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An in vitro organotypic culture model is needed to understand the complexities of carcinoma tissue consisting of carcinoma cells, stromal cells, and extracellular matrices. We developed a new in vitro model of carcinoma tissue using a rotary cell culture system with four disposable vessels (RCCSTM-4D) that provides a simulated microgravity condition. Solid collagen gels containing human pancreatic carcinoma NOR-P1 cells and fibroblasts or minced human pancreatic carcinoma tissue were cultured under a simulated microgravity condition or a static 1g condition for seven days. NOR-P1 cultures subjected to the simulated microgravity condition showed greater numbers of mitotic, cycling (Ki-67-positive), nuclear factor-κ B-activating cells, and a lower number of apoptotic cells than were shown by cultures subjected to the static 1g condition. In addition, human pancreatic carcinoma specimens cultured under the simulated microgravity condition maintained the heterogeneous composition and cellular activity (determined by the cycling cell ratio and mitotic index) of the original carcinoma tissue better than static culture conditions. This new 3-D rotary cell culture system with four disposal vessels may be useful for in vitro studies of complex pancreatic carcinoma tissue.

Background: Attention-deficit/hyperactivity disorder (ADHD) symptoms, including executive function, emotional regulation, and motivation, can persist into adulthood and are often associated with mental illnesses. Cognitive behavioral therapy (CBT) may help ADHD adults in Japan, but the lack of studies and the variability in group CBT approaches make its effects unclear. Japan lacks unified CBT programs and adult ADHD guidelines, making it difficult to implement international individual CBT recommendations due to cultural differences. This study will assess the feasibility of a novel CBT program for Japanese adult ADHD patients., Methods: This feasibility study will be open, nonrandomized, single-arm, multicenter study. Twelve ADHD patients aged 20-65 years who are currently receiving treatment will be included based on Conners' Adult ADHD Rating Scale (CAARS) clinical severity threshold. An intervention phase of 12-16 weeks and a 12-week follow-up will total 24-28 weeks for all participants. The intervention will use a new CBT program tailored to individual assessments., Results: The primary objective is to determine feasibility using dropout rates, adverse events, and CAARS score changes between Weeks 1 and 16. The secondary outcomes will assess long-term effects of treatment beyond the intervention period and provide descriptive statistics on sex, depression, quality of life, and autistic scores in relation to the intervention outcomes. The full analysis set and per protocol set will be used for statistical analysis., Conclusions: This study is essential for the development of CBT interventions in accordance with Japan's healthcare system that are tailored to the unique needs of its population., Competing Interests: Hisateru Tachimori and Hironori Kuga, PCNR Editors, are the Editorial Board members of Psychiatry and Clinical Neurosciences Reports and co‐authors of this article. To minimize the bias, they were excluded from all editorial decision‐making. The remaining authors declare no conflict of interest., (© 2024 The Author(s). Psychiatry and Clinical Neurosciences Reports published by John Wiley & Sons Australia, Ltd on behalf of Japanese Society of Psychiatry and Neurology.)

Background: To identify risk factors for mental distress and investigate whether the factors were different between men and women during the coronavirus disease 2019 (COVID-19), using KOKOROBO data, which is an online platform that aims to facilitate access to mental health services., Methods: We used baseline data on KOKOROBO users 13 years of age or older in Japan who accessed it from October 11, 2021, to April 6, 2023, excluding those receiving treatment for mental health problems. Global severity, based on the most severe measure on Patient Health Questionnaire-9 (PHQ-9), Generalized Anxiety Disorder-7 (GAD-7), and Insomnia Severity Index (ISI), was analyzed using multivariable logistic regression with baseline characteristics for each gender, and for under 30 and 30 years of age or older in women. We conducted the same analysis of suicidal ideation for each gender., Results: In the 686 men and 1274 women, 117 (17.1%) and 100 (7.8%) had minimal global severity respectively, and the rest suffered from mental distress to some extent. For women, ages under 30 years (adjusted OR (aOR): 0.352, 95%CI: 0.231-0.539, P < 0.001), marriage (aOR: 0.453, 95%CI: 0.274-0.746, P = 0.002), and concerns about COVID-19 infection were associated with global severity, while having children (aOR: 0.509, 95% CI: 0.284-0.909, P = 0.023) and decrease of going out during the COVID-19 pandemic had a protective effect on global severity and suicidal ideation for men, respectively. Living with family was a risk factor for mental distress in unmarried women over 30 years of age. Less communication with family or others and responding to the questionnaire late at night (00:00-05:59) were associated with severe global severity in both genders., Conclusions: Age, living arrangement, marriage, having children, concerns about COVID-19 infection, and lifestyle changes during the COVID-19 pandemic had gender-specific effects on mental distress, while frequent communication and regular life rhythm maintained mental health in both genders. Young women and, unmarried middle-aged women living with their families tended to experience mental distress during the COVID-19 pandemic., Trial Registration: The Ethics Committee of the National Center of Neurology and Psychiatry approved this study (approval number B2020141) on April 15, 2021., (© 2024. The Author(s).)

Purpose: Pancreatic adenosquamous carcinoma (PASC) is a subtype of pancreatic cancer with a poorer prognosis than pancreatic ductal carcinoma (PDAC). The pathogenesis of this histological subtype has not been fully explained due to its rarity., Methods: Of the 245 patients who underwent pancreatic resection for pancreatic cancer, six (2.3%) were diagnosed with PASC. They were retrospectively allocated to Group A (≥ 50% adenocarcinoma components) or Group S (≥ 50% squamous cell carcinoma components)., Results: The six patients with PASC were all males between the ages of 63 and 77 years, with tumors of 12 to 52 mm in diameter. Tumors were located in the pancreatic head (n = 2) and the pancreatic tail (n = 4). Relative to Group A, all three patients in Group S had larger tumors diameters, ≥ 40 mm with invasion to other organs. Cancer-specific survival of Group S was worse than that of the PDAC group (median survival, 1.5 years vs. 4.1 years). All patients in Group A were alive at the end of follow-up. Recurrence-free survival of Group S was inferior to that of the PDAC group (median survival, 0.2 years vs. 1.8 years; Group A, not defined). Immunohistochemistry revealed the MIB-1 positivity rate in squamous cell carcinoma regions was 1.8 times higher than that in adenocarcinoma regions in the same specimens., Conclusion: In PASC patients, an increased proportion of squamous cell carcinoma components was associated with aggressive behavior and a worse prognosis. This was due to the high MIB-1 positivity rate of squamous cell carcinoma components., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

The aim of this scoping review was to synthesize published studies and ongoing clinical trials of psychological interventions for mental health problems associated with COVID-19 infection. The study protocol was developed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) Extension for Scoping Reviews. We conducted systematic searches for studies published or registered between January 2020 and October 2022 using eight scientific databases and clinical trial registries, which identified 40 complete published studies and 53 ongoing clinical trials. We found that most studies were randomized controlled trials (74%) while the remaining used study designs of lower methodological quality. Most studies investigated interventions for acute COVID-19 patients (74%) and others explored post-COVID conditions (PCC) or recovered patients. Cognitive and behavioral therapies were the main intervention approaches (31%), followed by multidisciplinary programs (21%) and mindfulness (17%). The most frequently evaluated outcomes were anxiety (33%), depression (26%), quality of life (13%), and insomnia (10%). No studies on youths, older people, or marginalized communities were found. These findings summarize the burgeoning research on a range of psychological interventions for individuals infected with COVID-19. However, the field is in its infancy and further research to develop an evidence base for targeted care is necessary. The gaps identified in the current study also highlight the need for more research on youths, older people, and members of marginalized communities, and PCC patients. It is important to ascertain interventions and delivery strategies that are not only effective and affordable but also allow high scalability and accessibility., Competing Interests: Masaya Ito has received royalties for books and writings on psychological treatment from Shindan to Chiryo sha, Sogen sha, and several publishing companies in Japan. He has also received honorariums for workshops and supervision related to psychological treatments. Hironori Kuga is an Editorial Board member of Psychiatry and Clinical Neurosciences Reports and a co‐author of this article. To minimize bias, they were excluded from all editorial decision‐making related to the acceptance of this article for publication., (© 2024 The Author(s). Psychiatry and Clinical Neurosciences Reports published by John Wiley & Sons Australia, Ltd on behalf of Japanese Society of Psychiatry and Neurology.)

