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Yamauchi T.,National Institute of Mental Health | Inagaki M.,Okayama University | Yonemoto N.,Translational Medical Center | Iwasaki M.,Research Center for Cancer Prevention and Screening | And 4 more authors.
Psycho-Oncology | Year: 2014

Objective: There have been very few population-based prospective studies that have investigated the risks of deaths by suicide and other externally caused injuries (ECIs) among cancer patients in an Asian population. This study investigated whether the risk of death by both suicide and ECIs increases during the first year following the initial diagnosis of cancer. Methods: Data were analyzed from a population-based cohort of Japanese residents between 1990 and 2010, collected during the Japan Public Health Center-based Prospective Study. Poisson regression models were used to calculate adjusted risk ratios (RRs) for both suicide and ECI deaths. To adjust for unmeasured confounding factors, case-crossover analyses were conducted for all patients with cancer who died by suicide and ECIs. Results: A population-based cohort of 102,843 Japanese residents was established. During the follow-up period, there were 34 suicides and 48 ECI deaths among patients with cancer, as compared with 527 suicides and 707 ECI deaths among those who did not have cancer. Analyses revealed that those who were newly diagnosed with cancer were at a greatly increased risk of death by suicide and ECIs within the first year after their diagnosis (suicide RR = 23.9, 95% CI: 13.8-41.6; ECI RR = 18.8, 95% CI: 11.4-31.0). Furthermore, the case-crossover analyses generally confirmed the results of the Poisson regressions. Conclusions: The risks of suicide and ECI deaths within the first year after a cancer diagnosis were higher than those among cancer-free populations. A diagnosis of cancer is a critical experience that may increase the risk of fatal outcomes. Copyright © 2014 John Wiley & Sons, Ltd.


Yamauchi T.,National Institute of Mental Health | Inagaki M.,Okayama University | Yonemoto N.,Translational Medical Center | Iwasaki M.,Research Center for Cancer Prevention and Screening | And 4 more authors.
Psychosomatic Medicine | Year: 2014

OBJECTIVE: No large population-based prospective study has investigated the risks of suicide and death by other externally caused injuries (ECIs) among stroke patients. The purpose of this study was to examine whether stroke increases the risks of suicide and ECI deaths. METHODS: We analyzed data from the Japan Public Health Center-based Prospective Study between 1990 and 2010. Poisson regression models were used to calculate adjusted risk ratios (RR) for suicide and ECI deaths. To adjust for unmeasured confounders, case-crossover analyses of all stroke patients who died by suicide and ECIs were also performed. RESULTS: A population-based cohort of 93,027 Japanese residents was established. During the follow-up period, 4793 residents had been diagnosed as having stroke. During this period, there were 22 suicides and 53 ECI deaths among stroke patients and 490 suicides and 675 ECI deaths among those who were stroke-free. Stroke patients were at increased risk for death by suicide and ECIs within the first 5 years after a stroke (suicide: RR = 10.2, 95% confidence interval [CI] = 6.3-16.6; ECI: RR = 12.8, 95% confidence interval = 9.0-18.2). Furthermore, case-crossover analyses confirmed the results of the Poisson regression models. CONCLUSIONS: The RRs of suicide and ECI deaths within the first 5 years after a stroke were noticeably high. These findings underscore the need for clinicians and health care professionals to be aware of causes of death after a stroke and closely monitor patients during the first few poststroke years. Copyright © 2014 by the American Psychosomatic Society.


Ishii N.,Aiiku Hospital | Kono Y.,Jichi Medical University | Yonemoto N.,Translational Medical Center | Kusuda S.,Tokyo Women's Medical University | Fujimura M.,Research Institute for Maternal and Child Health
Pediatrics | Year: 2013

