Publications by authors named "Tomoya Hirota"

60 Publications

Associations of Social Capital with Mental Disorder Prevalence, Severity, and Comorbidity among U.S. Adolescents.

J Clin Child Adolesc Psychol 2021 Mar 3:1-12. Epub 2021 Mar 3.

Intramural Research Program, National Institute of Mental Health.

: To examine cross-sectional associations between social capital constructs and 1) adolescent lifetime mental disorders, 2) severity of functional impairment, and 3) psychiatric comorbidity.: Data were from the National Comorbidity Survey Adolescent Supplement, a nationally representative mental health survey of 6,483 U.S. adolescents aged 13-18 years. Information from fully-structured diagnostic interviews, including adolescent and caregiver reports, was used to measure seven social capital constructs and lifetime DSM-IV mental disorders (mood, anxiety, behavior, substance use and eating disorder classes). Disorder severity was divided into severe vs. mild/moderate. Comorbidity was measured as the number of different classes of lifetime mental disorders.: Adjusted for socio-demographics and caregivers' mental health, the most consistent associations with adolescent mental disorder were for supportive friendships (any disorder OR = 0.95, 95%CI = 0.91-0.99), family cohesion (OR = 0.81, 95%CI = 0.75-0.86), school bonding (OR = 0.76, 95%CI = 0.71-0.81), and extracurricular participation (OR = 0.90, 95%CI = 0.86-0.95), although results differed by disorder class. Caregiver-reported neighborhood trust and reciprocity and caregiver community involvement were less consistently associated with mental disorder. Medium levels of adolescent-reported affiliation with neighbors was associated with lower odds of mood (OR = 0.81, 95%CI = 0.66-0.98) and anxiety (OR = 0.78, 95%CI = 0.64-0.96) disorder, while high levels were associated with higher odds of behavior disorder (OR = 1.47, 95%CI = 1.16-1.87). Several associations were stronger for severe vs. mild/moderate disorder and with increasing comorbidity.: Although we cannot infer causality, our findings support the notion that improving actual and/or perceived social capital, especially regarding friendships, family, and school, (e.g., through multimodal interventions) could aid in the prevention and treatment of both individual adolescent mental disorders and psychiatric comorbidity.
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http://dx.doi.org/10.1080/15374416.2021.1875326DOI Listing
March 2021

Pediatric health-related quality of life and school social capital through network perspectives.

PLoS One 2020 2;15(12):e0242670. Epub 2020 Dec 2.

Department of Neuropsychiatry, Graduate School of Medicine, Hirosaki University, Hirosaki, Aomori, Japan.

Background: Despite their importance in population health among children and adolescents, our understanding of how individual items mutually interact within and between pediatric health-related quality of life (HRQOL) and school social capital is limited.

Methods: We employed network analysis in a general population sample of 7759 children aged 9-15 years to explore the network structure of relations among pediatric HRQOL and school social capital items measured using validated scales. Furthermore, network centrality was examined to identify central items that had stronger and more direct connections with other items in the network than others. Network structure and overall strength of connectivity among items were compared between groups (by sex and age).

Results: Our analysis revealed that the item related to school/academic functioning and the item related to shared enjoyment among students had the highest strength centrality in the network of HRQOL and school social capital, respectively, underpinning their critical roles in pediatric HRQOL and school social capital. Additionally, the edge connecting "I trust my friends at school" and "trouble getting along with peers" had the strongest negative edge weight among ones connecting school social capital and pediatric HRQOL constructs. Network comparison test revealed stronger overall network connectivity in middle schoolers compared to elementary schoolers but no differences between male and female students.

Conclusion: The network approach elucidated the complex relationship of mutually influencing items within and between pediatric HRQOL and school social capital. Addressing central items may promote children's perceived health and school social capital.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0242670PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7710098PMC
January 2021

Utilization of the Maternal and Child Health Handbook in Early Identification of Autism Spectrum Disorder and Other Neurodevelopmental Disorders.

Autism Res 2021 03 29;14(3):551-559. Epub 2020 Nov 29.

Department of Neuropsychiatry, Graduate School of Medicine, Hirosaki University, Aomori, Japan.

There is relatively little information about prospectively reported developmental milestones from caregivers of children who go on to be diagnosed with neurodevelopmental disorders (NDDs), including autism spectrum disorder (ASD). The current study examined rates of early skill attainment in 5-year-old children who participated in a comprehensive in-person assessment for NDDs in Hirosaki in Japan. Developmental milestone data were extracted from their Maternal and Child Health Handbook (MCHH), a booklet distributed to all pregnant women as part of universal health care. Seven hundred and twenty children underwent the assessment, among whom 455 received one or more NDD diagnoses (ASD: n = 124, non-ASD NDD: n = 331). Developmental skills were organized into four domains (motor, social interaction, communication, self-help), and the cumulative number of potential delays in each domain was calculated for each participant within three different age ranges (by 12 months, by 24 months, and by 36 months). Even by age 12 months, children with ASD/NDDs showed more potential delays across domains compared to those who received no NDD diagnosis. However, differences between those with ASD and those with non-ASD NDDs were not apparent until 24 months for social interaction and communication, and 36 months for self-help. These findings provide insights into specific behaviors that could be used to screen for ASD and other NDDs. In addition, the present study indicates the potential utility of the MCHH as a broadband screening tool to educate parents about what to look for in charting their child's early development. LAY SUMMARY: The present study examined prospectively charted developmental milestones from home-based records used as part of universal health care in 720 5-year-old children from Hirosaki, Japan. All children participated in a comprehensive evaluation to determine if they met criteria for a neurodevelopmental disorder (NDD), including autism spectrum disorder (ASD). Compared to those who received no NDD diagnosis, children with NDDs exhibited higher rates of potential delays across developmental domains, including social interaction, communication, and self-help. For some children, these delays were apparent before the age of 12 months. Differences between diagnostic groups became even more pronounced by 24 and 36 months, well before the average age of diagnosis. This suggests that home-based records can be useful tools to educate caregivers about what to look for in charting their child's early development and could assist with early screening efforts.
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http://dx.doi.org/10.1002/aur.2442DOI Listing
March 2021

Prevalence of and Factors Associated with School Bullying in Students with Autism Spectrum Disorder: A Cross-Cultural Meta-Analysis.