Competing Interests: Dr. Hironori Kuga is an Editorial Board member of Psychiatry and Clinical Neurosciences Reports and a co‐author of this article. To minimize bias, he was excluded from all editorial decision‐making related to the acceptance of this article for publication.

Objectives: To develop the Parenting Behavior Checklist to Promote Preschoolers' sleep (PCPP), quantify sleep-promoting parenting behaviors for children, and examine the scale's reliability and validity., Methods: The PCPP was developed based on the recommendations of the ABCs of SLEEPING for children's sleep, which is strongly supported by research evidence. Its validity and reliability were evaluated using data from 140 participants. Structural validity was estimated using exploratory factor analysis (EFA) and confirmatory factor analysis (CFA), and internal consistency was evaluated by Cronbach's α. Hypothesis testing was evaluated by analyzing the correlations between each factor of the Japanese Sleep Questionnaire for Preschoolers (JSQ-P) and the PCPP., Results: Regarding structural validity, EFA was conducted because CFA showed a poor model fit. The PCPP comprised one factor and six items. The JSQ-P subfactors of insomnia or circadian rhythm sleep-wake disorders, undesirable morning symptoms and behaviors, and insufficient sleep were moderately negatively correlated with the PCPP; the subfactor of undesirable daytime behaviors related to sleep problems was weakly negatively correlated with the PCPP. Thus, the sleep-promoting parenting behaviors listed in the PCPP were associated with better sleep in children., Conclusions: The PCPP showed sufficient reliability and validity. Future studies should use the scale to examine more effective interventions regarding sleep-promoting parental behaviors for children.

Aim: The Mental Health Supporter Training Program is a national project conducted in Japan. This study aimed to determine the effects on mental health-related stigma, mental health literacy, and knowledge about mental health difficulties and support techniques among program participants., Methods: The target population was local residents of a wide range of generations in Japan. Outcomes were assessed at baseline (T1), immediately postintervention (T2), and at the 6-month follow-up (T3). A mixed model for repeated-measures conditional growth model analyses were employed to examine the effects of the intervention over time (T1, T2, T3). We also calculated effect sizes using Cohen's d ., Results: The program had a significantly favorable pooled effect on the Japanese version of the Reported and Intended Behaviour Scale score after adjusting for covariates (reported behavior [ t  = 3.20, p  = 0.001]; intended behavior [ t  = 8.04, p  < 0.001]). However, when compared at each time point, only intended behavior from T1 to T2 showed a significant difference ( t  = 8.37, p  < 0.001). Significant pooled effects were found for mental health literacy (knowledge: t  = 19.85, p  < 0.001; attitude: t  = 15.02, p  < 0.001), knowledge of mental health ( t  = 28.04, p  < 0.001), and psychological distress ( t  = -2.41, p  = 0.016)., Conclusion: The results suggest that the program might be effective for improving intended, but not reported, behavior in the short term and for improving mental health literacy, knowledge of mental health, and psychological distress., Competing Interests: Dr Hironori Kuga is an Editorial Board member of Psychiatry and Clinical Neurosciences Reports and a co‐author of this article. To minimize bias, they were excluded from all editorial decision‐making related to the acceptance of this article for publication., (© 2024 The Authors. Psychiatry and Clinical Neurosciences Reports published by John Wiley & Sons Australia, Ltd on behalf of Japanese Society of Psychiatry and Neurology.)

Background: Recent advances in chemotherapy and chemoradiotherapy have enabled conversion surgery (CS) to be performed for selected patients with initially unresectable locally advanced (LA) pancreatic ductal adenocarcinoma (PDAC). Many studies indicate CS might extend the survival of patients with initially unresectable LA PDAC. However, several clinical questions concerning CS remain, such as the optimal preoperative treatment. Carbon-ion radiotherapy (CIRT) is a unique radiotherapy that offers higher biological effectiveness than conventional radiotherapy. Here, we report a long-term survival case with initially unresectable LA PDAC who underwent CS after chemotherapy followed by CIRT., Case Presentation: The patient was a 72-year-old Japanese woman with unresectable LA pancreatic head cancer with tumor contact to the superior mesenteric artery (SMA). She underwent four courses of chemotherapy (gemcitabine plus nanoparticle albumin-bound paclitaxel). However, the lesion did not shrink and tumor contact with the SMA did not improve after chemotherapy. Because the probability of achieving curative resection was judged to be low, she underwent radical dose CIRT, and chemotherapy was continued. She complained of vomiting 2 months after CIRT. Although imaging studies showed no tumor growth or metastasis, a duodenal obstruction which was speculated to be an adverse effect of CIRT was observed. She could not eat solid food and a trans-nasal feeding tube was inserted. Therapeutic intervention was required to enable enteral nutrition. We proposed several treatment options. She chose resection with the expectation of an anti-tumor effect of chemotherapy and CIRT rather than course observation with tube feeding or bypass surgery. Therefore, subtotal-stomach-preserving pancreatoduodenectomy with portal vein resection was performed as CS. Pathological examination of the resected specimen revealed an R0 resection with a histological response of Evans grade IIA. Postoperatively, she recovered uneventfully. Adjuvant chemotherapy with tegafur/gimeracil/oteracil (S1) was administrated. At the time of this report, 5 years have passed since the initial consultation and she has experienced no tumor recurrence., Conclusions: The present case suggests that multidisciplinary treatment consisting of a combination of recent chemotherapy and CIRT may be beneficial for unresectable LA PDAC. However, further studies are required to assess the true efficacy of this treatment strategy., (© 2024. The Author(s).)

Aim: The aim of this research was to create a scale to assess the competency of therapists who conduct group cognitive behavioral therapy (G-CBT). The scale is intended to serve as a tool to aid the training of therapists., Methods: Three stepped studies were conducted. Process 1: Through literature review and experts' consensus process, essential skills for G-CBT were articulated and categorized according to the criteria of the Cognitive Therapy Scale, a well-established rating scale for evaluating clinicians' skills in individual cognitive behavioral therapy. The list of those skills was organized into a rating scale. Process 2: Behavioral anchors were added to each skill and were classified by the levels of difficulty (beginner, intermediate, and advanced levels), based on the rating by G-CBT experts. Process 3: Inter-rater reliability and validity of the rating scale were examined in a sample of 41 videotaped G-CBT sessions of actual clinical sessions and educational role-plays., Results: The 12-item Group Cognitive Therapy Scale (G-CTS) was developed. It consists of 11 items that are adapted from the original Cognitive Therapy Scale, and a new 12th item called "Intervention using relationships with other participants," which describes therapists' skills to address group dynamics. The G-CTS showed excellent internal consistency (Cronbach's α : 0.95), satisfactory inter-rater reliability (interclass correlation coefficients: 0.65-0.88), and high predictive validity., Conclusion: A novel rating scale to evaluate therapists' competency in G-CBT was developed and successfully validated. The G-CTS behavioral checklist created in this study provides concrete guidelines that can be used by therapists to hone their skills in G-CBT., Competing Interests: The authors declare no conflict of interest., (© 2023 The Authors. Psychiatry and Clinical Neurosciences Reports published by John Wiley & Sons Australia, Ltd on behalf of Japanese Society of Psychiatry and Neurology.)

