty and its components among older Japanese adults. Methods This is a cross-sectional study. Participants were categorized into 3 groups based on the number of falls in the past year: no fall (none), a single fall (occasional), and more than one fall (recurrent). The participants who met 2 or more of the following criteria were defined as socially frail: living alone, going out less frequently compared with the previous year, rarely visiting friends, feeling unhelpful to friends or family, and not talking with someone daily. Results A total of 4,495 older Japanese adults living in a community analyzed in this study (51.0% women). Of the participants in this study, 3,851 (85.7%) were categorized as none, 443 (9.9%) as occasional, and 201 (4.5%) as recurrent. The proportion of participants considered socially frail was 11.5% in this study. Recurrent falls were associated with social frailty, even after adjusting for covariates (odds ratio [OR]: 1.49; 95% confidence interval [CI]: 1.01–2.19). The experience of recurrent falls was associated with the following components: "feeling unhelpful to friends and family" (OR: 1.62; 95% CI: 1.14–2.31) and "going outside less frequently compared with last year" (OR: 1.57; 95% CI: 1.06–2.31). Discussion Among older Japanese adults, recurrent falls were associated with social frailty and with 2 of its components in particular: social roles and social participation. Future longitudinal studies should be conducted to gain insight into any causal relationships between these variables. [ABSTRACT FROM AUTHOR]

Background: Thyroid storm (TS), a life-threatening condition that can damage multiple organs, has limited therapeutic options. Hypercytokinemia is a suggested background, but the pathological condition is unclear and there are no appropriate animal models. We aimed to develop a TS mouse model by administration of triiodothyronine and lipopolysaccharide, and then to examine the effects of ghrelin on this model. Methods: We evaluated the use of serum IL-6 levels as a representative marker of hypercytokinemia in patients with TS. To establish the mouse model, preliminary experiments were conducted to determine the non-lethal doses of triiodothyronine and lipopolysaccharide when administered individually. As a TS model, C57BL/6 mice were administered with triiodothyronine 1.0 mg/kg (subcutaneously, once daily for seven consecutive days) and lipopolysaccharide 0.5 mg/kg (intraperitoneally, on day 7) to develop a lethal model with approximately 30% survival on day 8. We assessed the survival ratio, mouse sepsis scores and blood biomarkers (IL-6, metanephrine, alanine aminotransferase) and evaluated the effects of ghrelin 300 µg/kg on these parameters in TS model. Results: Serum IL-6 was increased in patients with TS compared with those with Graves' disease as the diseased control (18.2 vs. 2.85 pg/mL, P <.05, n = 4 each). The dosage for the murine TS model was triiodothyronine 1.0 mg/kg and lipopolysaccharide 0.5 mg/kg. The TS model group had increased mouse sepsis score, serum IL-6, metanephrine and alanine aminotransferase. In this model, the ghrelin improved the survival rate to 66.7% (P <.01, vs. 0% [saline-treated group]) as well as the mouse sepsis score, and it decreased the serum IL-6 and metanephrine. Conclusion: We established an animal model of TS that exhibits pathophysiological states similar to human TS with induction of serum IL-6 and other biomarkers by administration of T3 and LPS. The results suggest the potential effectiveness of ghrelin for TS in humans. [ABSTRACT FROM AUTHOR]

Summary: Objectives: This study aimed to explore the association between the coronavirus disease (COVID‐19) pandemic and overweight incidence among preadolescent elementary school children in Japan. Methods: A population‐based longitudinal study was conducted in Adachi City, Tokyo, Japan, using data from the Adachi Child Health Impact of Living Difficulty (A‐CHILD) study. The control group (2016–2018) comprised 434 children, and the COVID‐19 exposure group (2018–2020) included 3500 children. Overweight was defined as a body mass index (BMI) z‐score of 1 SD or more according to the World Health Organization standards. The study design involved comparing BMI z‐scores before and after exposure to the pandemic, considering the associated lifestyle changes and potential consequences on physical activity, parental employment status and income. Results: By 6th grade, the prevalence of overweight increased from 17.7% to 19.2% in the control group and 22.5% to 29.5% in the COVID‐19 exposure group. Difference‐in‐differences analysis revealed that children's exposure to COVID‐19 significantly increased BMI z‐scores (coefficient 0.22, 95% confidence interval (CI) 0.14–0.29) and a higher odds ratio of overweight (odds ratio 2.51, 95% CI 1.12–5.62), even after adjusting for time‐varying covariates. Conclusion: The COVID‐19 pandemic has been associated with an increased prevalence of overweight among elementary school children in Japan. [ABSTRACT FROM AUTHOR]

Study Design: Retrospective study of data abstracted from the Diagnosis Procedure Combination (DPC) database. Purpose: This study aimed to investigate the effects of surgery in the early phase. Overview of Literature: The optimal timing of surgery for cervical fracture dislocation (CFD) remains unclear because only a few clinical studies with approximately 100 patients have been published. Methods: This study included 4,653 adult patients with a definitive diagnosis of CFD from the DPC database. The database contains nationwide inpatient data collected from >1,000 acute care hospitals in Japan. The DPC database contains information regarding hospitalization, such as diagnosis, treatment, medical history, complications, and hospitalization outcomes. This study identified 460 pairs of patients after one-to-one propensity-score matching (PSM). Treatment outcomes were compared between patients who underwent surgery for CFD within 72 hours (early group) and later (delayed group) after admission. The main outcomes included 30-day mortality, in-hospital death, and major complications. The secondary outcomes were improvement in the Barthel index, length of hospital stay, and discharged home rate. Results: After adjusting for PSM, the early group had a significantly higher 30-day mortality rates than the delayed group (3.0% vs. 0.4%, p=0.006). In the multivariate logistic regression analysis after PSM, the early group was associated with an increased risk of 30-day mortality (odds ratio, 8.05; 95% confidence interval, 2.15–5.26; p=0.007). Conclusions: This study indicated that early surgery for CFD resulted in increased 30-day mortality. [ABSTRACT FROM AUTHOR]

Background Published studies on mRNA coronavirus disease 2019 (COVID-19) vaccine effects focus on younger individuals, comprising the majority of the workforce. Studies in elderly adults are sparse. Methods In total, 107 subjects were recruited (median age 78; interquartile range [IQR], 58.5–90.5; range, 35–105 years). Factors associated with antibody titer after the third mRNA COVID-19 vaccination were compared between 49 elderly (age ≥80; median, 94; IQR, 86–97; range, 80–105 years) and 58 younger (age ≤79; median, 61; IQR, 46–71; range, 35–79 years) adults. Results Among body mass index (BMI) categories, the group of underweight elderly adults had a lower antibody titer compared to those with normal weight (P <.01 after 1, 3, and 5 months). Elderly adults were less likely to maintain effective antibody titer (≥4160 AU/mL) compared to younger adults: 76% versus 98%, P <.001 after 1 month, and 45% versus 78%, P <.001 after 3 months. Elderly adults who maintained effective antibody titer for 5 months had a higher BMI (22.9 kg/m2 vs 20.1 kg/m2, P =.02), and were less likely to have underweight BMI (0% vs 31%, P =.02) compared to the subjects who failed to maintain effective antibody titer. Conclusions These results highlight the impact of nutritional status and the deleterious effect of underweight BMI on antibody titer and its maintenance among elderly adults following booster mRNA COVID-19 vaccination. [ABSTRACT FROM AUTHOR]