Yonsei Med J 2020 Nov;61(11):909-922

Center for ASD and Neurodevelopmental Disorders, University of California, San Francisco, CA, USA.

Through this meta-analysis, we sought to examine the prevalence of, risks for, and factors associated with bullying involvement (victimization, perpetration, perpetration-victimization) among students with autism spectrum disorder (ASD). Additionally, we attempted to examine sources of variance in the prevalence and effect sizes of bullying in students with ASD across studies. Systematic database and literature review identified 34 relevant studies (31 for Western countries, three for Eastern countries). Pooled prevalence estimates for victimization, perpetration, and perpetration-victimization in general were 67%, 29%, and 14%, respectively. The risk of victimization in students with ASD was significantly higher than that in typically developing students and students with other disabilities. Further, deficits in social interaction and communication, externalizing symptoms, internalizing symptoms, and integrated inclusive school settings were related to higher victimization, and externalizing symptoms were related to higher perpetration. Finally, moderation analyses revealed significant variations in the pooled prevalences thereof depending on culture, age, school settings, and methodological quality and in the pooled effect sizes according to publication year and methodological quality. Our results highlight needs for bullying intervention for students with ASD, especially those who are younger, are in an inclusive school setting, and have higher social difficulties and externalizing/internalizing symptoms; for intensive research of bullying experiences among students with ASD in Eastern countries; and for efforts to improve the methodological quality of such research.
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http://dx.doi.org/10.3349/ymj.2020.61.11.909DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7593096PMC
November 2020

Network Analysis of Internet Addiction Symptoms Among a Clinical Sample of Japanese Adolescents with Autism Spectrum Disorder.

J Autism Dev Disord 2020 Oct 10. Epub 2020 Oct 10.

Department of Psychiatry, Okayama Psychiatric Medical Center, Okayama, Japan.

In the present study, we employed network analysis that conceptualizes internet addiction (IA) as a complex network of mutually influencing symptoms in 108 adolescents with autism spectrum disorder (ASD) to examine the network architecture of IA symptoms and identify central/influential symptoms. Our analysis revealed that defensive and secretive behaviors and concealment of internet use were identified as central symptoms in this population, suggesting that mitigating these symptoms potentially prevent the development and/or maintenance of IA in adolescents with ASD. Providing adolescents and their caregivers with psychoeducation on the role of central symptoms above in IA can be a salient intervention. Doing so may facilitate nonconflicting conversations between them about adolescents' internet use and promote more healthy adolescents' internet use behavior.
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http://dx.doi.org/10.1007/s10803-020-04714-xDOI Listing
October 2020

Distributional patterns of item responses and total scores of the Patient Health Questionnaire for Adolescents in a general population sample of adolescents in Japan.

Psychiatry Clin Neurosci 2020 Nov 29;74(11):628-629. Epub 2020 Sep 29.

Research Center for Child Mental Development, Graduate School of Medicine, Hirosaki University, Hirosaki, Japan.

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http://dx.doi.org/10.1111/pcn.13148DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7702070PMC
November 2020

A case of eosinophilic fasciitis without skin manifestations: a case report in a patient with lupus and literature review.

Clin Rheumatol 2020 Sep 24. Epub 2020 Sep 24.

First Department of Internal Medicine, Faculty of Medical Sciences, University of Fukui, 23-3 Matsuokashimoaizuki, Eiheiji, Fukui, 910-1193, Japan.

Eosinophilic fasciitis (EF) is a rare connective tissue disease that causes inflammation and fibrosis of the fascia, inducing pain and motor dysfunction. Characteristic skin manifestations, such as edema, erythema, induration, peau d'orange appearance, and the groove sign, are of diagnostic significance and observed in the majority of patients with EF. We herein report a case of EF without these characteristic skin manifestations. A 66-year-old Japanese woman developed progressive limb pain and motor dysfunction. No skin changes were observed. We diagnosed the patient with EF based on the clinical course, magnetic resonance imaging, and en bloc biopsy containing fascia and muscle. Oral prednisolone therapy markedly attenuated limb pain and motor dysfunctions. Through a systemic search of the medical literature, we retrieved 4 juvenile cases and 8 adult cases of EF without characteristic skin manifestations during the clinical course. We herein present a systemic review on EF without skin manifestations and discuss differences between the two proposed sets of diagnostic criteria of EF.
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http://dx.doi.org/10.1007/s10067-020-05416-6DOI Listing
September 2020

Neurodevelopmental Traits and Longitudinal Transition Patterns in Internet Addiction: A 2-year Prospective Study.

J Autism Dev Disord 2021 Apr;51(4):1365-1374

Department of Neuropsychiatry, Graduate School of Medicine, Hirosaki University, 5 Zaifu-cho, Hirosaki, Aomori, 036-8562, Japan.