OBJECTIVE: To provide instructive information on death and neurodevelopmental outcomes of infants born at 22 and 23 weeks' gestational age. METHODS: The study cohort consisted of 1057 infants born at 22 to 25 weeks in the Neonatal Research Network, Japan. Neurodevelopmental impairment (NDI) at 36 to 42 months' chronological age was defined as any of the following: cerebral palsy, hearing impairment, visual impairment, and a developmental quotient ,70. A systematic review was performed by using databases of publications of cohort studies with neonatal and neurodevelopmental outcomes at 22 and 23 weeks. RESULTS: Numbers and incidences (%) of infants with death or NDI were 60 (80%) at 22 weeks and 156 (64%) at 23 weeks. In logistic regression analysis, gestational ages of 22 weeks (odds ratio [OR]: 5.40; 95% confidence interval [CI]: 2.48-11.76) and 23 weeks (OR: 2.14; 95% CI: 1.38-3.32) were associated with increased risk of death or NDI compared with 24 weeks, but a gestational age of 25 weeks (OR: 0.65; 95% CI: 0.45-0.95) was associated with decreased risk of death or NDI. In the systematic review, the medians (range) of the incidence of death or NDI in 8 cohorts were 99% (90%-100%) at 22 weeks and 98% (67%-100%) at 23 weeks. CONCLUSIONS: Infants born at 22 and 23 weeks' gestation were at higher risk of death or NDI than infants at born at 24 weeks. However, outcomes were improved compared with those in previous studies. There is a need for additional discussions on interventions for infants born at 22 or 23 weeks' gestation. Pediatrics 2013;132:62-71. Copyright © 2013 by the American Academy of Pediatrics.


Kawashima Y.,National Institute of Mental Health | Yonemoto N.,Translational Medical Center | Inagaki M.,Okayama University | Yamada M.,National Institute of Mental Health
Journal of Affective Disorders | Year: 2014

Background The number of hospital admissions related to suicide attempts is increasing worldwide. The Emergency Department (ED) is recognized in Japan as an opportunity to intervene with suicide attempters however, the prevalence of suicide attempters in the ED is unknown. Therefore, a meta-analysis was conducted to provide this information. Methods We conducted searches of databases (PubMed, PsycINFO, CINAHL, ICHUSHI, CiNii) to identify studies about suicide attempters in the ED in Japan. A meta-analysis was used to calculate the pooled prevalence proportion of suicide attempters in the ED, and their prevalence proportion of psychiatric disorder and method of suicide in suicide attempters. Results The search of Japanese studies identified 3338 records, of which 70 were included in the meta-analysis. A total of 25 studies reported the psychiatric diagnosis and 62 studies reported the method of suicide. The pooled prevalence proportion of suicide attempters was 4.7%. Mood disorders were the most frequent psychiatric disorders (ICD: 30%, DSM: 35%), and poisoning was the most frequent method of attempting suicide (52%). Limitations There might be a publication bias because only published studies were included. There also might be an information bias, such as reporting bias or misclassification, because most of studies included in the analysis used retrospective designs. Conclusions The results provide clear evidence of the prevalence of suicide attempters in the ED in Japan. The results indicate that suicide attempters in the ED have a higher proportion of mood disorders, and that the most common method of suicide is poisoning. © 2014 Elsevier B.V.


Sueki H.,Wako University | Yonemoto N.,Translational Medical Center | Takeshima T.,National Institute of Mental Health | Inagaki M.,Okayama University
PLoS ONE | Year: 2014

Background: There has been no study that has allowed clear conclusions about the impact of suicide-related or mental health consultation-related internet use. Aim: To investigate the impacts of suicide-related or mental health consultation-related internet use. Methods: We conducted prospective observational longitudinal study with data collection at baseline screening (T0), 1 week after T0 (T1) and 7 weeks after T0 (T2). Participants with a stratified random sampling from 744,806 internet users were 20-49 years of age who employed the internet for suicide-related or mental health consultation-related reasons and internet users who did not. The main outcome was suicidal ideation. Secondary outcome measures comprised hopelessness, depression/anxiety, and loneliness. Results: The internet users who had employed the internet for suicide-related or mental health consultation-related reasons at T0 (n = 2813), compared with those who had not (n = 2682), showed a significant increase in suicidal ideation (b = 0.38, 95%CI: 0.20-0.55) and depression/anxiety (b = 0.37, 95%CI: 0.12-0.61) from T1 to T2. Those who disclosed their own suicidal ideation and browsed for information about suicide methods on the web showed increased suicidal ideation (b = 0.55, 95%CI: 0.23-0.88; b = 0.45, 95% CI: 0.26-0.63, respectively). Although mental health consultation with an anonymous other online did not increase suicidal ideation, increased depression/anxiety was observed (b = 0.34, 95%CI: 20.03-0.71). Conclusions: An increased suicidal ideation was observed in the young and middle-aged who employed the internet for suicide-related or mental health consultation-related reasons. Mental health consultation via the internet was not useful, but those who did so showed worsened depression/anxiety. © 2014 Sueki et al.