Nursing management activities are important in influencing staff nurses' action to prevent or withdraw physical restraints. However, limited studies have been conducted empirically to determine the nursing management activities required for minimizing physical restraints. Therefore, there is a need for basic standards of nursing management activities to minimize physical restraints in acute care settings. This study aimed to develop nursing management indicators to minimize physical restraint (MaIN-PR) in hospitalized older adult patients in an acute care setting. It was conducted between June and October 2021 in Japan using a Delphi consensus approach. Fifty nurses working at top or middle management levels or as certified nurse specialists in gerontological nursing enrolled as participants. The potential indicators obtained from the literature review and interviews were organized inductively to develop two types of draft indicators: (1) 35 items for top management and (2) 33 items for middle management. We asked the nursing managers and certified nurse specialists in gerontological nursing to assess the validity of each indicator in three rounds. Of the 50 initial panelists, 12 from top management and 13 from middle management continued till the third round. MaIN-PR contained 35 indicators for top management and 28 indicators for middle management and were classified into the following six metrics: planning, motivating, training, commanding, organizing, and controlling. To the best of our knowledge, the current MaIN-PR are the first set of nursing management indicators for minimizing physical restraint, including perspectives on geriatric nursing in acute care settings. These indicators could guide both top and middle nursing management, thus supporting staff nurses' judgment in minimizing physical restraints to enhance the quality of older adult patient care. [ABSTRACT FROM AUTHOR]

Background: The magnitude and durability of cell-mediated immunity in older and severely frail individuals following coronavirus disease 2019 (COVID-19) vaccination remain unclear. A controlled immune response could be the key to preventing severe COVID-19; however, it is uncertain whether vaccination induces an anti-inflammatory cellular immune response. To address these issues, a 48-week-long prospective longitudinal study was conducted. A total of 106 infection-naive participants (57 long-term care facility [LTCF] residents [median age; 89.0 years], 28 outpatients [median age; 72.0 years], and 21 healthcare workers [median age; 51.0 years]) provided peripheral blood mononuclear cell (PBMC) samples for the assessment of spike-specific PBMC responses before primary vaccination, 24 weeks after primary vaccination, and three months after booster vaccination. Cellular immune responses to severe acute respiratory syndrome coronavirus 2 spike protein were examined by measuring interferon (IFN)-γ, tumor necrosis factor (TNF), interleukin (IL)-2, IL-4, IL-6, and IL-10 levels secreted from the spike protein peptide-stimulated PBMCs of participants. Results: LTCF residents exhibited significantly lower IFN-γ, TNF, IL-2, and IL-6 levels than healthcare workers after the primary vaccination. Booster vaccination increased IL-2 and IL-6 levels in LTCF residents comparable to those in healthcare workers, whereas IFN-γ and TNF levels in LTCF residents remained significantly lower than those in healthcare workers. IL-10 levels were not significantly different from the initial values after primary vaccination but increased significantly after booster vaccination in all subgroups. Multivariate analysis showed that age was negatively associated with IFN-γ, TNF, IL-2, and IL-6 levels but not with IL-10 levels. The levels of pro-inflammatory cytokines, including IFN-γ, TNF, IL-2, and IL-6, were positively correlated with humoral immune responses, whereas IL-10 levels were not. Conclusions: Older and severely frail individuals may exhibit diminished spike-specific PBMC responses following COVID-19 vaccination compared to the general population. A single booster vaccination may not adequately enhance cell-mediated immunity in older and severely frail individuals to a level comparable to that in the general population. Furthermore, booster vaccination may induce not only a pro-inflammatory cellular immune response but also an anti-inflammatory cellular immune response, potentially mitigating detrimental hyperinflammation. [ABSTRACT FROM AUTHOR]

Background: The clinical value of the trajectory of temporal changes in acute kidney injury (AKI) biomarkers has not been well established among intensive care unit (ICU) patients. Methods: This is a single-center, prospective observational study, performed at a mixed ICU in a teaching medical institute in Tokyo, Japan. Adult ICU patients with an arterial line and urethral catheter were enrolled from September 2014 to March 2015. Patients who stayed in the ICU for less than 48 h and patients with known end-stage renal disease were excluded from the study. Blood and urine samples were collected for measurement of AKI biomarkers at 0, 12, 24, and 48 h after ICU admission. The primary outcome was major adverse kidney events (MAKE) at discharge, defined as a composite of death, dialysis dependency, and persistent loss of kidney function (≥ 25% decline in eGFR). Results: The study included 156 patients. Serum creatinine-based estimated glomerular filtration rate (eGFR), plasma neutrophil gelatinase-associated lipocalin (NGAL), and urinary liver-type fatty acid-binding protein (uL-FABP) were serially measured and each variable was classified into three groups based on group-based trajectory modeling analysis. While the trajectory curves moved parallel to each other (i.e., "low," "middle," and "high") for eGFR and plasma NGAL, the uL-FABP curves showed distinct trajectory patterns and moved in different directions ("low and constant," "high and exponential decrease," and "high and exponential increase"). These trajectory patterns were significantly associated with MAKE. MAKE occurred in 16 (18%), 16 (40%), and 9 (100%) patients in the "low and constant," "high and exponential decrease," and "high and exponential increase" groups, respectively, based on uL-FABP levels (p-value < 0.001). The initial value and the 12-h change in uL-FABP were both significantly associated with MAKE, even after adjusting for eGFR [Odds ratio (95% confidence interval): 1.45 (1.17–1.83) and 1.43 (1.12–1.88) for increase of initial value and 12-h change of log-transformed uL-FABP by 1 point, respectively]. Conclusions: Trajectory pattern of serially measured urinary L-FABP was significantly associated with MAKE in ICU patients. [ABSTRACT FROM AUTHOR]

Introduction: This analysis of two Japanese clinical trials evaluated efficacy and safety after galcanezumab (GMB) discontinuation in patients with episodic migraine (EM) and chronic migraine (CM). Methods: Data were from a 6-month, randomized, double-blind, placebo [PBO]-controlled primary trial (patients with EM) and a 12-month open-label extension trial (patients with EM/CM). Patients received 6 months' (primary) or 12/18 months' (extension) treatment with GMB 120 mg (GMB120) plus 240-mg loading dose or 240 mg (GMB240) with 4 months' post-treatment follow-up. Efficacy was assessed as number of monthly migraine headache days during post-treatment. Safety was assessed via post-treatment-emergent adverse events (PTEAEs). Results: The analysis population included 186 patients from the primary trial (PBO N = 93; GMB120 N = 45; GMB240 N = 48), 220 patients with EM from the extension trial (PBO/GMB120 N = 57; PBO/GMB240 N = 55; GMB120/GMB120 N = 55; GMB240/GMB240 N = 53), and 55 patients with CM (GMB120 N = 28; GMB240 N = 27). In patients with EM receiving 6 months' GMB120, mean standard deviation (SD) monthly migraine headache days increased from 5.69 (4.64) at treatment end to 6.24 (4.37) at end of follow-up but did not return to pre-treatment levels (8.80 [2.96]). In the extension trial, mean monthly migraine headache days in patients with EM receiving GMB120 were 4.13 (3.85) after 12 months and 4.45 (3.78) at end of follow-up, and 3.59 (3.48) after 18 months and 3.91 (3.57) at end of follow-up. Monthly migraine headache days in patients with CM (12 months' GMB120) were 10.71 (4.61) at treatment end and 11.17 (5.64) at end of follow-up (pre-treatment 20.15 [4.65]). Similar results were seen for patients receiving GMB240. The most observed PTEAE after GMB discontinuation was nasopharyngitis. Conclusion: Galcanezumab exhibited post-treatment efficacy for up to 4 months in Japanese patients with EM and with CM. No unexpected safety signals were observed. Clinical Trial Registration: ClinicalTrials.gov, NCT02959177 and NCT02959190. [ABSTRACT FROM AUTHOR]

Iriomote Island is a small continental island hosting approximately 40 rivers characterized by short, steep-gradient streams and small waterfalls. We examined the population genetic structure and diversity of the freshwater prawn Macrobrachium shokitai Fujino & Baba, 1973 (Palaemonidae) using the mitochondrial cytochrome c oxidase subunit I (COI) gene sequence. Specimens were collected from 19 sites along ten rivers on the island, covering the known geographic distribution of the species. Haplotype and nucleotide diversities were very low within each river on the island. Nearly all haplotypes were exclusive to a given river, confirming distinct population structures among rivers at a small geographical scale. Slight genetic differentiation was discerned between the upper and lower sites of waterfalls in only the Yuchin River. Phylogenetic tree reconstruction, haplotype network, and principle coordinate analysis classified five clades roughly correspond to geographical groups in the western, southern, central, and northern regions of the island. Extreme caution should therefore be taken when translocating individuals to other rivers to avoid introducing genetic disturbance, even during conservation and mitigation efforts. [ABSTRACT FROM AUTHOR]