Despite increasing attention to internet addiction (IA) in both clinical practice and research, our understanding of longitudinal changes of IA status is limited. In the present study, we employed latent transition analysis to investigate patterns of transitions and the stability of IA status among 5483 students (aged 9-12 years) over the two-year study periods. Additionally, we examined whether neurodevelopmental traits predicted certain transition patterns. The stability rate of IA class membership and the conversion rate from non-IA to IA status across the 2 years were 47% and 11%, respectively. The regression model revealed that autistic traits predicted the persisting IA pattern and that inattention traits predicted both the persisting and converting (from non-IA to IA status) patterns.
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http://dx.doi.org/10.1007/s10803-020-04620-2DOI Listing
April 2021

Atypical Sensory Processing Profiles and Their Associations With Motor Problems In Preschoolers With Developmental Coordination Disorder.

Child Psychiatry Hum Dev 2021 Apr;52(2):311-320

Department of Comprehensive Rehabilitation Science, Graduate School of Health Sciences, Hirosaki University, 66-1 Honcho, Hirosaki, Aomori, Japan.

The aims of this study were to identify sensory processing profiles specific to preschoolers with DCD in a community sample and examine the association of sensory processing problems with motor coordination difficulties in these children. Sixty-three 5-year-old children with DCD and without other neurodevelopmental disorders and 106 age-matched typically developing children participated in this study. Sensory processing problems were assessed using the Sensory Profile. Our results demonstrated problems in wide sensory processing patterns (low registration, sensitivity and avoiding) and areas (auditory, vestibular, touch and oral) in children with DCD compared with typically developing children. Additionally, the association of problems in sensory processing patterns (sensitivity and avoiding) and areas (touch and auditory) with motor coordination difficulties were identified in children with DCD alone. Our findings indicate that sensory processing abnormalities may contribute to the pathophysiology of DCD, suggesting the importance of assessing sensory processing functions in children with DCD.
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http://dx.doi.org/10.1007/s10578-020-01013-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7973923PMC
April 2021

Prevalence and cumulative incidence of autism spectrum disorders and the patterns of co-occurring neurodevelopmental disorders in a total population sample of 5-year-old children.

Mol Autism 2020 05 14;11(1):35. Epub 2020 May 14.

Department of Neuropsychiatry, Graduate School of Medicine, Hirosaki University, 5 Zaifu-cho, Hirosaki, Aomori, 036-8562, Japan.

Backgrounds: Whether there is a true increase in autism spectrum disorder (ASD) frequency or not remains unclear. Additionally, the rates of co-existing neurodevelopmental disorders (NDD) in a total population sample has not been fully examined before. Therefore, using a total population sample in Japan, we aimed to estimate the prevalence and cumulative incidence of autism spectrum disorder (ASD) annually, to determine whether there is a true increase in ASD prevalence by estimating the cumulative incidence of ASD annually, and to examine the rates of co-existing neurodevelopmental disorders (NDD).

Method: In this cross-sectional sequential design study, all 5-year-old children in the catchment area underwent the screening annually from the year 2013-2016. Screen-positive children were invited to participate in a comprehensive assessment, including child and parent interview, behavioral observation, and cognitive and motor function testing. All cases were reviewed by a multidisciplinary research team.

Results: Caregivers of 3954 children returned the screening, among which 559 children underwent the assessment with 87 children receiving an ASD diagnosis. Adjusted ASD prevalence was 3.22% (95% confidence interval (CI) 2.66-3.76%). The male to female ratio of the crude prevalence was 2.2:1. The cumulative incidence of ASD up to 5 years of age for the total study years was 1.31% (95% CI 1.00-1.62%). A generalized linear model revealed no significant linear trends in 5-year cumulative incidence over the study years. Only 11.5% of children had ASD alone; the remaining 88.5% were found to have at least one co-existing NDD.

Limitations: Modest sample size for a total population study.

Conclusions: Our findings demonstrate the stability of the 5-year cumulative incidence of ASD, implying no true rise in ASD incident cases over the 4-year study period in the study catchment area. High rates of co-existing NDDs reflect the importance of investigating broad developmental challenges in children with ASD.
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http://dx.doi.org/10.1186/s13229-020-00342-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7227343PMC
May 2020

Formation and Evolution of Disks Around Young Stellar Objects.

Space Sci Rev 2020 6;216(3):43. Epub 2020 Apr 6.

11Department of Earth Sciences, National Taiwan Normal University, 88, Sect. 4, Ting-Chou Road, Taipei, 11677 Taiwan.

Recent observations have suggested that circumstellar disks may commonly form around young stellar objects. Although the formation of circumstellar disks can be a natural result of the conservation of angular momentum in the parent cloud, theoretical studies instead show disk formation to be difficult from dense molecular cores magnetized to a realistic level, owing to efficient magnetic braking that transports a large fraction of the angular momentum away from the circumstellar region. We review recent progress in the formation and early evolution of disks around young stellar objects of both low-mass and high-mass, with an emphasis on mechanisms that may bridge the gap between observation and theory, including non-ideal MHD effects and asymmetric perturbations in the collapsing core (e.g., magnetic field misalignment and turbulence). We also address the associated processes of outflow launching and the formation of multiple systems, and discuss possible implications in properties of protoplanetary disks.
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http://dx.doi.org/10.1007/s11214-020-00664-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7136191PMC
April 2020

The Network Structure of Irritability and Aggression in Individuals with Autism Spectrum Disorder.

J Autism Dev Disord 2020 Apr;50(4):1210-1220

Department of Neuroscience, Psychology and Behaviour, University of Leicester, Leicester, UK.