Frailty is considered one of the most important indicators of a patient's general condition. However, only a few studies have investigated the association between preoperative frailty and postoperative complications in pancreatic cancer. Therefore, this study aimed to examine this association in patients with pancreatic cancer. We retrospectively reviewed 52 consecutive patients who underwent pancreatectomy for pancreatic cancer between July 2019 and March 2021. Patients were classified into two groups according to the presence of postoperative complications. Their characteristics and clinical parameters, including physical function, were analyzed. Patients with postoperative complications had a higher prevalence of frailty (58.8% vs 14.3%, p = 0.003) and a shorter 6-min walk distance (380 m vs 436 m, p = 0.020) than those without postoperative complications. Logistic regression analysis identified preoperative frailty as the only independent risk factor for complications after pancreatectomy ( p = 0.002). Preoperative frailty is associated with postoperative complications of pancreatectomy. Since preoperative frailty can be easily evaluated, it is a useful predictor of postoperative complications after pancreatectomy., Competing Interests: The authors declare no conflicts of interest associated with this manuscript.

Background: Mixed neuroendocrine-non-neuroendocrine neoplasms of the ampulla of Vater are rare and heterogenous, making it difficult to achieve a definitive preoperative diagnosis. Herein, we describe a patient in whom a provisional diagnosis of mixed neuroendocrine-non-neuroendocrine neoplasm of the ampulla of Vater was made preoperatively., Case Presentation: Computed tomography revealed an enhancing periampullary tumor in a 69-year-old man with obstructive jaundice. Subsequent duodenoscopy revealed an ulcerated lesion in the swollen ampulla of Vater, from which six biopsies were collected. Pathological examination revealed adenocarcinoma in five of them. The remaining one was a neuroendocrine neoplasm according to immunohistochemical analysis. With a provisional diagnosis of mixed neuroendocrine-non-neuroendocrine neoplasm of the ampulla of Vater, the patient underwent subtotal stomach-preserving pancreaticoduodenectomy with modified Child's reconstruction and was discharged without complications. Pathological examination revealed both adenocarcinoma and neuroendocrine carcinomas, each accounting for ≥ 30% of the tumor, resulting in a definitive diagnosis of mixed neuroendocrine-non-neuroendocrine neoplasm of the ampulla of Vater. Lymph node metastases with neuroendocrine components were also observed. Adjuvant chemotherapy was not administered because of the patient's renal dysfunction. Liver and lymph node metastases were detected 2 months after surgery, the neuroendocrine component being considered responsible for that relapse. The patient underwent platinum-based chemotherapy at 50% dosage, which initially resulted in significant tumor shrinkage; however, he died 6 months after surgery., Conclusions: While these tumors' heterogeneity make definitive preoperative diagnosis of mixed neuroendocrine-non-neuroendocrine neoplasm of the ampulla of Vater difficult, the possibility of this disease can be considered by careful examination. Further study is needed to establish the optimal diagnostic criteria and treatment strategy., (© 2023. The Author(s).)

There is insufficient research on the usefulness of psychological interventions, such as psychological first aid (PFA), during outbreaks. We searched for and critically appraised systematic reviews that examined the effectiveness of PFA during infectious disease outbreaks, such as the novel coronavirus disease (COVID-19). Systematic reviews that examined the efficacy of PFA in the severe acute respiratory syndrome, Middle East respiratory syndrome coronavirus, Ebola virus disease, and COVID-19 outbreaks were searched through PubMed on February 19, 2021. The three included systematic reviews were critically appraised and assessed using AMSTAR-2. One review's overall confidence in its findings was evaluated as "high," which suggested that PFA training had a favorable effect on healthcare personnel. Furthermore, the review also demonstrated that PFA was commonly used during outbreaks and could be delivered through multiple methods, such as a phone or video call. Although it was anticipated that PFA would improve subjective well-being, reports showed no evidence of reduced depression or insomnia. Future studies should examine additional numbers of PFA recipients and conduct quasi-experimental studies to better understand the effectiveness of PFA. Evidence on its effectiveness in infectious disease outbreaks is still lacking, along with research and evaluation methods. Quasi-experimental studies, such as comparisons with other psychological interventions, are required to better understand the effectiveness of PFA., Competing Interests: Masahide Koda received a Grant‐in‐Aid for Early‐Career Scientists (JP19K19462) from the Japan Society for the Promotion of Science (JSPS), and a medical research grant from Pfizer Health Research Foundation. Toru Horinouch received a scholarship to study abroad from the Japan Epilepsy Research Foundation. Morio Aki received honoraria for lectures from Sumitomo Pharma Co., Ltd. Nozomu Oya, Akihisa Iriki, Kazufumi Yoshida, Yusuke Ogawa, Hironori Kuga, and Tomohiro Nakao have nothing to disclose. The authors declare no conflicts of interest., (© 2023 The Authors. Psychiatry and Clinical Neurosciences Reports published by John Wiley & Sons Australia, Ltd on behalf of Japanese Society of Psychiatry and Neurology.)

Background: This study aimed to develop a unique online infection prevention and control (IPC) training on Covid-19 for healthcare workers in psychiatric institutes in Japan and to examine its efficacy based on its impact on the knowledge, attitude, and confidence about IPC for Covid-19 among the healthcare workers., Method: This quasi-experimental study was conducted using online training on Covid-19 IPC for healthcare workers in various psychiatric institutes from April 2021 to March 2022. An online training video on Covid-19 IPC was developed. Voluntary healthcare workers in psychiatric institutes located in five prefectures in Japan were recruited to participate in this training. The participants then completed 30 min of online training and surveys about knowledge, attitude, and confidence were conducted pre, post, and three months after the training. The video training and surveys were contextually validated by the experts, but not by any previous study., Results: A total of 224 participants were included, of which 108 (54.0%) were men. The mean (standard deviation (SD)) age and the mean occupational experience were 47.4 (9.5) and 18.0 (12.6) years, respectively. Among the participants, 190 (84.8%) completed the post-training, and 131 (58.5%) completed the three-month-later training surveys. The total score on the quizzes in the post-training (+ 31.1%, SD 15.7, p-value < 0.01) and three-month-later training (+ 14.9%, SD 16.8, p-value < 0.01) surveys had significantly increased from that in the pre-training survey. In contrast, the total score in the three-month-later training had significantly decreased from that in the post-training survey (-16.1%, SD 16.7, p-value < 0.01)., Conclusion: Thirty minutes of online training about IPC for Covid-19 had improved knowledge, confidence, and attitude among psychiatric healthcare workers. Regular online training would help in preventing the transmission or formation of clusters of Covid-19 in psychiatric healthcare institutes., (© 2023. The Author(s).)