Background: This phase 2b/3, randomized, placebo‐controlled trial explored the efficacy and evaluated the safety of ensitrelvir. This trial involved individuals with asymptomatic infection with severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) and patients with mild symptoms of coronavirus disease 2019 (COVID‐19). Methods: The trial was conducted at 57 medical institutions in Japan, South Korea, and Vietnam (study period: January 6–August 14, 2022). Eligible participants were randomized (1:1:1) to the ensitrelvir 125‐mg, ensitrelvir 250‐mg, or placebo group, received the allocated intervention orally, and were followed up until Day 28. Participants self‐rated the severity of 14 typical COVID‐19 symptoms and recorded the data in an electronic diary. Results: In total, 572 participants (194, 189, and 189 in the ensitrelvir 125‐mg, ensitrelvir 250‐mg, and placebo groups, respectively) were included in the intention‐to‐treat population. Ensitrelvir 125‐mg group observed a 77% reduction in the risk of developing any of the 14 COVID‐19 symptoms or fever and a 29% reduction in the risk of worsening of such symptoms or fever versus placebo (statistically nonsignificant). The viral RNA, viral titer, and time to infectious viral clearance observed a statistically significant decrease versus placebo. Most treatment‐related adverse events (TEAEs) were mild to moderate in severity, and the most common TEAE observed across groups was a decrease in high‐density lipoprotein. Conclusions: Our exploratory results suggest a potential reduction in the risk of development or worsening of COVID‐19 symptoms with ensitrelvir. Ensitrelvir showed antiviral efficacy and was well tolerated. Trial Registration: Japan Registry of Clinical Trials identifier: jRCT2031210350. [ABSTRACT FROM AUTHOR]

Background: The early detection and prevention of many cancers is possible. Therefore, public awareness about cancer risk factors and warning signs must be increased to ensure early diagnosis. Although Japan has implemented mandatory cancer education in junior high and high schools, few studies have evaluated teachers' cancer awareness. This study aimed to determine Japanese junior high and high school teachers' awareness of cancer and related factors. Methods: This cross-sectional study obtained data through an online questionnaire survey using questions from the Cancer Awareness Measure (CAM) developed by Cancer Research UK. Thirty items were selected from three CAM modules: cancer risk factors, cancer warning signs, and barriers to seeking help. Descriptive statistics were used for socio-demografic data and CAM module questions. The χ2 test was performed on the relationship between cancer awareness and socio-demographic data. Multiple logistic regression analysis was used to identify factors influencing cancer awareness. Results: Respondents included 316 junior high school and 463 high school teachers (541 men; 238 women; average age = 48.2 years; average teaching experience = 23.5 years). An average of 5.41 out of 11 cancer risk factors were recognized. More than 70% of teachers recognized smoking, exposure to another person's cigarette smoke, and having a close relative with cancer as risk factors. On average, 4.52 out of 9 cancer warning signs were recognized. More than 50% of teachers recognized the warning signs of unexplained lump or swelling, unexplained weight loss, and unexplained bleeding. Barriers to seeking help had a low average score of 4.51 out of 20. However, the most commonly recognized "barriers to seeking help" were "too busy to make time," "difficult to make an appointment," "worried about what the doctor might find," and "too scared." Moreover, the common factors that affected awareness of cancer risk factors and cancer warning signs were gender and cancer experience of relatives. Factors that affected awareness of "barriers to seeking help" were "participation in cancer-related workshops," age, gender, and cancer experience of relatives. Conclusions: Cancer awareness education should consider interventions that can improve knowledge of the symptoms and signs related to cancer without increasing the awareness of barriers to seeking help. [ABSTRACT FROM AUTHOR]

The magnitude of the effect of human T‐lymphotropic virus 1 (HTLV‐1) infection on uveitis remains unclear. We conducted a cross‐sectional study in a highly endemic area of HTLV‐1 in Japan. The study included 4265 residents (men, 39.2%), mostly middle‐aged and older individuals with a mean age of 69.9 years, who participated in our surveys between April 2016 and September 2022. We identified HTLV‐1 carriers by screening using chemiluminescent enzyme immunoassays and confirmatory tests, and the proportion of carriers was 16.1%. Participants with uveitis were determined from the medical records of all hospitals and clinics where certified ophthalmologists practiced. We conducted logistic regression analyses in an age‐ and sex‐adjusted model to compute the odds ratio (OR) and 95% confidence interval (CI) of uveitis according to HTLV‐1 infection status. Thirty‐two (0.8%) participants had uveitis. For HTLV‐1 carriers, the age‐ and sex‐adjusted OR (95% CI) of uveitis was 3.27 (1.57–6.72) compared with noncarriers. In conclusion, HTLV‐1 infection was associated with a higher risk of uveitis among mostly middle‐aged and older Japanese residents in a highly endemic HTLV‐1 area. Our findings suggest that physicians who treat HTLV‐1 carriers should assess ocular symptoms, and those who diagnose patients with uveitis should consider HTLV‐1 infection. [ABSTRACT FROM AUTHOR]

Background: Retifanlimab is a humanized monoclonal antibody targeting programmed death protein‐1, and INCB001158 is an oral arginase inhibitor. This phase Ib study investigated retifanlimab, INCB001158, and their combination in Japanese patients with advanced solid tumors. Methods: Patients received retifanlimab (500 mg every 4 weeks [Q4W] i.v.) or escalating doses of INCB001158 (75 or 100 mg twice daily [BID]) monotherapy in Part 1 and combination of retifanlimab (500 mg Q4W) and INCB001158 (100 mg BID) in Part 2. Primary endpoints were safety, tolerability, dose‐limiting toxicities (DLTs), and determination of recommended phase II doses in Japanese patients. Results: Eighteen patients (retifanlimab or INCB001158 monotherapy and combination; n = 6 each) were enrolled at 2 sites in Japan. There were no DLTs, fatal adverse events (AEs), or discontinuations due to AEs. Rash (all grade 1) was the most common treatment‐emergent AE with retifanlimab (n = 6). Treatment‐related AEs were reported with retifanlimab (n = 4) or INCB001158 (n = 2) monotherapy and with combination (n = 4); an immune‐related AE (thyroid disorder, grade 2) was reported with combination. Two responses were observed with retifanlimab monotherapy (1 complete, 1 partial) and 1 stable disease (SD), for an overall response rate of 33.3% (95% confidence interval [CI], 4.3–77.7) and disease control rate (DCR) of 50% (95% CI, 11.8–88.2). Three patients had SD with INCB001158 monotherapy (DCR 50%; 95% CI, 11.8–88.2). No responses or SD were observed with combination therapy. Conclusion: Retifanlimab, INCB001158, and their combination had acceptable safety profiles. Promising retifanlimab antitumor activity warrants further investigation in Japanese patients. [ABSTRACT FROM AUTHOR]

African-clawed frogs (Xenopus laevis) are invasive to many aquatic ecosystems across the globe worldwide. For an accurate and efficient determination of their distribution, the use of environmental DNA (eDNA) could facilitate broad surveys rooted simply in the collection of water samples from inhabited water bodies. Therefore, in this study, using species-specific primers, an eDNA method was developed to evaluate the distribution of African-clawed frogs in Japan. This newly developed method was tested in ponds in Wakayama Prefecture, Japan, and compared with conventional cage trap surveys. Overall, we successfully developed the abovementioned eDNA method and it was shown to be as effective as the conventional capture-related technique. [ABSTRACT FROM AUTHOR]