Endo Y.,Translational Medical Center | Endo Y.,National Institute of Neuroscience | Furuta A.,Juntendo University | Nishino I.,Translational Medical Center | Nishino I.,National Institute of Neuroscience
Acta Neuropathologica | Year: 2015

Danon disease is an X-linked disorder clinically characterized by the triad of hypertrophic cardiomyopathy, myopathy, and intellectual disability. Cardiomyopathy is a severe and life-threatening problem, for which cardiac transplantation is the only therapeutic option. The most striking finding in muscle biopsy samples is small basophilic granules scattered in myofibers, which are in fact small autophagic vacuoles surrounded by membranes with sarcolemmal features characterized by the recruitment of sarcolemmal proteins and acetylcholine esterase and by the presence of basal lamina on its luminal side. The mechanism underlying the formation of these autophagic vacuoles with unique sarcolemmal features (AVSF) still remains a mystery and its origin is unknown. In heart, cardiomyocytes show dramatically increased vacuolation and degenerative features, including myofibrillar disruption and lipofuscin accumulation. In brain, pale granular neurons and neurons with lipofuscin-like granules may be seen. Danon disease is caused by loss-of-function mutations in the LAMP2 gene, which encodes lysosome-associated membrane protein 2 (LAMP-2), a single-spanned transmembrane protein localized in the limiting membranes of lysosomes and late endosomes. Most mutations lead to splicing defects or protein truncation, resulting in a loss of transmembrane and/or cytoplasmic domains, leading to LAMP-2 protein deficiency. LAMP-2 is required for the maturation of autophagosomes by fusion with lysosomes; therefore, LAMP-2 deficiency leads to a failure in macroautophagy. There are three LAMP-2 isoforms, LAMP-2A, -2B, and -2C. Clinical features of Danon disease are thought to be mediated by loss of the LAMP-2B isoform which is the major isoform expressed in muscle. It is also known that LAMP-2 plays a role in chaperone-mediated autophagy and RNA- and DNA-targeting autophagy. However, the precise pathophysiological mechanism through which LAMP-2 deficiency causes Danon disease is still not fully understood and its elucidation would promote the development of new therapies. © 2015, Springer-Verlag Berlin Heidelberg.


Yonemoto N.,Translational Medical Center
The Cochrane database of systematic reviews | Year: 2013

Maternal complications including psychological and mental health problems and neonatal morbidity have been commonly observed in the postpartum period. Home visits by health professionals or lay supporters in the weeks following the birth may prevent health problems from becoming chronic with long-term effects on women, their babies, and their families. To assess outcomes for women and babies of different home-visiting schedules during the early postpartum period. The review focuses on the frequency of home visits, the duration (when visits ended) and intensity, and on different types of home-visiting interventions. We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (28 January 2013) and reference lists of retrieved articles. Randomised controlled trials (RCTs) (including cluster-RCTs) comparing different types of home-visiting interventions enrolling participants in the early postpartum period (up to 42 days after birth). We excluded studies in which women were enrolled and received an intervention during the antenatal period (even if the intervention continued into the postnatal period) and studies recruiting only women from specific high-risk groups. (e.g. women with alcohol or drug problems). Study eligibility was assessed by at least two review authors. Data extraction and assessment of risk of bias were carried out independently by at least two review authors. Data were entered into Review Manager software. We included data from 12 randomised trials with data for more than 11,000 women. The trials were carried out in countries across the world, and in both high- and low-resource settings. In low-resource settings women receiving usual care may have received no additional postnatal care after early hospital discharge.The interventions and control conditions varied considerably across studies with trials focusing on three broad types of comparisons: schedules involving more versus fewer postnatal home visits (five studies), schedules involving different models of care (three studies), and home versus hospital clinic postnatal check-ups (four studies). In all but two of the included studies, postnatal care at home was delivered by healthcare professionals. The aim of all interventions was broadly to assess the wellbeing of mothers and babies, and to provide education and support, although some interventions had more specific aims such as to encourage breastfeeding, or to provide practical support.For most of our outcomes only one or two studies provided data, and overall results were inconsistent.There was no evidence that home visits were associated with improvements in maternal and neonatal mortality, and no strong evidence that more postnatal visits at home were associated with improvements in maternal health. More intensive schedules of home visits did not appear to improve maternal psychological health and results from two studies suggested that women receiving more visits had higher mean depression scores. The reason for this finding was not clear. There was some evidence that postnatal care at home may reduce infant health service utilisation in the weeks following the birth, and that more home visits may encourage more women to exclusively breastfeed their babies. There was some evidence that home visits are associated with increased maternal satisfaction with postnatal care. Overall, findings were inconsistent. Postnatal home visits may promote infant health and maternal satisfaction. However, the frequency, timing, duration and intensity of such postnatal care visits should be based upon local needs. Further well designed RCTs evaluating this complex intervention will be required to formulate the optimal package.