Introduction: Mental health symptoms such as depression, anxiety and sleep problems are commonly observed in individuals suffering from acute COVID-19 infection to post-COVID-19 syndrome. Studies have provided preliminary evidence for the efficacies of cognitive behavioural therapy, mindfulness-based interventions, acceptance and commitment therapy, and many other treatments for this population. Although there have been attempts to synthesise the literature on these psychological interventions, previous reviews have been limited in terms of the sources, symptoms and interventions that they included. Furthermore, most studies reviewed were conducted in early 2020, when COVID-19 had only recently been classified as a global pandemic. Since then, substantial research has been conducted. As such, we sought to provide an updated synthesis of the available evidence of treatments for the range of mental health symptoms associated with COVID-19., Methods and Analysis: This scoping review protocol was developed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews. Systematic searches were carried out on scientific databases (PubMed, Web of Science, PsycINFO and Scopus) and clinical trial registries (ClinicalTrials.gov, WHO ICTRP, EU Clinical Trials Register and Cochrane Central Register of Controlled Trials) to identify studies that have or will assess the efficacy or any aspects of psychological treatment for acute to post-COVID-19 syndrome. The search was conducted on 14 October 2022 and identified 17 855 potentially eligible sources/studies published since 1 January 2020 (duplicates removed). Six investigators will independently carry out titles and abstract screening, full-text screening and data charting and the results will be summarised using descriptive statistics and narrative synthesis., Ethics and Dissemination: Ethical approval is not required for this review. The results will be disseminated through a peer-reviewed journal, conference presentations and/or academic newspapers. This scoping review has been registered with Open Science Framework (https://osf.io/wvr5t)., Competing Interests: Competing interests: SK reports grants and personal fees from Inter Reha CO., Ltd., Kyowa Pharmaceutical Industry CO., Ltd., Sumitomo Pharma CO., Ltd., Otsuka Pharmaceutical CO., Ltd., Teijin Pharma Limited, and Viatris Inc., outside the submitted work. MI received royalties for books and writings regarding psychological treatment from Shindan to Chiryo sha, Sogen sha, and several publishing companies in Japan. He also received honorariums for workshops and supervisions regarding psychological treatments. HK receives honorariums for workshops from Heartland Shigisan hospital, general incorporated foundation. The remaining authors have no conflicts of interest to declare. The submission is certified that it is original work and is not under review at any other publication., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: The aim of this study was to evaluate the association between the degree of religiosity and subsequent fractures and a decrease in bone mineral density in a Japanese population., Methods: We conducted a retrospective longitudinal study at St. Luke's International Hospital in Tokyo, Japan, from 2005 to 2018. All participants who underwent voluntary health check-ups were included. Our outcomes were any fractures and the change in T-score from baseline to each visit. We compared these outcomes by the self-reported degree of religiosity (not at all; slightly; somewhat; very) and adjusted for potential confounders., Results: A total of 65,898 participants were included in our study. Their mean age was 46.2(SD:12.2) years, and 33,014(50.1%) were male. During a median follow-up of 2,500 days (interquartile range (IQR):987-3,970), 2,753(4.2%) experienced fractures, and their mean delta T-score was -0.03%(SD:18.3). In multivariable longitudinal analyses, the slightly religious group had a statistically lower adjusted odds ratio (AOR) for a fracture than the nonreligious group(AOR:0.81,95% confidence interval(CI):0.71 to 0.92)., Conclusions: We demonstrated that slightly religious people, but not somewhat or very religious people, had a lower incidence of fracture than nonreligious individuals, although the T-scores were similar regardless of the degree of religiosity., (© 2023. The Author(s).)

Background: A number studies have been conducted on abnormalities in the cortical circuitry of gamma oscillations, including deficit in auditory steady-state response (ASSR) to gamma-frequency (≧ 30-Hz) stimulation, in patients with bipolar disorder (BD). In the current study, we investigated neural responses during click stimulation by blood oxygen level-dependent (BOLD) signals. We focused on Broadman 41 and 42, the main sources of ASSR., Materials and Methods: We acquired BOLD responses elicited by click trains of 80-, 40-, 30- and 20-Hz frequencies from 25 patients with BD to 27 healthy controls (HC) with normal hearing between 22 and 59 years of age assessed via a standard general linear-model-based analysis. We extracted contrast values by identifying the primary auditory cortex and Brodmann areas 41 and 42 as regions of interest (ROI)s., Results: BD group showed significantly decreased ASSR-BOLD signals in response to 40-Hz stimuli compared to the HC group in the right Brodmann areas 41 and 42. We found significant negative correlations between the BOLD change in the right Brodmann areas 41 and 42 and Structured Interview Guide for the Hamilton Depression Rating Scale (SIGH-D) scores, also the BOLD change in the right Brodmann areas 41 and 42 and the Positive and Negative Syndrome Scale (PANSS)-Negative scores., Conclusion: The observed decrease in BOLD signal patterns in the right primary auditory cortex during 40-Hz ASSR may be a potential biomarker option for bipolar disorder., Competing Interests: SF was employed by Medical Corporation Kouseikai. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Okamoto, Onitsuka, Kuga, Oribe, Nakayama, Fukushima, Nakao and Ueno.)

Objective: Time-processing disorders in adults is a priority area for intervention. Time management program, which has been demonstrated to be effective in children with ADHD, has not been examined in adults. We anticipate the need for the development of specialized programs for adults. This is because it has been reported that time processing disorders have different patterns in childhood and adulthood. This study aimed to evaluate the therapeutic effect of a gCBT program focusing on time management for adults with ADHD., Method: Adults with ADHD were randomly assigned to gCBT ( n  = 24) or a treatment as usual group ( n  = 24). Outcome measures were masked clinically rated, self-reported, and family-reported ADHD symptoms., Results: The gCBT group significantly reduced ADHD symptoms on all measures., Conclusion: Interventions focused on time management have been shown to be effective not only in children with ADHD but also in adult patients.

The clinical importance of social cognition is well acknowledged in patients with psychosis, in particular those with first episode psychosis (FEP). Nevertheless, its brain substrates and circuitries remain elusive, lacking precise analysis between multimodal brain characteristics and behavioral sub-dimensions within social cognition. In the present study, we examined face processing of social cognition in 71 FEP patients and 77 healthy controls (HCs). We looked for a possible correlation between face processing and multimodal MRI characteristics such as resting-state functional connectivity (rsFC) and brain volume. We observed worse recognition accuracy, longer recognition response time, and longer memory response time in FEP patients when compared with HCs. Of these, memory response time was selectively correlated with specific rsFCs, which included the right subcallosal sub-region of BA24 in the ACC (scACC), only in FEP patients. The volume of this region was also correlated with memory response time in FEP patients. The scACC is functionally and structurally important in FEP-associated abnormalities of face processing measures in social cognition., (Copyright © 2021 Elsevier B.V. All rights reserved.)

The number of people with coronavirus disease (COVID-19) has been increasing worldwide. Anxiety about potential infection, fear of severe illness, death, economic problems, and loneliness and isolation brought on by social distancing are increasingly being experienced by people. Therefore, it is imperative to address and improve such mental health-related problems during COVID-19. We aimed to investigate the current mental health care and psychological intervention statuses related to COVID-19 in Japan. In a questionnaire survey, 55 of 69 (80%) mental health and welfare centers and 194 of 931 (21%) psychiatric institutions across Japan responded. COVID-19 patients, their family members, and the general public often consulted the mental health and welfare institutions through telephone. The questionnaire included various information of mental health difficulties related to COVID-19 such as the numbers and contents of the consultations, and the type of the interventions. The contents of consultation included psychological symptoms (anxiety, depression, insomnia, and alcohol problems) and psychosocial problems (interpersonal problems, prejudice, and discrimination). Overall, 9% of mental health and welfare centers provided psychological first aid as psychological intervention and 28% of consultations involved cases requiring urgent care. In Japan, consultations about COVID-19-related mental health problems occurred mainly in mental health and welfare centers. There is urgent need to establish a system that enables mental health triage and brief psychological interventions that are feasible in the centers.

Background: Teleost fish are known to respond to environmental manipulation, which makes them an ideal model animal for testing relationships between the environment and behavior. The Siamese fighting fish, Betta splendens, is a solitary, highly territorial fish that displays fierce stereotyped aggressive behavior toward conspecifics or members of other species. Adult fish, especially males, are generally housed in isolation in captivity. Here we report evidence that an enriched rearing environment can decrease the level of aggression in bettas and enable adults to be housed in groups., Results: B. splendens individuals were hatched in our laboratory and raised in groups in an enriched environment. At the juvenile or subadult stage, some individuals were relocated to a poor environment and kept in isolation. To evaluate aggression, a mirror-image test was conducted at the juvenile, subadult, and adult stages for each fish, and body parameters as well as plasma concentrations of 11-ketotestosterone, estradiol, and cortisol were evaluated. Male and female adult bettas raised in a group showed lower levels of aggression than other adult fish. The magnitude of threatening behavior was greater in adult bettas isolated as subadults, whereas the magnitude of fighting behavior was grater in adult bettas isolated as juveniles. The influence of rearing conditions on behavior was greater in females than in males. Plasma cortisol concentrations of adult bettas isolated as subadults after the mirror-image test were higher than those in other experimental groups. Adult males isolated as subadults had significantly higher plasma concentrations of 11-ketotestosterone than males raised in a group and isolated as juveniles. Females isolated as subadults had a higher gonadosomatic index than females raised in a group and females isolated as juveniles., Conclusions: These results indicate that bettas can be kept in a group under enriched environments and that the timing of isolation influences the aggression and sexual maturity of bettas. Female and male bettas responded differently to environmental manipulation. Judging from their level of sexual maturity, bettas isolated as subadults show proper development., (© 2021. The Author(s).)