Analyses of feeding patterns of fish assemblages, common approaches for understanding their habitat use and habitat dependence, have been conducted infrequently in Japanese estuarine salt marshes. The present study, based on gut content analyses, revealed the food habits of fishes occurring in salt marsh estuaries in high- and low-salinity rivers with different sediment conditions (sandy mud and muddy bottoms) in the western Seto Inland Sea, Japan. Ontogenetic changes in food preference were recognized in six species (Lateolabrax japonicus, Acanthogobius flavimanus, Glossogobius olivaceus, Platycephalus sp. 2, Acanthopagrus latus and Gymnogobius breunigii) out of 22 species examined, small individuals generally feeding on calanoid and harpacticoid copepods, and terrestrial and aquatic insects, but subsequently switching to other larger prey items (e.g., crabs, shrimps, and fishes) with growth. A cluster analysis based on dietary overlaps showed that the fish assemblages of the two salt marshes comprised nine trophic groups (zooplankton, small crustacean, large crustacean, polychaete, mollusk, fish, insect, detritus, and plant feeders), large crustacean feeders being the most abundant, followed by fish feeders, compared with polychaete and mollusk feeders, represented by only two and one species, respectively. The most important food items for the overall assemblage comprised shrimps, fishes and detritus, represented by high gut volumes in all fishes and high consumption frequencies. Furthermore, the trophic structures of fish assemblages and important food items varied between the rivers, polychaete and insect feeders being more abundant, with increasing the consumption of their main food items in the low-salinity and muddy river. Some fishes also showed remarkably different diets between adjacent rivers, highlighting small spatial scale variations in food-use patterns of fishes at the community and species levels in salt marsh estuaries. [ABSTRACT FROM AUTHOR]

Background: Social networks and social participation have protective effects on cognitive function maintenance and Alzheimer's disease and general dementia development. Objective: We aimed to investigate the association between conversations and dementia incidence in older adults. Methods: This longitudinal prospective cohort study used population data from the National Center for Geriatric and Gerontology–Study of Geriatric Syndromes (NCGG–SGS) from September 2015 to February 2017. The database included 4,167 individuals in Japan aged ≥60 years who were generally healthy and without major cognitive impairment. Participants were classified into two groups according to six daily conversation measures at baseline. The conversation index was calculated as a composite score for these measures. Participants were tracked monthly over 60 months for new-onset dementia. Results: Data from 2,531 participants were analyzed (72.7±6.7 years; range: 60–96 years). Dementia incidence per 1,000 person-years was 15.7 (95% confidence interval, 13.6–18.1). The Youden index determined the cut-off point for dementia incidence, with a conversation index of 16/17 points. The low conversation group included more participants with new-onset dementia. Cox proportional hazards regression crude models showed remarkable relationships between dementia onset and specific conversation measurements, including conversation index. According to the Cox regression adjusted model, the cut-off point of the conversation index showed only a remarkable relationship with dementia onset. Conclusions: Dementia risk was extensively associated with low daily conversation statuses. The assessment of conversational factors may be useful as a risk indicator for the development of Alzheimer's disease and general dementia. [ABSTRACT FROM AUTHOR]

Background. The Coccomyxa sp. strain KJ (Coccomyxa KJ), a microalga found in Japan, has a potential function in controlling viral infections. Recently, its dry powder has been marketed as a health food product. Objectives. This pilot study investigated the effects of Coccomyxa KJ powder tablet intake on allergic reactions and immune functions in healthy participants. Materials and methods. Nine healthy volunteers (4 males and 5 females) who expressed interest in foods containing Coccomyxa KJ, and were willing to undergo blood tests, were recruited. Each individual was asked to take 2 Coccomyxa KJ powder tablets (0.3 g) before breakfast once a day for 4 weeks. The salivary immunoglobulin A (IgA) level and blood parameters (white blood cell (WBC) count, eosinophil and lymphocyte counts and percentages, natural killer (NK) cell activity, interleukin (IL)-6 level, and T helper (Th)1/Th2 cell ratio) were evaluated at baseline and weeks 2 and 4. Results. The 4-week intake of Coccomyxa KJ did not affect salivary IgA levels, WBC count, eosinophil and lymphocyte counts and percentages, or the Th1/Th2 ratio. There were significant differences in the NK cell activity after 4 weeks, with an average increase of 11.78 (95% confidence interval (95% CI): 6.80-16.76). None of the patients experienced adverse reactions during or after the study. Conclusions. Long-term Coccomyxa KJ intake improved NK cell activity without causing adverse effects on the indicators of local immunity, systemic inflammation and immune response balance. This study suggests that Coccomyxa KJ powder tablets can induce beneficial immune modifications without causing any adverse effects. [ABSTRACT FROM AUTHOR]

The association between maternal pre-pregnancy obesity and child behavior problems has been widely researched, leaving a gap in understanding the positive aspects of children's mental health. The present study aimed to investigate the association between maternal pre-pregnancy body mass index (BMI) and resilience and prosociality among 6–7 year-old children in Japan. A retrospective cohort study was conducted using data from the Adachi Child Health Impact of Living Difficulty (A-CHILD) study, a population-based study in 2017 and 2019 including all first-grade students in public schools in Adachi, Tokyo, Japan (n = 7328, response rate = 84.7%). Resilience and prosociality were measured by the Children's Resilient Coping Scale and the Strength and Difficulties Questionnaire, respectively. Maternal pre-pregnancy weight and height were reported based on the Mother and Child Health Handbook, and BMI was categorized as underweight (BMI < 18.5), normal weight (BMI 18.5–24.9), overweight (BMI 25.0–29.9), and obesity (BMI ≥ 30). Linear regression models were employed to control for covariates. Maternal pre-pregnancy obesity was found to be negatively associated with child resilience (coefficient: − 3.29; 95% CI − 6.42–-0.15), while maternal underweight was negatively associated with child prosociality (coefficient: − 0.12; 95% CI − 0.24–-0.005) compared to mothers of pre-pregnancy normal BMI. Perinatal factors, such as gestational weight gain, gestational age, and birth weight, did not mediate the association. Our findings suggest that maternal pre-pregnancy obesity is linked to decreased resilience and maternal underweight is linked to decreased prosociality in children aged 6–7 years. Maintaining an appropriate BMI range before pregnancy may be crucial for enhancing resilience and prosociality of offspring. [ABSTRACT FROM AUTHOR]

This paper proposes a control method for step voltage regulators (SVRs) to avoid voltage violations in distribution systems with unbalanced voltages due to photovoltaic (PV) generation and electric vehicle (EV) charging. Distribution system operators must effectively address voltage problems resulting from the widespread installation of distributed energy resources under the optimizing the utilization of existing voltage regulators to establish an efficient and rational infrastructure. Therefore, this study focused on advancements in voltage control using SVR based on line‐drop compensator (LDC) control, which is widely used in actual operations. We propose a method that utilizes voltage data from information technology switches to detect and address voltage unbalances in the control section, allowing for the sequential adjustment of the monitoring target in LDC control to maintain appropriate voltage limits under unbalanced conditions. We conducted power flow calculations using a distribution system model that represents an actual distribution system in the Hokuriku area. The effectiveness of the proposed method was evaluated in terms of its impact on PV and EV hosting capacity, as well as the frequency of tap operations. © 2023 The Authors. IEEJ Transactions on Electrical and Electronic Engineering published by Institute of Electrical Engineer of Japan and Wiley Periodicals LLC. [ABSTRACT FROM AUTHOR]

Aim: The present study aimed to examine whether dietary diversity is associated with cognitive impairment, including mild cognitive impairment (MCI), in community‐dwelling older Japanese adults. Methods: This cross‐sectional study was carried out in a general community setting. MCI and global cognitive impairment (GCI) were assessed using the Mini‐Mental State Examination and National Center for Geriatrics and Gerontology‐Functional Assessment Tool, which are multicomponent neurocognitive tests that include memory attention, executive function and processing speed. Dietary diversity was assessed using the diet variety score. The diet variety score assessed the 1‐week consumption frequency of 10 food groups, and either 0 or 1 point was allocated to each category based on the following responses: (i) "eat almost every day" (1 point); and (ii) "not eaten almost daily" (0 points). Older adults with a diet variety score of ≥3 points were defined as having high dietary diversity. Results: Data included 8987 older adults (mean age 73.9 ± 5.5 years; men 44.3%). The overall prevalences of MCI and GCI were 17.1% (n = 1538) and 8.4% (n = 753), respectively. The proportion of patients with a high dietary diversity was 69.9% (n = 6286). Multinomial logistic regression analysis revealed high dietary diversity was associated with MCI (OR 0.83, 95% CI 0.73–0.94) and GCI (OR 0.77, 95% CI 0.65–0.92) after adjusting for covariates. Conclusions: This study had a large sample size of older Japanese adults, and showed that high dietary diversity was associated with a lower proportion of MCI and GCI among older adults. Geriatr Gerontol Int 2024; 24: 75–81. [ABSTRACT FROM AUTHOR]