Su K.-P.,China Medical University at Heping | Su K.-P.,China Medical University at Taichung | Matsuoka Y.,Translational Medical Center | Pae C.-U.,Catholic University of Korea
Clinical Psychopharmacology and Neuroscience | Year: 2015

Psychiatric disorders in general, and major depression and anxiety disorders in particular, account for a large burden of disability, morbidity and premature mortality worldwide. Omega-3 polyunsaturated fatty acids (PUFAs) have a range of neurobiological activities in modulation of neurotransmitters, anti-inflammation, anti-oxidation and neuroplasticity, which could contribute to psychotropic effects. Here we reviewed recent research on the benefits of omega-3 PUFA supplements in prevention against major depression, bipolar disorders, interferon-α-induced depression patients with chronic hepatitis C viral infection, and posttraumatic stress disorder. The biological mechanisms underlying omega-3 PUFAs'psychotropic effects are proposed and reviewed. Nutrition is a modifiable environmental factor that might be important in prevention medicine, which have been applied for many years in the secondary prevention of heart disease with omega-3 PUFAs. This review extends the notion that nutrition in psychiatry is a modifiable environmental factor and calls for more researches on prospective clinical studies to justify the preventive application of omega-3 PUFAs in daily practice. Copyright © 2015, Korean College of Neuropsychopharmacology.


Heron-Delaney M.,University of Queensland | Kenardy J.,University of Queensland | Charlton E.,University of Queensland | Matsuoka Y.,Translational Medical Center
Injury | Year: 2013

Posttraumatic stress disorder (PTSD) is one of the most common psychological consequences for adult road traffic crash (RTC) survivors and can have serious and long-lasting consequences for recovery if left untreated. Prevalence rates of PTSD following a RTC vary from 6% to 45% (based on 51 prevalence estimates across 35 studies). Explanations for this wide variance are explored. A systematic review of published studies found 49 papers (44 unique studies) investigating predictors of later PTSD in RTC survivors. Consistent predictors of PTSD include rumination about the trauma, perceived threat to life, a lack of social support, higher Acute Stress Disorder symptom severity, persistent physical problems, previous emotional problems, previous anxiety disorder and involvement in litigation/compensation. Moderate predictors of PTSD are discussed, as well as factors, which consistently do not predict PTSD in RTC survivors. The results inform future models of post-RTC traumatic stress aetiology. Crown Copyright © 2013 Published by Elsevier Ltd. All rights reserved.


Takeda S.,Translational Medical Center
Clinical Neurology | Year: 2014

Exon skipping therapy by antisense oligonucleotide is a promising approach to Duchenne muscular dystrophy (DMD). We have reported the proof-of-concept studies using morpholino on mice or dog DMD model and on patient derived cells. Based on these results, we had promoted collaborative research with a Japanese pharmaceutical company and encouraged development of DMD gene exon 53 skipping drug, then finally started an investigator-initiated clinical trial from 2013. Furthermore, we are addressing exploratory researches to expand the possibility of AON; such as, an application of AON to Fukuyama congenital muscular dystrophy, and an elucidation of AON uptake mechanism.

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