Since patients with schizophrenia (SZ) and bipolar disorder (BD) share many biological features, detecting biomarkers that differentiate SZ and BD patients is crucial for optimized treatments. High-resolution magnetic resonance imaging (MRI) is suitable for detecting subtle brain structural differences in patients with psychiatric disorders. In the present study, we adopted a neuroanatomically defined and manually delineated region of interest (ROI) method to evaluate the amygdalae, hippocampi, Heschl's gyrus (HG), and planum temporale (PT), because these regions are crucial in the development of SZ and BD. ROI volumes were measured using high resolution MRI in 31 healthy subjects (HS), 23 SZ patients, and 21 BD patients. Right hippocampal volumes differed significantly among groups (HS > BD > SZ), whereas left hippocampal volumes were lower in SZ patients than in HS and BD patients (HS = BD > SZ). Volumes of the amygdalae, HG, and PT did not differ among the three groups. For clinical correlations, there were no significant associations between ROI volumes and demographics/clinical symptoms. Our study revealed significant lower hippocampal volume in patients with SZ and BD, and we suggest that the right hippocampal volume is a potential biomarker for differentiation between SZ and BD.

Elevated serum uric acid is a cardiovascular risk factor in patients with hypertension, even when blood pressure (BP) is well controlled. Xanthine oxidoreductase inhibitors (XORi) reduce serum uric acid levels and have several other potential effects. This multicenter, randomized, open-label study compared the effects of two XORi, topiroxostat and febuxostat, on arterial stiffness, uric acid levels, and BP in hypertensive patients with hyperuricemia. Patients received topiroxostat 40-160 mg/day or febuxostat 10-60 mg/day, titrated to maintain serum uric acid <6 mg/dl, for 24 weeks. The primary endpoint was change in the cardio-ankle vascular index (CAVI) from baseline to 24 weeks. There were no significant changes in CAVI from baseline to 24 weeks (from 9.13 to 9.16 [feboxustat] and 8.98 to 9.01 [topiroxostat]). Compared with baseline, there were significant reductions in serum uric acid (-2.9 and -2.5 mg/dl; both p < 0.001) and morning home systolic BP (-3.6 and -5.1 mm Hg; both p < 0.01) after 24 weeks' treatment with febuxostat and topiroxostat. BP decreased to the greatest extent in the subgroup of patients with uncontrolled blood pressure at baseline. Topiroxostat, but not febuxostat, significantly decreased plasma xanthine oxidoreductase activity versus baseline. The urinary albumin-creatinine ratio (UACR) decreased significantly from baseline to 24 weeks with topiroxostat (-20.8%; p = 0.021), but not febuxostat (-8.8%; p = 0.362). In conclusion, neither topiroxostat nor febuxostat had any significant effects on arterial stiffness over 24 weeks' treatment., (© 2021 The Authors. The Journal of Clinical Hypertension published by Wiley Periodicals LLC.)

In this study, we compare the results of a cross-sectional survey and secular changes between toner-handling workers and non-toner-handling workers, focusing on blood tests, urinalysis, respiratory function tests, and chest imaging results as indices of health effects. Of 116 employees who participated in the survey conducted at an office equipment manufacturer in Japan, 65 male employees who could be followed up for 10 years were included in the analysis. Thirty-eight workers engaged in toner-handling operations were considered toner-handling workers, and 27 not engaged in these operations were considered non-toner-handling workers. The blood tests (WBC, CRP, IgE, KL-6, and SP-D), urinalysis (8-OHdG), respiratory function tests (PEFR, VC, %VC, FEV 1.0 , and FEV 1.0% ), chest radiography, and chest CT results were compared between both groups. Non-toner-handling workers had significantly higher 8-OHdG/Cre at baseline and KL-6 at year 10 than did toner-handling workers. There were no significant differences between the results of the cross-sectional survey and a longitudinal survey of respiratory function test results. We conclude that there were no adverse health effects due to toner exposure.

Trastuzumab deruxtecan (T-DXd, DS-8201a) is an antibody-drug conjugate (ADC), comprising an anti-HER2 antibody (Ab) at a drug-to-Ab ratio of 7-8 with the topoisomerase I inhibitor DXd. In this study, we investigated the pharmacokinetics (PK), biodistribution, catabolism, and excretion profiles of T-DXd in HER2-positive tumour-bearing mice.Following intravenous (iv) administration of T-DXd, the PK profiles of T-DXd and total Ab (the sum of conjugated and unconjugated Ab) were almost similar, indicating that the linker is stable during circulation. Biodistribution studies using radiolabelled T-DXd demonstrated tumour-specific distribution and long-term retention. DXd was the main catabolite released from T-DXd in tumours, with exposure levels at least five times higher than those in normal tissues and seven times higher than those achieved by non-targeted control ADC. Following iv administration of DXd, it was rapidly cleared from the circulation ( T ; 1.35 h) and excreted mainly through faeces as its intact form.The PK profiles reveal that T-DXd effectively delivers the expected payload, DXd, to tumours, while minimising payload exposure to the systemic circulation and normal tissues. The released DXd is rapidly cleared from systemic circulation, presumably via the bile with negligible metabolism, and excreted through the faeces.1/2 ; 1.35 h) and excreted mainly through faeces as its intact form.The PK profiles reveal that T-DXd effectively delivers the expected payload, DXd, to tumours, while minimising payload exposure to the systemic circulation and normal tissues. The released DXd is rapidly cleared from systemic circulation, presumably via the bile with negligible metabolism, and excreted through the faeces.

There may be different neural bases between subjects with epilepsy only (EP) and interictal chronic epilepsy psychosis (EPS). However, there have been few structural MRI studies of EPS. The current study was conducted to investigate the neural substrate of EPS. T1-weighted images were analyzed in 14 patients with EPS and 14 strictly-matched patients with EP. We conducted volume comparison in the whole brain using voxel-based morphometry (VBM). The VBM method revealed that EPS patients exhibited significantly reduced gray matter volumes in the left postcentral gyrus and the left supra marginal gyrus compared with EP patients (adjusted p = 0.029, FDR corrected q; k = 319 voxels). For clinical correlations, there were no significant associations between psychotic symptoms and gray matter volumes in the left postcentral gyrus and the left supra marginal gyrus. VBM analysis revealed that reduced gray matter volumes in the left postcentral gyrus and the left supra marginal gyrus may be crucial regions for EPS.

Patients with alcohol use disorder (AUD) have difficulty controlling their alcohol cravings and thus exhibit increased use and early relapse. Although patients tend to respond more strongly to alcohol-related images than to non-alcohol-related images, few researchers have examined the factors that modulate cravings. Here, we examined whole-brain blood oxygen level-dependent (BOLD) responses to behavioural cues in individuals with AUD and in healthy controls (HCs). The participants included 24 patients with AUD and 15 HCs. We presented visual cues consisting of four beverage-related images (juice, drinking juice, sake, and drinking sake), and the cue reactivity of AUD participants was contrasted with that of HC participants. Multiple comparisons revealed that the AUD group had lower BOLD responses than the HC group in the left precuneus (p = 0.036) and the left posterior cingulate cortex (PCC) (p = 0.044) to images of drinking juice and higher BOLD responses than the HC group in the left PCC (p = 0.044) to images of drinking sake. Furthermore, compared to the HCs, the AUD patients had decreased BOLD responses associated with cue reactivity to drinking juice in the left precuneus during the periods from 15 to 18 s (p = 0.004, df = 37) and 18 to 21 s (p = 0.002, df = 37). Our findings suggest that HCs and AUD patients differ in their responses not to images of alcoholic beverages but to images related to alcohol-drinking behaviour. Thus, these patients appear to have different patterns of brain activity. This information may aid clinicians in developing treatments for patients with AUD., Competing Interests: The authors have declared that no competing interests exist.