The aim of the present study was to investigate changes in the gut microbiome both during and after consumption of malted rice amazake (MR-Amazake), a fermented food from Japan, in-home healthcare patients with disabilities, including patients with severe motor and intellectual disabilities. We monitored 12 patients who consumed MR-Amazake for 6 wk and investigated them before and after the intervention as well as 6 wk after the end of intake to compare their physical condition, diet, type of their medication, constipation assessment scale, and analysis of their comprehensive fecal microbiome using 16S rRNA sequencing. Their constipation symptoms were significantly alleviated, and principal coordinate analysis revealed that 30% of patients showed significant changes in the gut microbiome after MR-Amazake ingestion. Furthermore, Bifidobacterium was strongly associated with these changes. These changes were observed only during MR-Amazake intake; the original gut microbiome was restored when MR-Amazake intake was discontinued. These results suggest that 6 wk is a reasonable period of time for MRAmazake to change the human gut microbiome and that continuous consumption of MR-Amazake is required to sustain such changes. NEW & NOTEWORTHY The consumption of malted rice amazake (MR-Amazake) showed significant changes in the gut microbiome according to principal coordinate analysis in some home healthcare patients with disabilities, including those with severe motor and intellectual disabilities. After discontinuation of intake, the gut microbiome returned to its original state. This is the first pilot study to examine both the changes in the gut microbiome and their sustainability after MR-Amazake intake. [ABSTRACT FROM AUTHOR]

Background The genus Aeromonas is increasingly implicated in human infections, but knowledge of its clinical characteristics and antimicrobial resistance profiles has been limited owing to its complex taxonomy. Methods We conducted a multicenter prospective cohort study of patients with Aeromonas infections at hospitals across Japan. Patients were eligible for inclusion if they had an Aeromonas spp. strain in a clinical culture and were considered infected at the culture site. Clinical data were collected, and isolates underwent susceptibility testing and whole-genome sequencing. Results A total of 144 patients were included. Hepatobiliary infection accounted for a majority of infections (73% [105 of 144]), which mostly occurred in elderly patients with comorbid conditions, including hepatobiliary complications. The all-cause 30-day mortality rate was 10.0% (95% confidence interval, 4.9%–14.8%). By whole-genome sequencing, 141 strains (98%) belonged to 4 Aeromonas species —A caviae , A hydrophila , A veronii , and A dhakensis— with significant intraspecies diversity. A caviae was predominant in all infection sites except skin and soft tissue, for which A hydrophila was the prevailing species. The genes encoding chromosomally mediated class B, C, and D β-lactamases were harbored by 92%–100% of the isolates in a species-specific manner, but they often lacked association with resistance phenotypes. The activity of cefepime was reliable. All isolates of A hydrophila and A dhakensis carried an mcr-3- like colistin resistance gene and showed reduced susceptibility to colistin. Conclusions Hepatobiliary tract was the most common infection site of Aeromonas spp. with A caviae being the dominant causative species. The resistance genotype and phenotype were often incongruent for β-lactam agents. [ABSTRACT FROM AUTHOR]

Aim: Recent advances in natural language processing models are expected to provide diagnostic assistance in psychiatry from the history of present illness (HPI). However, existing studies have been limited, with the target diseases including only major diseases, small sample sizes, or no comparison with diagnoses made by psychiatrists to ensure accuracy. Therefore, we formulated an accurate diagnostic model that covers all psychiatric disorders. Methods: HPIs and diagnoses were extracted from discharge summaries of 2,642 cases at the Nara Medical University Hospital, Japan, from 21 May 2007, to 31 May 31 2021. The diagnoses were classified into 11 classes according to the code from ICD‐10 Chapter V. Using UTH‐BERT pre‐trained on the electronic medical records of the University of Tokyo Hospital, Japan, we predicted the main diagnoses at discharge based on HPIs and compared the concordance rate with the results of psychiatrists. The psychiatrists were divided into two groups: semi‐Designated with 3–4 years of experience and Residents with only 2 months of experience. Results: The model's match rate was 74.3%, compared to 71.5% for the semi‐Designated psychiatrists and 69.4% for the Residents. If the cases were limited to those correctly answered by the semi‐Designated group, the model and the Residents performed at 84.9% and 83.3%, respectively. Conclusion: We demonstrated that the model matched the diagnosis predicted from the HPI with a high probability to the principal diagnosis at discharge. Hence, the model can provide diagnostic suggestions in actual clinical practice. [ABSTRACT FROM AUTHOR]

Background: Rhabdomyosarcoma is the most common soft tissue sarcoma in children, but rare in adults. Para-meningeal rhabdomyosarcoma in head and neck (PM-HNRMS) is less applicable for surgery due to the anatomic reason. PM-HNRMS has a poor prognosis in children. However, its clinical outcomes remain unclear in adults due to the rarity. Further, there is almost no detailed data about salvage therapy. Methods: We retrospectively examined the adult patients with PM-HNRMS treated at institutions belonging to the Kyushu Medical Oncology Group from 2009 to 2022. We evaluated the overall survival (OS) and progression-free survival (PFS) of the patients who received a first-line therapy. We also reviewed the clinical outcomes of patients who progressed against a first-line therapy and received salvage therapy. Results: Total 11 patients of PM-HNRMS received a first-line therapy. The characteristics were as follows: median age: 38 years (range 25 – 63 years), histology (alveolar/spindle): 10/1, and risk group (intermediate/high): 7/4. As a first-line therapy, VAC and ARST0431-based regimen was performed in 10 and 1 patients, respectively. During a first-line therapy, definitive radiation for all lesions were performed in seven patients. The median PFS was 14.2 months (95%CI: 6.0 – 25.8 months): 17.1 months (95%CI: 6.0 – not reached (NR)) for patients with stage I-III and 8.5 months (95%CI: 5.2 – 25.8 months) for patients with stage IV. The 1-year and 3-year PFS rates were 54.5% and 11.3% for all patients. Median OS in all patients was 40.8 months (95%CI: 12.1 months–NR): 40.8 months (95%CI: 12.1 – NR) for patients with stage I-III and NR for patients with stage IV. The 5-year OS rate was 48.5% for all patients. Among seven patients who received salvage therapy, three are still alive, two of whom remain disease-free for over 4 years after completion of the last therapy. Those two patients received multi-modal therapy including local therapy for all detected lesions. Conclusion: The cure rate of adult PM-HNRMS is low in spite of a first-line therapy in this study. Salvage therapy might prolong the survival in patients who received the multi-modal therapy including local therapy for all detected lesions. [ABSTRACT FROM AUTHOR]

Japanese patients with very high‐risk cutaneous squamous cell carcinomas (cSCCs), based on the National Comprehensive Cancer Network guidelines, have been reported to display a higher cumulative incidence of relapse and disease‐specific death (DSD) than those with high‐risk cSCC. Therefore, prognosis prediction is crucial for Japanese patients with very high‐risk cSCCs. Herein, we aimed to evaluate the prognostic prediction ability of our novel Japanese Risk Factor Scoring Systems (JARF scoring) in a Japanese cohort of cSSC patients. Data of 424 Japanese patients with resectable very high‐risk cSCCs were analysed. We compared the prognostic ability of the following three staging systems: Brigham and Women's Hospital (BWH) tumour staging, number of NCCN very high‐risk factors, and JARF scoring, including recurrent tumour, high‐risk histological features, deep tumour invasion and lymphatic or vascular involvement as risk factors. The prognostic ability of these staging systems was evaluated according to the cumulative incidence of local recurrence (LR), regional lymph node metastasis (RLNM), DSD, and overall survival (OS). When BWH staging was used, high T stage led to significantly poor outcomes only in the cumulative incidence of RLNM (p = 0.01). The presence of very high‐risk NCCN factors led to significantly poor outcomes in terms of RLNM (p = 0.03) and OS (p = 0.02). Meanwhile, a high number of risk factors in the JARF scoring system clearly led to poor outcomes in terms of LR (p = 0.01), RLNM (p < 0.01), DSD (p = 0.03), and OS (p < 0.01). The JARF scoring system may accurately predict the risk of recurrence and death in very high‐risk cSCC patients in Japan. [ABSTRACT FROM AUTHOR]