Irritability and aggression (IA) are highly prevalent in individuals with autism spectrum disorder (ASD). Although clinical correlates of IA in this population have been previously examined, findings from existing studies capturing symptoms as a set of latent variables do not fully explain meaningful associations between the symptoms themselves. In the present study, we conducted network analysis which conceptualizes mental health difficulties as a complex network of directly associated symptoms in 2612 individuals who were diagnosed with ASD through rigorous diagnostic assessment and who were enrolled in the Simons Simplex Collection. Using the Aberrant Behavior Checklist, a validated scale, we investigated the network structure of IA and tried to identify bridge symptoms that link IA and other symptom domains. In our analysis, irritability symptoms had stronger and more direct associations with other nodes than aggression symptoms did. Additionally, depressed mood and oppositionality were identified to function as bridge symptoms. The network structures did not differ between individuals with and without intellectual disability. Our findings indicate that addressing these bridge symptoms through integrated care combining different modalities of treatment could ease the complicated symptom network and thereby reduce IA symptoms in individuals with ASD.
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http://dx.doi.org/10.1007/s10803-019-04354-wDOI Listing
April 2020

The 2-Year Course of Internet Addiction Among a Japanese Adolescent Psychiatric Clinic Sample with Autism Spectrum Disorder and/or Attention-Deficit Hyperactivity Disorder.

J Autism Dev Disord 2019 Nov;49(11):4515-4522

Department of Psychiatry, Shimane University School of Medicine, Shimane, Japan.

Internet addiction (IA) has been reported as prevalent in adolescents with autism spectrum disorders (ASD) and attention-deficit hyperactivity disorder (ADHD). However, the course of IA in this population has not been elucidated. The authors performed a 2-year follow-up study including 89 out of 132 adolescents with ASD and/or ADHD in a psychiatric clinical setting who participated in the original cross-sectional study assessing IA prevalence. Within this sample of participants from both the original and the follow-up study, results showed a 2-year IA remission and incidence rate of 60% and 5%, respectively. Our findings imply that the course of IA in psychiatric populations with ASD and/or ADHD might be similar to reports from previous studies with general adolescent populations.
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http://dx.doi.org/10.1007/s10803-019-04169-9DOI Listing
November 2019

Cross-cultural adaptation and psychometric properties of the Social Capital Questionnaire for Adolescent Students among preadolescents and adolescents in Japan.

Psychiatry Clin Neurosci 2019 Sep 15;73(9):601-602. Epub 2019 Jul 15.

Department of Neuropsychiatry, Graduate School of Medicine, Hirosaki University, Hirosaki, Japan.

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http://dx.doi.org/10.1111/pcn.12910DOI Listing
September 2019

Child and adolescent psychiatry in the Far East: A 5-year follow up on the Consortium on Academic Child and Adolescent Psychiatry in the Far East (CACAP-FE) study.

Psychiatry Clin Neurosci 2019 Feb 24;73(2):84-89. Epub 2018 Dec 24.

Faculty of Medicine, Centre for Child and Youth Mental Health and Child Protection, Norwegian University of Science and Technology, Trondheim, Norway.

Aim: Data pertaining to child and adolescent psychiatry (CAP) training systems are limited as extant research has mostly been derived from one-time data collection. This 5-year follow-up survey collects updated information on CAP training systems in the Far East, allowing for the tracking of system changes over the past 5 years.

Methods: Data were obtained from 18 countries, or functionally self-governing areas, in the Far East, 17 of which were also included in the original study. An online questionnaire was completed by leading CAP professionals in each country. Questions were expanded in the present study to capture the contents of CAP training.

Results: When compared to data from the original study, there has been progress in CAP training systems in the last 5 years. Specifically, there has been an increase in the number of countries with CAP training programs and national guidelines for the training. In addition, the number of CAP departments/divisions affiliated with academic institutions/universities has increased. Findings from 12 of 18 countries in the present study provide data on clinical contents. All informants of the present study reported the need for more child and adolescent psychiatrists and allied professionals.

Conclusion: Despite progress in CAP training systems over the last 5 years, the need for more professionals in child and adolescent mental health care in all the relevant areas in this region have yet to be adequately addressed. Continued national efforts and international collaborations are imperative to developing and sustaining new CAP training systems while facilitating improvements in existing programs.
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http://dx.doi.org/10.1111/pcn.12800DOI Listing
February 2019

Prevalence of pathological and maladaptive Internet use and the association with depression and health-related quality of life in Japanese elementary and junior high school-aged children.

Soc Psychiatry Psychiatr Epidemiol 2018 Dec 25;53(12):1349-1359. Epub 2018 Sep 25.

Research Center for Child Mental Development, Graduate School of Medicine, Hirosaki University, Hirosaki, 5 Zaifu-cho, Hirosaki, Aomori, 036-8562, Japan.

Purpose: Pathological Internet use has been predominantly studied in junior high/middle school-aged or older children; data from elementary/primary school-aged children, however, are scarce. The current study aimed to examine the prevalence of problematic Internet use, including pathological and maladaptive Internet use, in elementary and junior high school-aged children and the relationships between problematic Internet use and mental health problems and health-related quality of life.

Methods: The survey was conducted among children who attend national and public elementary and junior high schools in a medium-sized city in Japan; data were received from 3845 elementary school-aged and 4364 junior high school-aged children.

Results: Based on the Young's Diagnostic Questionnaire score, the prevalence of pathological and maladaptive Internet use was 3.6% and 9.4% and 7.1% and 15.8% in elementary and junior high school-aged children, respectively. The prevalence of problematic Internet use, including pathological and maladaptive Internet use, consistently increased from the 4th grade to the 8th grade. In addition, the prevalence sharply increased between the 7th grade and the 8th grade. Our study revealed that children with pathological and maladaptive Internet use exhibited more severe depression and decreased health-related quality of life than those with adaptive Internet use.