Hemodynamics is subject to change after eating meals, which may be related to various postprandial physical statuses such as hypotension or daytime sleepiness. Previous studies have shown that blood flow in the superior mesenteric artery (SMA) increases after meals, but conflicting results have been reported regarding blood flow in the common carotid artery (CCA). In those studies, the fasting interval before the meal was not taken into account. For example, eating breakfast shortly before lunch may affect hemodynamics in these vessels. The present study therefore investigated hemodynamics in the CCA and SMA after lunch, comparing cases with and without breakfast. Subjects comprised 24 healthy young adults (mean age, 22 ± 1 years). Duplex Doppler sonography was performed to measure blood flow values for calculating flow volume (FV) before and after lunch until 3 h postprandially, on each day with breakfast and without breakfast, respectively, in every subject. Net FV after lunch did not differ between cases with and without breakfast, either in the SMA or in the CCA. Blood FV in the SMA was significantly increased after eating lunch regardless of whether breakfast was eaten (P<0·05 each). However, FV in the CCA was significantly decreased until 1 h after lunch compared with the preprandial state in cases without breakfast (P<0·05), but not in cases with breakfast. In conclusion, a sudden decrease in FV in the CCA from the preprandial state is seen after lunch when breakfast is skipped., (© 2018 Scandinavian Society of Clinical Physiology and Nuclear Medicine. Published by John Wiley & Sons Ltd.)

Objectives: Earthquakes are a distressing natural phenomenon that can disrupt normal health-related behaviours. The aim of this study was to investigate changes in alcohol consumption behaviours in the immediate aftermath of mild to moderate earthquakes., Setting: This retrospective cohort study was conducted at a large academic hospital in Tokyo, Japan from April 2004 to March 2017., Participants: We included all adult patients presenting with acute alcohol intoxication in the emergency room., Primary and Secondary Outcome Measures: Our outcome was the number of such patients per 24 hours period comparing days with and without earthquake activity. We mainly focused on mild to moderate earthquakes (Shindo scale of less than 3). We conducted a simple generalised autoregressive conditional heteroscedasticity (GARCH) analysis, followed by a multivariate GARCH, including year-fixed effects and secular changes in alcohol taxation. Subanalyses were conducted by gender and age group., Results: During the study period, 706 earthquakes were observed with a median Shindo scale of 2 (IQR: 1). During this period, 6395 patients were admitted with acute ethanol intoxication; the mean age was 42.6 (SD: 16.9) years and 4592 (71.8%) patients were male. In univariate analyses, the occurrence of daytime earthquakes was marginally inversely related to the number of acutely intoxicated patients (β coefficient: -0.19, 95% CI -0.40 to 0.01). This finding remained similar in multivariate analyses after adjustment for covariates. In analyses stratified by gender, the inverse association between daytime earthquakes and alcohol intoxication was only observed among men (p<0.03 for males and p=0.99 for females). In subanalyses by age, older people were less likely to be admitted to the hospital due to acute alcohol intoxication on days with daytime earthquakes (p=0.11), but this was not the case for younger people (p=0.36)., Conclusion: On days when a mild to moderate daytime earthquake occurred, the number of patients with acute alcohol intoxication was lower compared with days without earthquakes. Even milder forms of potentially catastrophic events appear to influence social behaviour; mild to moderate earthquake activity is associated with the avoidance of excessive alcohol consumption., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objectives: This report shows the relationship between toner exposure and respiratory effects for individuals with a longterm occupational toner-handling history, from 2004 to 2013., Material and Methods: Authors studied 752 Japanese male workers in toner handling workshops. A total of 673 men who participated in an annual monitoring survey were analyzed in this study. The following monitoring was performed in the same season each year: personal exposure measurements, biological markers, respiratory function tests, a chest X-ray, chronic respiratory symptoms and incidences of respiratory diseases. To evaluate the toner exposure effect, the exposure categories suitable for each evaluation index were established., Results: For those with an occupational toner-handling history, the mean occupational toner-handling period was 14.36 years (standard deviation = 6.62); one participant had 35 years of exposure, which was the longest and one participant had 1 year of exposure which was the shortest. There were no statistically significant differences in the rate of change of respiratory function tests. An ANOVA conducted on blood and urine test results showed that statistically significantly differences were observed for a few items but all the values were very low and within the standard range., Conclusions: Authors conducted a 10-year ongoing study, but no obvious negative influences on health were attributed to toner exposure. In a work environment where adequate administrative controls are in place, personal toner exposure levels may be expected to be low, with no adverse effects on human health. Int J Occup Med Environ Health 2018;31(6):809-822., (This work is available in Open Access model and licensed under a CC BY-NC 3.0 PL license.)

Identification of biological markers for defining subtypes of major depressive disorder (MDD) is critical for better understanding MDD pathophysiology and finding effective treatment intervention. The " Yin and Yang " theory is a fundamental concept of traditional Chinese Medicine (TCM). The theory differentiates MDD patients into two subtypes, Yin and Yang , based on their somatic symptoms, which had empirically been used for the delivery of effective treatment in East Asia. Nonetheless, neural processes underlying Yin and Yang types in MDD are poorly understood. In this study, we aim to provide physiological evidence using functional magnetic resonance imaging (fMRI) to identify altered resting-state brain activity associated with Yin and Yang types in drug-naïve MDD patients. The Yin type and Yang type MDD patients showed increased amplitude of low-frequency fluctuation (ALFF) in different cortical brain areas in the parietal, temporal, and frontal lobe, compared to matched healthy controls. Differential ALFF is also observed in several cortical areas in frontal lobe and insula between Yin and Yang type group. Of note, although ALFF is increased in the inferior parietal lobe in both Yin and Yang type group, inferior parietal lobe-centered functional connectivity (FC) is increased in Yang type, but is decreased in Ying type, compared with matched healthy controls. These results suggest that differential resting-state brain activity and functional connectivity in Yin and Yang types may contribute to biological measures for better stratification of heterogeneous MDD patients.

Background: Suicide is a crucial global health concern and effective suicide prevention has long been warranted. Mental illness, especially depression is the highest risk factor of suicide. Suicidal risk is increased in people not only with mental illness but also with physical illnesses, thus medical staff caring for physically-ill patients are also required to manage people with suicidal risk. In the present study, we evaluated our newly developed suicide intervention program among medical staff., Methods: We developed a 2-h suicide intervention program for medical staff, based on the Mental Health First Aid (MHFA), which had originally been developed for the general population. We conducted this program for 74 medical staff members from 2 hospitals. Changes in knowledge, perceived skills, and confidence in early intervention of depression and suicide-prevention were evaluated using self-reported questionnaires at 3 points; pre-program, immediately after the program, and 1 month after program., Results: This suicide prevention program had significant effects on improving perceived skills and confidence especially among nurses and medical residents. These significant effects lasted even 1 month after the program., Limitations: Design was a single-arm study with relatively small sample size and short-term follow up., Conclusions: The present study suggests that the major target of this effective program is nurses and medical residents. Future research is required to validate the effects of the program with control groups, and also to assess long-term effectiveness and actual reduction in suicide rates., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Background and Objective: Human in vitro and dog in vitro/in vivo researches indicate that the drug-drug interaction (DDI) of decreased plasma valproic acid (VPA) concentration by co-administration of carbapenem antibiotics is caused by inhibition of acylpeptide hydrolase (APEH)-mediated VPA acylglucuronide (VPA-G) hydrolysis by carbapenems. In this study, we investigated VPA disposition and APEH activities in TK-NOG chimeric mice, whose livers were highly replaced with human hepatocytes, to evaluate the utility of this animal model and the clinical relevance of the DDI mechanism., Methods: VPA and VPA-G concentrations in plasma, urinary excretion of VPA-G and APEH activity in humanized livers were measured after co-administration of VPA with meropenem (MEPM) to chimeric mice., Results: After co-administration with MEPM to the chimeric mice, plasma VPA concentration more rapidly decreased than without the co-administration. An increase in plasma AUC and urinary excretion of VPA-G was also observed. APEH activity in humanized livers was strongly inhibited even at 24 h after co-administration of MEPM to the chimeric mice., Conclusion: The DDI of VPA with carbapenems was successfully observed in chimeric mice with humanized livers. The DDI was caused by long-lasting inhibition of hepatic APEH-mediated VPA-G hydrolysis by carbapenems, which strongly supports the APEH-mediated mechanism of the clinical DDI. This is the first example showing the usefulness of chimeric mice with humanized livers for evaluation of a DDI via non-cytochrome P450 enzyme.