Aim: This study aimed to develop a ward nurses' dietary support scale, including physical, psychological, and social background factors in preparation for older adult patients' life after discharge. Methods: We conducted a cross-sectional study using a self-reported questionnaire. Scale items were created based on a conceptual analysis, and refined by a Delphi survey. In total, 696 nurses across 16 acute care hospitals in Japan were eligible to participate. The questionnaire comprised 51 items that used a five-point Likert-type scale. These items were evaluated using exploratory factor analysis. Reliability was evaluated using Cronbach's alpha and intraclass correlation coefficients (ICC). Pearson's correlation coefficients were calculated to determine concurrent validity, and construct validity was analyzed using confirmatory factor analysis. Results: Altogether, 241 surveys were included in the data analysis; 236 nurses participated in both the test and the retest. The exploratory factor analysis identified 20 items from three factors as follows: "Assessment for healthy eating behavior," "Adjustment of the living environment, including family and caregiver, together with other professions," and "Continual frailty assessment." In the confirmatory factor analysis, the fitness indices supported these results. Cronbach's alpha was 0.932 and ICC was 0.867 for the overall scale. In the concurrent validity, the three factors had a moderate correlation (r = 0.295--0.537, P < .01 and r = 0.254--0.648, P < .01), except for one subscale. Conclusions: We developed a ward nurses' dietary support scale, including physical, psychological, and social background factors in preparation for older adult patients' life after discharge. Its reliability and validity were confirmed. [ABSTRACT FROM AUTHOR]

Abemaciclib-induced diarrhea (AID) impairs quality of life (QOL) and treatment adherence in patients with breast cancer. Supportive treatment with loperamide is associated with constipation. We hypothesized that probiotics and trimebutine maleate (TM) would decrease the frequency of AID without causing constipation. Hormone receptor-positive, human epidermal growth factor 2-negative advanced breast cancer patients were randomized into the probiotic Bifidobacterium (A) or probiotic Bifidobacterium and TM (B) groups. Endocrine therapy, Abemaciclib and probiotic Bifidobacterium three times a day for 28 days, was administered to both arms. Arm B was treated with TM upon the onset of diarrhea. The primary endpoint was the percentage of patients who experienced grade ≥2 diarrhea. The secondary endpoints were safety, frequency, and duration of all-grade diarrhea; frequency of emesis and constipation; usage of loperamide; and health-related QOL/patient-reported outcome during the study. We evaluated whether the primary endpoint of each arm exceeded the predetermined threshold. Fifty-one patients completed treatment. Grade 2 diarrhea occurred in 52% and 50% of patients in Arm A and Arm B, respectively. One patient experienced grade 3 diarrhea in each arm. The median duration of grade2 diarrhea was 2 and 2.5day, and only one patient required dose reduction. Grade ≥2 constipation was observed in 4% of Arm A and 3.6% of Arm B. Probiotic Bifidobacterium or the combination of probiotic Bifidobacterium with TM did not decrease the incidence of grade 2 or greater diarrhea compared with historical control, although the grade 3 or greater diarrhea was reduced. jRCT (Japan registry of clinical trials). jRCTs031190154. • We examined whether probiotic Bifidobacterium and TM would decrease AID frequency. • Probiotic Bifidobacterium and TM did not decrease the incidence of grade 2 or greater diarrhea. • The median duration of grade 2 diarrhea was 2 and 2.5 days in arms A and B; only one patient required dose reduction. [ABSTRACT FROM AUTHOR]

Little is known about antipsychotic prescription patterns among children and adolescents in Japan, particularly in outpatient settings. We investigated the prevalence and trends of antipsychotic prescription for outpatients aged ≤ 17 years receiving a first antipsychotic prescription from 2006 to 2012 based on a large-scale dispensation dataset. Measurements included age, sex, department of diagnosis and treatment, type of prescription (monotherapy or polytherapy), antipsychotic dosage, and concomitant psychotropic drugs. Of the 10,511 patients, 65.1% were aged 13–17 years, and 52.9% were males. Second-generation antipsychotic monotherapy prescriptions increased from 53.8% in 2006 to 78.3% in 2012. Risperidone was the most frequently prescribed antipsychotic, followed by aripiprazole and olanzapine. Approximately 25.0% of patients were prescribed an initial dose less than recommended. Second-generation antipsychotic monotherapy is currently the most frequent prescription pattern among outpatients aged ≤ 17 years receiving an initial antipsychotic prescription. [ABSTRACT FROM AUTHOR]

Background: Little League elbow, including humeral epicondylitis and osteochondritis dissecans, is a severe throwing injury in school-aged pitchers. Recent rule revisions have been implemented, and thus, prevention awareness may have increased. Purpose: To compare the incidence of elbow injury in 2011 from a previous study with that in 2021 and examine changes in the incidence and characteristics of players with elbow injuries. Study Design: Cross-sectional study; Level of evidence, 3. Methods: A survey based on the 2011 survey was conducted from September 1 to December 31, 2021, among 4060 third- to sixth-grade Little League players belonging to 203 teams in Kyoto, Japan. This survey included a 23-item checklist on physical condition and injury. The participants were classified into 2 groups according to the presence or absence of an elbow injury in the dominant arm during the season. The Wilcoxon rank-sum test was conducted to compare differences in basic information between the 2 groups. We also compared the differences in the 23 checklist items between the 2 groups using the chi-square or Fisher exact probability test. Results: Overall, 98 teams (1335 players; age range, 8-12 years) returned the questionnaires (collection rate, 32.9%). The final analysis population (excluding incomplete questionnaires) was 678 (mean age, 10.6 ± 1.1 years). Elbow injuries accounted for 30.7% of all injury sites in the players. Overall, 61 players (9.0%) reported elbow injuries in 2021 compared with 19.1% of the players in the 2011 survey (P <.01) A significantly higher percentage of players with elbow injuries had elbow pain in extension (item 2 on the survey checklist, P <.001) and flexion (item 4, P <.0024), were regular players (item 5, P =.0288), played baseball under fatigue (item 8, P =.0028), and had lower and upper limb inflexibility (item 17, P =.0379; item 18, P =.0146; and item 22, P =.0085). Conclusion: Study findings indicated that the incidence of elbow injuries has decreased significantly over the past 10 years, although the elbow joint still accounted for almost one-third of all injuries in Japanese youth baseball players. [ABSTRACT FROM AUTHOR]

Purpose: Many effective vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been developed, but a weaker response in individuals undergoing anticancer treatment has been reported. This study evaluates the immunogenic status and safety of SARS-CoV-2 vaccines for patients with non-small-cell lung cancer (NSCLC), receiving tegafur–uracil (UFT) as postoperative adjuvant chemotherapy. Methods: The subjects of this prospective study were 40 patients who underwent surgery for NSCLC and received SARS-CoV-2 vaccines postoperatively. We compared the antibody titers of SARS-CoV-2 vaccines and the adverse events between patients who received adjuvant UFT and patients who did not. Results: The mean anti-S1 IgG titers were not significantly different between the UFT and without-UFT groups (mean optimal density, 0.194 vs. 0.205; P = 0.76). Multivariate analysis identified the period after the second vaccination as an independent predictor of anti-S1 IgG titer (P = 0.049), but not the UFT status (with or without-UFT treatment; P = 0.47). The prevalence of adverse events did not differ significantly between the groups, and no severe adverse events occurred. Conclusions: The efficacy and safety of the SARS-CoV-2 vaccines for NSCLC patients who received postoperative adjuvant UFT chemotherapy were comparable to those for NSCLC patients who did not receive postoperative adjuvant UFT chemotherapy. Clinical trial registration: This study was registered with the University Hospital Medical Information Network (UMIN) in Japan (UMIN000047380). [ABSTRACT FROM AUTHOR]