Conclusions: Our results demonstrated that pathological Internet use is not uncommon even in elementary school-aged children and that those with pathological and maladaptive Internet use have severe mental health problems and decreased health-related quality of life, supporting the importance of providing these children with educational and preventive interventions against problematic Internet use and associated risk factors.
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http://dx.doi.org/10.1007/s00127-018-1605-zDOI Listing
December 2018

A systematic review of screening tools in non-young children and adults for autism spectrum disorder.

Res Dev Disabil 2018 Sep 4;80:1-12. Epub 2018 Jun 4.

Chapin Hall Center for Children at the University of Chicago, 1313 E 60th St., Chicago, IL, 60637, USA.

Background: Existing reviews of screening tools for Autism Spectrum Disorder (ASD) focus on young children, and not all screening tools have been examined against validated diagnostic procedures.

Aims: To examine the validity of screening tools for ASD in non-young children and adults to provide clinical recommendations about the use of these tools in a variety of clinical settings.

Methods And Procedures: Electronic databases, including MEDLINE, EMBASE, PsychINFO, Cochrane Library and CINAHL, were searched through March 2017. Studies examining the validity of ASD screening tools against the Autism Diagnostic Observation Schedule and/or the Autism Diagnostic Interview - Revised in non-young children (age 4 or above) and adults were included. Three authors independently reviewed each article for data extraction and quality assessment.

Outcomes And Results: 14 studies met the inclusion criteria, of which 11 studies were with children (4-18 years of age) and 3 studies included adults only (19 years of age and above). Included studies were conducted in a general population/low-risk sample (N = 3) and a clinically referred/high-risk sample (N = 11). In total 11 tools were included.

Conclusions And Implications: Only three screening tools (the Autism-Spectrum Quotient, the Social Communication Questionnaire, and the Social Responsiveness Scale) were examined in more than 2 studies. These tools may assist in differentiating ASD from other neurodevelopmental and psychiatric disorders or typically developed children. In young adult populations, the paucity of the existing research in this group limits definitive conclusion and recommendations.
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http://dx.doi.org/10.1016/j.ridd.2018.05.017DOI Listing
September 2018

Intractable Hemophagocytic Syndrome Associated with Systemic Lupus Erythematosus Resistant to Corticosteroids and Intravenous Cyclophosphamide That Was Successfully Treated with Cyclosporine A.

Intern Med 2018 Sep 18;57(18):2747-2752. Epub 2018 May 18.

Department of Internal Medicine, Faculty of Medicine, University of Tsukuba, Japan.

Hemophagocytic syndrome (HPS) associated with systemic lupus erythematosus (SLE), dubbed acute lupus hemophagocytic syndrome (ALHS), is an intractable complication of SLE. A 24-year-old man who had been diagnosed with SLE three months previously, presented with fever, rash, hallucination, and pancytopenia accompanied with hyperferritinemia and bone marrow hemophagocytosis. He was diagnosed with ALHS and neuropsychiatric (NP)-SLE. Although 4 courses of methylprednisolone pulse therapy and 1 course of intravenous cyclophosphamide (IVCY) improved his NP-SLE, his ALHS did not respond. However, the addition of cyclosporine A (CsA) led to a rapid remission from ALHS. This suggests the usefulness of CsA in the treatment of intractable, corticosteroid- and IVCY-resistant ALHS.
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http://dx.doi.org/10.2169/internalmedicine.0571-17DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6191589PMC
September 2018

Clinical practice guideline for Sjögren's syndrome 2017.

Mod Rheumatol 2018 May 13;28(3):383-408. Epub 2018 Mar 13.

a Department of Internal Medicine , University of Tsukuba , Ibaraki , Japan.

Objectives: The objective of this study is to develop clinical practice guideline (CPG) for Sjögren's syndrome (SS) based on recently available clinical and therapeutic evidences.

Methods: The CPG committee for SS was organized by the Research Team for Autoimmune Diseases, Research Program for Intractable Disease of the Ministry of Health, Labor and Welfare (MHLW), Japan. The committee completed a systematic review of evidences for several clinical questions and developed CPG for SS 2017 according to the procedure proposed by the Medical Information Network Distribution Service (Minds). The recommendations and their strength were checked by the modified Delphi method. The CPG for SS 2017 has been officially approved by both Japan College of Rheumatology and the Japanese Society for SS.

Results: The CPG committee set 38 clinical questions for clinical symptoms, signs, treatment, and management of SS in pediatric, adult and pregnant patients, using the PICO (P: patients, problem, population, I: interventions, C: comparisons, controls, comparators, O: outcomes) format. A summary of evidence, development of recommendation, recommendation, and strength for these 38 clinical questions are presented in the CPG.

Conclusion: The CPG for SS 2017 should contribute to improvement and standardization of diagnosis and treatment of SS.
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http://dx.doi.org/10.1080/14397595.2018.1438093DOI Listing
May 2018

Recurrent Kikuchi-Fujimoto Disease Successfully Treated by the Concomitant Use of Hydroxychloroquine and Corticosteroids.

Intern Med 2017 Dec 11;56(24):3373-3377. Epub 2017 Oct 11.

Department of Internal Medicine, Faculty of Medicine, University of Tsukuba, Japan.