Aim: Studies have reported that cognitive decline occurs after the onset of schizophrenia despite heterogeneity in cognitive function among patients. The aim of this study was to investigate the degree of estimated cognitive decline in patients with schizophrenia by comparing estimated premorbid intellectual functioning and current intellectual functioning., Methods: A total of 446 patients with schizophrenia (228 male, 218 female), consisting of three sample sets obtained from 11 psychiatric facilities, and 686 healthy controls participated in this study. The Wechsler Adult Intelligence Scale-III (WAIS-III) was used to measure the participants' current full-scale IQ (FSIQ). The premorbid IQ was estimated using the Japanese Adult Reading Test-25. Estimated cognitive decline (difference score) was defined as the difference between the estimated premorbid IQ and the current FSIQ., Results: Patients with schizophrenia showed greater estimated cognitive decline, a lower FSIQ, and a lower premorbid IQ compared with the healthy controls. The mean difference score, FSIQ, and estimated premorbid IQ were -16.3, 84.2, and 100.5, respectively, in patients with schizophrenia. Furthermore, 39.7% of the patients had a difference score of 20 points or greater decline. A discriminant analysis showed that the difference score accurately predicted 81.6% of the patients and healthy controls., Conclusion: These results show the distribution of difference score in patients with schizophrenia. These findings may contribute to assessing the severity of estimated cognitive decline and identifying patients with schizophrenia who suffer from cognitive decline., (© 2016 The Authors. Psychiatry and Clinical Neurosciences published by John Wiley & Sons Australia, Ltd on behalf of Japanese Society of Psychiatry and Neurology.)

Objective: As most reports concerning treatment with combinations of mood stabilizer (MS) with antidepressant (AD) drugs are based in the West, we surveyed characteristics of such cotreatment in 42 sites caring for the mentally ill in 10 Asian countries., Methods: This cross-sectional, pharmacoepidemiologic study used 2004 and 2013 data from the REAP-AD (Research Study on Asian Psychotropic Prescription Patterns for Antidepressants) to evaluate the rates and doses of MSs given with ADs and associated factors in 4164 psychiatric patients, using standard bivariate methods followed by multivariable logistic regression modeling., Results: Use of MS + AD increased by 104% (5.5% to 11.2%) between 2004 and 2013 and was much more associated with diagnosis of bipolar disorder than major depression or anxiety disorder, as well as with hospitalization > outpatient care, psychiatric > general-medical programs, and young age (all P < 0.001), but not with country, sex, or AD dose., Conclusions: The findings provide a broad picture of contemporary use of MSs with ADs in Asia, support predictions that such treatment increased in recent years, and was associated with diagnosis of bipolar disorder, treatment in inpatient and psychiatric settings, and younger age.

In this study, we sought to examine factors associated with dosing of antidepressants (ADs) in Asia. Based on reported data and clinical experience, we hypothesized that doses of ADs would be associated with demographic and clinical factors and would increase over time. This cross-sectional, pharmacoepidemiological study analyzed data collected within the Research Study on Asian Psychotropic Prescription Pattern for Antidepressants from 4164 participants in 10 Asian countries, using univariate and multivariate methods. The AD doses varied by twofold among countries (highest in PR China and RO Korea, lowest in Singapore and Indonesia), and averaged 124 (120-129) mg/d imipramine-equivalents. Average daily doses increased by 12% between 2004 and 2013. Doses were significantly higher among hospitalized patients and ranked by diagnosis: major depression > anxiety disorders > bipolar disorder, but were not associated with private/public or psychiatric/general-medical settings, nor with age, sex, or cotreatment with a mood stabilizer. In multivariate modeling, AD-dose remained significantly associated with major depressive disorder and being hospitalized. Doses of ADs have increased somewhat in Asia and were higher when used for major depression or anxiety disorders than for bipolar depression and for hospitalized psychiatric patients.

Recent MRI studies have shown that schizophrenia is characterized by reductions in brain gray matter, which progress in the acute state of the disease. Cortical circuitry abnormalities in gamma oscillations, such as deficits in the auditory steady state response (ASSR) to gamma frequency (>30-Hz) stimulation, have also been reported in schizophrenia patients. In the current study, we investigated neural responses during click stimulation by BOLD signals. We acquired BOLD responses elicited by click trains of 20, 30, 40 and 80-Hz frequencies from 15 patients with acute episode schizophrenia (AESZ), 14 symptom-severity-matched patients with non-acute episode schizophrenia (NASZ), and 24 healthy controls (HC), assessed via a standard general linear-model-based analysis. The AESZ group showed significantly increased ASSR-BOLD signals to 80-Hz stimuli in the left auditory cortex compared with the HC and NASZ groups. In addition, enhanced 80-Hz ASSR-BOLD signals were associated with more severe auditory hallucination experiences in AESZ participants. The present results indicate that neural over activation occurs during 80-Hz auditory stimulation of the left auditory cortex in individuals with acute state schizophrenia. Given the possible association between abnormal gamma activity and increased glutamate levels, our data may reflect glutamate toxicity in the auditory cortex in the acute state of schizophrenia, which might lead to progressive changes in the left transverse temporal gyrus., (Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.)

Objective: Pharmacotherapy of depression in children and adolescents is complex. In the absence of research into the efficacy and safety of antidepressants in this group of patients, their off-label prescription is common. This paper aimed to illustrate the prescription pattern of antidepressants in children and adolescents from major psychiatric centres in Asia., Methods: The Research on Asia Psychotropic Prescription Pattern on Antidepressants worked collaboratively in 2013 to study the prescription pattern of antidepressants in Asia using a unified research protocol and questionnaire. Forty psychiatric centres from 10 Asian countries / regions participated and 2321 antidepressant prescriptions were analysed., Results: A total of 4.7% antidepressant prescriptions were for children and adolescents. Fluoxetine, sertraline, and escitalopram were the most common antidepressants prescribed for children and adolescents. Almost one-third (30.3%) of prescriptions were for diagnoses other than depressive and anxiety disorders. There was less antidepressant polypharmacy and concomitant use of benzodiazepine, but more concomitant use of antipsychotics in children and adolescents compared with adults., Conclusion: Off-label use of antidepressants in children and adolescents was reported by 40 Asian psychiatric institutions that participated in the study. In-service education and regulatory mechanisms should be reinforced to ensure efficacy and safety of antidepressants in children and adolescents.