Estimation of the population size is essential for understanding population dynamics. Estimating animal density using multiple methods and/or multiple attempts is required for accurate estimations. Raccoon dog Nyctereutes procyonoides is native to East Asia, including Japan, and has become an invasive species in Europe. Information on raccoon dog density in their native range is important to understand their invasion; however, relatively few studies have been conducted on raccoon dog density in their native range. In this study, we extracted DNA from fecal samples of raccoon dogs inhabiting a small island in Japan and conducted density estimation over two periods using DNA capture‐recapture methods: CAPWIRE and SECR. We also investigated sex ratio using genetic sex identification. Density estimates using SECR were approximately threefold different between the two study periods: 17.2 individuals per km2 in 2018 and 49.0 individuals per km2 in 2020. In contrast, estimates using CAPWIRE were relatively stable: 21.7 individuals per km2 in 2018 and 24.3 individuals per km2 in 2020. A drastic increase or decrease is not expected during the study period, and thus, density estimates using CAPWIRE are more reasonable than those using SECR. The small number of samples per individual might result in low accuracy of density estimates by SECR. The density estimated by CAPWIRE was similar to that in the main island in Japan and higher than that in Europe. Feeding competition with other omnivorous carnivores and/or predation risk by wolves might maintain the low density in Europe. The sex ratio of raccoon dogs was 1:1, which was similar to the values in invasive raccoon dogs and other canids. Further genetic census, including sex identification in various landscapes in their native and invasive range, will enable us to understand not only the ecology of raccoon dogs but also their adaptations to their invading areas. [ABSTRACT FROM AUTHOR]

Background: The effectiveness of fetal echocardiography in reducing the mortality from congenital heart disease (CHD) is largely unknown. Objectives: This study aimed to evaluate whether the widespread use of fetal echocardiography owing to the initiation of insurance coverage in Japan was associated with a decreasing trend in the annual number of CHD‐related deaths. Methods: Data regarding the number of deaths from CHD in infants aged <12 months were extracted from Japanese demographic statistics (2000–2018). Segmented regression analysis was performed on the interrupted time series data by stratifying the sample into CHD subgroups based on ICD‐10 classification and sex. Results: After the initiation of insurance coverage for fetal echocardiography in 2010, a decrease was observed in the trends of annual deaths in patients with congenital malformations of aortic and mitral valves (ratio of trends before and after the initiation of insurance coverage for fetal echocardiography 0.96, 95% confidence interval 0.93, 0.99). In this group, the decrease persisted after adjusting for annual total infant deaths and cardiac surgery mortality and in the analysis of trends in the proportion of deaths in this group per total CHD deaths. However, a decrease in trends was not observed in other patient groups with CHD. In the sex‐stratified analysis, a decrease was noted only in male patients with congenital malformations of aortic and mitral valves. Conclusions: The nationwide trend in annual CHD deaths decreased after the initiation of insurance coverage for fetal echocardiography only among patients with congenital malformation of aortic and mitral valves. These findings suggest that prenatal diagnosis with fetal echocardiography has led to improved mortality outcomes among these patients in Japan. [ABSTRACT FROM AUTHOR]

Background: Coronavirus disease 2019 (COVID-19) remains a threat to vulnerable populations such as long-term care facility (LTCF) residents, who are often older, severely frail, and have multiple comorbidities. Although associations have been investigated between COVID-19 mRNA vaccine immunogenicity, durability, and response to booster vaccination and chronological age, data on the association of clinical factors such as performance status, nutritional status, and underlying comorbidities other than chronological age are limited. Here, we evaluated the anti-spike IgG level and neutralizing activity against the wild-type virus and Delta and Omicron variants in the sera of LTCF residents, outpatients, and healthcare workers before the primary vaccination; at 8, 12, and 24 weeks after the primary vaccination; and approximately 3 months after the booster vaccination. This 48-week prospective longitudinal study was registered in the UMIN Clinical Trials Registry (Trial ID: UMIN000043558). Results: Of 114 infection-naïve participants (64 LTCF residents, 29 outpatients, and 21 healthcare workers), LTCF residents had substantially lower anti-spike IgG levels and neutralizing activity against the wild-type virus and Delta variant than outpatients and healthcare workers over 24 weeks after the primary vaccination. In LTCF residents, booster vaccination elicited neutralizing activity against the wild-type virus and Delta variant comparable to that in outpatients, whereas neutralizing activity against the Omicron variant was comparable to that in outpatients and healthcare workers. Multiple regression analyses showed that age was negatively correlated with anti-spike IgG levels and neutralizing activity against the wild-type virus and Delta variant after the primary vaccination. However, multivariate regression analysis revealed that poor performance status and hypoalbuminemia were more strongly associated with a lower humoral immune response than age, number of comorbidities, or sex after primary vaccination. Booster vaccination counteracted the negative effects of poor performance status and hypoalbuminemia on the humoral immune response. Conclusions: LTCF residents exhibited suboptimal immune responses following primary vaccination. Although older age is significantly associated with a lower humoral immune response, poor performance status and hypoalbuminemia are more strongly associated with a lower humoral immune response after primary vaccination. Thus, booster vaccination is beneficial for older adults, especially those with a poor performance status and hypoalbuminemia. [ABSTRACT FROM AUTHOR]

Aim: We aimed to verify the therapeutic efficacy and safety of stereotactic body radiotherapy (SBRT) for previously untreated initial small hepatocellular carcinoma (HCC) in a multicenter, retrospective study. Methods: Patients who underwent SBRT for HCC at the Japanese Society of Clinical Oncology (JCOG) member hospitals in Japan between July 2013 and December 2017 and met the following eligibility criteria were included: (1) initial HCC; (2) ≤3 nodules, ≤5 cm in diameter; (3) Child–Pugh score of A or B; and (4) unsuitability for or refusal of standard treatment. We analyzed the overall survival, recurrence‐free survival, and cumulative incidence of local recurrence rate, and adverse events directly related to SBRT. Results: Seventy‐three patients with 79 lesions from 14 hospitals were analyzed. The median age was 77 years (range: 50–89 years), and the median tumor size was 23 mm (range: 6–50 mm). The median radiation dose was 40 Gy (range: 35–60 Gy) in five fractions (range: 4–8). The median follow‐up period was 45 months (range: 0–103 months). The 3‐year overall survival, recurrence‐free survival, and cumulative incidence of local recurrence rates were 69.9% (95% CI: 58.7%–81%), 57.9% (95% CI: 45.2%–70.5%), and 20.0% (95% CI: 11.2%–30.5%), respectively. Four cases (5.5%) of adverse events of grade 3 or higher were reported: three cases of grade 3 and one case of grade 4 (duodenal ulcer). No grade 5 toxicities were observed. Conclusion: SBRT is a promising treatment modality, particularly for small HCCs, as they are not suitable for standard treatment. [ABSTRACT FROM AUTHOR]

As the occurrence of second primary cancers (SPCs) is strongly related to the survival rate of patients with oral and pharyngeal cancers, early detection and treatment are important. Therefore, this study aimed to clarify the incidence of SPCs and their risk factors in patients with oral and pharyngeal cancer. This observational study was conducted using data from the administrative claims database of 21,736 participants with oral and pharyngeal cancer from January 2005 to December 2020. We evaluated the cumulative incidence of SPCs among patients with oral and pharyngeal cancers using the Kaplan–Meier method. The Cox proportional-hazard model was used for multivariate analysis. Of the 1633 patients with oral and pharyngeal cancer who qualified for analysis, 388 developed SPCs (incidence rate, 7.994/1000 person-months). The multivariate analysis showed that the risk of developing SPCs was affected by age at diagnosis of oral and pharyngeal cancer, cancer treatment, and anatomical site of the primary cancer. Patients with oral and pharyngeal cancers are at a high risk of developing SPCs. The data from this study may be useful in providing accurate information to patients with oral and oropharyngeal cancer. [ABSTRACT FROM AUTHOR]