Kikuchi-Fujimoto disease (KFD) is a benign disease of unknown etiology characterized by lymphadenopathy and a fever. For the majority of patients with KFD, the course is self-limited; however, the optimum method of managing recurrent cases has not yet been established. We herein report a case of a 42-year-old Japanese woman with KFD (confirmed by a lymph node biopsy). Although high-dose prednisolone (PSL) rapidly induced remission, she experienced four recurrences on treatment tapering. Concomitant use of hydroxychloroquine (HCQ) with low-dose PSL induced continuous remission. This is the first case to suggest the effectiveness of HCQ for recurrent KFD in a Japanese patient.
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http://dx.doi.org/10.2169/internalmedicine.9205-17DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5790731PMC
December 2017

Diffusion-weighted magnetic resonance imaging of parotid glands before and after abatacept therapy in patients with Sjögren's syndrome associated with rheumatoid arthritis: Utility to evaluate and predict response to treatment.

Mod Rheumatol 2018 Mar 19;28(2):300-307. Epub 2017 Jul 19.

a Department of Internal Medicine, Faculty of Medicine , University of Tsukuba , Tsukuba , Japan.

Objective: To compare parotid diffusion-weighted images (DWIs) taken before and after abatacept therapy in patients with Sjögren's syndrome (SS) associated with rheumatoid arthritis (RA) and to examine the utility in evaluation and prediction of response to therapy.

Methods: DWIs of the parotid glands taken at baseline and 52 weeks after initiation of abatacept were analyzed in nine SS patients with RA using relative standard deviation (RSD) of the entire glands and signal intensity ratio (SIR) within the residual parenchyma. The correlation between changes in RSD and SIR and changes in salivary secretion based on Saxon's test was examined. Furthermore, baseline characteristics were compared in patients with increased and decreased salivary secretion after treatment. The predictive power of the parameter at baseline was examined using receiver operating characteristic (ROC) analysis.

Results: Abatacept improved salivary secretion from 2076 ± 1535 at baseline to 2857 ± 1431 mg/2 min at 52 weeks (n = 9, p = .05). Increase of salivary secretion was significantly higher in patients with decreased RSD (n = 6) than increased RSD (n = 3) (1241 ± 713, -137 ± 142 mg/2 min, p = .02). The increase and decrease in RSD completely accorded with those of salivary secretion. Furthermore, SIR was the only parameter that was significantly different between patients with posttreatment increase and decrease in salivary secretion (p = .04). ROC analysis showed the sensitivity and specificity of SIR at baseline of ≥13.0 × 10 for the prediction of the response to abatacept were 75.0% and 83.3%, respectively.

Conclusions: Parotid DWI seems to be useful for evaluating and predicting the response in salivary secretion to abatacept in SS patients with RA.
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http://dx.doi.org/10.1080/14397595.2017.1349234DOI Listing
March 2018

Suppression of GPI-induced arthritis by oral administration of transgenic rice seeds expressing altered peptide ligands.

Nihon Rinsho Meneki Gakkai Kaishi 2017 ;40(1):28-34

Department of Internal Medicine, Faculty of Medicine, University of Tsukuba.

Objective: To investigate the effects and mechanisms of transgenic rice seeds expressing the altered peptide ligand (APL) of human glucose-6-phosphate-isomerase (hGPI) in mice model of GPI induced arthritis (GIA).

Methods: We generated transgenic rice expressing APL12 which was analog peptide of hGPI. The transgenic rice seeds were orally administered prophylactically before the induction of GIA. The severity of arthritis and titers of serum anti-GPI antibodies were evaluated. We examined IL-17 production from splenocytes and inguinal lymph node (iLN) and mesenteric lymph nodes (mLN) cells and analyzed the expression levels of functional molecules from splenocytes and iLN cells.

Results: Prophylactic treatment of GIA mice with APL12 transgenic rice seeds (APL12-TG) significantly improved the severity of arthritis, histopathological arthritis scores, and decreased titers of serum anti-GPI antibodies, BAFF mRNA in iLN cells, IL-17 production in splenocytes and iLN cells compared with non-transgenic rice-treated mice. APL12-TG-treated GIA mice showed upregulation of Foxp3 and GITR protein in CD4CD25 cells in the spleen.

Conclusion: APL12-TG improved the severity of GIA through a decrease in production of IL-17 and anti-GPI antibodies via upregulation of Foxp3 and GITR expression on regulatory T cells in spleen.
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http://dx.doi.org/10.2177/jsci.40.28DOI Listing
September 2017

Functional Analysis of Dendritic Cells Generated from T-iPSCs from CD4+ T Cell Clones of Sjögren's Syndrome.

Stem Cell Reports 2017 05;8(5):1155-1163

Department of Internal Medicine, Faculty of Medicine, University of Tsukuba, Tsukuba 305-8575, Japan. Electronic address:

Although it is important to clarify the pathogenic functions of T cells in human samples, their examination is often limited due to difficulty in obtaining sufficient numbers of dendritic cells (DCs), used as antigen-presenting cells, especially in autoimmune diseases. We describe the generation of DCs from induced pluripotent stem cells derived from T cells (T-iPSCs). We reprogrammed CD4+ T cell clones from a patient with Sjögren's syndrome (SS) into iPSCs, which were differentiated into DCs (T-iPS-DCs). T-iPS-DCs had dendritic cell-like morphology, and expressed CD11c, HLA-DR, CD80, CD86, and also BDCA-3. Compared with monocyte-derived DCs, the capacity for antigen processing was similar, and T-iPS-DCs induced the proliferative response of autoreactive CD4+ T cells. Moreover, we could evaluate T cell functions of the patient with SS. In conclusion, we obtained adequate numbers of DCs from T-iPSCs, which could be used to characterize pathogenic T cells in autoimmune diseases such as SS.
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http://dx.doi.org/10.1016/j.stemcr.2017.04.010DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5425788PMC
May 2017

The Prevalence of Internet Addiction Among a Japanese Adolescent Psychiatric Clinic Sample With Autism Spectrum Disorder and/or Attention-Deficit Hyperactivity Disorder: A Cross-Sectional Study.