1. Our previous in vitro studies suggest that inhibition of the acylpeptide hydrolase (APEH) activity as valproic acid glucuronide (VPA-G) hydrolase by carbapenems in human liver cytosol is a key process for clinical drug-drug interaction (DDI) of valproic acid (VPA) with carbapenems. Here, we investigated whether in vivo DDI of VPA with meropenem (MEPM) was caused via inhibition of APEH in dogs. 2. More rapid decrease of plasma VPA levels and increased urinary excretion of VPA-G were observed after co-administration with MEPM compared with those after without co-administration, whereas the plasma level and bile excretion of VPA-G showed no change. 3. Dog VPA-G hydrolase activity, inhibited by carbapenems, was mainly located in cytosol from both the liver and kidney. APEH-immunodepleted cytosols lacked VPA-G hydrolase activity. Hepatic and renal APEH activity was negligible even at 24 h after dosing of MEPM to a dog. 4. In conclusion, DDI of VPA with carbapenems in dogs is caused by long-lasting inhibition of APEH-mediated VPA-G hydrolysis by carbapenems, which could explain the delayed recovery of plasma VPA levels to the therapeutic window even after discontinuation of carbapenems in humans.

Introduction: Research in prescription pattern of antidepressants in Asia is lacking. This study aims to compare the antidepressants prescription pattern in Asia in 2003-2004 and 2013., Methods: The Research in East Asia Psychotropic Prescription Pattern on Antidepressants (REAP-AD) had worked collaboratively in 2003-2004 (REAP-AD 2003/2004) and 2013 (REAP-AD 2013) to study the prescription pattern of antidepressants in Asia. The REAP-AD 2013 study was conducted in China, Hong Kong, India, Indonesia, Japan, Korea, Malaysia, Singapore, Taiwan, and Thailand using a unified research protocol and questionnaire., Results: Forty psychiatric centers participated in REAP-AD 2013 and a total of 2,319 patients receive antidepressants were analyzed. In 2013, 39.6% of the antidepressant prescriptions were for diagnoses other thandepressive disorder compared with 38.4% in REAP-AD 2003/2004. Out of all the antidepressants listed in the Anatomical Therapeutic Chemical Classification index by the World Health Organization Collaborating Center for Drug Statistics Methodology (Oslo), only 38% antidepressants were prescribed in participating centers in 2013 compared with 46% in REAP-AD 2003/2004. The selective serotonin reuptake inhibitors were the most common antidepressant prescribed in the participating centers, which was similar to the 2003-2004 survey. Prescription of newer generation antidepressants had increased in 2013 survey; on the contrary, prescription of tricyclic antidepressants had reduced., Discussion: This study has contributed significantly in relation to the changing patterns of antidepressant use in all the participating Asian centers in the last 10 years. The findings are important in shaping optimal antidepressant prescription and future policy making., (© 2015 Wiley Publishing Asia Pty Ltd.)

Introduction: This study was to assess differences in the symptom profile of depressive illness across various countries/territories in Asia. The study was a part of the Research on Asia Psychotropic Prescription project. The participating countries/territories include China, Hong Kong, India, Indonesia, Japan, Korea, Malaysia, Singapore, Taiwan, and Thailand., Methods: The pattern of depressive symptoms in 1,400 subjects with depressive disorder from 42 psychiatric centers in 10 Asian countries/territories was assessed. We collected information on socio-demographic and clinical characteristics with a standardized protocol and data collection procedure., Results: The most common presentations of depressive symptoms were persistent sadness, loss of interest, and insomnia. Similar findings were found regardless of the region, country, or its income level. Patients with depressive disorder from high-income countries presented significantly more with vegetative symptom cluster (P < 0.05), while those from the upper middle-income countries had significantly more with both mood (P < 0.001) and cognitive symptom clusters (P < 0.01). In lower middle-income countries, patients with depressive symptoms had significantly less mood symptom cluster (P < 0.001) but significantly more cognitive symptom cluster (P < 0.05)., Discussion: This study demonstrates that in Asia, despite variations in the initial symptom reported by the patients, across different countries/territories, core depressive symptoms remain the same. Variations have been found in presentation of depressive symptoms with regards to the level of income of countries. Physical or vegetative symptoms were reported more by centers in higher income countries, while depressive cognition and suicidal thoughts/acts were more frequently reported from lower income countries., (© 2015 Wiley Publishing Asia Pty Ltd.)

Objective: To evaluate the prescription pattern of antidepressants in patients with medical co-morbidity from major psychiatric centres in Asia., Methods: The Research on Asian Psychotropic Prescription Pattern for Antidepressants (REAP-AD 2013) collected data from 42 psychiatric centres in 10 Asian countries and regions. Antidepressant prescriptions of 2320 patients with various psychiatric disorders were evaluated. Of these, 370 patients who had specified medical co-morbidities formed the study cohort., Results: Escitalopram (20%) and mirtazapine (20%) were the most commonly prescribed antidepressants in patients with medical co-morbidity followed by sertraline (16%), trazodone (15%), and paroxetine (12%). Overall, more than half (52%; 247/476) of prescriptions comprised selective serotonin reuptake inhibitors. Slightly less than two-thirds (63%; n = 233) of patients received at least 1 selective serotonin reuptake inhibitor. In addition, 79% of patients were prescribed only 1 antidepressant. The mean number of antidepressants used per patient was 1.25 (standard deviation, 0.56). There were subtle differences in the most preferred antidepressant across medical illnesses such as diabetes mellitus, liver dysfunction, acid peptic disease, and cerebrovascular disease. Differences were also seen in prescription patterns across different countries., Conclusion: Although selective serotonin reuptake inhibitors formed the bulk of antidepressant prescriptions in the presence of medical co-morbidity, mirtazapine was also commonly used in the presence of medical co-morbidities. Specified medical morbidities do influence the selection of antidepressants.

Background: Focusing on the respiratory function for health effect indices, we conducted a cross-sectional study on workers who did and did not handle toner to compare the longitudinal changes., Methods: Among 116 individuals who worked for a Japanese business equipment manufacturer and participated in the study, the analysis included 69 male workers who we were able to follow up for 4 years. We categorized the 40 workers engaged in toner-handling work as the exposed group and the 29 workers not engaged in these tasks as the referent group, and compared their respiratory function test results: peak expiratory flow rate (PEFR), vital capacity (VC), predicted vital capacity (%VC), forced expiratory volume in 1 second (FEV1), and forced expiratory volume in 1 second as a percent of forced vital capacity (FEV1%)., Results: The cross-sectional study of the respiratory function test results at the baseline and at the 5(th) year showed no statistically significant differences in PEFR, VC, %VC, FEV1, and FEV1% between the exposed and referent workers. Also, respiratory function time-course for 4 years was calculated and compared between the groups. No statistically significant differences were shown., Conclusion: Our study does not suggest any toner exposure effects on respiratory function. However, the number of subjects was small in our study; studies of larger populations will be desired in the future.

We examined clinical characteristics including serum olanzapine concentrations for acute schizophrenia patients who required above conventional doses. We performed a rater-blinded, randomized clinical trial in 12 psychiatric emergency sites. Eligible patients were 18-64 years old and met diagnostic criteria for schizophrenia, acute schizophrenia-like psychotic disorder, or schizoaffective disorder. A total of 42 patients were randomly assigned by means of sealed envelopes to receive risperidone (3-12 mg/day; n=20) and olanzapine (10-40 mg/day; n=22), with follow-up at 8 weeks. The Negative score of the Positive and Negative Syndrome Scale was significantly higher in patients who required high doses than in patients who responded to conventional doses. Serum olanzapine concentrations at the time of oral 20mg/day could be obtained from 5 out of 7 patients who subsequently required high-dose olanzapine. All values were more than 30 ng/mL after 11-16 h from dosing to sample collection, and the mean value was 47.876 (S.D. 21.546) ng/mL. Such concentrations are appropriate with respect to a therapeutic range of 20-50 ng/mL. The present study has shown evidence that the reason for requiring high-dose olanzapine cannot be explained by pharmacokinetics in the treatment of acute-phase schizophrenia., (Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.)