Background: Few studies have reported on the etiology, severity, or device usage of unilateral sensorineural hearing loss (UHL) compared to bilateral hearing loss. Therefore, this study investigated the characteristics of UHL in adults and children. Methods: We performed a survey using questionnaires for secondary and tertiary otolaryngology institutions. Results: We included 15,981 patients (1549 children and 14,432 adults) from 196 institutions with otolaryngology residency programs and 2844 patients (336 children and 2508 adults) from 27 institutions with board members of the Japan Audiology Society. The latter submitted audiological data. Among children, most diagnoses were made at age 0. Approximately half of them had profound hearing loss, and 37 children (2.2%) used hearing devices. Among adults, the number of cases increased with age, but decreased when people reached their 80s and 90s. More than half of them had moderate hearing loss. Sudden sensorineural hearing loss was the most common cause of UHL of all ages; 4.4% of UHL patients used hearing devices, and most of the device users (98.6%) selected a conventional hearing aid. Conclusions: Hearing aid use is limited in children and adults with UHL in Japan. There could be many candidates with UHL for intervention such as a cochlear implant. [ABSTRACT FROM AUTHOR]

Gastrointestinal stromal tumours (GISTs) are soft-tissue sarcomas of the gastrointestinal tract. Surgery is the standard treatment for localised disease, but the risk of relapse and progression to more advanced disease is substantial. Following the discovery of the molecular mechanisms underlying GISTs, targeted therapies for advanced GIST were developed, with the first being the tyrosine kinase inhibitor (TKI) imatinib. Imatinib is recommended in international guidelines as first-line therapy to reduce the risk of GIST relapse in high-risk patients, and for locally advanced, inoperable and metastatic disease. Unfortunately, imatinib resistance frequently occurs and, therefore, second-line (sunitinib) and third-line (regorafenib) TKIs have been developed. Treatment options are limited for patients with GIST that has progressed despite these therapies. A number of other TKIs for advanced/metastatic GIST have been approved in some countries. Ripretinib is approved as fourth-line treatment of GIST and avapritinib is approved for GIST harbouring specific genetic mutations, while larotrectinib and entrectinib are approved for solid tumours (including GIST) with specific genetic mutations. In Japan, pimitespib, a heat shock protein 90 (HSP90) inhibitor, is now available as a fourth-line therapy for GIST. Clinical studies of pimitespib have indicated that it has good efficacy and tolerability, importantly not displaying the ocular toxicity of previously developed HSP90 inhibitors. Additional approaches for advanced GIST have been investigated, including alternative uses of currently available TKIs (such as combination therapy), novel TKIs, antibody–drug conjugates, and immunotherapies. Given the poor prognosis of advanced GIST, the development of new therapies remains an important goal. [ABSTRACT FROM AUTHOR]

Environmental DNA (eDNA) has recently been developed for detecting the distribution of macroorganisms in aquatic systems and for estimating biomass/abundance. Although positive relationships between eDNA concentrations of species and biomass/abundance have been observed in previous studies, estimation of total biomass in a particular ecosystem based on eDNA concentration has not been investigated.To test this, we sampled eDNA from the littoral and pelagic zones of eight small ponds in Japan. Then, we drained ponds to capture all fish inhabiting each pond. We compared the eDNA copies measured by quantitative real‐time polymerase chain reaction analysis with the captured biomass of three dominant fish species (common carp, bluegill sunfish, and largemouth bass) obtained by direct capture. Differences in eDNA concentrations were compared between the littoral and pelagic zones of each pond.We found positive relationships between the eDNA copies and the whole captured biomass of all target species using Type II logarithmic equations, and the eDNA copies appeared to be saturated at a higher total biomass.We found positive correlations between the total number of eDNA copies and the total captured biomass of three fish species. This demonstrated the first step in estimating the population biomass of target fish species under natural conditions using eDNA measurement. [ABSTRACT FROM AUTHOR]

Aim: The effect of convection volume (CV) in patients on pre‐dilution online haemodiafiltration (Pre‐OL‐HDF) was evaluated. Methods: We conducted a retrospective, cross‐sectional study in 126 patients on Pre‐OL‐HDF. Dialysis conditions, laboratory data, and same day post‐dialysis body composition measurements using bioimpedance spectroscopy were assessed. Patients were divided into two groups according to their CV: ≥ median value and < median value. Linear regression analyses for reduction ratios (RRs) of β2‐microglobulin and α1‐microglobulin, and body composition, were conducted. Results: Age, dialysis vintage, and CVs of the study patients were 64 ± 12 years, 81 (48–154) months, and 43.2 (38.5–55.9) L/session, respectively. The higher CV (≥ 43 L/session) group (n = 66) had significantly higher RRs of β2‐microglobulin and α1‐microglobulin, lean tissue index, body cell mass index, total body water (TBW), extracellular water (ECW), and intracellular water (ICW) compared with the lower CV (< 43 L/session) group (n = 60, p <.01). Serum albumin and fat tissue index were not significantly different between the groups. CV/ECW, CV/TBW, and CV/ICW but not un‐adjusted CV, were significant determinants for β2‐microglobulin and α1‐microglobulin RRs (p <.05). Lean tissue and body cell mass indexes, but not the fat tissue index, showed significant associations with CV, and RRs of β2‐microglobulin and α1‐microglobulin (p < kb.05). Conclusions: Among patients on Pre‐OL‐HDF, higher values in the lean tissue index and body cell mass index were observed in those with higher CV versus lower CV, and CV adjusted to body water may be useful to prescribe individualized conditions for Pre‐OL‐HDF. SUMMARY AT A GLANCE: This retrospective study from Japan explores the effect of on line pre‐dilution haemodiafiltration with regard to the effect of delivered convection volume in relation to body composition using bioimpedance spectroscopy and reduction ratios of beta2‐microgloburin and alpha1‐microglobulin. [ABSTRACT FROM AUTHOR]

Assessment of risk-adjusted antibiotic use (AU) is recommended to evaluate antimicrobial stewardship programs (ASPs). We aimed to compare the amount and diversity of AU and antimicrobial susceptibility of nosocomial isolates between a 266-bed community hospital (CH) and a 963-bed tertiary care hospital (TCH) in Japan. The days of therapy/100 bed days (DOT) was measured for four classes of broad-spectrum antibiotics predominantly used for hospital-onset infections. The diversity of AU was evaluated using the modified antibiotic heterogeneity index (AHI). With 10% relative DOT for fluoroquinolones and 30% for each of the remaining three classes, the modified AHI equals 1. Multidrug resistance (MDR) was defined as resistance to ≥ 3 anti-Pseudomonas antibiotic classes. The DOT was significantly higher in the TCH than in the CH (10.85 ± 1.32 vs. 3.89 ± 0.93, p < 0.001). For risk-adjusted AU, the DOT was 6.90 ± 1.50 for acute-phase medical wards in the CH, and 8.35 ± 1.05 in the TCH excluding the hematology department. In contrast, the DOT of antibiotics for community-acquired infections was higher in the CH than that in the TCH. As quality assessment of AU, higher modified AHI was observed in the TCH than in the CH (0.832 ± 0.044 vs. 0.721 ± 0.106, p = 0.003), indicating more diverse use in the TCH. The MDR rate in gram-negative rods was 5.1% in the TCH and 3.4% in the CH (p = 0.453). No significant difference was demonstrated in the MDR rate for Pseudomonas aeruginosa and Enterobacteriaceae species between hospitals. Broad-spectrum antibiotics were used differently in the TCH and CH. However, an increased antibiotic burden in the TCH did not cause poor susceptibility, possibly because of diversified AU. Considering the different patient populations, benchmarking AU according to the facility type is promising for inter-hospital comparisons of ASPs. [ABSTRACT FROM AUTHOR]