J Autism Dev Disord 2017 07;47(7):2217-2224

Department of Neuropsychiatry, Okayama University Hospital, Okayama, Japan.

Extant literature suggests that autism spectrum disorder (ASD) and attention-deficit hyperactivity disorder (ADHD) are risk factors for internet addiction (IA). The present cross-sectional study explored the prevalence of IA among 132 adolescents with ASD and/or ADHD in a Japanese psychiatric clinic using Young's Internet Addiction Test. The prevalence of IA among adolescents with ASD alone, with ADHD alone and with comorbid ASD and ADHD were 10.8, 12.5, and 20.0%, respectively. Our results emphasize the clinical importance of screening and intervention for IA when mental health professionals see adolescents with ASD and/or ADHD in psychiatric services.
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http://dx.doi.org/10.1007/s10803-017-3148-7DOI Listing
July 2017

Comparison of performance of the 2016 ACR-EULAR classification criteria for primary Sjögren's syndrome with other sets of criteria in Japanese patients.

Ann Rheum Dis 2017 Dec 22;76(12):1980-1985. Epub 2017 Mar 22.

Department of Internal Medicine, Faculty of Medicine, University of Tsukuba, Tsukuba, Japan.

Objectives: To compare the performance of the new 2016 American College of Rheumatology (ACR)-European League Against Rheumatism (EULAR) classification criteria for primary Sjögren's syndrome (SS) with 1999 revised Japanese Ministry of Health criteria for diagnosis of SS (JPN), 2002 American-European Consensus Group classification criteria for SS (AECG) and 2012 ACR classification criteria for SS (ACR) in Japanese patients.

Methods: The study subjects were 499 patients with primary SS (pSS) or suspected pSS who were followed up in June 2012 at 10 hospitals in Japan. All patients had been assessed for all four criteria of JPN (pathology, oral, ocular, anti-SS-A/SS-B antibodies). The clinical diagnosis by the physician in charge was set as the 'gold standard'.

Results: pSS was diagnosed in 302 patients and ruled out in 197 patients by the physician in charge. The sensitivity of the ACR-EULAR criteria in the diagnosis of pSS (95.4%) was higher than those of the JPN, AECG and ACR (82.1%, 89.4% and 79.1%, respectively), while the specificity of the ACR-EULAR (72.1%) was lower than those of the three sets (90.9%, 84.3% and 84.8%, respectively). The differences of sensitivities and specificities between the ACR-EULAR and other three sets of criteria were statistically significant (p<0.001). Eight out of 302 patients with pSS and 11 cases out of 197 non-pSS cases satisfied only the ACR-EULAR criteria, compared with none of the other three sets.

Conclusions: The ACR-EULAR criteria had significantly higher sensitivity and lower specificity in diagnosis of pSS, compared with the currently available three sets of criteria.
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http://dx.doi.org/10.1136/annrheumdis-2016-210758DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5705843PMC
December 2017

Suppression of glucose-6-phosphate-isomerase induced arthritis by oral administration of transgenic rice seeds expressing altered peptide ligands of glucose-6-phosphate-isomerase.

Mod Rheumatol 2017 May 1;27(3):457-465. Epub 2017 Feb 1.

a Department of Internal Medicine, Faculty of Medicine , University of Tsukuba , Tsukuba , Ibaraki , Japan and.

Objective: To investigate the effects of transgenic rice seeds expressing the altered peptide ligand (APL) of human glucose-6-phosphate-isomerase (hGPI) in mice model of GPI-induced arthritis (GIA).

Methods: We generated transgenic rice expressing T-cell epitope of hGPI and APL12 contained in the seed endosperm. The transgenic rice seeds were orally administered prophylactically before the induction of GIA. The severity of arthritis and titers of serum anti-GPI antibodies were evaluated. We examined for IL-17 production in splenocytes and inguinal lymph node (iLN) cells, and analyzed the expression levels of functional molecules in splenocytes.

Results: Prophylactic treatment of GIA mice with APL12 transgenic (APL12-TG) rice seeds significantly reduced the severity of arthritis and titers of serum anti-GPI antibodies compared with non-transgenic (Non-TG) rice-treated mice. APL12-TG and hGPI transgenic (hGPI-TG) rice seeds improved the histopathological arthritis scores and decreased IL-17 production compared with non-TG rice-treated mice. APL12-TG rice-treated GIA mice showed upregulation of Foxp3 and GITR protein in CD4  CD25  Foxp3cells in the spleen compared with non-TG rice- and hGPI-TG rice-treated mice.

Conclusion: APL12-TG rice seeds improved the severity of GIA through a decrease in production of IL-17 and anti-GPI antibodies via upregulation of Foxp3 and GITR expression on Treg cells in spleen.
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http://dx.doi.org/10.1080/14397595.2016.1218598DOI Listing
May 2017

Effectiveness of abatacept for patients with Sjögren's syndrome associated with rheumatoid arthritis. An open label, multicenter, one-year, prospective study: ROSE (Rheumatoid Arthritis with Orencia Trial toward Sjögren's syndrome Endocrinopathy) trial.

Mod Rheumatol 2016 Nov 26;26(6):891-899. Epub 2016 Jul 26.

a Department of Internal Medicine, Faculty of Medicine , University of Tsukuba , Tsukuba-city , Ibaraki , Japan.

Objective: To clarify the efficacy and safety of abatacept for secondary Sjögren's syndrome (SS) associated with rheumatoid arthritis (RA).

Methods: The primary endpoint of this open-labeled, prospective, observational multicenter study for secondary SS with RA was the remission rate of Simplified Disease Activity Index (SDAI) at 52 weeks after initiation of abatacept. The secondary endpoints included Saxon's test and Schirmer's test. Adverse events and adherence rate during the study period were also analyzed.

Results: Thirty-six patients (all females) were enrolled in this study. The mean SDAI decreased significantly from 20.6 ± 11.2 (±SD) at baseline to 10.0 ± 10.5 at 52 weeks (p < 0.05). Patients with SDAI remission increased from 0 (0 week) to 12 patients (33.3%) at 52 weeks. Saliva volume assessed by Saxon's test increased significantly from 2136 ± 1809 (0 week) to 2397 ± 1878 (24 weeks) mg/2 min (n = 34, p < 0.05). Saliva volume increased significantly from 2945 ± 2090 (0 week) to 3419 ± 2121 (24 weeks) mg/2 min in 11 patients with Greenspan grade 1 or 2 of labial salivary gland biopsy (p < 0.05), but no change was noted in 18 patients with Greenspan grade 3 or 4. Tear volume by Schirmer's test increased significantly from 4.2 ± 4.8 (0 week) to 6.4 ± 7.8 (24 weeks) mm/5 min (n = 30, p < 0.05). The adherence rate to abatacept was 80.6% (29/36) over the 52-week period. Twelve adverse events occurred in 10 of the 36 patients, and 7 of these events were infections.

Conclusion: Abatacept seems to be effective for both RA and SS related manifestations.
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http://dx.doi.org/10.3109/14397595.2016.1158773DOI Listing
November 2016

Association of anti-Ro/SSA antibody with response to biologics in patients with rheumatoid arthritis.

Mod Rheumatol 2016 Nov 22;26(6):857-862. Epub 2016 Mar 22.

a Department of Internal Medicine, Faculty of Medicine , University of Tsukuba , Ibaraki , Japan.

Objective: To compare the effectiveness of three different biologics in anti-Ro/SSA antibody-positive and antibody-negative patients with rheumatoid arthritis (RA).

Methods: The study subjects were 110 biologics naïve patients with RA who started treatment with biologics and examined for anti-Ro/SSA antibody between December 2003 and March 2014. For patients treated with intravenous infliximab (IFX), tocilizumab (TCZ), or abatacept (ABT), we compared the clinical characteristics and changes in composite disease activity index, such as DAS28, SDAI, and CDAI, for 12 months in anti-Ro/SSA antibody-positive and antibody-negative patients.

Results: We examined 59 patients (nine were positive and 50 were negative for anti-Ro/SSA antibody) treated with IFX, 27 patients (5 positive and 22 negative) treated with TCZ, and 24 patients (13 positive and 11 negative) treated with ABT. For patients treated with IFX, parameters of disease activity did not change significantly from baseline in anti-Ro/SSA antibody-positive patients, whereas they improved in antibody-negative patients. On the other hand, treatment with TCZ and ABT significantly decreased disease activity, relative to baseline, in both anti-Ro/SSA antibody-positive and antibody-negative patients. Anti-Ro/SSA antibody-positive patients treated with IFX showed higher frequency of HACA and seroconversion of ANA, and lower serum TGF-β levels.

Conclusions: Positivity to anti-Ro/SSA in RA seems to confer resistance to IFX via production of HACA and ANA, and low serum TGF-β levels, but not to TCZ and ABT.
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http://dx.doi.org/10.3109/14397595.2016.1153567DOI Listing
November 2016

Antipsychotic medications for the treatment of delirium: a systematic review and meta-analysis of randomised controlled trials.

J Neurol Neurosurg Psychiatry 2016 Jul 4;87(7):767-74. Epub 2015 Sep 4.

Department of Psychiatry, Fujita Health University School of Medicine, Toyoake, Aichi, Japan.

Objectives: We performed an updated meta-analysis of antipsychotic treatment in patients with delirium, based on a previous meta-analysis published in 2007.

Methods: Included in this study were randomised, placebo-controlled or usual care (UC) controlled trials of antipsychotics in adult patients with delirium. Our primary outcome measure was response rate at the study end point. The secondary outcome measures included improvement of severity of delirium, Clinical Global Impression-Severity Scale (CGI-S), time to response (TTR), discontinuation rate and individual adverse effects. The risk ratio (RR), the number-needed-to-treat/harm (NNT/NNH), 95% CIs and standardised mean difference (SMD), were calculated.

Results: We identified 15 studies (mean duration: 9.8 days) for the systematic review (total n=949, amisulpride=20, aripiprazole=8, chlorpromazine=13, haloperidol=316, intramuscular olanzapine or haloperidol injection=62, olanzapine=144, placebo=75, quetiapine=125, risperidone=124, UC=30 and ziprasidone=32), 4 of which were conference abstracts and unpublished. When pooled as a group, antipsychotics were superior to placebo/UC in terms of response rate (RR=0.22, NNT=2), delirium severity scales scores (SMD=-1.27), CGI-S scores (SMD=-1.57) and TTR (SMD=-1.22). The pooled antipsychotic group was associated with a higher incidence of dry mouth (RR=13.0, NNH=5) and sedation (RR=4.59, NNH=5) compared with placebo/UC. Pooled second-generation antipsychotics (SGAs) were associated with shorter TTR (SMD=-0.27) and a lower incidence of extrapyramidal symptoms (RR=0.31, NNH=7) compared with haloperidol.

Conclusions: Our results suggested that SGAs have a benefit for the treatment of delirium with regard to efficacy and safety compared with haloperidol. However, further study using larger samples is required.
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http://dx.doi.org/10.1136/jnnp-2015-311049DOI Listing
July 2016